Talk:Vitamin D/Archive 6

Objections to DocJames' edits
Health effects section
 * 1) "The effects of vitamin D on health is uncertain.[3]" Well presumbly our bodies synthesize 'vitamin' D for good reason, you are talking about vitamin D supplemental to the body's synthesis here. What the ref says "The majority of the findings concerning vitamin D, calcium, or a combination of both nutrients on the different health outcomes were inconsistent. Synthesizing a dose-response relation between intake of either vitamin D, calcium, or both nutrients and health outcomes in this heterogeneous body of literature proved challenging." there is a diference between uncertain and inconsistent. Uncertain suggests that we don't know enough to say, but in fact there has been a exaustive report from the IoM out on the subject They  said there is no evidence that supplemental vitamin D has a positive effect on non-bone health outcomes. Since then, iethe IoM report, it is not uncertain.
 * Yes I am happy to add "supplementation" -- Doc James (talk · contribs · email) 06:55, 22 November 2011 (UTC)


 * 1) It doesn't mention the IoM report first to give the IoM report proper weight.No sooner have the IoM report's conclusions been given we read that some researchers think they are wrong. That implies that the IoM panel are on an equality of authoritativeness with their detractors. That is very misleading as to the balance of scientific opinion. In my edit the IOM report was given proper weight relative to its detractors.
 * Per WP:MEDRS we should give weight to both the IoM and other reviews. The IoM is quoted in the second sentence of health effects.-- Doc James (talk · contribs · email) 06:55, 22 November 2011 (UTC)


 * 1) "Low blood levels of vitamin D are associated with increased mortality.[39]" Observational study - derived right? So what if the IoM says suplementation has no effect on bone health outcomes. Not giving the best source proper weight again. "Supplemental vitamin D3 appears to decrease all cause mortality, with the best evidence of a benefit in elderly women.[7" What the source says "seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care." I really don't know how you got  "Supplemental vitamin D3 appears to decrease all cause mortality" from that very restricted and qualified (seems) finding.
 * The Cochrane review states "Overall, vitamin D decreased mortality (RR 0.97, 95% confidence interval (CI) 0.94 to 1.00, I(2) = 0%). When the different forms of vitamin D were assessed separately, only vitamin D(3) decreased mortality significantly (RR 0.94, 95% CI 0.91 to 0.98, I(2) = 0%; 74,789 participants, 32 trials) whereas vitamin D(2), alfacalcidol, or calcitriol did not." Thus where I got the text. -- Doc James (talk · contribs · email) 06:55, 22 November 2011 (UTC)


 * 1) "Low vitamin D levels are associated with some cancers" Observational study again. people are going to take that as meaning something other that what the most reliable scientific authorities (IoM panel) think it means. It sounds like tacit advice to supplement.
 * We immediately state following this "When supplementation is used to treat people with prostate cancer, however, there does not appear to be a benefit" thus I do not see the problem. Doc James (talk · contribs · email) 06:59, 22 November 2011 (UTC)


 * 1) "Vitamin D appears to have a protective effect against multiple sclerosis.[54][55][56]" The IoM did the biggest and best review of all the evidence on this issue and found no such thing, they didn't say that. You can't say that in WP's voice. Overagainst (talk) 19:05, 21 November 2011 (UTC)
 * These are review articles that are quoted. Do you have a quote from the IoM report that directly addresses MS? -- Doc James  (talk · contribs · email) 06:55, 22 November 2011 (UTC)
 * From the top, Health effects- instead of citing the IoM report you cite first a major study that that was  source which the IoM panel drew on for that report. You alter the wording slightly, but in my opinion, significantly with the use of "uncertain". there is no need for it just quote the best source.  My objection is to the use of the word "uncertain". The article now says " . The first text in red should not be in the article, the second part text in red should  be further down in a subsection called "dissenting opinions". The green text should be replaced with the following  That says it all, it has an impecable ref and there is no problem quoting as long as it is correctly attributed.


 * "Per WP:MEDRS we should give weight to both the IoM and other reviews" WP:MEDRS policy on the IoM relative to review articles can be interpreted that way but there are issues with the wording of WP:MEDRS it is currently under discussion.


 * Mortality ""."Low blood levels of vitamin D are associated with increased mortality}}". That could be the cause of people being ill or as a result of people being ill. It's pretty clear to me that you think it's the cause because the next thig we are told ." - Cochrane review author uses the following wording "Vitamin D in the form of vitamin D seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care." Seems is very much a qualifying word here and it's only a small, mainly insitutionalized subset of the population that seems to have any effect. ." is yet another paraphase making a stronger statment than is justified by the source. And it is preceeded by "". I think I detect the cloven hoof of synthesis!


 * Why is the IoM report data not given here- "large-scale pooled analysis (n = 2,285) found a statistically significant two-fold increased risk for pancreatic cancer in participants with serum 25OHD levels at or above 100 nmol/L compared with those with levels between 50 to 75 nmol" Dietary Reference Intakes for Calcium and Vitamin D (2011) p.436 100 nmol/L = 40ng/ml. Some soi-disant experts call anything below 40ng/ml 'low blood levels'. Overagainst (talk) 11:42, 22 November 2011 (UTC)
 * A quote on MS from the IoM report ?  They looked at the evidence Dietary Reference Intakes for Calcium and Vitamin D By Institute of Medicine P337 but it just doesn't stand up Institute of Medicine, Committee to Review Dietary Reference Intakes for Vitamin D P173. Overagainst (talk) 12:25, 22 November 2011 (UTC)
 * I think "could not be linked reliably with calcium or vitamin D intake and were often conflicting" can be summarized as "the health effects are uncertain" Doc James  (talk · contribs · email) 12:54, 22 November 2011 (UTC)
 * I think "could not be linked reliably with calcium or vitamin D intake and were often conflicting" can be summarized as "the health effects are uncertain" Doc James  (talk · contribs · email) 12:54, 22 November 2011 (UTC)

resource Science News News in Brief: Highlights from the Society for Neuroscience Annual Meeting
Vitamin D is good for aging brain by  Tina Hesman Saey December 3rd, 2011; Vol.180 #12 (p. 8) ...

99.190.86.16 (talk) 06:45, 26 November 2011 (UTC)


 * Per WP:MEDRS we use review articles for medical content. Especially when the topic is controversial such as this one. Thks -- Doc James (talk · contribs · email) 06:56, 26 November 2011 (UTC)

Inconsistent naming of 25(OH)D
I'm not sure which form is correct, but when reading the article 25(OH)D is, if I've understood correctly, referred to as "25(OH)D", "25OHD", "25-OH vitamin D", "25-hydroxyvitamin D", "25-hydroxy-vitamin D", "25-hydroxycholecalciferol" and "calcidiol". I understand that some are abbreviations and I think it makes sense to standardise on one abbreviation and one long form accross the article to make it easier to search for references to it. This could be possibly be complimented with a section listing the different names? Nickpeirson (talk) 11:16, 29 November 2011 (UTC)

Article wrongly suggests that Calcitriol is the only biologically active form of vitamin D
It is well known that calcidiol is also needed for calcitriol to work properly, see these articles:

http://www.wadeandersonpt.com/vitamind/articles/diagnosis-vitdd.pdf

"How can it be that a patient with normal or even high circulating levels of the active form of vitamin D is somehow vitamin D deficient? The most straightforward answer is that the endocrine and autocrine functions of vitamin D are quite different. However, that is too simple an explanation as serum 1,25(OH)2D is plainly delivered to the cells via the systemic circulation. A few points may help resolve the apparent paradox. First, patients with osteomalacia absorb calcium very poorly, despite their usually normal serum level of 1,25(OH)2D. For unclear reasons, 25(OH)D must also be present in the serum if the intestinal mucosal response to 1,25(OH)2D is to occur. Second, in many of the animal models or cell culture systems the concentration of 1,25(OH)2D needed to produce a particular effect is higher than can be achieved at physiological serum concentrations of 1,25(OH)2D. Apparently, the required higher concentration of 1,25(OH)2D must be produced intracellularly, in an autocrine manner, using circulating 25(OH)D as the substrate."

http://cjasn.asnjournals.org/content/3/5/1535.full

"The inadequacy of calcitriol as a substitute for vitamin D itself is further emphasized by three lines of evidence indicating that even the canonical function of vitamin D (facilitation of calcium absorption) cannot be achieved by calcitriol alone. (1) Without doubt, calcitriol is the principal regulator of calcium absorption in typical adults, but it has been recognized for many years that those with frank vitamin D deficiency (e.g., adults with osteomalacia) exhibit calcium malabsorption, despite frequently normal to high-normal levels of circulating calcitriol. This defect is corrected not by giving more calcitriol but by raising serum levels of 25(OH)D. (2) Furthermore, 25(OH)D, administered as such, has been shown to elevate calcium absorption efficiency in typical adults, and it does so without elevating serum calcitriol levels (7). (3) Despite high parenteral dosages of calcitriol (e.g., 2 μg intravenously three times per week), calcium absorption efficiency remains severely depressed in patients who have ESRD and are on renal dialysis (R. Lund, personal communication). A working conclusion is that the optimal regulation of calcium absorption requires both molecules [25(OH)D and calcitriol]. How 25(OH)D is functioning in this setting is unclear, but it may be through binding to membrane vitamin D receptors (8) that, in turn, open calcium channels in the enterocyte and thereby facilitate the transfer of calcium across the cell. "

Count Iblis (talk) 01:13, 20 December 2011 (UTC)

US RDA
Is there a particular reason why there is a discussion of the upper limit by the IOM, but no actual table of the RDA from the IOM report? That would seem to be vital encyclopedic material...Yobol (talk) 20:35, 29 December 2011 (UTC)

Rigorous proof of link between vitamin D and MS
See here:

"A rare genetic variant causing lower levels of vitamin D has been linked to multiple sclerosis (MS), according to scientists.

Mutations in the gene, CYP27B1, were identified by sequencing the genomes of 43 people from families where four or more members had MS. The team then examined the gene in 3,000 families of unaffected parents who had a child with MS. They discovered that all of the 35 parents who had one mutated copy of the gene had passed this variation onto their children.

'If inheriting the CYP27B1 gene variant was unrelated to MS, there would be a 50/50 chance of the child inheriting the variant from their parent', explained senior author Professor George Ebers from the University of Oxford. 'All 35 children inheriting the variant is like flipping a coin 35 times and getting 35 heads, entailing odds of 32 billion to one against'. "

Count Iblis (talk) 23:08, 12 December 2011 (UTC)
 * Please provide review articles not popular press pieces per WP:MEDRS Doc James  (talk · contribs · email) 05:27, 13 December 2011 (UTC)


 * That may take a year or longer. Count Iblis (talk) 01:02, 20 December 2011 (UTC)
 * Here is the original citation and conclusion  http://onlinelibrary.wiley.com/doi/10.1002/ana.22678/abstract
 * A causative role for CYP27B1 in MS is supported; the mutations identified are known to alter function having been shown in vivo to result in rickets when 2 copies are present. CYP27B1 encodes the vitamin D-activating 1-alpha hydroxylase enzyme, and thus a role for vitamin D in MS pathogenesis is strongly implicated. ANN NEUROL 2011;70:881–886
 * Does "strongly implicated" = "rigorous proof" ?  Tachyon 02:38, 23 January 2012 (UTC)  — Preceding unsigned comment added by Janopus (talk • contribs)

Allowable health claims
Apart from the above discussion on health effects or scientific evidence for lowering disease risk, governmental regulatory agencies stipulate for the food industry health claims allowable as statements on packaging. I believe we should have a summary by country of this information. Beginning a draft below with request for assistance on agencies outside the USA and Europe: --Zefr (talk) 19:13, 2 January 2012 (UTC)

EFSA
 * normal function of the immune system
 * normal inflammatory response
 * normal muscle function
 * reduced risk of falling in people over age 60

FDA
 * may reduce the risk of osteoporosis

Health Canada
 * adequate calcium and regular exercise may help to achieve strong bones in children and adolescents and may reduce the risk of osteoporosis in older adults. An adequate intake of vitamin D is also necessary

Other possible agencies with claim guidance: Japan FOSHU and Australia-New Zealand
 * Under the recommendations section may be? Doc James  (talk · contribs · email) 19:16, 2 January 2012 (UTC)

Vitamin D and cancer: a review of molecular mechanisms
http://www.ncbi.nlm.nih.gov/pubmed/22168439

"Fleet JC, Desmet M, Johnson R, Li Y.

