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Prof Trevor Marshall
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Well, it had to happen - FDA has at last noticed that Benicar is affecting Cardiovascular disease in Th1 individuals - specifically Diabetics.

http://www.reuters.com/article/idUSN1113920620100611

Click here for the official FDA announcement, with more details.

And here is an article in Nephrology Times which gives more details about the dosing - 40mg once a day

Since we first told the FDA (in 2005) that Benicar had a profound effect in sick individuals, and that frequent dosing was important, nobody at FDA has expressed interest in finding out how Benicar actually works.

Just this morning I submitted a set of slides to the FDA for a presentation I will be doing for a Public Hearing later this month, on the way FDA evaluates drugs.

If anybody's Doc gets nervous after reading the press releases, I will be happy to chat with them about what we have found -- that using the correct dosing of Benicar, the MP dosing designed to keep a continuous supply in the bloodstream, cardiovascular disease is actually reduced, and plaque gradually disappears from the carotid arteries.

I will keep you up-to-date as we continue to work the issue of Benicar's real actions with the FDA...

Meanwhile, please remember that when you stop Benicar your organs lose its protection. It is dangerous to stop benicar cold-turkey. Not very dangerous, but several members have gotten very ill after their physicians abruptly stopped prescribing the drug.

..Trevor..

  ps: Here is a report on the baseline (starting) observations for the ROADMAP trial
 
 

Last edited on Fri Jun 11th, 2010 13:27 by Prof Trevor Marshall

scooker48
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I view this as an opportunity, not a threat.

Sherry

Barney
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Ditto Sherry,

I am the one the FDA should look at. I have lost a kidney to sarc pre MP, I have taken large amounts of Benicar for 5 1/2 yrs now. My blood sugars have been thru the roof a lot and I have been unable to use any diabetic meds including insulin w/o vomiting, severe pain, etc. I am having to go very strict on the sugar and flour now to get it down and I am still walking the face of this earth. HELLO!!!!!!!!!!!....thanks to BENICAR.

HANG IN THERE, WE WILL MAKE IT!!!!BARNEY:D

Last edited on Fri Jun 11th, 2010 16:12 by Barney

Prof Trevor Marshall
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Sherry, I agree. That is why I put the links to the full articles up online. If Doc mentions a newspaper article, we will have the actual detailed stuff, and can explain why this isn't anything new (to us)...
 

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My observations after reading the provided charts...

ROADMAP was larger study with 3+ years with 40mg Benicar.
ORIENT was smaller study with varying doses and end points.

Looks like both were treating a very ill patient population.

The death rate for both studies were about the same between Benicar vs. placebo,
but the cause of death appears to have been different.

ORIENT's death rate for both Benicar and placebo was 7%
ROADMAP's death rate was 1% for Benicar vs. 0.7% for placebo

Both studies allowed and had most of patient population taking multiple anti-hypertensives. This is another difference between these studies and the Marshall protocol.

Of course, in both studies the Benicar was taken once per day which provided stimulation of the immune system, but none of the anti-inflammatory protection provided when taken every 4 to 6 hours. :?

Last edited on Fri Jun 11th, 2010 21:32 by Joyful

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What doesn't jive is the "sudden cardiac death" rates and the other research that says Benicar reverses CAD. I wonder what the causes of those sudden deaths were? The reports state, " In considering the results of these trials, it is important to remember that numerous clinical trials with olmesartan as well as trials with other ARBs have not suggested an increased risk of cardiovascular-related death. And......these drugs and a closely related group of drugs called angiotensin-converting enzyme inhibitors (ACEIs) have been evaluated in many studies involving thousands of patients at high-risk for cardiovascular events, such as patients who had a previous heart attack or had heart failure. No increased risk of cardiovascular-related death has been reported in these trials and, in fact, some of these studies indicate ARBs and ACEIs are useful as treatments for certain patients at high-risk for cardiovascular events.

I am not trying to minimize the report because I do think it is something that needs further investigation. I just wonder if this particular group of people, either because of their individual risk factors or other medications (as Joyful noted), had special complications that lead to the increased cardiovascular events? In other words, why are these two groups different than other groups that were tested in regard to cardiac deaths?

Joyful
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As I understand it, almost all drug trials purposely exclude people with preexisting conditions. That is, the people tested have one, and only one condition. The condition under study.

This means that typically they study people where if the condition is a Th1 disease, it is not very far along. And so most trials will not show the kinds of mortality that are commonly seen in people with multiple chronic conditions.

This also means that that they are not studying people whose level of disease that is too far along to stand the rigors of having the VDR switched on & off every day WITHOUT the palliation of keeping the Benicar levels high enough ALL THE TIME.

The early adopters of the MP were quick to learn that missing a Benicar dose could lead to an increase in symptoms... the inflammation would start to increase and they were aware of the cause (needing Benicar more often) and worked to find the optimal timing. These researchers did not have that understanding.

Not so long ago Alaska Dave posted that he was happy to discover how much easier his symptoms were when he finally (after many years on the MP) switched from q8h to q6h dosing. So even with our understanding, there is room for fine tuning the optimal approach. Most studies will not have patient feedback as an input into the structure of the trial.

The people in these studies were probably pushing themselves to keep life going at a 'normal' pace with three co-morbidities: diabetes, hypertension, and renal disease. They are probably not mentally prepared to watch for and respond quickly to cardiac symptoms. The researchers conducting the study didn't seem to be.

Add to that a drug that activates the VDR, thus stimulating their immune response, and you have a perfect recipe for exactly what they found, in my opinion.

It is easy to be caught unaware when the mindset is to treat various systems in the body as separate. But we know that the infections of chronic disease touch every organ and part of the body. And this includes the heart as all the blood in the body must be pumped through it every minute a person is alive.

ChrisMavo
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Joyful, a very well-thought out response to this FDA news!  I think you've made some very good points in your reply!  Let's hope that the FDA does not overreact to these studies without considering the points you have made ... the amazing results of the MP study and Dr Marshall's input.  I hope they might finally see the benefits of higher dosages of olmesartan and how it activates the VDR.  It is certainly not JUST a hypertensive drug and that is how most in the medical community continue to see it! 

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Multipharmacy appears to be one problem.
And of course, it is necessary to know how to use olmesartan.

One example: You can turn off fire blowing air. (a candle)
                       You can turn on fire blowing air.  (a fire bigger than that of a candle).

Excuse my language, sounds rather German.

Those people taking part in those studies surely suffered from a"bigger fire" inflammation...

Titta

Joyful
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Excellent analogy titta! :)

Prof Trevor Marshall
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Bane sent me a study just published in Lancet Oncology showing a 25% increased risk of Lung Cancer in people taking ARBs for blood pressure (with the wrong dosing, of course).

Here is the news release, I will post more details in the next day or two:

http://www.eurekalert.org/pub_releases/2010-06/uhcm-uhc061110.php

..Trevor..

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Dr Trevor Marshall wrote:  
Bane sent me a study just published in Lancet Oncology showing a 25% increased risk of Lung Cancer in people taking ARBs for blood pressure (with the wrong dosing, of course).

Here is the news release, I will post more details in the next day or two:

http://www.eurekalert.org/pub_releases/2010-06/uhcm-uhc061110.php

..Trevor..



Common blood pressure drugs may raise cancer risk

http://www.reuters.com/article/idUSTRE65C2C120100613

Most patients in the trials (86 percent) took German drugmaker Boehringer Ingelheim's telmisartan, sold as Micardis, which has annual sales of more than $1.5 billion.

Bane
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Visiting Professor Lecture Series, organized by the Center for Drug Evaluation and Research, a division of the FDA

http://mpkb.org/home/publications/marshall_fda_cder_2006

"What you see looking at this table is that there are an awful lot of numbers which are below one. Any of these numbers that are below one indicates that that drug is going to have a very significant impact on that receptor at the normal concentrations that these drugs are administered in pharmacology. Telmisartan, for instance, doesn’t really affect the thyroid receptors, the MCR or progesterone receptors very much, but it really knocks out the VDR and PPAR-gamma and PPAR-alpha."

Prof Trevor Marshall
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My in-silico discovery that Temisartan turns off the VDR, directly opposed to Olmesartan turning it on, was confirmed by the study Bane posted in April (as well as our anecdotal experience from testing it):

Interaction of angiotensin receptor type 1 blockers with ATP-binding cassette transporters.


http://www.ncbi.nlm.nih.gov/pubmed/20222053


ATP-binding cassette (ABC)-transporters, such as P-glycoprotein (P-gp/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs) and breast cancer resistance protein (BCRP/ABCG2) transport numerous drugs thus regulating their absorption, distribution and excretion. Angiotensin receptor type 1 blockers (ARBs), used to treat hypertension and heart failure, are commonly administered in combination therapy. However, their interaction potential is not well studied and their effect on ABC-transporters remains elusive. The study therefore aimed to elucidate the effect of various ARBs (telmisartan, candesartan, candesartan-cilexetil, irbesartan, losartan, olmesartan, olmesartan-medoxomil, eprosartan) on ABC-transporter activity in vitro. P-gp inhibition was assessed by calcein assay, BCRP inhibition by pheophorbide A efflux assay, and MRP2 inhibition by a MRP2 PREDIVEZ Kit. Induction of P-gp, BCRP and MRP2 was assessed by real time reverse transcriptase polymerase chain reaction and for P-gp also in a functional assay. Telmisartan was identified as one of the most potent inhibitors of P-gp currently known (IC(50)=0.38+/-0.2 microM for murine P-gp) and it also inhibited human BCRP (IC(50)=16.9+/-8.1 microM) and human MRP2 (IC(50)=25.4+/-0.6 microM). Moreover, the prodrug candesartan-cilexetil, but not candesartan itself, significantly inhibited P-gp and BCRP activity. None of the compounds tested induced mRNA transcription of P-gp or BCRP but eprosartan and olmesartan induced MRP2 mRNA expression. In conclusion, telmisartan substantially differed from other ARBs with respect to its potential to inhibit ABC-transporters relevant for drug pharmacokinetics and tissue defense. These findings may explain the known interaction of telmisartan with digoxin and suggest that it may modulate the bioavailability of drugs whose absorption is restricted by P-gp and possibly also by BCRP or MRP2.

Last edited on Mon Jun 14th, 2010 04:35 by Prof Trevor Marshall

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HI DR MARSHALL

This is Fred in WV.  On you post about about the "telmesartan with digoxin", I am on the Benicar and Digoxin, would this have any effect on me and my heart.  I have wondered if I should stop the Digoxin with the Marshall Protocol. 

When I started the MP the doctor took me off 2 other heart pills but keep me on the Digoxin.  I think the Digoxin was to make the heart muscle stronger?? This was because the ejection fraction was on the low side. I have been wondering about if I should stop the Digoxion for some time now.

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

Your friend in Sarcoidosis
Freddie

Prof Trevor Marshall
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Freddie,
Info on Digoxin can be found at Wikipedia
http://en.wikipedia.org/wiki/Digoxin

You might check the concentration you are taking against the 0.8 μg/L they mention there.

Adverse events do not seem VDR-related, and the molecule is too big to affect VDR, but I am not sure about PXR. It should be OK. Still, I would discuss with Doc whether you still need it, or can wean it slowly.
 

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Modest lung-cancer signal with angiotensin-receptor blockers

http://www.theheart.org/article/1087349.do

"This is a modest increase, similar to that seen with passive smoking; it's not a massive increase," lead author of the study, Dr Ilke Sipahi (University Hospitals Case Medical Center, Cleveland, OH), told heartwire. Nevertheless, this is the first time such an association has been made, he said. And although the number needed to treat to cause one excess cancer was calculated to be 105 patients for four years, meaning the risk for the individual patient is not huge, "given the millions of patients on these drugs, this is an important number, because it gives us an idea of potentially how many excess cancers could be caused by these medications. On a population level, I think these are very concerning signals."

Dr Michael D Peake (Glenfield Hospital, Leicester, UK), a spokesperson for the UK Lung Cancer Coalition, who was not involved in this research, told heartwire that the increase in lung cancer seen in this meta-analysis with ARBs "is fairly small." The risk of lung cancer is around 200% to 300% higher in a smoker than in a nonsmoker and is increased by about 60% in a person with a family history of lung cancer compared with an individual with no family history, he said.

"In this context, it's a relatively small risk, but if applied to large numbers of people, it might be quite important," he explained. The data are interesting but "would not stop me personally from taking an ARB if I needed one; it's not sufficiently powerful to influence prescribing at this point," he added.

-----------------------------------------------------

"Nevertheless, questions remain as to whether ARBs are associated with malignancies and whether there should be concern about a single drug, telmisartan, or all ARBs, he says."

"In the interim, ARBs, particularly telmisartan, should be used selectively, he urges. They can be reserved for patients with intolerance to ACE inhibitors, "which will also save money for healthcare systems, since nearly all ARBs are proprietary and ACE inhibitors are generic."

Last edited on Mon Jun 14th, 2010 09:57 by Bane

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Angiotensin-Receptor Blockers Linked to Elevated Risk, But Some Doctors Aren't Convinced

http://abcnews.go.com/Health/HypertensionNews/study-links-popular-blood-pressure-drugs-cancer/story?id=10909261

scooker48
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At the risk of being considered a moron, how are going to defend the use of Olmesartan to the FDA?

I can grasp some of the science presented, and am a firm believer in the MP.  But why are the studies showing a higher cardiovascular death rate flawed?

With puzzlement,

Sherry

 

 

Terri R.N.C.
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Hello Dr.Marshall,

First of all I would like to thank you for giving me my life back.  I have been on program for about 22 months now and I am doing impressively better.  I'm going to go back to work within the next few weeks.  I just have to interview for the first time in 15 years:shock:!  I will post my recovery soon as my most recent post was lost after spending an hour on it.  I'm back in nursing school working on my "Nurse Practitioner" degree.  My MD is so impressed with my recovery that I will be his "MP Nurse" after I complete my degree (about 2.5 years to go).  I'm writing to you in concern for my fiance.  He has Metabolic Syndrome.  He is a typical Th1 patient.  Cholesterol is elevated, elevated blood sugar, high blood pressure, you get the picture.  I have started him on Benicar but he can only tolerate one tab/day.  He takes 40mg qhs.  He is a carpenter and works outside and gets too dizzy and weak when he tries to take 2/day.  After reading about the cardiac precautions especially for diabetics it has caused me to become alarmed.  My plan is to get back to working full time so that Mark can go full time on the MP.  I know that it will knock him out for at least 18 months.  My question to you is that do you think that he is better off not taking Benicar until he can commit to full time MP?  He could take the Benicar that has HCTZ mixed with it until he is ready to go full time with the protocol or do you think that he should continue with Benicar 40mg qhs along with a baby ASA qhs.  He states that he likes the way Benicar makes him feel however he gets too sleepy with the am dose.  He is responsible for building large corporate buildings and fears that he will miss handle dangerous machinery if he increases his Benicar.  I think that with time he can handle the increase  in Benicar, but then again he is in the sun all day.  He follows the same low D diet as I, but he has an awfully heavy duty muscle demanding outside in the 100* temp job (his job sucks).  Does Benicar work as well as it should even though one has to be out in the sun?  If not, I guess Mark will have to wait until the first of the year to commit to the MP.  I"m just concerned that he should stop taking the Benicar until then.  I have so much respect for you.  Everything that you said would happen to me has happened.  You are right on with your research and should have received the Nobel Prize by now.  My MD is the same one that Mark goes to and he likes Benicar.  He has suggested that Mark take Azor (Benicar with HCTZ).  I don't want to lose Mark.  I've already been a widow once before.  I know that these questions are very demanding, but the Benicar and Diabetes has me concerned.  I guess what I am asking you is what does this latest research mean to you?   Thank you for taking time to read this.  I hope that evryone is doing better.  I never thought that I would be, but if you get away from the medical doctors who are so narrow minded you will get your health back.:D 

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Hello Terri,

I am not Dr Marshall....but I am a diabetic (type 2) since 1995 at about the same time I lost my right kidney to sarc. I am intollerable to all diabetic meds including insulin. Symptoms w/meds include bending over double in pain, vomiting, diarreha, dizziness, etc. and also not lowering my glucose levels.

I have been on MP for 5.5 yrs and still struggling w/the diabetes but have gotten real diet serious, NO SUGAR, NO FLOUR and NO POTATOES. I have really had to get inventive w/recipes. I would be will to send you what I have gotten together. Lots of good stuff that I am not feeling deprived with.

It is hard to hold your temper at the diabetes when you see people eating cake and other foods that you would be able to eat. But...I have come up some really great eats that are MP ok.

Unless Mark can take no less than 4 Benicar per day, I would have him wait to start, IMHO.

I am doing 60mg Benicar @ 6hrs and feeling great and actually have energy. I am not suggesting this for anyone, but wanted you to know that I am doing great despite diabetes.

After lots of time of losing my posts, I usually do it on Microsoft Word and then cut and paste to the MP site.

HANG IN THERE, WE WILL MAKE IT!!!!BARNEY:D

Prof Trevor Marshall
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Terri,
I would like a little more info. What is his 25-D level (measured with the ZRT test is good enough). Has he tried half a tablet morning and night? What does that do for him? Or even split the morning 20mg into two quarter-tablet 10mg chunks spaced q6h? That should give less immune activation, but better day-round organ protection. Still not perfect, but better than 40mg q24h.
 
