Talk:Vitamin D/Archive 3

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Away

I am very busy just now and can't see myself contributing here for the next few days or more. Sorry. Basically, Overagainst, my crit above boils down to original research, synthesis and reliable sources. A subject as mature and active as vitamin D should rely almost exclusively on authoritative reviews. Every conclusion reported here should be an accurate paraphrase from a systematic review. If it can't be fond in a high quality source like that, it doesn't belong here. I've asked SBHarris, who has some expertise and interest in the subject if he/she would like to get involved. Please continue your valuable work here, but please do it through the prism of SYN, MEDRS and OR. I should be back by Friday. Anthony (talk) 04:01, 6 April 2010 (UTC)

I would encourage people reporting mere associations between vitamin D (25-OH-D, or whatever) levels and disease, to remember that association is not causation. Very frequently associations are due to proxy variables, which in practice means that the association between A and B is caused by C, not because B causes A.

Remember how many times association studies have burned people when the prospective intervention trial was finally done. Vitamin E and hormone replacement for menopause looked GREAT in the epidemiological studies, then bombed (or nearly bombed) in the placebo-controlled intervention trials. People who take vitamins and hormones and supplements and get out in the sun, are just a different group of people than those who don't. People who marry and go to church are also healthier than people who don't, but does anybody really think that going to church might lengthen your life?? [Voice from the back: no, but it will SEEM longer...]

In the meantime, paying a lot of attention to uncontrolled retrospective epidemiological studies which are positive, amounts to giving them undue weight, since they mean very little. (Retrospective epidemiolgical which are NEGATIVE mean much more, for reasons you'll see if you think about it). So editors, have a care for this. Put the information in, but don't give it a lot of space, and explain somewhere that the quality of inference from it, is necessarily of a lesser grade. Unless you'd like to get burned again, like prevention people did with beta-carotene.

And by the way, I should mention that I personally take 4000 IU D3 per day, and have levels of 80 ng/mL of 25-0H-D. But that's because the stuff is cheap and probably not harmful, not because I think the evidence for it is great. And I don't recommend that dose for everyone; I recommend the blood test, based on history. SBHarris 18:51, 6 April 2010 (UTC)

My proposed text for 'Circulating 25(OH)D levels in highly sun exposed people' left Anthony wondering what it was getting at so it was poorly written, sorry. I will try for more clarity in future and will be giving the scientific consensus ( which I happen to agree with 100%) due weight. The current authorative scientific consensus is represented by the NIH Office of Dietary Supplements. "A concentration of <15 nanograms per milliliter (ng/mL) (or <37.5 nanomoles per liter [nmol/L]) is generally considered inadequate; concentrations >15 ng/ml (>37.5 nmol/L) are recommended. Higher levels are proposed by some (>30 ng/ml or >75 nmol/L) as desirable for overall health and disease prevention [12], but insufficient data are available to support them" The National Academies (formerly National Academy of Sciences) have an Adequate Intake (AI) for vitamin D, AIs are established when evidence is insufficient to develop an RDA and are set at a level assumed to ensure nutritional adequacy. Importantly the AIs for vitamin D (200IU a day up until 50 years old) are based on the assumption that the vitamin is not synthesized by exposure to sunlight. This is not the same as avoiding direct sunlight, see Latitudinal Variations over Australia of the Solar UV-Radiation Exposures for Vitamin D3 in Shade Compared to Full Sun They are really talking about people like submariners. It could be interpreted as sanctioning the talking of 200IU a day through the winter if you live where UVB is not strong enough to make vitamin D for some of the year but they do not specifically say that. (and it might be worth remembering that northern Europeans have been living with a UVB less winters for hundreds of generations). It would be possible to ignore the case being made by Holick, Vieth and company or the associations between vitamin D (25-OH-D, or whatever) levels and disease being given by the Garland brothers ect. but those who come to the article will get the wrong idea about the lack of weight that school of thought carries if its very widely publicized claims are not mentioned and debunked with relevant references. As an experienced editor do you think that the the arguments for the claim that the minimum 25(OH)D level for good health is 30-32 ng/ml should not be mentioned even in the thoroughly critical way I propose ? Overagainst (talk) 12:15, 7 April 2010 (UTC)

anorexia? no way

anorexia caused by a vitamin overdose? i seriously doubt it, requires a proper citation and not some obscure book-reference Markthemac (talk) 01:49, 7 April 2010 (UTC)