Purdue University Interdisciplinary Life Sciences Program, Purdue University, West Lafayette, IN 47907-2059, U.S.A.

Abstract

The population-based association between low vitamin D status and increased cancer risk can be inconsistent, but it is now generally accepted. These relationships link low serum 25OHD (25-hydroxyvitamin D) levels to cancer, whereas cell-based studies show that the metabolite 1,25(OH)2D (1,25-dihydroxyvitamin D) is a biologically active metabolite that works through vitamin D receptor to regulate gene transcription. In the present review we discuss the literature relevant to the molecular events that may account for the beneficial impact of vitamin D on cancer prevention or treatment. These data show that although vitamin D-induced growth arrest and apoptosis of tumour cells or their non-neoplastic progenitors are plausible mechanisms, other chemoprotective mechanisms are also worthy of consideration. These alternative mechanisms include enhancing DNA repair, antioxidant protection and immunomodulation. In addition, other cell targets, such as the stromal cells, endothelial cells and cells of the immune system, may be regulated by 1,25(OH)2D and contribute to vitamin D-mediated cancer prevention."

Count Iblis (talk) 22:59, 20 January 2012 (UTC)
 * We already basically say as much. Doc James (talk · contribs · email) 23:09, 20 January 2012 (UTC)


 * Yes, but I haven't read the whole article yet (I don't have acces from my present location). There may be interesting details in the article that can be included in this Wiki-article. Count Iblis (talk) 00:35, 21 January 2012 (UTC)

Sleep
Is there any known connection of vitamin D with sleep? I did what I could to look through the literature (http://www.gwern.net/Zeo#background) but didn't turn up anything, despite my own little double-blind randomized placebo-controlled trial turning up a noticeable negative effect on my sleep. Maybe I missed something? --Gwern (contribs) 20:58 14 February 2012 (GMT)


 * There probably is, but there are no reliable sources yet that report on rigorous research results. My own experience is that it does have an influence on sleep; since I started to take 5,000 IU/day some years ago I need more sleep, and since I increased the dose to 10,000 IU/day about two years ago, I need even more sleep, about 9 hours per day. Before I started to use high dose vitamin D, I could sleep 7 hours and wake up feeling well rested, but now I would feel sleepy. I think what has happened is that my body is now geared to maintain a higher fitness level. As we grow older, the body gives up on maintaining itself at a top fitness level and then you can get by with less sleep. Vitamin D activates a large number of processes that are involved in maintaing the body at top fitness level and the price for that is that you need more sleep.


 * My fitness levels have dramatically increased since I started om use vitamin D, I now exercise even more than I did when I was 20 years old, my resting heart rate has dropped to below 40 bpm. This is consistent with the observations in this paper. We all know that top athletes need a lot more sleep than average. Also, we all know that people who get by with 5 or 6 hours of sleep per day tend to be obese couch potatoes.


 * There is also a not well understood trend in the average time people spend sleeping. In the 19th century, people used to sleep for more than 8 hours on average, but in the US today the average is 6.5 hours. Of course, we know why people are sleep deprived today, but what is not well understood is how people could sleep more than 8 hours day after day more than a century ago. It could be that higher vitamin D levels (partially) explains this. Count Iblis (talk) 00:26, 15 February 2012 (UTC)

Organization
I feel strongly that this articles should be arranged as laid out at WikiProject_Pharmacology/Style_guide and that the content with respect to supplementation and dietary ingestion should be kept in the same subheading. Doc James (talk · contribs · email) 07:23, 26 February 2012 (UTC)
 * Thanks for opening the discussion!  This is actually something I view, also strongly, as a widespread problem on Wikipedia.


 * Here is the issue: dietary supplements are not medications.  You are a doctor.  You know this.  I know this.   But in the US especially, the line is increasingly blurred by the aggressive marketing of dietary supplement makers to make health claims about their products, and more and more Americans are using them in the search for wellness, (See for example, this report: http://www.npr.org/2011/10/17/141411363/americans-urged-to-reconsider-use-of-dietary-supplements), even though there is little serious clinical evidence that taking dietary supplements as "medicine" does anything.  (There is of course the placebo effect, and there are anecdotes, and there are the results of in vitro studies, and there are the reports from small, underpowered clinical studies.)  There are a few exceptions, like the use of zinc to prevent and ameliorate colds, the GSK fish oil story, and perhaps glucosamine for arthritis (in Europe it is accepted and used as a drug; in the US it is sold as dietary supplement).   Every large clinical trial the NIH has run to show a non-Vitamin-like benefit for a dietary supplement has failed -- in one case (Vitamin E)  the evidence is accumulating that taking it may actually be harmful (there was great preclinical evidence that taking Vitamin E, an antioxidant, would decrease the risk of getting cancer, but bizarrely it turns out to increase the risk (see results of the SELECT trials)).


 * The FDA constantly battles to hold the line.  They do allow certain "qualified health claims" (http://www.fda.gov/Food/LabelingNutrition/LabelClaims/QualifiedHealthClaims/ucm073992.htm) and see here for their effort to provide clear guidance about other health claims: http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/FoodLabelingNutrition/FoodLabelingGuide/ucm064919.htm.


 * Wikipedia is go-to resource for many people when they start looking for information - use of dietary supplements included.  I think Wikipedia does users a dramatic mis-service to the extent that it also blurs the line between drugs and dietary supplements.


 * Wikipedia articles for dietary supplements should therefore make a very bright line distinction between what is known (e.g vitamin deficiency absolutely causes certain diseases (e.g. lack of Vitamin C causes scurvy) versus what is speculative or under research (e.g. a potential role of vitamin D in MS). The line needs to be even more carefully kept for dietary supplements that are not vitamins.    Maybe we need a new template for dietary supplements?   But from my point of view I cannot see how the pharmacology template is appropriate.


 * This is why I reorganized the article to divide classic vitamin roles for Vitamin D, vs research, and why I asked for discussion when you reverted those changes.


 * Thanks again for opening the discussion!Jytdog (talk) 15:23, 26 February 2012 (UTC)
 * I disagree that there is a substantive difference between vitamins and pharmaceuticals. We have pharmaceuticals that cause more harm than benefit to (activated protein C). We have medications that do not require a prescription (ibuprofen). Both pharmaceuticals and vitamins need the same level of evidence before being recommended by the medical community. Zinc BTW is a mineral not a vitamin and glucosamin is neither a vitamin nor a mineral. I do agree that issues on breaking research should go at the end per WP:PHARMMOS. The balance here is difficult as there is a fair bit of research on vit D. Doc James (talk · contribs · email) 07:50, 3 March 2012 (UTC)
 * I am sorry, I thought you knew more than you did.  This sentence is not true:  "Both pharmaceuticals and vitamins need the same level of evidence before being recommended by the medical community."   If a company wants to market a drug to treat a disease or condition, it must get approval from regulatory authorities to do that -- they have to show that they can manufacture the drug safely and consistently, and the drug, when used at the dose recommended and for the recommended indication, is both safe and effective.  That is a high regulatory bar.   For dietary supplements, there are limits to what you can say (you cannot say it treats a disease or condition, but you can say it supports the structure or function of the body) and it is  assumed that your manfacturing is good - you don't have to prove this ahead of time. A much lower bar.  Dramatically different regulatory regimes, dramatically different uses.  The FDA explains clearly, here: http://www.fda.gov/food/dietarysupplements/default.htm


 * The big picture though -- vitamins and other essential minerals are part of a diet you need to eat in order not get sick. Taking them separately in order to meet the minimum requirements, makes them "dietary supplements"  That is what they are and limits how they can be legally marketed.   Drugs are developed to treat a disease.  A whole different thing.  Sure some drugs are sold OTC but those are drugs that have been used long enough and have a broad enough safety profile that they do not need to be prescribed. They are still drugs. Heck flouride in toothpaste is a drug that allows the toothpaste to be marketed as "preventing cavities," - a medical claim.


 * For both dietary supplements and drugs, there is always a lot of research going on, about other actitivies a compund might have.  I think we agree that all this speculative stuff needs to cordoned off from what is known -- what people can rely on.   I had a big tussle with a guy on the Human growth hormone page who kept wanting to make big claims about what hGH does, based on just a  few under-powered studies.   But that is just sloppy and provides information that while it could provide hope (or feer) but should not acted on without a doctor's care..Jytdog (talk) 17:43, 3 March 2012 (UTC)

It seems there is a little confusion. I am not discussing the regulatory system of the United States surrounding pharmaceuticals and alternative medicine products. I am discussing Wikipedia Medicine's policies surrounding what degree of evidence is required for health claims per WP:MEDRS. The quality of sources required here on Wikipedia for health claims for vitamins is the same as that for pharmaceuticals. So let me clarify "Both pharmaceuticals and vitamins need the same level of evidence before being "discussed" by the medical community here on Wikipedia". Doc James (talk · contribs · email) 11:34, 4 March 2012 (UTC)
 * But I guess your proposal is: should we divide the more well known conclusions regarding vitamin D from the less well known conclusions under different headings. I propose we put the best supported conclusions first and do not support the split. As long as all references are to recent review articles I think the evidence can speak for it self and does not need sub dividing. You are free to propose a RfC to get others opinion though.-- Doc James (talk · contribs · email) 11:43, 4 March 2012 (UTC)


 * Thanks, I read some about the regulatory context in Canada -- so people can make all kinds of efficacy claims about dietary supplements there with no evidence.... but there is strict GMP.  That's wild.  And I see why things look different to you.   THis does make things complicated.    I appreciate that your willingness to compromise by putting best supported conclusions first.     I really struggle with putting well accepted knowledge on par with speculation not backed up by randomized trials and feel that putting them on par does wiki readers a disservice - people are in general not medically sophisticated and overwhelmed by all the claims out there.    Broadly speaking, I would have a line  be, "supported by adequately powered randomized clinical trial" versus everything else.  I realize this causes some confusion for older medications like aspirin or even something like vitamin D but hopefully rational editor could sort that.  Before I request comments, could you clarify why you would not support such line-drawing?  Thanks.  Jytdog (talk) 19:06, 4 March 2012 (UTC)
 * We are not putting well confirmed knowledge on par with less confirmed knowledge. We state "Beyond its use to prevent osteomalacia or rickets, the evidence for other health effects of vitamin D supplementation in the general population is inconsistent.[3][4] The best evidence of benefit is for bone health[5] and a decrease in mortality in elderly women.[6]" in the lead. And thus give little prominence to other effects. When we discuss cancer we state "Low vitamin D levels are associated with some cancers. When supplementation is used to treat people with prostate cancer, however, there does not appear to be a benefit.[21] Results for a protective or harmful effect of vitamin D supplementation in other types of cancer are inconclusive.[4]" and I am sure our readers can figure out what this means. They will be reading more than just our headings. Feel free to request broader input. I feel strongly that whatever we do we need consistency across articles on similar topics per WP:MEDMOS -- Doc James (talk · contribs · email) 07:15, 11 March 2012 (UTC)
 * OK, you are right, we can leave it as is. Thanks for the discussion!Jytdog (talk) 17:23, 11 March 2012 (UTC)

Section on sources needed
I came to this article expecting to find something on dietary sources of Vitamin D, but this topic is not in the article. Other nutrients have articles in Wikipedia which do mention dietary sources, so this article could be improved considerably if this were added. ACEOREVIVED (talk) 00:20, 9 March 2012 (UTC)
 * Have at it! :) Jytdog (talk) 03:28, 9 March 2012 (UTC)

Did you mean "Have another look at it?" I missed the section called "Dietary sources" before - sorry! - but I still think that this could be enlarged. 16:03, 13 March 2012 (UTC)ACEOREVIVED (talk) 16:03, 13 March 2012 (UTC)
 * I think he means feel free to add this content. -- Doc James (talk · contribs · email) 13:09, 14 March 2012 (UTC)