The key piece of knowledge is that the receptors in sick people (not just the VDR) seem to break down more quickly (extra protease action, I suspect) and in really sick people dosing every 4 hours is necessary to keep palliation in place. Healthy people are fine q24h. So you can see that dosing interval is important...
 
 

Last edited on Wed Jun 16th, 2010 17:33 by Prof Trevor Marshall

Terri R.N.C.
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Hi Barney,

Thank you for the quick response.  I would love to have some of your recipes.  Mark needs to get off sugar.  I find candy wrappers in his car and if he grocery shops he will bring home cake and cookies.  I react to sugar so I have no problem avoiding it.  He needs to withdraw from it.  He is very cooperative and kind so I will show him your post and he will be receptive to it I'm sure.  You know how family is.  They have to hear it from someone else before they believe what they are being told.  Thanks so much.  My e-mail is tholzl@roadrunner.com if you prefer to use that.  God Bless and stay well!  Terri.

Terri R.N.C.
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Hi Dr.Marshall,

Thank you for your quick response.  He has not had a 25-D test yet.  He will have to take work off in order to go get labs done so that is something we are going to have to set up.  I can get him to take 20mg in the am and 40mg in the pm.  He states that he likes the way Benicar makes him feel (very sleepy), so that is why he is willing to take it at night, but not during the day.  Also, does the fact that he works out in the hot sun all day affect the Benicar's reaction in the body?  I hate to see him have to wait to start the MP as he has Metabolic Syndrome that is only going to get worse.  Thank you for your time.  Terri.

Prof Trevor Marshall
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Terri,
ZRT is a pin-prick test. Please search for ZRT using the search box above. The topic you want is "Now you can test your 25-D at home"
 

Joyful
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Here's the new link... http://mpkb.org/home/tests/homekit :)

Terri R.N.C.
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Thank you.  I've got Mark awfully scared:(.  He has witnessed what I have gone through the last 22 months and he realizes what he is in for.  I think that I would chicken out if I was the one to go on MP after caring for someone who was really sick from it.  I barely left the house for the first year!  He is not going to be able to start the MP until Dec/Jan so should we test his hormone "D" at that time?  Be well everyone!:)

Prof Trevor Marshall
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You can test it now and it will give you some idea of whether he may have difficulty lowering it into the therapeutic range. He will need to check it every few months once he starts therapy, until it gets reliably into the therapeutic range.
 

Terri R.N.C.
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Dr.Marshall,

Mark work's outside in the hot sun 5 days/week.  He follows low D diet along with me.  I'm thinking that after he completes this building project in Dec/Jan he can start MP and get out of the sun.  Right now he is very tan even with repeated application of sun screen.  Just his arms, face, and neck are exposed, but those areas are very tan.  Are you suggesting getting the "D" checked now to see where he stands with sun exposure and the use of Benicar?  He just increased the Benicar 2 days ago from 40mg qhs to 20mg qam and 40mg qhs.  He states that he does not feel well and he has developed diarrhea.  I think that I will get him an office visit with my MP doc and get labs done there as Mark has excellent health insurance.  He has to be very careful with his electrolytes as he is working in heat that is over 100* on many days.  He is 50 years old with Metabolic syndrome so no room for fooling around.  I will let you know what his labs come back as.  Should he go ahead and have 125 D checked as well?  Thanks so much for your time.  I know that you are a very busy (and brilliant) man;).  Terri

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Dr Trevor Marshall wrote: My in-silico discovery that Temisartan turns off the VDR, directly opposed to Olmesartan turning it on, was confirmed by the study Bane posted in April (as well as our anecdotal experience from testing it):

Interaction of angiotensin receptor type 1 blockers with ATP-binding cassette transporters.


http://www.ncbi.nlm.nih.gov/pubmed/20222053


 Dr. Marshall.

Does it mean that Olmesartan  still safe to use?
Thank you. Gene

Prof Trevor Marshall
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Gene,
Good to hear from you again :)

Olmesartan is not only safe to use, it provides protection to your body's organs from the inflammatory cytokines.

Stay away from the other ARBs, however, they are not the same as Olmesartan...
 

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Since the FDA are investigating, presumably they could find that it is not safe or that more testing is needed before it can be used in an off-label manner, such as on the MP. Who is doing the studies that will convince bodies such as the FDA of Benicar's safety?

While this may be an opportunity, it could be cause for concern too. If the MP is taken away from me, so is my life.

Prof Trevor Marshall
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Amy and I will be traveling to Washington DC to speak at a public hearing at the FDA on 29/30 June.  We are keeping our finger on the pulse. At this point there is no likelihood that FDA will do anything silly. Last year Olmesartan was a 1 Billion dollar market, worldwide, as were each of the other sartans. There would need to be problems much larger than have been reported before any of the sartans was withdrawn.

In any case, this Foundation has put in place contingency plans to guard against a withdrawal of Benicar from our members. I am not free to talk about them at the moment, but trust me, there is a very good reason we have been spending so much time with the FDA these past five years...

..Trevor..
 

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That's very good news.

Without the MP, my life too would be taken away.  And I'm very fond of it... having so recently got it back.  :)

Thanks always to you Dr Marshall, Amy and the rest of the team.

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So I think I'll cut back to every 8hr dosing and start saving up on Benicar. What is the shelf life on it?

 

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Shelf life of Olmesartan Medoxomil is not very good (a year or so). It is a very unstable molecule. I think there were some papers investigating this issue, maybe one of the members can help you track them down.

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Thank you.  That is good to know.  This means, I will finish out my current stockpile, except for a couple month's worth before ordering some more.  I thought the shelf life would be similar to a lot of other meds.  Thanks again.

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So are you recommending we stock-pile until we know the outcome of this? Or reduce our doses so it lasts longer? I have to say i'm very concerned. While i'm sure you and Amy have plenty to say at the public hearing, i'd imagine a body such as the FDA will be more impressed by clinical studies, and there is enough motivation and money out there to produce such studies.

From where i'm sitting, this doesn't look good for the "move to mainstream" which is the foundation's primary focus right now, right? I'm not really sure what your team is doing to promote this move to mainstream, but the unfortunate fact is the scientific world needs clinical studies, so why not produce a few and give it to them? What's happening with the West China study? Is it progressing? Are there any problems? We haven't heard much about that in a long time.

 

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I suggest we all keep cool heads, maintain an even more ample supply than we already do, use it in date order, and trust that everything appropriate is being done--which I am sure it is.

I realize this situation may make things more difficult for many of us. We probably need to arm ourselves with the facts about these studies--not Benicar; not round-the-clock dosing; etc.--before we next see our docs. And we may experience more supply difficulties for awhile. I'm not minimizing any of this.

I just think we need to keep our cool and view this as what it is: a potential problem requiring problem-solving skills. We are collectively and individually very good at problem-solving.

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Freddie Ash wrote: HI DR MARSHALL

This is Fred in WV.  On you post about about the "telmesartan with digoxin", I am on the Benicar and Digoxin, would this have any effect on me and my heart.  I have wondered if I should stop the Digoxin with the Marshall Protocol. 

When I started the MP the doctor took me off 2 other heart pills but keep me on the Digoxin.  I think the Digoxin was to make the heart muscle stronger?? This was because the ejection fraction was on the low side. I have been wondering about if I should stop the Digoxion for some time now.

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

Your friend in Sarcoidosis
Freddie

Popular Heart Drug May Be Unsafe for Some Kidney Patients

http://www.sciencedaily.com/releases/2010/06/100624183009.htm

The risk of death was 28 percent higher for dialysis patients taking digoxin, after adjustment for other factors. The increase in risk was greater for patients with higher levels of digoxin in their blood and in patients who had lower serum potassium levels, which is a well-known factor that contributes to digoxin toxicity.


 

gart
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I had collected  a  stockpile for 6 months of Benicar samples given me by my cardiologist and physician.It doesn't says when I should to discard and I don't know how long it stayed in doctor's offices.It is factory packed with aluminum seal on the top , seven tablets in bottle. They looks absolutely perfect, white and solid.Can I use them?

 Thank you.Gene

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HI GENE

This is Fred in WV.  I get some of these samples from my family doctor from time to time to make sure I do not run out.  If you look on the side of the bottle there should be:  

                  LOT NUMBER
                  EXP DATE - Like the one I am looking at right now has 05/11

So you should be able to find an exp date telling you when you should not use it.  I hope this helps.

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

Your friend in Sarcoidosis
Freddie

gart
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Hi Freddie.

Yes,  I found it.

Thank you very much.

Gene

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There is a discussion about this over on Bacteriality with Amy and a research scientist. He says it is most likely going to get pulled. It is not a very widely used drug and Daiichi Sankyo is not going to put up much of a fight.

There are many other anti-hypertensives on the market so who cares!

Phillyguy
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madhouse wrote: There is a discussion about this over on Bacteriality with Amy and a research scientist. He says it is most likely going to get pulled. It is not a very widely used drug and Daiichi Sankyo is not going to put up much of a fight.

There are many other anti-hypertensives on the market so who cares!


With respect to a comment made to Amy by this researcher:

Tim Ayers made the following comment: 

"I do however find it hard to believe that it would do alot of interaction invivo. Olmesartan is very tighly bonded to the AT1 receptor as it was designed to do. Considering the volume of distribution of olmesartan and the amount of AT1 receptors that sample the blood stream it is unlikely that any of the drug is available for interaction with other weaker ligands…..remember that at typical doses (even 3 times the normal dose as you suggest) there is still 100s of times the AT1 receptors as there is drug in the serum. This is further compromised as blockade of AT1 leads to an up regulation of AT1 on vascular SM cells…thus as time goes by there are more and more recptors available for bonding."

http://www.ncbi.nlm.nih.gov/pubmed/18078928

Moreover, angiotensin AT(1) receptor antagonist dose-dependently inhibited TNF-alpha-induced PAI-1 production. Interestingly, high-dose olmesartan, but not candesartan, reduced the increased expression of the angiotensin AT(1) receptor.

Of course we now know per the Kidney International paper that VDR activation downregulates the AT1 receptors....

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Dody wrote: I just think we need to keep our cool and view this as what it is: a potential problem requiring problem-solving skills. We are collectively and individually very good at problem-solving.

I have just arrived in Maryland, ready for the presentation I will be giving at the FDA on Tuesday. Amy is joining me here tomorrow.

The video should be on YouTube by the weekend...

..Trevor..

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I had a read of this discussion which is very interesting indeed. Tim Ayers makes some excellent points and it's interesting to hear about the "grumblings" that have been going on about olmesartan for years. He is an industry insider and predicts olmesartan will be pulled within 6-12 months. This has now put us all in a terrible position, because once pulled it will take many years and lots of $$$ to do the studies to get it back. Why would a big pharmaco do that when, according to Tim, sales aren't very good anyway? Tim makes some good points about the lack of proper research to convince these scientific bodies of the safety of olmesartan. I can't imagine the FDA deciding to allow continued use of olmesartan because of the theories put forward by ARF when there is clinical evidence mounting against it's safety.

I think we all need some answers now. We have trusted that the ARF is doing everything in our best interests, but the fact this is happening is proof ARF is behind the 8-ball. People have long been asking for proper clinical proof, and because none have been produced, we are in trouble.

I, for one, can't imagine surviving long without the MP. I have no desire to function like that again. I'm not sure if others are thinking similarly, but I had made a decision before I started the MP that if I couldn't find a cure for whatever the he'll was going wrong with me, I would take my life. That was the only hope I had of escaping the suffering, and now that seems a real prospect again. I'm sorry Trevor, but we need answers.

What happens if olmesartan is pulled from the market? What do we do?

Prof Trevor Marshall
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Look, I don't have time to look into this Tim fellow, and who he is, but he is dead wrong when he postulates that all the Olmesartan would be bound by the Angiotensin receptors. The obvious reason he is wrong is that if so, all the ARBs would be identical in their actions, which they are not. Clearly they affect other receptors, each ARB in its own particular way.

Sankyo sells a billion (1000,000,000) dollars worth of Olmesartan a year. To the USA alone they ship 26 tons of the product every year. He is wrong about the size of their market. take a look at the market sizes I posted after i got back from the sartans summit in Shanghai earlier this month :)
 
http://marshallprotocol.com/view_topic.php?id=13788&forum_id=39

I am still taking Olmesartan. My brain is still getting clearer (and calmer) month by month. I suggest it would be a good idea to wait until you see me start to get worried, and not listen to some self-appointed 'industry-insider' :)
 
 

Last edited on Sun Jun 27th, 2010 21:17 by Prof Trevor Marshall

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It should be obvious that the types of studies that would get the attention of the FDA nearly always require funding levels only available to the researchers that work within the current mindset on chronic disease. And the foundation has worked hard to get what they could with the orphan status designation on two antibiotics for sarcoidosis in March of 2006. Countless hours have been spent working on applications and then reworking each time they are rejected.

Please do note that Dr. Marshall has already said the foundation is working hard behind the scenes to be proactive in this. I have a great amount of confidence that the foundation will find a way to deal with whatever comes down the line.

Let's not borrow from tomorrow's trouble ... may I suggest that we all keep "positive minds" concerning the issue. :)

positiveminds
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I should change my monicker to "realistic minds." I don't mean to be negative, but these are some valid concerns, I think.

What you say Joyful is exactly what I fear - that those bodies with the money will spend it on proving Benicar's dangers before any research will be produced confirming the MP's hypotheses and hence Benicar's safety, and if Benicar is withdrawn we and the ARF are firmly on the back-foot and I doubt the ARF has the funding to do anything much about it.

If "tomorrow's trouble" wasn't related to my health and ability to function in the world and live a life free of suffering, I wouldn't worry so much. I really do hope the ARF have a back-up plan for the worst-case scenario of Benicar being withdrawn from the market, but I just don't see how they could do anything about it if that happened, with all due respect. Again, the FDA would not be investigating were they not considering withdraing the drug. At this stage, it appears the evidence is in our favour, but that could change.

I'll butt-out for now, and will try to stop worrying. But I've held these concerns for some time and now that this FDA investigation is happening, wanted to air them.

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Your concerns are all of our concerns as well. It's just so damaging to our diseased bodies to allow anything to provoke a stress response. :?

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Positiveminds, let me repeat what I said above. Wait for the announcement. We are best to work within the system right now, and the cogs of progress turn very slowly. But there has been progress, and my first priority has always been to protect our members...

Dody wrote: I just think we need to keep our cool and view this as what it is: a potential problem requiring problem-solving skills. We are collectively and individually very good at problem-solving.

I have just arrived in Maryland, ready for the presentation I will be giving at the FDA on Tuesday. Amy is joining me here tomorrow.

The video should be on YouTube by the weekend...

Hogan
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Keep in mind also that just because a med is taken off the market in the US doesn't mean that it is a death sentence for the drug. 

For example in 1994 when my son was an infant he was diagnosed with colitis and severe GERD and by 3 months was taking a new drug that had been recently approved by the FDA.  The drug was called propulsid. 

 http://www.rxlist.com/propulsid-drug.htm


It was the only drug that worked in the way the GI docs wanted for him at the time to control his severe GERD.  He used it for about 3 years until I read a new study regarding its safety in connection with LQTS.

http://en.wikipedia.org/wiki/Long_QT_syndrome

My family has a history of LQTS and eventhough my son had tested negative by EKG I hadn't had the genetic screening done yet to eliminate the possiblity of him having a genetic marker.  Since he had made great strides by then I discontinued his taking the drug.  By 2000 the drug was voluntarily withdrawn from the US market but the maker didn't stop selling it.  Today it is still available via the internet and used in many countries.  Looks like I could buy it if I wanted and have it sent in.  This is just one example I could give you more.  I even found Vioxx online and we all know the story of that.

As long as there is a market for a drug someone will produce it and sell it.  That is the economics of it regardless of what the FDA says.

So even in what would be the worst case scenario.  Where there is a will there is a way. 

Karen



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I do not post very often, but I can't sit on the sidelines on this one.   Having worked for the FDA for most of my career I can tell you that once a drug is on the market it is very difficult to get it removed, and here I am talking about some real bad stuff.  Putting that aside for a moment you have to recognize, and if you don't or can't, you have to trust that what I am about to tell you is correct.  Olmesartan, was and  still is one of the safest drugs on the market.  Even the so called experts have come out on this recent study release saying that they will not be changing how they prescribe this medication.   Unfortunately, "Tim" does not have a good grasp or understanding about what he is talking about.   At the moment I must drop this dicussion because I am in the middle of something else.  I will be on later today.  In the meanwhile for those of you worried, and to those of you needlessly worrying others, there is no need for this alarm.  I ask you to trust me on this one and get back to your real lifes.   I will be on later today.  Joyful, if this message needs to be also placed on Bacteriality, please do so.  I really have to go for the moment, but you can reach me on my cell if you need to.    Thank you

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Hello all,

whatever happens, in this forum there are so many people with different backgrounds and abilities that we all together will find ways.

I want to mention that I am full of respect for what the ARF has done.
Despite a lack of money so much has been achieved by those active.
Thank you for that.

Titta

positiveminds
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I don't think i'm needlessly worrying others. I think what i'm doing is airing valid concerns I have, and trying to get answers for myself and others with similar concerns about this, which I believe i'm entitled to do on a public discussion forum. Many of us have had to take our health into our own hands and do not trust medical professionals. I have much respect for Dr Marshall and his team, but that does not mean we cannot be critical or question what is happening. We didn't have this information before. I don't know how the FDA works from the inside so I think my concerns were valid. Also, there is a lot of criticism out there about the MP and ARF, including from people previously working for the ARF, so it's hard to know what is what from a lay-perspective and I think we are entitled to be critical and ask for answers and more transparency in what the ARF is doing, since our lives (or quality of life) depend on it.

