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Prof Trevor Marshall
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I have been trying to find out what is the component in coffee which so clearly affects Th1 patients. Caffeine doesn't make the cut, as, although it has some effect on the Type 1 Nuclear Receptors, the affinity is low, and the observed symptomatic effects would require high concentrations of the drug, which are just not present in the diet of the average coffee drinker. Yesterday Wrotek suggested Chlorogenic Acid, and I have verified that he is correct. This is a culprit, and probably the major culprit. Here is an image of Chlorogenic acid (yellow backbone) as docked into the VDR, with the Xray structure of the docked 1,25-D for comparison. Note that the oxygens at the key helix 4 residues are effectively coincident.


Chlorogenic Acid forms hydrogen bonds with the same residues as 1,25-D; ARG274, SER237, SER278 and (weaker) TYR143. However, it does not have a 'tail' to stabilize the lower part of the VDR receptor, so at best it is a partial agonist, and is more probably a total antagonist of Type 1 Nuclear Receptor activity.

The affinity of Chlorogenic Acid for the VDR is consequently very high, with Ki calculating at 8 nanomolar. Assuming that this paper's concentration data are correct, and this one too, then just one cup of coffee contains several orders of magnitude more chlorogenic acid than would be needed to notice an profound effect on the VDR (and an effect the other Type 1 Nuclear Receptors, such as the Thyroid Receptors).

Here is a summary of the concentration issues, which looks to be (at first glance) fairly reliable:
http://www.cosic.org/coffee-and-health/antioxidants

So another mystery succumbs to the magic of molecular genomics. Thanks to all who helped...

------------------------
(Scientists who want to build this discovery into their own papers should cite:
Marshall TG, Lee RE, Marshall FE: Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b. Theor Biol Med Model. 2006 Jan 10;3(1):1, together with the URL for this thread)

wrotek
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Absolutely, no problems :)
LOL, really ?

Chlorogenic acid is also present with higher quantities in apples.

Chlorogenic acid is marketed under the tradename Svetol® in Norway and the United Kingdom as a food additive used in coffee, chewing gum, and mints to promote weight reduction. from http://en.wikipedia.org/wiki/Chlorogenic_acid

Last edited on Sun Jan 28th, 2007 10:27 by wrotek

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Damn!  I enjoy about 3 or 4 cups per week.  Looks like I will be switching to tea.  Even so, I want to be perfectly healed so thank you Trevor. - John

Prof Trevor Marshall
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Let me know if it makes your immunopathology more predictable, John:)

wrotek
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Finally i have a strong motivation to quit drinking coffee, starting tomorrow :) I drink 1-2 cups a day but my coffees are espresso, dunno if espresso has less chloragenic acid but probably considering high amount of it there + high affinity, it won't matter.

Prof Trevor Marshall
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Wrotek,
There is some Chlorogenic Acid in pears, too.
http://tinyurl.com/2slrbn

Not as much as in coffee, though. And the skin contains some neutralizing enzymes... Probably one or two fruit would not give problems. It does explain why I steadfastly stuck to one type of pear, Bosc pears, and avoided apples (including Asian pears) during all those dark years:):X

Now I don't feel so bad about having come down with Scurvy in 1979 - and therein lies a moral to this tale - MP'ers need to eat their fresh pears and/or apples, to make sure they get enough Vitamin C and other nutrients... But in moderation, like all things... And try out different types and brands, too...

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Does this apply to decaff????? :X:X:X

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Ok, so now do we have to quit coffee to heal all of the way?  I drink about 2 cups every morning.  What differences could/would I see if I quit?  I mean, what would you suspect would change?  more herx?  less herx? different symptoms?

Trevor, thanks for all of your wonderful work... I think.  :P:cool::P

P.R.N.
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It looks like black tea is out for the same reason as coffee:

http://www.ajcn.org/cgi/content/full/73/3/532

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Dr. Marshall - you are breaking my heart! Couldn't you have left us in a state of blissful ignorance when it comes to the pit falls of consuming that much cherished cup-a-joe's? Stop your molecular modelling, before there is nothing left but water! Now, us coffee drinkers will have no choice but to start another support group!;)

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When I decided it would be OK to add coffee back into my diet, I did a little research on coffee and the liver.  Although the reasoning for avoiding coffee would be different here, is it really necessary to totally cut it out or is moderation the key here too? 

P Bear,

Why wouldn't green tea be the same then as black tea?  From what I understand, BOTH teas are actually the same plant although processed differently.  So is it the process that changes the acid content?  Or is it just that the study didn't include green tea? :cool:

Last edited on Sun Jan 28th, 2007 13:32 by Reenie

Prof Trevor Marshall
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Reenie asks:Ok, so now do we have to quit coffee to heal all of the way?
This is more about making sure that the immunopathology you feel really is immunopathology, and not your immune system being modulated by outside factors. Healing time or completeness is probably not going to be affected all that much.

Drug effect is dose dependent. If you drink a lot of coffee, or strong black tea, you should be on the lookout. Actually, everybody should be on the lookout, but you only need to change things if you get to the point where you can't manage your meds dosage because cause and effect of the abx dosing becomes too complicated. If so, then there is probably this additional factor present.

Julia, I am sure that if tea is not steeped for more than a few seconds, then fewer tannins, and I suspect other compounds too, will infuse into the brew. Green tea is typically steeped less than black tea, especially if you don't use a pot. The take-home message is don't use a pot, and dip the bags only until the taste is strong enough to be OK.

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I think green tea could be a problem too. No wonder the weak dip method came about. There was good reason. And here I am backsliding to stronger green tea.:X  P.B.

Prof Trevor Marshall
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Hey, PB, you should be healing pretty well by now. You need to worry less and less as time goes by, you know:):):)

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Trevor, I was thinking about decaff coffee.  If it isn't the caffeine that's the problem, than presumably decaff is bad too.  But I only have one or two cups of very weak decaff a day...  ppppleeease... :?

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OH NO! :shock: PLEASE don't tell me! :X

I have been celebrating the fact that after 20 years of refraining from drinking my beloved coffee because of bad side effects. (Even one cup gave me heart palpitations or skipping heart beats) I can finally drink it without problems.

I thought! :X

Isn't there a way to filter out that immunosuppressive chlorogenic acid you mentioned? We buy organic coffee and grind it ourselves using nice thick brown filters. Also is there a difference in coffee c. acid content depending on bean and process?

Another thought is that I have plenty of IP response with very little abx ramping. So why can't I continue to drink coffee? Please know I say this with all due respect. I just recently started drinking coffee again a couple months ago and I have not noticed less IP response. :)

I eat at least one apple everyday ... my favorite fruit. Glad you said in moderation that it is fine. Thankful for that anyway. 

CL :dude:

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CL,
As you heal on the MP, then the need to micromanage the control of your body becomes less important, and of course you can (and will) 'ease-up'. You have been healing on the MP long enough for your body to be able to take coffee, as you have found, without it being a problem for you. Drink it and enjoy...

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Awwwwww. Thank YOU for your reply! Those are such good words to hear. :D

CL :dude:

Prof Trevor Marshall
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Err, EggplantChlorogenic acid, a type of phenolic, accounted for 96% to 63.4% of total phenolics in most eggplants
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=143006

It would be nice to look at the fulltext to see the actual quantities involved...

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My wife drinks about 10 cups of regular tea daily (with soy milk) and not too strong. She feels horrible (pain mostly, but nausea and fatigue too) all the time. Should she consider reducing the amount she drinks?

Last edited on Sun Jan 28th, 2007 14:51 by Rico

Prof Trevor Marshall
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Rico,
Yes, weak tea, black or green, where the bag is only steeped for less than a minute, would likely be best. Try to avoid the milk, I think. Personally, I like Trader Joes Jasmine Green Tea, dipping the teabag for about 20-30 seconds, sweetened with Splenda.

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Her tea is steeped less than 1 minute and she adds unfortified soy milk (no D) - is 10 still too much, IYO?

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Go ahead Trevor, tell us about chocolate. Let's just get it over with. I know Clorogenic acid is in there, but how much?

Giving up coffee may be one of the hardest things the MP has asked me to do, but if I gotta, I gotta. But my wife is going to be heatbroken when she finds she can't make her grandmother's Apple-coffee-eggplant casserole! :)

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Chocolate is fine.

A good cup of sugar-free drinking chocolate mixed with Splenda for sweetening will warm the heart without interfering with the immune system...

I personally prefer Droste brand Cocoa, "Importe des Pays-Bas," which I buy in bulk. It still costs about $7 a box, though :) Still, its good... I mix two parts of this with one part of non-fortified whole milk powder and three parts of splenda in a jar, which can then be spooned out into a cup of hot water :)

Walmart has Splenda in large bags at about half the supermarket price... their brand is "Altern"

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[filelink]

A review of chlorogenic acid and genistein

We've been discussing two substances recently, chlorogenic acid which is a phenolic compound and genistein which is an isoflavone. Both act as antioxidents. Dr. Marshall has recently determined that both chlorogenic acid and genistein affect (modulate) the immune system if consumed in large enough quantities. This may may make it harder to judge progess of the MP.

Chlorogenic acid

The quanty of chlorogenic acid in most plants is miniscule. However, a few plants accumulate chlorogenic acids in quantities sufficient to have a physiological effect. The primary dietary source of chlorogenic acid is coffee; green coffee beans typically contain 6-7% of this component (range: 4-10%); roasted coffee beans contain somewhat less, as the roasting transforms chlorogenic acids into other molecules, which may still retain the same functions. Coffee that is not fresh (two weeks past roasting) is said to contain fewer antioxidants (chlorogenic acid). Apples, pears and eggplant contain small amounts of chlorogenic acid. It is somewhat neutralized by an enzyme in the skin of the fruit. Eating these foods in moderation is fine.

Decaf coffee

Dr. Vinson, researcher at the University of Pennsylvania, who has studied decaffeinated coffee said both caffeinated and decaffeinated coffee provides similar levels of antioxidants (chlorogenic acid).

Coffee substitute

An herbal coffee-like beverage is sold at this website:
http://www.teeccino.com/decaf.aspx

Cocoa

Cocoa contains chlorogenic acid but the amount is very small.

Genistein

The major source of genistein is soy products.

Green tea

Green tea contains some genistein but the amount seems to be very low. If you enjoy green tea, we suggest that you make it very weak by allowing the tea bag to steep for 30 seconds or less.

Black tea

The processing of black tea is reputed to remove most of the antioxidents (genistein) but this is disputed. Again, drink it weak.

Caffeine

Caffeine is not the problem with either tea or coffee.

Moderation is the key to consumption

Although these substances are not immunosuppressive, they modulate the immune system in unknown ways. The effect of chlorogenic acid and genistein on the immune system is dose dependent. Most foods that contain these substances may be eaten.

Soy products are the most worrisome and should be limited to a very small amount each day. If you consume these substances, they may affect your progress on the MP or make it more difficult for you to recognize immunopathology. If you are having problems, an assessment of your food intake should be added to your problem-solving checklist.

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I remember a time (long before the MP) when my morning coffee reliably produced a few hours of reduced joint pain.  The action of chlorogenic acid that Dr Marshall describes explains why.  This hasn’t happened in a long time and I can’t say that I know what’s different.  

I still really, really, really enjoy my morning coffee, but I am not aware that it does more than provide the standard caffeine-related benefits.  Nonetheless, I’ll sure be re-evaluating the effects of this habit on my symptoms. 
......Carol

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Meg or Trevor,

So modulate, in the way that it suppresses the immune system when ingested?so hince less IR? Is that why it makes IR less predictable..is that why you say it impedes judging progress on the MP...it instead of benicar docking into the VDR causes less IR?

Just making sure I am getting this...Jeannine:)

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(Voor de nederlanders onder ons:)
For the Dutchies amongst us:

Chlorogenic acid translates to: chlorogeenzuur

Oh my, another quest for things to stay away from...

Best to all, Frans

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Dr Trevor Marshall wrote:
Chocolate is fine.


 

My mother thinks you're wonderful for many reasons. Your statements on Chocolate among them :D

As yet, I haven't told her about the coffee aspect though ;)

Lottie :)

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Carol wrote:

I remember a time (long before the MP) when my morning coffee reliably produced a few hours of reduced joint pain.

Carol, maybe it is just a matter of a few hours.  I intend to experiment but I don't seem to have 2 days alike in any 10  day cycle , so it will be tough to control this experiment.  I have long since lost my addiction to coffee.  In the long gone past I needed a cup by 9A or I would have a headache and nasty crankiness.  Now I can do with or without and only have coffee when traveling (which, however is often).  But working at a desk without a mug of warm beverage is just wrong.

I reckon that I will now save coffee for a treat for those travel days that severely require one.

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Meg quotes, "...Coffee that is not fresh (two weeks past roasting) is said to contain fewer antioxidants (chlorogenic acid)."

Is it possible that we aren't getting alot of chlorogenic acid from coffee anyway due to this? 

I personally don't know anyone or anywhere one would get fresh roasted coffee beans.  Now, fresh ground I would understand, which would also prob contain more antioxidants than my store bought, already ground, canned coffee. 

Maybe I ought not refrigerate the can once I open it since it seems less fresh is better for our purposes? :cool:  

PS And I'm not giving up my occasional eggplant parmigiana either! :P:cool::P

Last edited on Mon Jan 29th, 2007 08:56 by Reenie

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I'm not sure if this experience might reinforce this coffee effect,  but.....the following event was the primary motivation for me to re-visit sarcinfo.com and make the decision to try the MP.

Sarcinfo educated me a bit about heart arrhythmia,  and it dawned on me,  that what doc and I had assumed was some sort of exercise or cold induced asthma,  was probably arrhythmia.  It happened predictably when I was in the habit of driving up  into the mountains, (to the 8000 foot level) to cross country ski, while sipping my second large strong mug of coffee of the morning.  I could strap on my skis, and fairly comfortably ski up the long uphill section to get to our trail system.  When I stopped at the top of this section,  I would feel very strange, wonder if I was going to be able to keep breathing,  light headed and maybe a bit anxious.  Definitely quite alarmed and concerned. 

Interestingly,  my neighbor, doctor, and fellow skier, (when I lived in Wyoming)  had been noticing something similar when he skied,  and scheduled both of us for a treadmill test. I told him I was starting to suspect the high coffee dose was my problem,  so I backed off the coffee,  and I don't recall if I did have further arrhythmia, however at that time, I started the MP,  and really backed off on pushing myself too hard physically.  I never did take the treadmill test.

I know I tried to back off  coffee somewhat and even decaffeinate for a while during the last three years on the MP,  but I guess I have gradually slipped back to old habits by drinking a pot of strong coffee every morning now.  I'm really hoping I can continue recovery on the MP, without having to consider eliminating one of the last few vices I really enjoy and would hate to give up. 
(Oh!.....I've also routinely consumed soy milk with my breakfast Kashi Crunch every morning. Guess I'll revisit the rice milk section at the store.)

Last edited on Mon Jan 29th, 2007 08:48 by John D

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Coffee looses its freshness by exposure to air, light, and moisture.

Sherry

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Dr Marshall, did You try to calculate Chlorogenic Acid, Carnosic Acid, Genistein affinity to other receptors ? Thyroid, etc... ?

Last edited on Tue Jan 30th, 2007 23:38 by wrotek

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I'm not a coffee drinker but will drink tea.  I've been using the Trader Joe's Jasmine exclusively since starting the protocol.  I always leave the tea bag in the cup while it cools and even while drinking it.  I see that's a big no-no now.  Thanks for the good info.

Prof Trevor Marshall
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Hey, Wrotek, not so fast:):)
It takes a huge amount of computing power to run these molecular simulations, hours for each run. I have looked first at Genistein and Quercetin into Estrogen receptors alpha and beta, as they are known to be ligands of those receptors. I still have to get more data before I want to draw any conclusions, but my feeling is that once again VDR is the elephant in the room that everybody has been ignoring. Sure, these drugs affect the other receptors, but often not as much as they affect VDR. I am also not satisfied that we are seeing the primary action yet - the Ki values are still quite high, even though the 'wet biologists' have confirmed activity in their lab environment.

The message for chlorogenic acid is much clearer, however. With Ki in the 8 nanomolar range, this is a good ligand of VDR, definitely active. The only things working to reduce its effect are bioavailability and clearance issues, which have been shown to vary 10:1 between individuals. Thus, the concentration in the cytoplasm is relatively imponderable, but anecdotal clinical experience confirms it is likely very active (IMO).

I will give you my overview of the activities of these ligands in the other receptors once more data starts coming our of the server, which has been churning away for several days now... I usually load it up with 4 to 12 concurrent simulation jobs and let the Linux kernel multi-tasking allocate resources...

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http://www.ajcn.org/cgi/content/full/73/3/532 I can't find one sentence in this study that says unquestionably that black tea contains chlorogenic acid.

It compares coffee containing chlorogenic acid to black tea (not black tea with chlorogenic acid ) by their ability to increase homocysteine levels.

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I agree Wrotek. Many, many foods have chlorogenic acid in them, as it is part of one mechanism by which leaves (and fruit) achieve their color. The issue at hand is whether the amount of chlorogenic acid which reaches the nucleated cells is sufficient to activate the VDR. In most cases there is not enough. Coffee, however, definitely has sufficient concentration to cause a problem. Tea seem OK, as far as I have been able to tell, but there are very few quantitative studies to get the data from...

However, there are other low solubility substances in tea which primarily come out as the tea is allowed to steep. So steeping is not a good idea, in any case.

wrotek
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I have found this list of 210 studies about chlorogenic acid,
maybe there will be something interesting.
http://www.coffeeberry.org/chlorogenic.htm

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aha!  Just this morning I indulged in a cuppa coffee for the first time in weeks... and a couple of hours later, also for the first time in weeks, the crickets stopped chirriping in my head! (tinnitus) It was quite noticeable - so much so that I jotted it down in my MP notebook.  So from this I gather that: The tinnitus is an immunopathology problem and the coffee dampened the IP by interfering with that. 

Bother.

I've been hearing that coffee is bad for me for over 25 years... will I ever learn?

:( How depressing... I'm off to eat some chocolate. :P

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Claudia,
Not surprising, I guess. Chlorogenic acid hits Thyroid-beta very hard, and Thyroid beta produces a key protein used in hearing.

To all:
Would somebody have the time to look through the literature and find out what the total chlorogenic acid content is in the smoke from a cigarette? (that way I can focus on finishing off the simulations instead of searching PubMed:)) I need to know the number of milligrams of the susbstance one inhales...

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I remember Dr Marshall was saying about study when mice were breed without beta thyroid receptor and seemed fine, except hearing lose :)

And now is the kicker for me, can chlorogenic acid be a contributing factor for feeling an ear pressure which I am struggling for years ?

How strong affinity has chlorogenic acid to beta thyroid receptor ?

Prof Trevor Marshall
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Ki is 0.9 nanomolar. That is real high, Wrotek. Depending on individual's clearance, ingesting levels in the 100's of milligrams would certainly be a big, big, problem.

Here is a link to the paper about Thyroid receptors and Prestin, a protein needed by the cochlea
http://www.pnas.org/cgi/content/full/99/5/2901

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i'll be back in a minute and find a 'free' paper......

i found this real quick though,

The determination of chlorogenic acid in cigarettes by inhibited chemiluminescence analysis

http://tinyurl.com/28977f

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Would somebody have the time to look through the literature and find out what the total chlorogenic acid content is in the smoke from a cigarette?
Trevor, searching for "chlorogenic acid cigarette smoke" in PubMed only brings up five papers.  None answers your question, though one looks quite interesting (to my layperson's view!).

Putting the same into Google, I can't get any actual figures, but one book, Environmental Tobacco Smoke: Measuring Exposures and Assessing Health Effects (1986) says

...chlorogenic acid or rutin. These components are likely to be found only in trace amounts in ETS (Environmental Tobacco Smoke), and, thus, only minute quantities would be found in the circulating blood of passive smokers, making the development of assays difficult.
This source says
Since the phenols and polyphenols present in tobacco leaf play an important role in the curing and smoking quality of tobacco, a great deal of investigative work has been done on the estimation, separation, and identification of complex tobacco phenols such as rutin and chlorogenic acid. The presence of simple phenols in tobacco smoke was established as early as 1871. The phenol content of smoke became of increasing importance with the demonstration that phenol and substituted phenols can function as cocarcinogens; that is, they promote the appearance of skin tumors in mice following application of a single initiating dose of a known carcinogen. Furthermore, the smoke from one cigarette contains as much as 1 mg. of phenols.
I've done 12 pages of Google without coming up with any other figures than this.  Perhaps someone more knowledgeable will turn something up.

Julia 

Last edited on Wed Jan 31st, 2007 15:36 by Julia

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1mg.
OK, that's a good start. I had a quick look too, but decided that it was going to take a lot of my time, and it was a task I could 'delegate'. Thanks for helping out.

1mg inhaled, so there is no clearance by the liver before it gets to work on the cells in the lung tissue, is probably enough to start to affect the VDR (8nmolar) and even more easily the Thyroid-beta (0.9) and PPAR (4-7). Hmmm... How many folk have a 10-a-day habit? Hmm.. thats 10mg... certainly enough... hmmm...

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Some folks know that coffee and cigarette is an "excellent" connection :)

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Well, here's one done by the Chinese:

Capillary Electrophoresis with Chemiluminescence Detection of Rutin and Chlorogenic Acid Based on Its Enhancing Effect for the Luminol-Ferricyanide System

By: Suqin HAN, Anal. Sci., Vol. 21, p.1371, (2005).

Page 3, Table 1. States 8.90mg/gram of Chlorogenic Acid in their tobacco sample and 4.30 mg/g Rutin. I have no idea what Rutin is.  The graphical representation is right next the the table. I don't understand what table 2 means...."recovery".

It's hard to estimate the grams per cigarette, however I came up with 0.413g of tobacco leaf per cigarette in the U.S. using this pdf's numbers. The WHO foundation did the pdf. The WHO estimated that in 2000, 0.91 lbs of leaf were used in the production of 1000 cigarettes in the U.S. 0.91lbs = 413g. 413g/1000cigs=0.431g/cig.

So 8.9mg/g X 0.431g ~ 3.7mg of Chlorogenic acid per cigarette.

I would like to say that, that number varies due to decline in tobacco leaf in product over the years, and will vary widely from country to country. But for the U.S. this seems to be a good number.

Well, this is only a preliminary estimate. The number sounds good, but i'll need to find another reference hopefully to back it up. Maybe find an American tobacco sample number.

~Grego

Last edited on Wed Jan 31st, 2007 19:50 by tickbite

tickbite
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Scary! but uninteresting.

Engineering plants with increased levels of the antioxidant chlorogenic acid.

The goods:

This 1973 resource Correlation Between Chlorophyll and Chlorogenic acid content in Tobacco Leaves gives different tobacco plant strains and their respective levels of chlorogenic acid.....page 2, table 1. From 6mg/g to 17mg/g dry weight chlorogenic acid.........

So, 6mg/g x 0.431g(average tobacco leaf in cig) = 2.6mg of chlorogenic acid

and 17mg/g x 0.431g = 7.3mg of chlorogenic acid.......

it's going to differ brand to brand, country to country, plant to plant.

~Grego

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Tickbite,
I remember that when I 'had a hypersensitivity' for sidestream cigarette smoke, there was a huge difference between Asian/European cigarettes and American brands. Especially between "roll your owns" of rural Asia and processed cigarettes from the US manufacturers. So what you found all fits together, anecdotally, I guess. One remaining variable is how much of the chlorogenic acid is chemically changed by the heat of combustion so that it is no longer biologically active.

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No wonder I was craving apples there for a while (I don't even like apples all that much).  Could this be why "An apple a day keeps the doctor away"...at least temporarily?

Since the worst of the recent 12-day herx has passed, I haven't been interested in apples.  Perhaps an apple (or a cup of coffee) can be one palliative tool in calming a particularly bad herx without resorting to...whatever it is we might resort if we needed to temporarily shut down/dampen the immune response. 

Interestingly, I've gone off of all teas (never steeped them anyway) and coffee since beginning the abx--have no desire to ingest them.

Claire

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Claire,
Pure Quercetin is a palliative you will find in your MP guides:) It seems a much less aggressive and more certain path to palliation, when you really need it.

ps: some folk have found it exacerbates problems in early phase 1, so please be careful until you get your bacterial load down to manageable levels...

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Thanks so much for reminding me.  I think I am too early in the process (and having quite a time of it) to try the Q, but I do look forward to having another tool in the future.  Claire

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Thanks to my past carcinoid diagnosis, I'm aware of the fact that coffee, tea, eggplant, bananas, tomatoes and a few other foods contain amounts of serotonin. Because of that, these foods, but especially coffee and strong tea, have been off-limits many times in my past. I'm glad to learn about other substances and their effects.

Some carcinoid patients have excess serotonin and that causes eventual fibrosis of tissues, including the right valve of the heart, so tachycardia is an early but heart failure a late symptom. In the small bowel, symptoms start as IBS, but with progression one can end up with life threathening kinking and blockage. In the lungs, excess serotonin induces asthma like bronchospasms first, fibrosis later.

Excessive serum serotonin produces many unpleasant effects, so very early into disease, carcinoid patients show sensitivity to these foods, which increases as disease advances. Serotonin recycling/reuptake drugs are anatema (truly life threathening via a so called carcinoid crisis), but serotonin receptor blocking drugs are palliative to a carcinoid patient.

Since carcinoid and other neuro endocryne tumours are quite a rarity, vast majority of people enjoy the extra serotonin coffee and other foods deliver. I assume it is because of a stimulatory effect on smooth muscle and neural tissues.

I have not found any information on serotonin levels in Th1 diseases. But serotonin affects tryptophan and niacin levels and has many implications in the overall chemistry in the body. I wonder if there's a relationship between chlorogenic acid and serotonin, since some of the foods overlap.

Keep up the good work.

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Senja,
Seratonin is not the problem. We have just discovered the problem. Please just read what we are saying until we have finished working through the available science on Chlorogenic Acid.

tickbite
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I'm looking for cigarette smoke concentrations......it's a bit tough

found this enticing piece though:

The Chemical Compostiion of Tobacco and Tobacco Smoke

http://pubs.acs.org/cgi-bin/abstract.cgi/chreay/1968/68/i02/f-pdf/f_cr60252a002.pdf?sessid=6006l3

tickbite
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Well, crap. I can't find much from my end. Found this abstract:scroll to page 18.



A study of the degradation process of chlorogenic acid during pyrolysis.




Other than that, that's all i've come up with with a few hours looking. The answer is out there, the paper that I posted up above may contain the answer. However, since it's so old we need a librarian to get it for us (not electronic).




~G




p.s. chewing tobacco goes straight in I would guess....

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One more thing, how much of chlorogenic acid in cigarette smoke is inhaled and how much breathed out by smoker ?

Last edited on Thu Feb 1st, 2007 12:12 by wrotek

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Maybe we should be looking at serum levels in humans after cigarette consumption?

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could  you do that for lyrica they have molecule images on website.

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GulfVet,
Lyrica is a "small" molecule. It is therefore very non-specific in what it targets in the body. There are tens, probably hundreds of potential targets for a molecule that small. It would be a fruitless task to try and identify all the actions of Lyrica, including all its potential adverse actions.

When I gave my "Visiting Professor" presentation at the FDA I did include several drugs other than those of most interest to us, but it takes a long time to compute this, and I have decided that "small" molecules are a waste of time. Especially when I looked at the frequency and type of adverse events the FDA was listing for Lyrica. I would never use it, and I would never recommend its use.

Sorry about that.

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I know of the following source for much info about tobacco and ciagarettes:

UCSF's "the cigarette papers".  It contains original research the tobacco companies did a long time back, and its now been digitized.  But it does take time to wade through..I'll bet if you asked a librarian at UCSF they could help.

Sherry

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Dr Marshall, do You have some new interesting Ki numbers for chlorogenic Acid to share? :) VDR, beta thyroid were high, i wonder what is ther rest.

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From the piece on Wikipedia about antioxidants...

"Studies have suggested antioxidant supplements has benefits for health, but several large clinical trials did not demonstrate a definite benefit for the formulations tested, and excess supplementation may even be harmful."

Are the chemical structures of antioxidants similar enough to suggest that an antioxidant such as vitamin C can also affect the VDR?

Most doctors tell their patients to supplement with large amts of antioxidants ( I know mine did pre-MP!). It seems your findings confirm that this idea is harmful. Am I correct?

Would you recommend that consumption of antioxidants such as vit C also be kept under a certain level?

Thanks!

Amy

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So if there is a correlation of chlorogenic acid and chlorophyll in tombacco leaves, might there be that correlation to chloraphyll in other leaves (green leafy vegetables or wheatgrass- which I drink regularly)?  I hope not.

Thanks,
Norman 

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Norman,
Drink? I hope you eat green leafy vegetables, and not 'drink' them. If you are using prepared supplements or food concentrates you really need to discuss them with the moderators:)

Amy,
I am not sure how one establishes that a substance is an "antioxidant." Yes, I have seen the lab test, but am not convinced they are actually doing what biologists think they are doing. My methodology is to first look at the 3D chemical structure, and match up substances by similarities of size and charge in the molecules.

the structure of ascorbic acid, for example
http://www.hmdb.ca/scripts/show_card.cgi?METABOCARD=HMDB00044.txt
is nothing like chlorogenic acid
http://www.hmdb.ca/scripts/show_card.cgi?METABOCARD=HMDB03164.txt

So why would we expect them to function as analogues of the same thing, as 'antioxidants?' Maybe they do, but I remain to be convinced...

..Trevor..

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Yes Trevor what you say does indeed make a lot of sense!

After taking organic chemistry in college I got the impression that scientists DO try to classify molecules based on chemical structure, charge, size etc.

That's why I assumed that antioxidants would all possess a certain basic chemical structure that is modified in the case of each particular antioxidant.

I see now that in the case of antioxidants I am wrong. How silly that scientists/doctors have created a class of molecules that seem to have so little in common.

Thank goodness you are doing molecular modelling...your models provide the only valid feedback for my questions!

Thanks for getting back to me,

Amy

PS I will read more about antioxidants on my own. Because I have limited mental energy to spend on the computer and reading sometimes I assume things when I ask you a question. Hopefully I will make less assumptions as little by little I am once again able to read all the scientific papers my heart desires.

Last edited on Mon Feb 5th, 2007 15:28 by Ames

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Amy,

Vitamin C supplementation is mentioned in this FAQ. Funny how easy it is to believe the claims re antioxidants. Vitamin C is not stored in tissues so I believed it was harmless. It was one of the hardest supplements to give up (mentally) but I'm going great without it. :)

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Hi everyone,

While we are talking about ascorbic acid, I have a question about orange juice. How many cups of unfortified, real, organic, fresh orange juice per day is good to consume? I want to know what is the maximum limit for the most efficient use it's nutritional properties. I had no idea calcium doesn't occur naturally in orange juice. I'm also assuming fortification of calcium is probably not good that occurs here in the U.S.A.

What is the optimal amount of fresh, organic, unfortified, "virgin" juice and fruit in total we should be consuming? that may be a hard question to ask, but any rough ball park estimates? Our distant ancestors must have all eaten lots of fruit :? and probably started squeezing it for juice pretty quickly after we developed stone cutting tools :?. Some can't be all bad.

~Grego

 

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I had to weigh in on the calcium in the orange juice comment. 

I am becoming more and more incensed that while some (including some big business) want to regulate supplements in health food stores, big business is making all sorts of decisions about what supplements we will find in the every day foods we eat.  A matter that might best be made by ourselves or between us and our health care provider. 

As most of us know, when you suffer from a Th1 illness, lots of things that don't seem to bother other people bother us and discovering what those things are can be difficult.  It took me a long time to discover that increased intestinal distress was being caused by the then new trend to add calcium to everything.  Now, of course, it is D.  What is next?  It is so frustrating and maddening.  Perhaps this is the social issue on which I should concentrate my efforts!

Claire

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Trevor,

Well, I have been drinking wheatgrass for quite some time. I believe I have mentioned that before w/o incident. It is not a "prepared supplement" as I would normally think one would be catagorized. It is just young wheat, at the grass stage ( so there is no gluten, etc). It's full of chlorophyll, etc. Basically the grass is just pressed and then you drink a small amount of it ( approx 1 oz).

Is there any suggestion here that juicing raw vegetables can be bad for you?

Thanks

Norman
Moderator add: Why do I have to stop taking supplements?

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HI ALL

This is Fred in WV.  Clair said, "IT TOOK ME A LONG TIME TO DISCOVER THAT INCREASED INTESTINAL DISTRESS WAS BEING CAUSED BY THE THEN NEW TREND TO ADD CALCIUM TO EVERTHING. NOW, IT IS D.  WHAT IS NEXT?"  On the Today Show last week they had a segment about fortified foods, and they now want to add Omega-3 to a lot of foods.  Also, about a year or so ago I read in out local paper that they wanted to add potassium to everthing also. 

I agree with Clair that they should not add anything to our foods and let us make our own mind up as to get extra additives if we need they by buying it in a pill to add to our diets only if we need it.  The Today Show those people did say that we did not need the additives unless we did not have a good diet.

Also, we don't know how many out there that might have TH1 problems(additives puts all TH1 diseases at risk).  Remember, Dr Marshall told us once that the NIH started a study to see how many people had TH1 diseases and they found 50%-60% had them and they stopped the study.

Remember, we are all in this together and I am pulling for us.

Your friend in sarcoidosis

Freddie

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Maybe this is why nightshades are contraindicated for RA (and presumably all AI diseases) rather than their supposed vit D content:
http://www.noarthritis.com/research.htm

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Grego,

Orange juice isn't the best food from which to get vitamin C.  Just one cup of orange juice has more sugar carbs than my body can handle, and can't be a wise choice on a low carb diet.  It's the opinion of many so-called health experts, including the paleo 'experts', that fruit should only be eaten in limited quantities, because of its high sugar content, (and the fact that it wasn't available in the profusion it is now, and the fruits were smaller in paleo times), and that fruit juice is really unhealthy, because of the high concentration of sugar.  By the way even small amounts of sugars and carbs in foods like fruit, milk, grains etc. affect me, I know they are powerful chemicals.  (Doesn't matter if they're natural foods.  Granulated sugar gives me hives no more than milk sugar, or the carbs in grains.)

Besides all that, there is more vitamin C in many vegetables than there is in orange juice.  I think orange juice has only been promoted as the top food for vitamin C, because everyone is so addicted to sweet foods that it was an easier sell than broccoli.  A cup of fresh squeezed unsweetened o.j. contains 124 mg vitamin C, according to the USDA, but 1 cup of cooked broccoli contains 150 milligrams.  And, broccoli is much lower in pathogen feeding carbs.

But, take it all with a grain of salt, if you like.  One could possibly say I'm just jealous because you can eat fruit and I can't!  :D  Although, if you do the research, I think you'll find what I've said is correct.

Carol

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Ah yes...it's wonderful to add vit C to the list of compounds I was told to supplement with in extreme excess amts by my doctor pre-MP. Supplement happy doctors need to be stopped. I used to eat flavored vit C tablets instead of candy..1000's and 1000's of mg a day.

Meg, since starting the MP I only comsume a small amt of vit C present in the foods I eat..and of course I have only been feeling better and better.

I was just talking to my sister and she has a cold. She is taking high levels of vit. C. I said NO!!!! The idea that vitamin C supplementation can cure a cold seems like another convention that needs to be changed.

Amy

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The idea that vitamin C supplementation can cure a cold seems like another convention that needs to be changed.
But it works - why does it work?  My very healthy teenage son eats a good diet and hardly ever gets sick, but if the occasional head cold threatens he can greatly reduce or curtail it with 3gm vit C a day.  I taught him this in our some-supplements-are-good days, and it's the only supplement left in our medicine cupboard.  Please somebody, explain why it works :?

