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Joyful
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Posted: Sat Jun 21st, 2008 04:51 |
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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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Lyme?1980 Lyme/Babs/Bart?05 CFS?06 | Start 125D(50) 25D(32) Jun07 | Ph1Jul07 ModPh2Sep07 Ph2Feb08 Ph3Aug08 | Latest 25D(9) Apr09 | ABC of MP
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John McDonald
Foundation Director
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Posted: Sun Jun 22nd, 2008 22:14 |
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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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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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wrotek
Member in Phase 3
| Joined: | Fri Dec 31st, 2004 |
| Location: | Wroclaw, Poland |
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Posted: Sun Jul 20th, 2008 01:08 |
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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 Sun Jul 20th, 2008 01:19 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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Dr Trevor Marshall
Research Team
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Posted: Sun Jul 20th, 2008 01:19 |
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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...
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wrotek
Member in Phase 3
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Posted: Mon Jul 21st, 2008 20:20 |
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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 20:21 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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Russ
Member in Phase 3
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Posted: Tue Jul 22nd, 2008 13:30 |
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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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Lyme, MCS | Phase 1: Jul '06 | Phase 2: Nov '06 | Phase 3: Jul '07 | 25D: 5 ng/ml (Oct '09)
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Dr Trevor Marshall
Research Team
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Posted: Tue Jul 22nd, 2008 14:11 |
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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.
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Carricol
Member in Phase 3
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Posted: Wed Jul 23rd, 2008 04:14 |
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| Are we talking about Vitamin A or its precursor Vitamin A?
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Sarcoidosis 1-25D 16, 21 Oct 08; Ph1 Nov07, Synthroid, 5-HTP, tyrosine, digestive enzymes, NOIRs lite exp r/t commute cover up, Ph2 Jan 08, Ph 3, 6 May 09, 25D 5, Jul 09
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Dr Trevor Marshall
Research Team
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Posted: Wed Jul 23rd, 2008 05:14 |
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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...
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Russ
Member in Phase 3
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Posted: Wed Jul 23rd, 2008 12:22 |
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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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Lyme, MCS | Phase 1: Jul '06 | Phase 2: Nov '06 | Phase 3: Jul '07 | 25D: 5 ng/ml (Oct '09)
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wrotek
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Posted: Thu Jul 24th, 2008 22:52 |
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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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Lyme reflux chronic pain fatigue depression 125D36 Ph1Sep05 Ph2Oct06 Ph3Apr07 homebound in low lux NoIRs 25D<7 Oct06
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wrotek
Member in Phase 3
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Posted: Wed Jul 30th, 2008 06:28 |
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Ability of decaffeinated instant coffee extract to block the effects of morphine
http://tinyurl.com/6ne2evLast edited on Wed Jul 30th, 2008 08:04 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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wrotek
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Posted: Sat Aug 16th, 2008 02:54 |
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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 Sat Aug 16th, 2008 03:15 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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wrotek
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Posted: Tue Oct 28th, 2008 03:42 |
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Since we use stevia as a sweetener, perhaps i should post this.
Chlorogenic Acid in Leaves and Lyophilized Extracts Of Stevia
http://www.springerlink.com/content/j2573u7341495341/
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Lyme reflux chronic pain fatigue depression 125D36 Ph1Sep05 Ph2Oct06 Ph3Apr07 homebound in low lux NoIRs 25D<7 Oct06
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Sunset
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Posted: Tue Oct 28th, 2008 04:10 |
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Wrotek wrote:
Since we use stevia as a sweetener, perhaps i should post this.
Note that Table 1 of this article lists residue after extraction of leaves of chlorogenic acid content as 3.4 grams of biomass per kilogram.
For the amount of stevia I use, I think I will stick with it as a sweetener vs. artificial sweeteners or sugar. It took me 2 years to use up the last bottle of stevia extract I bought and this was a small 25g bottle.
