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Dr Trevor Marshall Research Team

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Posted: Sun Oct 18th, 2009 02:26 |
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It is nice to see one's 'hypotheses' proven correct by others 
A study has just been published which shows that the amount of Vitamin D produced in the skin of people exposed to UVB radiation is not dependent on their skin pigmentation.
Further, those with low values of 25-D at the outset of the trial produced less 25-D from UVB radiation than those who were healthy at the outset.
http://www.nature.com/jid/journal/vaop/ncurrent/abs/jid2009323a.html
..Trevor..
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Jigsaw Health Professional

| Joined: | Fri Jul 14th, 2006 |
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Posted: Mon Oct 19th, 2009 01:28 |
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"The increase in 25(OH)D level after UVB exposure was negatively correlated with baseline 25(OH)D level (P<0.001) and positively correlated with baseline total cholesterol level (P=0.005)"
I think this means those with a lower 25OH)D level increased it more.
____________________ MP1.Arthritis30+yrs.3/98>3X50mgdoxy/wk.6/06 limitation.9/06:Noirs.11/06:25-D,15;1,25-D,29.4.20/07:25-D.7.
2/2/07:Beni40mg,Q6H.20/2:Mino25mg,Q2-3D.3/6:Beni40,Q8H.3/8Mino50Q2-3D.3/24Mino75Q2-3D.4/16Mino100Q2D.4/29,pH2.
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Dr Trevor Marshall Research Team

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Posted: Mon Oct 19th, 2009 03:07 |
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Oops - you win
I fell into the same trap as all the Vit D researchers fall into - we know the answer before we start 
Anyway, the fulltext is on its way via inter-library loan so that I can double-check 
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RobertTownsend Health Professional
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Posted: Sun Oct 25th, 2009 01:53 |
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Trevor
Is it not the precursor D3 which is synthesised in the skin, rather than the mono-hydroxy 25OH-D3 - which is largely synthesised elsewhere in the body from precursor D3.
Don't most of the previous studies suggest that the only thing skin pigmentation effects is the exposure time needed before D3 levels in the skin reach their saturation level ?
RobertT
____________________ CFS 4yrs,crippled knees;Oct05 Phase 1;Feb 06 Phase 2 ; Mar06 1,25D-61pMol/L 25D-23nMol/K;Jul06 Ph3 start ;July 08 dose tapering some abx,daytime fatigue much lower, skin still very light sensitive ;knee mobility very constrained with limited walking
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Dr Trevor Marshall Research Team

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Posted: Sun Oct 25th, 2009 08:16 |
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Ah, yes, the precursor step, from 7-dehydro-cholesterol to Vitamin D (mono-hydroxy 25OH-D3). Something about which I have not written a lot. But if you look at Figure 1 of my Bioessay, you can see that I show this step is shown as being catalyzed by "Energy - eg UVB"
http://TrevorMarshall.com/BioEssays-Feb08-Marshall-Preprint.pdf
The commonly accepted pragma is that this precursor is only synthesized in the keratinocytes of the skin under the influence of specific wavelengths in the UVB spectrum. I have been 'testing' this pragma this since these comprehensive papers written by Lehmann, et al, in 2001/2003:
UVB-induced conversion of 7-dehydrocholesterol to 1alpha,25-dihydroxyvitamin D3 in an in vitro human skin equivalent model
http://www.ncbi.nlm.nih.gov/pubmed/11710930
Demonstration of UVB-induced synthesis of 1 alpha,25-dihydroxyvitamin D3 (calcitriol) in human skin by microdialysis:
http://www.ncbi.nlm.nih.gov/pubmed/12709817
Recently, Lehmann wrote two good reviews which bring some of the early concepts up-to-date:
Role of the vitamin D3 pathway in healthy and diseased skin--facts, contradictions and hypotheses:
http://www.ncbi.nlm.nih.gov/pubmed/19146580
Wavelength-dependent induction of CYP24A1-mRNA after UVB-triggered calcitriol synthesis in cultured human keratinocytes:
http://www.ncbi.nlm.nih.gov/pubmed/16902422
The primary problem I have with the skin pragma is the lack of evidence supporting a keratinocyte-only role for the conversion of 7-dehydro-cholesterol, and also the paucity of good studies which have attempted to explore the pragma.
Like most of the pragma adopted surrounding the synthesis and actions of Vitamin D, I think this pragma (keratinocytes only) is incorrect. I look at the human body at the level of the proteins (and etc) within cells, not at the level of tissue. When I consider the level of activity within the cells, I find the concept that Vitamin D can only be formed in keratinocytes to be not at all convincing. IMO, the concentration gradient over the cell membranes is the factor that other researchers are failing to fully comprehend.
As support, I would first advance this study showing that UVB can induce Vitamin D in cells other than keratinocytes:
UVB-induced 1,25(OH)2D3 production and vitamin D activity in intestinal CaCo-2 cells and in THP-1 macrophages pretreated with a sterol Delta7-reductase inhibitor
http://www.ncbi.nlm.nih.gov/pubmed/16598763
But I find even more persuasive the anecdotal observation that nocturnal mammals do not need exposure to UVB to survive and flourish. Additionally, an elegant 1998 experiment with fish showed that neither exogenous Vitamin D nor UVB is necessary for fish to flourish. Indeed, it did not matter whether these fish were exposed to UVB, Vitamin D, or neither, - they lived identical lives in all cases:
"Vitamin D is not an essential nutrient for Rora (Labeo rohita) as a representative of freshwater fish"
http://www.ncbi.nlm.nih.gov/pubmed/9675700
I have advanced the hypothesis that the obvious, and probably accelerated, production of Vitamin D in the skin is a protective response to prevent damage to the skin produced by the UVB. I do not think it plays an essential role in human metabolism. I believe Homo sapiens functions perfectly well with enzymatic synthesis of Vitamin D in cells far away from the skin surface. This hypothesis would seem to be in line with the recent observation that the increased synthesis in keratinocytes correlates with apoptosis:
Lipidome of narrow-band ultraviolet B irradiated keratinocytes shows apoptotic hallmarks.
http://www.ncbi.nlm.nih.gov/pubmed/19845761
and is closely involved with the release of a key innate immunity cytokine:
Role for tumor necrosis factor-alpha in UVB-induced conversion of 7-dehydrocholesterol to 1alpha,25-dihydroxyvitamin D3 in cultured keratinocytes:
http://www.ncbi.nlm.nih.gov/pubmed/15225839
but more study is clearly needed. In the absence of such study I have rejected the pragma that UVB is necessary for normal Vitamin D metabolism in man. I suspect that more study will discover an enzyme which can provide the 'energy' for that stage of metabolic conversion. I have for 21 years myself lived without direct, conscious, exposure to daylight. A bone scan shows my own skeleton is right where it should be, regardless of the hideous disease I had to suffer during so many of those 21 years. Further I have seen no signs that an indoors lifestyle is harming anybody in our cohort (other than cabin sickness). So this is another pragma that I believe will fall, and along with it the concept that systemic "Vitamin D deficiency" is correlated in any way with skin pigmentation.
I hope that helps,
Trevor
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Perezt Foundation Director

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Posted: Mon Oct 26th, 2009 03:31 |
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Trevor,
What you have described makes allot of sense. Considering the importance of confirming the actual role of our skin in performing, or not, the conversion it amazes me that it has not been followed-up and done in humans. Then we can focus on the other alternatives.
Tom
____________________ Dx Sarcoid 1989 / Oct05 1,25-D=126 & 25-D=30; Began: MP Dec2405 / P2 Mar2206 / P3 May2106 / P4 Feb0108
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