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Dr Trevor Marshall
Research Team
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Posted: Sun Jan 28th, 2007 15:46 |
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I have been trying to find out what is the component in coffee which so clearly affects Th1 patients. Caffeine doesn't make the cut, as, although it has some effect on the Type 1 Nuclear Receptors, the affinity is low, and the observed symptomatic effects would require high concentrations of the drug, which are just not present in the diet of the average coffee drinker. Yesterday Wrotek suggested Chlorogenic Acid, and I have verified that he is correct. This is a culprit, and probably the major culprit. Here is an image of Chlorogenic acid (yellow backbone) as docked into the VDR, with the Xray structure of the docked 1,25-D for comparison. Note that the oxygens at the key helix 4 residues are effectively coincident.
Chlorogenic Acid forms hydrogen bonds with the same residues as 1,25-D; ARG274, SER237, SER278 and (weaker) TYR143. However, it does not have a 'tail' to stabilize the lower part of the VDR receptor, so at best it is a partial agonist, and is more probably a total antagonist of Type 1 Nuclear Receptor activity.
The affinity of Chlorogenic Acid for the VDR is consequently very high, with Ki calculating at 8 nanomolar. Assuming that this paper's concentration data are correct, and this one too, then just one cup of coffee contains several orders of magnitude more chlorogenic acid than would be needed to notice an profound effect on the VDR (and an effect the other Type 1 Nuclear Receptors, such as the Thyroid Receptors).
Here is a summary of the concentration issues, which looks to be (at first glance) fairly reliable:
http://www.cosic.org/coffee-and-health/antioxidants
So another mystery succumbs to the magic of molecular genomics. Thanks to all who helped...
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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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wrotek
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Posted: Sun Jan 28th, 2007 16:03 |
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Absolutely, no problems 
LOL, really ?
Chlorogenic acid is also present with higher quantities in apples.
Chlorogenic acid is marketed under the tradename Svetol® in Norway and the United Kingdom as a food additive used in coffee, chewing gum, and mints to promote weight reduction. from http://en.wikipedia.org/wiki/Chlorogenic_acidLast edited on Sun Jan 28th, 2007 17:27 by wrotek
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Lyme reflux chronic pain fatigue depression 125D36 Ph1Sep05 Ph2Oct06 Ph3Apr07 homebound in low lux NoIRs 25D<7 Oct06
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John McDonald
Member Advocate
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Posted: Sun Jan 28th, 2007 18:41 |
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| Damn! I enjoy about 3 or 4 cups per week. Looks like I will be switching to tea. Even so, I want to be perfectly healed so thank you Trevor. - John
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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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Dr Trevor Marshall
Research Team
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Posted: Sun Jan 28th, 2007 18:44 |
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Let me know if it makes your immunopathology more predictable, John
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wrotek
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Posted: Sun Jan 28th, 2007 19:03 |
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| Finally i have a strong motivation to quit drinking coffee, starting tomorrow I drink 1-2 cups a day but my coffees are espresso, dunno if espresso has less chloragenic acid but probably considering high amount of it there + high affinity, it won't matter.
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Lyme reflux chronic pain fatigue depression 125D36 Ph1Sep05 Ph2Oct06 Ph3Apr07 homebound in low lux NoIRs 25D<7 Oct06
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Dr Trevor Marshall
Research Team
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Posted: Sun Jan 28th, 2007 19:12 |
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Wrotek,
There is some Chlorogenic Acid in pears, too.
http://tinyurl.com/2slrbn
Not as much as in coffee, though. And the skin contains some neutralizing enzymes... Probably one or two fruit would not give problems. It does explain why I steadfastly stuck to one type of pear, Bosc pears, and avoided apples (including Asian pears) during all those dark years
Now I don't feel so bad about having come down with Scurvy in 1979 - and therein lies a moral to this tale - MP'ers need to eat their fresh pears and/or apples, to make sure they get enough Vitamin C and other nutrients... But in moderation, like all things... And try out different types and brands, too...
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Julia
Board Staff (on leave)
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Posted: Sun Jan 28th, 2007 20:03 |
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| Does this apply to decaff?????
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Always consult a physician.
Sarc/uveitis/hypercalcaemia/ankle osteoarthritis/eczema. MP May04. 25D June08:9.6. Life is good! Julia's story
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Reenie
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Posted: Sun Jan 28th, 2007 20:14 |
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Ok, so now do we have to quit coffee to heal all of the way? I drink about 2 cups every morning. What differences could/would I see if I quit? I mean, what would you suspect would change? more herx? less herx? different symptoms?
Trevor, thanks for all of your wonderful work... I think.  
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P.Bear R.N.
Research Team
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Posted: Sun Jan 28th, 2007 20:14 |
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It looks like black tea is out for the same reason as coffee:
http://www.ajcn.org/cgi/content/full/73/3/532
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Nothing contained in this site is or should be considered, or used as a substitute for, medical advice, diagnosis or treatment by your physician.
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migsies
Member in Phase 3
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Posted: Sun Jan 28th, 2007 20:20 |
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Dr. Marshall - you are breaking my heart! Couldn't you have left us in a state of blissful ignorance when it comes to the pit falls of consuming that much cherished cup-a-joe's? Stop your molecular modelling, before there is nothing left but water! Now, us coffee drinkers will have no choice but to start another support group!
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Sarcoidosis FM Lyme babesia 25D>7(Feb07) Ph1Aug05 Ph2Oct05 Ph3 Jun06 Valium Lyrica Ambien NoIRs limited outings covered Phase I 8/05, II 10/05, III 6/06.