  Julia

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Is it really 'a head-cold', or is it something else?

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Ok....so is wheatgrass juice considered a supplement ? What about juicing raw vegetables- is that somehow considered taboo here? I would have thought it would be better for you. Does anyone know if wheatgrass juice contains any vitamin D? I have searched and not found anything to date.

Thanks,
Norman

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Norman,
Please do not spend our time complaining that your progress is not as fast as you would have liked, and then turn around and make semi-sarcastic comments about "taboo." Of course wheatgrass is a supplement. It is not the food of your grandmother (as Meg so aptly puts it). Similarly, juicing vegetables can increase the concentrations of individual ingredients to a level which your body cannot handle.

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Didn't mean to sound sarchastic...I just could not understand how a raw food could be considered a supplement. I have read here over and over that we should eat raw foods preferably, and organic as well if possible. So, I have tried to to that. I have talked previously to some of the moderators here and have recently stopped taking a protein powder because of that. I guess I was just a bit confused. Sorry to use the word taboo here. I was wondering, however, if juicing vegetables was ok or not. I guess it is not. Again, sorry to offend. Thanks

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Is applesauce okay? I've been eating organic applesauce for more years than I can remember. Not much, just about 2 T on my morning cereal, plus around 1/4 to 1/3 of an apple a day (with skin, no skin in applesauce).

Is this okay to continue on the MP?

I'm already struggling to give up tofu now, which I've eaten for a good 25 years, at least 175 g four times a week (and have added soy milk for cereal these past 10 years also). Not much of a coincidence, I think, that I've been getting sick with Th1 for 25 years also. But apples will be a hard one for me! (Coffee went away many years ago, as did tea, wheat, eggs of course, and recently nuts due to their arginine content.) Won't have much left to eat soon.

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A review of chlorogenic acid and genistein states:

Apples contain small amounts of chlorogenic acid. It is somewhat neutralized by an enzyme in the skin of the fruit. Eating these foods in moderation is fine.

What is your concern regarding arginine?

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Well, I guess 2 tablespoons of applesauce a day plus 1/4 apple sounds moderate to me, so will continue. Will try and vary it with different fruits in the summertime.

I've been having a lot of trouble with constant shingles outbreaks, which got worse when I started the MP. Over in my personal thread on the Ph 2 forum, Joyce Waterhouse suggested I take lysine and look at the arginine ratio in my foods. When I printed out a chart of the lysine/arginine ratio in foods I found nuts at the very top of it, and my favorites, which I'd been eating twice a day for six months or so, walnuts, at the very top of the chart. So having drastically cut that down, and the walnuts out altogether, I haven't had a shingles outbreak since doing so. I think she hit on something for me, there, as my lysine/arginine ratio was way imbalanced. So for now, nuts are not a possible snack food. Which is a drag when you're trying to focus on eating more protein, but the constant outbreaks were driving me crazy.

And now cutting out the tofu/soy is my next big challenge. I've been living on that for about 30 years now. It's not that hard, actually, and I will probably feel way better from doing so. So thanks, Meg, for all your info on that. I was being stubborn and a holdout, until I saw Trevor's explanation, then bingo, the light went on and that's the end of soy for me.

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I recently discovered Gogi berries and have been having about a  handful of them with my plain yoghurt and mueseli each day. Apparently, these berries have more vitamin C in them than an orange, more iron than a steak and have numerous health benefits. I just enjoy the tartness of the berries and since eating them have noticed increased energy levels and a sense of well- being, which I rather enjoy. Best of all though, I have not contracted any of the colds or flus going around to date, and I work in a very high - risk environment. I know that these berries are a powerful anti - oxidant, but I have not read anywhere about them being an immune modulator, although that could be a possibility, I am sure. I am hoping that the fact that I eat them in moderation will not hamper my progress on the MP.

Since I drink no coffee,only occasionally have steeped black or green tea and am a lover of rooibos tea ( steeped about 30 secs in a cup of boiling water) and eat no more than an apple a day, I am hoping I can continue enjoying the berries in my diet. I used to love coffee in my youth, but once I became pregnant with child number one, I went totally off it, and the desire to consume it, never returned. I do, however, enjoy a good cuppa herbal tea and a piece of dark chocolate here and there is a pleasure I would hate to give up!!!

My one downfall, is sugar - free chewing gum. I enjoy a good chew and find it aids with digestion, but I am concerned about the aspartime etc, but still feel I don't want to chew gum laden with real sugar. I know I should give up the habit completely, and I have tried, but since flying, it has returned. Is anyone else out there on the MP also a gum chewer?

I don't smoke, I don't drink, I try and eat healthy foods and buy a few organic products ( apples, being the main one), I avoid D foods like the plague, I gave up my vitamins and supplements, so I am really hoping that a few follies can still be enjoyed here!

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Kas,
When I look at all the stuff written about the 'nutritional' benefits of Goji berries, and I see they are part of eastern herbal medicines, I have to advise you to stay away from them. When you get symptom-free at later phases of the MP then you can enjoy them again, but right now, the ingredients I have seen listed on some of the suppliers' websites, and the list of immune conditions they are supposed to 'cure', make me draw back in alarm.

Click here for more info on antioxidents.

Last edited on Sun Feb 18th, 2007 19:18 by

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Kas,

Yes, I'm a gum chewer, and for the same reason as you, with the same worry as you.  I've tried to quit, but it helps my digestion so much that, if I try to stop, I end up taking baking soda several times a day, or Alka Seltzer, or chewing mounds of tums and I don't think those things, or prescription meds for digestion, will be any better for me.  Chewing gum works better than all those things too.  I'm hoping the MP will sove the problem, because I'm sure it's related to my IBS. 

Carol

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Thank you for the Goji berry information, Trevor. Do we have to be wary of all food used in Eastern herbal medicines? I will stop consuming my berries until I am further along the MP. I rather liked the fact that they are supposed to be so high in iron, help control blood sugar levels and support liver function, but at the same time, I do not want to mess around with modulating my immune system at this point of the MP. As I am still using my natural progesterone cream, it would be wise not to add more to the mix. Other than red meat, what are the best sources of iron from food?  I know about raisins and chocolate, but prefer not to consume too much in the way of sugary foods and my stomach does not do well with diabetic products.Also, how can we be sure that other food products we are consuming also do not modulate the immune system to some extent?

Glad to hear that I am not the only gum chewer out there, Carol. I guess if we do everything in moderation, it should not be too bad. I certainly do not chew gum all the time, or even every day, but I agree with you that it works wonders for digestive problems.

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Trevor's comment, "I see they are part of eastern herbal medicines, I have to advise you to stay away from them." would indicate that it seems wise to avoid all eastern herbal medicine.

Food sources of iron.

To be reasonably sure you are not consuming other food sources that may interfere with immune system function, eat nonprocessed foods close to their natural state and in moderation.

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How about soluble coffee, does it have chlorogenic acid ?

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Wrotek,
We do not have answers to every conceivable question. If you want to drink 'soluble' coffee then it is your responsibility to assess the relevance of the data we have gathered:):)

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Kas - I like to chew Jilla brand, here in Australia, but don't know what you'd get there. It has xylitol (and manitol, I think) but not aspartame. It's hard to find any "sugarless" gums without aspartame!! :X Is there anything wrong with xylitol for MPers? Gosh, I hope not. (We will be reduced to sucking our thumbs soon!):P

Trevor - I've been reading reports about studies showing that people who drink lots of coffee (and green tea) are less likely to get type II diabetes.  Naturally, they quote the scientists as saying "it MAY be the caffeine" but of course, they don't know exactly what is at work there... I am supposing it's the chlorogenic acid. Probably not so much preventing it as postponing it, I guess!

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If you delay the onset of cancer long enough then it just becomes a 'disease of aging', and not an 'unexpected' disease:):)

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Claudia,

I don't know how it is for MPers in general, but I get hives from xylitol, just like I do from sugar, and other high carb foods, so there is some property in common between them.  I have read that xylitol ferments in the small intestine and feeds bacteria there, causing small bowel intestinal dysbiosis, leading to gas, bloating etc., and it certainly seems to do that to me.  I personally believe it feeds bacteria all through the body, and that's why I get hives from it.  But, my theory there is only based on my own egocentric experience. :)

Carol

Claudia
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oh dear! :shock:  i was only trying to avoid cavities.  It doesn't seem to do me any harm and it keeps my mouth busy when I'm driving. I would only go through a pack in a month so it isn't likely to do me any harm. It has been purported to actually kill bacteria in the mouth and act against "bad" bacteria (like H pylori) in the gut, so it must be very active and therefore perhaps not a good mix with the MP...

But holy cow!  I went searching for more info and found some interesting references to xylitol potentially improving calcium-absorption in osteoporosis.  The scientists - as usual - have no idea really how this works and went on with much theorising and surmising, including many references to it possibly having some interaction with the various Vitamins D. 

Here is a link to one such story: http://www.vrp.com/art/717.asp

 

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Will chlorogenic acid displace Olmesartan from VDR, when Olmesartan Ki=10 nanomols and Chlorogenic Acid Ki = 8 nanomols ?

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I can see now (with the Molecular Dynamics) that Olmesartan actually has a higher affinity than is calculated by the static configurations. This is because the receptor changes shape a little to move into a shape which is a stronger fit with the Olmesartan molecule.

However, based on the numbers you cite, and assuming that the concentrations were the same, then about 50% of the Olmesartan would be displaced by the same concentration of Chlorogenic acid, as their KIs are essentially equal. Reemember the S-shaped curve from my FDA presentation:):)

wrotek
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So the static configuration does not include receptor "plasticity" ? Fascinating branch of science, especially when modeling molecule "behavior". Is there a special software for examining molecular dynamics ?

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Exactly, the conventional simplification is to assume that the receptor is fixed, not flexible. This gets you pretty close, in fact, close enough.

I would suggest getting familiar with the basic software before venturing into molecular dynamics:):):)

wrotek
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Dr Marshall i don't know if it is necessary or required but maybe if You lack of PC computing powers, we could join BOINC project (Berkeley Open Infrastructure for Network Computing) http://boinc.berkeley.edu/ .
There are many projects
http://boinc.berkeley.edu/projects.php
Maybe we could do some nice work with them :)

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I can see now (with the Molecular Dynamics) that Olmesartan actually has a higher affinity than is calculated by the static configurations. This is because the receptor changes shape a little to move into a shape which is a stronger fit with the Olmesartan molecule.

However, based on the numbers you cite, and assuming that the concentrations were the same, then about 50% of the Olmesartan would be displaced by the same concentration of Chlorogenic acid, as their KIs are essentially equal. Reemember the S-shaped curve from my FDA presentation:):)


So, if we will consume chlorogenic acid, won't we lose benicar protective blockade due to chlorogenic acid - benicar competition ?

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Yes, if the concentration gets high enough, the chlorogenic acid will displace Benicar from the VDR, exactly as too much 25-D would. You would thus lose the benefits from Benicar.

wrotek
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So maybe this is why i think i felt more pain in certain regions like legs, after drinking coffee and simultanously taking antibiotics. Hmmm.... Interesting.

But then from the other side i drank coffee because it made me feel better. So maybe it made me feel better when antibiotics actions subsided and worse when antibiotic actions kicks in.

Last edited on Fri Mar 16th, 2007 00:55 by wrotek

wrotek
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I wonder, how much coffee one has to drink to achieve the same chlorogenic acid concentration in the body as benicar concentration. Or there are too many things to take into account to assess this.

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In further to the discussion on drinking raw vegetable juices.  I personally went on the Linus Pauling programme a few years back ie taking copious quantities of Vit C per day (40-60gm)  This in turn made me extremely and violently ill.  To this day I can not take any Vit C supplements or foods with added Vit C.  I can not eat citric acid, tartaric acid, malic acid, lactic acid etc.  I can not eat any raw fruits except for bananas, melons, and lychees.  Most canned or frozen fruits are OK except for canned mandarin oranges, canned grapefruits etc. I have been putting red bell peppers thru the juicer as they give a sweet, pleasant tasting juice reminiscent of fruit juice but without the acid, but still having large amounts of Vit C.  Am I doing the right thing?

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Wrotek, PA,
One of the things about science is that it is a gloriously uncertain career. Managing the areas of uncertainty, such as the concentrations which any particular individual might be experiencing, is an art, and it distinguishes a good scientist from a great one. I have no hard and fast answers for either of you, just a wooly warm conceptual overview in my head that would take ages to try and put on paper. I hope you understand:)

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PA
FOOD TIPS  has Links to all Food Topics
Juicing vegetables can increase the concentrations of individual ingredients to a level which your body cannot handle.
Thanks, Barb ...

wrotek
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I see.

Frankly i have to admit i am scared to quit coffee now entirely because i am on so high doses of phase 2 meds.

What if this improve my bacteria killing significantly?

I think i remember that when i was in a hospital i quit drinking coffee, two days later i was taken off antibiotics because of strong reaction, vomiting, increased liver titers.

I don't know if i am right on this one and if I remember this situation well enough but i have a feeling,that subconsciously my body knows that when i quit i feel worse, maybe quitting coffee improved my innate immunity that time and caused that problems.

When i quit usually from time to time, after these magic two days, i have different symptoms like some heart irregular beat one or two, my body warms up and flu like symptoms increase. :)

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I am not medically qualified (my only experience is that of a fellow sufferer :) ) and definately not a scientist but would like to add to the discussion re juice.

One thing that I remember VERY distinctly in my what appears to be a far longer history of illness than I cared to admit at first...is that there was a moment in time (late 2002) when I first started to cough. At the time we had been on an almost raw food diet for several months and been drinking copious amounts of vegetable juice. I developed a fever, a cough and at the same time my blood pressure became high for the first time in my life and I became pre-diabetic. And almost at exactly the same time I developed a very strong aversion for vegetable juice. In fact the carrot juice I had been enjoying made me gag and I have never really been able to take to it in a big way since.

So...not sure if that was related to the diabetes but now I feel my body was telling me something already then...that these "power" foods / supplements were not good. I listened re the juice, unfortunately not re the supplements. And I also now know that this is when my Rickettsiosis first became an issue/ activated.

Not sure if this info is of use to anyone....but the previous posts made me think of it.

I understand Trevor's comments. Lots of things are "woolly". And the variables in this particular area are unfathomable! So bottom line is I guess....stick to what we know and experiment at our own risk :D

Inge. 

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Wrotek, Just wean the coffee slowly and you should be OK. If need be you can reduce the antibiotic dosages and/or take tapering doses of caffeine pills to help with withdrawal. best, P.B.

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The thing is P.Bear and i forgot to mention it, i drink mostly decaf LOL :) But of course decaf or not, i will quit definitely very soon. But i drink a little caffeinated beverages so they my increase discomfort.

I have a interesting idea. Since vitamin D has an effect on muscles,like Dr Marshal vit. d chart shows, i wonder if chlorogenic acid may have these muscle twitching
properties through VDR receptor, which are thought to be caused via magnesium deficiency( also thought to be caused by coffee). On the chart 1,25-D acts directly on muscles, so i assume through VDR.

Many healthy people experience muscle twitches after coffee, my father did :)

Last edited on Tue Mar 20th, 2007 09:20 by wrotek

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Wrotek,
Why do you assume your father was 'healthy,' as Th1 disease tends to run in families?

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Dr Marshall my father is not complaining about his health at all. Only my grandmother from the site of my mother had apparently Th1 disease, she had osteoporosis, "pains of unknown origin', facial pain etc so i am almost sure she was Th1. My father's family site does not suffer Th1 ailments. Interesting is that my mother is not sick also, thankfully. Maybe my grandmother became sick after giving birth to my mother.

With father we were just talking about muscle twitches i was experiencing that time, when i started being sick and when i did not know were they came from so i tried to explain them connecting to different things like coffee consumption, and he said he occasionally has or had muscle twitches following coffee ingestion, that's all.

Last edited on Tue Mar 20th, 2007 12:21 by wrotek

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Wrotek,
Based on what we know at this point in time, most of the population suffers from Th1 disease at some point in their life, and many die from it. Now that we understand Th1 pathogens to be behind cardiovascular disease, memory loss, hearing loss, vision loss, and a host of other "diseases of the aging" it is easier to see that the Th1 microbes have been around for a very long time, living in symbiosis with human beings.

During the 20th century a sun-loving lifestyle emerged, as well as Vitamin-D supplementation of foods, and inappropriate use of antibiotics. Together these factors caused a shift towards the survival of the symbiotic bacteria, and away from the well being of the host.

It is perfectly usual for people to not recognize they have a chronic disease. They don't, in fact, have a disease diagnosable by modern medicine. But the pathogens might still eventually kill them...

I hope this helps...

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HI WROTEK

This is Fred in WV.  With all the heart problems I have I want to add something here.  I get a Cleveland Clinic Health Advantage booklet every quarter and I received one yesterday.  I had been wondering for the last few months if TH1 caused aneurysms in any way.  Will here is what was in the booklet.

The exact cause of aneurysms is unknown, but risk factors include atheroscierosis(heardening of the arteries) and hypertension (high blood pressure).  Abdominal aortic aneurysms may be caused by an infection, a congenital weakening of the connective tissue of the artery wall or from trauma.

I have not looked at this site but you may find this info at                                clevelandclinic.org/health

So the infection I think is the TH1 diseases working on the blood vessels.

Remember, we are all in this together and I am pulling for us.

Your friend in sarcoidosis

Freddie

Your friend in sarcoidosis

Freddie

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I probably sholdn't even bother opening my mouth here, but I was just curious....if one was taking benicar on a continuous basis, wouldn't the benicar  "attach" to the VDR's so that the chlorogenic acid would have no place to attach? 

Say one took a benicar at 6am, then had a cup of coffee at 8am, wouldn't those receptors already be "taken" , again so that the chlorogenic acid would not be able to attach, or at least enough to make a difference? Just curious...........

Thanks,
Norman

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This is good question : I have another, what makes molecule leave receptor and when :) Maybe when concentration of other more compatible molecule rises pushing out less compatible molecule.

Last edited on Wed Mar 21st, 2007 07:47 by wrotek

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Trevor wrote:
The message for chlorogenic acid is much clearer, however. With Ki in the 8 nanomolar range, this is a good ligand of VDR, definitely active. The only things working to reduce its effect are bioavailability and clearance issues, which have been shown to vary 10:1 between individuals. Thus, the concentration in the cytoplasm is relatively imponderable, but anecdotal clinical experience confirms it is likely very active (IMO)
I have very strong reactions to a lot of foods with chlorogenic acid, so it is conceivable that I have a very low clearance rate. Now whether it is chlorogenic acid alone or some group of phenols with a similar mechanism of action remains to be seen. I do, however, have a couple of questions.

Wouldn't a substance which suppresses the immune system as does CA make you (that is, me) feel better? Is it because, as TM says, CA is also activating some of the other type I nuclear receptors?

Also, how do we know CA is not the tip of the iceberg-- and that there are not dozens of other substances that can interfere with healthy VDR functioning?

thanks,
Paul

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Paul,
The problem is that 1,25-D affects many other receptors, if its concentration rises too high. If the VDR is blocked, then there is no way for CYP24 to be made, and no way for the 1,25-D to be broken down to inactive metabolites. So if you are ill, and the VDR is blocked, the 1,25-D level rises very high and it knocks out the Thyroid and Glucocorticoid receptors, inter alia. There may be fewer cytokines, however, as many of them result from VDR expression.

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I drink a lot of coffee.

I have never been able to tolerate much in the way of abx because of the herx.

Is the coffee the reason?

I admit to some confusion, here.

madwolf

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Coffee would add an element of instability from day to day that would make things tough. That's why we suggest everybody pares right back to the Benicar and abx. It's tough to balance them to give the right level of immunopathology, and downright impossible if you add any more variables (IMO):)

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Sigh.

I'll start cutting back. It will take a while to get to zero.

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is there any way you can check olive oil for any immunosuppresant properties? ive always been suspicious about it.

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Not any that I can think of right now. I will keep it in mind as we move forward.

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oh, please, PLEASE don't find anything wrong with olive oil !!!

There are some things, like Motherhood, Swiss chocolate and olive oil, that are sacrosanct.  We've given up apple pie. That's the epitome of sacrifice.

:P

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Since everyone is in an asking mood, what about this new thing the media has been bleating about recently? Forskolin. It seems to be getting combined with antibiotic therapy to clear tough bladder infections. For those of us with considerable bladder involvement, it's something to wonder about. Any genomic data available on this compound yet?

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Knochen,
Forskolin enhances cAMP, which underlies the PKA signalling pathway through which several enzyme systems are enabled, including the CYP27B1 enzyme which converts 25-D to 1,25-D. Increasing CYP27B1 will not help folk with Th1 disease, they already have too much 1,25-D due to a dysfunctional VDR. Benicar makes the VDR competent again.

Summary:
There is a difference between healthy mice and sick people:):)

See? It's soooo simple....

Knochen
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Benicar makes the VDR competent again.

Boy, if it ever gets around at work that I am incompetent all the way down to the cellular level, it's gonna take a long time to live it down.:cool:

Thanks for the rundown on forskolin. That's why we ask the experts! I figured it would come up on the board eventually.

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I see an article in my local paper today stating that cocoa could be good for lowering blood pressure. http://archinte.ama-assn.org/cgi/content/abstract/167/7/626

I wonder how that fits with our usual low blood pressure symptoms? After tea and coffee and chlorogenic acid, cocoa was sounding pretty good to me!!

Moxie

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Moxie,
I drink a lot of (Quality) Dutch cocoa, and have done all through recovery. I doubt it does any harm, and the warm boost it gives to one's morale is often immeasurable.

Do be careful if you use powdered milk in the cocoa mix. Even in Oz the powdered milk is 'fortified' with Vitamin D. In the US you can get unfortified powdered milk from
http://tinyurl.com/ys2bas

wrotek
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What to drink cocoa with if milk is prohibited ? Raw ? For now i drink it raw :)

Last edited on Sun Apr 15th, 2007 00:48 by wrotek

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unfortified rice milk

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Rice milk ? Never heard of it. Every food is in America isn't it :)

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A little bit of unfortified powdered milk in cocoa will probably not hurt you...

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The Diploma skim milk powder I bought here in Australia states: No preservatives; no additives; and as ingredient it just says : Sim Milk.

Can I assume that this means it is not fortified?

Also...the rice milk and oat milk for sale in Australia has sunflower oil added so not a good milk replacement.

Inge.

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Wait a minute - what's wrong with apple pie made (by me) with unfortified flour and organic butter? Not every day of course, but at holidays. Is it the apples?

I know this isn't a really important issue, but it's the one dessert I can make without any sugar.

Thank you, Kathleen

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Everything is OK in moderation, Kathleen. the cooking might reduce the 'acidity' of apples, in any case. Additionally, a lot of the chlorogenic acid is just under the skin (to protect the fruit from intruders, I guess).

Good Heavens! We have to leave 'Motherhood and Apple Pie' intact :):)

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I see there is a lot of alternatives for cacao
;)
I never liked eating apples with the skin, always removed it.
Does Chlorogenic acid is an ingredient responsible for coffee acidic taste which some people don't like very much ?

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No idea, sorry, Wrotek.

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To Trevor re your posting of Jan 28 '07 at 16:48 about your use of Splenda (Sucralose) sweetener.

[In my daily cocoa cup, I use stevia with inulin or with maltodextrin]

I always felt uneasy about the chlorine atom substituting for a carbon atom in the Splenda molecule. What I saw at mercola.com gives me even more concern

Last edited on Sun Apr 15th, 2007 14:37 by

Prof Trevor Marshall
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Dr Joe Mercola is a well-meaning and thoughtful physician. He gave us valuable help back in 2002, publishing the "Remission from Sarcoidosis" article on his website when nobody else would listen. Unfortunately he has failed to keep pace with the advances in scientific knowledge over the last five years. He is just plain wrong about the biological effects of Splenda. I am sorry that his writings on that topic have caused you un-necessary concern.

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I was about to jump in here to recommend people suffering coffee and tea withdrawals try the Celestial Seasonings Caffeine-Free Tea substitute. Really tastes like proper English black tea when doctored with a dab of honey and D-free milk. I've been enjoying it almost nightly for awhile now.

But examining the ingredients I am horrified to see hawthorn berries right in there as one of the main ingredients. The foods list says hawthorn is not advisable while on the MP. Dr. D'Adamo (the Eat Right 4 Your Blood Type Diet naturopath) says hawthorn is the most beneficial herb for Type A's (which I am), and he cannot recommend it highly enough. I wonder why it doesn't work on the MP? Any insights?

Oh well, so that goes in the bin along with everything else now.

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Joy,

I'm sure you already know this, but I don't think it's the caffeine per-se in tea and coffee but the chlorogenic acid.

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So what is the word on Stevia? I cannot use splenda. Jeannine

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Tickbite,

Yes, I know that. This is just something I've used as a substitute for some years now because I can't tolerate caffeine. For a good 20 years I've gotten rapid pulse and heartbeat from it. Even 1/4 cup Starbucks decaf will keep me up till 4 a.m. I've never known why before, but my mother is also equally sensitive to it.

Funny, though, as I used to handle it just fine when I was younger. About 20 years ago I started to not be able to handle it (concurrent with the onset of RA and other Th1 illnesses -- coincidence??)

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Hi Jeanninehope: here is more info
Sugar Substitutes on stevia and other substitutes. Neither Stevia nor Splenda are contraindicated on the MP. Regards, Inge.

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Maybe decaf has some caffeine in it after all ?

Withdrawal is from caffeine, so i don't understand really using any caffeine free substitutions to decrease withdrawal symptoms.

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Wrotek.
No, withdrawal is from anything your body (or mind) has become dependent upon. For example, one's body has withdrawal symptoms from prednisone, and one needs to wean very slowly...

Similarly, one would need to withdraw from Chlorogenic Acid, if one had been ingeting it in sufficient concentrations to have been suppressing the immune system...

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Wrotek,

I'm not so sure withdrawal is solely from the caffeine. Obviously the CGA was sort-of modulating your herx too. Which would mean that the withdrawal symptoms for Th1 sufferers would be a tad more than usual :) I couldn't imagine what those pots of coffee some of us were drinking was doing to their recovery progress......

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Very interesting idea that chlorogenic acid can so be addictive :). I wonder if it is addictive to healthy people as well.

It would explain why people trying to quit coffee, switch to decaf.

Last edited on Wed Apr 18th, 2007 08:00 by wrotek

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there is also the taste thing! If you like coffee but want to give up caffeine then decaf at least still has the taste...nothing else is quite like it....hot chocolate is too sweet and herbal teas are just not the same...neither are the herbal coffees...unfortuantely doesn't help us.....they don't  make caffeine free and cga free and probably by the time that is extracted you won't recognise the taste anymore :D Inge.

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Thanks Inge for the link....However I was referring to the content of Chlorogenic Acid in Stevia as it is from a plant...Guess I should have been more specific...but the link helped

I know things in moderation are ok....but just wanted to see if anyone else had anything to say about the Chlorogenic Acid level in Stevia....

I found a scienific article but I dont have access to it...

http://www.springerlink.com/content/j2573u7341495341/

....I did find this on the web...

http://www.rain-tree.com/stevia.htm

I guess with the amount of steiva on would use that it might not really matter??

Just interesting......Jeannine

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It's called water people, dang! :) haha. Someone has always gotta be trying to drink something other than water! It's only temporary!

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Joy,

Folks are advised not to take hawthorn supplements because they might lower blood pressure. I doubt the amount of hawthorn in a cup of tea is enough to be of concern. :)

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Thanks, Meg. I may continue with it, then, just occasionally. It gives your mind and taste-buds the feeling of drinking something like real tea, and I do miss my English tea. Probably wouldn't do much physically for a caffeine/CA withdrawal, but at least you're drinking something similar this way and don't feel quite as deprived.

The ingredients are:

Blackberry leaves
roasted chicory root
hawthorn berries
beet root
natural tea flavor
hibiscus flowers

Hopefully the blackberry leaves are okay? Someone said blackberries may contain chlorogenic acid, hopefully not the leaves?

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And apples too?!!  Dang.

Dody

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Is garlic safe??? We eat lots of it in our family. Hubby's cholesterol is a bit high and he won't take statins. His dad had heart problems his whole life (well from his  30's on). I've heard that garlic is great for heart disease.

Much thanks,

Martha

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i'm getting confused by reading all of this.  Will a few cups of coffee a week interfere with  my progress on the MP?  It helps to keep me awake when I need to do something.  What does it do to the 1,25 d level?

thanks lisa

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A few cups a week is fine. Two cups a day is marginal:) A few cups every day might be a problem:)

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thanks so much for simplifying it for me.  Sometimes my lyme brain can't understand all of the science stuff :)

lisa

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Greg found this really interesting study :)

Caffeine decreases vitamin D receptor protein expression and 1,25(OH)2D3 stimulated alkaline phosphatase activity in human osteoblast cells.
http://tinyurl.com/2dzdn7

"Caffeine dose dependently decreased the 1,25(OH)(2)D(3) induced VDR expression and at concentrations of 1 and 10mM, VDR expression was decreased by about 50-70%, respectively."

Last edited on Mon Apr 30th, 2007 08:35 by wrotek

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Wow, and Thank you.

The levels of caffeine quoted in this study would translate to how many cups of weak green tea?  Steeped 15 seconds?

Sherry

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Good question, how much coffees too.
Here is full text http://tinyurl.com/ytdreo

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I am very curious, how much CGA is in tea ?

Last edited on Tue May 1st, 2007 17:09 by wrotek

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I can't tell you the amounts.  I just know that when I made strong tea (soaking one bag for several minutes) it seemed to react almost as strongly as some coffee we got from a donut place.  I'm sure different teas and coffees differ and would give a range of values.  And weak tea (only steeped about 15 seconds) was less reactive, but still way up there.

Joyce

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Reverting way back up to the study on caffeine/alkaline phosphatase/bone status:  Aren't there too many variables in peoples' status relative to 1,25 D levels, alkaline phosphatase level and maybe even VDR genotype, to take anything concrete from the study to use upon ourselves?  I would think they'd be starting with subjects who had 'normal' levels in those areas.

I'm wondering if, like so many studies, what means one thing for one individual, may mean something entirely different for another.  As a very primary and somewhat unrelated example, but to explain my slant on this:   I used to take a lot of vitamins/supplements, because I'd read this or that study that said, a particular vitamin was good for this or that part of the bodily system.  After years of taking these supplements, and then having some testing done, I found that I'd gotten myself out of balance in many areas, with too much of this or too little of that in my system, and it was causing material results in my body.  In other words, the studies I was reading only applied to people who had certain base chemistries, presumably 'normal' or average ones, and my chemistry was not normal or average.  (Possibly because I had Th1 disease through the whole time.)  So I was taking a lot of things that were making my situation worse, and vice versa, not taking things I really needed. 

Healthy people need certain levels of 1,25 D and alkaline phosphatase, but if you're not starting out with healthy levels, how does that affect what you carry away from the study?

Maybe I'm missing something here, but I found the abstract inconclusive for me, especially when I read the long version. 

If you see something wrong with my reasoning, let me know, I'd really like to fully understand the abstract and its meaning for us.

Carol   

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Joyce,
Thanks for collating this list of foods. Not all of us have a reaction to foods, but when I was ill, I remember that the foods which used to give me the worst migraines are roughly in the same positions on your list (at the top) as I remember I used to rank them.

I don't know whether these foods would affect bug-killing in any way, in any case I remember that I wasn't so worried about long-term prognosis when lying on the bed for 24 hours wating for a paralytic migraine to ease:X

Once you eat a balanced diet, with a moderation of Vit-D-supplement-free cheese or yoghurt, a moderation of greens and fruits, and a moderation of other proteins, you should be able to avoid the ups-and-downs that excesses can cause.

The body can make many things by itself. Certainly the human body can make all the Vitamin D it needs by itself, and no supplementation is necessary, or desirable. But a healthy body needs a good balanced diet, with everything in moderation.

As to "How Much?" the answer is fairly simple. If you can go for 24 hours without feeling the need for more of something, then you are probably not addicted to it. If you absolutely have to have 3 coffees a day to avoid withdrawal, then you have a problem. One a day is fine. Two might be OK. Similar for juicing. If you can allow your digestion to settle 24 hours between cups then you probably are not having too much, and haven't developed a dependency (remember not to replace the coffee with pomegranate, for example, the effects of CA would be cumulative across all food intake).

Last edited on Fri May 4th, 2007 00:14 by Prof Trevor Marshall

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Joyce,

It seems that if we eliminate everything with vitamin D and Chlorogenic Acid, there isn't much left to eat - at least in terms of any generally recognized well balanced diet. :(  It seems now that fish green leafy vegetables, berries and a fair amount of fruits are now not recommended here. It seems ( no offense really) that we might make a list of foods that we can eat. It's SOOO frustrating!

 My belly aching aside, I'm wondering what effects you and others are noticing when ingesting too much c. acid? I'm trying to understand what this c.acid is doing. Is it giving people bad side effects ? If so, what types of affects so I can see if I am being affected ? Also, it seems that this acid could be a reason why some are not seeing faster results with the MP, is that what is being suggested?

As for my progress, it seems to be very slow now, but was QUICK and fairly dramatic for the first 6 months ( not just about 2 years into it) , but then things tapered off after 6 mos to a year. Even then my D levels were high - initially 68/32. The last test was 27/ less than 5 , and my diet hasn't changed except for eating less D and staying out of the sun. So I guess I am wondering how much importance we have to place in this vs vitamin D levels and other dietary considerations. I'm just wondering where the powers that be feel this fits into the overall treatment.


Thanks....hope I worded so as to be inquisitive, but fair.

Last edited on Thu May 3rd, 2007 07:24 by norman

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Isn't decreased VDR expression always a bad thing, regardless of person?

If this is so, then I wonder why lithocholic acid (LCA), a potent VDR ligand, still induces colon cancer, despite the increased immunity.

http://www.oncolink.com/resources/article.cfm?c=3&s=8&ss=23&id=8406&month=05&year=2002

Could someone knowledgeable comment on LCA because a high-fat diet increases it and they say in this article that high-fat diet should be avoided because of that.

Also, I vaguely recall reading something like apples having 1/5th or 1/10th the amount of chlorogenic acid compared to coffee so it should be a minor problem. But maybe it isn't.

Last edited on Thu May 3rd, 2007 10:49 by Jacko

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Norman,

Joyce said,

Due to my extremely high sensitivity, I am going much farther in avoidance, at least temporarily, than most people would need to. At present, I limit myself to the foods without any chlorogenic acid. Most people on the MP would probably only need to avoid getting a very large amount of chlorogenic acid. My thought is that people who are advancing very well on the MP may not need to change their diet at all.
Rarely would someone need to alter their diet this extremely. Moderation is the key to consumption. Please see Chlorogenic Acid.

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Jacko,
I suspect that study is flawed. For a start, they didn't measure (or consider) the PXR receptor. That imperils just about everything they did, and all they concluded. Sometime I will get around to taking a closer look.

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Well...Thank You

I was doing just fine on the phase 3 abx when one morning my husband was making his morning coffee using the expresso machine - he has this coffee ritual. I don't know why but I saw him mixing his elixir with absolute ecstasy and thought why not so I asked him to make me a cup. He looked at me with this 'are you sure about this' look on his face and I thought it can't do any harm. I only drink tea and I stay away from the green - I already had some bad reactions from the green.

Well holly cow! I had symptoms soon afterwards and I mean really bad. that was three weeks ago. As the symptoms waned I have been sleeping like a baby though. The coffee was delicious; was it worth it? Nope. All this at the tail end of the abx too. Now I know why - thanks!

