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Dr Trevor Marshall
Research Team
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Posted: Sun Jan 28th, 2007 00:41 |
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Many of you have noticed that Soy doesn't always work well in your diets. Well, I finally got around to looking into an isoflavone called Genistein, which is a primary Soy isoflavone. Here is the picture of 1,25-D and Genistein as they dock into the VDR.
The molecule with the green spine is Genistein. Interestingly, it is a partial agonist, forming hydrogen bonds with SER278, TYR143, ARG274 and SER278, the same residues as 1,25-D hydrogen-bonds to. However, it doesn't have the 'tail' of Vitamin D or Benicar, and cannot transcribe those DNA genes which need coactivators requiring helix 12 to be stabilized. Ki calculates at about 0.5 micromolar.
In summary, Genistein will interfere with the operation of the VDR, as well as the PPAR-gamma and PPAR-alpha receptors, all key to the immune system.
This paper implies that 40mg of isoflavones a day is likely to produce concentrations capable of affecting the VDR (about 500 nanomolar). This paper suggests that 20 grams of roasted soyabeans (equiv. 37mg isoflavones) will give more than enough plasma concentration to mess up an already compromised immune system.
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(Scientists who want to build this discovery into their own papers should cite:
Marshall TG, Lee RE, Marshall FE: Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b. Theor Biol Med Model. 2006 Jan 10;3(1):1, together with the URL for this thread)
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John McDonald
Foundation Director
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Posted: Sun Jan 28th, 2007 03:06 |
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Trevor,
Just to be sure on this, does this mean that we should add all soy products to the do-not-eat list?
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RA 125D38, MP 9/05 Ph2 12/05 Ph3 09/06, Oct07 2510, NoIRs lite exp r/t work covered up
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scooker48
Member in Phase 3
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Posted: Sun Jan 28th, 2007 03:17 |
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Dr. Marshall,
Isn't this found in green tea?
Sherry
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Necrotizing granulomas biopsy 10/88; Dx 12/04 Sarcoid liver spleen. 2/2/05: VitD 25/VitD125 62. 5/9/09 D25, D3 6; D25 D2 <4, Liver function normal 4/08; Wear NoIRs outside. No K creme used. 5/09 Liver and kidneys normal.
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tickbite
Member in Phase 2/3
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Posted: Sun Jan 28th, 2007 05:26 |
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| Thanks Dr. M for looking at that more closely. Something has made me aware that fermented soy is okay because it has released most of the "bad" stuff. Would this be at all accurate? There are so many constituents in soy......
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"Lyme","CFS", Meningitis
Phase3 8-2-07, MP on hold 11/2007
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Dr Trevor Marshall
Research Team
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Posted: Sun Jan 28th, 2007 06:06 |
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Any problems will be dose-dependent. Anything up above the cited "20 grams of roasted soybeans," or 40mg of isoflavones, is likely to be a problem.
Benicar should be able to take back the VDR, especially at higher Benicar doses (eg 40mg q6h).
You should aim to keep soy content in diet below this level. As the body recovers during the MP, any potential problems will be reduced.
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Posted: Sun Jan 28th, 2007 08:53 |
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John asked, "Just to be sure on this, does this mean that we should add all soy products to the do-not-eat list?"
Greg said, "Something has made me aware that fermented soy is okay because it has released most of the "bad" stuff."
You'll want to minimize your intake of soy because it is immunosuppressive and focus on fermented soy products for other health reasons.
I stopped eating processed soy products some time ago because they made my stomach feel odd....I could tell I'd eaten something unnatural.
Please see Why you should minimize your consumption of soy and soy products for an article by Dana Carpender that discusses other heath risks of soy products and offers suggestions for vegetarians about products that might be safer (in limited quantities).
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Posted: Sun Jan 28th, 2007 09:11 |
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Sherry,
Yes, green tea contains genistein. Genistein is found abundantly in soy beans. The amount in green tea beverages varies, depending on how green tea is brewed and the type of green tea used.
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Dr Trevor Marshall
Research Team
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Posted: Sun Jan 28th, 2007 09:54 |
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Genistein seems to be low in concentration in Green Tea. I am still trying to find out reliable concentration data, but as far as I can see, Green Tea is OK, because the concentration of Genistein is not high enough to be a problem. I would welcome anybody sharing numerical data on this
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Frans
Member in Phase 2
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Posted: Sun Jan 28th, 2007 13:01 |
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Dr Trevor Marshall wrote: The molecule with the green spine is Genistein. Interestingly, it is a partial agonist, forming hydrogen bonds with SER278, TYR143, ARG274 and SER278, the same residues as 1,25-D hydrogen-bonds to. However, it doesn't have the 'tail' of Vitamin D or Benicar, and cannot transcribe those DNA genes which need coactivators requiring helix 12 to be stabilized. Ki calculates at about 0.5 micromolar.
Trevor, since it misses the 'tail', do you know which genes aren't transcribed?