Joyful - I wouldn't say i've provoked a stress-response over this one, just airing some reasonable concerns, in my opinion.

Perezt, I'm living my life, still working etc, thank you. I just think we need some answers to settle worried minds, and your post, giving us a little insight into the workings of the FDA, helped.

Perhaps i'm the only one with these concerns? Perhaps i'm being completely irrational and neuro-herxing? If so, I apologise for taking up this thread with my worries. 

Last edited on Mon Jun 28th, 2010 10:04 by positiveminds

scooker48
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The discussion on this subject at the bacteriality site can be read, starting with the third post down, at:

http://bacteriality.com/2010/06/01/symbiosis/

Sherry

Personally, I feel much better after reading the discussion at bacteriality.

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Question: can the shelf-life of Olmesartan be extended by freezing it, or refrigeration?

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Lowering the temperature of a chemical reaction will slow its rate. I would expect the same with Olmesartan Medoxomil, which tends to form an Olmesartan dimer, and other decomp components which are not harmful, in any case. Freezing a drug is a little dangerous, as there is a good chance that moisture will enter the equation at that point :)

The problem is that the medoxomil ester is trying to break the olmesartan backbone in half:


eClaire
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I had the sales rep ask the pharmacist whether freezing or refrigeration of Benicar was a good idea.  He recommended that I do neither as long as I had air conditioning or a cool place (like a cool closet or dry basement).  Whatever the case, freezing was definitely out.  Just relaying what I heard today....

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Of course a pharmacist would be fully up-to-date with his knowledge of the drug, and how it decays, and its propensity to do so.


Not being critical of you Claire, just trying to point out that authority figures are not necessarily the ones to ask for specialized information...

eClaire
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So ... are what you saying is that you think refrigeration is better than a cool dry place?

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As long as you keep them in a tightly sealed bag(s), and make sure there is no condensation in the refrigerator compartment you are using (I use the bottom 'crisper'), then drugs and LiION rechargable batteries will last longer there...

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Dr Trevor Marshall wrote: Shelf life of Olmesartan Medoxomil is not very good (a year or so). It is a very unstable molecule. I think there were some papers investigating this issue, maybe one of the members can help you track them down.


 

hi mr. marshall


I use hipersar(other brand name of olmesartan)exp date 9.12 .long enough to store.

Joyful
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Dear positiveminds, I was not criticizing your posting on this topic at all. Concerns need to be voiced so they can be addressed. No problem there. Especially because there are some, as you pointed out, that have cast the foundation in a pretty negative light. They are sadly wrong on many important points, but it can get you doubting if you don't have input from any other source.

Thank you Tom for contributing your 'insider' perspective! That is pretty much the general idea I had from reading the articles referenced at the top of the thread, but it's always nice to get the level of reassurance your comments bring.

Titta, thank you for affirming what I know to be true. These forums are the meeting place for an international group of intelligent, stubborn, never-say-die people who will find a way to make the MP science work in the face of any obstacle thrown in our path!

Sherry, I'm so glad you posted the link to the discussion where the questions were raised and discussed at length (http://bacteriality.com/2010/06/01/symbiosis). Quite a refreshing interchange of comments. :)

So, now...

Onto the mundane topic of preserving medications for long periods, I think I recall Alayne used a "Food Saver" to vacuum seal her medications before refrigeration. I've got one of those devices, but it's buried in the garage... so ...

I usually put the pills into a zip-lock plastic bag (maybe with a silica gel pack). I seal the bag, place it in the bottle (for identification), close the bottle, and then place the bottle inside two more layers of zip-lock plastic bags. It seems to keep the pills dry.

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My working theory for the (still unpublished) work out of the ROADMAP and ORIENT cohorts is that the small increase in bad outcomes are the results of olmesartan breaking up arterial plaque.
http://www.ncbi.nlm.nih.gov/pubmed/19124398

As I read when researching the KB's now somewhat polished cardiovascular disease article, breaking up plaque (even though it sounds healthy and may be good in the long-term) can cause pieces to flick off, travel through the arteries, and become lodged in tiny passageways, leading to adverse events in the short-term such as stroke.
http://mpkb.org/home/diseases/cardiovascular

One of the papers the above KB article cites is on how macrophages upset plaque stability:
http://www.ncbi.nlm.nih.gov/pubmed/15337206

Until reading the above paper, I didn't think anyone would want stable plaque.

For patients intent upon recovering atherosclerosis, I don't know any way around it. Whatever treatment ends up clearing plaque is going to run into this problem, IMO – whether it's olmesartan or green cheese.

Paul

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Paul,

Minocycline is thought to minimize the effects of stroke and, in fact, is actually being used experimentally immediately post stroke to mitigate long term sequelae.

Perhaps it is important that people with existing cardiovascular disease make an effort to maintain some kind of baseline dose of mino?

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Phillyguy,

Thanks for sharing. I wonder if the dose used in the trial your referred to is immunosuppressive, and that would explain why it shows some therapeutic promise.

Paul

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This may be totally ignorant (since I know nothing of the science), but it seems to me that a working immune system would create plaque by virtue of killing off bacteria.  I may be wrong, but if the plaque on teeth, which is linked to heart health, is related to the plaque in arteries, then I did not develop plaque until I went on the MP, as I virtually had NO plaque on my teeth, which to me has become a sign of a poorly functioning immune system (not that I was so healthy I didn't have any, though that might be the possibility for "healthy" individuals).  (I didn't even need to get my teeth cleaned every 10 or 12 years when I did.) 

All this says to me, is that people need intervention earlier and perhaps plaque on teeth is yet another sign (or perhaps none at all with other Th1) symptom to indicate that intervention is needed, and then, as Paul says, risk has to be taken into account as the plaque breaks up.

Claire

Last edited on Tue Jun 29th, 2010 05:17 by eClaire

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eClaire,

I don't know about plaque in arteries, but plaque on teeth is a biofilm created by the bacteria. I think it could increase on the MP as the bacteria are trying to protect themselves from the ABX. On the other hand, if you are not on the MP and have a lot of plaque biofilm on your teeth, that would indicate you probably have a lot of bugs all over, and have poor heart health.


@paul albert, well said

eClaire
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Thanks for the explanation.  Result is nearly the same (whether die off or biofilms).  The MP has the bacteria on the run!  :D  As for me, no plaque prior to the MP and so much plaque after that at times I had to scrape my own teeth four times in a day.  That has slowed down of course, but whenever my IP picks up, I still notice an increase in plaque on my teeth.  This also happened for a brief time in my life (about 8 months) when my immune system kicked into gear.  I thought I was getting worse, but it was my immune system making me better.  I had some plaque then, not anything like the MP though.

I would venture to guess that even without the plaque on my teeth I had poor heart health, particularly given the symptoms pre-MP and IP after starting the MP.

Slap me if someone has to explain this to me again!:shock:

Last edited on Tue Jun 29th, 2010 10:36 by eClaire

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Hi Claire....don't want to confuse the issue,  but my experience with plaque is just the opposite.  No plaque all my life till my health (assuming immune system) started failing.  Then almost immediately after starting MP no more plaque.  Yeh!!!

scooker48
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If I may chime in, the reason for the difference is the almost infinite variety of populations of bacteria, fungi and virus organisms different people are carrying within and on the skin.

The common theme is you both noticed a change in dental plaque once starting the MP, correct?

I myself had black stuff sticking to my teeth while taking the abx.  Ugh. 

Sherry

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Yes, you are right many times we seem to be a pile of opposites here and it is no doubt due to our specific microbiota and what it is doing to us.  I've seen a lot of people report lots of problems with plaque pre-MP, but I must not be alone in my experience.  :cool:

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at 18 months on MP some of my teeth feel clean and others feel microbe-filmed
judging by my erratic brain function it is like that between the headphones also

PS I learned to keep Olmesartan carefully wrapped and refrigerated during my first summer, when some of the tablets tasted 'off' particularly noticed since I would keep a spare sheet everywhere including in glovebox (do not do that anymore! our winter resembles the summers some of you have)

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Would a small plastic airtight container put inside of the crisper be sufficient to prolong drugs in the fridge? There are plenty of those at the supermarket.

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HI ALL

This is Fred in WV.  My 2 cents worth on how long the Benicare will be good is more than 1 year.  The reason is I have some in the sample bottles (but well sealed with foil on top) that has an exp date of Sept 2012.  I am not sure is these were the ones the doctor gave me a few days ago or not but that would be close to a 1 - 1/2 years looks to me like.

Right now is the time of year that I have my MP doctor call Medco and get the ok for the 3 pills they have been paying for, for the last 3 years.  I saw the doctor last week and the nurse was to take care of this for me, but when I tried to order yesterday I had problems.  I called and the man took my order with no problem.  I have been paying $84 for 270 pills and I ask how much it would be today (it use to raise every so often) and the man told me no charge today.  A little while late the phone rang and it was a recording from Medco saying they could not fill that order and they were sending me a letter to tell me why.

I do not know if it is because they do not want to pay for it, my doctor did not call to get the ok like he said he would, or it could be all the stuff that is going on with the ARBs right now.  I will have to wait and see what the letter says and move from there.

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

Your friend in Sarcoidosis
Freddie

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Back to FDA, Benicar and Arteries subject a bit here.

Take a gander at wikipedia picture of atheroma and enjoy reading some about errant macrophage involvement (sigh... hints seem to be mounting, somebody at the FDA is bound to get it eventually... maybe????).

Course, one must always take wikipedia content with a grain of salt, but that picture sooo helps me want to stop errant macrophage problems like none other.

Any study with Benicar at dose levels lower than what the MP recommends just reminds me of my first experience with advanced disease and olmesartan at non-MP "typical" dose. It's enough to set off fireworks.

I'm actually surprised at study data, not that olmesartan can set off the fireworks but that there weren't --more-- serious outcomes. Maybe, it seems even at hypertensive levels Benicar might still be preventing the worst outcomes.

I vote for cleaning up errant macrophages the safest way possible. More olmesartan the MP way, please.

Best to all--Janet

.....

Later edit: I have noted a lot of plaque changes during the time I was first dx with Sarc and then when I have been on the MP. One of the most recent changes I was looking at recently was teeth and tongue. Tongue has lost a coat and teeth are not growing plaque so much.

After looking at the artery on Wikipedia, I'm pretty glad about plaque reduction at present and hoping arteries and other places like calcified lymph nodes (also an errant macrophage problem) eventually clear up. Yup, I know, fibriotic stuff takes time.

Last edited on Thu Jul 1st, 2010 10:41 by jrfoutin

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HI ALL

This is Fred in WV.  I think that the main problem that is happening is that the Benicar is much more than just a B/P pill and the doctors are not aware of this.  So I think it can be dangerous to use with out the MP knowledge.  Benicar starts the immune system working and doctor in general are getting problems and blameing the Benicar for the problems.

I say all of this because when I first started the Benicar my family doctor told me he gave Benicar to a patient and had to send them for dialysis because he said it caused the kidneys to fail.  My doctor even told me I was going to be there if my kidneys keep going the way they were going.  He said I was just 2 months form being there.  I told him no I wasn't because I was taking the Benicar at the correct dose to prevent that from happening.  And I did prove him wrong becuse my BUN went up to 109 then droped to about 40, CREATININE went up to 3.9 then fell to 1.7 over time.

So once again I think some of the problems is not the Benicar but the doctors knowledge of how it should be used.

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

Your friend in Sarcoidosis
Freddie

baypilot
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Dr Trevor Marshall wrote:

I have just arrived in Maryland, ready for the presentation I will be giving at the FDA on Tuesday. Amy is joining me here tomorrow.

The video should be on YouTube by the weekend...

..Trevor..


mr marshall

what about presentation.did u give it?

Prof Trevor Marshall
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Yes, the videos are nearly ready :)

Bane
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Review of angiotensin II receptor inhibitors started

http://www.ema.europa.eu/pdfs/human/press/pr/27209310en.pdf

The Committee has begun looking at the possible risk of cancer in patients taking angiotensin II receptor inhibitors. This follows the publication of a meta-analysis reviewing nine randomised controlled trials involving almost 95,000 patients, which suggests that these medicines may be linked with a modestly increased risk of new diagnoses of cancer when compared with placebo or other heart medicines.


The CHMP will review the meta-analysis thoroughly, together with any other available non-clinical and clinical data (including data from clinical trials and epidemiological studies) on angiotensin II receptor inhibitors, to clarify whether there is an increased risk of cancer in patients taking these medicines. The Committee will also issue an opinion on whether a future change to the product information or risk-management plans for these medicines might be necessary.

baypilot
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How long does the review? and Is there a plan B for negative news? If bad news comes How long does it take drugs to be collected. any idea ?

thank u

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How long?
Look at Tom's post:

http://www.marshallprotocol.com/view_topic.php?id=13795&forum_id=39&jump_to=197165#p197165
 

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Meta studies are good for some things, and not for others.

........

The entire class of inhibitors do not act the same.

Please reference kd chart, click here. 

........

Full 2006 transcript of FDA whitewater presentation:

http://mpkb.org/home/publications/marshall_fda_cder_2006

 

Best to all--Janet

Bane
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FDA Drug Safety Podcast for Healthcare Professionals: Ongoing safety review of Benicar and cardiovascular events

http://www.fda.gov/downloads/Drugs/DrugSafety/DrugSafetyPodcasts/UCM217336.mp3

http://www.fda.gov/Drugs/DrugSafety/DrugSafetyPodcasts/ucm217335.htm

Welcome, my name is Jennifer Shepherd, a pharmacist in the Division of Drug Information. I am updating you on the ongoing safety review of Benicar and cardiovascular events. The FDA is evaluating data from two clinical trials ROADMAP and ORIENT in which patients with type 2 diabetes taking Benicar, also known as olmesartan, had a higher rate of death from a cardiovascular cause compared to patients taking a placebo.

FDA's review is ongoing and the Agency has not concluded that Benicar increases the risk of death. FDA currently believes that the benefits of Benicar in patients with high blood pressure continue to outweigh its potential risks.

Benicar is in the class of drugs called angiotensin II receptor blockers or ARBs. These drugs and a closely related group of drugs called angiotensin-converting enzyme inhibitors (ACEIs) have been evaluated in many studies involving thousands of patients at high-risk for cardiovascular events, such as patients who had a previous heart attack or had heart failure. No increased risk of cardiovascular-related death has been reported in these trials and, in fact, some of these studies indicate ARBs and ACEIs are useful as treatments for certain patients at high-risk for cardiovascular events.

The Randomized Olmesartan and Diabetes Microalbuminuria Prevention Study or ROADMAP was a randomized, double-blind, placebo-controlled, multicenter trial conducted in Europe. The trial included 4,447 patients with type 2 diabetes and at least one additional cardiovascular risk factor, but without overt evidence of nephropathy. Patients were randomized to receive either 40 mg of olmesartan or placebo daily. Patients were permitted to receive other antihypertensive medications, but not ACEIs or ARBs.

The primary objective was to evaluate whether olmesartan could delay the onset of microalbuminuria. The majority of patients had 3 to 5 cardiovascular risk factors and 80% of patients were using other antihypertensives. The mean duration of exposure to olmesartan was 39 months.

The Olmesartan Reducing Incidence of End Stage Renal Disease in Diabetic Nephropathy Trial or ORIENT was a randomized, double-blind, placebo-controlled, multicenter trial conducted in Japan and Hong Kong. The trial included 566 patients with type 2 diabetes and overt nephropathy who were randomized to receive olmesartan 10 mg to 40 mg or placebo daily. Patients were permitted to take additional antihypertensives including ACEIs, but excluding ARBs. The primary composite endpoint was the time to first event of doubling of serum creatinine, end stage renal disease, and all cause death.

An unexpected finding observed in both trials was a greater number of deaths from a cardiovascular cause, such as heart attack, sudden death, or stroke, in the Benicar-treated patients compared to placebo. In ROADMAP, there were 15 cardiovascular related deaths in the Benicar group compared to 3 in the placebo group. In ORIENT, there were 10 cardiovascular-related deaths in the Benicar group compared to 3 deaths in the placebo group. The summary of findings from these trials can be found in tables which are available in the full drug safety communication on the FDA website at http://www.fda.gov.

To evaluate the possible association with olmesartan and increased cardiovascular-related death, FDA plans to review the primary data from the two trials and the total clinical trial data on olmesartan. Also, the Agency will evaluate additional ways to understand the findings from ROADMAP and ORIENT, in light of information supporting the use of ARBs and ACEIs in certain patients at high risk for cardiovascular events.

At this time, FDA recommends that Healthcare Professionals be aware that:

  1. FDA has not concluded that Benicar increases the risk of death. The Agency is reviewing information related to the safety concern and will update the public when additional information is available.
  2. FDA believes the benefits of Benicar in patients with high blood pressure continue to outweigh the potential risks.
  3. In the ROADMAP and ORIENT trials, there were a greater number of cardiovascular-related deaths in the Benicar group compared to the placebo group.
  4. Additional information about ROADMAP and ORIENT can be found at http://www.clinicaltrials.gov.
  5. Other controlled clinical trials evaluating Benicar and other angiotensin II receptor blockers have not suggested an increased risk of cardiovascular-related death.
  6. Recommendations in the drug label should be followed when prescribing Benicar.
  7. Adverse events involving Benicar can be reported to the FDA MedWatch program at http://www.fda.gov/medwatch.