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I have found a very large(involving 1,514 men and 1,528 women = 3000 people!), interesting study about positive association between coffee drinking  and inflammatory markers .

An abstract (and full version )  http://www.ajcn.org/cgi/content/abstract/80/4/862

And here is the same study different article with nice comparison table between coffee drinking and inflammatory markers http://www.ajcn.org/cgi/content/abstract/80/4/862


Coffee mostly increases Interleuking 6 production.
This quote is from full version of the article
In the present work, we report a positive association between coffee consumption and IL-6 concentrations. It could be hypothesized that coffee increases IL-6 synthesis, which then affects CRP and SAAproduction in the liver.TNFis also involved in the acute-phase protein synthesis, but it was suggested that only IL-6 can stimulate synthesis of all acute-phase proteins involved in the inflammatory response—namely CRP, SAA, fibrinogen, and others (23). So coffee increases directly IL-6 and then the rest happens

Now it starts to be interesting.

When i was reading about Interleukin-6  http://www.thefutureforum.com/EmergingRiskMarker/Interleukin6.aspx

i have found this, just at the end of the article in "Perspective Treatments section"
Statins have been shown to reduce IL-6 levels in patients with familial and non-familial hypercholesterolaemia, and in individuals with obesity (Int J Cardiol 2001;77:247-53; Arterioscler Thromb Vasc Biol 2002;22:1194-9; Clin Chem 2002;48:877-83; Atherosclerosis 2003;169:283-91; Horm Metab Res 2003;35:479-85). These studies all used simvastatin or atorvastatin. However, atorvastatin did not reduce IL-6 levels in patients in the MIRACL trial, all of whom sustained a recent acute coronary syndrome (Circulation 2003;108:1560-6).

 Patients recovering from an acute coronary syndrome have shown a reduction in IL-6 levels in response to cyclo-oxygenase-2 inhibition (rofecoxib; Chest 2004;125:1610-5). In addition, the angiotensin receptor blocker irbesartan, has been shown to reduce IL-6 levels in patients with CAD, who have undergone angioplasty (J Am Coll Cardiol 2004;44:362-8). In poorly controlled diabetics, improvements in glycaemic control also appear to reduce plasma IL-6 levels (Diabet Med 2003;20:930-4).

Both simvastatin ( atorvastatin did not reduce IL-6 levels)and irbesartan have been associated with a deacrease in IL-6 production and identified as a VDR agonist by Dr Marshall, which can be read in here http://curemyth1.org/view_topic.php?id=39&forum_id=2&highlight=simvastatin

Is it probable then, that inflammatory markers increase resulting from coffee consumption, is from chlorogenic acid content  and it's antagonistic properties on a VDR ?


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Sedona, do You have any reactions like these after black or green tea ?

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hi,

does drinking coffee make the MP not work?

thanks

lisa

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Lisa,
Being addicted to coffee generally indicates a physical need for its immunosuppressive properties, which will slow the ability of the MP to restore your immune system.

The paper just cited by Wrotek says that amounts under 100ml a day should have little effect. I guess that's about one smallish cup.
 

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Wrotek asked "Is it probable then, that inflammatory markers increase resulting from coffee consumption, is from chlorogenic acid content  and it's antagonistic properties on a VDR ?"

The answer is not simple. The human immune system consists of many inter-dependent activities, and when the innate immune response is inhibited, whether by Th1 disease or by a drug (eg Chlorogenic Acid) then a cascade of actions will occur downstream amongst the cytokines. In the past I have taken the position that this immune cascade is imponderable, and have focused on the innate immune defect, which has turned out to be solvable. Once the VDR is restored to competence, the rest of the immune system also returns to balance.

What I mean by "I have taken the position that this immune cascade is imponderable" is that I consider it a waste of time to concentrate on the Trees, instead of standing back and observing the Forest.
 

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I see.

Dr Marshall do You think these two compounds may have some VDR activity ?
http://www.food-info.net/uk/products/coffee/kahweol.htm

Their shapes are somehow similar to steroids i think.

Last edited on Fri Dec 7th, 2007 03:03 by wrotek

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They look too rigid.
But the only way to be sure is to run the computations, and I am too busy to do that right now.
 

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I wish i knew how to run computations :) Btw it would be nice to start a global project  (like SETI) to search for VDR ligands

Dr Marshall  is there any plug and play computation software ?

Last edited on Fri Dec 7th, 2007 03:09 by wrotek

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You folk want answers sooner, rather than later, so the infrastructure built by SETI would be a hindrance, rather than a help.

Look at  http://www.Gromacs.org
That is the molecular dynamics software, it is open source.

..Trevor..

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Thank You Dr Marshall i will do some reading.

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I don't know how important it is, but cafestol has been identified as a agonist for nuclear receptors, Farnesoid and Pregnane X Receptors (FXR and PXR)
http://mend.endojournals.org/cgi/content/abstract/me.2007-0133v1

(PMID: 17456796 [PubMed - indexed for MEDLINE])

I know also that relations between nuclear receptors exist, and are very complex .

Also Cafestol, a diterpene present in unfiltered coffee brews such as Scandinavian boiled, Turkish and Cafetière coffee, is the most potent cholesterol-elevating compound known in the human diet.
It is i think very important to notice, that cafestol and kahweol are exclusively present only in coffee, no where else, which cannot be said about chlorogenic acid.


http://ntp.niehs.nih.gov/ntp/htdocs/Chem_Background/ExSumPdf/Cafestol.pdf
Cafestol and kahweol, which are naturally occurring diterpenes found only in coffee,

I have also noticed that FXR, PXR, VDR are all a bile sensors.
http://www.kumc.edu/pharmacology/Pei-zhen_Song.html The bile acid sensors that have been identified include FXR, PXR, and VDR. FXR is the major bile acid sensor.
It is just a common sense, but i think that messing additionally with nuclear receptors cannot be a good thing :)


Last edited on Tue Dec 11th, 2007 00:06 by wrotek

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The Pregnane X Receptor, PXR, is in the same sub-family as VDR and is key to balance of the D metabolism. Our new paper, which I will be able to put on the web at Christmas, goes into its role in some detail.

PXR is a receptor which is believed activated by quite a number of molecules, including Rifampin, the primary antibiotic used in Tuberculosis  therapy.

PXR downregulates CYP24A1, the enzyme that breaks down 1,25-D into inactive 24,25 and 25,26 metabolites after the VDR has done its job. It is also responsible for transcribing the CYP27A1 enzyme that changes Vitamin D to 25-hydroxyvitamin-D.

25-D and 1,25-D both block the actions of PXR, regulating the enzymes to maintain balance. All this is shown in Figure 1 and Figure 2 of the new paper.

So any chemical which activates or deactivates the PXR directly affects the D metabolism, and the transcription of thousands of genes.

Thanks for the tip, Wrotek. I will look more closely at cafestol...

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http://en.wikipedia.org/wiki/Cafestol
coffee is 0,6% cafestol by weight.
I have measured my cup of coffee  and it weights 9,300mg. It means that in one cup of coffee there is 55,8mg of cafestol.

I wonder how strong affinity of this ligand is and how strong it's actions.

Dr Marshall i have found Your post in this topic http://tinyurl.com/2a7wqw about cyp24a1
-------------------------------------------------

Ruth,
The mechanism is simpler than that.
I have just written a review paper (which will hit print later this year) which explains it all in some detail, but briefly, if you were a persistent intracellular bacterium it would make sense for you to want to evade the immune system. Imagine your surprise when you found you could knock out both the Cathelicidin and beta-Defensin anti-microbial defenses by blocking the operation of just one receptor, the VDR!

When you block the VDR you interrupt the down-regulation of the production of 1,25-D (via the CYP27B1 and [highlight= rgb(255, 255, 136);]CYP24A1 metabolisms), and therefore the level of 1,25-D rises to dangerously high levels. This in turn depresses the transcription of CYP27A1 by the PXR receptor, lowering the level of generated 25-D, but that doesn't worry you either (the bug).

However, the high level of 1,25-D also interrupts the PXR receptor transcribing a number of Xenobiotic enzymes (detoxifying enzymes)(pXr) as well as CYP27A1. This is not good for the safety of your host. The high 1,25-D levels also stop the Thyroid and Glucocortiocid receptors from working properly, as well as GPCRs in, for example, the retina (Rhodopsin). But again, this doesn't affect the bacterium, only the host. The trick is to make sure the host just stays pretty sick, but doesn't die...

It would be a neat plan of action, don't you think? The only problem might arise if a VDR agonist happened on the scene, capable of displacing your ligand from the VDR, making the VDR work properly again, and restart transcription the genes producing those nasty anti-microbial thingys...

..Trevor..
-----------------------------------------------------------

very complex and difficult :(


Last edited on Tue Dec 11th, 2007 02:07 by wrotek

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very complex and difficult
No, very interesting and exciting :):)
 

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:) So we have a chlorogenic acid which decreases competence of VDR by binding to it antagonistically, and cafestol which increases  1,25-D.  Both reactions we try to reverse with MP, i think ?

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Perhaps this can be an interesting lecture.
Selective activation of vitamin D receptor by lithocholic acid acetate, a bile acid derivative

http://www.jlr.org/cgi/content/full/46/1/46#FIG2 http://www.biochem.wisc.edu/courses/biochem911/materials/readings/Adachi.pdf
(first link stopped working somehow)

And other fresh 2008 study http://tinyurl.com/2h74kh

Lithocholic acid derivatives act as selective vitamin D receptor modulators without inducing hypercalcemia.
Ishizawa M, Matsunawa M, Adachi R, Uno S, Ikeda K, Masuno H, Shimizu M, Iwasaki KI, Yamada S, Makishima M.
1alpha,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], a vitamin D receptor (VDR) ligand, regulates calcium homeostasis and also exhibits noncalcemic actions on immunity and cell differentiation. In addition to disorders of bone and calcium metabolism, VDR ligands are potential therapeutic agents in the treatment of immune disorders, microbial infections, and malignancies. Hypercalcemia, the major adverse effect of vitamin D(3) derivatives, limits their clinical application. The secondary bile acid lithocholic acid (LCA) is an additional physiological ligand for VDR, and its synthetic derivative, LCA acetate, is a potent VDR agonist. In this study, we found an additional derivative, LCA propionate, is a more selective VDR activator than LCA acetate. LCA acetate and LCA propionate induced expression of the calcium channel transient receptor potential vanilloid type 6 (TRPV6) as effectively as that of CYP24A1, while 1,25(OH)(2)D(3) was more effective on TRPV6 than on CYP24A1 in intestinal cells. In vivo experiments showed that LCA acetate and LCA propionate effectively induced tissue VDR activation without causing hypercalcemia. These bile acid derivatives have the ability to function as selective VDR modulators.
PMID: 18180267 [PubMed - as supplied by publisher]

Detection of lithocholic acid in multiple sclerosis brain tissue
http://www.springerlink.com/content/q145g045j1712g51/

Lithocholic acid can carry out in vivo functions
of vitamin D

http://www.pnas.org/cgi/reprint/0703512104v1.pdf?ck=nck

LCA is poorly absorbed so it is likely that 10 g per day is absorbed. From these calculations, it would appear that LCA has in vivo activity of 1/1,000 that of 1,25-(OH)2D3



Last edited on Thu Jan 10th, 2008 11:29 by wrotek

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The role of the bile acids acting on the VDR is why I believe my immunopathology increases during the period following a meal with fat in it (peak effect is 50-90 minutes after the meal).  I wonder if that is part of the reason why I used to think I felt better when I ate a low fat diet.  I would not expect everyone to react this way, as there might be differences in levels of VDR blockage/activation.

I have mentioned this effect in my PR:  Joyce Waterhouse's Progress Report

Joyce Waterhouse

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I thought only 1,25-d can activate VDR.

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Lithocholic acid seems too large and too inflexible to agonize the VDR. On the other hand, it could well be a ligand for VDR's sister, the PXR (Pregnane Xenobiotic Receptor) which has a more promiscuous binding pocket.

Wet biologists would probably not be able to notice the difference, especially if they were following the methodology outlined in the paper Joyce cites. In other words, I think they made a mistake saying that Lithocholic acid is a VDR agonist. It may well affect gene expression via PXR or some unknown secondary mechanism, but I would want to see it dock into the VDR before declaring it a VDR agonist.

Figure 1 of my soon-to-be-on-the-streets new paper goes into the role of PXR in more detail.

I am at a conference this weekend, so I can't do any checking beyond what I have already done - the conclusion of which was that the study cited by Joyce drew its conclusions in error.

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I have been reading about a new patented supplement called AC-11 on the market that has in contrast to many, been through some controlled research studies. It is touted to improve DNA repair by around 10%, increase apoptosis in a cancer cell line (HL-60) massively, increase lymphocyte production around 8%, and reduce lipopolysaccharide induced TNFalpha production by between 65-85%. The LD50 is greater than 8g/Kg so it is very non-toxic.
 
Could we be looking at a VDR agonist here? The proposed ligand would be a building block of the aqueous extract from Cats Claw called quinovic acid:
 
http://pubs.acs.org/cgi-bin/abstract.cgi/orlef7/2004/6/i18/abs/ol048787b.html
 
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=1367339&dopt=AbstractPlus
 
By the way even if it does not activate the VDR does activation of the VDR by 1,25D or Benicar improve DNA repair processes? - if so I presume that would not include mitochondrial DNA?

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NickBowler,
It is absolutely essential than someone on the MP not take any supplements or medications without first checking with the moderators. In the unlikely event that the supplement actually does what is advertised, and your body's  immune system is restored in some way,  the results could kill you.

IMO, this is what happened in the TeGenero study.

For the last couple of days I have been getting my mind around DNA repair, and other advanced genomic topics, at a conference at the Salk Institute led by two Nobel laureates in the field of genomics. Please do not believe anything you read about cat's claw, or any other sort of claw, as correct and definitive. There are very few people in the world that have the capability of truly grappling with that topic...

As for believing something because it is published in a peer-reviewed journal, well, you are all still ill, despite decades of papers being published about your condition. Do you really believe that any of those authors really knew what they were doing? Or their peer-reviewers?
 

wrotek
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Dr Marshall, is this like molecule has to have broken 4 steroid ring structure, so it could change alignment inside LBP, to switch the VDR on ? I understand that rigid 4 steroid ring structures can anter LBP but are not enough flexible to do their job, so i wonder if 1,25-D has to take similar to 4 ring tight shape before entering LBP.

Can we somehow see entrance of the receptor and inside of the walls of VDR LBP ?
I would be nice to see total video of 1,25-D entering the receptor and aligning inside.

When i look at conformation of 1,25-D inside receptor, i see that it is "stretched" through this one broken steroid ring.

Photograph taken from http://www.rcsb.org/pdb/explore.do?structureId=1DB1

NickBowler
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O no, you misunderstand me, I have no intention of volunteering myself as a guinea pig with this new supplement, I am just fascinated by the whole unfolding science. If this product does have vdr activity then it ought to be pointed out to the manufacturer what the implications might be as it may have potential (when properly studied of course). And the whole concept of possible DNA repair in relation to the VDR modulation is a whole new dimension to the science that you are pioneering is it not?

Claudia
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Earlier you said that CA is "cumulative" so I am wondering how long it takes to get it out of our system? I absolutely love coffee and for years I have known it is bad for me. :(:(:(The first time I was told to stay away from coffee it was by a chiropractor/natural health practitioner back around 1980. She said, "It will interfere with your immune system." Too right. If I have just one cup, I feel wonderful and am bouncing off the walls for at least 12 hours (which means if I have coffee with dinner, I'm charging around the house untill 4am - LOL). I try to limit this sort of personal excess (to anyone else it would be a trifle) to once a week and probably shouldn't do it at all.

Anyway, the question is, I know the caffein wears off in a matter of hours, but is the chlorogenic acid staying active a similar amount of time? OR lingering for days or whatever? I'm trying to figure out if my effect is mostly the caffein, which is bad enough, or if I'm getting IP relief from the CA, which of course would be worse.

Thanks ~ Claudia:dude:

wrotek
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What about hyperforin http://www.ncbi.nlm.nih.gov/pubmed/10852961

St. John's wort (Hypericum perforatum) is an herbal remedy used widely for the treatment of depression. Recent clinical studies demonstrate that hypericum extracts increase the metabolism of various drugs, including combined oral contraceptives, cyclosporin, and indinavir. In this report, we show that hyperforin, a constituent of St. John's wort with antidepressant activity, is a potent ligand (K(i) = 27 nM) for the pregnane X receptor, an orphan nuclear receptor that regulates expression of the cytochrome P450 (CYP) 3A4 monooxygenase. Treatment of primary human hepatocytes with hypericum extracts or hyperforin results in a marked induction of CYP3A4 expression. Because CYP3A4 is involved in the oxidative metabolism of >50% of all drugs, our findings provide a molecular mechanism for the interaction of St. John's wort with drugs and suggest that hypericum extracts are likely to interact with many more drugs than previously had been realized. PMID: 10852961 [PubMed - indexed for MEDLINE]So hyperforin acts in the same way on the same receptor - PXR - as cafestol does. So if Hypericum Perforatum is a natural 'remedy'  or rather masqerader of a depression, is not coffee then too ?

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Good find, Wrotek, thanks. So it hits the PXR...

I never could handle St John's Wort, and I guess this is why :)
 

wrotek
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That is nice to hear :) When i was looking at wikipedia's PXR description, there was a link to CYP3A4 gene. I followed it and found enormous table in the end of the page http://en.wikipedia.org/wiki/CYP3A4

It is divided into 3 sections : Substrates, Inhibitors and Inducers of CYP3A4 .
Inducers section contains among others rifampicin, dexamethasone, hyperforin.

Perhaps it is worth looking since it is pretty large.

Quercetin is said to be a strong inhibitor of CYP3A4 (i don't know if inhibition of CYP3A4 is the same as inhibition of PXR every time) for example :)

Bergamottin (constituent of grapefruit  juice) is also on the inhibitors list, maybe that is why people use it in grape fruit seeds extracts.

Last edited on Wed Jan 16th, 2008 15:53 by wrotek

wrotek
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Stay tuned to PXR: an orphan actor that may not be D-structive only to bone

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=539210

Pregnane X receptor (PXR) plays an important role in detoxifying xenobiotics and drugs. In this issue of the JCI, Pascussi et al. provide convincing evidence that PXR can also induce vitamin D deficiency and bone disease because of its ability to cross-talk with the vitamin D–responsive gene that catabolizes 25-hydroxy-vitamin D and 1,25-dihydroxyvitamin D. This cross-talk behavior has important health ramifications and can be mitigated through the identification and treatment of PXR-induced vitamin D deficiency.Since these initial observations were made, there have been a multitude of reports of abnormalities in calcium, vitamin D, and bone metabolism in subjects chronically treated not only with antiepileptic drugs but also with glucocorticoids, rifampin, and antiretroviral drugs (3–6). The disturbances observed in antiepileptic drug–treated patients were noted to be very similar to those of patients with vitamin D deficiency.More than 50% of children and adults receiving chronic antiepileptic drug therapy are at risk for developing abnormalities in calcium, vitamin D, and bone meta-bolism (3). However, cardiac patients who had been treated with conventional doses of phenytoin for control of arrhythmias were found to be free of these abnormalities (7).Antiepileptic drug–induced alterations in calcium and bone metabolism can include biochemical abnormalities such as hypocalcemia, hypophosphatemia, and elevated serum concentrations of alkaline phosphatase, parathyroid hormone, and 1,25-dihydroxyvitamin D [1,25(OH)2D]. The biochemical hallmark for this disorder is reduced serum concentration of 25-hydroxyvitamin D [25(OH)D], the major circulating form, which is a barometer for a person’s vitamin D status Hahn et al. (6) noted that rats that initially received phenobarbital had increased blood levels not only of 25(OH)D but also of 24, 25-dihydroxyvitamin D3 [24,25(OH)2D3], while the 1,25(OH)2D3 levels were unchanged. However, after 21 days of treatment, both 25(OH)D3 and 24,25(OH)2D3 concentrations and intestinal calcium absorption were significantly decreased, while 1,25(OH)2D3 concentrations increased by 80%.
interesting...

Last edited on Sat Jan 19th, 2008 16:01 by wrotek

Santa Monica
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Is CA an additive, or does it appear naturally in coffee? My BF roasts his own coffee from organic green beans. Would this be off limits to me?

Also, I remember reading that coffee filtered through paper is better than coffee filtered through the gold filters, because it reduces the amount of some chemical that is known to cause high cholesterol. I just can't remember what the chemical is. Will try to look it up.

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It is reasonable to expect that any method of processing coffee beyond the usual roasting and grinding occurs for a purpose. Given the large number of folk who are not feeling well these days (from low-level immune disease) you should expect that some degree of 'feeling better', and some degree of physical dependence, is involved in the extra processing effort.
 
Best to get rid of the bugs causing the problem, and then it all tastes nice again...
 

migsies
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Has anyone seen the recent Kaiser study linking caffeine (two cups of coffee or more, roughly?) and increased risk of miscarriage? The authors seem puzzled as to causal factors. Could it be the VDR is involved?;)

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I saw the piece on TV.  How I wish someone would open their eyes and look at the invaluable info offered by Dr. M's many many years of research.  It would be nice if we could get a spot on the morning news ...then Oprah ...Dr. Phil (if he's still around) ...20/20.  

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Toni,
I can travel anywhere, at any time :):)
 

Toni D
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Wish I was in that circle~~would be my honor to network you/MP.  It's coming though, I can see it.  The vision is yet for an appointed time ...at the end it shall speak and not lie.  We [MP community] won't tarry much longer:D.

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Yes, i just saw a reference to that in a newspaper yesterday in Australia, and wondered the same thing.

wrotek
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http://tinyurl.com/2f644k

Azole antimycotics differentially affect rifampicin-induced Pregnane X Receptor (PXR)-mediated CYP3A4 gene expression

Azole antifungal drug ketoconazole has recently been demonstrated as an inhibitor of a ligand-induced PXR-mediated transcriptional regulation of CYP3A4 gene through disruption of PXR interaction with steroid receptor coactivator-1 (SRC-1). In contrast, other clotrimazole-derived antifungal agents are known as potent inducers of CYP3A4 through PXR.
So, ketokonazole is different from other Azole's.

Last edited on Thu Jan 24th, 2008 10:24 by wrotek

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Ah, but is there anything published yet about Metronidazole (Flagyl) and PXR?
 

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Does this mean we should or should not use the K-creme?

In puzzlement,

Sherry

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This implies that it is likely that K-Cream is working as an local, topical, immunosupressant, which I have always said it does, since it has affinity for the VDR as well as the PXR.
 

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Dr Marshall, i have yet found only that metronidazole is among chemicals in table http://en.wikipedia.org/wiki/CYP3A4 as "unspecified CYP3A4 antagonist" (enigmatic description for me ).
But I can't find where this information came from, cause wikipedia (about metronidazole) does not say anything about it.

Last edited on Thu Jan 24th, 2008 11:16 by wrotek

Prof Trevor Marshall
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LOL, good ol' unreliable Wackypedia. See if you can find any 'original research paper':)

 

wrotek
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LOL it is a challenge no questions about it, cause i can' find anything and i try hard :).
But i have found something else about ketoconazole http://tinyurl.com/yufucr

Activated pregnenolone x-receptor is a target for ketoconazole and its analogs.

These studies show that some azole compounds repress the coordinated activation of genes involved in drug metabolism by blocking PXR activation
and another one...

http://www.nature.com/onc/journal/v26/n2/abs/1209788a.html

Inhibition of drug metabolism by blocking the activation of nuclear receptors by ketoconazole

We have found that xenobiotic-mediated induction of CYP3A4 and MDR-1 gene transcription was inhibited by ketoconazole, a commonly used antifungal drug. Ketoconazole mediated its effect by inhibiting the activation of NRs, human pregnenolone X receptor and constitutive androstene receptor, involved in regulation of CYP3A4 and MDR-1. The effect of ketoconazole was specific to the group of NRs that control xenobiotic metabolism. Ketoconazole disrupted the interaction of the xenobiotic receptor PXR with the co-activator steroid receptor co-activator-1. Ketoconazole treatment resulted in delayed metabolism of tribromoethanol anesthetic in mice, which was correlated to the inhibition of PXR activation and downmodulation of cyp3a11 and mdr-1 genes and proteins. These studies demonstrate for the first time that ketoconazole represses the coordinated activation of genes involved in drug metabolism, by blocking activation of a specific subset of NRs. Our results suggest that ketoconazole can be used as a pan-antagonist of NRs involved in xenobiotic metabolism in vivo, which may lead to novel strategies that improve drug effect and tolerance.

Last edited on Thu Jan 24th, 2008 13:42 by wrotek

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CYP3A4 is listed in Wang et al's supplemental table 4 as one of the 27,000 genes possibly transcribed by VDR, so it is certainly possible that PXR could actually be the transcription factor. Or maybe a PXR-VDR heterodimer. Who knows?
 

GeorgeinRollaMO
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Do I understand this material correctly that Ketoconazole, an anti-fungal, is immunosuppressive?

I wonder if this action that Ketoconazole works is reason that a German (?) doctor was able to make some borreliosis patients FEEL better and get them off government support roles by using Diflucan, an anti-fungal.

The use of Diflucan was a "hot thing" for borreliosis/Lyme in 2004.

I tried Diflucan for a short period pre-MP, but found that it did not do anything for me.

Wishing all wellness!!! :)

Dark Vader...aka, George

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Yes, George, that is exactly our point. Diflucan has a profound effect on the human body, not just on fungal pathogens. See, for example http://tinyurl.com/yolbh9
 
The effect on the body's enzymes is exacerbated at the high concentrations typcally used by the Lyme Literate Physicians (LLMD).
 

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OK, I've been wanting to ask this for a long time: some fungi are capable of manufacturing vitamin D, and apparently they do this when exposed to sunlight. Apart from wondering what use the compound is to the fungus, I wonder if our skin is doing anything like the same thing, chemically speaking. Since we are using K-cream, which is supposed to kill fungus, is it interfering with the same process in our skin (or similar) as it affects the fungus?
I know you may have already explained it above, but can I have it in English, please?
Are we - :shock: shock, horror - really a bunch of mushrooms, too?

Or just a coincidence?

:dude: Claudia - sitting in the dark, decomposing.

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The VDR Nuclear Receptor is ancient.
For example, the Lamprey has a VDR. How it manufactures the Vitamin D to activate its VDR beneath the waters of the Great Lakes is something I will leave our Canadian Vit D fanatics to figure out :):):)

http://www.ncbi.nlm.nih.gov/pubmed/12746335

I haven't done much work with yeast, my focus has been on mammals. So I can't tell you if there is a VDR homologue in yeast. Probably is, though,as there is in Drosophila... You might like to review this:
http://www.biomedcentral.com/1471-2148/7/222

As far as K Cream is concerned, it doesn't much care if you are yeast, a mushroom, a mouse or a human, it will mess with your VDR and enzymes as much as it can. That is why it is toxic, if ingested in quantity.
 

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I'm not sure if the Canadian Vitamin D fanatics will ever figure it out.

There is so much Vitamin D in the food supply in Canada most of the country seems to be walking around in a Vitamin D induced haze.  

sunflower
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i have taken diflucan in the past, two separate times (100 mg day/or qod), for many months to treat chronic candidiasis....i always felt so horrible while on it.  i just assumed it was massive herxing from the dying off of the yeast, but maybe something alot more sinister was going on :shock:.  other than suppressing the immune system and allowing the l-form bacteria to proliferate, do you think the drug could have caused permanent damage to my body?   thanks....sun

Last edited on Fri Jan 25th, 2008 14:34 by sunflower

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Back to the coffee issue.  There are a number of specialty coffees that are advertized as low acid.  Does anyone know if these are low in chlorogenec acid or have the majority of the chlorogenec acid removed?

wrotek
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I think there is an important question to ask, what is more disturbing for VDR metabolism in coffee, high chlorogenic acid content (which exhibits VDR antagonism) or cafestol (PXR, FXR agonist, most potent cholesterol elevating factor known to men).

wrotek
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Hmmm and another thing. One can buy a decaffeinated coffee and pour it through a paper filter, to get rid of cafestol. So now one has a decaffeinated and decafestolated coffee, with a sour taste - from the lack of the lipid content.
So is it enough to get rid of all measurable effects that coffee exerts on human body ? Well, apparently not, because study linking inflammatory markers rise and moderate coffee drinking includes also a decafeinated -filtered coffee, so if not chlorogenic acid, then there is something else in coffee, that rises inflammatory markers.

Last edited on Wed Jan 30th, 2008 18:53 by wrotek

tickbite
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How about this Wrotek........don't drink coffee and sweat the recovery.......we all know you love coffee. It's time to let go :)

Knochen
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If I can quit coffee, anybody can.  I think I put Juan Valdez's kids through college!

wrotek
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:)

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Lately, I have been trying a little caffeine from a pill (No Doze).

I use about 1/4 when I get up and about 1/4 at noon.  The total is the amount in a cup of coffee (100 mg).  I find it helpful for alertness and perhaps mood and don't detect any sign it affects my immunopathology (based on a variety of symptoms). 

I used to think caffeine made me shakey (at least above a certain level), but this amount seems fine and there is no worry about all the other ingredients in coffee or tea.  I also saw caffeine supplements sold online (don't know if they have No Doze type things in the stores in Poland).

Joyce Waterhouse


PS  Nov. 2008 note:  I have stopped caffeine.  See Nov. 12, 2008 post in my progress report for my thoughts on my experiment with taking it:

Joyce's good progress on MP - Phase One Alumni Forum - PROGRESS REPORTS page 3

Last edited on Wed Nov 12th, 2008 16:07 by jcwat101

wrotek
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This is an idea.
But I have been lurking recently into effects caffeine has on brain tryptophan and serotonin levels .  And i have found some interesting data

Tea consumption in many cases is the main source of caffeine intake in humans. In the present study neurochemical and behavioural effects of long-term tea intake are monitored in rats. Long-term tea administration did not alter plasma tryptophan (TRP) but significantly attenuated brain TRP and 5-hydroxytryptamine (5-HT, serotonin) levels. Brain 5-hydroxyindole acetic acid (5-HIAA) was comparable in both tea-treated and control rats. An increase in home cage activity was observed after one week in rats taking tea as sole source of liquid, whereas no change on the activity was observed in an open field. Caffeinism has been associated with depression. The decreases of brain monoamine metabolism observed in present study are discussed as lowering of mood observed in tea or coffee consumers. PMID: 16414819 [PubMed]
Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain.

http://tinyurl.com/24efzm
  Chronic ingestion of caffeine by male NIH strain mice alters the density of a variety of central receptors. 2. The density of cortical A1 adenosine receptors is increased by 20%, while the density of striatal A2A adenosine receptors is unaltered. 3. The densities of cortical beta 1 and cerebellar beta 2 adrenergic receptors are reduced by ca. 25%, while the densities of cortical alpha 1 and alpha 2 adrenergic receptors are not significantly altered. Densities of striatal D1 and D2 dopaminergic receptors are unaltered. The densities of cortical 5 HT1 and 5 HT2 serotonergic receptors are increased by 26-30%. Densities of cortical muscarinic and nicotinic receptors are increased by 40-50%. The density of cortical benzodiazepine-binding sites associated with GABAA receptors is increased by 65%, and the affinity appears slightly decreased. The density of cortical MK-801 sites associated with NMDA-glutaminergic receptors appear unaltered. 4. The density of cortical nitrendipine-binding sites associated with calcium channels is increased by 18%. 5. The results indicate that chronic ingestion of caffeine equivalent to about 100 mg/kg/day in mice causes a wide range of biochemical alterations in the central nervous system.]
The amounts of caffeine mice ingest are very high, so probably changes in people consuming caffeine will be significantly smaller. Nonetheless, we can see a tendency which direction brain will try to adapt, that nicotinic receptor increase(maybe that is why caffeine potentates nicotine addiction) and serotonin receptors  and benzodiazepine receptors also increase.

Last edited on Sun Feb 3rd, 2008 01:41 by wrotek

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Here is an interesting link:

MDR- and CYP3A4-mediated drug–herbal interactions
Dhananjay Pal and Ashim K. Mitra,  

http://www.ncbi.nlm.nih.gov/pubmed/16442130

/Lottis, following the thread and soon on the MP again:)

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I tried St John's Wort once. It was a disaster:( :(

Maybe that points at CYP3A4 as taking over from CYP24 to degrade 1,25-D when the VDR isn't working right. Hmmm...
 

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Those mice were certainly getting a lot.  I am getting only 100 mg and I weigh far more than a kilogram :)

Also, I wonder if they were getting it around the clock.  I am getting it in two small pulses and so my serum levels of caffeine should be pretty low by bedtime.

I also figure that there have been at least a few people on the MP who have improved or recovered who were drinking at least some caffeinated tea or a little coffee, and caffeine is not prohibited on the MP.  And caffeine has been studied a great deal and is very widely used in the population.  I think I read that well over 80% of the population consumes some caffeine-containing beverage regularly.  Anyway, I have only begun recently, but so far, this small amount at about 7 am and noon seems to be working fine and seems to be helping with alertness and mood.

I did read that taking the birth control pill causes caffeine to have a longer half life (closer to 6-8 hours), so I figure when I am on the bc pill (as I am off and on), I should not take any after noon, as it will take longer to clear and I want it to mostly clear from my system (or much reduced anyway) by night time.

I'm not advocating a lot of caffeine and I would rather not use it at all.  But, I think while I need a little more alertness while I still am killing the bacteria affecting my brain, some judicious use of caffeine in the No Doze is probably better than other alternatives (eg., prescription drugs).  But I would not be in favor of high doses. 

And I am also concerned about some of the ingredients we have discussed here and elsewhere that are found in soft drinks, coffee and even tea.  Also, for people like myself, who are prone to food sensitivities, these drinks are not hypoallergenic enough, so that is why I like the caffeine in pill form.

Here are three links that I think cover the pros and cons pretty well:

Caffeine - Benefits and Risks

Health Benefits of Caffeine - Coffee, Caffeine and Weight Loss - Caffeine Burn

Pros and Cons of the Caffeine Craze

Anyway, that is my current view after several weeks of using the No Doze and we'll see if I change my opinion over time.

Joyce Waterhouse

PS  The No Doze I get is 200 mg per tablet, which is equivalent to 2 cups of coffee.  I take a 1/4 tablet when I wake up and 1/4 at around noon, like trying a cup of coffee in total.

Last edited on Sun Feb 3rd, 2008 18:10 by jcwat101

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i tried st john's wort for depression on 2 separate occasions and it was a disaster for me, too....i had so much brain fog i couldn't see straight :shock:.  sun

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Now there's an interesting theraputic probe for identifying those with 1,25D disregulation: trial St. John's Wort. :?

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Both Caitlin & Mom stopped sleeping and became very mean on St. John's Wort.

Mindy
BTW I have never been able to tolerate coffee or tea. Makes my back hurt horribly and meds won't help it.

Last edited on Sun Feb 3rd, 2008 19:58 by Caitiegirl

Linda J
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I became increasingly more and more irritable and angry on St. John's Wort, and I kept raising the dose, trying to compensate. When I finally got up to the maximum dose after about 9 months on it, and figured out it was the St. John's Wort that was responsible for my anger and irritability, I stopped it cold turkey. And ended up in a psychiatric ward two days later from being suicidal, with very disjointed and slow thinking processes, and a lot of confusion/brain fog and severe depression. That was also close to the start of my burgeoning health degredation back in 1999, and I had a lot of other health problems on top of that besides the emotional issues. The health problems had actually started long before I started using St. John's Wort. But it definately did NOT make me feel emotionally better, and my health problems began to snowball around that same period of time. And stopping it so abruptly also screwed my brain up royally, or at least started a chain reaction that caused me to develop other neurological problems.