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Reenie
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Posted: Sun Jan 28th, 2007 20:28 |
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When I decided it would be OK to add coffee back into my diet, I did a little research on coffee and the liver. Although the reasoning for avoiding coffee would be different here, is it really necessary to totally cut it out or is moderation the key here too?
P Bear,
Why wouldn't green tea be the same then as black tea? From what I understand, BOTH teas are actually the same plant although processed differently. So is it the process that changes the acid content? Or is it just that the study didn't include green tea? Last edited on Sun Jan 28th, 2007 20:32 by Reenie
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Dr Trevor Marshall
Research Team
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Posted: Sun Jan 28th, 2007 20:44 |
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Reenie asks:Ok, so now do we have to quit coffee to heal all of the way?
This is more about making sure that the immunopathology you feel really is immunopathology, and not your immune system being modulated by outside factors. Healing time or completeness is probably not going to be affected all that much.
Drug effect is dose dependent. If you drink a lot of coffee, or strong black tea, you should be on the lookout. Actually, everybody should be on the lookout, but you only need to change things if you get to the point where you can't manage your meds dosage because cause and effect of the abx dosing becomes too complicated. If so, then there is probably this additional factor present.
Julia, I am sure that if tea is not steeped for more than a few seconds, then fewer tannins, and I suspect other compounds too, will infuse into the brew. Green tea is typically steeped less than black tea, especially if you don't use a pot. The take-home message is don't use a pot, and dip the bags only until the taste is strong enough to be OK.
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P.Bear R.N.
Research Team
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Posted: Sun Jan 28th, 2007 20:46 |
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| I think green tea could be a problem too. No wonder the weak dip method came about. There was good reason. And here I am backsliding to stronger green tea. P.B.
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Nothing contained in this site is or should be considered, or used as a substitute for, medical advice, diagnosis or treatment by your physician.
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Dr Trevor Marshall
Research Team
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Posted: Sun Jan 28th, 2007 20:48 |
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Hey, PB, you should be healing pretty well by now. You need to worry less and less as time goes by, you know
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Julia
Board Staff (on leave)
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Posted: Sun Jan 28th, 2007 20:53 |
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Trevor, I was thinking about decaff coffee. If it isn't the caffeine that's the problem, than presumably decaff is bad too. But I only have one or two cups of very weak decaff a day... ppppleeease... 
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Always consult a physician.
Sarc/uveitis/hypercalcaemia/ankle osteoarthritis/eczema. MP May04. 25D June08:9.6. Life is good! Julia's story
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CelticLadee
inactive member
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Posted: Sun Jan 28th, 2007 20:53 |
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OH NO!  PLEASE don't tell me!
I have been celebrating the fact that after 20 years of refraining from drinking my beloved coffee because of bad side effects. (Even one cup gave me heart palpitations or skipping heart beats) I can finally drink it without problems.
I thought!
Isn't there a way to filter out that immunosuppressive chlorogenic acid you mentioned? We buy organic coffee and grind it ourselves using nice thick brown filters. Also is there a difference in coffee c. acid content depending on bean and process?
Another thought is that I have plenty of IP response with very little abx ramping. So why can't I continue to drink coffee? Please know I say this with all due respect. I just recently started drinking coffee again a couple months ago and I have not noticed less IP response.
I eat at least one apple everyday ... my favorite fruit. Glad you said in moderation that it is fine. Thankful for that anyway.
CL 
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FM Dx 9/2002| Pericarditis Dx 7/2002| CF migraines MCS IBS food sens <Shingles 2001| NoIRs/ZO 25% cream| MP8/04| PH2 1/05| PH3 7/06| 25D/1,25D: 27.9/63.9 (07/04) 25D: <4 (02/08)
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Dr Trevor Marshall
Research Team
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Posted: Sun Jan 28th, 2007 21:02 |
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CL,
As you heal on the MP, then the need to micromanage the control of your body becomes less important, and of course you can (and will) 'ease-up'. You have been healing on the MP long enough for your body to be able to take coffee, as you have found, without it being a problem for you. Drink it and enjoy...
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CelticLadee
inactive member
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Posted: Sun Jan 28th, 2007 21:19 |
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Awwwwww. Thank YOU for your reply! Those are such good words to hear. 
CL
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FM Dx 9/2002| Pericarditis Dx 7/2002| CF migraines MCS IBS food sens <Shingles 2001| NoIRs/ZO 25% cream| MP8/04| PH2 1/05| PH3 7/06| 25D/1,25D: 27.9/63.9 (07/04) 25D: <4 (02/08)
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Dr Trevor Marshall
Research Team
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Posted: Sun Jan 28th, 2007 21:36 |
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Err, EggplantChlorogenic acid, a type of phenolic, accounted for 96% to 63.4% of total phenolics in most eggplants
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=143006
It would be nice to look at the fulltext to see the actual quantities involved...
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Rico
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Posted: Sun Jan 28th, 2007 21:41 |
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| My wife drinks about 10 cups of regular tea daily (with soy milk) and not too strong. She feels horrible (pain mostly, but nausea and fatigue too) all the time. Should she consider reducing the amount she drinks? Last edited on Sun Jan 28th, 2007 21:51 by Rico
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No diagnosis/some symptoms; wife with Sarc on MP; Olm 40mg q6h| avoid D| 1,25D=63 25D=32 (May 2006) 1,25D=44; 25D=10(Dec 2006)PhaseI(May06) PhaseII(Aug06) PhaseIII(Aug07)
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