Bane
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ARBs and Cancer -- Are We Looking at Junk Science?

http://www.medscape.com/viewarticle/724008

 

copy this link into google and do a search, you should be able to see it without being registered?

Last edited on Mon Jul 5th, 2010 05:51 by Bane

Prof Trevor Marshall
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"You have to start out with some biological reason why that might happen"
total focus on Angiotensin receptors...
"Studies for FDA" "large numbers of experimental animals, mostly mice and rats and occasionally rabbits to see whether there is any increase in cancers"

Sigh. Well, cancer was detected during the FDA studies in hamsters, but that was discounted as it didn't appear in rats, mice or rabbits. That is detailed in the FDA approval documents. Second, they obviously haven't Googled for my 2007 DMM poster:

http://AutoimmunityResearch.org/transcripts/dmm2007-harvard.pdf

And of course none of the experts has any clue as to what is really happening....

..Trevor..

Deedee
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Bane, I signed in to watch the video you posted above from medscape

http://www.medscape.com/viewarticle/724008 and it is very persuasive.

I would just like to recommend to anyone that is frightened by the news reports to watch the video. The speaker is Henry R. Black, MD,
Clinical Professor of Internal Medicine, New York University School of Medicine, New York, NY; Director, Hypertension Research, Center for the Prevention of Cardiovascular Disease, New York University School of Medicine, New York, NY.

He explains why the information from the clinical trials that generated the study of the safety of Benicar is flawed and he states the individual data and the pattern of the cancers were not consistent. He said the study needs to be dissected very, very carefully.

He noted that the populations in the study were from all over the world, and the groups were compared to people (presumably in the US) of ages 65 to 69 (the average age in the study). He noted populations from different parts of the world and incidents of cancer will differ widely. He said this is not comparative data and called this "irresponsible" and junk science.

He said that to cause alarm over Benicar is "irresponsible and dangerous, and can causes patient harm."

Take the time to sign up and watch the video. Thanks, Bane.

Looking forward to viewing your presentation, TM.

Last edited on Mon Jul 5th, 2010 08:07 by Deedee

Bane
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Deedee wrote: Bane, I signed in to watch the video you posted above from medscape

http://www.medscape.com/viewarticle/724008 and it is very persuasive.

I would just like to recommend to anyone that is frightened by the news reports to watch the video. The speaker is Henry R. Black, MD,
Clinical Professor of Internal Medicine, New York University School of Medicine, New York, NY; Director, Hypertension Research, Center for the Prevention of Cardiovascular Disease, New York University School of Medicine, New York, NY.

He explains why the information from the clinical trials that generated the study of the safety of Benicar is flawed and he states the individual data and the pattern of the cancers were not consistent. He said the study needs to be dissected very, very carefully.

He noted that the populations in the study were from all over the world, and the groups were compared to people (presumably in the US) of ages 65 to 69 (the average age in the study). He noted populations from different parts of the world and incidents of cancer will differ widely. He said this is not comparative data and called this "irresponsible" and junk science.

He said that to cause alarm over Benicar is "irresponsible and dangerous, and can causes patient harm."

Take the time to sign up and watch the video. Thanks, Bane.

Looking forward to viewing your presentation, TM.


Deedee there are two studies being discussed in this thread, the one i mention is on telmisartan, not olmesartan.

This one:

Common blood pressure drugs may raise cancer risk

http://www.reuters.com/article/idUSTRE65C2C120100613

 

the one on olmesartan is this one

 

UPDATE 2-FDA looking into death risk from Daiichi's Benicar

http://www.reuters.com/article/idUSN1113920620100611

Last edited on Mon Jul 5th, 2010 08:19 by Bane

Deedee
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Thanks, Bane, I see that now. The study that generated the cancer-increase concern was based on the drug Telmisartan, a different ARB. He mentioned another ARB, too. The video just groups them all together for discussion as ARB drugs.

Last edited on Mon Jul 5th, 2010 08:43 by Deedee

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He mentioned Candesartan, which has no VDR effect and Telmisartan, which is the strongest VDR antagonist (switcher off) I have ever seen... I have for years told people to stay away from Telmisartan (Micardis) at all costs...
 

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EMA to review ARBs and cancer, infuriating experts, who point to missing data and adverse consequences

http://www.theheart.org/article/1091359.do

At the same time, hypertension experts are up in arms about the paper, calling it deeply flawed. They contend that it is extremely unlikely that ARBs are associated with an increased risk of cancer—one physician even says he has data that, if added to the analysis, would wipe out any cancer signal. Overall, they say, the media splash this paper has made could cause irreparable damage to the reputation of ARBs, which they consider vital tools in their armamentarium, and may unfortunately prompt many patients to stop taking the medicines, putting themselves at increased risk of cardiovascular and renal events.

Sunset
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Dr. Trevor Marshall wrote

Posted: Sat Jul 3rd, 2010 07:47

Yes, the videos are nearly ready


Queston: Are these videos available now? (Just wondering)


Thanks :D

Deedee
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Sunset:
http://www.marshallprotocol.com/forum39/13818.html

Prof Trevor Marshall
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You can always see the latest posts by using this URL:
http://www.marshallprotocol.com/recent.html

or by clicking on the "Recent" tab at the top left of the forum.
 

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What's The Evidence for the Link Between ARBS and Cancer? Ileana Piña Talks With Ilke Sipahi

 

http://www.medscape.com/viewarticle/725043?src=rss

Copy this link/video to Google, you should be able to see it without registering.

Deedee
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Thanks, Bane. Very interesting. Interesting too, is that it always gets down to the funding, doesn't it?

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This article was released today and may help explain multiple allergy response and why some people need a lot of medication with little bebefit.
http://www.physorg.com/news199082379.html

jrfoutin
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Bacteria get energy from glucose/sugars/etc.

Suggested reading at MPKB.org:

Carbohydrates and sugars


Per FDA investigating the safety of Benicar" topic of this thread, we might want to keep the topic on track.

Ute
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Yesterday the Drug Commission of the German Medical Profession (AkdÄ) commented on the side of sartanes:
 
http://tinyurl.com/3y9fvon
Drug commission takes position to Sartanen and cancer risk
Berlin – the drug commission of the German medical profession (AkdÄ) sees no necessity to change at this moment the recommendations for the regulation from Sartanen. The drug commission reacted in a current statement to an US-American Metanalyse for the occurrence of tumors in connection with the gift of Sartanen. This study appeared in June in the magazine Lancet Oncology (2010; 11:627 - 636) and resulted in a small, but statistically significantly increased risk of cancer conditions in the case of gift of a Sartans. From view of the AkdÄ the US-Metaanalyse has however some clear methodical weaknesses. Beyond that the biological plausibility is not given a tumor-promoting effect of Sartanen. „The results of the study should be taken to the cause to accomplish further investigations to the cancer risk with use of Sartanen “, so the AkdÄ. © hil/aerzteblatt.de

Prof Trevor Marshall
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I would like to be encouraged by this pronouncement, but sadly the phrase "the biological plausibility is not given a tumor-promoting effect of Sartanen" indicates that we have the blind leading the blind here.

Even AkdÄ has no concept of how drugs work, beyond what has been clinically observed and published. It is sad, really.
 

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Angiotensin receptor blockers and cancer - Relationship dismissed by VALUE data while waiting for EMA and FDA reports.

http://www.ncbi.nlm.nih.gov/pubmed/20858047

Bane
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Editorial: Meta-Analysis Concludes Angiotensin Receptor Blocker Use Increases the Risk of Developing Cancer: Concerns About the Science and the Message

http://onlinelibrary.wiley.com/doi/10.1111/j.1751-7176.2010.00369.x/full

"In conclusion, we think that this situation highlights the need for us to better educate the mass media about levels of evidence. The fact that the publication of this finding from a study with a low weight of evidence was given such widespread national attention is troubling. According to well-established rules of evidence-based medicine, studies such as this should never dictate clinical care and should remain hypothesis-generating. Perhaps the American Society of Hypertension (ASH) should develop a panel of experts that could be available to help the media appropriately evaluate the strength and significance of publications related to hypertension.


We feel that based on the evidence presented to date, there is no need for physicians to change their prescribing of ARBs or for any regulatory change to occur at this time. We do recommend the following steps be taken to clarify the issue of a potential link between ARBs and incident cancer: (1) a better-designed patient level meta-analysis of all relevant ARB studies, including VALUE, be performed; (2) administrative claims databases such as those available from the Veterans Administration (VA) should be examined to determine whether there is an association between ARB use and incident cancer; (3) any clinical investigators with cancer-related data and ARB use should contact the authors of the present study so they can perform an updated meta-analysis (submitted as a Letter to the Editor of Lancet Oncology); and (4) future trials using ARBs should collect cancer data as a pre-specified end point of interest. Societies such as ASH need to work with the media to properly position and explain the results"

rbcolo12
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Is there any concern about the use of titanium dioxide in manufacturer of Benicar. I have found no Manufacturer that does not use Titanium Dioxide and it is raising concerns of being a carcinogenic,

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Titanium Dioxide is used in a wide variety of drugs. Where did you read it might be a carcinogen?

rbcolo12
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I read this Article on AOL and then did some research these are some sites ,

http://www.aolnews.com/nanotech/article/amid-nanotechs-dazzling-promise-health-riskgrow/19401235

http://www.ccohs.ca/headlines/text186.html

It made me look for Benicar that was not made with Titanium Dioxide, But there is not one,It is used in all most every drug made. 

 

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Hi Bob.
I am thinking that your reading was about nano-technology?

Typically the titanium dioxide used in drugs is not "nano" sized particles. :cool:

Prof Trevor Marshall
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Thanks for that article :) Interesting :)
I have previously raised questions about nano-particles in sunscreens :) It is important though to notice that it is the nano-particles which are known to cause the most trouble, not the powdered titanium dioxide in the GI tract which results from digesting tablets.

With that being said, I have been working on a solution to the excipients in Benicar tablets. It is still too early to discuss our results. Keep an eye open for press announcements over the next six months. I think you will find that we have figured out how to deal with the problem of excipients, at least in the long term...

rbcolo12
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Thanks Dr Marshall

mabluhm
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Yes--thanks Dr. Marshall!

jlunn247
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i think using nano as a advertisement gimmick is a good way to get the public interest in new tech i hope it keeps going till we have the real deal adjusting our metabiome.

Bane
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Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324 168 participants from randomised trials

http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(10)70260-6/fulltext

Our analysis refutes a 5·0—10·0% relative increase in the risk of cancer or cancer-related death with the use of ARBs, ACEi, β blockers, diuretics, and CCBs. However, increased risk of cancer with the combination of ACEi and ARBs cannot be ruled out.

 

Last edited on Wed Dec 1st, 2010 10:41 by Bane

Bane
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Effect of RAAS Inhibition on the Incidence of Cancer and Cancer Mortality in Patients with Glomerulonephritis

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012851/?tool=pubmed

In conclusion, patients with GN show a higher incidence of cancer and cancer mortality compared with the general population. Prescription of ACEI or ARB in patients with GN does not increase cancer incidence and recipients of ARB show rather to be lower rates of all-cause mortality and cancer mortality.

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Yet another reason to stay on olmesartan.

Bane
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Angiotensin II Receptor Blockers and Risk of Cancer in Patients With Systemic Hypertension.

http://www.ncbi.nlm.nih.gov/pubmed/21256465

In conclusion, long-term use of ARBs is associated with a lower incidence of cancer occurrence, thereby suggesting that ARBs may prevent cancer development.

Joyful
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Interesting study because it was nationwide population study.

What they did:

    1. looked at data from 1 million members of national insurance database (1998-2006)
    2. identified 109,002 members with newly diagnosed hypertension
    3. identified 40,124 that had ARBs prescribed for the new diagnosis (and 68,878 that did not)
    4. identified any that reported a new cancer diagnosis during the study period (3,082 in ARB group-my calc: 7.7%; 5,985 in no-ARB group-my calc: 8.6%)
    5. statistically messed with the results to smooth out the variables in a scientifically approved manner
    6. published their finding that those on ARBs have a decreased risk for cancer occurance

What is good: those on any type of ARB had a gross reduction in cancer risk of about 1%.
What would be better: refining search to get results by ARB type. We believe some are better than others. :)

What else to improve the study: go longer. We know that cancer pathologies are best understood over decades. We suspect ARB benefits are similar.

My opinions only. :cool:

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Related to the Study, Ute quoted on top of this side:

I quote and translate from the book: Ursel Siebner, Gesunder Zweifel (Healthy doubts), Berlin Verlag 2010, page 128:

"In einer Metaanalyse (...) zeigt sich, dass die Zahl der Krebsfälle in der mit Sartanen behandelten Patientengruppe erhöht war - signifikant bei Lungenkrebs und leicht erhöht bei Prostatakrebs. (...) Die meisten einbezogenen Teilstudien wurden mit Telmisartan durchgeführt, zu einer Zuordnung des erhöhten Krebsrisikos zu einem bestimmten Sartan sehen sich die Autoren der Metastudie allerdings nicht in der Lage.

In English:
It was shown by Metaanalysis, that the number of cancer cases in the group of people, who had been treated with Sartans, was elevated - significantly for lungcancer and slightly elevated for cancer of the prostate. Most of the included Studies used Telmisartan, however, the authors of the studie consider themselves unable, to relate the elevated cancerous risk to a specific Sartan".

Well. Please correct me, if I am wrong, but isn't  Telmisartan on of the the Sartans, that nearly completely knocks out the VDR?

Verena


Last edited on Thu Jan 27th, 2011 02:00 by Verena

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Yes, Telmisartan completely reverses the action of Olmesartan. My in-silico work alerted me to this, and then I confirmed it by taking the dreadful stuff, just to be sure :)

..Trevor...

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LOL! Is Liz always aware of your experiments..? ;)

Anyway, thanks for being the guinea pig (again). :):D:)

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Dr Marshall,

:shock: to the Telmisartan experiment.  But thank you!  I hope it didn't knock you off for too long...


Pipistrelle

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Dr. Daredevil, brave of you, are you allright?

:)Annemarie

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Expert opinion on drug safety. 2011 Jan 23;
Safety and efficacy of olmesartan: an observational pooled-analysis of 156,682 hypertensive patients.
Scholze J, Schäfer A, Kreutz R
Background: Angiotensin type 1 receptor blockers are recommended for first-line antihypertensive treatment. Methods: We performed a pooled-analysis of 20 post-authorization surveys of olmesartan involving 156,682 hypertensive patients. Olmesartan was used as monotherapy or in combination with other antihypertensive drugs, for example, hydrochlorothiazide. Objectives: We assessed the safety of olmesartan by monitoring adverse drug reactions (ADRs). The number of patients achieving systolic and diastolic blood pressure (BP) targets (< 140/90 mmHg in the overall population, < 130/80 mmHg in high-risk patients) or responding to treatment (BP decrease of ≥ 20/10 mmHg) was also determined. Results: In all, 43.8% of patients received olmesartan monotherapy, 29% olmesartan with hydrochlorothiazide and 27.2% olmesartan in combination with other antihypertensives. The frequency of ADRs was 0.4% and not altered by dose, age ≥ 65 years or presence of co-morbidities. About 90% of patients were responders. Blood pressure targets were achieved in 52.8 and 35.7% of patients without risk factors and in the overall cohort, but only in 8.1 and 27.5% of patients with renal dysfunction or taking NSAIDs. Conclusion: Olmesartan was very well tolerated. Responder rates to olmesartan were high, although BP targets were only achieved in a minority of patients at high risk, with renal dysfunction or taking NSAIDs.

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Limburg wrote: Dr. Daredevil, brave of you, are you allright? :)Annemarie
It was a long time ago, Annemarie. I tried the other ARBs too, just to make sure my in-silico results were roughly in line with what could be observed in-vivo.

I still check out potential IP-modifying drugs today. All have had major side effects...
 

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Okay Dr. Marshall, so are you okay :D ?

You still are a daredevil, even more, since you try so many ARB's :dude:

Have a nice weekend,

 

Annemarie

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Amazing...

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Blood Pressure Meds May Lower the Risk of Cancer, Study Finds

http://www.aolhealth.com/2011/02/04/blood-pressure-meds-cancer-risk/

"Even more surprising: The longer patients were on the medications, the better their chances of avoiding cancer, with those on ARBs for a year or more having a 50 percent lower risk, according to The American Journal of Cardiology findings"

"To me, it's very clear, but other groups have suggested the jury is still out on this topic," Sipahi said.
 

Guess he is still convinced Telmisartan cause cancer?;)




Last edited on Thu Feb 10th, 2011 23:47 by Bane

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Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138 769 individuals


http://tiny.cc/c1cdp

Background: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) reduce cardiovascular disease (CVD) events, but a recent meta-analysis of selected studies suggested that ARBs may increase cancer risks.

Objective: Candesartan, irbesartan, telmisartan, valsartan, and losartan were assessed for incident cancers in 15 large parallel long-term multicenter double-blind clinical trials of these agents involving 138 769 participants.

Patients and methods: Individuals at high CVD risk were randomized to telmisartan (three trials, n = 51 878), irbesartan (three trials, n = 14 859), valsartan (four trials, n = 44 264), candesartan (four trials, n = 18 566), and losartan (one trial, n = 9193) and followed for 23-60 months. Incident cancer cases were compared in patients randomized to ARBs versus controls. In five trials (n = 42 403), the ARBs were compared to ACEi and in 11 trials (n = 63 313) to controls without ACEi. In addition, in seven trials (n = 47 020), the effect of ARBs with ACEi was compared to ACEi alone and in two trials ARBs with ACEi versus ARB alone (n = 25 712).