However, I do know quite a few people who have symptoms of Th1 illnesses who claim that St. John's Wort made them feel better. So I'm not sure that using it as a probe to determine Th1 problems would work.

VEZ R.N.
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Maybe many of us with Th1 inflammatory diseases tried St. John's Wort with poor results. I tried it as well and it was a very bad experience.

VEZ:D

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http://www.dadamo.com/bloggers/ask/archives/00000058.htm

maybe a lot of you guys with bad reactions to SJW are blood type O

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Nope, I am A+
 
Well, at least I was when I was sick. Haven't had the blood type tested recently...
 

Linda J
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No. I'm A-. What would blood type have to do with it, though?

Kas
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 Can your blood type actually change?

I thought it was one of those things you were born with.

I am an AB+ and in my youth, was a regular blood donor. Hope I never passed TH 1 illness onto anyone in my quest to save lives.

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Not O.  Had major irritability to St. John's Wort and also to Celexa and Wellbutrin.  Nearly identical symptoms for all three.  Claire

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Isn't it interesting how St. John's wort is also capable of causing light sensitivity?

I'm O+, tried it for insomnia which it didn't help and got depressed instead. I also got depression from trying elavil for insomnia.

Pam

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St. John's Wort did not do anything for me either.  I know it works for some people.  However, there seems to be several individuals in this thread that have not benefited from it. 

Is it possible that this is a possible marker for Th1 infection?

The hypothesis would go like this:  If you suffer from depression and are not helped by St. Johns Wort you are more likely than the general population to suffer from Th1 infection.  Would anyone like to study this or comment on it.   

 

Last edited on Tue Feb 5th, 2008 18:26 by Cairo123

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I rather doubt one would have to react negatively to St. John's wort to qualify as Th1.  I think most cases of depression have some degree of Th1 disease.  Among Th1 people I know, some find an anti depressant that relieves their depression and others can't find any that work.

Joyce Waterhouse

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The blood type  is just a genetic marker for a bunch of other important metabolic and immune related genes at the same chromosome locus. The phenomenon is known as 'linkage disequilibrium' - you can read about it in a fairly clear description here:

http://www.economist.com/science/displaystory.cfm?story_id=10283306

Blood type O (at chromosome locus 9q34), and particularly ABO-nonsecretors (at 19q13) both of which are recessive phenotypes, have associations with auto-immune prone individuals according to Dr.D'Adamo:

http://www.dadamo.com/forum/archivea/config.pl?read=90479

There may be an over representation of these two markers in the MP cohort, particularly amongst those with frank so called 'auto-immune' disease.

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There may be an over representation of these two markers in the MP cohort, particularly amongst those with frank so called 'auto-immune' disease
Or Dr D'Adamo may be completely wrong.

I have no data, I am just reminding us all of the alternate hypothesis.
 

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I don't think his work goes as far as making any hypothesis of a mechanism for auto-immunity such as you have made with the VDR associations. It is merely that he has noted a link, and blood types are easily measurable parameters so could be of some usage to the MP cohort later on. There are no doubt many other gene locii involved as well, the MHC on chromosome 6 is often cited as being involved with auto-immunity for example. Certainly his work in no way contradicts yours, hopefully it will supplement it further down the line;)

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I also tried St. John's Wort in fairly high doses for at least a few months after reading (or mis-reading) something about it helping nerve regeneration.  This was after my spinal cord injury.  Ever since then I sunburned much easier although I didn't really start getting ill from sun exposure until after the tick bites.  I've always wondered if the stupid SJW experiment caused permanent damage to something in my skin.

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Coffee is closely related to the Solanaceae phylogenetic tree http://www.sgn.cornell.edu/about/about_solanaceae.pl which are causing the nightshade intolerance of the immune system.  It has been found that some of these plants produce 1,25 D, according to this article: http://noarthritis.com/vitaminD3.htm 

and this
http://dx.doi.org/10.1016/0031-9422(95)00883-7

/Lottis:)

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Foods don't necessarily have to contain vitamin D or vitamin D analogues to affect important receptors like the VDR. For example this gigantic molecule can behave as an insulin mimic and strongly binds to the insulin receptor:
http://160.114.99.91/astrojan/protein/pictures/agglutin.gif

http://www.pnas.org/cgi/reprint/70/2/485.pdf
WGA has been implicated in insulin resistance as these molecules are not easily cleared from the body (apologies to all you pasta lovers)

There may be other glycoproteins lurking in common foods which bind the VDR.

wrotek
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Interesting case reports about coffee drinking and anxiety.
Switching to tea eleminated it, so it can't be a caffeine that causes it.
http://www.healthcentral.com/anxiety/c/8146/5936/comments/


I began having chronic anxiety and panic attacks during a very stressful period in my life.  As time passed and the stresses went away, my anxiety got much better, but never fully left.  For years I lived with a the constant sense of dread and that feeling that something was off.  I had medication in case of emergency, but I rarely took it.  I am not a person who is comfortable taking medication on a regular basis and I never wanted to be dependent on a substance to get through the day.  So I lived with it.
I stopped drinking coffee because I noticed that it was making me feel a bit nauseated on a regular basis.  I didn't remove caffeine completely -- I started drinkine tea instead.  It was about two weeks without coffee when I realized that the anxious feeling was gone.  Completely.  The ONLY change I made in my life at the time was cutting out the coffee.  That was more than two years ago and the anxiety has never returned, even in stressful situations.  It may sound crazy, but I'm a firm believer that coffee was the cause of my anxiety.




from comments
I'd get an intensely paranoia about my relationship (with a great guy and completely unfounded), and a general sense of anxiety and panic. It only occurs after having drank coffee. I switched to a stronger green tea/pomegranate drink (a few cups each morning) and have eliminated that awful feeling of dread/paranoia/pani A month ago, I stopped drinking coffee because of extreme anxiety/ panic attacks related to relationship problems. I started drinking tea and found I could deal with the stress more easily without the physical effects. Today I had coffee with a friend this morning and found that anxious thoughts I was having before came quickly back. No more coffee! I have had the exact same experience Linda. When i was drinking coffee regularly, i was getting panic attacks. I recall one time that i did not want to go the local carnival, because i was in no state of mind for it. My girlfriend thought i was going a bit funny but also understood there was something wrong. As soon as i switched to tea the panic and anxiety dissappeared.

Last edited on Tue Feb 12th, 2008 18:20 by wrotek

maggie weeks
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 Correct me  if I am wrong but I thought tea had as much caffeine in it as coffee. I have read that coffee cuts oxygen to the brain by 20%. May be that is why people are having panic attacks?? Just  thought.  I have never been a coffee drinker but have suffered from anxiety.

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 Strangely, when I do have the odd cup of coffee to bump my BP up when it is super- low, I feel really good! It certainly does not seem to lessen the oxygen to my brain, and in fact, it makes me feel far more energetic. I only have about a cup once a week or less. Regular tea has no effect on my BP and oddly, I can no longer eat my beloved dark organic chocolate - it drops my BP even further!! I suppose we are all different in what affects us.

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I deleted two posts which had wandered into the realm of speculation, repeating common pragma about the mode of action of caffeine.

Please keep this thread on-topic, focused on the immune activities of chlorogenic acid.
 

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Since quitting coffee I have tried a cup a couple of times.I get the worst feeling which is hard to describe,sort of like an extreme nervousness/anxiety,and a creepy crawly sensation in my skin,along with insomnia.Is it the caffeine? HELL NO!!! I take a 200 mg caffeine pill and drink 4 cans of Diet Coke sweetened with Splenda, daily,and have no insomnia or weird sensations.Tea gives me the same sensation,but on a smaller scale.

Last edited on Mon Feb 18th, 2008 07:39 by shamutooth

maggie weeks
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 Can you get me up to date please I followed your advice ages ago and started drinking Roobis tea, is that a no no now? Are all teas bad, what about herbal teas?

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Maggie, I have no idea what 'Roobis tea' is, and am certain that I have never suggested its use.
 

maggie weeks
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 Hi Trevor! I spelt it wrong!!It was Rooibos caffeine free amd I must have dremt up that you drank it with your Benicar  to help it" diffuse better in the tissues." I am usually pretty  good about following your ideas so maybe the new spelling will ring a bell!! Question, do all teas have to be avoided now?

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Rooibos, often called "red tea", because of the color released during brewing, possesses a flavor similar to that of black tea. Also, like black tea and green tea, Rooibos provides beneficial antioxidants-but without the caffeine. 

The brand Good Earth original tea is mainly made from Rooibos (Masai) tea. 

HERE are one of the links I found that contains a little more info about Rooibos tea. :cool:

PS I think you're thinking of Trader Joe's jasmine green tea that Dr M drinks.

Last edited on Tue Mar 11th, 2008 21:05 by Reenie

Prof Trevor Marshall
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Thanks, Reenie, the word "anti-oxidant" is all I need to know.
You don't want to mess with 'oxidants'  or 'anti-oxidants'. Folk who simplify the behavior of the body to terms as simple as these really don't understand what they are talking about.

I have suggested warm water sweetened with Splenda, perhaps adding the Jasmine Green Tea from Trader Joes, allowed to steep only for about 15 seconds, until just a little bit of flavor is added to the water.
 

maggie weeks
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Thanks Trevor I will switch to Green tea at once. I have some already but I loved the flavour of Rooibos so much what a shame, it has been bad to drink it after 2 years of thinking I was SO good to give up my regular cuppa!

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Keep it very, very weak, Maggie. Steep about 15 seconds. Trader Joe's Jasmine Green transfers just a hint of color and flavor to the water, and shouldn't give you any problems, while efficiently 'washing down' the Benicar and keeping those kidneys flushed...
 

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I have been drinking Rooibos tea for years. It comes from South Africa and is filled with anti- oxidants is and safe enough to give to babies when cooled. It contains no caffeine whatsoever, and once you get used it, it makes for a very pleasant beverage. It is also contained in some creams and is apparently beneficial in the topical treatment of minor skin ailments and wrinkles!

Just seen Trevor''s comment, so will now switch to weak Green tea! Another treat on hold until recovery....

Last edited on Tue Mar 11th, 2008 21:41 by Kas

maggie weeks
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 Thanks for your care and concern.Just had some sad news, my bridsmaid has just died of cancer. Thanks to the MP  I am holding up as well as can be expected, years ago I would have been a total basket case, it has really helped me with my emotions and stress.

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So sorry to hear of your news Maggie.

I was just reading the latest comments about Rooibos tea. I have several friends (South African and British) who drink Rooibos and love it. But when I started to drink it ten years ago I found myself having awful stomach cramps. I have IBS (well I think that's what it is - never diagnosed by doctor) and wondered what was going on. After I had drunk about five cups  and realised I was getting the same crippling cramps each time, I gave the box away to someone else! I have often mentioned this to people who 'swear by it' as a healthy option - they just look at me as tho I'm a nutter.

maggie weeks
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 Excuse my ignorance but what have you found that is SO harmful in Antioxidants. In all my reading they are touted at attacking the free radicals in our body and freeing them up and preventing aging etc etc. Is it just that us folks with the TH1 inflammtory disease  that cannot process them. Can "healthy" people eat food that are high in antioxidants ie pomegranates. I have aways had a quarter of a cup of blueberries everyday for years with my oatmeal and drink small quantities of of pomegranite juice ie 1/4 cup.Is is the same as a little in moderation or is there a scientic molecular reason we should'nt be ingesting these in small amounts. Thanks for your imput

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Maggie,
Please show me one of your 'free radicals'. Then I will take another look at these silly, simplistic, and ineffective anti-oxidant theories.

Highly polar molecules will instantly bond to the nearest protein, enzyme, etc. They will not wait around for a Vitamin C, or other 'anti-oxidant' molecule to pass by.

Concentrated fruit juices, especially those which need to be repeated daily, are almost certainly acting as immunosupressants in Th1 compromised individuals.
 

Last edited on Fri Mar 14th, 2008 16:30 by Prof Trevor Marshall

Twilight
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Carricol wrote: Back to the coffee issue.  There are a number of specialty coffees that are advertized as low acid.  Does anyone know if these are low in chlorogenec acid or have the majority of the chlorogenec acid removed?
I would really like to know the answer to this too, if anyone knows. Thanks. :)

shandym
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is it ok to have the daily cup of OJ without D of course or Pom juice? I have eliminated these from my diet but would love to have the daily glass in the morning. My diet is not very good and would like to get some form of vitamins. :)

Also is weight watchers sugar free soda ok to drink?
INGREDIENTS: Crystal clear carbonated water, natural and artificial flavors, citric acid,potassium benzoate, spelenda, acesulfame potassium,red#40,caramel color and blue #1

I dont mean to drink this in excess but would a can a day be too much for someone on the MP???

Thanks very much!

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Shandy,
A cup of OJ is fine.  One or two cans of that drink, assuming that there are no ingredients other than those listed, should also do no harm.
 

shandym
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Thank you!! :)

Those were the only ingredients listed....

maggie weeks
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 So if I am correct there is NO scientific proof done to support the theory of Free raidcals and antioxidants ?Why is there so much confusing information out there or is it a way to sell products and supplements which support this supposed theory.

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Maggie,
The talk about oxidants and anti-oxidants is a model. A way of trying to describe what a group of people thought was going on in the body. These days, about the only ones who continue to espouse it are those selling supplements. Molecular discovery has long made the whole concept look ridiculous.

The cytoplasm of a cell, where the Th1 pathogens have their metagenomic communities, also consists of literally thousands of molecules drifting around, bumping into other proteins, other peptides, and drugs, bonding with the ones which have sufficient attractive force. Then those bonds are in turn broken by higher affinity bonding to a different protein which comes by, or by 'conduction' into receptor binding pockets.

When I simulated how 1,25-D was pulled into the binding pocket of the VDR, I began to realize how mind-boggling is the number of molecular interactions which never evolve into anything biologically useful. You might wonder why you need to take Benicar so frequently. Once it is in the binding pocket of the VDR, surely it will stay there for ever? No - firstly the VDR itself is in constant motion - second, that motion is affected by the forces on the VDR from adjacent molecules. Olmesartan has an ability to stay in that binding pocket for only a few hours before it is either ejected, the VDR itself is pulled apart by outside forces, or an aggregation disables transcriptional capability.

High-school physics and chemistry, and even undergraduate physics and chemistry, do not prepare us for the reality of 21st Century Medicine. It is going to take several generations of med-school graduates before a better understanding evolves, I fear...
 

maggie weeks
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 Thanks so much for taking the time with the explanation, as I am in the medical profession I do come across people wanting to sell supplements and they have supposedly back up trials to quote, so it could be confusing to the general public who are after a quick cure for various ailments . They are also promoting anti aging benefits when taken everyday. I am so glad I have been able to get this straightened out. I have been approached by several people in the  medical profession who are touting products which can shrink tumours and help diabetes etc etc and it would be wonderful if it were that simple.

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There have been some studies lately showing anti oxidants not living up to previous expectations.  I'm thinking of vitamin E and beta carotene/vitamin A, at the moment, but there are others.

Joyce Waterhouse

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A question:

If CA is in tomatoes, would tomato sauces be a no-no?  I hate tomatoes and never eat them fresh, but I love a good tomato pasta sauce (with whole grain pasta, of course), and salsa fresca (the only "fresh" tomato I'll eat -- a real California girl takes advantage of all the great Mexican food here).

I made a pasta sauce tonight with canned chopped tomatoes and canned sauce (all organic and natural), along with lots of fresh ingredients.

I drink maybe one cup of coffee a week, and usually stick to herbal teas (peppermint, chamomile, sleepytime), so I avoid other sources of CA.


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There isn't that much chlorogenic acid in tomatoes.  I don't think the FAQ says one really needs to worry about the levels in foods.  It mainly says just don't drink more than a cup of coffee a day.  So, go ahead and have tomatoes :)

Joyce Waterhouse

wrotek
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Hmmm, is this true ?

Coffee contains potent opiate receptor binding activity

http://www.nature.com/nature/journal/v301/n5897/abs/301246a0.html
Isolation of opiate receptor ligands in coffee.
http://www.ncbi.nlm.nih.gov/pubmed/2832110?dopt=Abstract

Last edited on Wed Mar 19th, 2008 10:42 by wrotek

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Good find, Wrotek. Those studies look OK (at first glance).

"with no significant difference between normal and decaffeinated coffee"
Hmm.. that seems to mirror what members have been reporting here.

Note that the opioid receptors are expressed on Lymphocytes, and are therefore active in the immune system, in ways yet to be properly defined.

Finally, Olmesartan appears to be active in the opioid-delta receptor, with about the same level of affinity as Naloxone. But it docks into a different part of the receptor binding pocket, and its actions are therefore totally unknown. I haven't looked really closely.

..trevor..

wrotek
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Very interesting...
I have been looking at Naltrexone(opioid antagonist) side effects  http://www.minddisorders.com/Kau-Nu/Naltrexone.html

Side effects The following represents the most common side effects associated with naltrexone:
  • nausea, vomiting, diarrhea, cramps
  • headache, insomnia, anxiety, irritability, depression, dizziness
  • joint and muscle pain
  • rash
Does not look like something Th1 person would want :]

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I'm confused by the mention of St. John's Wort being negative... It induces the metabolism of Vitamin D via increasing (<--- I guess this where I don't know) its respective hydroxylase, much like phenytoin and phenobarbitol.

"Here we show that these drugs lead to the upregulation of 25-hydroxyvitamin D(3)-24-hydroxylase (CYP24) gene expression through the activation of the nuclear receptor pregnane X receptor (PXR; NR1I2). CYP24 is a mitochondrial enzyme responsible for inactivating vitamin D metabolites. CYP24 mRNA is upregulated in vivo in mice by pregnenolone 16alpha-carbonitrile and dexamethasone, 2 murine PXR agonists, and in vitro in human hepatocytes by rifampicin and hyperforin, 2 human PXR agonists . Moreover, rifampicin increased 24-hydroxylase activity in these cells, while, in vivo in mice, pregnenolone 16alpha-carbonitrile increased the plasma concentration of 24,25-dihydroxyvitamin D(3)."


So is the paper simply illustrating the differences in cyp24 metabolism between mice and glass? I would not believe it be difficult to give rifampicin to a mouse, maybe they should have....

So if cyp3a4 induction is bad, would inhibition be positive. Or am I discussing an irrelevant biochemical pathway?

Last edited on Wed Mar 26th, 2008 20:33 by hullcrush

wrotek
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This paper has interesting graph showing how xenobiotics(for example cafestol or St. John's worth hyperforin, rifampicin) react with PXR which is compared how 1,25-D reacts with VDR.
Stay tuned to PXR: an orphan actor that may not be D-structive only to bone

http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=539210&blobtype=pdf


Figure 1 A schematic illustrating how xenobiotics and drugs that activate PXR can disrupt vitamin D metabolism and vitamin D function. The kidney is responsible for converting 25(OH)D to 1,25(OH)2D. Once formed, 1,25(OH)2D enters the blood and travels to its calcium-regulating target tissues, where it interacts with its specific nuclear VDR. This complex binds RXR, and the resulting heterodimeric complex binds to specific VDREs in the DNA, leading to regulation of gene expression responsible for calcium and bone metabolism. 25(OH)D can also be metabolized in a wide variety of tissues, including colon, prostate, breast, and skin, where it acts either as an autocrine or paracrine hormone to regulate cell growth and carry out other physiologic functions. Xenobiotics and drugs that activate PXR bind RXR. This heterodimeric complex is recognized by the VDRE of CYP24, which is responsible for the destruction of 1,25(OH)2D into a water-soluble, inactive metabolite. The activated PXR-RXR complex may also be able to alter other VDREs that have wide-ranging biologic functions in cell growth and maturation, immunomodulation, renin and insulin production, and osteoblast function. Understanding of the consequences of this potential interaction and alteration of VDRE gene expression on noncalcemic functions of vitamin D requires further investigation.
So, xenobiotics downregulate both 25-D and 1,25-d  ?

Last edited on Fri Mar 28th, 2008 08:42 by wrotek

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Except that PXR activation downregulates CYP24 and PXR antagonists upregulate CYP24 (see my latest paper, fig 1.). This is the danger of people who don't fully understand Molecular Biology trying to form hypotheses by groping about in the dark.

Michael Holick himself (the author) says he takes 11,000 IU of Vitamin D a day. No wonder his brain is oddled:):)
 

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I see, so it happens inversely :) Both 25-D an 1,25-D will increase upon PXR agonists ?

Last edited on Fri Mar 28th, 2008 08:56 by wrotek

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Not necessarily, because 25-D and 1,25-D are themselves antagonists of PXR. There is a complex feedback loop set up. Look at Fig 1 of my latest paper. Carefully!:)
 

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Is there a possibility that  bugs also disable(act on) other nuclear receptors so 1,25-D cannot be dowregulated through them too, like PXR ?

Last edited on Fri Mar 28th, 2008 16:28 by wrotek

wrotek
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Nicotine is a PXR agonist ?

http://lib.bioinfo.pl/pmid:15364541
Nicotine, the psychoactive and addictive chemical in cigarettes, and a known inducer of brain CYP2B6, was an efficacious activator of PXR and inducer of CYP3A4 transcription. Because nicotine activation of PXR will enhance metabolism of nicotine to the non-psychoactive cotinine, these results provide one molecular mechanism for the development of tolerance to nicotine. Moreover, the identification of PXR in many human tissues, such as brain, and activation by tissue specific ligands (such as neurosteroids) suggests additional biological roles for this receptor in these tissues.

Last edited on Tue Apr 8th, 2008 18:17 by wrotek

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Hmmm. That would make sense. I have often noted that smoking is reported to sometimes abate Th1 symptoms, and activation of PXR would be a loose enough perturbation to the D metabolism to correlate with the minor symptomatic observations that people have been recounting to me.

Thanks for this, Wrotek, it makes sense. It will take a lot of effort for me to confirm, however, as nicotine is rapidly metabolized in the body, and I don't know which of the intermediate compounds (or glycosylates) might be PXR-active. This is one time where wet biology has the experimental advantage (of simplicity) over molecular modeling :)

When I have some time spare I will check all the well-known metabolites:
http://tinyurl.com/5dd3vv
 

ps: the Danish study on smoking found that 25-D and 1,25-D levels were lower in smokers than in non-smokers. Which would correlate with PXR-agonism, as reported in the study you forwarded:)
http://www.ncbi.nlm.nih.gov/pubmed/10602348
 
 

Last edited on Tue Apr 8th, 2008 19:12 by Prof Trevor Marshall

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Does that mean I should start smoking or stop smoking?  :?

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You should stop smoking, for all the reasons that smoking is regarded as being bad for you.
 

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Coffee and cigarettes composition starts to be very interesting in regard to vitamin D metabolism :)

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http://www.ncbi.nlm.nih.gov/pubmed/17053540

Association between coffee consumption and markers of inflammation and cardiovascular function during mental stress. Hamer M, Williams ED, Vuononvirta R, Gibson EL, Steptoe A. Department of Epidemiology and Public Health, University College London, London, UK. m.hamer@ucl.ac.uk BACKGROUND:

Coffee is widely consumed in the Western diet and therefore has important implications for public health. Research findings pertaining to the effects of coffee consumption on cardiovascular health are conflicting, and the role of caffeine is not clear. OBJECTIVE: To examine the relationship between coffee intake, inflammation and cardiovascular function at baseline and during mental stress, both cross-sectionally and after a 4-week period of withdrawal of coffee during which intake of caffeine was maintained. METHODS: Eighty-five healthy, non-smoking men with varying coffee-drinking habits were recruited. Blood pressure, heart rate, and markers of inflammation [C-reactive protein (CRP), von Willebrand factor antigen (vWF)], were measured at baseline and during mental stress. These measures were repeated after a 4-week period of withdrawal of coffee, during which intake of caffeine was maintained. Habitual levels of coffee and caffeine consumption were assessed from a self-reported questionnaire, and saliva samples for the analysis of caffeine concentrations were collected regularly throughout the period of withdrawal, to confirm compliance. RESULTS: Multiple linear regression analysis of pre-withdrawal data, adjusted for age, body mass index and intake of tea, red wine, fruit, vegetables, oily fish and dietary supplements revealed that coffee consumption was positively related to baseline systolic blood pressure, and increased heart rate and vWF responses to mental stress. Four weeks after withdrawal of coffee, the heightened vWF and heart rate responses to stress in habitual coffee drinkers persisted, whereas baseline systolic blood pressure had decreased. Total caffeine intake was unrelated to any measures of physiological function. CONCLUSIONS: Habitual coffee consumption is associated with heightened acute vascular inflammatory responses to mental stress, although these effects are not affected by short-term abstinence from coffee. These findings suggest that the relationship between coffee and markers of cardiovascular risk may be explained by residual or unmeasured confounding factors. PMID: 17053540 [PubMed - indexed for MEDLINE]

Very interesting, long lasting effects of coffee on inflammation(after abstinence even for 4 weeks), not caffeine related.

Last edited on Sat Apr 19th, 2008 18:09 by wrotek

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Toni,

I have written to Oprah 3 times to do a show about Sarcoidosis and the Marshall Protocol. Maybe we should all write and see if she wants to be instrumental in taking the blinders off the Medical World. What do you think?

Thank God for all of you!

Last edited on Sun Apr 20th, 2008 15:17 by patsysweeney

wrotek
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Anecdotal story from oxyplus yahoo discussion group
Hi Laurie, There was a woman I know that suffered from fibro for years who recently found out it was the coffee bean that was causing her symptoms. She came off coffee and all the symptoms went away. She had her life back. But one cold winter day she thought she'd have some coffee and, low and behold, the pain came back. For her it was really significant and it took years to discover!
:)
some quotes from our discussion

Hi Wrotek, The woman is a beautician and our conversation was over a hair cut so I don't have a lot of details. She mentioned once having had fibromyalgia, and yes, it did cause years of fatigue/pain.Her comment about it being the coffee bean (she specifically said coffee bean, not caffeine) that was the enemy for her.

Last edited on Sat Apr 26th, 2008 15:16 by wrotek

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It has been said by a doctor at our hospital that we would not be able to run it without coffee, because coffee is the fuel to the complete machinery! :D

Now if we combine the coffee, the cigarettes, the prions in the urine and all the L-form bacteria from the medications, the bio films on the tools and and all the blood from operations and lab tests, we have a deep understanding why coffee is so important and that many women working in hospitals have a problem stopping smoking! :?

Women working in hospitals are the most sick occupational unit, and now we can clearly see why. What an enormous sacrifice being done to nurse and help others! :shock:

/Lottis

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is it ok to have one cup a day? 

thanks much

lisa

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Hi Lisa,

I love my coffee...and have really had a tough time having to adjust to not having it....so I take 1/2 cup and add water to this to weaken it in the morning.  I'm trying to wean off of it to completely to see how I react.  I usually have to microwave my coffee/water mixture as it is not hot enough once I dilute!

Try it...it is 1/2 the coffee yet gives me the satisfaction I still need of that cup in the morning.  :D

 

schesche
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does this mean--apples should be avoided?

i eat about 10 a week

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"An apple a day keeps the Doctor away"
 
but I am not sure about two...
 

wrotek
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Maybe worth mentioning.

http://tinyurl.com/48u7x7

The Flavonoid Apigenin Suppresses Vitamin D Receptor Expression and Vitamin D Responsiveness in Normal Human Keratinocytes

http://en.wikipedia.org/wiki/Apigenin
Apigenin is a flavone that is the aglycone of apiin, isolated from parsley and celery, and apigetrin. It is a yellow crystalline solid that has been used to dye wool.

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Resveratrol upregulates dose-dependently the expression of 1,25(OH)(2)D-3 nuclear receptor.

Resveratrol inhibits myeloma cell growth and promotes healthy bone marrow

According to recent research from Denmark, Multiple myeloma is characterized by the accumulation of clonal malignant plasma cells in the bone marrow, which stimulates bone destruction by osteoclasts and reduces bone formation by osteoblasts. In turn, the changed bone microenvironment sustains survival of myeloma cells. Therefore, a challenge for treating multiple myeloma is discovering drugs targeting not only myeloma cells but also osteoclasts and osteoblasts.

"Because resveratrol is reported to display antitumor activities on a variety of human cancer cells," wrote P. Boissy and colleagues at South Denmark University Network in Vejle, "we investigated the effects of this natural compound on myeloma and bone cells. We found that resveratrol reduces dose-dependently the growth of myeloma cell lines (RPMI 8226 and OPM-2) by a mechanism involving cell apoptosis."

In cultures of human primary monocytes, resveratrol inhibits dose-dependently receptor activator of nuclear factor-kappa B (NF-kappa B) ligand-induced formation of tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells, TRACP activity in the medium, upregulation of cathepsin K gene expression, and bone resorption, scientists reported.

These inhibitions are associated with a downregulation of RANK expression at both mRNA and cell surface protein levels and a decrease of NFATc1 stimulation and NF-kappa B nuclear translocation, whereas the gene expression of c-fins, CD14, and CD11a is upregulated, the authors said.

Finally, resveratrol promotes dose-dependently the expression of osteoblast markers like osteocalcin and osteopontin in human bone marrow mesenchymal stem cells (hMSC-TERT) and stimulates their response to 1,25(OH)(2) vitamin D-3 [1,25(OH)(2)D-3].

"Moreover," Boissy continued, "resveratrol upregulates dose-dependently the expression of 1,25(OH)(2)D-3 nuclear receptor."

Researchers concluded, Taken together, these results suggest that resveratrol or its derivatives deserve attention as potential drugs for treating multiple myeloma.

Source:

Boissy, et.al. Resveratrol inhibits myeloma cell growth, prevents osteoclast formation, and promotes osteoclast differentiation. Cancer Res, 2005;65(21):9943-9952).

wrotek
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Novel class of vitamin D receptor modulator   (see page 343 of the document)

http://tinyurl.com/4fgjr7

Dermatologic drugs Researchers at Lilly and the University of Tokyo have identified a novel class of vitamin D receptor mod-ulators with therapeutic potential in the treatment of psoriasis. LY- 2108491 and LY-2109866 are two nonsecosteroidal vitamin D receptor (VDR) ligands that were investigated in vitro and also in vivo in a surrogate model of psoriasis. Both compounds were characterized as potent VDR ligands since they promoted heterodimerization of VDR with RXR (retinoid X receptor) with EC50 values of 11 nM for LY-2108491 and 13 nM for LY-2109866, in a ligand sensing assay in SaOS-2 cells. Both compounds were more potent inhibitors of keratinocyte proliferation than calcitriol, and induced the expression of vitamin D-responsive genes in keratinocytes, but not in intestinal cells, as effectively as calcitriol. In vivo, these two VDR modulators decreased Th1 cytokine response, by reducing the expression of proinflammatory cytokines interferon gamma and interleukin- 2.Agents that inhibit keratinocyte proliferation in psoriatic lesions have also been shown to induce epidermal proliferation in normal skin. Based to this rationale, LY- 2108491 and LY-2109866 were applied topically to hairless mice, where these compounds increased epidermal thickness with a higher therapeutic index than calcitriol. Interestingly, VDR modulating agents did not cause epidermal proliferation in VDR-defective mice. Furthermore, both topical and oral administration of these VDR modulators did not cause hypercalcemia compared with calcitriol, indicating a better safety profile (Ma, Y. et al. J Clin Invest 2006, 116(4): 892).


Last edited on Sun May 25th, 2008 19:07 by wrotek

wrotek
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Plant Flavonoid In Celery And Green Peppers Found To Reduce Inflammatory Response In The Brain

http://www.sciencedaily.com/releases/2008/05/080520094115.htm

this is luteolin



And this is apigenin, compond found also in celery i have mentioned  few  posts before.


Are not they very similar ?

Last edited on Tue May 27th, 2008 09:23 by wrotek

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How about this - you might not even need to drink the stuff to alter gene expression!


'DRINKING a cup of coffee can wake you up, but perhaps just a whiff of Java is enough to reverse the effects of sleep deprivation on the brain. A team led by Yoshinori Masuo at the National Institute of Advanced Industrial Science and Technology in Tsukuba, Japan, deprived rats of sleep for a day. When they examined their brains they found reduced levels of mRNA - messenger molecules that indicate when a gene is being expressed - for 11 genes important to brain function. When the rats were exposed to the aroma of coffee, the mRNA for nine of the genes was restored to near normal levels, and pushed to above normal levels for two - GIR, involved in neuro-endocrine control, and NFGR, thought to control oxidative stress (Journal of Agricultural and Food Chemistry, DOI: 10.1021/jf8001137).
We don't know if the same genes are suppressed in sleep-deprived humans, nor whether we would feel tired if they were, but many of these genes do have human equivalents. So the team says gene suppression may help explain why people feel bad when they haven't had enough sleep - and that gene reactivation could explain why people love the smell of coffee.
Next the team hopes to identify the molecules in coffee aroma that affect gene expression. They suggest pumping them into factories to help revive tired workers who can't sip coffee while operating machinery.'
From issue 2660 of New Scientist magazine, 13 June 2008, page 16

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At least these scientists are contemplating the possibility that their rat genes may not have human equivalents.

That is the degree of precision which Biology now enjoys, as long as the researchers are smart enough to comprehend that mice and men are not 100% equals:):)
 
 

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http://tinyurl.com/52ubaq

Novel Nutritional Ligands for VDR

VDR also selectively binds certain omega3/omega6 polyunsaturated fatty acids (PUFAs) with low affinity, leading to transcriptionally active VDR-RXR complexes. Moreover, the turmeric-derived polyphenol, curcumin, activates transcription of a VDRE reporter construct in human colon cancer cells. Activation of VDR by PUFAs and curcumin may elicit unique, 1,25(OH)(2)D(3)-independent signaling pathways to orchestrate the bioeffects of these lipids in intestine, bone, skin/hair follicle, and other VDR-containing tissues.

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I read about this a couple of months ago and wasn't sure if this has ever been brought up on the board.  Its about Green Tea Boosting Antibiotics.

If the topic has already been addressed my apologies.

http://www.healthfinder.gov/news/newsstory.asp?docid=614042


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I have been wondering about this green tea antibiotic boosting effect myself.
But i am afraid this is only an in-vitro work, and also they don't know how it works.

wrotek
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4-Caffeoyl-1,5-quinide in roasted coffee inhibits [ 3H]naloxone binding and reverses anti-nociceptive effects of morphine in mice
http://www.springerlink.com/content/e8ttltnn13015lbc/

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I agree based upon personal experience.
I had two boxer dogs who both developed similar symptoms to my disorders.
I did try to treat my last surviving dog but the protocol was too much for her.
She did respond initially and I watched her start to get better.
But I could not afford the benicar. She had some nervous system repair.
Except her hip muscles still atrophied.

I know now that  her dose of benicar was too low and not frequent enough.
her bladder & bowel control stayed normal even to the day I euthanised her.

Her untreated mother lost bladder control at the end.
 I am very proud of her treated daughter she gave me lots of hope for my own recovery.

She was the smartest bravest and toughest dog I ever knew.:dude:

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http://www.newscientist.com/channel/health/dn14151-guzzling-coffee-may-cut-heart-disease.html?feedId=online-news_rss20

Journal reference: Annals of Internal Medicine (vol 148, p 913)

A strong cup of coffee in the morning can feel like a life saver. Now, one of the largest and longest studies of coffee drinking suggests that coffee may indeed boost your lifespan – providing you drink enough of the stuff, that is.
The study tracked 129,000 men and women over two decades. It found that people who consumed several cups of coffee every day were less likely to die of heart disease than those who shied away from the stuff. Heart disease is an umbrella term for conditions including heart attacks, stroke, and arrhythmia.
The researchers found that women who drank four to five cups per day were 34% less likely to die of heart disease, while men who had more than five cups a day were 44% less likely to die.