MS and causal interpretation of observational studies
Article currently says "Vitamin D appears to have a protective effect against multiple sclerosis." Ascherio who 'appears' to be the main source for that statement (ref 22) has a more recent paper -Mult Scler. 2011 Dec; Prevention and treatment of MS: studying the effects of vitamin D. He says "Observational studies suggest that adequate vitamin D nutrition may reduce the risk of MS and affect the course of the disease. Inherent limitations in these studies, however, preclude a causal interpretation". What article says about MS is not fully supportd by the ref. Still less by Ascherio's latest paper. I don't think there is the scientific backing to say "Vitamin D appears to have a protective effect against multiple sclerosis." The scientific consensus, as represented by the IoM is that the evidence has failed to stand up under scutiny. It should properly be presented as an opinion from a certain school of thought and not as the overwhelming scientific consensus. Overagainst (talk) 16:41, 17 March 2012 (UTC)
 * Due to a flood of new results on this topic, the IoM report is now completely useless except as a reference work for the older literature. Not only has it now been proven using independent methods that vitamin D does play a role in MS, but also a lot of progress has now been made to understand the precise mechanism that leads to vitamin D having a protective effect. Count Iblis (talk) 00:14, 18 March 2012 (UTC)
 * Could you please provide the secondary source that supports this statement. Thanks Doc James  (talk · contribs · email) 00:58, 18 March 2012 (UTC)


 * I think that's irrelevant. It is quite clear to me that his whole issue of secondary and tertiary sources is being gamed by particularly Overagainst here to the point that makes thoughtful discussions about the content, impossible. Count Iblis (talk) 15:14, 19 March 2012 (UTC)

Safety concerns
It really will not do to have the article baldly stating in Wikipedia's vioce that "Based on the non-observation of toxicity at daily intakes of up to 50,000 IU per day, leading to calcidiol levels of more than 600 nmol/L, and the similar effect of supplementation and whole body exposure to one erythemal dose, it is believed that 250 micrograms/day (10,000 IU) in healthy adults are safe and can thus be adopted as the tolerable upper limit.[79]" The ref for this is wholly inadequate. A souce widely considered authoritative on medical matters, ie the Institute of Medicine, were commissioned by the US and Canadian governments to examine the data. A team of leading experts reported that:  Dietary Reference Intakes for Calcium and Vitamin D (2011) p481 These conclusions of the IoM should be quoted in the article. The text insouciantly claiming that "it is believed that 250 micrograms/day (10,000 IU) in healthy adults are safe" should be removed. Overagainst (talk) 17:59, 17 March 2012 (UTC)


 * "Emerging" is an euphemism for "there is no evidence for it, but we still want to mention it". It has been more than a year since that IoM report was published, and nothing of substance has emerged since that time about harmful effects of taking low doses (less than 10,000 IU/day) of vitamin D. But what has emerged since the IoM report appeared, is a flood of evidence for positive health effects on issues other than bone health. Count Iblis (talk) 00:06, 18 March 2012 (UTC)
 * This is about safety concerns, as no further source has been forthcoming I must conclude that the sole ref for the statement I am objecting to is Hathcock JN, Shao A, Vieth R, Heaney R (January 2007). "Risk assessment for vitamin D". The American Journal of Clinical Nutrition 85 (1): 6–18. . http://www.ajcn.org/content/85/1/6.full.pdf. It is an inadequate reference for text that verges on medical advice. The offending statement has to go. Overagainst (talk) 14:52, 19 March 2012 (UTC)
 * But that's a review article based on loads of evidence, there are many other review articles that make similar statements. Count Iblis (talk) 15:03, 19 March 2012 (UTC)
 * Cite me a study of people who took that amount.Overagainst (talk) 15:19, 19 March 2012 (UTC)


 * That article by Vieth et al. cites many. The IoM did something completely different than what other review articles on this issue do. They pointed out that one cannot rule out based on trials only that doses below 10,000 IU/day contribute to adverse health effects, because in some trials some hints of this was seen (but I think this wasn't even statistically significant). So, they didn't play their role as a tertiary source, they even went beyond what secondary sources do. They actually nmade an original argument about this issue, so on this point the IoM should be regarded as a primary source. Count Iblis (talk) 15:41, 19 March 2012 (UTC)


 * The IoM report on the study, by Heaney(2003). Here "As suggested by the study, vitamin D intakes of 5,000 IU/day achieved serum 25OHD levels that range between 100 and 150 nmol/L, but do not surpass 150 nmol/L after 160 days of administration. Almost no other studies have assessed the safety of long-term maintenance of serum 25OHD levels in this range in relation to chronic disease risk and all-cause mortality, so the information about the increases in serum levels is useful for the purposes of establishing a UL. Given the uncertainties surrounding the data and the reliance on a single report, the UL is set 20 percent below the level identified by Heaney et al. (i.e., 5,000 IU), specifically at 4,000 IU/day."


 * Heaney (2003) gave 5000IU for 20 weeks. Not 10,000 IU a day for years. Overagainst (talk) 16:58, 19 March 2012 (UTC)


 * Count Iblis, would you like to tell us how much vitamin D you take each day? Overagainst (talk) 17:04, 19 March 2012 (UTC)


 * The Hadzabe and Maasai have an average calcidiol level of 115 nmol/l, probably for the last 200,000 years. It is also well known that breast milk of mothers does contain enough vitamin D for the baby, provided the mother takes at least 5000 IU/day. A Hadzabe baby therefore doesn't need to use vitamin D supplements.


 * Not only does the IoM recommend low calcidiol levels of 50 nmol/l, it also accepts as biologically normal that breast milk of mothers who have that calcidiol level, doesn't contain enough vitamin D for the baby, and that babies must therefore be given vitamin D supplements. But, of course, vitamin D supplements were not availiable to our recent ancestors, therefore, according to the IoM, human biology regarding vitamin D is fundamentally flawed. The fix happens to be to live according to a Western lifestyle, which involves staying indoors during office hours. What a coincidence! Count Iblis (talk) 21:04, 19 March 2012 (UTC)
 * The article can not state that Vitamin D supplements of 10,000IU a day are believed to be safe when a major report of the world's leading medical authority stated in 2011 that the Upper Limit for vitamin D is 4000IU a day.Overagainst (talk) 11:36, 20 March 2012 (UTC)
 * But as written now, the article suggests that above 4000 IU/day a healthy person could get the classical symptoms of vitamin D overdose, and that's just nonsense. I think we should go into more detail, and explain the real issues. So, instead of just mentioning the 4000 IU/day IoM upper limit, we should also on what this is based. Not the technical details about the computation of the 4000 IU/day using safety margins, but simply the adverse health effects that could exist that is then prevented by staying below that UL.


 * Then, one can also write about the 10,000 IU/day UL advocated for by many experts, but this is of course to make sure that you don't get the classical vitamin D overdose. Here, one can mention a bit about how hypercalcemia arises from vitamin D overdose, basically that above about 750 nmol/l calcidiol itself starts to influence gene transcription (this is also mentioned in the IoM report). A sustained intake of at least 40,000 IU/day is estimated to be the lower limit necessary to get to that point. Count Iblis (talk) 15:32, 20 March 2012 (UTC)


 * Whether hypercalcemia can be blamed on vitamin D excess is complicated by the fact that hypercalcemia can be caused by a vitamin K2(ME7) deficiency. Vitamin K2(MK7) is converted from phylloquinone in the intestines by gut bacteria. (See Vermeer and Braam, "Role of K vitamins in the regulation of tissue calcification" in Journal of bone and mineral metabolism, 2001, vol 19, issue 4, pages=201–206, pmid=11448011, doi=10.1007/s007740170021).  Use of antibiotics can deplete the gut bacteria that produce vitamin K2(ME7) which may result in hypercalcemia and calcification of soft tissue in people who have optimal vitamin D in their blood. This should not be interpreted as a vitamin D excess, but rather as a vitamin K deficiency. I hope somebody will find a reliable source that connects the dots for this. Greensburger (talk) 17:02, 20 March 2012 (UTC)
 * The article should be clear and simple. The only way to do that is to summarize the IoM committee's findings Overagainst (talk) 22:06, 20 March 2012 (UTC)

Confusing wording in Health Effects section
"Results for a protective or harmful effect of vitamin D supplementation in other types of cancer are inconclusive.[4]". It is not true there is no evidence for a harmful effect "A congruence of diverse data on health outcomes ranging from all-cause mortality to cardiovascular risk suggests that adverse health outcomes may be associated with vitamin D intakes that are much lower than those classically associated with hypervitaminosis D and that appear to occur at serum 25OHD levels achievable through current levels of supplement use"}} The IoM say many lines of evidence converge to show current levels of supplement use may be associated with damage to health.Here. Saying results for a "protective or harmful effect" are "inconclusive" is incredibly bad wording. It implies that there are not indications of supplementation damaging health, but that is not what the IoM have said. There are similar problems with most subsections in "Health Effects". Overagainst (talk) 19:18, 17 March 2012 (UTC)


 * The IoM report makes clear that they used weak evidence that merely vaguely suggests harmful effects while it demanded extremely high standards for evidence for positive health effects. The IoM is pretty open about this method. They arrived at the 4000 IU/day maximum safe dose as an estimate of the dose needed to avoid the calcidiol values associated with the suggested harmful effect (for which there is no good evidence).


 * So, it would be wrong to treat the two issues of harm and benefit by simply quoting out of context from the IoM report for this Wikipedia article. In our article, we cannot on the one hand dismiss good evidence of positive healt effects just because it hasn't been proven in a randomized controlled trial and then admit "evidence" of harmful effects that is even weaker than that of the positve health effects which we decided not to include.


 * The IoM did have good reasons to apply this double standard, but we don't. Count Iblis (talk) 23:59, 17 March 2012 (UTC)


 * There is no benefit, but with a large data-set there are concrete indications that levels of vitamin D supplementation higher than the upper limit recommended by the  IoM  (4000iu) supplementation can be harmful - "vitamin D intakes of 5,000 IU/day achieved serum 25OHD levels that range between 100 and 150 nmol/L." What is the problem with being over 100 nmol/L? This - Dietary Reference Intakes: Vitamin D (2011) P436 "To address the dissimilarity in results from individual large cohort studies, Stolzenberg-Solomon et al. (2010) conducted a pooled nested case–control analysis of participants from several cohorts (the ATBC Study, CLUE, the Cancer Prevention Study II Nutrition Cohort, the New York University Women’s Health Study, the PLCO Cancer Screening Trial, and the Shanghai Women’s and Men’s Health Studies) to determine associations between serum 25OHD levels pre-diagnosis and risk for incident pancreatic cancer. This large-scale pooled analysis (n = 2,285) found a statistically significant two-fold increased risk for pancreatic cancer in participants withserum 25OHD levels at or above 100 nmol/L compared with those with levels between 50 to 75 nmol. Further, the association was strongest for whites, participants in northern latitudes (> 35°N), and participants whose blood was collected in summer months. Thus, a pooled analysis of large cohort studies suggests an association for increased risk of pancreatic cancer with serum 25OHD levels greater than 100 nmol/L that is not consistently seen in analyses of individual large cohorts."


 * The effect was strongest for whites, those whose blood was collected in the Summer months, so this could well be due to too much Sun exposure. Count Iblis (talk) 21:14, 19 March 2012 (UTC)
 * Too much sun ? Their vitamin D level was certainly lower than someone taking 10,000IU per day, that's the difference between sun synthesis (natural and subject to evolved mechanisms of homeostasis) and supplements (unnatural and uncontrolled). I am still wondering how much vitamin D you take each day.Overagainst (talk) 21:51, 20 March 2012 (UTC)
 * If you expose, say, a quarter of your skin to the Sun, then you won't produce much more than about 3000 IU/day, no matter how long you expose that part of the skin to the Sun. To get to 10,000 IU/day, you must expose most of your skin to the Sun, that's not something modern people do on a regular basis. However, the Hadzabe people in Tanzania do have calcidiol levels of about 120 nmol/l, which is equivalent to taking 5000 IU/day. Also there is a big spread in the population, some have calcidiol levels as high as 170 nmol/l. So, there isn't much difference between vitamin D from Sun exposure and taking supplements, unless you go well above 10,000 IU/day.
 * Thing is that the IoM has been consistently wrong about harmful effects of vitamin D in most of their reports on vitamin D from the 1960s onwards. They never bothered looking at indigenous people in Africa, rather they used Western people as their model. Flawed science suggesting harmful effects to the fetus when pregnant women take vitamin D was included in IoM report after IoM report. Today, most doctors "know" that pregnant women should't take vitamin D, despite that it is completely harmless for pregnant women to take 10,000 IU/day.
 * Then, the reason why there are no large randomized controlled trials showing an unambiguous benefit to vitamin D supplementation beyond bone health, is simply because of all this previous scaremongering by the IoM. If it is "known" that 1000 IU/day may damage a fetus, then getting permission to give pregnant women 5000 IU/day or more becomes rather difficult. It's only recently that such trials have been done.
 * Note that the lead author of the latest IoM report JoAnn E. Manson had to cut back on the vitamin D dose she planned to use in her own trial, because of the 4000 IU/day upper limit (trials with higher doses can be conducted, but you then need monitor the people more closely to get permission, which makes large scale trials impractical). It will now be done with only 2000 IU/day instead of the previously planned 5000 IU/day. But this means that benefits beyond bone health that arise around 120 nmol/l or higher cannot be found. Count Iblis (talk) 22:41, 20 March 2012 (UTC)
 * "The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D [25(OH)D] response that is surprisingly flat up to 250 μg (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 μg (4000 IU)/d is required." (Vieth, 1999) If it was beneficial the stuff would be hoovered into the blood (IE the a curve for vitamin D dose versus serum 25-hydroxyvitamin D [25(OH)D] response would not be flat). A dose response flat curve is a warning, one that you would do well to heed.