Results: Overall, there was no excess of cancer incidence with ARB therapy compared to controls in the 15 trials [4549 (6.16%) cases of 73 808 allocated to ARB versus 3856 (6.31%) of 61 106 assigned to non-ARB controls; odds ratio (OR) 1.00, 95% confidence interval (CI) 0.95-1.04] overall or when individual ARBs were examined. ORs comparing combination therapy with ARB along with ACEi versus ACEi was 1.01 (95% CI 0.94-1.10), combination versus ARB alone 1.02 (95% CI 0.91-1.13), ARB alone versus ACEi alone 1.06 (95% CI 0.97-1.16) and ARB versus placebo/control without ACEi 0.97 (95% CI 0.91-1.04). There was no excess of lung, prostate or breast cancer, or overall cancer deaths associated with ARB treatment.

Conclusion: There was no significant increase in the overall or site-specific cancer risk from ARBs compared to controls.

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By considering ARBs as a class of drugs, this study has drawn the wrong conclusions. I would be very surprised if Telmisartan alone exacerbated the long-term  risk of cancers, as it suppresses VDR-mediated inflammation.

Then again, maybe the studies just didn't run for long enough to see the cause and effect relationships :)
 
 

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Would't one also expect that people who are on ARBs in the first place probably have higher baseline systemic inflammation and are therefore probably more prone to develop cancers?

Its also important to consider that while some drugs may exert anti-proliferative effects in target tissue, they may also have similar anti-proliferative effects on certain aspects of the immune system.

An example of this would be the mtor inhibitors - immuno-suppressants with paradoxical anti-viral and anti-cancer effects. They work well in cell culture (anti-cancer effects in target tissues) but are associated with increased cancer in vivo (block proliferative ability of immune system). Mtor fuels cancer growth but is also required for an optimal cytotoxic adaptive response. Kind or a trade-off. This is my primary concern with 'longevity drugs' like resveratrol and rapamycin.

Its possible that the ARBs are similar in this regard. Anti-proliferative (in target tissue but also the immune system). It seems to me that if you are taking a drug that inhibits the adaptive response by inhibiting cytokinesis (All ARBs), its probably also a good idea that the drug exert anti-proliferative effects in target tissues (olmesartan).

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Phillyguy,
mTOR  is at the heart of dozens, perhaps hundreds, of biological pathways.  A lot of studies have been done in mice on mTOR, yet it was not obvious to me that the mouse studies will directly translate to humans. Since mTOR is short for "Mamalian Target of Rapamycin," and Wikipedia seems to consider the drug Rapamycin to be immunosuppressive, I have personally taken the drug on two separate occasions to see what its effects might be for people on the MP.

My assessment is that any of our members who take Rapamycin run the risk of their IP becoming totally unstable, and becoming very ill indeed. In my case, the postural hypotension that has been gone these past few years came back with a vengeance, general IP and malaise increased, and trying to wean was very difficult (and painful) with high vascular permeability (quite powerful migraines) and an overall IP surge..

Please stay away from mTOR inhibitors like Rapamycin. Even at quite low doses they affect the human body in far more profound ways than the more common corticosteroids, which have also proved to be dangerous. I fear the emphasis on Rapamycin and mTOR in the media might tempt MP members to experiment, members whose bodies are still too ill to withstand the cardiovascular effects of this drug.

It is important to understand that what you read in PubMed is written by people who (largely) have little idea what they are doing. They are trying to elucidate some individual pathway which interests science. Not one is looking for a cure (well, very few, anyway). They are looking for drugs which will make them famous and rich (sadly, this is what drives many research biologists these days). They tend to overlook potential risks from the drugs they are exploring.

It is also important to remember that "the overall death rate from Sarcoidosis is only 5%," well, at least that is what Clinical Medicine will tell you. You see, deaths from heart failure, stroke, liver failure, cancers, and other systemic maladies could not be due to the Sarcoidosis, as Medicine considers Sarcoidosis as a lung disease :) :X :)

In other words, medical specialization tends to hide dangerous drug side-effects. Sarcies dying of cancer, heart-attack, etc are not determined to die from the Sarcoidosis, but from "another disease." Medicine buries its mistakes. When people are adversely affected by a complex drug like Rapamycin, I am sure that very few of the deaths are logged as being due to the drug...

I keep my eye open for anything which might help members recover more quickly, with less pain, or less disruption of lifestyle. But many of our members are desperate for quick solutions. Before posting about new drugs in future, why not drop me a note and see what I (and my colleagues) already know about it? There may be "primary concerns" that we already know about. :) :)
 

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http://www.nejm.org/doi/full/10.1056/NEJMoa1007994

"The higher rate of fatal cardiovascular events with olmesartan among patients with preexisting coronary heart disease is of concern." They only used 40mg once a day.

Physicians First Watch notes: "An editorialist writes that the finding of delayed microalbuminuria was not unanticipated. And given the increased cardiovascular mortality found with olmesartan, she asks why wouldn't other renin-angiotensin blocking drugs be prescribed if they are not associated with fatal complications?"

Why wouldn't they?? :shock: Huge assumptions/simplifications!

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Hello,

I looked at the article, but the differences are hardly statistical relevant. I am used to take technical decisions. To draw conclusions from less than 10% difference in this test is less than 2 sigma. I probably have to become used to medical practice.

When you go to your doctor you hope to get a 99% sure cure, and not well it did 0.7% better than the other cure. But both did not help a big number of people.

Best regards Erik

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Trevor wrote~

My assessment is that any of our members who take Rapamycin run the risk of their IP becoming totally unstable, and becoming very ill indeed. In my case, the postural hypotension that has been gone these past few years came back with a vengeance, general IP and malaise increased, and trying to wean was very difficult (and painful) with high vascular permeability (quite powerful migraines) and an overall IP surge..

Wow...besides the obvious conclusion that this is dangerous for the MP, what other thoughts do you have as to why these reactions may have occurred?

It's particularly interesting as curcumin also inhibits mTORC1.

When my PhD friend Steve Creacy[ on MP] experimented with curcumin he went through terrible IP and developed open lesions on his face.

It seems odd that something that is considered immunosuppressive like Rapamycin would increase or bring back old symptoms...why would it do that?

Or maybe not. Everything that I used to suppress my immune system eventually seemed to bring out more symptoms and make me sicker.

 

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Seanlake--

My ideas about bacteria, fungi and viruses are simplistic.  However, it appears they can go dormant for long periods of time, and then spring forth and multiply.  One study I read somewhere dated the dormancy period to 34,000 years (no joke).  We apparently do not understand their life cycles.

Understanding our own immune system is the best strategy I have ever read, thanks to the MP.  I too have had issues with food:  cinnamon, oregano, and yes mustard.  So I respectfully stay away from the substances, or suffer.

And of course, I always honestly admit that I at much cinnamon as a child and young adult.  Miss Gingersnap here.  And plenty of oregano in Italian cooking.  And my recipe box has an old favorite for "milk and half a cup of mustard" tossed onto a pork chop, a chicken breast, or even fish.  And then baked.  YIKES.  Obviously, I do not eat that way any more.

Thanks to this community and ARF, I think we're providing some very useful information.

"Hold the mustard".

Sherry



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Sherry,

Those products, "...cinnamon, oregano, and yes mustard.", will give me cramps in my lower legs at night if I consume them now.  I used to consume them in goodly amounts when younger.  The one common thing between them that I have found is that they contain salicylates.  I have found that all products that contain salicylates, as well as artificial food dyes and flavors, most "natural flavors" such as the spices and mints [spearmints & peppermints] will do the cramps for me, too.  The only thing that I have found to counteract the affect is to take quinine sulfate [260 mg tablet for which one needs a Rx order], and that ability is limited, also.  I need to restrict my intake of the salicylates, etc.  Someone else's symptom(s) may be different than mine, but an affect, nevertheless, IMHO.  My list of foods/drinks that I can partake is rather limited because of that.

One can obtain a listing of the salicylate contain of most foods/drinks with doing a Google search.  There are three such lists that I am aware of.  Two of them give just a five-degree ranking, and a third list gives a listing by quantity of the salicylate.... most foods are under a numerical amount of twenty per unit of measure.  The spices are in the hundreds.

Wishing all wellness!!!  :D

Dark Vader...aka, George

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ROADMAP published, but no news on FDA safety review of ARB

http://www.theheart.org/article/1196817.do

Haller told heartwire, "The data [published in the journal] are the same" as were presented at the European Society of Hypertension (ESH) meeting in Oslo last summer, but some of the analyses reported there do not appear in the manuscript; "there will be follow-up publications."

The results show there was a cumulative incidence of microalbuminuria of 8.2% with olmesartan and 9.8% with placebo; the primary end point, time to onset of microalbuminuria, was delayed by 23% with olmesartan (hazard ratio 0.77, p=0.01), with the majority of this effect being BP independent.

But in ROADMAP, there were 15 cardiovascular deaths in the olmesartan group—seven cases of sudden death, five fatal MIs, two fatal strokes, and one death related to coronary revascularization—compared with a total of three CV deaths—one sudden death and two fatal strokes—in the control group (0.7% vs 0.1%, p=0.01).

Most of the excess cardiovascular mortality in the olmesartan group occurred in those with preexisting cardiovascular disease (11 events vs one with placebo, p=0.03) and among patients in the lowest quartile of BP, the investigators point out.

In contrast, fewer patients in the olmesartan group than in the placebo group had nonfatal cardiovascular events, 3.6% vs 4.1% (p=0.37), they note.

"The fact that these signals go in opposite directions, together with the feeling that the study was underpowered to determine cardiovascular risk, has led many to comment that these results may well be due to chance," says Ingelfinger in her editorial. Haller et al agree, and last year, at the ESH meeting, Haller told heartwire: "It's clear-cut, it's not a problem of olmesartan; we are sure about that."

Nevertheless, Haller et al now appear to be hedging their bets somewhat, admitting in their paper that the CV mortality finding is "of concern." Excessive reduction of BP in some high-risk patients may confer a predisposition to an increased risk of death, a finding that is consistent with the well-known, somewhat-controversial "J-curve-effect," they observe, pointing out that the ESH states that doctors should avoid lowering BP excessively to values below 120/70 mm Hg in people with underlying CVD.

They also concede that "a direct effect of olmesartan cannot be ruled out" and point out that the FDA is currently reviewing the existing data on the drug.

Ingelfinger adds that olmesartan has been promoted as a medication that helps patients reach BP goals rapidly and that the dose used in ROADMAP, 40 mg, was higher than that used in many other studies. In the other smaller trial being looked at by the FDA, ORIENT, 500 patients were randomized to receive olmesartan at 10 mg/day to 40 mg/day or placebo. There were 10 cardiovascular deaths in the olmesartan group compared with three in the control group.

 

Target those with high BP, low eGFR or albuminuria for most benefit

Haller et al say their findings extend the results of other trials and suggest that olmesartan delays the time to onset of microalbuminuria in type 2 diabetes, "even when BP control is excellent according to current recommendations."

"These results provide hope that it may be possible to prevent chronic kidney disease in the many persons worldwide who have type 2 diabetes mellitus," says Ingelfinger in her editorial.

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Dr Trevor Marshall wrote: Well, it had to happen - FDA has at last noticed that Benicar is affecting Cardiovascular disease in Th1 individuals - specifically Diabetics. 
 

Trevor-

It would seem [at least IMO] the MP disease model and treatment protocol continues to suffer greatly at the hands of the critics, including the FDA, for the simple fact no study data has been set forth correlating increased levels of antimicrobial peptides, including β-defensins (hBDs) and cathelicidins, as having been directly up-regulated solely by the introduction of therapeutic doses of Olmesartan.  Unless, of course, I missed that some where along the way?

Given the sensitivity with which metabolites, and their by-products, can so easily be detected now a days, I have often wondered how this might dampen down speculation as to the efficacy of Olmesartan in modulating the innate immune response through VDR transcription.

TikBitten

p.s. BTW, today, 3/15/2011, is my three anniversary of being on the MP!!!  I'm happy to report that significant progress has been made and would like to take a moment to express my deep gratitude to Dr. Marshall and all of the MP volunteers, past and present, for the time and effort they put forth so selflessly -- thank you all very much.

Last edited on Tue Mar 15th, 2011 18:59 by TikBitten

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Good to hear from you again :) And happy anniversary :) :) 
"Given the sensitivity with which metabolites, and their by-products, can so easily be detected now a days"

This is actually mistaken. It is very difficult to measure what is happening inside the phagocytic cells. With only a few exceptions (the video of HIV invasions, for example) all the current research is focused at much larger blobs of tissue. And much of it is performed in animals and cell lines, which are not the same as a living, breathing, human being...

As I sat and listened to the speakers at last week's NIH Human Microbiome conference, all bewailing the fact that their carefully done (expensive) experiments still had not produced firm hypotheses as to the cause of each disease, let alone confirm a cure, I couldn't help but feel a little warm about the success we achieved, and the way we achieved it - pure scientific understanding :)

We are keeping our eyes open for ways to definitively demonstrate the pathogenesis we have advanced, but no opportunities have arisen yet. Whenever I am contacted, it has always been by a scientist or physician  who doesn't have a clue which foot to put in front of the other, and who hasn't even read our recent papers.

It is therefore not surprising that none of them have yet managed to knock down our  hypothesis, which is, after all, the way that science is supposed to work...
 
ps: One of the microbiome studies showed that the ratio of microbial populations in the gut, an issue so exquisitely researched by Prof Jeff Gordon's group in mice, does not mirror the situation in humans. Obesity in humans is not related to gut microbial balance. You have no idea how sad that was making many of the delegates.. they have had to think it through again...
 
 

Last edited on Tue Mar 15th, 2011 19:14 by Prof Trevor Marshall

TikBitten
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Dr Trevor Marshall wrote: It is very difficult to measure what is happening inside the phagocytic cells. With only a few exceptions (the video of HIV invasions, for example) all the current research is focused at much larger blobs of tissue. And much of it is performed in animals and cell lines, which are not the same as a living, breathing, human being... 


Very interesting response....

Little doubt you've thought long and hard on how to fully substantiate Olmesartan immune modulating properties.  So I don't for a second question your response but, what came as surprise in your answer, however, is the manner by which you tied AMP production strictly to phagocytic cells. 

My question, as previously posed, was formulated on my belief that the majority of human tissue expresses VDR and that Olmesartan not only up-regulates adaptive (Th2) immune response but innate (Th1) response as well.  With the result being widespread increase in AMPs and, hence, potential plethora of readily detectable metabolites. 

I have looked forward to the possibility that the West China study might reveal such a correlation.  Am I wrong in all of my thinking here?

Quite concerned/TB

Last edited on Tue Mar 15th, 2011 20:04 by TikBitten

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The key to the level of damage done by the microbiota is their suppression of the innate immune system by infecting and neutralizing phagocytic cells. If the innate immune system continued to operate correctly, there would be no disease from the microbiota, no delayed healing response. That is why the phagocytes are so important.

Have you read our recent papers:

http://www.nature.com/cmi/journal/vaop/ncurrent/abs/cmi201077a.html
http://autoimmunityresearch.org/preprints/Proal2010CellularMolecularImmunologyPreprint.pdf
http://autoimmunityresearch.org/preprints/Proal_MHB_Chapter_preprint.pdf

or seen the recent presentations? http://www.youtube.com/user/DrTrevorMarshall

I do think we have a pretty good handle on the pathogenesis at this point, enough to guide anybody who wants to learn :)
 

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How embarrassing at this point in the treatment protocol, eh, but thanks for clearing things up!! 

Guess that's what happens when you venture off for too long. ;)  Be assured, I will readdress my understanding of phagocytic cell neutralization and its impact on innate immunity before posting further. 

Sincere apology for sapping up time and energy.

R/TB

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Feel free to keep posting :) I prefer it that way. The community is now pretty active, and will be able to steer you to new stuff from time to time :)
 

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Just to be clear, the first two links posted above refer to the same article "Immunostimulation in the Era of the Metagenome" albeit the first points to the published article the second to Amy's original preprint? 

Want to make sure I'm not missing something...

TXS/TB

Last edited on Tue Mar 15th, 2011 20:52 by TikBitten

Prof Trevor Marshall
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Yes, since we are only allowed to put preprints online, and not the actual full Nature.com papers, we link to the "official" abstract as well as give you the "unofficial" full text :)

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Dr. Marshall,

You posted:

It is very difficult to measure what is happening inside the phagocytic cells. With only a few exceptions (the video of HIV invasions, for example) all the current research is focused at much larger blobs of tissue. And much of it is performed in animals and cell lines, which are not the same as a living, breathing, human being... 


I have some understanding of the Marshall Protocol hypothesis, but no understanding of the technology supporting biological research. If human and financial resources were available, would it be possible to confirm that recovery with the MP actually involves restoring normal function of the VDR, killing bacteria, normalization of function in other nuclear receptors, etc.

I believe that the MP has been responsible for many people recovering their lives. I am sure that your model is very sophisticated. However, in my own work, I have found a great difference between modeling and reality.