Sincerely, Frans
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Burn-out/nervous breakdown Jan01 125D 48 25D8.48 Ph1Nov06 ModPh2Jan07 Ph2Apr08 Cipramil Seroquel NoIRs lite exp r/t work cover up 25D3.9(Oct07)
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Dr Trevor Marshall
Research Team
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Posted: Sun Jan 28th, 2007 19:01 |
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Frans,
This really is an imponderable question right now. The conference I recently attended at the Salk Institute discussed "Diseases of Transcription" and really impressed on me that we know very little about the exact transcription coactivators, and the heterodimeric conformations of these Type 1 Nuclear Receptors. Between them, they are probably transcribing 10,000 genes, maybe 100,000 genes.
As I summarize in my recent presentations, the two words I use to describe the Nuclear Receptors are "Redundancy and Complexity." Most scientists would say that unless a molecule's tail exerts forces on helix 12, preventing its folding, then no genes would be transcribed. As somebody who has been well-taught statistics, when I have a sample size of 100,000 or so, then I rarely use the word "never." And that is why I say these may be "partial" agonists. We just don't know yet enough about how the Nuclear receptors work. The co-location of the interatomic forces on all the same residues alerts me to the possibility of some as-yet-undocumented, actions...
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lionel forbes
Member in Phase 3
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Posted: Sat Feb 24th, 2007 05:34 |
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| ahh gosh, i used to consume heaps of soy milk, but i gave it up 3 years before mp, in order to conquer epilepsy,because soy is the food highest in phytates, a substance that binds to magnesium -required to calm nerve and muscle- and other minerals . this proceedure worked.
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sarcoidosis phase 1 jan 2006,phase 2 march 2006, phase 3 september 2006
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Dr Trevor Marshall
Research Team
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Posted: Sat Feb 24th, 2007 13:25 |
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Lionel,
That's a load of hogwash. Phytates? Show me exactly how they work. In fact, show me exactly how chelation 'works'. IMO the 'side-effects' of the drugs being used in those procedures are what folk see and feel. We know now exactly how the immune system is weakened by the chronic bacteria. The fallacies underlying these other concepts disappear into oblivion as one starts to reconcile them with the knowledge that pathogens are fundamentally responsible, not mercury, or phosphorus, or...
Never mind. These concepts will disappear in time. As Max Planck said "Science advances one funeral at a time"
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Jacko
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Posted: Tue Mar 6th, 2007 13:45 |
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Do you think this study has any significance in this? It was odd that they found the hormonal effects of soy protein isolate were independent of isoflavone content.
http://jn.nutrition.org/cgi/content/full/135/3/584
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Soon Ph1| Dx asperger,probably CFS| Freegan 01-06| 02/07 NoD/Lite| NoIRs 03/07| Meds-Risperdal 3mg iv,Deprenyl 10mg| Supps-Phenylalanine, minerals w/0.5mg Kelp,B-vit w/o folate
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sunflower
Member in Phase 2/3
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Posted: Fri Jun 1st, 2007 02:33 |
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dr marshall,
i decided to add my question to this thread, because if i understand correctly , resveratrol may have an effect similar to genistein on the VDR. i have been very interested in resveratrol for a few years, now, and decided to see what i could find in relationship to vitamin d. i quickly found a couple of abstracts: here and here.
if you have time, could you please explain what effect you think this substance has on the VDR ....if it suppresses innate immunity or stimulates it? i am curious and can't understand this stuff unless it's explained simply..................thanks so much......sun
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lyme,fibro,candida,allergies,gerd,osteopenia/ pain,fatigue,dizzy,memoryloss20+yrs/ celexa,vicodin,cal-mag/beni 40mg q6h 11-05/phase 3,8-06/1,25d=34 25d=36,18,17,10,13,5,7
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Natalia
Member in Phase 3
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Posted: Mon Jul 9th, 2007 11:38 |
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Dear Research Team
As a soy sauce lover I am concerned about my soy sauce consumption interfering with the MP. While I note the above comments about the fermentation process lowering the amount of genistein in soy products, I have come across some studies which have found that while the fermentation lowers the overall content of isoflavone (thus genistein), it appears to increase its bioavailability. The studies were carried out by measuring the isoflavone content of urine of subjects who had eaten either fermented and unfermented soy products. (References are listed below)
Could someone from the research team please have a look at this and advise on the appropriate amount of fermented soy that can be consumed? I would loath to give it up but am concerned at these findings.
Thanks
Natalia
Here are the references to the relevant articles that I came across (there are probably more):
Hutchins AM, Slavin JL, Lampe JW. (1995) ‘Urinary isoflavonoid phytoestrogen and lignan excretion after consumption of fermented and unfermented soy products.’ J Am Diet Assoc. 1995 May;95(5):545-51.
JL Slavin, SC Karr, AM Hutchins and JW Lampe, (1998) ‘Influence of soybean processing, habitual diet, and soy dose on urinary isoflavonoid excretion,’ American Journal of Clinical Nutrition, Vol 68, 1492S-1495S.