 * Count Iblis said "But this means that benefits beyond bone health that arise around 120 nmol/l or higher cannot be found." NHANES III found higher all-cause mortality above 122.5 nmol/L". If you don't beleve me here it is in black and white -Table 2. User:Overagainst|Overagainst]] (talk) 12:02, 21 March 2012 (UTC)
 * But the evidence for that higher all cause mortality is quite weak, and the IoM only uses this (and another result) to set the 4000 IU/day upper limit because of lack of strong evidence for benefits (if you're not sure that there are benefits, then weak evidence for harm is significant). However, the IoM does mention that there may well be benefits at higher calcidiol levels.


 * Obviously, JoAnn E. Manson would not have started her own trial if the IoM report she significantly contributed to herself, had made a definitive conclusion that there are no benefits (beyond bone health), only harm, to having higher calcidiol levels. Count Iblis (talk) 14:42, 21 March 2012 (UTC)
 * Instiute Of Medicine say Dietary Reference Intakes for Calcium and Vitamin D (2011) p481.For the  the article say something different there have to be references from a reliable source.  No such references have been provided. Overagainst (talk) 16:18, 21 March 2012 (UTC)
 * This is a quote out of context. The context that has to be provided here is the IoM definition of proof of benefits, the bar for that is set extremely high. The definition of "emerging problems" is merely some vague suggestions that there could be harm. If there were the same congruence of data suggesting improved health outcomes (and there actually is), the IoM would have not used it, because of the assymetric way evidence for harm and benefit is treated. This is what the IoM has to do, but Wikipedia must treat both issues in a neutral way. Count Iblis (talk) 22:36, 21 March 2012 (UTC)

Health effects section should be trimmed and moved to the bottom of the article
The health effects of vitamin D supplementation is a controversial subject, the IoM has been conservative about this due to a lack of strong evidence of effects beyond bone health. But what then happens is that because the IoM should be given a lot of weight, this makes the article quite one sided.

Also, one has to ask oneself why there has to be so much focus on the health effects of vitamin D in the first place. When writing about any subject, it's obviously much better to focus mainly on what is known well, rather than on what is not known well. In case of vitamin D, a lot is known that the article doesn't mention at all. Count Iblis (talk) 15:52, 20 March 2012 (UTC)
 * I think the health effects section is confusing, it repeatedly gives apparently positive results from observational studies and then leaves the reader wondering why studies of supplements have turned up no real evidence of benefit.Overagainst (talk) 21:41, 20 March 2012 (UTC)
 * The problem is that big-enough, controlled clinical trials are expensive, and private industry has no reason to fund them because vitamin D is generic (in other words, no patent protection that would allow a company to charge a high enough price for investors to get their money back).  As a result, there have not been any, so there is nothing definitive to say.  Only an organization like the NIH will fund clinical trials on vitamins.   Because the NIH is spending taxpayers' money, it has to pick very very carefully.  It funded big clinical trials on Vitamin E to prevent cancer, since there was TONS of in vitro and animal showing that its antioxidant qualities might prove useful to prevent cancer in humans.  Surprisingly - shockingly - people in the intervention arm actually had a slightly higher chance of getting cancer.  Crazy.  Anyway, very recently there was a great article on clinical trials for Vitamin D in particular in the magazine called The Scientist.  Check it out -- http://the-scientist.com/2012/03/01/vitamin-d-on-trial/ Jytdog (talk) 01:09, 21 March 2012 (UTC)
 * "since there was TONS of in vitro and animal showing that its antioxidant qualities might prove useful to prevent cancer in humans." Effect of oral cholecalciferol supplementation at physiological and supraphysiological doses in naturally vitamin D3-deficient subterranean damara mole rats (Cryptomys damarensis)." Data indicate that a pathological response to D3 intoxication occurred and that hepatic and renal excretory functions were impaired. It appears, therefore, that these animals function optimally at the low concentrations of D3 metabolites found naturally. Supplementation at both physiological and supraphysiological doses of D3 may disadvantage the damara mole rat." You see the naked mole rat has no source of vitamin D but it has adapted to that, by natural selection. But the Naked Mole Rat is a short lived animal, right? No, it is extremely long lived. the only animal that has a greater  longevity quotient is a bat, IE another low vitamin D mammal. The Naked Mole rat never gets cancer - never.
 * Nobody would argue that lower is better for vitamin D levels in humans of course. The natural level (IE the level that evolution has adapted people to) is best. The ingestion of high dose vitamin D supplements can raise levels far beyond what is possible with sunbathing. It seems to me - and this is a very telling point I think - that if whites have retained the limitations on sun induced vitamin D levels for the 30,000 years they have been wearing clothes in N. Europe and going though 'D'-less winters there is good reason. Concomitantly there is good reason for not overwhelming the naturaly selected homeostatis of vitamin D by ingesting evolutionarily unprecedented amounts of 'D'. It's simply not credible that European still have limits on vitamin D synthesis from the sun (there are several including receptor polymophisms) because the limiting mechanism has been inaccessable to natural selection since modern humans left Africa, as Vieth asserts.


 * Private industry does fund vitamin D research " CBC Canada journalist Steven Strauss wrote about this "Heaney and Vieth had co-authored the toxicity study with two employees of the Council For Responsible Nutrition, a Washington D.C.-based lobby group and trade association for ingredient suppliers and manufacturers in the dietary supplement industry — that is to say, the official representatives of the people who would make vitamin D." Overagainst (talk) 10:56, 21 March 2012 (UTC)


 * Some interesting points there Overagainst.


 * On your last point, I have no idea what you are talking about here so I cannot respond. What report did the two employees Council for Responsible Nutrition co-author?  (employees authoring an article is not the same as CRN funding research, much less funding a clinical trial).


 * I hear your line of reasoning about european evolution.. but I don't see how it makes sense. People have always eaten;  there is vitamin D in food.  So there are more variables driving natural selection than just sun exposure.   Right?  I also struggle with notions of "natural levels" of any metabolite.   I just don't know what that means.   Finally, is there any biological data showing evolution in human vitamin D processing pathways among europeans? (for example study of DNA from some frozen ice age person compared to people from today)?  Otherwise it is just reasoning and could be true, could be not true...  biology is often surprising.  Which (to change the topic back to the original question of this thread) is why interventions like Vitamin supplementation really need big clinical trials to show if they are real.  When things unexpectedly fail... we often never know why, for sure.  Lots of speculation but we often really know why.   btw another study just published today on an antioxidant intervention having  - again surprisingly - negative results.  This time the disease was Alzheimer's:  http://www.fiercebiotech.com/press-releases/clinical-trial-examining-effects-antioxidants-alzheimer-disease-cerebrospinJytdog (talk) 16:08, 21 March 2012 (UTC)
 * 'Heaney reported in 2006 that he had a “financial relationship with SmithKlineGlaxo” — a company which directly produces vitamin D.' Vieth "had been angered when his name had been taken off some scientific papers after he, in complete openness, told agencies and journals that he and his wife have set up a vitamin D company in Toronto called Ddrops Inc. She is now the company’s president and it sells a year’s supply of 1,000 IU liquid vitamin D for about $20. “I was told my name was being taken off papers because of my wife’s occupation. That is something I find infuriating and upsetting,” he said. A little additional research found that Elaine Vieth has told the Hamilton Spectator that pharmacies initially had little interest in selling her product, which can be sprinkled on food or in drinks, but that after the Creighton cancer study appeared she sold 30,000 bottles within two days." The Strauss article was linked too when it was online, it has been mention by several people on Talk.


 * Vieths own data on dose response show that oral intake and synthesis of vitamin D in the skin do not increase blood levels of vitamin D in proportion to sun exposure or supplementation, the reason is that the body resists levels higher than are good for it.Vieth says we have got these limiting mechanisms because we our metabolism has  not caught up with leaving Africa. So evolution has stalled . But he also claims that white skin evolved for greater vitamin D synthesis since we left Africa ! Can't have it both ways. A natural level is what most people have.Overagainst (talk) 16:43, 21 March 2012 (UTC)
 * Most of the Hadzabe people in Tanzania have 120 nmol/l, this debunks what you wrote some time ago about people in the tropics having low values. The reason for that is that those measurements were done on people who live a Western lifestyle in Africa, they sit indoors in aircondioned rooms all day long. Basically the normal intake of vitamin D is 5,000 to 10,000 IU/day, anything less puts you at risk from diseases like cancer, MS, heart disease, diabetes, Alzheimers, Crohn's disease etc. etc. For every peer reviewed article suggesting harm at values above 50 nmol/l there are hundreds of peer reviewed articles in which benefits are demonstrated. Count Iblis (talk) 22:47, 21 March 2012 (UTC)


 * Africans with an outdooor lifestyle who live within a few degrees of the equator in Tanzania have high blood levels from the intense sun they are subjected to. And does their high vitamin D level make then healthy? No. The Life of a Maasai Woman- "Her life expectancy is 45 years." Read the study, the Maasai and Hadzabe avoid the midday sun.


 * The vitamin D 'Council' says "Yesterday, Dr. Martine Luxwolda and colleagues at the Dutch University Medical Center Groningen reported the vitamin D levels of 60 pastoral “hunter-gatherers” (35 Maasai and 25 Hadzabe), who live within a few degrees of the equator in Tanzania. All of the subjects had skin type 6, which is the black shiny skin common to those who come from equatorial regions, and also the skin type which needs the most sunlight to produce robust amounts of vitamin D." So they are saying under the same circumstances blacks will have lower levels due to their skin type. But they also claim there is no other difference between Europeans and African for example- Vieth 2005"Since early human evolution occurred under UV-rich conditions, typical 25(OH)D concentrations were surely higher than 100 nmol/L. Levels like this are now seen only in lifeguards and farmers. This range of 25(OH)D concentration reflects an adult vitamin D input of 200–500 �g/day (Vieth, 1999). Since our genome was selected through evolution under these conditions, it should be evident that our biology was optimized for a vitamin D supply far high than what we currently regard as normal".