Respectfully, Tammy 

 

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Tammy, there is a lot more to the actions of the microbiota than we typically discuss, and we also know much more about the actions of Olmesartan than you will find here. I try and keep the science summarized enough so that everybody can understand the key points. I travel to the medical major conferences, and nobody is bothered about 'modeling' there :) In fact, Prof Vieth can be heard at the end of the Q&A session at the Scottish Vit D Summit saying that he wishes he had the research tools which we have :)

Have you really read all that is in the paper and book chapter just published? There is a lot of science in them that goes way beyond what the early emulations taught us.
 
http://autoimmunityresearch.org/preprints/Proal_MHB_Chapter_preprint.pdf
http://autoimmunityresearch.org/preprints/Proal2010CellularMolecularImmunologyPreprint.pdf

It is a terrible mistake to think that the MP science is shallow or incomplete. :) Remember what Arthur C. Clarke mused: "Any sufficiently advanced science is indistinguishable from magic."

To pierce that veil of 'magic' takes a lot of understanding and hard work :) A good start would be to start discussing the intricacies in the paper and chapter above :)
 

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Dr. Marshall,

I highly respect you personally and your foundation, and believe that the MP has turned many peoples lives around.

I have read your (meaning your team) recent work. (I first started reading about it in Dec. 2008.) I am still a little weak in the area of genetic expression and the work in genetic sequencing (end of book chapter).

I have often said that you present the best science that I have ever read, but I am not qualified judge your work. I believe you when you say that your model is judged by your peers as being extremely sophisticated. But I don't know the work involved in developing software that is capable of simulating biological models. I only know things from my limited perspective. I am not of Nobel Prize material, and I battle brain fog.

I only personally know what I have seen in conventional electrical power system work. Many people perform simulations with "excellent results" in the framework of the modelling tools, which are not always accurate representations of the real world. In my own field I deal with stoichastic - not deterministic - phenomenon. There any many influences which affect phenomenon that I try to model that are beyond what I can encompass in a simple model. Yet, I know and can see the effects of these parameters, but I cannot grasp them quantitatively due to complexity and limited/difficulty acquiring such data. I have spent enough time in my field to see and understand significant shortcomings of esteemed work which I used to highly admire.


I have also seen people develop extremely compelling arguments for models or theories related to electrical power systems. I have even felt persuaded, and then I wake up, and based on only my own experiences/work realize and see exactly why they are entirely wrong.

I am not trying to be disrespectful, and I hope that you will allow me to continue to be part of your community and to learn. My work is truly very simple compared to yours.


Your theory seems flawless to my untrained mind. However, I am also a pragmatist. If your theory is complete, perfect, and flawless (say r2=1), I don't understand why many people have to continue taking the olmesartan, sometimes with antibiotics, to maintain the level of recovery they have achieved after several years of MP protocol. (As an analogy, even r2=0.95 is excellent in terms of accurate modeling.)

At this point in my life, if I am able to turn my life around with MP (it has been a bumpy ride for me personally) -- I will consider it nothing short of a miracle, your good science, and Dr. Blaney's patience. Taking the meds will just be what I need to do to have a good quality of life.

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I am one of the people who has had their life turned around by MP despite what many of the "peers" believe to be true.

I am not a peer, I am a patient and my interest in peers is along the lines of "pay attention".

I joined the study group because the "peers" had nothing but textbook medicine to fall back on as an excuse when the patient died.:shock:

That said we are not a done deal yet!
I give my time willingly in an attempt to provide more feedback to the team to streamline the protocol, making it safer and quicker and more available.
It helps when members post regularly and interact with each other as it increases the size of the information pool we can access.

I quite agree there are other "cures" around the world which are proven false over time, Vitamin D is a classic example.
People still push it though, plenty of money to be made yet!
It takes years for the word to get around even with the internet so unscrupulous people will continue to clean up.:X

I don't know if MP will change the world, but it changes our world and that is enough.;)

Grateful Survivor
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Eloquently said, Keith. :dude:

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Good to read your discussion Tammy.

You asked

"I don't understand why many people have to continue taking the olmesartan, sometimes with antibiotics, to maintain the level of recovery they have achieved after several years of MP protocol."

I'm not sure people --have-- to continue taking olmesartan to maintain the level of recovery. My own personal experience had me off all olmesartan and abx for a year when the economic crisis hit my personal wallet.

I returned to olmesartan when I could, because I wanted to see if there was more I could get out of the process, --not-- because I need to continue the process to survive.

There are several paradigm shifts in comprehending immune function and the extent of immune capability when it is enabled that are worth exploring. Some paradigms associated with what we've been seeing in our cohort just don't match up to paradigms created from decades of seeing medical intervention through the prism of immune suppression and sans new technologies that allow cutting edge researchers to see farther than test tubes, Petri dishes and animal models.

Take some time to read MPKB.org (search by topic). Read Marshall's and others' articles, and follow the MP in one's own life by doing the MP and only the MP. Science is interesting stuff.

Best to you Tammy--Janet

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tammy1000 wrote: ....I don't understand why many people have to continue taking the olmesartan, sometimes with antibiotics, to maintain the level of recovery they have achieved after several years of MP protocol....


Thought I might take a stab at addressing the statement above... 

Please keep in mind my response, however, is predicated on the understanding that everyone is burdened with some level of microbiota, as even a typical healthy individual harbors 1.2kg on average, and probably always will be…. 

In the case of those of us who finally turned to the MP, probably often as a last resort, the microbiota burden was likely extensive (overall load) and virulent.  The term “virulent” implying down regulation of VDR expression so significant as to undermine adaptive and then innate immunity, and homeostatic imbalance from the plethora of non-human metabolites including neurotoxins and biotoxins. 

That being said, if we fast forward our thinking a few years, to the point where a normal state of health is achieved, the question arises as to why one would want to expose themselves to a risk of relapse?  Especially as there is likely little chance of clearing the body entirely of microbiota and only a slight chance of fundamentally changing the shared genetic makeup and mix.  

Improving diet, of course, in favor of food sources that tend to harbor bacterial forms less favorable toward biofilm formation may be a good step, but it's probably only a small step at best.  But this leads to an obvious question and hope Dr. Marshall has compiled enough study data to be able to answer it:

Q) In contrast to the therapeutic dose of 40mg/q6h of Olmesartan usually required during MP recovery, what is the “minimum” therapeutic dose needed to prevent VDR re-impairment of phagocytes beyond the 48-60 month MP time frame?  (ie. 40mg/q24h? 40mg/q12h? 40mg/q8h? or possibly 20mg/q24h? 20mg/q12h? 20mg/q8h?)       

Hopefully I've theorized correctly.

Regards/TikBitten

Last edited on Wed Mar 16th, 2011 18:07 by TikBitten

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Tikbitten, as the body recovers, the intervals between olmesartan dosing tend to stretch. Eventually you don't notice when you don't take it at all...

I hypothesize (for there is no other way I know to figure it out) that the microbes attack VDR by all means possible, including via hostile protease activity. A recent paper identified that the species Shigella does indeed increase the activity of Caspase 1, and it is likely that Caspase 3, thought to be the VDR's primary nemesis, is also targeted by one of the thousands of species present in the human microbiome. Aeromonas also targets protease activity.

So here is what I think. As the microbes become more virulent, the VDR which are expressed are also quickly broken down by proteases, after perhaps just a few hours of activity. It is important to keep a significant concentration of Olmesartan in the blood at all times, so it is there when the VDR are looking for ligands. This leads to the 4-6 hour optimum dosing interval (3 hours when somebody is in distress with IP).

Thus the dosing interval is inversely proportional to the degree of microbial activity. Which is certainly true in the limiting situation -- healthy people get no IP :)

You can read more about this in the MPKB :)
 

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Does this mean Benicar for life?

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No, only until you are happy that you are close enough to "healthy" not to want any more healing...
 

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I remember in the old notes a one month program every year to clean up was recommended, is that still valid?

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Sort of valid :)
One starts to use antibiotics again for the job they were designed to do - deal with acute pathogens. I use Bactrim when traveling in Asia -- to allow me to eat local foods without diarrhea, and a single clindy is good for dealing with the bugs picked up after 15 hours in an aircraft cabin.

But there is not much point scheduling any special "clean-up" of the chronic microbiota as the body seems to do the job well enough with Olmesartan.
 
Oh -- eventually you get to the point where there is no IP induced by the abx any more...
 

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Does the point where anti-biotics have no affect come before or after stage 5?

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Not everybody suffers from Stage 5.  In my case, I had little antibiotics sensitivity left when Stage 5 hit. Stage 5 was at the 5 year mark..

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Is this still current information?

A smaller dose taken more frequently such as 20mg every two, three, or four hours may keep symptoms more tolerable. Some very symptomatic patients find they feel best taking 20mg of Benicar every three hours during the day and then 40mg at bedtime with the next dose six hours later. A typical schedule would be 20mg at 6am, 9am, noon, 3pm, 6pm, 9pm and then 40mg at midnight. That would be equivalent to 40mg every six hours or 160mg in a 24-hour period.

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An average 40mg every 4-6 hours is our current guidance. It is better to take 40mg than 20mg, as the higher peak concentration has a greater effect on the nuclear receptors. But by juggling the dose, and interval, one has some minimal control over the balance between IP and immunostimulation.

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Thank you, Dr. Marshall. We appreciate your guidance. ;)

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Although some people report relief by taking olmesartan 20mg q2h, I discovered that, for me, while it got rid of the peak unpleasant response (brought on by the waning of the drug), I felt consistently uncomfortable to a greater degree taking 20mg q2h. For me, it is worth the sudden "Oh it must be time for my next Benicar" than to miss the positives that come with a 40mg dose.

I understand that this is person specific, but I'm glad that my experience coincides with the recommended best practices.

Last edited on Thu Mar 24th, 2011 02:34 by eClaire

Prof Trevor Marshall
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FDA has issued preliminary guidance:

http://www.fda.gov/Drugs/DrugSafety/ucm251268.htm

..Trevor..
 

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Relief that it isn't pulled off the shelves. Will Sankyo have any obligation to address the VDR agonist properties of Olmesartan in the "additional studies"?

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Nope. Not unless Sankyo tells them about it. But that would open up a can of worms - Imagine the FDA suddenly having to recognize that all drugs hit multiple targets. Wow - in a short while there would be very few drugs left on the market, I reckon...

..Trevor..

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No cancer risk elevation from ARBs: Two new analyses

http://www.theheart.org/article/1211465.do

"His group's findings, published online April 11, 2011 in Circulation, were based on the public-health records of >300 000 people in Denmark. They showed no significant rise in risk of incident cancer and even suggested reduced overall cancer mortality among those taking ARBs compared with others taking ACE inhibitors—independent of sex, type of ARB, and duration of ARB exposure"

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Thanks for that citation Bane. Good to have additional reassurance for those who worry. :)

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FDA Drug Safety Communication: No increase in risk of cancer with certain blood pressure drugs--Angiotensin Receptor Blockers (ARBs)

http://www.fda.gov/Drugs/DrugSafety/ucm257516.htm

The U.S. Food and Drug Administration (FDA) has completed a review of the potential risk of cancer associated with the class of medications known as angiotensin receptor blockers (ARBs). FDA has concluded that treatment with an ARB medication does not increase a patient’s risk of developing cancer.

Bane
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Angiotensin Receptor Blockade and Risk of Cancer in Type 2 Diabetes Mellitus: A Nationwide Case-Control Study.

http://www.ncbi.nlm.nih.gov/pubmed/21690476

PURPOSE The objective of this case-control study was to evaluate the risk of malignancy in diabetic patients who received angiotensin receptor blockers (ARBs). PATIENTS AND METHODS A total of 21,750 new diabetic patients who started antihypertensive treatment were identified from the Taiwan National Health Insurance claims database during the period from July 1, 2000, to December 31, 2000. As of December 31, 2007, patients with incident cancer were included as cases and up to four age- and sex-matched controls were selected by risk-set sampling. Logistic regression models were applied to estimate the odds ratios (ORs) and 95% CIs between ARB use and cancer incidence, adjusted for other types of antihypertensive drugs, insulin, oral hypoglycemic agents, statins, and underlying diseases. Results Among the 1,281 patients with incident cancer and 5,104 controls, 333 (26.0%) and 1,341 (26.3%), respectively, received ARBs (OR, 0.98; 95% CI, 0.85 to 1.14). There was no statistically significant association between the effect of ARBs as a class and cancer incidence after adjustment for covariates (OR, 0.94; 95% CI, 0.80 to 1.10). Among the individual ARBs, losartan decreased the risk (OR, 0.78; 95% CI, 0.63 to 0.97) and candesartan (OR, 1.79; 95% CI, 1.05 to 3.06) and telmisartan (OR, 1.54; 95% CI, 0.97 to 2.43) possibly increased the risk of occurrence of malignancy. CONCLUSION The results did not show an effect of ARBs as a class on increasing cancer incidence in patients with diabetes. However, there was a negative association of losartan but a positive one of candesartan and telmisartan with the overall occurrence of cancer. The underlying mechanism certainly requires further investigation.

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continuation

Study rekindles cancer-ARB question, this time in diabetics

http://www.theheart.org/article/1243675.do

"One explanation for this finding of null association is that cancer risk associated with ARBs might not be a class effect, and examining different ARBs as a group will dilute the risk estimates for individual drugs,"

"This new epidemiologic study not only shows an increased risk of cancer with candesartan, it also shows a very strong statistical trend toward increased risk with telmisartan," said Sipahi. "Now we have additional epidemiologic studies showing an increased risk of cancer with two different ARBs."

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More data reignite debate on ARB-lung cancer risk

http://www.theheart.org/article/1286017.do

"This is a nonrandomized observational study. I would think that smokers have higher risk of both cancer and severe cardiovascular disease. More severe CV disease [entails] more ACE inhibitors and ARBs; blaming these drugs would be like accusing the piano player of falsely singing. Confounded by indication cannot ever be corrected by multivariate adjustments in such a registry," says Kjeldsen.

 

Reduced Risk of Breast Cancer Recurrence in Patients Using ACE Inhibitors, ARBs, and/or Statins.

http://www.ncbi.nlm.nih.gov/pubmed/21936625

The use of ACE-inhibitors/ARBs, statins, and the combination of both were all associated with a reduced risk of breast cancer recurrence. This observation should prompt further exploration.

Last edited on Mon Oct 3rd, 2011 05:19 by Bane

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Use of angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers and cancer risk: a meta-analysis of observational studies

http://www.cmaj.ca/content/183/14/E1073.full

Results: Of 3970 screened articles, 12 cohort studies and 16 case–control studies were selected for analysis. We found no significant association between the use of ACE inhibitors or angiotensin-receptor blockers and the overall risk of cancer (relative risk [RR] 0.96, 95% confidence interval [CI] 0.90–1.03). We found a decreased risk of cancer associated with use of either medication when we restricted the analyses to cohort and nested case–control studies (RR 0.90, 95% CI 0.83–0.97) or to studies with long-term follow-up of more than five years (RR 0.89, 95% CI 0.83–0.96). In the subgroup meta-analyses by cancer site, a decreased risk was identified for esophageal cancer, whereas an increased risk was found for melanoma and kidney cancer.

Interpretation: No significant association was found between the use of ACE inhibitors or angiotensin-receptor blockers and overall risk of cancer. A possible beneficial effect associated with use of either medication was suggested in sensitivity analyses, including those of studies with long-term follow-up. Large randomized controlled trials with long-term follow-up are needed to specifically test the effect of each of these medications on the risk of cancer.

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EMA review concludes: No cancer risk with ARBs

http://www.theheart.org/article/1297005.do

"The CHMP reviewed all available data on the risk of cancer in patients taking ARBs, including the meta-analysis," the statement reads. "It found that the evidence from the meta-analysis was weak, noting several problems with the quality of the data, specifically that patients in the trials were not followed up for long enough to clearly establish a link between ARBs and cancer, information on the risk of cancer before start of treatment was lacking, and there was a possibility of publication bias, whereby studies that showed a link with cancer were more likely to have been included in the analysis."

As chronicled by heartwire over the past year, researchers have published a raft of studies and analyses either supporting or rejecting a link between ARBs and cancer, the most recent in the October 4, 2011 issue of CMAJ, by Dr Chan Yoon (Seoul National University of Medicine, South Korea) and colleagues, actually pointing to a beneficial effect of ARBs and ACE inhibitors on the risk of cancer. Another recent study, however, in diabetic patients treated with ARBs, suggested that candesartan (Atacand, AstraZeneca) was associated with a significant risk of cancer, while there was a trend toward an increased risk with telmisartan (Micardis, Boehringer Ingelheim).

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Long-term use of drugs affecting the renin-angiotensin system and the risk of cancer. A population-based case-control study.
http://www.ncbi.nlm.nih.gov/pubmed/22243442

"No consistent dose-duration or dose-response association could be demonstrated for ARB or ACEI"

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Angiotensin receptor blockers and risk of cancer: cohort study among people receiving antihypertensive drugs in UK General Practice Research Database

http://www.bmj.com/content/344/bmj.e2697

Results Follow-up ended a median of 4.6 years after the start of treatment; 20 203 cancers were observed. There was no evidence of any increase in overall risk of cancer among those ever exposed to angiotensin receptor blockers (adjusted hazard ratio 1.03, 95% confidence interval 0.99 to 1.06, P=0.10). For specific cancers, there was some evidence of an increased risk of breast and prostate cancer (1.11, 1.01 to 1.21, P=0.02; and 1.10, 1.00 to 1.20, P=0.04; respectively), which in absolute terms corresponded to an estimated 0.5 and 1.1 extra cases, respectively, per 1000 person years of follow-up among those with the highest baseline risk. Longer duration of treatment did not seem to be associated with higher risk (P>0.15 in each case). There was a decreased risk of lung cancer (0.84, 0.75 to 0.94), but no effect on colon cancer (1.02, 0.91 to 1.16).
Conclusions Use of angiotensin receptor blockers was not associated with an increased risk of cancer overall. Observed increased risks for breast and prostate cancer were small in absolute terms, and the lack of association with duration of treatment meant that non-causal explanations could not be excluded.