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Heck, Nick, you would have to be fit and healthy to cope with more than 5 cups a day. One cup of the stuff used to make me sick. How is it possible the investigators didn't think of that:):)
 

Markt9452
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Trevor  - You have to "Guzzle" the Coffee  - You probably weren't drinking it fast enough.
mt

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Five cups is nothing.  I used to drink more than that.  Sometimes I would have the 5 cups by mid-morning. I knew others in the past that drank that much or more also.

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Count me among the coffee guzzlers.  I always amazed my wife in being able to drink coffee right up until bedtime and still be able to sleep soundly.  I thought it was a genetic ability among those of scandinavian descent.

A morning cup is still the fastest and most reliable way of clearing the morning herx.

- Chris

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I really like Coffee but I have noticed that in the last week or so it makes me feel bad when I drink it.  It upsets my stomach and I feel generally uncomfortable after a cup.

Makes it easier to cut back though. 

jr_md
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Just don't overdo the tea either.
Read this from the Mayo clinic
http://www.mayoclinicproceedings.com/pdf%2F8206%2F8206briefreport.pdf

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guys:

being with a batman suit, staying at home,avoiding light, not eating eggs, no beer either,hasn´t been sooo tough as not drinking my beloved coffee!!!

I must confess I drink a cup, when it is very desired.:P. and I doesnt feel anything odd...

wrotek
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Chlorogenic acid compounds from coffee are differentially absorbed and metabolized in humans.
http://www.ncbi.nlm.nih.gov/pubmed/17884997


Chlorogenic acids (CGA) are abundant phenolic compounds in coffee, with caffeoylquinic (CQA), feruloylquinic (FQA), and dicaffeoylquinic (diCQA) acids being the major subclasses. Despite the potential biopharmacological properties attributed to these compounds, little is known about their bioavailability in humans. In this study, we evaluated the distribution profile of the major CGA isomers and metabolites in plasma and urine of 6 healthy adults for 4 h after brewed coffee consumption. Three CQA isomers and 3 diCQA isomers were identified in the plasma of all subjects after coffee consumption, whereas 2 FQA were identified in only 1 subject. Two plasma concentration peaks were observed, the first at 0.5-1.0 h and the second at 1.5-4.0 h after coffee consumption. The molar ratio CQA:diCQA was 12.2 in the brewed coffee, whereas in plasma it ranged from 0.6-2.9. The molar ratios 5-CQA:3-CQA and 5-CQA:4-CQA were consistently higher in plasma than in the brew. The main CGA metabolites identified in urine after coffee consumption were: dihydrocaffeic, gallic, isoferulic, ferulic, vanillic, caffeic, 5-CQA, sinapic, rho-hydroxybenzoic, and rho-coumaric acids (gallic and dihydrocaffeic acids being the major ones). This study indicates that the major CGA compounds present in coffee are differentially absorbed and/or metabolized in humans, with a large inter-individual variation. Moreover, urine does not appear to be a major excretion pathway of intact CGA compounds in humans. PMID: 17884997 [PubMed - indexed for MEDLINE

Perhaps this can me useful.

Last edited on Fri Jun 20th, 2008 18:04 by wrotek

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Hi wrotek,

There was an interesting article to the right of the summary you linked to.

It was titled: "Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats."

There's been discussion previously about the gut microflora in Th1 disease.

Interesting.

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I believe the science. I have no doubt that coffee is bad for me. I go a week or two without any and then work jets me off to some lonely city to a sterile hotel room, and to a week in a fluorescent lit semiconductor lab with pressures to solve the problems that brought me there. I miss my home and family, I have trouble sleeping, I don't enjoy the work and I usually resent being there. On every trip I have been too weak to pass up the morning cup of coffee at the damned hotel breakfast. So I try to just limit myself to a cup or two on traveling days. Maybe that's why phase-3 neuro-herxing seems to last so long....

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http://mend.endojournals.org/cgi/content/full/21/7/1603/F1




Fig. 1. Determination of the Ability of Cafestol to Interact with a Range of Nuclear Receptors in Vitro

HepG2 cells were cotransfected with the Gal4 luciferase reporter and a series of chimeras in which the Gal4 DNA-binding domain is fused to the indicated nuclear hormone receptor ligand-binding domain. The cells were treated with a known receptor-specific agonist or 20 µM cafestol. Results are expressed as normalized luciferase activity relative to the known ligand control (set at 100%) (mean ± SEM). Gal4 with cafestol was normalized to the transactivation value obtained with the Gal4-receptor chimera with ligand, which was set at 100%. The ligands used were as follows. Mouse constitutive androstane receptor (mCAR): 250 nM 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP); estrogen receptor-{alpha} (ER{alpha}): 1 µM estradiol (E2); FXR: 100 µM CDCA; glucocorticoid receptor (GR): 100 nM dexamethasone; LXR{alpha}: 1 µM LG101268; peroxisome proliferator-activated receptor (PPAR){alpha}: 300 nM clofibrate; PPAR{gamma}: 1 µM roziglitazone; mPXR: 10 µM PCN; RAR{alpha}: 1 µM all-trans retinoic acid; RXR: 1 µM 9-cis-retinoic acid; thyroid hormone receptor (TR)ß: 1 µM T3; vitamin D receptor (VDR): 100 nM 1{alpha},25-dihydroxyvitamin D3.

Looks like FXR is more extensively activated than PXR, by cafestol.

This paper says http://www.aapspharmaceutica.com/meetings/files/84/Downesforweb.pdf

(3rd page) that PXR is activated by xenobiotics, FXR by bile acids.
FXR activation leads to down regulation of CYP7A1 and CYP8B1 (page 4) .

I understand that cafestol activates PXR, but should it activate FXR ?

Last edited on Sat Jul 19th, 2008 15:19 by wrotek

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Pity they didn't look at inverse-agonists (antagonists), which seem just as important to the functioning of the body :)
 
Another mistake the wet-biologists make is shown from the concentration of 1,25-D they used - 100 nanomolar. The level measured in Blood is less than 100 picomolar, or 1000 times less :) And they never seem to see the need to explain why they use so much...
 

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The 11th page of the document http://www.aapspharmaceutica.com/meetings/files/84/Downesforweb.pdf says that FXR is highly expressed in the liver and intestines. I wonder if this is the reason why some people get strong bowel movements soon after ingesting coffee.

Last edited on Mon Jul 21st, 2008 10:21 by wrotek

Russ
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Dr. Marshall, what do you make of these studies that indicate that there is antagonism between Vitamin A and Vitamin D at the receptor level?  The one about blocking certain actions of 1,25D in human kerotinocytes is interesting since vitamin A is touted for giving one smooth skin and reducing acne.  Some of the other studies deal with rats and chickens so I guess might not be as applicable. 

I am curious what you think because I am eating a low-carb, high-fat diet which includes lots of meat, butter, and cream...all pretty high in vitamin A.  By my calculation I'm consuming about 6000 IU per day, or about twice the RDA (3000 IU).  This is well below the established "Upper Limit" of 10,000 IU, however the last study on this list indicates that chronic consumption of two-times the RDA is right at the level where Vitamin A can cause an increased risk of osteopororis and hip fracture due to it's interaction with vitamin D and parathyroid hormone.  Then again, we know that most of what they think they know about vitamin D and osteoporosis is wrong.  Anyways, just want to make sure that I'm not somehow adversely affecting the function of the VDR and vitamin D metablolism and curious what your thoughts are in relation to this supposed antagonism between Vitamin A and Vitamin D.

"Vitamin A antagonizes the action of Vitamin D in rats":

http://www.ncbi.nlm.nih.gov/pubmed/10573558

"All-trans retinoic acid antagonizes the action of calciferol and its active metabolite, 1,25-dihydroxycholecalciferol, in rats."

http://www.ncbi.nlm.nih.gov/pubmed/15987844

"All-trans retinoic acid blocks the antiproliferative prodifferentiating actions of 1,25-dihydroxyvitamin D3 in normal human keratinocytes."

http://www.ncbi.nlm.nih.gov/pubmed/9397150

"PML/RAR alpha+ U937 mutant and NB4 cell lines: retinoic acid restores the monocytic differentiation response to vitamin D3."

http://www.ncbi.nlm.nih.gov/pubmed/7519122

"The influence of vitamin A on the utilization and amelioration of toxicity of cholecalciferol, 25-hydroxycholecalciferol, and 1,25 dihydroxycholecalciferol in young broiler chickens."
 
http://www.ncbi.nlm.nih.gov/pubmed/9565243
 
"The acute and chronic toxix effects of vitamin A"
 
http://www.ncbi.nlm.nih.gov/[highlight= #ffff88]pubmed/16469975

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The metabolites of Vitamin A are very active, right throughout the body. At high enough concentrations it can displace the Vit D metabolites. But it performs important physiological functions in conjunction with Vit D, especially in VDR transcription. I would try to keep my Vit A consumption at about the RDA.
 

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Are we talking about Vitamin A or its precursor Vitamin A?

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I am talking about the Retinoids, Retinoic Acid, and all the metabolites that dietary Beta-carotene and dietary Vitamin A finish up as...
 
 

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My understanding is that any concerns about consuming too much Vitamin A only apply to the pre-formed Vitamin A found in meat and dairy products and does not apply to the beta-carotene found in vegetables.  The reason for this, as I understand it, is that the body regulates the conversion from beta-carotene to Vitamin A and will only convert as much as it needs.    

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Interesting study about adenosine controlling T cells infiltration into Central Nervous System in mice. I ignore conclusions made by the authors of this study, that caffeine can help MS.

But i am interested  if adenosine facilitates entry of T cells into CNS, would it not be unwise to drink caffeine and prevent them from entering CNS if one has CNS infection, since T cells won't be able to clean CNS from bacteria, infected cells, waste products ? http://tinyurl.com/49f73m




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Ability of decaffeinated instant coffee extract to block the effects of morphine

http://tinyurl.com/6ne2ev

Last edited on Tue Jul 29th, 2008 22:04 by wrotek

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This is very interesting I think

Adenosine A2a blockade prevents synergy between -opiate and cannabinoid CB1 receptors and eliminates heroin-seeking behavior in addicted rats




http://www.pnas.org/content/103/20/7877.abstract

Last edited on Fri Aug 15th, 2008 17:15 by wrotek

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Since we use stevia as a sweetener, perhaps i should post this.

Chlorogenic Acid in Leaves and Lyophilized Extracts Of Stevia

http://www.springerlink.com/content/j2573u7341495341/


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Wrotek wrote:

Since we use stevia as a sweetener, perhaps i should post this.

Note that Table 1 of this article lists residue after extraction of leaves of chlorogenic acid content as 3.4 grams of biomass per kilogram.

For the amount of stevia I use, I think I will stick with it as a sweetener vs. artificial sweeteners or sugar. It took me 2 years to use up the last bottle of stevia extract I bought and this was a small 25g bottle.

Sunset :cool:

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Sunset,
Chlorogenic acid is immunosuppressive in nano-molar concentrations (10**-9). There are lots of nanomoles in 3.4 grams. Why not try to interleave Stevia and Splenda? Three days of each, interleaved, should let you know in a few weeks whether Stevia really is innocuous. Frankly I don't know, one way or the other. I didn't like Stevia when I tried it :)
 

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Honestly, I don't use stevia very often, maybe in one or two beverages a week. A serving size according to my bottle of stevia is 1/40 teaspoonful or 25mg. I rather like the taste, but do keep me posted if it turns out that stevia extract is not a recommended sweetener to use.

Thanks,
Sunset :cool:

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Stevia is not allowed for sell in Poland, perhaps due to sugar monopoly rather chemical composition, so i don't know much about it - is it a powder or lyophilized extract, how it is packaged etc.



Sunset, You are suggesting number 7. in the table is sold as a final product.

I thought this is what is left in the sample to be discarded, after final product extraction. And the only extraction is number 6. - lyophilization .

Chlorogenic acid contents can reach 8% in coffee beans, paper says.

From the photographs on google i see it is sold as a white powder or dried leaves.

Dry leaves (position nr 4 in the table) contain 116mg/Kg, which is 11.6% .

But if product is sold as a lyophilized extract, it will reach as much as 16.7% CGA concentration.

Perhaps the white powder product is not a big problem since it is further processed to contain stevioside mostly, and the rest ingredients, including chlorogenic acid, are removed.

Hmmm complex stuff, all depends from the plant processing.

It is even more interesting if one uses stevia for coffee, adding more chlorogenic acid to the coffee chlorogenic acid content.

The paper also says "of 204 randomly selected plant species, chlorogenic acid was found in almost 90" Unfortunately the paper is incomplete, and i would like to see this plant list.

Last edited on Tue Oct 28th, 2008 06:47 by wrotek

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Sunset, once or twice a week is usually fine, as the body tends to excrete most things in a 24 hour cycle. I tend to worry when folk have to eat stuff daily, and especially multiple times a day :)
 

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Stevia...Just when you think it is safe to go into the water....

Trevor, if I can't use any of the artificial sweetners (which I still can't, including splenda), and only use stevia on occassion, is a teaspoon of sugar here and there (for a real cuppa tea w/half and half...when I'd prefer 2% milk) going to do much harm?  (Once or twice a week...right now, I do that about every two weeks as it is a real comfort to me, but winter is coming on and this is going to be a cold one and there's nothing like a cup of tea in winter...I could reduce it to 1/2 teaspoon and get used to it.)  I can't even handle the sweetner in the chocolate that is recommended and so have to dole out wee bits of Lendt when I feel desperate for chocolate.

Thanks, Claire

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Claire,
What forms of Splenda have you tried? The small packets? The cooking granules? The liquid?

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The small packets...it causes intestinal upset and I've been living with diarrhea since 2000 and cannot tolerate things that make it worse--this is what happens with the sweetner in the chocolate as well, and the same would happen if I consumed a lot of sugar (a lot for me...I've never been able to consume a lot), but a small amount of sugar doesn't seem to upset my gut at all.  (I forgot to say that I don't steep the teabag...I'm a week tea drinker always.) 

Thanks, Claire

Last edited on Tue Oct 28th, 2008 09:48 by eClaire

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Hi!
I've read some where on protocol ( I think Dr Marshall post) that Splenda  doesn't contradict MP. I am taking 4-5 small packets a day. Is it OK?

Thank You, Gene

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Splenda is regarded as the most safe of all the artificial sweeteners, and many of our members (including me myself) use it. I have been using maybe a dozen packets a day for several years, and, except for my hair continuing to thin, don't seem to be any the worse for eating it:):):)
 

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Thank You Dr Marshall.
Gene

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Ok, I really don't want to restart this whole conversation... :? ... but ...

I have been on the protocol 16 months. With strong IP reactions the whole time. Just recently I have low enough Hct and Hgb (tied to inflammation of IP) that I need to 'put on the brakes' and I am really at only the lowest doses of the main phase 3 antibiotic combination.

And... I have used about a dropper full of SteviaClear liquid as a sweetner pretty much daily all throughout these 16 months...

Something is just not adding up. It seems that either the processed liquid called SteviaClear no longer has the chlorogenic acid levels that would hinder IP, or is there another explanation for the fact my IP doesn't seem to be slowed by using it?

:? ... Not trying to be difficult. Just trying to understand.

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Joyful,
We don't have enough data on Stevia. That doesn't mean it is necessarily a problem, but we just don't know yet. Splenda, on the other hand, is frequently reported here as OK.

Additionally, because some drugs can cause instability, the best time to assess the adequacy of one's own diet is when one is stable, not when one is having difficulty. I understand what you are saying, but just letting you know what is in my mind. Additionally, as I said to Sunset, it is best to abstain from a suspect substance every few days, from time to time. That is the best way to assess any interactions.
 

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Ok, Dr. Marshall. :)

I do try to rotate my foods, even lotions, and so on. But I've only taken a few 'holidays' from the stevia. I know that I may eventually reach a point where I am looking for anything that would hinder my immune system from chasing down the last of my microbial 'uninvited guests.' But it is obvious that I'm not there yet.

I did take a look at the particular product I am using's page to see if I could determine their processing technique and it seems to be different than the one used in the presented paper. As far as I can tell without writing the manufacturer, they may just soak the leaves in water. Perhaps other processing methods (such as using a centrifuge) would yield a higher concentration of chlorogenic acid?

From what I've read so far (including the article wrotek highlighted), many fruits and vegetables may contain cholorgenic acid at comparable levels to the stevia. I eat a fair amount of carrots (peeled), celery, lettuce, zuccini (unpeeled), cucumber, onions, and red bell pepper in a given week. Not to mention cooked onions, brocolli, green beans, peas, zuccini, and califlower. Plus perhaps 2 or 3 small fuji apples. Sometimes I make a smoothie with frozen blueberries, strawberries, and a banana. I may not be remembering well (I need to research this again), but I think the earlier advice was it was ok to eat these foods.

I understand that any processed food is 'guilty until proven innocent.' Simply because manufacturers regularly add undeclared substances (like vitamin D :shock:). So, I appreciate your guarded response to using any unproven item, especially concentrates. :cool:

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http://tinyurl.com/5u9c3w
Background: Caffeine, used for treating neonatal apnea, is eliminated 3-fold slower in breastfed infants than in formula-fed infants. Caffeine is metabolized by cytochrome P450 (CYP) 1A and CYP3A4, which are regulated by aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) respectively.
So, that is how nicotine increases caffeine metabolism, by increasing PXR activity.

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My wife and I just had a baby. He's premature. So they have him on caffeine for his apnea. Works like a charm to up his breathing rate. They have him on a human milk fortifier with a ton of vitamin D. :X

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Congratulations :D , hope the Kid won't have any Th1 problems.

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:cool: i'm sure he'll be fine. thanks amigo.

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:dude: hurray congratulations!

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Drink coffee, see dead people

http://www.theaustralian.news.com.au/story/0,25197,24911629-12335,00.html
Interesting study suggesting that perhaps steroids can provoke hallucinations.
I wonder whether this could contribute for example to schizophrenia
"This is a first step towards looking at the wider factors associated with hallucinations," said lead author, Simon Jones, a PhD student at the university's psychology department. "Previous research has highlighted a number of important factors, such as childhood trauma, which may lead to clinically relevant hallucinations. "Given the link between food and mood, and particularly between caffeine and the body's response to stress, it seems sensible to examine what a nutritional perspective may add." When under stress, the body releases a stress hormone called cortisol. More of this stress hormone is released in response to stress when people have recently had caffeine. It is this extra boost of cortisol which may link caffeine intake with an increased tendency to hallucinate, say the scientists.

Last edited on Wed Jan 14th, 2009 04:04 by wrotek

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I used to have visions and premonitions of future events, many have been documented.
My ex boss, fellow employees and relatives can confirm this.
My best explanation is everybody can have them but few have had them consistently
enough to know they are experiencing anything but daydreams.
This protocol was one of those premonitions back in 1995.
I think some how my nervous system connected with the energy expressed from quantum entanglement of possible future realities. So I would see words and symbols and occasionally images.
Good to know the living horror show i have been through can be contributed to  "just a bit of undigested mustard" or too much chlorogenic acid.

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Perhaps scientists misinterpret their findings, maybe it is not cortisol that causes this. Maybe it is not caffeine, but cafestol or chlorogenic acid that are responsible.

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Please don't think i am mocking you.
Its just my way of introducing what stressful events
helped me become immune compromised.
My sober response is those experiences were just co incidental.
but my stress was still very real thank goodness i did not develop cancer.

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Coffee may improve psoriasis treatment response

http://findarticles.com/p/articles/mi_hb4393/is_7_37/ai_n29279794

Dr. Helfrich said she believes the observed effect of coffee is due to the caffeine, so presumably other caffeinated beverages would have similar impact, but this remains to be determined by future research.

Interesting

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Caffeine is now used in many creams, potions and lotions for various skin problems and aging!  Maybe coffeee with caffeine could be used as a home remedy on skin lesions?!  Sugar scrubs are popular now as well ....:cool:

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In this study they suspect caffeine, but test only coffee, they only think other caffeinated beverages will have similar effect

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New buzz on coffee: It's not the caffeine that raises blood pressure

http://tinyurl.com/dnf77h


http://news.bio-medicine.org/medicine-news-2/New-buzz-on-coffee-3A-Its-not-the-caffeine-that-raises-blood-pressure-6496-1/



Swiss scientists studying caffeine's effects in a small group of people report markedly elevated blood pressure and increased nervous system activity when occasional coffee drinkers drank a triple espresso, regardless of whether or not it contained caffeine. The results suggest that some unknown ingredient or ingredients in coffee not caffeine is responsible for cardiovascular activation, he explains. Coffee contains several hundred different substances.

Last edited on Wed Mar 11th, 2009 07:16 by wrotek

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wrotek wrote: Coffee and cigarettes composition starts to be very interesting in regard to vitamin D metabolism :)


The Aryl Hydrocarbon Receptor Activator Benzo[a]pyrene Enhances Vitamin D3 Catabolism in Macrophages.

http://www.ncbi.nlm.nih.gov/pubmed/19244278

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Wow, interesting... if it states what it is that I think it says, given that "ligand" and "catabolism" aren't really in my vocabulary.

:?dette

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Smoking tobacco lowers d 1,25.
Now that's atomic good one wrotek.;)
 
 

Last edited on Sun Mar 15th, 2009 10:41 by Prof Trevor Marshall

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Modulation of vitamin D signaling by AhR may represent a mechanism underlying cigarette smoking-related diseases.

lilke lung cancer ?

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BaP enhanced the hydroxylation of 1,25(OH)(2)D(3) by CYP24A1 in THP-1 cells. Thus, AhR activation by BaP stimulates vitamin D(3) catabolism.
All right, does this mean that smoking can reduce the problems of Hypervitaminosis-D?  I think it is saying that BaP helps get rid of 1,25D.  Which would support  the notion that smoking is a form of self-medication.

1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], a potent ligand for the nuclear receptor vitamin D receptor (VDR), has been shown to decrease the risk of osteoporosis, some types of cancer, cardiovascular disease, suggesting an opposing effect of vitamin D(3)
The terminology here seems not to follow what I've read elsewhere.  Elsewhere 'D2' and 'D3' refer to forms of 25D, that are converted to 1,25D in the body.  So, is there a D3 form of 1,25D as well as a D3 form of 25,D?

-- Chris

Last edited on Sun Mar 15th, 2009 09:34 by Chris

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Elsewhere 'D2' and 'D3' refer to forms of 25D, that are converted to 1,25D in the body.  So, is there a D3 form of 1,25D as well as a D3 form of 25,D?


Chris,

Yes. Globally:

Ergosterol -> D2 -> 25D2 -> 1,25D2

Cholesterol -> D3 -> 25D3 -> 1,25D3

1,25 (OH2) D3  -->  the OH2 between brackets are the two Hydroxyl (OH) groups. 

In 25 (OH) D3  there is ony one hydroxyl group, so we could spell it 25 (OH1) D3

Hope this helps,

Frans

Last edited on Sun Mar 15th, 2009 06:02 by Frans

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Good find, Bane. This lines up with my anecdotal observations of symptom palliation in Sarcies. It would also explain the difference between effects of second-hand and mainstream smoke.

Note that health-care workers (esp. nurses) have a much higher rate of smoking than other professionals. Hmm...
 

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Oh, good work Wrotek.  It took you a while but you managed to show we really shouldn't still be enjoying that morning cup of java.  Let me go jump off a bridge now...:cool:

Just please don't pick on resveratrol next, I'm pretty darn sure that evening glass of wine is palliative, too... :shock:

Ruth

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Does anyone know if marijuana is also an immune system modulator????

Best to everyone, Martha

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Martha,
That question is best asked in the Health Professionals' forum:)
 

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Could my progress be inhibited by my medium iced coffee almost everyday?

lisa

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Re: Coffee and black tea

In case it's of interest...

I've pretty much avoided coffee for most of the MP. I can take a sip or two, then that's enough. It doesn't "feel" right when I drink filter coffee. I would drink a cup or two of weak black or green organic tea on and off in the morning.

However, about a month ago, I started drinking more tea. I'd found some decaf black tea that I like, so I ended up drinking about 4 cups of tea a day. About a week into that, I started drinking a heavenly mix of instant coffee (with whole raw milk and splenda).  Seems the instant coffee didn't make me feel as instantly yucky as the "Starbucks" type.

Rather belatedly, I realized that I have felt like absolute crap for the past few weeks - along with a  "life out of body" sensation. My DH as well. He started the morning coffee thing and I was also giving him a cup or two of decaf black tea a day.

Sooo, we both decided yesterday to drop the coffee and black tea (we've never really experimented much with anything else). I must say that I felt some better today. Him too. Or at least, not so "weird."  And, we both slept a bit better last night (sleep has gone to absolute pot over the past few weeks).

It'll be interesting to see if this is all directly connected the topic of this thread and not "just" that sometimes overwhelming IP that comes with a new dose of Clindy.

RE: Tobacco

I smoked for many years when younger. I could NEVER stand the smell of smoke from others though. It'd make me feel ill. However, when I smoked myself, I felt better.  I just blew the smoke out the window. Interesting that it could have been palliative - makes sense when I think about it because I would feel better. I would smoke even when feeling very ill. Hmmm.  

I never had a smoker's cough. And the lung infections I caught from a young age on didn't diminish even after years of quitting cigs. On the other hand, I could  breathe more deeply at higher altitudes without them. :?

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looks like i'm going to have to give up my daily mcdonalds medium iced coffee.  I hope I can drink iced tea at least.

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does anyone know about NT factor and how it can help with energy?  is it contraindicated in the MP?

 

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Ala
RE: Tobacco

I smoked for many years when younger. I could NEVER stand the smell of smoke from others though. It'd make me feel ill. However, when I smoked myself, I felt better.  I just blew the smoke out the window. Interesting that it could have been palliative - makes sense when I think about it because I would feel better. I would smoke even when feeling very ill. Hmmm.  

I never had a smoker's cough. And the lung infections I caught from a young age on didn't diminish even after years of quitting cigs. On the other hand, I could  breathe more deeply at higher altitudes without them. :?
  
My story is very similar i smoked cigarettes from 1999 till 2008 and still cant stop craving them. 

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i quit smoking in 1994 when I got lyme disease.  I still have cravings for it.  Although i can't stand the smell yuck!!!

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Don't get me started.  :X  I will go to the grave wanting a cigarette even though I haven't allowed smoking in my house for 24 years :shock: and get grossed out being around people who've been smoking.

:cool:dette

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Never mind the coffee and the ciggies, hold the cookies!!

http://www.ncbi.nlm.nih.gov/pubmed/8055906

http://www.jbc.org/cgi/content/full/280/49/40901

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I wish I could understand one word of what they are saying!!

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i broke down and had a coffee, i'm disappointed in myself.  I love my coffee.  Will it really affect me getting well with the MP?
i need prayer for this i think.

lisa

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Thank you Diana!

But on that first one, if I ignore all the numbers and just look at the words "VDR" and "inhibit", they seem to point to the culprits being "wheat germ" :shock: and "energy depletion" [which they defined as accomplished by chilling, but I define as accomplished by exercise :P]. 

It's all gobbledy gook to me, too.

:Ddette


Last edited on Tue Mar 17th, 2009 11:35 by expate

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Diana,

I'm with you.  I didn't see anything about cookies in there.

Chris

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Yes it is a bit obtuse, I'm sorry I couldn't find anything clearer so far. Basically nuclear receptor peptides (like VDR) are formed in the cytoplasm and have to be transported into the nucleus before they can transcribe the genes. This is an energy dependent active process so it doesnt just 'happen'. Incidentally 1,25D, also has to be bound to 'vitamin d binding protein' for transport to it's binding sites, as reported on by Garyv recently in 'vitamin d claims in the news'. NO, not true, - see my post below.. Trevor..

The protein involved with the transport to the nucleus in the case of the VDR appears to be inhibited in it's action by WGA (wheat germ agglutinin), a well known lectin found in some cereal products. So maybe that is one reason why cookies etc. are such comfort foods, because they slow the innate immune response.

Last edited on Tue Mar 17th, 2009 18:04 by Prof Trevor Marshall

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You know, one of the problems of relying upon peer-reviewed papers is that so many of them are incorrect, and most (nearly all) are more than a few years old, and of questionable value (the translocation papers are too old to be useful, IMO).

Mouse were recently bred without the D Binding Protein (DBP), and lived perfectly normal lives, reproducing normally. Yet they had zero (yes, ZERO) circulating levels of 1,25-D in their bloodstreams.

http://www.ncbi.nlm.nih.gov/pubmed/18372326

This tells us that Adams et al's hypothesis that DBP is necessary for translocation is almost certainly not true, because the mice would not be healthy without translocation.

Secondly, this tells us that 1,25-D is not a circulating signal hormone, but a metabolite leaking through the cell wall into the bloodstream. Which is why it is at such a low concentration. Look at this diagram: (the I and V are vertical arrows, BTW)

25-D  in bloodstream at 40nanomolar
|
V
20 times attenuation
|
V
Cell Cytoplasm, 25- D and 1,25-D both at about 2 nanomolar
|
V
20 times attenuation
|
V
1,25-D transported by DBP in the bloodstream at 100 picomolar

Which implies that 25-D leaks from the bloodstream through the phospholipid bilayer (which forms the cell wall) into the cytoplasm, and 1,25-D leaches out from the cytoplasm into the bloodstream (each with about a 20 times concentration attenuation compared to the cytoplasm).

It also implies that the cell gets all the Vitamin D it needs from its own internal sources, and the circulating 25-D contribution from diet, etc, is purely collateral damage from eating and hunting, as it is ultimately immunosuppressive.


See, it's quite easy to turn the whole scientific world on its head :)

..Trevor..

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Fascinating Trevor, but I find it intriguing that DBP does appear to have an important involvement with the immune response anyway. These are the Yamamoto papers that Garyv referred to - how do you think they might relate to MP thinking?
 
http://www.ncbi.nlm.nih.gov/pubmed/18058096

 

Last edited on Wed Mar 18th, 2009 00:50 by Prof Trevor Marshall

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D Binding protein has a pretty low affinity for the Vitamin D metabolites, by comparison with the VDR. I suspect that binding the D metabolites is not its primary role.

Yamamoto's papers are exploring what could be the DBP primary role. Note that the role explored by Yamamoto has nothing to do with the DBP protein's ability to bind the D metabolites.
 

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Trevor: this qestion is very silly, but I couldnt refrain myself:D:

Can you invent a pill which stop us to produce D stuff???

It would be soo nice...

kiss

Last edited on Wed Mar 18th, 2009 11:46 by marion villa

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Marion, Unfortunately, D-stuff does a lot of things on a variety of receptors throughout the body, and I doubt we would survive if it was fully blocked :)
 

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:(,;)

thanks!

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Anecdotally, coffee makes me feel bloody fantastic!  (I first indulged after being on the MP about 14 months, during which time I hadn't had any coffee).  Because it made me feel so great, I knew that it had to be seriously interfering with my system (as this thread indicates).  So I continue to abstain.  But occasionally weaken and indulge in a weak cup.
regards, k

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http://www.ncbi.nlm.nih.gov/pubmed/12460875
Coffee acutely increases sympathetic nerve activity and blood pressure independently of caffeine content: role of habitual versus nonhabitual drinking.

full paper http://circ.ahajournals.org/cgi/content/full/106/23/2935

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i  really don't understand alll the science of it all.  Basically my question is if i continue to have a medium iced coffee almost everyday will it affect my MP progress?  What will it do to the immune system?

Ps does anyone know about NT factor for energy?

 

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Basically my question is if i continue to have a medium iced coffee almost everyday will it affect my MP progress?  What will it do to the immune system?

Nobody knows the answer. All we can do is alert you to probable problems. You will need to stop this activity for a few days, and see if it makes any difference.
 

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Mercuryspice, i look at it all in a very simple way.. What is not necessary, should be avoided.
Our body runs on certain type of fuel.
Proteins, fats, carbohydrates, vitamins (where vitamin D is not a vitamin anymore :) ) minerals & water. Nothing more is needed.
Anything more can be either harmful because biologically active, or a waste, that body will have to use energy to detoxify.
And coffee contains hundreds of chemicals.

Last edited on Sat Mar 21st, 2009 00:34 by wrotek

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Wrotek, you forgot one thing. The Beatles claimed; All you need is love!

wrotek wrote: 
Nothing more is needed.
Anything more can be either harmful because biologically active, or a waste, that body will have to use energy to detoxify....

If the coffee and the cigarettes makes you a more loving person, that might be a necessary fuel for many of us, to go on.
But on the other hand, love can be harmful. What good brings a broken heart...;)

If I do not get my coffee in the morning, I am a total mess and close to dangerous. :XAnd a few times in my life, I have gone back to smoking cigarettes, just to prevent something much, much worse to happen.
My conclusion is;
If it comes down to life and death, of course we must choose immediate palliation! :)

Last edited on Sat Mar 21st, 2009 02:02 by Lottis

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:)
If I do not get my coffee in the morning, I am a total mess and close to dangerous. That sums up exactly what coffee is.

but i am still struggling to quit it too

Last edited on Sat Mar 21st, 2009 02:11 by wrotek

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Everything in moderation – even moderation!

 

Cheers

 

Guss

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I would like to say something about the taste and why is it for.

Taste is the mechanism that evolved to inform us whether food in our mouth has a nutritional value.

Now, lest take a look how raw black tea, raw coffee and  raw cocoa taste like, without any additional sugar, milk. They are bitter and very distasteful.

Moreover, black tea is created by fermentation of the leaves of green tea. It means that green tea leaves lay down and the bacteria come and eat all the sugar left and all nutritional value in them, then bacteria die and  leave all the rest that cannot be converted into energy anymore, to serve as a food for bacteria.

We have made a culture out of these "waste"  products that we call  a black tea or coffee or cacao :]   When we add sugar or rmilk, they have nutritional value again and taste better ;]

Last edited on Sun Mar 22nd, 2009 11:34 by wrotek

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"Caffeine and join pain" discussion

http://tinyurl.com/dc35ev  these are higly interesting stories of coffee users,

personally i like this one

Joint pain and Coffee
Postby john.631 on Sun Nov 21, 2004 6:46 pm I am a very lucky 73 year old male who has no chronic pains and who is not on any prescription or over-the-counter drugs. I usually don't drink coffee, but I make 4 cups a day in the morning for my wife. Recently I started saving her coffee leftovers in the refrigerator since I found I like iced coffee. Normally, I would sip hot coffee, but I found myself chug-a lugging 8 ounces of the cold stuff in a few minutes. Then I began to suffer very serious neck and back pain from what before had been temporary discomforts. (One night I was awake at 4 AM seriously considering going to the emergency room.) I would have to avoid further irritation of that particular pain for two days before it would abate. And then another injury would occur and I began to think my pain free days were over and that I had suddenly contracted arthritis. Remember I have been in good spirits and chronic pain free for 73 years. I was beginning to panic. The only thing I could think of to do was to quit drinking all that coffee. And that was the end of it. I was back to my old pain free self


http://tinyurl.com/dljzx7

and here are other stories, much unique and harder, with stronger psychological reactions - very unique.

  some quotesFinally I have found someone else with similar problems with caffeine. I have just resently (three weeks ago) solved my problem with panic disorder and stress.