Last edited on Mon Jul 9th, 2007 11:46 by Natalia
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CFS 9.5 years| 4mg melatonin & 10mg Stilnox/night| 1-25D 6/06 51.25pg/ml, 7/07 29.6pg/ml| 25D Jun06 18ng/ml, Jun07 11.2ng/ml, Oct07 <8 ng/ml| Feb08 5ng/ml| Avoid light| NOIRs| 27Feb07 Ben q6h| Mino 12Mar07| Ph2 4Aug07|Ph3 24Sep08
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SophieDawson
Member in Phase 2/3
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Posted: Mon Jul 9th, 2007 15:03 |
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Natalia, I also like a bit of soy sauce here and there, in cooking and even on home made dim sims.
would someone be able to give us a "yes its fine in low ammounts" or "no, dont have it at all"
i am learning so much about food that its getting crazy. over the dinner table i can tell my husband whats in what food and why its good or bad while on the MP.
thanks,
Sophie
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CFS ricketsia FM 125D43 25D17 Ph1Mar07 NoIRs covered up low lux home lite exp r/t work Rivotril Lamictal Luvox hydralazine Ph2 Dec07
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Foundation Staff
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Posted: Mon Jul 9th, 2007 17:40 |
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Dr. Marshall has said that any problems with the genistein in soy products will be dose-dependent and amounts higher than 20 grams of roasted soybeans or 40mg of isoflavones, is likely to be a problem.
The Benicar blockade somewhat offsets genistein's effect on the immune system and as the body recovers during the MP, any potential problems will be reduced.
If you think your consumption of soy sauce, based on these figures and its supposedly higher bioavailability, leads to a high level of genestein then you should reduce your intake. This is a small price to pay to avoid jeopardizing your return to health.
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Natalia
Member in Phase 3
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Posted: Tue Jul 31st, 2007 14:39 |
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Megan,
As the effect of the genistein in soy sauce is dependent on both its concentration (which is different in soy sauce to soy beans) and its bioavailability (which appear to be greater than in soy beans), it is difficult for a lay person to hazard a guess as to how much soy sauce is 'safe' based on current data. Further information on concentration and bioavailability needs to be deduced in a lab to give a meaningful result.
If anyone on the research team returns to the question of soy sauce and genistein content in future, it would be great to obtain firmer figures on the question of how much soy sauce is 'safe' (as has been done for roasted soy beans)- as soy sauce is a common cooking ingredient. This would take the guess work out of eating soy sauce for many patients who are probably compromising their treatment because they think that fermented soy is 'safe' and are being too liberal with it. (Mind you I, for one, have cut back after this discussion).
Cheers
NataliaLast edited on Tue Jul 31st, 2007 14:44 by Natalia
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CFS 9.5 years| 4mg melatonin & 10mg Stilnox/night| 1-25D 6/06 51.25pg/ml, 7/07 29.6pg/ml| 25D Jun06 18ng/ml, Jun07 11.2ng/ml, Oct07 <8 ng/ml| Feb08 5ng/ml| Avoid light| NOIRs| 27Feb07 Ben q6h| Mino 12Mar07| Ph2 4Aug07|Ph3 24Sep08
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RxAngel
Health Professional
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Posted: Thu Aug 2nd, 2007 17:50 |
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Well, poopie.
I have just moved to Wichita, KS (more details, if interested, under my normal post, RxAngel), where there is a large population of Vietnamese, and have fallen in love with Pho, their noodle soup, and some of their other lighter dishes, and I have been craving this since I've been here, and much of it is soy based, and has tofu as an ingredient (I never thought I'd even consider tofu, being a beef-eating, venison-eating, good ole Texas gal).
I also discovered some time ago that Soy milk doesn't have Vitamin D, and I have found some cereals that aren't supplemented with Vit. D, so I have also been eating that, as well as graham crackers dipped in the milk (one of my favorite nighttime snacks that I had to give up b/c I couldn't find milk without Vit. D).
I have noticed that my irritable bowel is much better, and that my stomach doesn't bother me nearly as much when I eat these foods.
So, what's a girl to do? Stop eating the soy-based products, even though I am feeling much better intestinally?
Thanks for all of your research and hard work, even though I can't eat mushrooms, salmon, shrimp..........  .......I know, a small price to pay to rid the body of these creepy bugs floating around.
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Lyme|heart Effexor XR 75mg BID; Zanaflex 4mg QID prn; MS Contin 15mg BID; Corgard 20 hs (migr. prev); LoEstrin 1/20; Imitrex Nasal 20mg prn h/a|Started 01-6-06|Ph 2 7-06|Struggling w/Ph2
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Foundation Staff
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Posted: Thu Aug 2nd, 2007 20:14 |
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Are you sure your decrease in gastric symptoms is due to your new food preferences? Or is it because you have taken a break from the MP and immunopathology?
Soy products vary greatly. Those that are low in quality should be avoided completely. Higher quality products should be limited to 40mg of isoflavones a day to ensure your immune system is able to function properly.
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