Sunset 
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FM, CFS, migr HA, low adrenal, RBC coinfection 11/07 1,25D70, 25D48, 7/08 25-D 21;11/08 25-D 22; 2/09 25-D 15.6; 7/09 25-D 11; 10/09 25-D 5ng/mL. olmesart 40mg+20mg SL, T4 37.5mcg QAM, T3 10-15mcg/d. NoIRs/limit lite exp
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Dr Trevor Marshall
Research Team
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Posted: Tue Oct 28th, 2008 06:29 |
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Sunset,
Chlorogenic acid is immunosuppressive in nano-molar concentrations (10**-9). There are lots of nanomoles in 3.4 grams. Why not try to interleave Stevia and Splenda? Three days of each, interleaved, should let you know in a few weeks whether Stevia really is innocuous. Frankly I don't know, one way or the other. I didn't like Stevia when I tried it
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Sunset
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Posted: Tue Oct 28th, 2008 08:00 |
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Honestly, I don't use stevia very often, maybe in one or two beverages a week. A serving size according to my bottle of stevia is 1/40 teaspoonful or 25mg. I rather like the taste, but do keep me posted if it turns out that stevia extract is not a recommended sweetener to use.
Thanks,
Sunset
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FM, CFS, migr HA, low adrenal, RBC coinfection 11/07 1,25D70, 25D48, 7/08 25-D 21;11/08 25-D 22; 2/09 25-D 15.6; 7/09 25-D 11; 10/09 25-D 5ng/mL. olmesart 40mg+20mg SL, T4 37.5mcg QAM, T3 10-15mcg/d. NoIRs/limit lite exp
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wrotek
Member in Phase 3
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Posted: Tue Oct 28th, 2008 16:33 |
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Stevia is not allowed for sell in Poland, perhaps due to sugar monopoly rather chemical composition, so i don't know much about it - is it a powder or lyophilized extract, how it is packaged etc.
 
Sunset, You are suggesting number 7. in the table is sold as a final product.
I thought this is what is left in the sample to be discarded, after final product extraction. And the only extraction is number 6. - lyophilization .
Chlorogenic acid contents can reach 8% in coffee beans, paper says.
From the photographs on google i see it is sold as a white powder or dried leaves.
Dry leaves (position nr 4 in the table) contain 116mg/Kg, which is 11.6% .
But if product is sold as a lyophilized extract, it will reach as much as 16.7% CGA concentration.
Perhaps the white powder product is not a big problem since it is further processed to contain stevioside mostly, and the rest ingredients, including chlorogenic acid, are removed.
Hmmm complex stuff, all depends from the plant processing.
It is even more interesting if one uses stevia for coffee, adding more chlorogenic acid to the coffee chlorogenic acid content.
The paper also says "of 204 randomly selected plant species, chlorogenic acid was found in almost 90" Unfortunately the paper is incomplete, and i would like to see this plant list.
Last edited on Tue Oct 28th, 2008 16:47 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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Dr Trevor Marshall
Research Team
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Posted: Tue Oct 28th, 2008 16:49 |
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Sunset, once or twice a week is usually fine, as the body tends to excrete most things in a 24 hour cycle. I tend to worry when folk have to eat stuff daily, and especially multiple times a day
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eClaire
Member in Phase 2
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Posted: Tue Oct 28th, 2008 19:24 |
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Stevia...Just when you think it is safe to go into the water....
Trevor, if I can't use any of the artificial sweetners (which I still can't, including splenda), and only use stevia on occassion, is a teaspoon of sugar here and there (for a real cuppa tea w/half and half...when I'd prefer 2% milk) going to do much harm? (Once or twice a week...right now, I do that about every two weeks as it is a real comfort to me, but winter is coming on and this is going to be a cold one and there's nothing like a cup of tea in winter...I could reduce it to 1/2 teaspoon and get used to it.) I can't even handle the sweetner in the chocolate that is recommended and so have to dole out wee bits of Lendt when I feel desperate for chocolate.
Thanks, Claire
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34mo on MP; CFS FMS MCS COPD hypermob. IBS/GERD osteopor.; 125D48 25D<4;
NoIRs during most daylight outings & covered up; home w/o NoIRs
Ph1.Dec06 * ModPh2.Jun07 * AbxBrk.Mar-May08 * Ph2.Oct-Nov08 * Ph1.Jan2009
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