I had your exact experience with caffeine, also in my early thirties. Although I was in excellent health, within a year of starting to drink coffee I experienced anxiety attacks, mania, depression and--horrifyingly--psychosis. In the last few weeks of my coffee habit I was walking around like a zombie and could hardly speak above a whisper. When I quit caffeine my symptoms vanished.

eClaire
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I haven't been following this discussion in a while and I am wondering if the advice that maybe one small coffee a day is out, is the idea that I can use one apple a day as a palliative out as well.  (Same chemical I believe.)  I only eat 0 to 2 apples a week, but if going through a really terrible time, I might eat more.  I usually only eat what I need (e.g., 1/3 of an apple if that is all that is needed). 

So far an apple is the only thing I've found (aside from icing for pain) as an all round sx palliative.

Thanks for the clarification.

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Hi Claire,

Apples are a source of quercetin, so perhaps that is why you are finding it palliative. Have you tried taking quercetin caps ( around 250 ml) at a time? I find them to be very helpful for certain IP's.

I have cut coffee back to one weak cup of the instant stuff once every week or two weeks, as I find it sometimes helps with my IP's and it gives me the lift I need, but I often go without any for weeks at a time. I use about a small teaspoon of coffee and add some almond ( no D added) organic milk. It's a good treat once in a while!

Feel better.

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Quercetin itself (the caps) has caused pretty severe rebound IP and so I've been nervous about trying it again.  Apples have worked from the beginning; I stumbled onto that before we started talking about it here.  I thought that apple skins (and most pears) also had Chlorogenic Acid, which is why I posted this here.  Thanks for the information KAS.

Claire

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I want say that if you need a little palliation, and you find it works for you, a little apple would be O.K.  Tea also has chlorogenic acid and we haven't ruled that out.  But I would keep it to a low level and suggest that antibiotic and other adjustments are preferable for managing the IP level than other methods (like chlorogenic acid containing substances).  My own experience indicates pear does not have a significant amount of chlorogenic acid.

Joyce Waterhouse

Last edited on Wed Apr 22nd, 2009 19:50 by jcwat101

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Thanks Joyce.  I do try to keep apple ingestion to a minimum and change abx instead (and at the same time, not throw every apple out of the house...I try to keep three on hand in case I get a strong IP that needs palliation...before a decrease in abx can help).  So sometimes I enjoy an apple when I don't need it for palliation.  I rarely drink tea (never coffee), and I tend to drink it for pleasure very weak when I do, as apples are the real deal when it comes to palliation for me.  Thanks again, Claire

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Like CelticLadee noted early in this thread, I eat an apple every day in the a.m. (that plus a few frozen sour cherries from my orchard is my sole breakfast/lunch), and I do not notice any palliative effects at all.

However, I DO PEEL my apples (and have for well over a decade) for 2 reasons other than their potential chlorogenic acid content:
  1. They are not organic (although I do pick them myself at an orchard in the mts.)
  2. Apple skin is a "harsh" fiber (like that in raw celery, broccoli, cauliflower, carrots and other root veggies) which can irritate the ileocecal valve in many with a sensitive gut (most all of us here?) and put stress on the gall bladder, thereby causing weakened fat absorption which decreases cell membrane strength and innate immunity in general.
This last tidbit I learned from a book by Jonn Matsen, N.D. (republished as "Eating Alive") and found the truth of it through my own experience. It's also worth noting here that one of the significant improvements at my 10-month mark on the MP was improved fat digestion (smaller, more frequent and sinking, rather than floating, stools).

Matsen also says when the ileocecal valve is irritated by sharp cutting fiber such as that in apple peel and wheat bran, this compromises it's function of preventing microbes in the colon from getting into the small intestine where their waste products (and CWD forms?) can potentially be absorbed.

It would be interesting to find out, Clair, whether the palliation you note is derived from the apple itself or from the skin. As we all know, palliation from certain substances (like Vitamin D and sunshine) may not be desirable in the long term.

I have also found that avoiding all nightshade vegetables (tomatoes, potatoes, peppers, eggplant, tobacco) may be critical in reducing the inflammatory symptoms that many of us experience as immunopathology (I'll be posting about that in another thread).


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Matsen also says when the ileocecal valve is irritated by sharp cutting fiber such as that in apple peel and wheat bran, this compromises it's function of preventing microbes in the colon from getting into the small intestine where their waste products (and CWD forms?) can potentially be absorbed.
What rubbish. Why do scientists try to simplify complex systemic behavior to this level? All cells are porous to L-forms. Infected immune cells travel throughout the body. Macro concepts such as advanced by Matsen have no role to play in modern Medicine.


As for apples,
if I remember correctly, the Chlorogenic Acid is in a layer beneath the skin, to prevent entry to the fruit by pathogens.
 

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Dr. Marshall, forgive me if I misled. Matsen said nothing about L-forms; that was my own ignorant editorial (parenthetical) speculation.

I doubt very much if Matsen knows anything at all about L-forms. In any case, the book I was referencing was published 22 years ago.

His observation on ileocecal valve functioning, however, I found to be true in my own experience, and my digestive function took a giant leap forward when I eliminated scratchy fiber from my diet. After all, we're not exactly designed by Nature to eat a lot of cellulose like cows and sheep, are we? ;)

Having had years of rather severe gut problems behind me now (ongoing from about age 25 to 45), I found out just how debilitating and discouraging they can be. As I've said before, my gut immunopathology has been minimal since going on the MP nearly 14 months ago (and for a decade prior), while kidney/anemia/muscle herxing continue unabated into at least the 10th month now.:P

So IMHO elucidation of certain food and gut function issues may be helpful to those who are still experiencing significant gut immunopathology.

Just trying to "pay it forward.":):)


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Gary,
I know it might sound reasonable for you to think in terms of "scratchy" fibre, but I will guarantee that the scratchyness of the fibre in your diet has little or nothing to do with reflux of bacterial species from the colon to the intestine.

Our whole understanding of GI tract science has changed within the last several years, especially with the understanding that  innate immunity is active, more so than adaptive immunity (as was previously believed).
 

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In 1995, NASA’s Dr. David Noever and his fellow researchers at the Marshall Space Flight Center studied the webs spun by common house spiders (Araneus diadematus) dosed with several drugs, including LSD, marijuana, benzedrine, chloral hydrate and caffeine. The more toxic the drug, the less organized the web the spider created.


The spider on marijuana drifted off before finishing the job. The spider on benzedrine, an upper, worked energetically but without much planning. The spider dosed with chloral hydrate, a sedative, soon fell asleep.

To the surprise of Dr. Noever et al, caffeine did the most damage of all the substances tested. The spider dosed with it proved incapable of creating even a single organized cell, and its web showed no sign of the “hub and spokes” pattern fundamental to conventional web design...

http://caffeineweb.com/        .....go to the end of the page

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What an interesting article Lottis. Oh, the poor spider on caffeine! :shock: I've never been able to tolerate caffeine since the time I was a child. Even in small amounts it makes me feel very anxious!

I was reading a quote written by Roland R. Griffiths, Ph.D, The Johns Hopkins University School of Medicine on this same webpage that you posted. He states that "It has been noted that caffeine intoxication can occur in someone who has been using caffeine for many years with no prior apparent problems."

This makes me think that perhaps Th1 illness is involved here. It seems to me like there's a tipping point; that a person's particular bacterial load or even the status of his immune system is involved. For example, could one trigger be an excess intake of Vit D followed by suppressed immune function. This could lead to the accumulation of pathogens in the liver which in turn could lead to a decreased clearance of caffeine in the body.

I wonder if a caffeine clearance test could be useful in determining the likelihood of whether or not an individual is reaching that "tipping point" before the development of the symptoms of Th1 illness?

Best regards,
Sunset :cool:

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Oh, if only medicine could be as simple as "liver clearance," then the chelation proponents would have been able to effect a cure, rather than just a temporary palliation.

The precise operation of the human metabolism is infinitely more complex than any of us can ever hope to comprehend...  The more we understand, the more we realize we don't know...
 
In 1978 my early medical research colleagues booked me into hospital to be weaned off a plethora of medicinal drugs, including strong, fresh-brewed coffee, upon all of which I had become dependent for palliation. Today I can drink coffee without any effect whatsoever - it's just another drink (although it does smell good :) )
 

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Dr. Marshall you give me hope that one day I'll be able to enjoy the great treat of coffee.  It wasn't until about two months before starting the MP that I discovered coffee was good!  I'd always tried it with cream, thinking I could not tolerate it black.  I don't know how people tolerate it with cream!!!:D  I discovered that black coffee w/ just a tiny bit of sugar (or agave) tastes like liquid chocolate to me and what a treat that would be if I could have it once a day!

In thinking about early signs for TH1, I am thinking we may already have one in the form of allergies of any sort.  Family history would be a good early detector as well.  I mean, if family members are dropping from disease at an early age, then it is probably likely that the children of such people are well on their way to being sick.  At any rate, that makes sense to me.

Prof Trevor Marshall
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Indeed, as Amy just wrote:

http://www.aacijournal.com/content/5/1/8/comments#384657
 

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Recently I consumed a very small amount of coffee for no more than five days, and then went to my routine bimonthly visit to the MP doctor.

My blood pressure systolic number jumped to 140; I don't recall what the diastolic was.  My MP doctor asked me to monitor it twice a day, and said she would be "forced to take action" if it didn't come down.

I d/c the coffee and my blood pressure is now 90/65 for the last week. 

The MP journey is long and quite fascinating, no?

Sherry

P.S.  Hot water with small amounts of half & half flavored with vanilla is a suitable substitute.

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A new paper is out - summarized at: http://bit.ly/5KTctp

"Coffee May Lower Risk of Aggressive Prostate Cancer"

"Dr. Wilson, who presented study findings at the American Association for Cancer Research Frontiers in Cancer Prevention Research Conference in Houston, said caffeine is not the key factor in this association"

hmmm...
 

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What I'd like to see is those stats in a particular age group of men who are then followed for the next 20 years to see what, if any other, conditions they develop eventually.

Claire

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Perhaps of some interest, I am having a couple of cups of coffee in the morning, and occasionally a one or 2 more a little later.  Have noticed that my herxing is a little more obvious in the later part of the day and during the night.  Since I seem to be over the hump in terms of being slowed down by the MP, and my significant other is scheduled to go on the MP in January, his education to get him over his skepticism being a prime mover in my urge to moved rapidly thru the early part of the MP, I am quite happy with this slowed rate of progress on the MP.  Cynthia

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Just as another data point here: A couple of times I have had a cup of decaf coffee when eating out. Each time I have felt a break from some symptoms for a couple of hours after.

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Chlorogenic Acid and interferon gamma

http://www.lifexonline.com/luteolin_pdfs_1/Luteolin_Im_IFN-G_IL-5_49.pdf


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Different plant chemicals and their effect on interferon gamma concentration.


wrotek
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Please dellete my previous post, something went wrong with it :)

The Chlorogenic Acid and Caffeine Content of Yerba Maté
http://www.latamjpharm.org/trabajos/24/1/LAJOP_24_1_2_5_8KBZFG0I38.pdf

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wrotek wrote:
Different plant chemicals and their effect on interferon gamma concentration.




:) Interesting how high the PHA and the ConA is. I wonder in what plants these chemical are high and what that might do. And in this case Chl.acid compares very low.

A Googling gave me this link about the indirect effect on the lymphocytes:
http://www3.interscience.wiley.com/journal/112214369/abstract

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Lottis, what was the source citation for this graph?
 

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It is from the post before the graph.

Chlorogenic Acid and interferon gamma

http://www.lifexonline.com/luteolin_pdfs_1/Luteolin_Im_IFN-G_IL-5_49.pdf

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Shaping of monocyte and macrophage function by adenosine receptors
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228265/?tool=pubmed

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mice again though:

http://pubs.acs.org/stoken/presspac/presspac/full/10.1021/jf904062c

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I have been such an idiot.
I have decided to get rid of coffee and thus bought 'muckeF***'
made of barley, rhye and chicory. And then I felt very, very ill.
Then I read again through this forum. Should have read it before....
I am back on 'coffee' (moderate) and enjoy the smell....

Titta

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It seems we all fall back on coffee at some point ...:?  I was wondering if a chickory coffee blend would wreak less havoc?  TIA!!  Lee

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I have been such an idiot. I have decided to get rid of coffee and thus bought 'muckeF***' made of barley, rhye and chicory. And then I felt very, very ill. Then I read again through this forum. Should have read it before.... I am back on 'coffee' (moderate) and enjoy the smell.... Titta That is a huge reaction to coffee. Are You saying that coffee decreases your symptoms from totally intolerable to tolerable ?

wrotek
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It seems we all fall back on coffee at some point ...:? I was wondering if a chickory coffee blend would wreak less havoc? TIA!! Lee I dont know what is chickory coffee but substituting coffee with anything Is in my opinion impossible, nothing works and tastes like it.

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Hello Wrotek,

I imagine that you can buy similar coffee surrogat in Poland, too.
I grew up with it as the 'poor people coffee' or  "mucke f u c k" or coffee for children.
The latter part of the word is deleted in this forum but it has nothing to do with that f word. Coffee surrogate looks like coffee, tastes similar to coffee and smells a bit like coffee (and of course I have my memories...).
Tja, there is even the Cafe Cantate by Mr. Bach.....

Titta

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I have never really been much of a coffee drinker, but my husband is hooked on it, and even roasts his own, so I would have a cup or two a week with no discernible problems before the MP.

Since I started the MP, however, I barely ever have coffee anymore, unless it's tempered with a lot of ice and half&half, as in a frozen drink.  When I drink it black (the way I should, with all the amazing-smelling gourmet stuff in my house) it makes me feel jittery, I get stomach cramps, headaches and brain fog within five minutes or so.

This could be partly due to caffeine, but I don't react this way to other forms of caffeine:  diet coke and those "5 Hour Energy" Drinks (I indulge in these very rarely) increase my energy, without the undesirable side effects.

I used to drink a lot of Diet Coke.  Now just a couple per month.  I'm lucky to be free of the caffeine "jonze" and prefer to keep it that way, so I really don't miss it.

Lee
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 Luzianne and Community are two brands of coffee/chickory blends that are decent.  I too, get such an immediate relief from IP for a few hours with plain decaf coffee.  I also think it regulates my blood sugar, maybe?  The chickory/coffee blends do not have as profound effect as coffee does for my IP.  Not easy finding these blends in decaf at my small stores though.  I am off "real coffee" for now.  I am just interested to know if chickory is as bad as coffee for us, since I don't feel it effects me like coffee ...:?  Cheers!  Lee

wrotek
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Since chlorogenic acid hits beta thyroid receptor so hard...

Thyroid Hormones Regulate ß-Amyloid Gene Splicing and Protein Secretion in Neuroblastoma Cells1

http://endo.endojournals.org/cgi/content/full/139/6/2692

wrotek
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Green tea also has chlorogenic acid apparently, don't know how much though.

http://www.ncbi.nlm.nih.gov/pubmed/1614995

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http://healthfreedoms.org/2010/06/23/coffee-and-cancer-risk-java-junkies-less-likely-to-get-tumors-study-says/........

I was not able to drink coffee for years and when allergy tested it was the only substance for which they could not find a tolerable dilution.  But since the MP and MELITA,CLASSIC LITE, with reduced caffine and acidity,  I am able to have a cup or two a day several times a week with no apparent ill effects.  I must say I really enjoy it!!!

Dian

wrotek
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Role of chlorogenic acid in the toxicity induced by Chinese herbal injections

http://informahealthcare.com/doi/abs/10.3109/01480540903580055?journalCode=dct

wrotek
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There are 3 isomers of chlorogenic acid(Caffeoylquinic acid), does it make a difference ?
http://www.freepatentsonline.com/20040213881-0-large.jpg

3-Caffeoylquinic acid

4-Caffeoylquinic acid
5-Caffeoylquinic acid

wrotek
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Determination of Chlorogenic Acids with
Lactones in Roasted Coffee

http://www3.interscience.wiley.com/cgi-bin/fulltext/16251/PDFSTART


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On the Marsall Protocol Knowledge Base website at
http://mpkb.org/home/food/chlorogenic_acid#coffee_and_tea
in the information (last modified: 04.02.2010) on Chlorogenic Acid, under the subtopic, Coffee and Tea is written the following:

“MP patients should limit their daily coffee consumption to no more than two cups.”

Given the recent posts on this forum, is this still the recommendation?  I drink about 200ml (less than a cup) of coffee (medium-to-weak strength) daily.  May I continue?
le

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Le,
it may help to think of any coffee you drink as medicine to relieve symptoms.
That is, it is ok to take something to relieve a bad cough so lungs are not damaged by the cough: if you drink cough mixture without needing to, that's a bad sign
Sallie    :(
(coffee addict)

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Sallie, thank you for your response. 

However, given that the information that I quoted above is from the MPKB site, I stlll would appreciate a response from someone (please refer to my previous post today, 6/6/2010) regarding whether this is still the current recommendation regarding coffee intake.    
le

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Hello Le. :)

Sallie Q has got it right in her response... Sallie is right more often than not. :);):cool:

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I don't actually think coffee makes symptoms better, rather worse. Think about it.
Bacteria shut down VDR and we feel worse due to too much 1,25-D affecting other receptors. Chlorogenic acid shuts down VDR also, why should we feel better because of it ?

wrotek
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Or Is it that coffee makes symptoms coming from bacteria killing better, but symptoms from Th1 inflammation connected to VDR blockage worse ?

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I only feel better after coffee in the short term ...long term I feel worse ...:(  Lee

wrotek
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Yup. But after a while of ingesting i get dizzy from coffee. I tried to replicate the same effect with proper amount of tea having the same amount of caffeine, and the same effects aren't there.

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I use decaff ...:P  Lee

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Someone put the kettle on! Mine's Rooibos tea with 2sm!:D

No noticable effects either way.
Keith:dude:.

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Crisps and coffee highest acrylamide levels, warns UN
Another 'wonderful' substance found in coffee.
http://www.foodproductiondaily.com/Quality-Safety/Crisps-and-coffee-highest-acrylamide-levels-warns-UN

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wrotek wrote: I don't actually think coffee makes symptoms better, rather worse. Think about it.
Bacteria shut down VDR and we feel worse due to too much 1,25-D affecting other receptors. Chlorogenic acid shuts down VDR also, why should we feel better because of it ?


My perspective is that it is for people who's VDR is not so very blocked and who are beginning to get IP from it being activated by 1,25-D and thus killing bacteria at a higher rate.  Thus it reduces symptoms from the IP.

I suppose it might also counter the VDR activation of the Benicar to some degree and thus reduce immunopathology in that way.

Joyce Waterhouse

PS  For more discussion and observations of the effects of chlorogenic acid on IP, see http://www.marshallprotocol.com/forum11/13726.html

Last edited on Thu Jul 15th, 2010 15:12 by jcwat101

wrotek
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Coffee contains cholinomimetic compound distinct from caffeine
http://www.ncbi.nlm.nih.gov/pubmed/1941565

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Cholinomimetic compound distinct from caffeine contained in coffee. II: Muscarinic actions.
Tse SY.

Department of Neurology, Georgetown University, Washington, D.C. 20007.


Abstract
An extract with cholinergic activities was isolated from instant regular and decaffeinated coffees and purified. Intravenous injection of this cholinomimetic extract of coffee produced an abrupt depression in blood pressure and heart rate, changes that were distinct from those of known components of coffee, including caffeine, trigonelline, catechin, and chlorogenic acid. Pretreatment of the animals with naloxone, propranolol, isobutylmethylxanthine, hexamethonium bromide, and hemicholinium-3 chloride or bilateral vagotomy did not affect the cardiodepressive effects of the extract, whereas atropine completely abolished them. Direct injection of the cholinomimetic extract of coffee (20-100 micrograms) into the periaqueductal gray area of the midbrain did not produce any cardiovascular effect. However, the extract of coffee did cause relaxation of isolated rat and rabbit aortic ring preparations that were contracted under norepinephrine. The cholinomimetic extract did not inhibit purified acetylcholinesterase. This pharmacologic profile indicates that the cholinomimetic extract of coffee acts as a direct muscarinic agonist.

wrotek
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exactly

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Sorry to be so ignorant. I probably knew this once and forgot it again... What is a "muscarinic agonist"? And how does that translate into effects in our diseased body? Thanks. :cool:

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No idea regarding vitamin d or VDR, but chemicals acting on muscarinic receptors tend to be strong poisons. Muscarine, atropine, nicotine...  http://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptor

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Joyful, glad you asked (I think Muscari is a pretty little flower) but
anyway wiki mentions Ca
The M3 muscarinic receptors are located at many places in the body. They are located in the smooth muscles of the blood vessels, as well as in the lungs. Because the M3 receptor is Gq-coupled and mediates an increase in intracellular calcium, it typically causes constriction of smooth muscle, such as that observed during bronchoconstriction. However, with respect to vasculature, activation of M3 on vascular endothelial cells causes increased synthesis of nitric oxide, which diffuses to adjacent vascular smooth muscle cells and causes their relaxation, thereby explaining the paradoxical effect of parasympathomimetics on vascular tone and bronchiolar tone. Indeed, direct stimulation of vascular smooth muscle, M3 mediates vasconstriction in pathologies wherein the vascular endothelium is disrupted

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I'm not sure I have many "receptors" working today. :?

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any mention of calcium moving gets my attention.

It fascinates me that I hold scans, one of which is decades old. One mentions some calcification in an ovary,  one mentions some calcification of the aorta.

Aorta! I know where that is and I certainly wonder why the local doctor who ordered the scan for whatever reason, made no comment whatever about any implication of calcifying in the aorta.

Now, back to coffee
It seems to have the complexity usually to the half informed mind associated with cannabis sativa

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http://www.ncbi.nlm.nih.gov/pubmed/20606307

Nuclear factor-kappaB/signal transducers and activators of transcription-1-mediated inflammatory responses in lipopolysaccharide-activated macrophages are a major inhibitory target of kahweol, a coffee diterpene.Shen T, Park YC, Kim SH, Lee J, Cho JY.
School of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Korea.


AbstractDiterpene kahweol, one of the major components in coffee, has anti-cancer, anti-oxidative, and anti-inflammatory activity. In this study, we explored the molecular mechanism of the anti-inflammatory activity of kahweol. Lipopolysaccharide (LPS)-activated RAW264.7 cells were used to explore the modulatory role of kahweol on nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production and the activation of signaling proteins and transcription factors using immunoblotting and reverse transcription-polymerase chain reaction (RT-PCR). Kahweol diminished both the production of NO and PGE(2) and the mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. Interestingly, this compound suppressed the phospho-signal transducers and activators of transcription (STAT)-1 and p65/nuclear factor (NF)-kappaB levels in the nucleus but not c-Jun and c-fos. In conjunction, the phosphorylation of Akt and Janus kinase (JAK)2 also decreased. Therefore, our data suggest that kahweol in coffee may be an anti-inflammatory modulator with NF-kappaB/STAT-1-targeted inhibitory properties in LPS-activated RAW264.7 cells.

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http://tinyurl.com/3y3jg9v

A coronary vasoconstrictor substance is present in regular and “decaffeinated” forms of both percolated and instant coffee



References and further reading may be available for this article. To view references and further reading you must purchase this article.

Stanley Kalsnera
aDepartment of Pharmacology, Faculty of Medicine, University of Ottawa, Ottawa, Canada
Revised 18 April 1977.  Available online 8 November 2002.
Abstract Coffee contains a previously unrecognized vasoactive material with potent constrictor action on the coronary arteries of the heart when tested in two types of preparations. Contractions of beef coronary vessel strips developed in response to both regular and caffeine-reduced forms of coffee (0.02 – 1.0 ml/15 ml Krebs solution), and they were specifically blocked by the cholinergic antagonist atropine. A perfused slab of beef left ventricle also showed a vasoconstrictor response to coffee which was antagonized by atropine. In contrast, tea, in comparable volumes to those of coffee elicited only vascular relaxation, as did the methylxanthine caffeine. The possibility should be considered that the cholinomimetic substance described here is linked to the reported increased incidence of myocardial infarction in coffee but not in tea drinkers.

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Why in the world is she drinking soy milk (sugar plus soybeans)?  Both are immunosupressors.

I have have no IP lowering effect from green tea 2-3x/day at the end of a meal.  1 cup with caffeine the rest without.

Condolences to all the coffee drinkers. 

Good detective work there Trevor.

wrotek
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I have just noticed that flavonoids are antagonists od Adenosine  receptors.
flavone, flavanone http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=21&familyId=3


And so is quercetin ...

http://onlinelibrary.wiley.com/doi/10.1002/ptr.1975/abstract

Keywords: * flavonoids; * A1 adenosine receptors; * guinea-pigbrain; * guinea-pigileum

Abstract

This study aimed to investigate the potential for flavonoid action at A1 adenosine receptors in vitro. In a radioligand binding assay for A1 adenosine receptor occupancy in particulate preparations from guinea-pig cerebral cortex, flavonoids competed in concentration-dependent manners with Hill slopes typically not different from unity. Of the flavonoids tested, quercetin showed highest affinity (pKi value of 5.33). At a concentration of 28 mm, quercetin evoked a rightward shift in the N6-cyclopentyladenosine-induced inhibition of electrically evoked contractions of the guinea-pig isolated ileum, allowing the calculation of a pKi value of 4.71. These data suggest, therefore, that flavonoids represent an additional dietary source of A1 adenosine receptor antagonists (beyond the methylxanthines, caffeine and theophylline). Copyright © 2006 John Wiley & Sons, Ltd.


wrotek
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According to this article,  new chlorogenic acid containing foods.

http://livefitblog.com/2010/07/16/chlorogenic-acid-in-coffee-antioxidant/



Sunflower Seeds  1900 - 28000
Artichokes
        3200 - 3800         
Blueberries         3000
Cilantro
            305-320
Carrots
             70-150
Potato                22-71
Tomato               21
Peanut               18

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Claudia, I think it was Woody Allen who said, "You can live to be 100 years old if you give up everything that would make you want to."  It seems that there may be some truth in that while on the MP.  Just keep telling yourself, "It's temporary, it's temporary." 

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That's interesting.  Their list agrees to some extent with my list in terms of foods containing it but not entirely.  Of course, my chlorogenic acid list could relate to reactions to substances that are distinct from chlorogenic acid (CGA), but that cross react with it (e.g., probably the case with peanuts) -- and could even relate to containing more than one of these cross reacting substances (vitamin D, vitamin A, cga and other unknown ones).  Whether the unknown ones actually bind the VDR or not can't be known.

My list is in section F of http://synergyhn.com/cga .

There is also the possibility for the content to vary from one harvest to the next, as is apparently the case with salicylates.

Joyce Waterhouse

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It appears that filtered coffee, without nuclear receptor interacting, cholesterol rising diterpens cafestol and kahweol, also raises cholesterol levels.

http://www.ncbi.nlm.nih.gov/pubmed/12947437
Filtered coffee raises serum cholesterol: results from a controlled
study.



Filtered coffee raises serum cholesterol: results from a controlled study.Strandhagen E, Thelle DS. Department of Medicine, Cardiovascular Institute, Sahlgrenska University Hospital/Ostra, Göteborg, Sweden. elisabeth.strandhagen@hjl.gu.se AbstractOBJECTIVE: Earlier studies and trials have shown a serum cholesterol raising effect of unfiltered coffee, which is reduced by about 80% in filtered coffee. Recent cross-sectional studies and trials, however, have indicated that filtered coffee may have a more pronounced serum cholesterol raising effect than previously anticipated. The objective of this controlled study was to assess the effects of the intake and abstention of filtered brewed coffee on blood lipids. DESIGN: A prospective, controlled study with four consecutive trial periods. The first and third periods were 3 weeks of total coffee abstention. The second and fourth periods consisted of 4 weeks with the subjects consuming 600 ml filter brewed coffee/day. SETTING: Free-living population. Volunteers. SUBJECTS: A total of 121 healthy, nonsmoking men and women aged 29-65 y. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Serum total cholesterol, serum HDL cholesterol, serum triglycerides, serum lipoprotein (a) (Lp(a)), blood pressure and heart rate. RESULTS: The two coffee abstention periods were associated with a decline in serum cholesterol of 0.22 mmol/l (95% CI -0.31, -0.13) and 0.36 mmol/l (95% CI -0.46, -0.26), respectively. Filtered coffee/day 600 ml increased serum cholesterol by 0.25 mmol/l (95% CI 0.15, 0.36) and 0.15 mmol/l (95% CI 0.04, 0.26) during the two coffee drinking periods. CONCLUSIONS: Coffee abstention for 3 weeks decreased total serum cholesterol by 0.22-0.36 mmol/l. A volume of 600 ml (about four cups) of filtered coffee/day during 4 weeks raised total serum cholesterol by 0.15-0.25 mmol/l. PMID: 12947437 [PubMed - indexed for MEDLINE]
Could it be due to chlorogenic acid ?



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http://www.rt-pcr.com/showabstract.php?pmid=20580705

Induction of CYP3A4 and MDR1 gene expression by baicalin, baicalein, chlorogenic acid, and ginsenoside Rf through constitutive androstane receptor- and pregnane X receptor-mediated pathways. Y Li, Q Wang, X Yao,

The herbal products baicalin, baicalein, chlorogenic acid, and ginsenoside Rf have multiple pharmacological effects and are extensively used in alternative and/or complementary therapies. The present study investigated whether baicalin, baicalein, chlorogenic acid, and ginsenoside Rf induced the expression of the cytochrome P450 3A4 (CYP3A4) and multi-drug resistance 1 (MDR1) genes through the pregnane X receptor and constitutive androstane receptor pathways. Real time PCR, western blotting, and a luminescent assay were used to assess the induction of gene expression and activity of CYP3A4 and MDR1 by the test compounds. The interactions of baicalein/chlorogenic acid/ginsenoside Rf with constitutive androstane receptor and pregnane X receptor were evaluated using luciferase reporter and gel shift assays. Baicalein induced the expression of CYP3A4 and MDR1 mRNA by activating pregnane X receptor and constitutive androstane receptor. Chlorogenic acid and ginsenoside Rf showed a relatively weak effect on CYP3A4 promoter activation only in HepG2 cells co-transfected with constitutive androstane receptor and demonstrated no effects on MDR1 via either the constitutive androstane receptor or pregnane X receptor pathways. Baicalin had no effect on either CYP3A4 or MDR1 gene expression. In conclusion, baicalein has the potential to upregulate CYP3A4 and MDR1 through the direct activation of the constitutive androstane receptor and pregnane X receptor pathways. Chlorogenic acid and ginsenoside Rf only induced constitutive androstane receptor-mediated CYP3A4 expression.

Last edited on Mon Dec 13th, 2010 07:51 by wrotek

twiggy
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Awwww I wish I had read these articles before. I just bought a new keurig B60 and thought I could have a freshly perked cup of coffee. I have used coffee and the caffiene for years to keep me plugging along. I have noticed lately though that I usually feel itcky short time after my second half cup of coffee. I guess I am realizing something very new, is that I don't need tp push myself. If I don't have the energy forget the coffee just go lie down. Hmm new concept. Mentally though it will be tough. I also have loved a good brew of coffee first thing in the AM. This will be very hard.

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http://www.ncbi.nlm.nih.gov/pubmed/21203700


Bone quality associated with daily intake of coffee: a biochemical, radiographic and
histometric study
.

Lacerda SA, Matuoka RI, Macedo RM, Petenusci SO, Campos AA, Brentegani LG.
Department of Morphology, Stomatology and Physiology, Ribeirão Preto Dental School, University of São Paulo, Ribeirão Preto, SP, Brazil.
Abstract
Caffeine induces loss of calcium and influences the normal development of bone. This study investigated the effects of coffee on bone metabolism in rats by biochemical measurement of calcium, bone densitometry and histometry. Male rats, born of female treated daily with coffee and with coffee intake since born, were anesthetized, subjected to extraction of the upper right incisor, and sacrificed 7, 21 and 42 days after surgery. Blood and urine samples were taken, and their maxilla radiographed and processed to obtain 5-µm-thick semi-serial sections stained with hematoxylin and eosin. The volume and bone quality were estimated using an image-analysis software. The results showed significantly greater amount of calcium in the plasma (9.40 ± 1.73 versus 9.80 ± 2.05 mg%) and urine (1.00 ± 0.50 versus 1.25 ± 0.70 mg/24 h) and significantly less amount in bone (90.0 ± 1.94 versus 86.0 ± 2.12 mg/mg bone), reduced bone mineral density (1.05 ± 0.11 versus 0.65 ± 0.15 mmAL), and lower amount of bone (76.19 ± 1.6 versus 53.41 ± 2.1 %) (ANOVA; p≤0.01) in animals treated with coffee sacrificed after 42 days. It may be concluded that coffee/caffeine intake caused serious adverse effects on calcium metabolism in rats, including increased levels of calcium in the urine and plasma, decreased bone mineral density and lower volume of bone, thus delaying the bone repair process. PMID: 21203700 [PubMed - in process]Free Article

Is it caffeine or coffee ?



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You are right, they really make a serious mistake by drawing the conclusion that it is caffeine. Nothing in the study shows that.
Of course they can only relate the study to coffee. :)

wrotek
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Yes, that is why I would like to see the same study with tea, for example.
I don't know why it is so hard for them to use pure caffeine with the water, for mice to drink.

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Caffeine decreases vitamin D receptor protein expression and 1,25(OH)2D3 stimulated alkaline phosphatase activity in human osteoblast cells.

Rapuri PB, Gallagher JC, Nawaz Z
Of the various risk factors contributing to osteoporosis, dietary/lifestyle factors are important. In a clinical study we reported that women with caffeine intakes >300 mg/day had higher bone loss and women with vitamin D receptor (VDR) variant, tt were at a greater risk for this deleterious effect of caffeine. However, the mechanism of how caffeine effects bone metabolism is not clear. 1,25-Dihydroxy vitamin D(3) (1,25(OH)(2)D(3)) plays a critical role in regulating bone metabolism. The receptor for 1,25(OH)(2)D(3), VDR has been demonstrated in osteoblast cells and it belongs to the superfamily of nuclear hormone receptors. To understand the molecular mechanism of the role of caffeine in relation to bone, we tested the effect of caffeine on VDR expression and 1,25(OH)(2)D(3) mediated actions in bone. We therefore examined the effect of different doses of caffeine (0.2, 0.5, 1.0 and 10mM) on 1,25(OH)(2)D(3) induced VDR protein expression in human osteoblast cells. We also tested the effect of different doses of caffeine on 1,25(OH)(2)D(3) induced alkaline phosphatase (ALP) activity, a widely used marker of osteoblastic activity. Caffeine dose dependently decreased the 1,25(OH)(2)D(3) induced VDR expression and at concentrations of 1 and 10mM, VDR expression was decreased by about 50-70%, respectively. In addition, the 1,25(OH)(2)D(3) induced alkaline phosphatase activity was also reduced at similar doses thus affecting the osteoblastic function. The basal ALP activity was not affected with increasing doses of caffeine. Overall, our results suggest that caffeine affects 1,25(OH)(2)D(3) stimulated VDR protein expression and 1,25(OH)(2)D(3) mediated actions in human osteoblast cells.

wrotek
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PhillyGuy, yes this study is in this topic already, but i am afraid the concentrations in it are way above toxic levels, to humans. So i wonder, what would be VDR expression in normal doses.

Normal blood concentration of a average coffee drinker is 1-10mg/L, Lethal dose for humans is 80mg/L says this paper http://www.cs.uwaterloo.ca/~alopez-o/Coffee/caffaq.html .
Chronic high-dose caffeine intake can lead to nervousness, irritability, anxiety, tremulousness, muscle twitching, insomnia, palpitations and hyperreflexia. For blood testing, cross-reaction with theophylline assays will detect toxic amounts. (Method IA) Blood concentration of 1-10 mg/L is normal in coffee drinkers, while 80 mg/L has been associated with death.


