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The Marshall Protocol Study Site > DR MARSHALL'S PERSPECTIVE > Dr Marshall's Perspective > Chlorogenic Acid in Coffee is powerful Immune modulator


Chlorogenic Acid in Coffee is powerful Immune modulator
 Moderated by: Dr Trevor Marshall  

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Joyful
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 Posted: Sat Jun 21st, 2008 00:51

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Hi wrotek,

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

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

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

Interesting.



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John McDonald
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 Posted: Sun Jun 22nd, 2008 18:14

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



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wrotek
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 Posted: Sat Jul 19th, 2008 21:08

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




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

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

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

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

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

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

Last edited on Sat Jul 19th, 2008 21:19 by wrotek



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Dr Trevor Marshall
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 Posted: Sat Jul 19th, 2008 21:19

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

wrotek
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 Posted: Mon Jul 21st, 2008 16:20

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

Last edited on Mon Jul 21st, 2008 16:21 by wrotek



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Russ
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 Posted: Tue Jul 22nd, 2008 09:30

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

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

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

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

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

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

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

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

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

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

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



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Dr Trevor Marshall
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 Posted: Tue Jul 22nd, 2008 10:11

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

Carricol
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 Posted: Wed Jul 23rd, 2008 00:14

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



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Dr Trevor Marshall
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 Posted: Wed Jul 23rd, 2008 01:14

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

Russ
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 Posted: Wed Jul 23rd, 2008 08:22

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



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wrotek
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 Posted: Thu Jul 24th, 2008 18:52

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

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






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wrotek
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 Posted: Wed Jul 30th, 2008 02:28

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

http://tinyurl.com/6ne2ev

Last edited on Wed Jul 30th, 2008 04:04 by wrotek



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wrotek
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 Posted: Fri Aug 15th, 2008 22:54

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This is very interesting I think

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




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

Last edited on Fri Aug 15th, 2008 23:15 by wrotek



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