 * I have previously cited Blood vitamin d levels in relation to genetic estimation of African ancestry. "The effect of high vitamin D exposure from sunlight and diet was 46% lower among African-Americans with high African ancestry than among those with low/medium ancestry." Hence what I was saying was that Blacks' lower blood vitamin D is not a side effect of their dark skin but a metabolic adaptation which protects them against high vitamin D levels from any source. A 2011 study shows Blacks' vitamin D levels are lower than whites and  do not vary over the year in the way whites do. Factors influencing the vitamin D status of 10-year-old urban South African children "White  Seasonal variations in 25(OH)D levels were found only in white children, with 25(OH)D levels being significantly higher in white than in black children " In Europe there is no vitamin D sythnesis for part of the year.  Europeans are adapted to this by having seasonal variation in their bloood levels of vitamin D. When Europeans live in Africa their vitamin D levels still vary over the year because of their genetic heritage. So the Vitamin D 'Council' is wrong that we are all the same, and  one  vitamin D level can not be described as correct for everybody irrespective of ancestry. Overagainst (talk) 10:08, 22 March 2012 (UTC)


 * These studies you both are citing deal with vitamin D levels overall - a function of sun exposure and diet.  These say nothing about genetics/epigenetics or evolution.   Again it is all fine reasoning but unless you can show some inherited genetic difference it is all just reasoning.... interesting but nothing to hang your hat on.   I wonder what is at stake for you that argue for this so fiercely, past what the data can sustain.  What is at stake for you?   (just curious)  Also,  you keep referring to some scandal around Vieh but since you are not citing original articles that are under discussion I cannot respond..  And I remain interested to see what substantial, controlled clinical trial you think a company paid for...can you provide a citation?  Thanks Jytdog (talk) 13:47, 22 March 2012 (UTC)
 * I agree, little is known about the evolutionary aspects. The main problem I have with Overagainst's arguments here is not so much some position he takes, rather that he wants his POV to be the main POV the article should mention. There are quite a few different POVs about vitamin D, the IoM has come down on there being no strong evidence from randomly controlled trials for higher calcidiol values. That should be mentioned prominently, but Overagainst wants to go much furhter and remove mention of other significant opinions that are held by a large number of experts. The IoM was commissioned to write the IoM report, not this Wikipedia article.


 * About evolution/vitamin D, I think one has to take into account that unlike other vitamins like e.g. vitamin B12 without which the body cannot function, calcitriol only plays a trivial role in the body. It only switches on or off certain genes. The question is why you need to use a substance that can only be made using Sun exposure for that. Indeed, in some animals the very same gene that codes for the enzyme that helps to get calcium from food is also expressed in the brain, but there it is switched on/off using a different substance that the body can make itself (without Sun exposure).


 * I therefore think that the switching on/off of genes by calcitriol which changes when there is a shortage of vitamin D is a deliberate outcome of evolution. Biologically, there is no such thing as "vitamin D deficiency", what we call vitamin D deficiency is just a signal that the body uses to optimize gene expression. When the Sun doesn't shine for a long period, or when due to droughts animals have to live in holes underground for prolonged periods, their vitamin D levels will drop significantly, and their physiology will then be optimized to survive these circimstances.


 * In particular, I believe that low vitamin D means the body will cut back on energy expenses. First this will happen where it has the lowest impact, like maintaining the body in a top fitness state, then at lower levels, it will cut back on the immune system and at even lower levels on the enzymes that get the calcium from food. In all these cases, we're dealing with cutting back on luxery systems. E.g. if the food you eat contains enough calcium, the calcium is absorbed via diffusion. Only when the concentration of calcium is low, do you need enzymes to transprt it to the blood. Count Iblis (talk) 15:47, 22 March 2012 (UTC)
 * Jytdog you asked me about evidence for genetic diferences between Europeans and other poplulations. "Finally, is there any biological data showing evolution in human vitamin D processing pathways among europeans?" The study I cited showed Europeans have seasonal variation in blood vitamin levels even when they are living in Africa, hence that seasonal veriation in blood vitamin D  levels among Europeans living in Africa must be genetic. I also cited  Blood vitamin d levels in relation to genetic estimation of African ancestry which shows people with African ancestry have lower blood vitamin D levels compared to Europeans. Africans are genetically adapted to African conditions, Europeans are genetically adapted for European conditions. I responded to your request for information about Veith and Heaney in relation to their assertion that 10,00IU a day is safe.  I'm puzzled that you think I'm talking about an article that is not under discussion, I thought it was obvious which paper we are talking about.  Heaney and Vieth are 2 of the 4 authors of Risk assessment for vitamin D whch says that 10 000 IU vitamin D3 a day is safe. It is there in black and white that the other two authors are John N Hathcock, Andrew Shao From the Council for Responsible Nutrition, Washington, DC ". Now you're asking "I wonder what is at stake for you that argue for this so fiercely, past what the data can sustain.  What is at stake for you?   (just curious)". I am afraid answering your enquiries takes me off the point, whereupon you remonstrate with me. Lets just stick to discussing proposed improvements to the article from now on.


 * It is not POV to say there are such genetic differences if I have an unimpeachable reference. My reference is not my interpretation/ reasoning of the above studies which i discussed in response to Count Iblis. My sole source and reference is the IoM report, which made it perfectly  clear, and explicitly stated in  Dietary Reference Intakes for Calcium and Vitamin D (2011)  page 435 that such genetic differences exist. "However, the data are clearly suggestive of a U-shaped or reverse-J-shaped risk curve between serum 25OHD level and all-cause mortality; increases in risk are suggested at thresholds in the range of 75 to 120 nmol/L for the white population, with lower levels for the black population""Dietary Reference Intakes for Calcium and Vitamin D (2011)  page 435 Overagainst (talk) 15:58, 22 March 2012 (UTC)


 * Hi Overagainst. Thanks for explaining and for providing the reference about Vieh.  There are 3 Vieh citations and I couldn't figure out which you meant.   You brought this article up in response to my statement that industry will not fund large, randomized clinical trials of dietary supplement, so organizations like the NIH have to do it - which they do only rarely; hence there is little compelling clinical trial data from which to draw definitive conclusions about various uses for Vitamin D.   However, this article describes no original clinical research -- it is a review of existing literature.   So it is not on point.
 * WIth respect to the argument you are trying to make about genetics -- as far as I can tell all the studies you cite just measure vitamin d levels in blood.  As I mentioned, the level of vitamin D in blood depends on two things -- the body's synthesis and use of vitamin d, and diet.   It seems to me that in every one of these studies, diet is a confounding factor.  It seems to me that the only evidence for evolution that would be non-confounded by diet, would be studies showing that there is actual genetic difference -- some difference in DNA.  That is what I mean by "evolution in human vitamin D processing pathways".   You have not responded to this.   You can or cannot respond, of course, but that is the question I have putting to you.    It is one thing to make large scale recommendations for vitamin D intake based on race;  it is quite another to ascribe the reason for the differential recommendation by evolution, which you are doing.  You are making a leap.  Jytdog (talk) 13:24, 23 March 2012 (UTC)


 * The Vieth & Heaney paper was the same one as discussed above at length Health concerns Heaney et al 2003 is ref (26) in that paper. The Vieth & Heaney paper was discussed because it was the  reference for a statement that 10,000IU per day was safe. I said that statement was out of line with the IoM Upper Limit and had to go. The paper is a review of existing literature you say. YES and the most important study which it reviews was by Heaney. Again, 'The IoM report on the  study, by Heaney(2003). Here "As suggested by the study, vitamin D intakes of 5,000 IU/day achieved serum 25OHD levels that range between 100 and 150 nmol/L, but do not surpass 150 nmol/L after 160 days of administration. Almost no other studies have assessed the safety of long-term maintenance of serum 25OHD levels in this range in relation to chronic disease risk and all-cause mortality, so the information about the increases in serum levels is useful for the purposes of establishing a UL. Given the uncertainties surrounding the data and the reliance on a single report, the UL is set 20 percent below the level identified by Heaney et al. (i.e., 5,000 IU), specifically at 4,000 IU/day."' Heaney did the most imprortant study. A reputable science journalist seems to have thought Heaney's  financial relationship with SmithKlineGlaxo and Vieth's wife owning a Vitamin D supplement company worth mentioning in view of their paper being the one cited for the assertion that 10,000IU a day is safe. I think that information casts light on your statement that industry will not fund large, randomized clinical trials of dietary supplements well.
 * I'll just quote Blood vitamin d levels in relation to genetic estimation of African ancestry. "BACKGROUND: African-Americans generally have lower circulating levels of 25 hydroxyvitamin D [25(OH)D] than Whites, attributed to skin pigmentation and dietary habits. Little is known about the genetic determinants of 25(OH)D levels nor whether the degree of African ancestry associates with circulating 25(OH)D.
 * METHODS: With the use of a panel of 276 ancestry informative genetic markers, we estimated African and European admixture for a sample of 758 African-American and non-Hispanic White Southern Community Cohort Study participants. For African-Americans, cut points of <85%, 85% to 95%, and >or=95% defined low, medium, and high African ancestry, respectively. We estimated the association between African ancestry and 25(OH)D and also explored whether vitamin D exposure (sunlight, diet) had varying effects on 25(OH)D levels dependent on ancestry level.
 * RESULTS: The mean serum 25(OH)D levels among Whites and among African-Americans of low, medium, and high African ancestry were 27.2, 19.5, 18.3, and 16.5 ng/mL, respectively. Serum 25(OH)D was estimated to decrease by 1.0 to 1.1 ng/mL per 10% increase in African ancestry. The effect of high vitamin D exposure from sunlight and diet was 46% lower among African-Americans with high African ancestry than among those with low/medium ancestry.
 * CONCLUSIONS: We found novel evidence that the level of African ancestry may play a role in clinical vitamin D status.
 * IMPACT: This is the first study to describe how 25(OH)D levels vary in relation to genetic estimation of African ancestry. Further study is warranted to replicate these findings and uncover the potential pathways involved".
 * Dietary Reference Intakes for Calcium and Vitamin D (2011) page 435  "However, the data are clearly suggestive of a U-shaped or reverse-J-shaped risk curve between serum 25OHD level and all-cause mortality; increases in risk are suggested at thresholds in the range of 75 to 120 nmol/L for the white population, with lower levels for the black population""Dietary Reference Intakes for Calcium and Vitamin D (2011)  page 435. No, it is not me saying there is an 'actual genetic difference'.
 * Anyway, all this is neither here nor there as regards the article. I do not, and never have, proposed adding anything to the article suggesting why black people suffer increases in risk at lower thresholds than the white population.Overagainst (talk) 10:32, 24 March 2012 (UTC)


 * I am happy you have no intention of adding anything to the article about the evolution stuff. I was concerned because above, you made arguments based on evolution.
 * About clinical trials and industry -- for Pete's sake you have not cited any large randomized clinical trial funded by industry.  The Heaney et al 2003 study (http://www.ajcn.org/content/77/1/204.full.pdf+html) was funded by something called the Health Futures Foundation, which is a nonprofit that supports all kinds of research at Creighton (http://www.guidestar.org/FinDocuments/2010/470/675/2010-470675662-074096ce-9.pdf).  And in any case this study is not a large randomized clinical trial designed to determine whether administering vitamin D confers some specific health benefit.  That is what I was referring to.   This study does however argue that people should take more Vitamin D.  I finally managed to find the Strauss article you keep talking about.  The link you give doesn't work -- I had to go the internet archive to find the article:   http://web.archive.org/web/20110120062100/http://www.cbc.ca/news/viewpoint/vp_strauss/20080213.html   And now having read it, I see what you have been concerned about with respect to conflicts of interest that may have influenced the authors to argue for a higher daily dose.    But again, conflict of interest is not the same as actually funding a clinical trial.  You have a good point about using caution when considering that article to consider daily dose, but you lose credibility when you smear things together. Jytdog (talk) 14:27, 24 March 2012 (UTC)
 * I answered arguments by Count Iblis. The toxicity review by Vieth and Heaney stated it had John N Hathcock, Andrew Shao employees of "one of the dietary supplement industry's leading trade associations " as the other two authors. Whoever pays their wages is also paying for work done on the study, Mrs Vieth owns a supplement company. I was not the one who brought up the issue of funding of research. It was you and you seemed to imply the comercial firms were not supporting vitamin D trials and research. I just mentioned an article which was discussed by others on this Talk page long before I was around.  "A large randomized clinical trial" would require a  toxicity study to show the dose used was safe.  Fortunately Vieth Heaney Hathcock and Shao's study was not accepted by the leading authority (the IoM)and Manson's trial did not procede at the dose originally intended. Smearing? Others will decide who has credibility. Edits are based on references.  Overagainst (talk) 22:38, 24 March 2012 (UTC)
 * Which just proves my earlier point that the IoM is not a bona-fide tertiary source. If they are not going to accept certain published secondary sources, but will start to argue who is right and who is wrong, even disagreeing with the authors of primary sources about their results (see here), then it's much more of a primary or secondary source than a tertiary source summarizing the existing literature. Of course, the IoM has good reasons to do this, but what we have to do here is write a good WIkipedia article that includes all significant POVs published by the experts. If the IoM has taken sides (again with good reasons given what their job is), then we can't read the IoM report pretending it gives due weight to all views held by experts. Count Iblis (talk) 00:37, 25 March 2012 (UTC)
 * Outta here! Jytdog (talk) 02:45, 25 March 2012 (UTC)

A lot of relevant information is missing in the article
We've had big discussions above about health effects, whether we should use the IoM report to the explcusion of other sources on that issue. But the net result of all this is that we've ended up with a bad article. As things stand now, you can't find uncontroversial information about vitamin D on many issues at all. If I e.g. want to know what the rationale is for clinical trials on heart disease and vitamin D, I won't be able to find it.