1 mol of caffeine is 194.19 g

1mM is 0.19419g/L = 194.19mg/L (2.5 times lethal dose)
10mM is 1.9419g/L = 1941.9mg/L (25 times lethal dose)

Am I right ?

Last edited on Fri Jan 14th, 2011 10:31 by wrotek

wrotek
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Adenosine Receptors and Mammalian Toll-Like Receptors: Synergism in Macrophages

http://molinterv.aspetjournals.org/content/3/7/370.full

wrotek
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Caffeine raises cAMP so...

Cyclic adenosine 3',5'-monophosphate up-regulates 1,25-dihydroxyvitamin D3 receptor gene expression and enhances hormone action.

http://www.ncbi.nlm.nih.gov/pubmed/1314957

keithw
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Here is a little "food for thought"
Not exactly off topic...

http://www.smh.com.au/national/energy-drink-on-tap-a-recipe-for-disaster-experts-20100403-rkqm.html

wrotek
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Cannabidiol (CBD) exerts its anti-anxiety effects by adenosine receptors…

Inhibition of an equilibrative nucleoside transporter by cannabidiol: A mechanism of cannabinoid immunosuppression

http://www.pnas.org/content/103/20/7895.full

Our data indicate that CBD is a competitive inhibitor of adenosine uptake by an ENT.…

wrotek
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Perhaps it is a little off topic, but still interesting that caffeine can stimulate cancer

Caffeine stimulates the proliferation of human lung adenocarcinoma cells and small airway epithelial cells via activation of PKA, CREB and ERK1/2.
http://www.ncbi.nlm.nih.gov/pubmed/16391865

wrotek
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Adenosine Teaches The Lungs To Cope With Low Levels Of Oxygen
http://www.medicalnewstoday.com/articles/63737.php

Juan Ibla and colleagues from Children's Hospital Boston, show that if mice undergo HPC their lungs exhibit an attenuated inflammatory response to severe hypoxia compared with mice that received no HPC. In particular, the expression of genes regulated by the pro-inflammatory regulator NF-kappa-B was decreased. This decrease in NF-kappa-B activation was mediated by adenosine produced by cells exposed to HPC. Further analysis showed that adenosine inactivated a protein (cullin-1) that is required for NF-kappa-B activation by a process known as deneddylation. This study identifies an anti-inflammatory mechanism activated in the lungs by HPC and mediated by adensosine. Future studies will investigate whether the same mechanism protects other tissues from the severe effects of hypoxia.

Last edited on Sun Apr 24th, 2011 08:56 by wrotek

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I found this article in the news about beta-amyloid being suppressed by coffee but not decaffeinated coffee. Even when they tried to add back the caffeine into the decaf this didn't suppress beta amyloid. 

Is chlorogenic acid, water soluble just like caffaine? making it filtered out with caffaine?

http://www.myfoxtampabay.com/dpp/health/doctor_jo/caffeine-and-alzheimers-062211

a more detailed article from USF

http://hscweb3.hsc.usf.edu/health/now/?p=19816

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This looks like another caffeine industry sponsored article, part of never ending campaign in main stream media, to promote "health" benefits of coffee, tea, green tea, chocolate etc...

In my opinion, if an article says that something is healthy, it is suspicious and probably isn't healthy. Body is an engine, it runs on strict fuel... Fats, proteins, vitamins, minerals, carbohydrates, water and oxygen. Anything else is not needed, or potentially bad for the body.

Did you know that caffeine in dose 250mg, decreases cerebral blood flow by 32% ? And Alzheimer disease brain scans show decreased cerebral blood flow also - question is, if the decrease is a result of a disease or contributing factor or both, perhaps.

Last edited on Thu Jun 23rd, 2011 10:37 by wrotek

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Well, they found out its definitely not caffeine.  But whatever that mysterious substance in coffee that suppressed beta-amyliod is (perhaps chlorogenic acid?), I hope they will eventually not label it as another essential vitamin.

I always thought of beta-amyliod as an anti microbial peptide.

I'm just wondering if they ever thought it could be chlorogenic acid behind it. Or does chlorogenic acid stimulate the immune system?

wrotek
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Well, something in coffee definitively stimulates inflammatory process http://findarticles.com/p/articles/mi_m0887/is_11_23/ai_n7578036/ there is something called serum amyloid-a SAA increased also

What interests me recently is a process called blood rouleaux http://en.wikipedia.org/wiki/Rouleaux .

Wiki says that high protein levels cause stacking of Reb Blood Cells, and cells like that cannot transfer nutrients or remove waste efficiently because of impaired circulation.

Beta amyloid is a protein, so if we could only decrease production of beta amyloid, without removing reason for it's build up, how much could it help people with alzhiemers, delay Disease progress or decrease cognitive decline ?

Last edited on Fri Jun 24th, 2011 03:05 by wrotek

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Now, if there are so many caffeine addicts on the MP, I think the relevant question is:

Will someone now please figure out the way to remove chlorogenic acid?

:cool:

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I am one of those coffee ( and nicotin) addicts, so I would be very happy if there was a way (other than stop drinking coffee and smoking) to remove this chlorogenic acid out of my body.

:D,

Annemarie

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According to that article, if chlorogenic acid is water soluble just like caffeine then decaffeination filtering will remove  some or most of chlorogenic acid.  There are also different ways of decafinating the coffee, so it would be unreliable.



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This website says Chlorogenic acid is "100% water soluble":
http://www.organic-herb.com/Product/OHI-000239.html

A supposed material safety data sheet says it is "Soluble in hot water." (page 3):
http://www.sciencelab.com/msds.php?msdsId=9923423

Another supposed material safety data sheet says its water solubility is "25 mg/ml at 25.0 C" (page 2):
http://www.caymanchem.com/msdss/70930m.pdf

A Cayman Chemical information sheet says its solubility in phosphate buffered saline (buffered water) at a ph of 7.2 is 25 mg/ml (page 1):
http://www.caymanchem.com/pdfs/70930.pdf

Marty.K
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According to wikipedia caffeine's solubility is  2.17 g/100 mL making chlorogenic acid just little more soluble at 25 mg/ml.
Now lets just wait for the study to be published to see what decaff method they used.

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Theophylline leukotrienes and innate immunity
Theophylline is competitive nonselective phosphodiesterase inhibitor,[11] which raises intracellular cAMP, activates PKA, inhibits TNF-alpha [12][13] and inhibits leukotriene [14] synthesis, and reduces inflammation and innate immunity [14]


http://en.wikipedia.org/wiki/Theophylline#cite_note-LT-Peters-Golden-13

Leukotrienes: Underappreciated Mediators of Innate
Immune Responses



http://www.jimmunol.org/content/174/2/589.full

It is also of interest to ask whether commonly used medications might have unintended effects on LT synthesis and, thereby, on innate immunity. Increases in intracellular levels of cAMP can inhibit LT synthesis by a variety of enzymatic mechanisms (90), and commonly used cAMP-elevating drugs such as -adrenergic agonists, theophylline, and phosphodiesterase inhibitors have been reported to inhibit LT synthesis by leukocytes (91). Although its clinical significance is unclear, in vivo cAMP elevation has been reported to impair pulmonary bacterial clearance in an animal model of pneumonia

I wonder if this can have negative impact on asthma, if microbiome is involved .

Last edited on Tue Jun 28th, 2011 04:49 by wrotek

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http://www.sciencedirect.com/science/article/pii/0006300255902729
 - Another good reason not to eat sunflower seeds.
Apparently they removed the chlorogenic acid with a 50/50 water/ethanol mix.

wrotek
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Caffeine works like strychnine ?

Caffeine inhibition of ionotropic glycine receptors

We found that caffeine is a structural analogue of strychnine and a competitive antagonist at ionotropic glycine receptors (GlyRs). Docking simulations indicate that caffeine and strychnine may bind to similar sites at the GlyR.

http://jp.physoc.org/content/587/16/4063



bigger picture http://jp.physoc.org/content/587/16/4063/F2.large.jpg

Figure 2. Structural similarities between caffeine and strychnine A,
electrostatic potentials (EPS) and B, hydrogen bonding maps of caffeine (left) and strychnine (right). Both molecules have three electronegative (blue) atoms (colour scale: red, most positive; purple, most negative) that are also hydrogen acceptors (colour scale: blue, high H acceptor density; red, high H donor density). C, alignment of caffeine (green) and strychnine (hydrogen atoms omitted) based on closest distance between three atom pairs (O2, O6, N9 on caffeine and O10, O24, N19 on strychnine). D, simulated docking of strychnine (blue) and caffeine (red) to an α1 dimer. The GlyR ligand binding domain model was obtained through homology modelling with nicotinic AChR ligand binding domain (see Methods). Using this model, caffeine and strychnine were docked to an overlapping binding region on the interface between two α1 subunits.

Last edited on Wed Jun 29th, 2011 12:10 by wrotek

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theophylline really screwed me up last April:X

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Really crude in-silico analysis in that paper. They just can't leave old concepts behind. Instead of talking about force-fields and potentials they need to be using stochastic automated docking methods (eg AutoDock).

AutoDock's authors are now producing software to produce sub-standard analyses such as this. "It is what the industry wants" the group leader, Art Olsen, told me recently...

Sigh...
 

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Dr Marshall, are You saying that there is high probability that this paper is wrong ?
I wonder if high toxicity of theobromine in dogs could be explained by this paper.

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http://www.ncbi.nlm.nih.gov/pubmed/21422521

Caffeine Synergizes with Another Coffee Component to Increase Plasma GCSF: Linkage to Cognitive Benefits in Alzheimer's Mice.

treatment with caffeinated coffee greatly and specifically increased plasma levels of granulocyte-colony stimulating factor (GCSF), IL-10, and IL-6. Neither caffeine solution alone (which provided high plasma caffeine levels) or decaffeinated coffee provided this effect, indicating that caffeine synergized with some as yet unidentified component of coffee to selectively elevate these three plasma cytokines.

this is interesting.

Last edited on Thu Aug 11th, 2011 09:28 by wrotek

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Twenty five years ago when my Grandmother was suffering from Alzheimer's it was always noticeable that when we took her out for coffee and a cookie she would for a very short time become lucid again.  She could go from thinking she was a child in one sentence to remembering what stage in life she was after just one small cup.  Of course as the disease progressed that went away but for a few years it was a good way to be able to have a conversation with her again.:D

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wrotek wrote: Dr Marshall, are You saying that there is high probability that this paper is wrong ?.
Yes.

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Differential regulation of HIF-1alpha isoforms in murine macrophages by TLR4 and adenosine A(2A) receptor agonists.

http://www.ncbi.nlm.nih.gov/pubmed/19477908

Abstract
Adenosine A(2A)R and TLR agonists synergize to induce an "angiogenic switch" in macrophages, down-regulating TNF-alpha and up-regulating VEGF expression. (...)

Last edited on Sat Aug 20th, 2011 05:36 by wrotek

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Adenosine mediates IL-13–induced inflammation and remodeling in the lung and interacts in an IL-13–adenosine amplification pathway

http://www.jci.org/articles/view/16815
----------
http://en.wikipedia.org/wiki/Interleukin_13#Functions

IL-13 is more importantly implicated as a central mediator of the physiologic changes induced by allergic inflammation in many tissues.

Last edited on Fri Aug 26th, 2011 01:19 by wrotek

Sunset
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Interesting wroteck, according the wikipedia site you list above in your last post:

IL-13 specifically induces physiological changes in parasitized organs that are required to expel the offending organisms or their products.

and


The eggs of the parasite Schistosoma mansoni may lodge in a variety of organs including the gut wall, liver, lung and even central nervous system, inducing the formation of granulomas under the control of IL-13. Here, however, the eventual result is organ damage and often profound or even fatal disease, not resolution of the infection. An emerging concept is that IL-13 may antagonize Th1 responses that are required to resolve intracellular infections. In this immune dysregulated context, marked by the recruitment of aberrantly large numbers of Th2 cells, IL-13 inhibits the ability of host immune cells to destroy intracellular pathogens.

wrotek
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Oh, i did not read that far before :D

In the first paper, the Discussion paragraph is very interesting.



The A2A receptor is typically associated with anti-inflammatory effects of adenosine (47), while the A1, A2B, and A3, adenosine receptors have been implicated in proinflammatory



Our studies demonstrate that IL-13 causes striking changes in adenosine receptor expression in the murine lung, with the inhibitory A2A receptor being unaltered or decreased, while the expression of the stimulatory A1, A2B, and A3 receptors is markedly increased (Figures 3–6)

These findings demonstrate that the effects of adenosine are cell specific and depend on the type(s) of receptor that is activated.


Caffeine antagonizes A1 and A2a receptor... iuphar database
http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?familyId=3&objectId=19 (click green S next to caffeine for selectivity)

So it shuts down the only one antinflammatory adenosine receptor - A2a .
Ane one proinflammatory - A1.

Theophylline antagonizes all 4 adenosine receptors.

Last edited on Fri Aug 26th, 2011 07:40 by wrotek

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Some of us are not cognitively able to digest the above posts. Could you please clarify in plain English why coffee is bad and how bad it is?

Is it bad for everyone?
Is it bad for all MPers? 
Or, is it bad only for MPers with sarcoidosis?

My MP doc said, "You may put a little milk in your coffee", so I am surmising he does not think coffee is all that bad, although he did advise me to avoid foods with a lot of D. (I use raw milk, with no added D.)

Will ingesting coffee inhibit my recovery? It seems to ameliorate IP.

Any/all clarification greatly appreciated!

 

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You can check out more information about chlorogenic acid in earlier entries in this thread here as well as read about it on the MPKB site. Here's one link:

http://mpkb.org/home/food/chlorogenic_acid

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Thank you, Sunset!  Sorry for the bad navigation/non-comprehnsion!

wrotek
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Yesterday I had a visit from my cousin and his wife, she never drinks coffee but recently she tried one. It was just instant coffee, soluble but she felt really bad and had hand shakes. I made my brother an espresso, and he usually drinks soluble coffee, and he had hand shakes too .

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If you look up Chlorogenic Acid in the MPKB database it says that during roasting some of the chlorogenic acid in coffee is reduced and says:

"MP patients should limit their daily coffee consumption to no more than two cups per day."

wrotek
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Coffea charrieriana

http://en.wikipedia.org/wiki/Coffea_charrieriana

This plant is the only known caffeine-free coffee plant


But i don't think it can be bought.

Chloe Ringer
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This might be hard for coffee lovers to contemplate, but Ayurvedic medicine recommends, ". . . drinking plain, hot water throughout the day to aid flow from the gut."  I tried drinking plain, hot water and found it to be very satisfying and calming, especially before bedtime.

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Chloe: Speaking of drinking water, I used to see a brilliant Chinese Medical Doctor/Herbalist/Acupuncturist who told me one should not drink iced drinks, including ice water, especially if one is ill (unless it is really hot out and you need to cool down) as drinking iced drinks takes energy away from the body to warm it back up again. It makes a lot of sense to me. I used to get completely chilled after drinking ice tea in a restaurant that also had air conditioning (I get cold easily) and it would take me a long time to warm up again. Something for people to keep in mind.

wrotek
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Hogan wrote:
Twenty five years ago when my Grandmother was suffering from Alzheimer's it was always noticeable that when we took her out for coffee and a cookie she would for a very short time become lucid again.  She could go from thinking she was a child in one sentence to remembering what stage in life she was after just one small cup.  Of course as the disease progressed that went away but for a few years it was a good way to be able to have a conversation with her again.:D


Hogan, did Your Grandmother have the same experience after other caffeinated beverages like black/green tea ?

Last edited on Thu Sep 29th, 2011 01:25 by wrotek

Limburg
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I found this, unfortunately in Dutch, but maybe you can use a translator:

1. Barranco Quintana et al. Alzheimer's disease and coffee: a quantitative review. Neurological Research (2007); 29:91-95(5).
2. Eskelinen MH. Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study. Journal of Alzheimer’s Disease (2009); 16(1):85-91.
3. Dall'lgna OP et al. Neuroprotection by caffeine and adenosine A2A receptor blockade of beta-amyloid neurotoxicity. Br J Pharmacol (2003); 138 (7): 1207-09.
4. Lindsay J et al. Risk Factors for Alzheimer's Disease: A Prospective Analysis from the Canadian Study of Health and Aging. Am J Epidemiol (2002); 156: 445-53.
5.Maia L, de Mendonça A. Does caffeine intake protect from Alzheimer’s disease? Eur J of Neurology (2002); 9 (4): 377-82.


Regards, Annemarie

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Is Resveratrol immunosuppressive(like mariquana?)



Role of resveratrol-induced CD11b(+) Gr-1(+) myeloid derived suppressor cells (MDSCs) in the reduction of CXCR3(+) T cells and amelioration of chronic colitis in IL-10(-/-) mice.
Brain Behav Immun. 2011 Jul 23;
Authors: Singh UP, Singh NP, Singh B, Hofseth LJ, Taub DD, Price RL, Nagarkatti M, Nagarkatti PS
Resveratrol, a naturally occurring polyphenol has received significant attention as a potent anti-inflammatory agent. Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce proinflammatory cytokines. Myeloid derived suppressor cells (MDSCs) are a heterogeneous population characterized by the co-expression of CD11b(+) and Gr-1(+) and have long been known for their immunosuppressive function. We report that resveratrol effectively attenuated overall clinical scores as well as various pathological markers of colitis in IL-10(-/-) mice by down regulating Th1 responses. Resveratrol lessened the colitis-associated decrease in body weight and increased levels of serum amyloid A (SAA), CXCL10 and colon TNF-α, IL-6, RANTES, IL-12 and IL-1β concentrations. After resveratrol treatment, the percentage of CXCR3 expressing T cells was decreased in the spleen, mesenteric lymph nodes (MLN), and intestinal lamina propria (LP). However, the percentage and absolute numbers of CD11b(+) and Gr-1(+)cells in the lamina propria (LP) and spleen were increased after resveratrol treatment as compared with the vehicle treatment. Co-culture of resveratrol-induced CD11b(+) Gr-1(+) cells with T cells, attenuated T cell proliferation, and most importantly reduced IFN-γ and GM-CSF production by LP derived T cells from vehicle treated IL-10(-/-) mice with chronic colitis. The current study suggests that administration of resveratrol into IL-10(-/-) mice induces immunosuppressive CD11b(+) Gr-1(+) MDSCs in the colon, which correlates with reversal of established chronic colitis, and down regulation of mucosal and systemic CXCR3(+) expressing effector T cells as well as inflammatory cytokines in the colon. The induction of immunosuppressive CD11b(+) Gr-1(+) cells by resveratrol during colitis is unique, and suggests an as-yet-unidentified mode of anti-inflammatory action of this plant polyphenol.
PMID: 21807089 [PubMed - as supplied by publisher]

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Emerging role of extracellular nucleotides and adenosine
in multiple sclerosis


http://www.ncbi.nlm.nih.gov/pubmed/21792574

full paper
http://www.springerlink.com/content/t6x6j76371751uqn

wrotek
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More, detailed informations, about anti-opioid activity of coffee
http://aminotheory.com/coffee/

Experiments with rats at levels comparable to human coffee drinking indicate that 4-Caffeoyl-1, 5-quinide does significantly inhibit the pain-blocking actions of morphine.

So will coffee affect perception of immunopathology ? Make it more unbearable ?

Last edited on Mon Oct 24th, 2011 09:28 by wrotek

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So will coffee affect perception of immunopathology ? Make it more unbearable ?

Possibly true if you are using morphine to kill the pain of IP.  But I think the general experience is that coffee definitely cuts back IP. 

God would really have to hate us to make coffee taste so good and be so evil as to increase IP.

wrotek
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I never liked coffee taste, that is why i drank espresso.
Fast shot and i could run.
But i like grounded coffee smell.

God made all psychoactive chemicals bad 4 U after a longer use. Is not that weird ? U can have some, but not too much. Otherwise You get ill.

Last edited on Tue Oct 25th, 2011 00:46 by wrotek

jlunn247
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I hate the withdraw headaches. i try avoid caffeine and coffee.
You gotta know what helps & what hurts thanks you guys.

Last edited on Tue Oct 25th, 2011 02:46 by jlunn247

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HI JIM & ALL

This is Fred in WV .  Jim said, "I HATE THE WITHDRAW HEADACHES".  I use to take a pill for migraines called CAFERGOT.  It had 100mg of caffeine in it.  You could not take more than 7 in one week or 3 per day I think.  So it looks like caffeine could not be good for you.  It has been a long time since I had that pill.  It was getting hard to even find it some time in the 1980s.

Remember. we are all in this together and I am pulling for us.

Your friend in Sarcoidosis
Freddie

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Freddie, perhaps this personal story about caffergot and caffeine will Interest You.

http://www.youtube.com/watch?v=6QS5StIDr4o

Freddie Ash
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HI WROTEK

This is Fred in WV.  I live in the back woods and my computer service is not the best, so mine could not get that up to see.  Thanks Wrotek for you help.  Keep up the great work and keep on MPing.\

One of my sons is to come in a few days to see what he can do about a better service.

Your friend in Sarcoidosis
Freddie

jlunn247
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http://youtu.be/mJGRWfJc9xw

I heard this routine on coast to coast with art bell years ago.
Could he be the same caller???
No it was a different voice he used to tell art he was a great big sinner. His girlfriend fell off his bike.

Last edited on Tue Oct 25th, 2011 08:43 by jlunn247

wrotek
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Freddie , You can wait until video loads fully and then play it, unless You have data download limit.

jlunn247, I saw this video before too. Nice chain :)

Last edited on Tue Oct 25th, 2011 08:48 by wrotek

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I used to get severe coffee withdrawal symptoms in the morning, if that first cup was delayed by more than an hour or two.   That doesn't happen any more.   For a short while, some months ago, I even went cold turkey with no problem.

I went back to using the coffee, as it really helps with the current fatigue and fog that is the primary IP. 

I'm not sure what the withdrawal is about, but I'm pretty sure it's not the caffeine for me, as tea didn't cure any of the headaches.

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Chris that is very good observation, in my opinion, that tea does not alleviate headaches caused by coffee.
Here is paper

Coffee Acutely Increases Sympathetic Nerve Activity and Blood Pressure Independently of Caffeine Content



http://circ.ahajournals.org/content/106/23/2935.full.pdf

So there is chemical in coffee, which is not caffeine, that constricts blood flow - is vasoactive

Last edited on Wed Oct 26th, 2011 03:55 by wrotek

wrotek
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Coffee Consumption and Circulating B-Vitamins in Healthy Middle-Aged Men and Women

http://www.clinchem.org/cgi/content/full/54/9/1489

eClaire
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Hmmm... wouldn't the reducing folate be a good thing for many of us... I'm confused.

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From Janet in Mikes thread: http://www.dailymail.co.uk/health/article-1177258/Are-wrecking-brain-Chilling-pictures-reveal-shocking-effects-alcohol-cigarettes-caffeine-mind.html

I am sure this isn't typical but it is still scary.

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Yikes and Thank you for posting these pictures.

"A picture is worth a thousand words."

Sherry

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Yes KeithW, i am familiar with Dr Amen work.
But his presentations look more like a tv shows, than a scientific presentationa.

His brain scans are very interesting but lack of detailed description.
As i understand they show brain blood flow, caffeine is indeed very strong cerebral vasoconstrictor - 30% decreased brain blood flow at dose of 250mg.

Last edited on Sun Nov 13th, 2011 07:37 by wrotek

keithw
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Well yes, and we get the same TV shows as commercials for the antismoking lobby too.
Not everybody dies from the effects of tobacco either, some get run over or shot or die in a hundred other ways but it never hurts to show a worst case scenario.

I watched a food science show a few days ago that demonstrated it takes five days to wean off caffeine cold turkey, pity smokers can't do that eh?

:dude:

wrotek
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Induction of C-reactive protein by cytokines in human hepatoma cell lines is potentiated by caffeine.

http://www.ncbi.nlm.nih.gov/pubmed/2165398?dopt=Abstract

Abstract
Induction of C-reactive protein (CRP) by conditioned medium from lipopolysaccharide-stimulated human monocytes in two human hepatoma-cell lines, Hep 3B and NPLC/PRF/5, was potentiated 3-6-fold by the methylxanthine caffeine. The induction observed in the presence of conditioned medium plus caffeine was as much as 180-fold , comparable with that seen after many stimuli in vivo. This potentiation was accompanied by an increase in the levels of CRP mRNA. By contrast, no potentiating effect on CRP induction by conditioned medium was found when we tested theophylline, forskolin, 8-bromo cyclic AMP or two Ca2+ ionophores, namely ionomycin and A23187. None of the above compounds, including caffeine, when tested alone, had any detectable effect on the synthesis and secretion of CRP. Our previous study [Ganapathi, May, Schultz, Brabenec, Weinstein, Sehgal & Kushner (1988) Biochem. Biophys. Res. Commun. 157, 271-277], employing defined cytokines, had shown that induction of CRP in Hep 3B cells requires IL(interleukin)-6 plus IL-1, whereas, in the NPLC/PRF/5 cell line, IL-6 alone is effective. Caffeine similarly potentiated induction of CRP by these defined cytokine signals in these two cell lines. Changes in synthesis of other acute-phase proteins, including serum amyloid A (SAA), alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin and albumin, induced by conditioned medium or, in some cases, by IL-6 and/or IL-1 alpha, were only minimally affected by caffeine. Thus these results indicate that the mechanism by which caffeine potentiates CRP induction by cytokines appears to be independent of increases in intracellular concentrations of the two second messengers, cyclic AMP and Ca2+; the precise nature of this mechanism is unclear at the present time. Our results also indicate that the intracellular mechanisms by which cytokines regulate synthesis of CRP may differ from those regulating synthesis of some other acute-phase proteins. The differential response of CRP and SAA to caffeine is of particular interest, since induction of both of these two major acute-phase proteins can be accomplished by identical extracellular signals.

Last edited on Sun Nov 20th, 2011 05:59 by wrotek

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I have developed M.C.S. over the last 15 yrs and had many allergies before that. I cant smoke every day like I did years ago. And I really get anxious from strong doses of caffeine. So I had to adapt to less or none.

lots of fun foods and smoking are harmless compared to the Immediate risks of life so thank you for agreeing with me Keith & Wrotek. I will bet bernie mac did not want any cigars his last days.

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I just had to add this:



;)

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A more useful note:

I have been looking at coffee substitutes such as chicory tea, etc.
Unfortunately, most of them contain chlorogenic acid as well. A drink made with the chicory/coffee/barley mix I ordered last week would contain approx twice as much chlorogenic acid as a standard coffee (chicory has about 3x as much CGA as coffee).
Dandelion coffee has about 30% less than Arabica coffee (which has lower CGA than other types of coffee).

The only coffee substitute I found that has negligible chlorogenic acid (if any) is the 100% Barley coffee. This is also caffeine-free.

Since the smell of tea and coffee puts me off it lately, I'm left with hot chocolate, which is nice, but if you've ever been a coffee drinker you know its hard to replace it with something else.

More info on chlorogenic acid in foods here:
http://www.marshallprotocol.com/forum43/14566.html

wrotek
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I have recently stumbled upon an information about doctor Alfred Nickel, who apparently cured his type 1 diabetes quitting coffee he was drinking excessively in work.

When he did that, he stopped using insulin.
He did some research and found out that caffeine is metabolised into alloxan, extremely toxic substance for beta cells of pancreas, also used to kill beta cells in laboratory experiments

I dont know if this information is accurate, could find any data about caffeine being metabolized into Alloxan.

This could be huge blow in the head for caffeine industry :)

http://en.wikipedia.org/wiki/Alloxan
Biological effects

Alloxan is a toxic glucose analogue, which selectively destroys insulin-producing cells in the pancreas (that is beta cells) when administered to rodents and many other animal species. This causes an insulin-dependent diabetes mellitus (called "Alloxan Diabetes") in these animals, with characteristics similar to type 1 diabetes in humans. Alloxan is selectively toxic to insulin-producing pancreatic beta cells because it preferentially accumulates in beta cells through uptake via the GLUT2 glucose transporter. Alloxan, in the presence of intracellular thiols, generates reactive oxygen species (ROS) in a cyclic reaction with its reduction product, dialuric acid. The beta cell toxic action of alloxan is initiated by free radicals formed in this redox reaction. One study suggests that alloxan does not cause diabetes in humans.[2] Others found a significant difference in alloxan plasma levels in children with and without diabetes Type 1. [3]

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wrotek wrote:
This could be huge blow in the head for caffeine industry :)

But who funds most of the research into coffee...

wrotek
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There is no research I think :) Every now and then, article comes out about health benefits of coffee or green tea, chocolate etc...
But You can never find reference to scientific study they based the article on...You just read " scientist discovered that coffee lowers risk of this or that.
So no need for expensive study :)
Often there is no even single name of a scientist, who discovered claimed health benefits.

Last edited on Sat Feb 4th, 2012 00:41 by wrotek

wrotek
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I think i have noticed that coffee additional stimulatory effects, to those of caffeine, disappear when I am not on olmesartan.
I once skipped 2 doses of olmesartan in a row :) by mistake.

Last edited on Sun Feb 12th, 2012 03:25 by wrotek

wrotek
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Adenosine signaling and the regulation of chronic lung disease

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743314/

wrotek
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Lung turns to AA (adenosine analogues) to dry out

http://www.nature.com/nm/journal/v13/n4/full/nm0407-406.html

Adenosine helps maintain proper fluid levels in the lung alveoli.

Last edited on Wed Feb 15th, 2012 10:56 by wrotek

Sallie Q
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does something in coffee promote OCD ?

wrotek
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OCD - Obsessive Compulsive Disorder ?

Well OCD is a sort of nervous condition, and coffee makes one nervous for sure.

I used to have nervous tics( do now confuse with ticks :) ) , so did my brother, when i was very young, and the only drug i was taking was black tea and chocolate, did not even drink coffee.

Last edited on Wed Feb 15th, 2012 22:37 by wrotek

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Respiratory stimulant effects of adenosine in man after caffeine and enprofylline.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1386409/

Venous pCO2 fell and pH rose after adenosine. Caffeine significantly reduced the adenosine-induced changes of minute ventilation, tidal volume, venous pCO2 and pH, whereas no changes occurred after enprofylline. Our results suggest that adenosine stimulates respiration in man by binding with specific P1-purinoceptors, which can be blocked by caffeine, but not by enprofylline.

wrotek
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Theophylline induces neutrophil apoptosis through adenosine
A2A receptor antagonism


http://www.jleukbio.org/content/67/4/529.full.pdf

Meanwhile, neutrophils are well recognized as
important inflammatory cells in respiratory infection, and upper
respiratory infection is the major cause of asthma exacerbations


Caffeine, as theophylline, blocks A2a receptor
http://www.ehow.com/how-does_5376438_long-do-blood-cells-last.html
http://tinyurl.com/7el8b5w
BTW WBCs come in several types that have a wide range of life spans. Neutrophils, a type of white blood cell of special importance in fighting infections live for an average of 6 hours

So it is quite short lifetime. Could caffeine make them live even shorter and do not perform their function for enough long time?

Last edited on Tue Feb 28th, 2012 10:16 by wrotek

wrotek
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Regarding Alloxan, more datails but unfortunately anecdotal

http://www.hepatitis-central.com/mt/archives/2005/01/caffeine_hepati.html
Caffeine Causing Diabetes?


BEYOND HEALTH? News

by Raymond Francis

Diabetes is a disease condition distinguished by an inability to control blood-sugar levels, due to insufficient production of or heightened resistance to the hormone insulin. Interestingly, diabetes researchers induce diabetes in laboratory animals by feeding them small doses of a chemical called alloxan. Alloxan poisons insulin-producing cells in the pancreas, killing those cells and thus creating the conditions of diabetes. Knowing this, imagine the surprise of Dr. Alfred Nickel, an oral surgeon with degrees in biochemistry and pharmacology, who discovered in the scientific literature that alloxan is produced in the body from caffeine. Dr. Nickel theorized that caffeine could be a significant cause of diabetes in humans. People who consume a lot of caffeine will produce a lot of alloxan; this could cause diabetes or make existing diabetes worse.

Dr. Nickel was a heavy coffee drinker himself and had also developed adult diabetes. His diabetes got worse over time, and he was taking insulin to manage his disease. He decided to experiment?first on himself. He went off of all caffeine; after two weeks he was able to go off of insulin, and has remained off ever since! This had a profound effect on Dr. Nickel's health in general. His eyesight returned to where it had been fifteen years prior and his energy levels soared. He then passed this information on to his patients, and 40 out of 45 diabetics were able to reverse their disease by removing caffeine from their diet. Dr. Nickel witnessed patients, who were so sick with diabetes they were unable to climb up stairs, suddenly able to throw away their crutches away and run! He observed blood glucose levels return to normal after only a few weeks on a caffeine-free diet.

Caffeine consumption in the US is now at pharmacological (medically significant) levels. The dose of caffeine that will produce noticeable biological effects is roughly 200 mg. The average per capita consumption is now 206 mg/day, however, someone consuming 6 to 8 cups of coffee per day can be getting as much as 4000 mg/day. Due to biochemical individuality, some people are more or less tolerant to specific toxins than others. Those who are less tolerant to caffeine-produced alloxan, will likely get sick.
Alloxan is a free radical generator. Free radicals are known to damage the body, causing it to age and develop disease, including cancer. Since alloxan damages the pancreas, it may specifically be a contributor to pancreatic cancer. In fact, while Dr. Nickel and I were discussing this topic on my radio show, a woman called in and told us about her husband who died of pancreatic cancer after consuming as many as 16 cups of coffee a day for many years.
Many caffeinated products are popular with kids, and diabetes is rapidly growing in that age group. Medical experts have expressed alarm at the increasing rates of adult diabetes found in children. Meanwhile, caffeine has blossomed into a multi-billion dollar industry, largely aimed at teens and college students. Manufacturers are putting it into just about everything they can think of. Wrigley has a chewing gum in which one stick contains the caffeine equivalent of a cup of coffee. Pepsi and Coke have always contained substantial amounts of caffeine, and these companies have other products (Mountain Dew and Surge) with even higher quantities. Jolt Cola, a soda aimed at the 15-21 year-old market, contains 50 percent more caffeine than other sodas and continues to increase in its popularity. Jolt Cola even has a candy called Jolt, which is advertised as, "America's most powerful candy." Even orange juice and bottled water are now available in caffeinated versions. A few years ago, Celestial Seasonings introduced a highly caffeinated "Fast Lane Tea." Caffeine is a prolific toxin in our diet, and consumption keeps going up!
While there is rarely a single cause of disease, it appears that caffeine is a major contributor to disease. Caffeine is a significant contributor to our epidemic of diabetes, depression, and perhaps pancreatic cancer as well as other diseases. Interestingly, it is well known that caffeine can produce a "high," but less known that it can also cause depression. So why consume all this caffeine? Because we need it to get through the day. The U.S. population is not healthy, and we lack the boundless energy of traditionally healthy populations. Instead, we look to stimulants like caffeine to rev up the system. This is like constantly whipping a tired horse-eventually that horse will collapse.
Anyone with diabetes should absolutely avoid all caffeine from any source. Those wishing to prevent diabetes should sharply limit caffeine intake from coffee, soft drinks, tea, chocolate, or any other source. The damage done to the pancreas by alloxan from caffeine is cumulative; the longer it goes on, and the more caffeine one ingests, the more irreparable damage is done. Even decaffeinated products should be avoided, because the decaffinating process removes only the unbound, soluble caffeine. These products still contain a bound form of caffeine that is capable of producing alloxan.
Raymond Francis is an M.I.T.-trained scientist, a registered nutrition consultant, author of Never Be Sick Again, host of the Beyond Health Show and an internationally recognized leader in the emerging field of optimal health maintenance.