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ACE inhibitors and angiotensin receptor blockers use and breast cancer outcomes in patients treated with neoadjuvant systemic chemotherapy.

http://abstract.asco.org/AbstView_114_96713.html

Conclusions: No differences in pCR and survival outcomes were seen between ACEI/ARB users and non-users among breast cancer patients receiving neoadjuvant chemotherapy. ARB use may be associated with improved relapse-free survival. Further research is needed to validate this finding.

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This is my first posting on the official website and I want to thank everyone involved with the MP. It brought me back from the dead (and I literally mean that.) Forever I felt like a pain in the butt to everyone I met and now thanks to my P.A. and especially my homeopathic I am back among the living, waiting for my first grandchild, and feeling like I LOVE myself just exactly how I am. I also learned that I'm not crazy or a hypocondriac(spelling) and that with a long road to haul I am on a journey of a lifetime. Even with as hard as it gets, I wouldn't change my journey for anything (except to get this FDA approved.) My blessings to all and let the game begin!!!! Shellie

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Welcome back Shellie, you are in good company here!:)

:dude:

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Common Blood Pressure Drug Linked to Severe Gastrointestinal Problems

http://www.sciencedaily.com/releases/2012/06/120621130722.htm

ScienceDaily (June 21, 2012) — Mayo Clinic researchers have discovered an association between a commonly prescribed blood pressure drug, Olmesartan, and severe gastrointestinal issues such as nausea, vomiting, diarrhea, weight loss and electrolyte abnormalities -- symptoms common among those who have celiac disease. The findings are published online June 21 in the medical journal Mayo Clinic Proceedings.

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cathys2007 wrote: Common Blood Pressure Drug Linked to Severe Gastrointestinal Problems

http://www.sciencedaily.com/releases/2012/06/120621130722.htm

ScienceDaily (June 21, 2012) — Mayo Clinic researchers have discovered an association between a commonly prescribed blood pressure drug, Olmesartan, and severe gastrointestinal issues such as nausea, vomiting, diarrhea, weight loss and electrolyte abnormalities -- symptoms common among those who have celiac disease. The findings are published online June 21 in the medical journal Mayo Clinic Proceedings.

Severe Sprue-Like Enteropathy Associated With Olmesartan

http://www.youtube.com/watch?v=KjIWzIUN-eA

2:36 "and we also used steroids"

Last edited on Thu Jun 21st, 2012 13:18 by Bane

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glad you found that...nice catch Bane!

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Hi Cathy,

I read the link to the article.  I am sure that the patients  described were taking 20 or 40 mg of Olmesartan once a day and (through no fault of their own) getting the worst of possible results.  We are fortunate to know that the beneficial effects of Olmesartan come from keeping the concentration high enough, around the clock, instead of turning things on for a little while then off for the rest of the daily cycle.

All best,
Dody

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Thanks for finding this, Cathy and Bane! And thanks, Dr. Marshall, for posting the comments on YouTube.

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Ron, I find is utterly amazing, and negligent, for this type of article to be published without a decent search for our prior art on either PubMed, YouTube or Google. Sadly, that is the state of Medicine I see as I travel around -- a very few bright sparks who have adapted to the 21st Century, while most remain firmly locked in the past :X
 

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Always get worried when I see these articles about negative effects of Olmesartan.  I dread the day when I can walk into a store and buy a pack of smokes for $10 but Olmesartan has been taken off the market for my "protection".  Federal agencies have been such a big help so far with these diseases that an outcome like this seems par for the course. 

So was glad to hear the Mayo clinic doctor, at around the 2m 50s point in the video, say that this was a "very rare" association and that "the vast majority of patients on this medication should not change it at all".  He repeats this sentiment towards the end.

Also, at around 5m he admits that "we've described an association, not necessarily cause and effect".  Then goes on to say they need to figure out what the mechanism is and if this is confirmed elsewhere.  Hopefully they will see Dr. Marshall's comments and review his papers and presentations.

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Russ, we have Pure Olmesartan in the wings, which, from the outset, is being properly described to the FDA. No need to lose any sleep just yet :) :)
 

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Good to hear.  Dr. Marshall, do you think it's possible that researchers like these at the Mayo clinic do search the internet and find your work but don't consider it "mainstream" enough to cite?  That would be an even bigger offense in my opinion.

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No, I don't think so, Russ. Relevant peer-reviewed papers should have been cited, if known to the author. Mainstream, by its very definition, is peer-reviewed papers.

You would be surprised how insular most researchers really are :)
 

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Long-term use of angiotensin II receptor blockers and risk of cancer: A population-based cohort analysis.

http://www.ncbi.nlm.nih.gov/pubmed/22709730

"All ARBs significantly correlated with lower rates of cancer. Malignancies from the 7 most common sites were fewer in ARB users with the relative risk reduction of 28 to 49%. ARBs were associated with a decrease in incident cancer across subgroups including prior and concomitant exposure to angiotensin-converting enzyme inhibitors"

CONCLUSIONS:
In the cohort with indications for ARB treatment, exposure to ARBs was associated with lower risk of overall and site-specific cancers compared to nonusers. These findings reassure the safety of ARBs and support further investigations on ARBs and cancer prevention at the molecular level.

Russ
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Fyi, just did a Google search on "olmesartan celiac" and another one on "olmesartan gastrointestinal".  The first MP related hit shows up on page 4 and page 8 of the results respectively.  In both cases it's the MPKB page on Managing Immunopathology which does not talk about those symptoms in relation to Olmesartan but as potential non-IP symptoms caused by gluten intolerane or NSAIDS.  Of course, the majority of results are for the recent report from the Mayo clinic, so if searching before they went public the MP related hits would have been higher.

On YouTube, "olmesartan celiac" returns 13 results of which 5 are MP related including the third result.  "olmesartan gastrointestinal" returns 13 results of which 1 is MP related and it is the second result.

HealthyAgain
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Angiotensin II receptor blockers

In 2008, they were reported to have a remarkable negative association with Alzheimer's disease (AD). A retrospective analysis of five million patient records with the US Department of Veterans Affairs system found different types of commonly used antihypertensive medications had very different AD outcomes. Those patients taking angiotensin receptor blockers (ARBs) were 35—40% less likely to develop AD than those using other antihypertensives.[7][8]

[7],[8]http://en.wikipedia.org/wiki/Angiotensin_II_receptor_antagonist#cite_note-6

Taken from Wikipaedia

[8]

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Hi - I've trusted Olmecip Q4 for over a year, then recovered enough to think I could take a break from the MP while my husband was recovering from a stroke and heart surgery. I became sick again. When recently returning to the MP (thank God!) I felt so comfortable - even with the fatigue it causes me - because I knew I was returning to the "Benicar Blockade" Dr. Marshall has described. With the "Blockade" in place, I can begin the antibiotics again. I'm relieved to hear that Olmesartan is still being proven safe (loved the catch Bane made on "steroids"). From a couple of the recent entries, I'm wondering: Is it possible to obtain Olmesartan here in the U.S.??
For Dr.Marshall: Thanks so much for saving my life! How can countless numbers of people you've helped ever thank you enough?! Whenever telling others about the MP, I also speak of your character - a man who could have made millions of dollars, yet instead chose to save millions of lives! You are amazing.

Dixie
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Dear Dr. Marshall,

Is there ANY means by which I can obtain Pure O living in the U.S?

Thank you for responding to my request.:)

Dixie (Deborah Cleaveland)

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PatsyAnn, olmesartan is still under patent in the US as Benicar.  The patent does not expire for a few years yet.  So, if you can afford the ~6x higher price, or can cajole your insurance company into paying for it, most of us can't, then you just need to go to any pharmacy with a prescription and pay 3 or more dollars per pill.

Cynthia

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Pure olmesartan is not available, as it hasn't been approved by the FDA for any purpose.  Dr Marshall is working on this.

Olmesartan Medoximil (Benicar, Olmecip, etc.) is the only approved and available form anywhere outside of research efforts.

SanDiegoJoy
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Patsy Ann: What most of us do who live in the US is order generic Olmesartan (usually called Olmecip) from a reputable Canadian pharmacy which requires a prescription. The cheapest one I've found is PlanetDrugsDirect.com, I order 180 tablets x 2 (for a total of 360 tablets which is about a 3 month supply) and the cost is $204. If you want to order 180 tablets it is $102. It takes about a week to process the order and 3 weeks to receive it, so that's why I order a 3 mos. supply at a time, and they will take refills so I try to get my doc to authorize 1 or 2 refills at the time they fax their prescription.

PlanetDrugs has been great to do business with and are very responsive. I've communicated with them via e-mail and on the phone several times. (They will follow up with a fax to you after you place your order reminding you that they need to get a prescription from your doc and your doc should reference your order # when they fax your Rx.)

Last edited on Sat Jun 23rd, 2012 09:39 by SanDiegoJoy

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Thanks so much for the response(s) to my Olmesartan question . . . and the details you gave, SDJoy, are very informative. I, too, have ordered the O from an international pharmacy - but this one sounds better! By the way, we previously lived in San Diego for many years - and our eldest daughter & family are there. We'll be there the week of the Fourth to celebrate our 35th Anniversary AND our first Grandaughter's 18th birthday! :)

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How Does Inhibition of the Renin-Angiotensin System Affect the Prognosis of Advanced Gastric Cancer Patients Receiving Platinum-Based Chemotherapy?

http://content.karger.com/produktedb/produkte.asp?doi=337979

Conclusion: ACEI/ARB in combination with standard chemotherapy might improve survival in patients with AGC and hypertension. These results support further investigation into the anticancer effects of ACEL/ARB.

Bane
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Long-Term Use of Angiotensin Receptor Blockers and the Risk of Cancer

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0050893

"This study provides additional evidence that the use of ARBs does not increase the risk of cancer overall or any of the four major cancer sites"

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Effects of angiotensin receptor blockade (ARB) on mortality and cardiovascular outcomes in patients with long-term haemodialysis: a randomized controlled trial.

http://www.ncbi.nlm.nih.gov/pubmed/23355629

Hypertension is a major risk factor for death and cardiovascular disease (CVD) in patients undergoing chronic haemodialysis (HD), but there is uncertainty surrounding the effects of blood pressure (BP) lowering on this high-risk patient group.MethodsIn a multicenter, prospective, randomized, open-label, blinded-endpoint trial, 469 patients with chronic HD and elevated BP (140-199/90-99 mmHg) were assigned to receive the angiotensin receptor blockade (ARB) olmesartan (at a dose of 10-40 mg daily; n = 235) or another treatment that does not include angiotensin receptor blockers and angiotensin-converting enzyme (ACE) inhibitors (n = 234). The primary outcomes were the following: (i) composite of death, nonfatal stroke, nonfatal myocardial infarction and coronary revascularization and (ii) all-cause death. Results: During a mean follow-up of 3.5 years, the mean BP was 0.9/0.0 mmHg lower in the olmesartan group than in the control group (not significant). A total of 68 patients (28.9%) in the olmesartan group and 67 patients (28.6%) in the control group had subsequent primary composite endpoints [hazard ratio (HR) in the olmesartan group 1.00, 95% confidence interval (CI) 0.71-1.40, P = 0.99]. All-cause deaths occurred in 38 patients (16.2%) in the olmesartan group and 39 (16.7%) in the control group (HR, 0.97; 95% CI, 0.62-1.52, P = 0.91). Olmesartan did not alter the risks of serious adverse events. Conclusions: BP-lowering treatment with an ARB did not significantly lower the risks of major cardiovascular events or death among patients with hypertension on chronic HD.

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So it is a pretty good placebo, then?

Pretty amazing that none of these researchers stumble upon the immune modulating effects of the drug.

I doubt anybody here would agree that the drug does nothing :) :) :)
 

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I was about to make a suggestion, then realised how wrong it would be (use 4x or 5x the dose and redo the study).
Obviously, then they would be well-advised to prevent vitD consumption, sun exposure and various foods, as well as management of IP, that is, IF that particular drug did have any effect..  ;)

It kind of exposes the limited/faulty thinking behind a lot of trials - the ignorance of other factors and existing knowledge and the expectation that one factor alone might produce significant results.

Actually, just doing simple addition, and since I commented on another statistic of sorts recently - another 77 deaths occured while limited thinking is happening.. it's kind of shocking.

Last edited on Wed Jan 30th, 2013 14:15 by Seth

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Hm...

How about: high bloodpressure alone is nothing, that makes people die early?

Or the other way around: artificially lowering high bloodpressure does not solve the underlying problem?

I mean, if you are old, your veins are narrow and you have put on to much weight, your body might need higher bloodpressure to make sure, that enough blood arrives in the outer areas of the body?

I would bet, that after "cleaning" the veins and reopening some stuffed pathways the bloodpressure would go down without any medicamentation.

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Bane wrote: Effects of angiotensin receptor blockade (ARB) on mortality and cardiovascular outcomes in patients with long-term haemodialysis: a randomized controlled trial.
http://www.ncbi.nlm.nih.gov/pubmed/23355629
  469 patients with chronic HD and elevated BP (140-199/90-99 mmHg) were assigned to receive the angiotensin receptor blockade (ARB) olmesartan (at a dose of 10-40 mg daily; n = 235) or another treatment that does not include angiotensin receptor blockers and angiotensin-converting enzyme (ACE) inhibitors (n = 234). All-cause deaths occurred in 38 patients (16.2%) in the olmesartan group and 39 (16.7%) in the control group (HR, 0.97; 95% CI, 0.62-1.52, P = 0.91). Olmesartan did not alter the risks of serious adverse events. Conclusions: BP-lowering treatment with an ARB did not significantly lower the risks of major cardiovascular events or death among patients with hypertension on chronic HD.

olmesartan (at a dose of 10-40 mg daily)  would be insufficient to sustain ongoing activation of the VDR. While it would be providing significant blockage of the ATR1, this action would be countered by feedback to increase the level of RAAS components which would maintain the damaging action of these mediated by signalling through ATR1 and the (pro)renin receptor. 
  Higher levels of olmesartan, such as the 4 x 40mg or 6 x 40 mg used in the MP, would provide activation of the VDR to inhibit production of the RAAS components: angiotensinogen, prorenin and renin, ATR1 and the (pro)renin receptor. This would help prevent the levels of these rising through feedback and so limit the damaging action of the RAAS.

Last edited on Thu Jan 31st, 2013 15:36 by Jigsaw

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Angiotensin Receptor Blockers and Risk of Prostate Cancer Among United States Veterans.

http://www.ncbi.nlm.nih.gov/pubmed/23686462

"There was no significant difference in Gleason scores between the two groups. We found a small, but statistically significant, reduction in the incidence of clinically detected PrCA among patients assigned to receive ARB with no countervailing effect on degree of differentiation"

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Even the passionate scientists don't understand:(

http://online.wsj.com/article/SB10001424127887324682204578515172395384146.html?mod=djemalertNEWS

Dr. Marciniak's analysis didn't include data from trials on some ARB drugs, including Benicar, but he concluded "that the increased incidence of lung cancers with ARB use is likely a class effect of ARBs" and that it would be "inappropriate" to classify specific ARBs as safe due to a "lack of adequate studies."

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Thanks Hogan.  Amazing how he is able to talk back to his boss like that and ignore his orders without getting fired.  I guess firing someone because they insisted on looking into a safety concern would be a bad PR situation.

It's weird being on the side of the big bureaucratic government agency and the drug companies and against the rougue scientist emphasizing safety of drugs, but in this case I guess we are.  Although we wouldn't have to be, if he would just look at the ARBs individually instead of as a class.

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I wonder if this is a factor in the FDA's stonewalling of Dr Marshall's request to approve pure olmesartan for study in ONE patient!!!  :X:X:X:X:X:X:X:X:X:X

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It really is infuriating.  With so many wacky "therapies" being approved (of course they're usually very profitable...), it's just awful what an uphill climb this is Chris.  It is so not fair.  Whatever happened to the patient's well-being truly being the goal of everyone involved in health care???  I used to work for one of the early health maintenance organizations and that really was the goal, despite all the well-financed pressure toward other goals.

Love you Chris.

Dody

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Thanks Dody!!

I agree that the FDA has lost the focus on the patients and what is best for them.  I don't know if pure olmesartan would stop and turnaround this horrible disease.  But I feel I have the right to find out!!  There should be different guidelines and procedures for terminally ill patients.  It is utterly ridiculous that the FDA is treating the application for pure olmesartan as any old new drug for a lesser disease ... meanwhile ignoring the fact real people are suffering and dying with ALS!!!  There is no sense of urgency at all.  Everything has to go through the same frustrating bureaucratic mill!!!

Love you too!!
Chris


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Money talks.

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"Money doesn't talk, it screams." Bob Dylan

I consider myself well read on the topic of Benicar or olmesartan as a treatment for chronic illness. I have studied the science for more than 8 years, and observed the documented changes for the better in my own health. And others on the MP.

The study in question is rubbish, IMHO.