To find such information I need to read the literature. To show that this sort of thing does not contradict the recent IoM report and is not related to the heated discussioins above, let's use an article written by the lead author of the IoM report, Joann Manson that appeared after the IoM report was published, e.g. this article. This contains a lot of information that one should be able to get from this Wiki-article. It explains why, despite the current lack of clinical evidence, scientist think vitamin D may have an effect on cancer and heart disease. This should be mentioned in the article. Other articles explain the rationale for believing that vitamin D plays a role in infections diseases, MS etc. etc.

Without this information, it looks like vitamin D is or has been tested against many diseases without any rationale at all. And because of lack of clinical evidence for such effects beyond bone health, a reader may think that this lack of evidence is strong evidence against such effects. But then such a reader won't understand why such research is still ungoing.

Count Iblis (talk) 02:50, 27 March 2012 (UTC)

WP:MEDRS
Can people please use proper secondary sources per WP:MEDRS. Thanks Doc James  (talk · contribs · email) 11:28, 12 April 2012 (UTC)
 * Please do not re add primary research. Also one sentence sections are not recommended.-- Doc James (talk · contribs · email) 22:01, 13 April 2012 (UTC)

Low blood levels of vitamin D are associated with ...
The article repeatedly mentions low blood levels of vitamin D associated with health outcomes (increased mortality, cancer, falls ect ect). This is all very interesting but these assertions are included in almost every subsection on a specific disease. This is synthesis IMO. The clear implication of the article is that the reader could reduce their risk of various diseases by increasing their vitamin D level. The IoM findings were that this is not true. Mentioning the associations of vitamin D with numerous diseases, as is currently done in the article, is synthesis. It's verging on medical advice. I think the repeated mention of the association of vitamin D levels in the same section as health outcomes should be removed, or at least moved into it's own section and put in context of the IoM findings.Overagainst (talk) 21:02, 10 May 2012 (UTC)
 * Everyone has heard "correlation is not causation" so no I do not think our readers will get confused. We state most prominently "the evidence for other health effects of vitamin D supplementation in the general population is inconsistent".-- Doc James (talk · contribs · email) 21:51, 10 May 2012 (UTC)


 * The reader can certainly dramatically reduce the risk and negative effects of diseases not related to bone health, by increasing their vitamin D level. The IoM report did not say that this is not the case. What the IoM report says is that the hypothesis that this is not the case cannot be ruled out at a high confidence level, based on studies that the IoM has decided not to argue with. There are results published by leading experts that strongly point to 80 nmol/l being better than 50 nmol/l for bone health. The IoM report did not include that result on face value, what they did was to re-analyze what the authors of the paper did by removing some data and adding other data, and then the satistical signicance for the 80 nmol/l vanished.


 * The lead author of the study strongly disagrees with this analysis by the IoM. But without taking sides in this dispute, what this does show is that you can't treat the IoM report as simply a tertiary review artcle, in some respects it is far more a primary or secondary review article, as they re-analize the data and come to different conclusions than the authors of the original study. So, it doesn't necessarily reflect what the scientific opinion is in some cases.


 * Even for bone health, the IoM position that 50 nmol/l is sufficient is an opinion held by only a minority of the experts. Then this subject is controversial, so by no means can one pretend that everyone thinks that 80 nmol/l is better, but it's clear that treating the IoM report as gospel is not going to lead to an NPOV Wiki article that fairly reflects all significant opinions held by reputable experts in the field. Count Iblis (talk) 23:25, 10 May 2012 (UTC)


 * Doc James, The article is currently mentioning over and over again that low levels are associated with a very wide range of diseases. And the reader is not going to draw the obvious conclusion: that raising vitamin D levels will reduce the risk of getting these diseases? You are giving the reader a lot of credit there! WP:MEDRS requires the article to summarize scientific consensus; that requires that the article cease implying that raising vitamin D levels beyond some unspecified level (described as "low') by means of supplementation, will be good for the reader. The section on supplementation ought to include something summarizing the following important statement -  Dietary Reference Intakes for Calcium and Vitamin D (2011) p481. The IoM says 20ng/ml is more than sufficient, that represents the balance of scientific opinion and should be in the article. The following may also merit inclusion, as it is part of an inexorably hardening scientific consensus against supplementation. 25(OH)D at a level ≥21 ng/ml is associated with an increase in serum CRP


 * "Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited (ref.102)" This should be deleted from article It's nonsense and contradicts other well supported text.Overagainst (talk) 20:28, 11 May 2012 (UTC)
 * Then, why on Earth is the lead author of the IoM, JoAnn E. Manson conducting this double blind study:


 * "VITAL is a research study in 20,000 men and women across the U.S. investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk for developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. Recruitment for the study began in 2010 and is continuing throughout 2012."


 * ??????????????????? Count Iblis (talk) 20:55, 11 May 2012 (UTC)
 * The exhaustive report from the Institute of Medicine's panel of experts said 20ng/ml is sufficient and higher levels can damage health, they recently repeated that advice. The study I linked to above, 'Relation Between Serum 25-Hydroxyvitamin D and C-Reactive Protein in Asymptomatic Adults (From the Continuous National Health and Nutrition Examination Survey 2001 to 2006), a big data set,  found that vitamin D levels  over 21 ng/ml are associated with an increase a marker of inflamation. A Reverse J-Shaped Association of All-Cause Mortality with Serum 25-Hydroxyvitamin D in General Practice, the CopD Study used blood samples from 247,574 Copenhageners. Here is what they found
 * So yet another HUGE study finds the ideal vitamin D level is the one virtually everyone has: 20ng/ml. What a surprise!Overagainst (talk) 11:04, 6 June 2012 (UTC)
 * So yet another HUGE study finds the ideal vitamin D level is the one virtually everyone has: 20ng/ml. What a surprise!Overagainst (talk) 11:04, 6 June 2012 (UTC)


 * Nonsense, this is about natural levels of people living in Denmark who get their vitamin D from diet or the Sun and how that correlates with their health. Note that Denmark is at the same lattitude as Northern Canada, where icebears roam. For them, you have to ask how they end up getting the various levels of vitamin D, this will be very strongly correletated with diet and other life style issues that themselves strongly affct mortality risk independent of vitamin D.


 * The 1% of the people with high vitamin D levels who had levels above 140 nmol/l and who had a slightly higher motality risk (40% higher) should actually be grouped toghether with the low vitamin D level. Because such levels can only be achieved using supplements in Denmark, but almost no one in Denmark uses high dose supplements by themselves. If they are prescribed high dose supplements, they were most likely long term severely vitamin D deficient people, and thus they would still suffer from having been severely vitamin D deficient for such a long time. Count Iblis (talk) 15:29, 6 June 2012 (UTC)

More evidence linking MS to vitamin D
http://news.ninemsn.com.au/health/8506632/vitamin-d-links-to-ms-supported-by-study

"Scientists have moved a step closer to understanding how to better treat multiple sclerosis (MS) after more evidence emerged of a crucial link to vitamin D.

In the latest study, University of Tasmania researchers discovered that MS sufferers treated with interferon-beta, a common MS drug, had higher vitamin D levels than those not on the treatment.

Interferon-beta caused patients to become far more efficient at making vitamin D in their skin, senior researcher Professor Bruce Taylor said.

MS sufferers taking the drug had nearly three times as much vitamin D from the same amounts of sun exposure than those who didn't take interferon-beta, he said.

The results also shed light on how the therapy works, which has previously been unclear although it was thought to effect the immune system.

Interferon-beta only reduced the risk of having an MS attack if patients had sufficient levels of vitamin D in their system, Prof Taylor said.

MS sufferers in Tasmania and other areas of low latitude, where it was impossible to absorb enough vitamin D from sunlight in winter, may need to consider vitamin D supplementation, he said.

The study analysed around 200 people living with MS in southern Tasmanian between 2002 and 2005.

The research was instigated by the high rates of MS in the state, Prof Taylor said. The condition is more common in populations living further from the equator.

Tasmanians are seven times more likely to have MS than people in Northern Queensland and the Northern Territory and rates are three times higher than in NSW, Prof Taylor said.

He said the findings would need to be tested further in clinical trials.

However, the discovery will also be examined in an upcoming Australian study investigating the effect of taking vitamin D supplements on people with early MS symptoms.

That research will be carried out between 2012 and 2016 by MS Research Australia and the Florey Neuroscience Institutes in Melbourne.

"Hopefully, there will be a major public health initiative in the future about how to treat or prevent MS," Prof Taylor told AAP.

The study was published in the journal Neurology."

Count Iblis (talk) 21:25, 27 July 2012 (UTC)
 * kind of interesting but these kinds of "links" are really meaningless, medically.  there is no way to know if the higher vitamin D levels are just a sideshow or are somehow meaningful.  nor does it make it clear if taking vitamin D will be helpful. Jytdog (talk) 13:30, 28 July 2012 (UTC)

POV tag
I've put a POV tag on this article. This article was already too biased for my taste, but then I'm jsut one editor who may be biased himself. However, the latest edits by Overagainst make this article too far removed from what you find reading the scientific literature on this subject.

The way to fix this is to include stuff on the motivations of the research on on skeletal effects of vitamin D. So, while supplementation has as of yet not been proven to be effective there are good theoretical reasons to believe why they may be (published in many review articles) and in this article you don't read anything at all about that. YOu geta one sided account of the ineefctiveness of supplementation without that being put in the proper context (why are people conducting these tests in the first place).

This makes this whole article one big propaganda article against vitamin D supplementation instead of an article about vitamin D that would then include something about the research on vitamin supplementation. Count Iblis (talk) 18:22, 13 August 2012 (UTC)


 * Dearest Count Iblis, what are you after?  I disagree that the article is any kind of "propaganda."  In the english speaking world we just had three (really 2) big reviews.  One was a review for new dietary recommended intakes for the US (first AHRQ did a bunch of shovel work, which they published separately, then the IOM committee reviewed that work and other work and published their own thing.   Then Cochrane in the UK led  a big review.   Lots of experts doing lots of reading and thinking about the current state of evidence.  And for vitamin D they pretty came down to:  don't have less than DRI (duh, right? this is what vitamins are for); and extra supplementation seems ~maybe~ useful for old women to preserve bone.  maybe.  But other than that, we can't say it is good for anything.  I liked your comment while editing that "not enough evidence to say it works is not the same as saying it doesn't work" - this is good and subtle point.  And i agree that the article shouldn't say "doesn't work" - it just say "insufficient evidence to say it does work"  or that some specific study showed no effect... But I think the POV tag is a bit... overdone.Jytdog (talk) 00:03, 14 August 2012 (UTC)
 * Is there conclusive evidence of benefit in the general population, no. Is there tentative evidence, yes but it is off both harm as well as benefit. Do we mention this. Sure looks like it. I do not see the POV. Doc James  (talk · contribs · email) (if I write on your page reply on mine) 01:15, 14 August 2012 (UTC)
 * I have been thinking more about Count Iblis's complaint. Sorry this is a bit of a ramble.  What is difficult here is that Count Iblis is right that there has been a ton of work done understanding what endogenous Vitamin D does, and that work was the motivation for clinical testing.   As a general point, the continual failure of these trials shows how strange the whole field of vitamin studies is.  Vitamins are small molecules that we have to take in via diet and that play super important roles... not getting enough of them makes you sick!  And we can manufacture them and they are cheaply available as supplements.  This sets up a strong temptation for scientists  to push further and try to use them as drugs to treat diseases, and a temptation for the public to think of them and try to use them like drugs.   And the marketing of them sure pushes all that as hard as it can.  So this idea - this temptation -- is all around us - it is the framework we all think in.   But clinical study after clinical study of these and other endogenous small molecules (coenzyme Q, for example) has failed. (I hope nobody takes that as bias or POV... it is just true)  Which, when you step back, kind of makes sense.  We evolved to need X amount of these things every day, more or less... and our bodies use them in specific ways and specific amounts.   They are not at all like small molecule drugs that have no endogenous role and are true interventions.  I don't know of any small molecule or protein that has an endogenous role and is useful as a drug for anything other than a disease where it is grossly lacking and its lack causes terrible disease (we give some proteins for genetic diseases like Gaucher's where the protein is lacking;  we give vitamin D for rickets...)  Does anybody have any examples?   Anyway... to the extent that this temptation exists, we have spent millions of taxpayer dollars on basic research and clinical trials pursuing it.   Count Iblis is right that we could have buckets more text describing the mountains of basic research that has been done to understand the role Vitamin D plays in various systems and tissues.    But the place to look for that is NOT in the "health effects" section - which I think people go to, to find information about the results of taking the supplement in a drug-like way.    The place to put the information about studies directed to understanding what Vitamin D normally does in the body, is down in the "Mechanism of action" section which is badly named - it follows the temptation.   We think about the mechanism of action of drugs.  A better name might be something like "Biological activity".  Anyway, end of ramble.