Last edited on Thu Mar 1st, 2012 12:15 by wrotek

Kas
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On my one cup of coffee a day, my sugar levels have remained consistent and have not risen at all, but at the same time, my liver enzymes came back into range and have largely remained there.

It’s so confusing, as there are studies which state that coffee is beneficial for diabetes out there.

wrotek
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Blood levels of alloxan in children with insulin-dependent diabetes mellitus

http://www.ncbi.nlm.nih.gov/pubmed/7888696

Other source of Alloxan is Maida flour

http://xa.yimg.com/kq/groups/13587953/171479547/name/index.php.pdf

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Wrotek,

Nice work on tracking down the harmful affects of caffeine in our body. This has been your speciality for some time :). Given that it is being stated increased consumption of coffee can cause Diabetes and other illnesses I think the best scenario for all of us is to do what we have always done since being on the MP. Be aware and focussed on our day to day lifestyle in every facet and do things in moderation and it should be ok. I think coffee intake would fall into this category.

Cheers,

Ralph

Kas
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http://www.theglobeandmail.com/life/health/coffee-may-help-keep-diabetes-at-bay/article1509476/


This article seems to conclude that coffee may prevent type 2 diabetes.

All very confusing!!!

wrotek
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Ralph wrote:
Wrotek,

Nice work on tracking down the harmful affects of caffeine in our body. This has been your speciality for some time :).
Ralph


More like a hobby.
But do poison in moderation ? :) well.....


Kas,
some "studies" are simply marketing, some are badly made, some draw wrong conclusions and some are good studies.

One just has to know which are which.
Dr Marshall once said that You have to know how sort through them.

Regarding diabetes and caffeine, read story of Adrew Bauman
- some experiences are good clues, even more useful than studies
http://tinyurl.com/7ka5gdr ,

I like putting these together, have u ever had an increased thirst perception after coffee ? Dry mouth ? Found Yourself drinking more water while having some coffee? It can be a sign of excess sugar in the blood in diabetic ppl, symptoms of which is fatigue, for example.

Could it be that coffee does that by affecting pancreatic Beta cells ? Having toxic effects on them ?

White flour contains diabetes-causing contaminant alloxan
http://www.naturalnews.com/008191.html

Last edited on Sat Mar 3rd, 2012 00:16 by wrotek

wrotek
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I like very much an artist Chris Rea, and I noticed he recently had Pancreatic Cancer .
http://news.softpedia.com/news/Cancer-Nearly-Killed-Me-Saved-Me-Chris-Rea-Reveals-122913.shtml

I think he really likes coffee, it appears in his work extensively

Soft Top, Hard Shoulder song
http://www.youtube.com/watch?v=mdYrtoYAmDc      49 second, 1m:02s, 1m06s, 1:20, and so on...

Blue coffee series
http://www.youtube.com/watch?v=7pYwZQDQEb4

espresso logic song
http://www.youtube.com/watch?v=H4X5_9HGV4A  


I would like to know how much caffeine Steve Jobs consumed or Bill Hicks

Last edited on Sat Mar 3rd, 2012 01:05 by wrotek

wrotek
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TOO MUCH COFFEE COULD TRIGGER HALLUCINATIONS

http://www.dcbssa.org/too-much-coffee-could-trigger-hallucination.html

And it is believed to be attributed to chemical called cortisol which is a steroid

wrotek
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A1 Adenosine Receptor Upregulation and Activation
Attenuates Neuroinflammation and Demyelination in a
Model of Multiple Sclerosis


http://www.jneurosci.org/content/24/6/1521.full.pdf+html

wrotek
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Maybe it is good observation, maybe not. But I have noticed that 4 foods, on chlorogenic acid containing food list http://mpkb.org/home/food/chlorogenic_acid , are from nightshade family. Tobacco, tomato, eggplant, potato.
Only Paprika is missing.

There are reports on the internet that nightshade family can increase symptoms of arthritis.

Really interesting

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For those extremely sensitive, this might be a problem, but my own experience is that the only severe reaction I've had is to potatoes that have been allowed to sit exposed to light for a while, and when the potato starts to turn green, there is a tremendous amount of a chemical that can cause aches in arthritic or even maybe non-arthritic joints.  I had so much pain in knee joints one night after eating potatoes that I could not sleep.  Now I have arthritis in my back and hips, but not any that I know of in my knees.  Maybe subclinical, but this was a number of years ago when I was only aware of back issues.

Cynthia

http://simplyrecipes.com/recipes/about_green_potatoes/

wrotek
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I wish we had presise amounts of how much cga these foods have in them. Potatoes can be consumed in high quantities so are the other nightshades.

Last edited on Mon Mar 12th, 2012 09:16 by wrotek

Sallie Q
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as a potato loving gal with Irish ancestry, when many different varieties of potato showed up in the supermarket I tried a few, but the more colorful and strange shaped they were, the more likely they were to give me significant digestive problems
Nightshades can be deadly for the Celiacs among us :(

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Nightshades and celiacs?   What's the connection?  (Asking for friend with this; fortunately dont have it myself)               Thanks.

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http://en.wikipedia.org/wiki/Coeliac_disease
http://www.nightshadefree.com/nightshade-allergy-symptoms/

From the above you can see that they have much in common though they have different triggers, the symptoms can be similar and a blood test can help to identify the problem.

MPers usually play it safe and avoid both wheat and any of the nightshades they are suspicious of, usually chilli and tomato/eggplant though cutting out white potato is a good idea too.

:dude:

wrotek
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From second link that Keithw gave.

“Of the 52% rigidly on the diet [with­out night­shades], 94% reported com­plete or sub­stan­tial relief of arthri­tis…”– Jour­nal of Neu­ro­log­i­cal and Ortho­pe­dic Med­ical Surgery

Other interesting experience with nightshades.
http://www.youtube.com/watch?v=WQ5Nau-p0-o

Person from them above movie, had 80% decrease in arthritic pain, but still he did not quit smoking :D

[Could it be that adverse effects attributed to nightshades, might actually have an explanation in chlorogenic acid actions ?

BTW coffee (cga ?) makes me laxative extremely :) , and wikipedia lists chlorogenic acid containing prunes as laxative.
http://en.wikipedia.org/wiki/Chlorogenic_acid

Tea is much less intense laxative.


http://www.youtube.com/watch?v=LDnFVDGb1wE

Last edited on Wed Mar 14th, 2012 15:00 by wrotek

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I always thought it was the oil in coffee, as I never got the same reaction from instant.  Cynthia

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Cynthia,
Thats interesting. I wonder if the extra processing (freeze-drying,etc) removes the chlorogenic acid from instant coffee.

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I drink the Nescafe instant coffee and have no reaction whatsoever. Just one cup every now and then - have cut back from daily, but see no difference yet. lLiver enzymes were better on coffee, but kidneys seem better off it on one test. I will wait and see what the next one shows.

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Solanecae contain interesting steroid like compounds that come from cholesterol http://www.plantphysiol.org/content/131/4/1792/F1.expansion.html
like

solanine http://en.wikipedia.org/wiki/Solanine

chaconine http://en.wikipedia.org/wiki/Chaconine

tomatine http://en.wikipedia.org/wiki/Tomatine




Potato glycoalkaloids and adverse effects in humans: an ascending dose study.
http://www.ncbi.nlm.nih.gov/pubmed/15649828

There can be as much as 200mg/kg of Tocal Glycoalkaloids in potatoes.

In the following paper, on second page, are compared structures of alkaloids found in solanecae plants http://www.ib-pan.krakow.pl/pubs-pdf/Wiadomosci%20Botaniczne/1973/17_a23-32.pdf

Last edited on Fri Mar 16th, 2012 04:54 by wrotek

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Here is an interesting book http://unilibrium.net/healthfiles/NightshadefreePainFree!e-BookbyMichaelFowler.pdf

about nightshades. I like especially similarity between
cardiac glycosides like this - oleandrin and nightshade toxins.

We know that patients with immunopathology can experience quite dagerous heart palpitations...
Apparently this toxins can constribute to heart beating faster.

Last edited on Fri Mar 16th, 2012 06:30 by wrotek

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some testimonials http://www.30bananasaday.com/forum/topics/nightshade-testimonials

Hello,

I have been sick for so long that I had given up hope of ever feeling better. I have been diagnosed with trigger fingers, jumper's knee, tennis
elbow and I don't shoot guns, jump hurdles or play tennis. My C Reactive Protein was so high the doctor's thought I had ALS. I have been
checked for RA, Lupus, MTG on and on.... I was practically bed ridden. I could only walk a few feet without pain and my joints throbbed
24/7. Last month I started seeing an acupuncturist for the pain, he suggested I do a cleansing and stop eating nightshades. I had heard of
nightshades but did not realize they were actually killing me...slowly. I have thyroid problems, borderline diabetes, joint pain and
inflammation, vitamin D deficiency. I was researching nightshades when I stumbled across this website. All my conditions can be traced back
to nightshades. I eat tomatoes like apples and potatoes are a staple in my diet. NO MORE! I stopped eating nightshades immediately and
Thank God I did! I have been pain free for two weeks now. I can work in my garden and I can walk long distances without stopping.
Thank you for all that you do in researching this condition. Without this information, I would still be suffering needlessly.
Carolyn

Last edited on Sat Mar 17th, 2012 08:22 by wrotek

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Personally, I consider both nightshades and gluten as like pouring petrol on the fire.

If you leave them out of your diet they can't hurt you and things have to settle at a lower level even for MPers.

There is a lot of truth in the old adage that a balanced diet is healthy and drinking several cups of coffee every day and living on potatoes and bread have to change the overall chemistry of the body away from the norm.

It's just common sense, if you are sick try and find the cause rather than compensating for it, removing the irritants from your diet will lower your overall IP and make MP so much easier and that means lower drug costs as the need for palliation also drops.

:dude:

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I have pretty much finished reading the book "Nightshade free pain free" as posted by Wrotec above.
The first part is mostly taken from the poisoners handbook and not much use to us but the latter parts have some realistic information taken from works by many researchers including Wang who we base some of our own work on so I am forced to take it seriously.

For those that follow this thread it seems likely that they could significantly ease their progress by following some of the dietary guidelines as mentioned in this book and I would like to see some of the info copied into MPKB as a resource for patients that can be quickly linked to rather than posting a URL to someone elses web page which may have contrary and confusing info.

Not sure if I can do it as I don't have editing access to MPKB but maybe I can help put something together.

:dude:

jlunn247
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC523841/
with out the mp i had developed a food avoidance obsession.
for few months before the mp untill i was just eating turkey and navy beans:shock: I know i can have "some" pizza just not everyday:)

is oatmeal a low gluten food or not?
i can eat 2-3 servings it never bothers me
is it ok for the mp?

Last edited on Mon Mar 19th, 2012 01:33 by jlunn247

wrotek
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Personally, I consider both nightshades and gluten as like pouring petrol on the fire.

But this can be also due to high carbohydrate content of potatoes or bread

Grateful Survivor
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Jjunn,

I'm not really savvy about gluten, but my impression is that oatmeal is gluten-free.  Hopefully someone will correct me if I'm wrong.

Oatmeal (old fashioned, slow-cooked; not instant) has a much lower glycemic index that most other grains especially wheat.  I eat oatmeal, with a lttle fruit and a big spoonful of almonds, for breakfast every day.  I cook a 3-day batch every 3 days, refrigerate it, and reheat  it in the microwave the other 2 mornings.

All best,
Dody

wrotek
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There are a lot of products that contain a potato flour, which is used as a thickening agent.

It is not so easy avoiding nightshades, if one was inclined to do that.

from wikipedia
Potato starch and potato starch derivatives are used in many recipes, for example in noodles, wine gums, cocktail nuts, potato chips, hot dog sausages, bakery cream and instant soups and sauces, in gluten-free recipes[3] in kosher foods for Passover[4] and in Asian cuisine.[5] In pastry, e.g. sponge cake, it is used to keep the cake moist and give a soft texture. It is also occasionally used in the preparation of pre-packed grated cheese, to reduce sweating and binding. Helmipuuro is a porridge made from monodisperse grains of potato starch and milk.

Last edited on Wed Mar 21st, 2012 06:59 by wrotek

wrotek
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Solanine and Chaconine

http://www.inchem.org/documents/jecfa/jecmono/v30je19.htm

Interesting summary

Reef
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is oatmeal a low gluten food or not?
i can eat 2-3 servings it never bothers me
is it ok for the mp?


You have to buy gluten free oatmeal/oats in order to be certain that it is gluten free. Oatmeal is easily cross contaminated with gluten as it is usually grown in close proximity to wheat. Regular oatmeal is probably a low gluten food, but not gluten free.

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Hi wrotek,

I do not eat potato's for the last 25 years after a test on food alergies potato proved to be wrong. It gives me a headage and makes me tired. On the MP I also developed a in-toloreance for the other nightshades. Tomato and chili peppers and parika and eggplant. Potato starch is so purified that it never bothered me. If the poison is out the strach is harmless ( to me).

Now there is the difficult chalange where is the poison? I did not find any other alternative than slimply try. The labels on food do not mention less than 1 % or so fractions in the food, which makes it impossible to be sure, unless you cook from cratch.

best regards erik ( roelof)

wrotek
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Potato glycoalkaloids and adverse effects in humans: an ascending dose study.

http://www.ncbi.nlm.nih.gov/pubmed/15649828

Abstract
Glycoalkaloids in potatoes may induce gastro-intestinal and systemic effects, by cell membrane disruption and acetylcholinesterase inhibition, respectively. The present single dose study was designed to evaluate the toxicity and pharmacokinetics of orally administered potato glycoalkaloids (alpha-chaconine and alpha-solanine). It is the first published human volunteer study were pharmacokinetic data were obtained for more than 24 h post-dose. Subjects (2-3 per treatment) received one of the following six treatments: (1-3) solutions with total glycoalkaloid (TGA) doses of 0.30, 0.50 or 0.70 mg/kg body weight (BW), or (4-6) mashed potatoes with TGA doses of 0.95, 1.10 or 1.25 mg/kg BW. The mashed potatoes had a TGA concentration of nearly 200 mg/kg fresh weight (the presently recognised upper limit of safety). None of these treatments induced acute systemic effects. One subject who received the highest dose of TGA (1.25 mg/kg BW) became nauseous and started vomiting about 4 h post-dose, possibly due to local glycoalkaloid toxicity (although the dosis is lower than generally reported in the literature to cause gastro-intestinal disturbances). Most relevant, the clearance of glycoalkaloids usually takes more than 24 h, which implicates that the toxicants may accumulate in case of daily consumption.

wrotek
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http://worldofcaffeine.com/the-great-duality-coffee-tea/

The Great Duality: Coffee & Tea
The Disparate Cultures of Coffee and Tea


I think comparison reflects different effects two beverages have on people personalities :)

Last edited on Sat Mar 24th, 2012 13:46 by wrotek

wrotek
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Do Nightshades contain Vitamin D 3 ?
http://noarthritis.com/research.htm

Osteoarthritis appears to be a result of long-term consumption and/or use of the Solanaceae which contain naturally the active metabolite, vitamin D3, which in excess causes crippling and early disability (as seen in livestock). Rigid omission of Solanaceae, with other minor diet adjustments, has resulted in positive to marked improvement in arthritis and general health.

:?

I found this reading Mr Fowler Nightshade book

Last edited on Thu Mar 29th, 2012 07:14 by wrotek

scooker48
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Wow!

This is fascinating.

Thanks,

Sherry

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Wrotek - great find !!

>  The Solanaceae cause at least two known health problems. They contain cholinesterase inhibiting glycoalkaloids and steroids [6,34,35,36] including, among others, the drugs solanine in potato and eggplant, tomatine in tomato, nicotine in tobacco, and capsaicin in garden peppers. When these inhibitors accumulate in the body, alone or with other cholinesterase inhibitors such as caffeine or food impurities containing systemic cholinesterase inhibiting pesticides, the result may be a paralytic-like muscle spasm, aches, pains, tenderness, inflammation, and stiff body movements

Does this mean that we should add these foods, to the list of foods to be avoided !

:(



Nick B

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Sorry to interrupt in your thread, but if this is right, how to fit in bacteria as a cause of disease?
I mean, how can we tell the difference between bacteria and Solanaceae/caffeine/pesticides/etc.etc. as a cause of disease/symptoms?

I'm just a lay person in research items, but reading all this is rather confusing.

It could mean the MP is rather unnecessary and avoiding all the (pathogenic) substances is the way to heal.

Or the MP is the right way and will eliminate the above?

Or a combination of the two above is a better way to heal?

Anyway, you can see that I'm confused :shock:

I respect your searches and hope it contributes to the way we function as human beings and brings more solutions to healing.

Last edited on Thu Mar 29th, 2012 13:09 by Limburg

wrotek
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Nick B. wrote:
Wrotek - great find !!
> The Solanaceae cause at least two known health problems. They contain cholinesterase inhibiting glycoalkaloids and steroids [6,34,35,36] including, among others, the drugs solanine in potato and eggplant, tomatine in tomato, nicotine in tobacco, and capsaicin in garden peppers. When these inhibitors accumulate in the body, alone or with other cholinesterase inhibitors such as caffeine or food impurities containing systemic cholinesterase inhibiting pesticides, the result may be a paralytic-like muscle spasm, aches, pains, tenderness, inflammation, and stiff body movements

Does this mean that we should add these foods, to the list of foods to be avoided !





Nick B




Lets not get too much excited, Dr Marshall needs to comment on that. I dont know how reliable these informations are.

Last edited on Thu Mar 29th, 2012 13:44 by wrotek

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There is little doubt that nightshades are a major problem in society due to marketing and convenience and could be considered a poisonous substance when taken in large amounts.
The body can process them and extract food value but the toxins build up and are slow to be voided which is where I believe the problem lies, we eat far too many of them.

Bacteria are a different matter as are virus strains as they move in and breed which changes us and MP is about teaching the immune system to recognise them and kill them.

Oxygen is another matter, we don't get enough!
Life on this planet developed under an Oxygen content of about 30% but since the industrial revolution this has dropped to about 20% and if you live in a major city with a high pollution index the level may be as low as 10%!

Then there are the other additives which we consume, Coffee in point on this thread and this is the purpose of posting on forums, we spread information.

We advise on MP and help you understand the treatment but we sometimes have to look outside the square for reasons why some people seem to progress faster than others and at the moment we are having some success with advising people to eliminate or at least minimise the amount of nightshades in there diet.

At the moment we are short on info on this topic so I am starting a new topic called Nightshades and I will copy this post into it so the coffee people can have their thread back!

http://www.marshallprotocol.com/view_topic.php?id=14732&forum_id=39

:dude:

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wrotek wrote: Do Nightshades contain Vitamin D 3 ?
http://noarthritis.com/research.htm

Osteoarthritis appears to be a result of long-term consumption and/or use of the Solanaceae which contain naturally the active metabolite, vitamin D3, which in excess causes crippling and early disability (as seen in livestock). Rigid omission of Solanaceae, with other minor diet adjustments, has resulted in positive to marked improvement in arthritis and general health.

Hi Wrotek, thanks for drawing attention to the nightshade plants, maybe awareness of possible problems and avoiding them could help some members relieve IP. However, I don't think the insights of Dr. Norman F. Childers are very accurate.

http://noarthritis.com/vitaminD3.htm

In our early work, arthritic cooperators were warned against excess intake of vitamin D3 (ten times more active than vitamin D) from consumption and use of nightshades- potato, tomato, eggplant, tobacco, and peppers of all kinds except black pepper (another plant family, Piperaceae). Later, it was found that a deficiency of vitamin D also could be a problem with osteoporosis and other health problems. So, monitoring of vitamin D intake is paramount to get about 400 to 500 IU per day from either 20 to 30 minutes of sun daily or from a multivitamin/mineral pill if confined or during a low-light winter period.
See also Prof. Marshall's comments in this thread:

http://www.marshallprotocol.com/forum11/13722.html

Best,
Ron

wrotek
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I see the subject was discussed at this level and the little compendium is already available. Thanks Ron .
The fact that 1.25-D degrades fastly is strong argument.

Hi Wrotek, thanks for drawing attention to the nightshade plants, maybe awareness of possible problems and avoiding them could help some members relieve IP.

Relieving IP ? Intersting idea, escpecially that not everybody seems to experience symptoms from nightshades.
Or maybe people dont realize symptoms until they quit.
Data indicate that solanecae toxins accumulate in fat.
It takes 6-7 weeks of nightshade abstinence to observe significant to moderate relief .

Last edited on Fri Mar 30th, 2012 02:40 by wrotek

wrotek
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Since caffeine increases blood sugar levels(i am trying to find out how much)...
Caffeine Blocks Insulin
Gabe Mirkin, M.D.

http://www.drmirkin.com/diabetes/9897.html


It is amazing how increased blood sugar levels can be bad for health, which of course is very visible in diabetic patients.

Another interesting article
New Zealand woman’s Coca-Cola habit cited in death
http://lifestyle.inquirer.net/44197/new-zealand-womans-coca-cola-habit-cited-in-death

Last edited on Fri Apr 20th, 2012 02:12 by wrotek

Kas
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http://www.independent.co.uk/life-style/health-and-families/researchers-report-surprising-news-about-coffee-and-diabetes-2188259.html


I am a pre diabetic. I allow myself about one cup of week coffee with some almond milk once a week or so, and I have never found that my sugar numbers were raised afterwards.

Seems there are such different opinions about coffee out there....

wrotek
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Caffeine ingestion elevates plasma insulin response in humans during an oral glucose tolerance test.

http://www.ncbi.nlm.nih.gov/pubmed/11478588

Abstract

We tested the hypothesis that caffeine ingestion results in an exaggerated response in blood glucose and (or) insulin during an oral glucose tolerance test (OGTT). Young, fit adult males (n = 18) underwent 2 OGTT. The subjects ingested caffeine (5 mg/kg) or placebo (double blind) and 1 h later ingested 75 g of dextrose. There were no differences between the fasted levels of serum insulin, C peptide, blood glucose, or lactate and there were no differences within or between trials in these measures prior to the OGTT. Following the OGTT, all of these parameters increased (P < or = 0.05) for the duration of the OGTT. Caffeine ingestion resulted in an increase (P < or = 0.05) in serum fatty acids, glycerol, and plasma epinephrine prior to the OGTT. During the OGTT, these parameters decreased to match those of the placebo trial. In the caffeine trial the serum insulin and C peptide concentrations were significantly greater (P < or = 0.001) than for placebo for the last 90 min of the OGTT and the area under the curve (AUC) for both measures were 60 and 37% greater (P < or = 0.001), respectively. This prolonged, increased elevation in insulin did not result in a lower blood glucose level; in fact, the AUC for blood glucose was 24% greater (P = 0.20) in the caffeine treatment group. The data support our hypothesis that caffeine ingestion results in a greater increase in insulin concentration during an OGTT. This, together with a trend towards a greater rather than a more modest response in blood glucose, suggests that caffeine ingestion may have resulted in insulin resistance.

PMID:
11478588
[PubMed - indexed for MEDLINE]

wrotek
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And here some regarding decaffeinated coffee
The Effect of green, roasted and decaffeinated coffee on
serum glucose, insulin and serum lipid profile in diabetic rat models.

http://www.jofamericanscience.org/journals/am-sci/am0610/114_3760am0610_968_977.pdf

Conclusion :   The observed improvement in glucose ,insulin profile , triacylglycerol and HDL-C confirm the
potent biological action of green, roasted and decaffeinated coffee and suggest that chlorogenic acid (a component in
coffee ) might have an antagonistic effect on glucose transport.
Suggesting a novel function of coffee on lowering
the risk factors of diabetes and delaying the progress of diabetes complications as well. [

wrotek
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Caffeine and theophylline block insulin-stimulated glucose uptake and PKB phosphorylation in rat skeletal muscles.

http://www.ncbi.nlm.nih.gov/pubmed/20180783

Caffeine and theophylline completely blocked insulin-stimulated glucose uptake in both soleus and epitrochlearis muscles at 10 mm.

wrotek
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Decaffeinated coffee and glucose metabolism in young men.

http://www.ncbi.nlm.nih.gov/pubmed/19918017

IngeD
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Kas wrote:
http://www.independent.co.uk/life-style/health-and-families/researchers-report-surprising-news-about-coffee-and-diabetes-2188259.html


I am a pre diabetic. I allow myself about one cup of week coffee with some almond milk once a week or so, and I have never found that my sugar numbers were raised afterwards.

Seems there are such different opinions about coffee out there....


Hi Kas. I can't imagine 1 cup a week could cause issues?

wrotek
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Caffeine Impairs Glucose Metabolism in
Type 2 Diabetes


http://care.diabetesjournals.org/content/27/8/2047.full

Santa Monica
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OK, so as a non- coffee drinker, I have been hypnotized by the green coffee bean craze. One popular website says:


"Chlorogenic acid is a compound present in coffee which has been long known for its beneficial properties. It is an antioxidant, which means it destroys the free radicals formed in the body as a result of metabolism. These free radicals if left as they are, destroy cell membranes and contribute to symptoms of aging. By destroying these harmful free radicals, green coffee bean extract actually slows down the onset of aging.

The chlorogenic acids present in the extract also help alleviate high blood pressure levels and can be helpful in treating hypertension. By neutralizing free radicals and regenerating vitamin E, Green Coffee Bean Extract has been shown to inhibit lipid and LDL peroxidation, thereby promoting cardiovascular health.

Because this green bean has not been boiled, it lacks cafestol, which is a diterpene. Cafestol is associated with the negative effects of using coffee as a stimulant, and increases the levels of bad cholesterol or LDG.

"Green coffee bean extract has also been found to promote weight loss. This weight loss is due to the natural chemical compounds, caffeine and chlorogenic acid. The caffeine from the coffee releases fatty acids from stored body fat, while the chlorogenic acid assists the liver in processing the fatty acids more efficiently, which together contribute to weight loss. Also, the green coffee bean extract boosts metabolism by altering the way in which glucose is absorbed in the body. The caffeic acids act as a stimulant and boosts the energy levels as well.

Green Coffee Bean Extract promotes glucose regulation and balance by inhibiting the activity of glucose-6-phosphatase, an enzyme involved in the release of glucose from liver stores, thus slowing the release of glucose into the blood."

Ok, so the thing I'm looking at is: "Because this green bean has not been boiled, it lacks cafestol, which is a diterpene. Cafestol is associated with the negative effects of using coffee as a stimulant, and increases the levels of bad cholesterol or LDG."

Could it be that cafestol is the thing that we react to, and not chlorogenic acid? Cafestol is a known anti inflammatory. Could it be cafestol, and not chlorogenic acid, that inhibits wellness?

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Well, as far as the cooking (boiling) to produce Cafestol, remember that fresh apple skins are a known IP reducer, so that sort of puts a monkey wrench in your idea that cafestol is the active ingredient in coffee that is mildly immune suppressive.

These people put forth a great many effects of their green coffee bean extract.  I have to ask the question how they have so much technical info.  I would be willing to bet that a great deal of it is supposition from outward effects.  Certainly the loss of weight can be the reduction of inflammation, and the resulting loss of water that accompanies inflamed tissue.

Cynthia

wrotek
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Sure, cafestol was discussed in this topic, and the cholesterol rising effect means that it has big effect on human body.

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Ah crud. was hoping for a miracle:(

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Adenosine Receptors and Wound Healing

http://goo.gl/nJsoS

Sallie Q
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bingo
the last explains why all the methtrexate that US doctors prescribed for my daughter did not prevent her from being certifiably crippled by RA
She is as badly addicted to coffee as I am :D

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http://www.huffingtonpost.com/2012/06/07/coffee-alzheimers-disease-onset-caffeine_n_1571090.html

They are saying it's the caffeine that delays the onset of alzheimers....I thought it was the Chorogenic acid?

wrotek
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Yeah it looks like they are using coffee for study very often

It would mean that folks in Britain would have different alzheimer outcomes, since they are tea drinkers I think.

Last edited on Thu Jun 7th, 2012 02:29 by wrotek

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Hmmm, I wonder who was behind that study, certainly not a tea drinker!;)

Personally I credit Rooibos tea (no caffeine) for keeping my mental faculties sharp but what do I know?:shock:

:dude:

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My mother was sharp up until her death at 85 and drank a few cups of real coffee daily.  My step-dad had to use de-caff products due to heart problems and a pace-maker.  He passed of late onset Alzheimers at 87 ...:(  Needless to say I still covet a little "real coffee" daily!  Lee

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What about a cup of tea /better tea-pot/? ;)
I drink much tea a day, but thin and with milk. Pure green china tea and exclusively bulk /no dust in bags/.
I  have not drunk coffee the third summer now. I feel much more fresh and coffee of poor quality smell me.:? 

Last edited on Sat Jun 9th, 2012 11:07 by Daki

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I love green tea!  After my tiny cup of coffee I make a large glass of green tea using one bag and dilute this throughout the day until is is plain water.  As TM suggests I only steep the bag a short time, perhaps 1-2 minutes.  When the weather is very hot, like now, I do forget the coffee as it is not worth heating up the RV to make coffee.  Lee

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Good idea, Lee. Change tea for coffee. But sometimes is difficult to fall asleep when drink tea continuosly through whole day.
Daki

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Decaff, Daki ....:P

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I had an experience with the palliative effects of (decaf) coffee last week. I posted about it in great detail in my progress thread if anyone is interested.

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Growth regulation of the vascular system: an emerging role for adenosine

Abstract The importance of metabolic factors in the regulation of angiogenesis is well understood. An increase in metabolic activity leads to a decrease in tissue oxygenation causing tissues to become hypoxic. The hypoxia initiates a variety of signals that stimulate angiogenesis, and the increase in vascularity that follows promotes oxygen delivery to the tissues. When the tissues receive adequate amounts of oxygen, the intermediate effectors return to normal levels, and angiogenesis ceases. An emerging concept is that adenosine released from hypoxic tissues has an important role in driving the angiogenesis. The following feedback control hypothesis is proposed: AMP is dephosphorylated by ecto-5′-nucleotidase, producing adenosine under hypoxic conditions in the extracellular space adjacent to a parenchymal cell (e.g., cardiomyocyte, skeletal muscle fiber, hepatocyte, etc.). Extracellular adenosine activates A2 receptors, which stimulates the release of vascular endothelial growth factor (VEGF) from the parenchymal cell. VEGF binds to its receptor (VEGF receptor 2) on endothelial cells, stimulating their proliferation and migration. Adenosine can also stimulate endothelial cell proliferation independently of VEGF, which probably involves modulation of other proangiogenic and antiangiogenic growth factors and perhaps an intracellular mechanism. In addition, hemodynamic factors associated with adenosine-induced vasodilation may have a role in the development and remodeling of the vasculature. Once a new capillary network has been established, and the diffusion/perfusion capabilities of the vasculature are sufficient to supply the parenchymal cells with adequate amounts of oxygen, adenosine and VEGF as well as other proangiogenic and antiangiogenic growth factors return to near-normal levels, thus closing the negative feedback loop. The available data indicate that adenosine might be an essential mediator for up to 50–70% of the hypoxia-induced angiogenesis in some situations; however, additional studies in intact animals will be required to fully understand the quantitative importance of adenosine.
Since we are dealing with vascular problems, CCSVI for example...

Last edited on Thu Aug 23rd, 2012 04:42 by wrotek

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http://www.vitasearch.com/get-clp-summary/37363
GLUCOSE HOMEOSTASIS, DIABETES TYPE 2 - Coffee, Caffeine, Insulin


"Caffeinated coffee consumption impairs blood glucose homeostasis in response to high and low glycemic index meals in healthy men," Moisey LL, Kacker S, et al, Am J Clin Nutr, 2008; 87(5): 1254-61. (Address: Terry E. Graham, Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1. E-mail: terrygra@uoguelph.ca ).


 In a study involving 10 healthy men, consumption of caffeinated (5 mg/kg) coffee was found to impair acute blood glucose management and insulin sensitivity. Subjects consumed either caffeinated (5 mg/kg body weight) coffee or decaffeinated coffee, followed by a 75 gram oral glucose load (either a high glycemic index (GI) cereal or a low GI cereal mixed meal tolerance test), one hour later. Results found that compared to consuming decaffeinated coffee prior to the high GI meal, when subjects consumed caffeinated coffee followed by the high GI meal, areas under the curve were higher for glucose (147%), insulin (29%), and C-peptide (40%). After consumption of the low GI meal, areas under the curve were also greater for glucose (216%), insulin (44%), and C-peptide (36%), when caffeinated coffee had been consumed. Moreover, insulin sensitivity was significantly reduced (by 40%) when the high GI meal was consumed following caffeinated coffee, and it was reduced by 29% after consumption of the low GI meal. The authors conclude, "Future investigations are warranted to determine whether caffeinated coffee is a risk factor for insulin resistance."

wrotek
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coffee & gluten

http://drclark.typepad.com/dr_david_clark/2011/09/coffee-and-gluten-sensitivity-surprising-news.html

It would make sense since coffee berries are seeds

Last edited on Fri Sep 28th, 2012 11:44 by wrotek

norman
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Fascinating ! I am going to get tested shortly ...see what happens

wrotek
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norman wrote: Fascinating ! I am going to get tested shortly ...see what happensTest what and how ?

wrotek
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Coffee promotes cortisol production and weight gain
http://www.naturalnews.com/034674_coffee_cortisol_weight_gain.html

This cortisol-induced demand for blood sugar causes us to feel hungry, encouraging us to eat more despite our best intentions.

Some people eat a lot when stressed, right ? Women eat ice cream by buckets :)

Last edited on Sun Sep 30th, 2012 02:33 by wrotek

Cynthia S
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Women?  It is my significant other that is the ice cream-holic in the family.  Cynthia

wrotek
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Cynthia Schnitz wrote: Women?  It is my significant other that is the ice cream-holic in the family.  Cynthia
Base on what I saw in the movies :D
When woman has boyfriend problem, she devours bucket full of ice-cream. And it is always big bucket.

Last edited on Sun Sep 30th, 2012 09:01 by wrotek

Cynthia S
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Male screen writers no doubt.  Cynthia

eClaire
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I've been following all of this with interest.

I never drank coffee and only discovered that I liked it a couple of months before starting the MP. A few years into the MP, I started having a cup every two weeks.

Last winter (early March), I found that having about 5 cups a week in the morning resulted not only in better energy for the entire day (taking a break every two or three days) but a more normal sleep pattern.

When I pushed myself too much while my mother was dying and shortly there after (month of July), I experienced a crash and stopped the coffee. I also put on 12 pounds after stopping the coffee (I am assuming that the weight gain was part consolation eating and part the CFS crash, as crashes in the past have always resulted in quick weight gain for me).

I have CFS and people with CFS have abnormally low cortisol levels in the morning, which screws with our sleep. Also, we have poor carbohydrate metabolism.

Feeling more rested from mostly bed rest 24/7, I began drinking coffee in the morning again on Monday and have had more energy and slept much better, feeling more rested from the sleep I am getting (versus not feeling rested at all from the sleep I was getting). Going from 2 to 4 hours of sleep a night to 5 to 8. The day I drank my coffee around noon, I got a poor night's sleep.

I'm continuing with the MP (40mg Benicar q5h), of course, but wonder what my 5 cups a coffee a week might be doing to me... whether it might actually be hurting me.


Last edited on Wed Oct 3rd, 2012 05:19 by eClaire

Cynthia S
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Have you experimented to see what effect decaffeinated coffee does?  Is the desirable part the caffeine, or something else like the chlorogenic acid?  I also have to limit my high octane coffee to at least before 3 pm, or I don't sleep.  Decaffeinated is OK later in the day tho.  Dr. Marshall says that coffee has no effect on him now.  Cynthia

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