Sherry

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Angiotensin receptor blockers: are they related to lung cancer?

http://www.ncbi.nlm.nih.gov/pubmed/23822929

"In this large nationwide cohort of United States Veterans, we found no evidence to support any concern of increased risk of lung cancer among new users of ARBs compared with nonusers. Our findings were consistent with a protective effect of ARBs"

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Comparative effectiveness of angiotensin-receptor blockers for preventing macrovascular disease in patients with diabetes: a population-based cohort study

http://www.cmaj.ca/content/early/2013/07/08/cmaj.121771

"Compared with other angiotensin-receptor blockers, telmisartan and valsartan were both associated with a lower risk of admission to hospital for acute myocardial infarction, stroke or heart failure among older adults with diabetes and hypertension"

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Bane wrote: Compared with other angiotensin-receptor blockers, telmisartan and valsartan were both associated with a lower risk of admission to hospital for acute myocardial infarction, stroke or heart failure among older adults with diabetes and hypertension"
Olmesartan was not assessed.

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Ignore the prior link, it is old news....LOL.

This is the link for the skinny....

http://www.medscape.com/viewarticle/807289?src=wnl_edit_medn_wir&uac=43453BN&spon=34

Too bad they haven't been following the MP science or they would understand why this is happening. I think someone needs to post a reply to the 14 providers that haven't a clue.

Happily Healing,
Trudy

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Trudy, the linked site is asking for a password.

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Verena wrote: Trudy, the linked site is asking for a password.

http://www.fda.gov/downloads/Drugs/DrugSafety/UCM359496.pdf

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Does this mean that it "seems" (to them) like benicar is causing intestinal problems, but really it's helping to heal existing problems?
Pam

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It is exposing sub-clinical existing problems. Early-stage disease which cannot yet be identified by symptoms or markers.

My research on "Predictive and Preventative Medicine" covers the topic of sub-clinical disease, how to tell if somebody is going to get ill, and prevent it before they really get sick.
 

Pamela H-F
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Thanks. That's what I thought. If it actually caused gut troubles I suppose we'd all be in quite a state.
Pam

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Is that paper in the site somewhere?

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@dogster
Hmmm. There is a book chapter due to be released in September. That is the most comprehensive. There is also a series of conference abstracts. Not sure if I ever put any of those videos online, though. I will look into it.

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Talk about sub-clinical disease existing undiagnosed. I was seeing a patient in the ED the other day for another problem (heat exhaustion) and he gave as his Past Medical History "celiac sprue" and nothing else. Being on the MP and now having become alerted to the fact that rarely do we find one of these "autoimmune phenomena" existing completely alone, I began poking around to see if I could find anything else. Any psoriasis, lupus, RA, etc? Went through a whole list of them. Has your doctor thought you are ill in any other way? No, no and no. Then the mother speaks up from the other side of the room and say, "XXXX, why don't you tell the doctor about how you are absolutely so tired all the time and can sleep all day long and barely get out of bed sometimes"? The Ah-Ha moment..... :-)

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:)

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Whenever someone asks me if anything has improved while on the MP, I love to mention how many NEW symptoms I have developed as a result of the exposure of subclinical ailments.  Then I love to go on and tell them how, if it weren't for the MP, that subclinical thing would have popped up in a few months or years to knock me on my can.  One person told me I made her miserable, because now she has to wonder how many time bombs she's carrying.  I told her to find out - use the MP.

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Cardiac mortality in users of olmesartan, other angiotensin-receptor blockers and angiotensin-converting enzyme inhibitors.

http://www.ncbi.nlm.nih.gov/pubmed/24375940

"The results of this well-powered study do not raise concerns for the risk of SCD or death from all causes among olmesartan users in comparison with users of other ARBs or ACE inhibitors"

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An interesting blog in the NY Times by Dr. Lisa Sanders: Think Like a Doctor: Stomach Bug Solved!

http://well.blogs.nytimes.com/2014/02/07/think-like-a-doctor-stomach-bug-solved/

I answered the blog and directed them to the mpkb.org....

:shock::):D

Trudy

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Hi Trudy,

I looked at the blog, but did not see your comments. Is there a delay involved in the posting of the comments?

Trudy.Heil_NP
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Yes, there is a delay.
Trudy

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I am looking forward to reading what you said.

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Well done Trudy, it's unbelievable to us Mp'ers.

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I haven't been able to see Trudy's comments yet either. 

My thought is that Benicar even at conventional dosage was provoking immunopathology--without the stabilizing effects of the steadier round-the-clock concentrations we are getting.  Blaming the agent that used properly could be curative.

Benicar at MP dosage is what, over the course of 6 years, transformed my borderline Crohns colon to a colon in which no inflammation could be seen.  Now I get diarrhea only from an occasional acute bug or, unfortunately several times this winter, when I have to use my abdominal muscles to lift a little too much weight, bothering the adhesions left from surgery in 1989 that removed my ascending colon to which multiple old abscesses were attached.  (Other than the need to restrict lifting, especially lifting with twisting, the resection was a complete success.)

Dody

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The same 4 comments that have been there all along are there with nothing from Trudy. I do not know what the delay time is. I wonder if her comments have been censored for not supporting the thesis of the article.

Last edited on Sun Feb 9th, 2014 10:20 by Cairo123

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It is very important to cite our peer-reviewed papers, rather than websites, when talking with TPTB (including your own Doctor).
 

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I'm attempting again....

"'Can you share with the rest of us why the mechanism of action of an angiotensin receptor antagonist results in such severe diarrhea?'

Glad you asked, Jen SJ. It is because of a characteristic of the drug Benicar that stimulates the innate immune system with each dose. See: http://mpkb.org/home/publications/marshall_theoretical_2006 for an explanation of why this happens."

Trudy

PS: If I need to quote some other scholarly paper, let me know. Let's see if this one gets through....

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Yes, I would use a scholarly paper such as this:

Proal AD, Albert PJ, Blaney GP, Lindseth IA, Benediktsson C, Marshall TG: Immunostimulation in the Era of the Metagenome. Cell Mol Immunol. 2011 Jan 31

http://www.ncbi.nlm.nih.gov/pubmed/21278764
http://dx.doi.org/10.1038/cmi.2010.77


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I don't see *any* comments. What am I missing?

The GI symptoms and relation to celiac disease sure sound familiar to me, but I had all that pre-benicar.

leroybrown
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Nevermind - I enabled javascript and saw the comments link.

Trudy.Heil_NP
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The MP is in the NY Times.....

http://well.blogs.nytimes.com/2014/02/07/think-like-a-doctor-stomach-bug-solved/?_php=true&_type=blogs&comments&_r=0#permid=11118976

http://well.blogs.nytimes.com/2014/02/07/think-like-a-doctor-stomach-bug-solved/?comments#permid=11137419

My comments were finally vetted and published.

I also added this comment:
"Good question, Sandy. Now you are asking the right questions! In fact , it is not a side effect of the other ARB or ACE drugs with or without HCTZ. Only Benicar/Olmesartan Medoxomil alone (no HCTZ) has this unique property to stimulate the immune system. It was discovered during the clinical drug trials back in the early 2000's. It is being re-targeted for this purpose. See Proal AD, Albert PJ, Blaney GP, Lindseth IA, Benediktsson C, Marshall TG: Immunostimulation in the Era of the Metagenome. Cell Mol Immunol. 2011 Jan 31

http://www.ncbi.nlm.nih.gov/pubmed/21278764
http://dx.doi.org/10.1038/cmi.2010.77

It is very exciting to see chronic inflammatory diseases begin to succumb to our immune system by stimulation and not suppression of this body system."

:cool:

Trudy

Last edited on Wed Feb 19th, 2014 07:20 by Trudy.Heil_NP

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Hooray Trudy!

Take a bow for a job well done.:)

Sherry

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Your comment was thoughtful, and your responses well measured. I wonder if anyone will be willing to take a further look?

Trudy.Heil_NP
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We can only hope....;)

Trudy

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:dude:

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Wow Trudy :cool::cool::cool:

love it and you,
linda a.k.a. the microbe terminator

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cathys2007 wrote: Common Blood Pressure Drug Linked to Severe Gastrointestinal Problems

http://www.sciencedaily.com/releases/2012/06/120621130722.htm

ScienceDaily (June 21, 2012) — Mayo Clinic researchers have discovered an association between a commonly prescribed blood pressure drug, Olmesartan, and severe gastrointestinal issues such as nausea, vomiting, diarrhea, weight loss and electrolyte abnormalities -- symptoms common among those who have celiac disease. The findings are published online June 21 in the medical journal Mayo Clinic Proceedings.

Olmesartan, Other Antihypertensives, and Chronic Diarrhea Among Patients Undergoing Endoscopic Procedures: A Case-Control Study.http://www.ncbi.nlm.nih.gov/pubmed/25023670


RESULTS: We identified 2088 patients undergoing EGD and 12,428 patients undergoing colonoscopy meeting inclusion criteria. On multivariate analysis, there was no statistically significant association between olmesartan and diarrhea among those undergoing EGD (odds ratio, 1.99; 95% CI, 0.79-5.00) or colonoscopy (odds ratio, 0.63; 95% CI, 0.23-1.74). Review of pathology reports of the EGD and colonoscopy groups showed no association between the use of olmesartan and the histologic diagnosis of celiac disease (P=.61) or microscopic colitis (P=1.0), respectively

CONCLUSION: Our findings suggest that neither olmesartan nor other ARBs were associated with diarrhea among patients undergoing endoscopy. The spruelike enteropathy recently associated with olmesartan is likely a rare adverse effect and milder presentations are unlikely.

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Nice work, Cathy and Bane. I'll send this off to the fine doctors at Flat Earth Hospital, who advised me that olmesartan was the cause of my diarrhea.

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FDA Finds Olmesartan Does Not Cause Cardiovascular Events

http://www.fda.gov/drugs/drugsafety/ucm402323.htm
http://www.lgmpharma.com/blog/fda-finds-olmesartan-does-not-cause-cardiovascular-events/


"There was no viable evidence found to cause the FDA to deem Olmesartan unsafe, and earlier concerns from study investigators claiming there was an increased risk for heart attack in patients taking Olmesartan was nullified"

"Patients ages six and older may safely be prescribed Olmesartan, which is in a class of medications deemed angiotensin II receptor antagonists. While tablet form of Olmesartan is most common a liquid form can be made for children who have trouble swallowing the tablet"

Last edited on Sun Aug 17th, 2014 11:31 by Bane

Sallie Q
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Bane wrote:
Olmesartan, Other Antihypertensives, and Chronic Diarrhea Among Patients Undergoing Endoscopic Procedures: A Case-Control Study.http://www.ncbi.nlm.nih.gov/pubmed/25023670


.....
CONCLUSION: Our findings suggest that neither olmesartan nor other ARBs were associated with diarrhea among patients undergoing endoscopy. The spruelike enteropathy recently associated with olmesartan is likely a rare adverse effect ....



Seems to me that all the "adverse effects" which occasionally inspire doctors to stop prescribing Olmesartan, are the to-be-expected MP Immuno-Pathology (in various individual organs) which kicks in as immunity begins recovery.
:D

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That's what I believe, Sallie.  I tried to explain to the Flat Earth Hospital docs, but they weren't operating their brains in parachute mode, i.e. works better when open.

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Lack of an Association between Angiotensin Receptor Blocker Based Therapy and Increased Risk of Cancer: Evidence from Large Observational Studies

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366349/

"Overall, ARB-based therapy was not associated with increased risk of cancer. However, its use may be related to decreased incidence of lung cancer; this finding should be considered carefully and confirmed with further studies"

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its use may be related to decreased incidence of lung cancer
When they say its use may be related to decreased incidence of lung cancer, it would seem they are trying to differentiate between types of cancers, right?

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the subgroup analysis gives no statistic for eprosartan or olmesartan, I guess there exists at present no long term large population study for either in isolation, a pity :?

and of course I have a personal interest, as my skin cancer seems to be disappearing, my breast cancer has not returned
Also my Sjogren's has gone and so apparently I am now highly unlikely to meet with the associated lymphomas :)

Trudy.Heil_NP
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:D:D:D:D:D

Trudy

Bane
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Location: Norway
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Immunopathogenesis of olmesartan-associated enteropathy.

http://onlinelibrary.wiley.com/doi/10.1111/apt.13413/epdf

"Olmesartan-associated enteropathy shares many features with coeliac disease, including symptoms and immunopathogenic pathways, such as increased numbers of CD8+ cells and corresponding overexpression of IL15 by epithelial cells"


IP???

Prof Trevor Marshall
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Joined: Fri Jul 9th, 2004
Location: Thousand Oaks, California USA
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Sure looks like it :) :)

Ron
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Location: Eindhoven, Netherlands
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Wow, Olmesartan - IP. It really does say so. Nice find Bane! :cool:

Bane
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Gastrointestinal Disorder Associated with Olmesartan Mimics Autoimmune Enteropathy.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477936/

"Among seven olmesartan-treated patients who developed villous atrophy refractory to a gluten free diet, three had extra-intestinal autoimmune diseases, two had antibodies reacting with the 75 kilodalton antigen characteristic of AIE and one had serum anti-goblet cell antibodies"


"Before olmesartan discontinuation, remission was induced in all patients (7/7) by immunosuppressive drugs. After interruption of both olmesartan and immunosuppressive drugs in six patients, remission was maintained in 4 but anti-TNF-α therapy was needed in two"

"This case-series shows that olmesartan can induce intestinal damage mimicking AIE. OIE usually resolved after olmesartan interruption but immunosuppressive drugs may be necessary to achieve remission. Our data sustain the hypothesis that olmesartan interferes with intestinal immuno regulation in predisposed individuals"

Bane
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Bane wrote:
Immunopathogenesis of olmesartan-associated enteropathy.

http://onlinelibrary.wiley.com/doi/10.1111/apt.13413/epdf

"Olmesartan-associated enteropathy shares many features with coeliac disease, including symptoms and immunopathogenic pathways, such as increased numbers of CD8+ cells and corresponding overexpression of IL15 by epithelial cells"


IP???


Olmesartan gets immune function rolling?

IL-15 Links TLR2/1-Induced Macrophage Differentiation to the Vitamin D-Dependent Antimicrobial Pathway

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2678236/

" In this study, we found that TLR2/1-induced IL-15 was required for induction of CYP27b1, the VDR and the downstream antimicrobial peptide cathelicidin. Although both IL-15 and IL-4 triggered macrophage differentiation, only IL-15 was sufficient by itself to induce CYP27b1 and subsequent bioconversion of 25-hydroxyvitamin D3 (25D3) into bioactive 1,25D3, leading to VDR activation and induction of cathelicidin"


Vitamin D Is Required for IFN-γ–Mediated Antimicrobial Activity of Human Macrophages

http://pubmedcentralcanada.ca/pmcc/articles/PMC3269210/

"demonstrating that IL-15 is a critical cytokine for activating the antimicrobial program in human macrophages. Together, these data show that both the innate and the acquired immune responses converge on a common antimicrobial pathway by inducing IL-15, which is required for up-regulation of CYP27b1 and the subsequent induction of cathelicidin and DEFB4"

Bane
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Angiotensin receptor blockers use and the risk of lung cancer: A meta-analysis

http://jra.sagepub.com/content/early/2015/10/03/1470320315607391.long

"This meta-analysis indicated that ARBs may be associated with decreased risk of LC"

Bane
Research Team


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Potential coeliac disease markers and autoimmunity in olmesartan induced enteropathy: A population-based study

http://www.dldjournalonline.com/article/S1590-8658(15)30042-6/abstract

"Incidence of severe olmesartan-associated enteropathy was low. Autoimmune phenomena were present in a subset of cases and reversed after olmesartan removal"

Prof Trevor Marshall
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Location: Thousand Oaks, California USA
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Today's researchers are absolutely clueless, and unable to even Google for ideas...

http://lmgtfy.com/?q=autoimmune+olmesartan

..Trevor..

Sallie Q
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not knowing who this is
Olmesartan and Recovery from Autoimmune Disease ... but I really like the sunnies :cool:

Bane
Research Team


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Location: Norway
Posts: 974
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The effect of angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) on cancer recurrence and survival: a meta-analysis.

http://www.ncbi.nlm.nih.gov/pubmed/27158979

"This meta-analysis provides evidence that the use of ACEIs or ARBs in cancer patients can lead to a 40 and 25% reduction in the risk of cancer recurrence and mortality"

scooker48
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Good news:).

Sherry

Bane
Research Team


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Location: Norway
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scooker48 wrote:
Good news:).

Sherry


yes:)

Is angiotensin-converting enzyme inhibitors/angiotensin receptor blockers therapy protective against prostate cancer?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872747/

Overall, this study indicates that use of RAS inhibitors may be associated with a decreased risk of prostate cancer. Large-scale well designed studies are needed to further explore this association.


Angiotensin receptor blockers (ARBs) reduce the risk of lung cancer: a systematic review and meta-analysis

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612864/

In conclusion, our meta-analysis demonstrated that ARBs was significantly associated with lower lung cancer.

Nyima
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Great find:).  And I'm assuming these benefits were noted at 'normal' doses, so researchers are only viewing the very fringe of what is possible with ARBs.

Bane
Research Team


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Mortality benefit of long-term angiotensin-converting enzyme inhibitors or angiotensin receptor blockers after successful percutaneous coronary intervention in non-ST elevation acute myocardial infarction.

https://www.ncbi.nlm.nih.gov/pubmed/27865680

CONCLUSIONS:
In this observational study of patients with NSTEMI, all of them treated successfully by PCI, the use of ACEIs/ARBs was significantly associated with a lower risk of four-year all-cause mortality.



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