 * I propose that we edit this page and similar ones to keep really bright lines between descriptions of basic research studies showing what vitamins do and descriptions of clinical research studies This page does that pretty well.  It might be better to more clearly name the "Health Effects" section to something like "Clinical Research on Vitamin D" and move it to the bottom.   Jytdog (talk) 14:06, 14 August 2012 (UTC)
 * Yes these health effects are tentative at best and for much of it there is evidence of no benefit. This however is what most people are looking for and thus it should be kept first. People care less about how it is syntheses. They what to know if supplementation has health benefits and the answer is that the research does not support this for most conditions. Doc James  (talk · contribs · email) (if I write on your page reply on mine) 14:28, 14 August 2012 (UTC)
 * But then you can easly reach the opposite conclusion from the literature about vitamin D, and don't focus too much on clinical trials (very few clinical trials have been done with high dose supplements that lead to significantly elevated calcidiol levels anyway). This is because you can extract from the known facts about vitamin D that an intake of between 5000 to 10,000 IU/day is the natural intake we would get from the Sun, and the calcidiol levels we would then achieve is then of the order of 120 nmol/l or higher. The question should be about the effects of low vitamin D levels lower than 50 nmol/l. The burden of proof should be on the people advocating that low levels that Western people who spend most of their days indoors typically have, has health benefits over the natural levels


 * Note that there was an idea that the 50 nmol/l or lower was perhaps normal after all, because many people in the tropics are in that deficient range. But this was recently debunked when measurements of vitamin D levels of the Hadzabe and Maasai people were performed, see here. The reason why many people in, say, India have low levels of vitamin D is simply because they spend the whole day in AC rooms and offices.


 * Then, it may well be that vitamin D does not directly have significant effects on serious diseases at all, yet having levels above 100 nmol/l may help keep you in better physical shape (vitamin D may help boost the effect of exercise) which then does influence health on the long term. You won't then see this in clinical trials that only last for a few years. And in retrospective studies, you have to subtract the known effects of other indicators of health so, you would then not see the effect of vitamin D, because it may not have an independent health effect. But if taking vitamin D makes it possible for people to exercise harder and stay fitter, there will very likely be benefits in taking vitamin D, despite all these benefits being attributed to factors other than vitamin D in statistical studies.


 * Now, the general thrust of my argument can be found in the literature as well, the previous IOM committee has criticized the last OM report on the grounds of biological plausibility. The issue of the burden of proof is debated in the literature, and it is a non-trivial matter. I'm not saying that we should simply adopt my POV here, but we should mention whatever significant POVs exists in the literature on this matter. Count Iblis (talk) 16:09, 15 August 2012 (UTC)


 * Count, is your issue (a) that people say that the DRI should be higher than what the recent IOM report said, so that people take the "right" amount of vitamin D and thus don't get sick; or (b) that the various drug-like interventions that have been tested should be stated more promisingly?    If it is (a) then you are thinking  of Vitamin D as a standard dietary supplement; if (b) then you are thinking of it like a drug.   If you are thinking of (a) then I am all with you - - debate about DRI should be well aired.   But if you are thinking about (b), then I feel you have no leg to stand on.  We cannot say "Vitamin D is safe and effective to treat condition X" unless there is clinical data showing that.  I mean we can say it without data, but it would be terribly unethical. So where are you coming from?


 * Yes, I'm arguing for (a), not for (b). Count Iblis (talk) 01:21, 16 August 2012 (UTC)

My review of this article
I am a researcher with the nonprofit Consumers Union, publisher of Consumer Reports, based in Yonkers, NY, US. I am reviewing this article according to the instructions at WP:HealthReview.

I think that this article could be improved by adding this statement:

In the Bone Health section, this statement is correct and very timely but I think needs some additional content so the reader understands the details about the dosages and form being addressed here better:  The United States Preventive Services Task Force issued a draft statement on 12 June 2012 recommending that healthy postmenopausal women should not take low doses of calcium or vitamin D supplements to prevent fractures.

In terms of the "healthy postmenopausal women should not take low doses of calcium or vitamin D supplements to prevent fractures" part, the USPSTF draft statement recommended against daily supplementation with 400 IU or less of vitamin D3 and 1000 mg of calcium carbonate for the primary prevention of fractures in postmenopausal women.

This reference supports the above statement: http://www.uspreventiveservicestaskforce.org/draftrec3.htm

Thank you for your attention.

(I am not a regular Wikipedia editor so if you post on my Wikipedia user page I may not get your message.)

(If you need help implementing any of these changes please go to WP:HealthReview and request support there, as I cannot help you.)

Thank you,ChrisHendel (talk) 20:30, 18 June 2012 (UTC)


 * Thanks for your note!Jytdog (talk) 00:08, 14 August 2012 (UTC)


 * I must say the quote above (also in the article) is so ambiguous that it defies logic. I have tried to find the basis of the comment and it sounds like scare mongering. It seems that 10 to 33% of people in a study taking 1 to 12 times the indicated dose of vitamin D had elevated levels of urinary and/or blood calcium at some point in a year long study (no kidney stones reported though these are a possible result). The calsium levels did not correlate with the vitamin D dosage so are not even relevant. What is the purpose of this statement other than to confuse the reader?  The link above no longer works. I think the wording should be changed to indicate that 400 IU might be an inadequate dose as it did not show theraputic effect and a 12 times dose has shown no incidence of kidney stones. The recomendation is 800 IU after all in many regions. Idyllic press (talk) 12:56, 4 September 2012 (UTC)


 * The US Preventive Services is no joke.http://www.uspreventiveservicestaskforce.org/index.html   Links are here - took about 2 seconds of googling to find this http://www.uspreventiveservicestaskforce.org/uspstf12/vitamind/vitdfact.pdf Jytdog (talk) 13:10, 4 September 2012 (UTC)


 * You can get 400 IU in a matter of seconds of Sun exposure, this is thus best compared to some homeopatic treatment. We know that homeopathic drugs are safe primarily because of the underlying theoretical issues that prive that they cannot work. Lacking such a theoretical understanding, you could always have people claiming that it may do harm and demanding rigorous double blind tests to rule out any harm. With that attitude, you would never be able to rule out harm.
 * In case of vitamin D, we have a good theoretical understanding of vitamin D as far as the calcium metabolism is concerned. We know that unless there is unregulated calcitriol production you can't get hypercalcemia, unless your calcidiol level is at least 500 nmol/l and to reach such high calcidiol levels you need to take at least 40,000 IU/day for many weeks.


 * There is an extensive literature about how extremely high calcidiol levels cause hypercalcemia (while this is not 100% clear yet, a lot is known), but here on Wikipedia, none of our articles write anything about this, not even the article about hypervitaminosis D. This then gives the false impression to readers that in medicine nothing is known about this issue, and that then implicitely suggests that the very low RDAs and ULs areneeded to protect against some well established harm that occurs at higher doses. Count Iblis (talk) 16:05, 4 September 2012 (UTC)

Confused
"The best evidence of benefit is for bone health[8]:5 and a decrease in mortality in elderly women."

But what is a decrease in mortality? "Mortality is the condition of being mortal, or susceptible to death; the opposite of immortality", what does it mean in this case? A supplementation for prevention of mortality? That doesn't even make the slightest sense. — Preceding unsigned comment added by 77.98.145.247 (talk) 03:06, 13 July 2012 (UTC)


 * Sorry that is kind of medical-jargony.

mortality /mor·tal·i·ty/ (mor-tal´it-e) 1. the quality of being mortal. 2. see death rate, under rate. 3. the ratio of actual deaths to expected deaths.

note: death rate is an expression of the number of deaths in a population at risk during one year. The crude death r. is the ratio of the number of deaths to the total population of an area; the age-specific death r. is the ratio of the number of deaths in a specific age group to the number of persons in that age group; the cause-specific death r. is the ratio of the number of deaths due to a specified cause to the total population.

So a reduction in "mortality" in a population of old people - what would that mean? If I have two hundred people and life expectancy is 72 years old, and 30 people are over 72 years that year, I would expect to have a mortality of 15%. Let's say I give half of the group vitamin D. And let's say that 10 people in that group die. As I expected 15 people in the other group die. I have a mortality of 10% instead of 15% - a reduction in mortality. Jytdog (talk) 00:57, 14 August 2012 (UTC)


 * I think you mean "Let's say I give a test group of 100 people a daily dose of vitamin D during a 5-year period. And let's say that 10 people in that group die during the 5-year period. During that 5-year period a second control group (matched for age and sun exposure) of 100 people who are not taking vitamin D, are given sugar pills instead. 15 people in the control group die during that 5-year period. That is a mortality of 10% for the test group compared to 15% for the control group - a reduction in mortality of 5%. This is to illustrate only the use of the word "mortality".  The numbers are fiction. Greensburger (talk) 16:28, 5 September 2012 (UTC)
 * I don't see a huge difference but yes that is good!Jytdog (talk) 16:38, 5 September 2012 (UTC)

It is unclear what is meant by "The loose association between the team members Bourdillon, Rosenheim, King and Callow was very productive . . " in the "History" section. Who are these people, and what are their first names? What did their loose association entail(talk) 23:47, 16 October 2012 (UTC)
 * I took a shot at addressing this in the article. great questions.Jytdog (talk) 01:58, 17 October 2012 (UTC)

Health effects
The article should have a summary of what the most reliable source says as to the effects of raising vitamin D levels by supplementation. The Institute of Medicine's panel of experts said 20ng/ml is sufficient and higher levels can damage health. They aren't 'tentative', they say the evidence for benefit from supplementation does not stand up and there is real evidence harm may result. The article should mention that is the IoM's position (the IoM panel have recently formally reiterated it). It would be deceptive to say that the balance of opinion is that evidence is lacking that raising vitamin D levels via supplementation does improve health, and not mention that a most authoritative study cautioned that there is evidence suggesting that raising vitamin D levels through supplementation can damage health. I think the article is privileging fringe science and not reflecting the balance of medical opinion. Only the biggest and best studies should be mentioned in the article, but I think the studies I have recently cited are worth noting as they indicate that the IoM report does reflect a consensus, one which is inexorably hardening against supplementation.

Serum 25-hydroxyvitamin D concentration and risk for major clinical disease events in a community-based population of older adults: a cohort study.. Medical site Journal WATCH says "Comment: The Institute of Medicine (IOM) recommends a 25(OH)D target of 20 ng/mL, a cutoff that is substantially lower than that recommended by other organizations (JW Dermatol Dec 17 2010). In this observational study, researchers evaluated multiple outcomes (beyond bone health) and determined the optimal 25(OH)D level to be approximately the same as that recommended by the IOM. However, vitamin D levels are notoriously affected by clinical and demographic variables that make it difficult to discern cause-and-effect. Until randomized trials help us determine the optimal vitamin D level, it may be prudent to follow the IOM recommendation." Overagainst (talk) 18:45, 22 August 2012 (UTC)

The subsections in the health effects section on mortality, cancer ect ect are clearly trying to say there is evidence that higher levels not only are associated with, but may actually CAUSE positive health outcomes. The IoM looked at all this question closely and found that the evidence didn't stand up. A 2009 review cited for the text 'Low blood levels of vitamin D are associated with increased mortality' is not a sufficient ref for that rather leading statement. Most people will think the article is contradicting itself, I think quoting the much more authoritative and up to date IoM report should suffice. The Cochrane review on supplementation cited in the section on mortality is like a lot of the studies, very weak ('seems'). It does not warrant adding text .Overagainst (talk) 20:08, 22 August 2012 (UTC)


 * I've reverted your deletions of criticisms of the views of the IOM. Your arguments here are totally wrong, they misrepresent completely the way the IOM looked at the situation. Count Iblis (talk) 21:00, 22 August 2012 (UTC)
 * I would prefer a more reliable authority. Overagainst (talk) 17:11, 23 August 2012 (UTC)

POV
As can be seen from a search of his name or a look at his user page. Count Iblis is a net activist for vitamin D supplements. He shouldn't be editing the article or using this talk page to argue for his views. The Institute of Medicine were asked to look at the issue by the US government. The Institute of Medicine's report found that, apart from bone health, the evidence does not support a causual relationship between vitamin D levels and health outcomes. An encyclopedic article should say that and not imply the opposite as Doc James's edits in the heath effects subsections repeatedly do. EG "Low levels of vitamin D are associated with multiple sclerosis." and "Low vitamin D levels are associated with some cancers and with worse outcomes in other cancers". The health effects subsections are synthesis and should not be there. The Cochrane review on mortality is weak evidence for benefit from supplementation in elderly women in care homes only. It should not be used in synthesis after the text "Low blood levels of vitamin D are associated with increased mortality,[12]"

Doc James says there is "tentative evidence, yes but it is of both harm as well as benefit", and that both should be given. I think that is wrong. If a Institute of Medicine report says evidence of vitamin D having a causual relationship on MS, cancer ect does not stand up, it is not an editor's function to decide that evidence of causation and/or benefit rejected by a such a reliable authority actually stands up, and give the reader that impression by citing it in the article.

An encyclopedic article would be referenced to Dietary Reference Intakes for Calcium and Vitamin D, and say something liker this 'The Institute of Medicine are widely considered a reliable authority on health. According to a government commissioned Institute of Medicine report the evidence suggests there is no causual relationship between vitamin D levels and non-bone health outcomes. There is evidence for an adverse effect on health by vitamin D levels that are achievable by current levels of supplementation'. Overagainst (talk) 11:24, 24 August 2012 (UTC)


 * Except that I am pretty good at putting my POV aside while you are not. The IOM has not ruled out positive health effects of having higher clacidiol levels of, say, 150 nmol/l. There is a lot of evidence for the relation between MS and higher vitamin D levels that was not available at the time the IOM report was written. E.g. the discovery of a genetic mutation that causes calcidiol to be broken down a lot faster than normal in families who have a far greater incidence of MS. The probability of that being a concidence is one in many billions.


 * Any article on vitamin D based on my POV would be radically different froim the current article, and I never advocated writing up someting here. However, I've noted what 'you have done to the Hypervitaminosis D article (this is largely written by you). Wat is that article about? Is this really about hypervitaminosis D? No it isn't! I can find very little about hypervitaminosis D from reading that article. Only the lede and the first section are about that subject and you only give very scant information, it would be barely enough for a primary school student who wants to give a school presentation on that subject. The rest of the article is about fringe theories of long term effects of using vitamin D supplements in normal doses (below 10,000 IU/day). Almost no medical professionals take this seriously, vitamin D supplements are routinely prescribed in doses that are much higher e.g. 50,000 IU/week so the described effects would be much higher, yet few doctors would worry about cardiovascular disease etc. via the effect described in the article. So, the article is completely misleading.


 * An article that is really about hypervitaminosis D would write about what is known about the mechanisms that cause hypervitaminosis D. Nothing whatsoever can be found in the article about that. You have to use Google to search for articles to read about such simple data that the calcidiol level in case of hypervitaminosis D is typically above 500 nmol/l, that at those levels calcidiol then likely starts to bind to sites that normally only calcitriol binds to, causing hypercalcemia etc. etc. Count Iblis (talk) 16:06, 24 August 2012 (UTC)
 * It is not the function of this article to give medical advice. That is why text that said supplements of 10,000IU a day were safe was removed from the article. The Institute of Medicine panel of experts who wrote the report on vitamin D stay current I think  see here,  it is quite absurd to claim their report is outdated. IMO the 'Health effects' subsection that DocJames wrote synthesize a variety of souces to imply (on any common sense reading) that evidence shows associations between vitamin D levels and health are or may be of a causative nature. In fact the massive US government-commissioned IoM report states the evidence available indicates precisely the opposite. Those health effects subsections are out of line with the most authoritative source for medical information's exhaustive report on the subject. They are synthesizing and setting a particular Wikipedia editor (Doc James) up as a more reliable medical source than a recent major report from the Institute of Medicine.


 * More seriously the same IoM report cautions that weight of evidence suggests vitamin D levels achievable by current levels of supplementation can damage health. This important statement is not given in the article. So the average reader would conclude that there is some evidence that vitamin D supplements of several thousand IU a day say may improve health and no evidence that they will damage health. In fact the Institute of Medicine do not recommend taking any vitamin D supplements, and specifically caution against doing so. Overagainst (talk) 21:00, 26 August 2012 (UTC)


 * This article is about vitamin D, it isn't about giving people advice on supplements on the basis if some precautionary principle that would necesarily be POV in favor of assuming danger and be biased against positive health effects. The job of the IoM is to give such advice so they have to weigh up the evidence that way. The IoM report itself makes that clear, you then cannot take statements from the IoM report and assume that equal weight has been given to the evidence for benefits and harm, as they obviously didn't do that.


 * No credible evidence of adverse health effects exists, there are only a few reports of slightly more falls in elderly people who got injected with 600,000 IU. If you then assume the null hypthesis that vitamin D at dosages higher than 4000 IU/day may be dangerous (because are no double blind results that falsify that null hypothesis) then this particular observation can be seen to support this. The cautionary principle would then prompt you to oppose increasing the upper limit for vitamin D, you would keep it at 4000 IU/day until new results rigorously rule out harm.


 * But other health agencies find this approach too conservative. The French pediatric organization is e.g. recommending that babies be given 2000 IU/day, and motivates that on positive health outcomes for a whole host of diseases that the IoM has not (yet) accepted. Also they obviously have dismissed all the arguments for possible harm. Count Iblis (talk) 21:39, 26 August 2012 (UTC)


 * Response to Grant Letter on Reverse J-Shaped Association of All-Cause Mortality with Serum 25-Hydroxyvitamin D in General Practice, the CopD Study"The design of many studies does not allow for analyzing the very low and very high levels of 25(OH)D, because they compare reference values with 1 to 4 categories. To see the real shape of the curve, we believe that the data need to be analyzed either by a cubic spline analysis or by dividing the 25(OH)D levels into categories where the extreme values are apparent, since the association between vitamin D status and mortality might be driven by individuals in the very low and high levels of 25(OH)D as we state in our paper. However, this may not always be possible, since it may require a large sample size, with sufficient observations at the extremes." Overagainst (talk) 10:47, 19 October 2012 (UTC)

"The recent paper by Durup and colleagues found a J-shaped relation between serum 25-hydroxyvitamin D [25(OH)D] concentrations and all-cause mortality rates (1). While not unprecedented, this result is nonetheless surprising given the benefits of vitamin D in reducing the risk of many types of cancer, cardiovascular disease, infectious diseases, and other diseases associated with large numbers of deaths in Denmark (2).

One reason for this finding may be that women, who comprise 71.2-73.7% of those with serum 25(OH)D concentrations above 75 nmol/liter, are more likely than men to be diagnosed with low bone mass density and instructed by their physician to take supplemental vitamin D. Since many of the vitamin D-sensitive diseases are long-latency diseases, these diseases could be progressing due to low serum 25(OH)D concentrations earlier in life. Some of the effects, such as calcification of the arteries, may not be reversed through increasing serum 25(OH)D concentrations. This hypothesis is supported by two studies of the association of serum 25(OH)D concentrations with frailty status in the United States. For men, there was a monotonic decrease in frailty status with increasing serum 25(OH)D concentrations (3), while for women, there was a minimum in frailty status near 57 nmol/liter, with much higher frailty status near 12 nmol/liter and 150 nmol/liter (4). Ensrud et al. (4) considered the possibility that "fail women might be preferentially prescribed vitamin D supplements and thus have higher levels". This possibility could not be ruled out. Thus, it would be interesting to see the analyses in (1) repeated separately for men and women.

Regarding the discussion in Durup et al. (1) of U-shaped 25(OH)D-all-cause mortality rate findings, a recent meta-analysis of 11 such studies found an apparent minimum mortality rate near 80 nmol/liter (5). However, the upper 95% confidence interval of the relation at 80 nmol/liter in Figure 4 was higher than the regression fit at 115 nmol/liter. Thus, in general, these 11 all-cause mortality rate studies do not find a significant U-shaped 25(OH)D-all-cause mortality rate relation.

A concern with the Copenhagen study is that in clinical practice, when patients are found to have low have 25(OH)D concentrations, they are usually placed on vitamin D supplements to improve their status. Patients who have 25(OH)D levels in the sufficient range are much less likely to go on supplemental vitamin D. It is likely that the 2-3 year mortality in the group with low 25(OH)D is significantly underestimated as they would have had 2-3 years benefit of being on additional vitamin D, while the group with the better 25(OH)D concentrations is more likely appropriately represented in the study data as they are much less likely to have been placed on the supplement. Since the study was retrospective and the patients along with their providers were aware of the findings, the low range patients would have been managed upward potentially reducing their mortality range in the near term. If true, this would mean that the curve would be much higher in the low range and about the same in the upper range.

References

1. Durup D, Jorgensen HL, Christensen J, Schwarz P, Heegaard AM, Lind B. 2012 A reverse J-shaped association of all-cause mortality with serum 25-hydroxyvitamin D in general practice, the CopD Study. J Clin Endocrinol Metab. 2012 May 9. [Epub ahead of print]

2. Grant WB 2011 An estimate of the global reduction in mortality rates through doubling vitamin D levels. Eur J Clin Nutr 65:1016-1026

3. Ensrud KE, Blackwell TL, Cauley JA, Cummings SR, Barrett-Connor E, Dam TT, Hoffman AR, Shikany JM, Lane NE, Stefanick ML, Orwoll ES, Cawthon PM; Osteoporotic Fractures in Men Study Group 2011 Circulating 25- hydroxyvitamin D levels and frailty in older men: the osteoporotic fractures in men study. J Am Geriatr Soc 59:101-106

4. Ensrud KE, Ewing SK, Fredman L, Hochberg MC, Cauley JA, Hillier TA, Cummings SR, Yaffe K, Cawthon PM; Study of Osteoporotic Fractures Research Group 2010 Circulating 25-hydroxyvitamin D levels and frailty status in older women. J Clin Endocrinol Metab 95:5266-5273.

5. Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S 2012 Vitamin D deficiency and mortality risk in the general population: A meta- analysis of prospective cohort studies. Am J Clin Nutr 95:91-100.

Conflict of Interest: WBG receives funding from the UV Foundation (McLean, VA), Bio-Tech Pharmacal (Fayetteville, AR), the Vitamin D Council (San Luis Obispo, CA), and the Vitamin D Society (Canada). DAM is a clinician who does not receive any outside funding and has no conflicts of interest to report." Count Iblis (talk) 15:50, 19 October 2012 (UTC)

Low D equals longer life
Levels of 25-hydroxyvitamin D in familial longevity: the Leiden Longevity Study "Compared with controls, the offspring of nonagenarians who had at least one nonagenarian sibling had a reduced frequency of a common variant in the CYP2R1 gene, which predisposes people to high vitamin D levels; they also had lower levels of vitamin D that persisted over the 2 most prevalent genotypes. These results cast doubt on the causal nature of previously reported associations between low levels of vitamin D and age-related diseases and mortality. " Overagainst (talk) 10:32, 8 December 2012 (UTC)


 * Reading the article, I don't see any convincing arguments that the effect is due to low vitamin D. Since all that vitamin D does is to switch on or off certain genes, it can also be the case that nonagenarians have the same gene expression that a normal person only has if they have high vitamin D levels. Count Iblis (talk) 22:36, 11 December 2012 (UTC)