I've removed reference to hypertension in intoxication, as I haven't seen a reliable source for the claim, and have paraphrased and cited Merck. Anthony (talk) 01:48, 9 April 2010 (UTC)

New lead

I have rewritten the lead so that it more accurately reflects the sources cited, and have left out the recommended daily intake because, as it stood, the lead misrepresented the sources, and it is too controversial and complex to cover in the lead. Briefly, the lead said

• Up until 51 years of age 200IU is an adequate intake of vitamin D to maintain bone health and normal calcium metabolism in healthy people assuming no synthesis by exposure to sunlight.

But

The first ref, [1] relying on a 1998 Department of Health report, recommends per day:
0-6 months = 8.5μg (340IU)
7 months - 3 years = 7μg (280IU)
4-65 years = nil
65+ years = 10μg (400IU)
During pregnancy & lactation = 10μg (400IU)
So, according to these UK guidelines, 200IU/day is not adequate for children up to 3 years or pregnant or lactating women.

The lead accurately paraphrased a portion of the second ref [2] describing the recommendations of the Food and Nutrition Board (FNB) of the US Institute of Medicine but the lead failed to mention that its source goes on to say "The current Dietary Reference Intakes for this nutrient were established in 1997, and since that time substantial new research has been published to justify a reevaluation of adequate vitamin D intakes for healthy populations... The FNB established an expert committee in 2008 (due to report late 2010) to review the DRIs for vitamin D (and calcium)."

The source then points out that in 2008 the American Academy of Pediatrics (AAP) issued recommended intakes for vitamin D that exceed those of FNB. "AAP recommends that exclusively and partially breastfed infants receive supplements of 400 IU/day of vitamin D shortly after birth and continue to receive these supplements until they are weaned and consume ≥1,000 mL/day of vitamin D-fortified formula or whole milk [20]. (All formulas sold in the United States provide ≥400 IU vitamin D3 per liter, and the majority of vitamin D-only and multivitamin liquid supplements provide 400 IU per serving.) Similarly, all non-breastfed infants ingesting <1,000 mL/day of vitamin D-fortified formula or milk should receive a vitamin D supplement of 400 IU/day. AAP also recommends that older children and adolescents who do not obtain 400 IU/day through vitamin D-fortified milk and foods should take a 400 IU vitamin D supplement daily". Anthony (talk) 15:04, 11 April 2010 (UTC)

"Vitamin D insufficiency"

"Insufficiency' is commonly used to mean anything under 30-32ng/ml nowadays, Why not just use 'deficiency' as the very low levels associated with bone disease are being referred to.

"When synthesized by monocyte-macrophages, calcitriol acts locally as a cytokine, defending the body against microbial invaders".[3]

Does this belong in the header?; it's a piece of news which could have implications for vitamin D intake but it does seem to be implying that in the presence of an infection the more D you have the better. That might not be true, see cytokine storm

"Vitamin D also modulates neuromuscular function, reduces inflammation",

"Plays an important role' or 'helps maintain' is maybe more faithful to the ref than using "modulates". "Modulates" goes a bit further than just paraphasing the ref IMO. I couldn't find where it says vitamin D " reduces inflammation" in ref 4, Vitamin D is used for counteracting some of the side effects of corticosteroid medications such as prednisone which are are often prescribed to reduce inflammation. Overagainst (talk) 21:25, 13 April 2010 (UTC)

Ref 4 linked to two web versions, one from 2007 and one from 2009. The lead refers to the 2009 version. I have unlinked the 2007 ref.
1. Vitamin D insufficiency. Insufficiency is the term used in the ref.
2. Does this belong in the header? Certainly; hormone and cytokine are the two roles of vitamin D.
3. Modulates neuromuscular function, reduces inflammation. It is a fair paraphrase of the 2009 version: "Vitamin D has other roles in human health, including modulation of neuromuscular and immune function and reduction of inflammation. Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D." Anthony (talk) 09:36, 14 April 2010 (UTC)

Re 1. Lead says- "Vitamin D insufficiency can result in thin, brittle, or misshapen bones, while sufficiency prevents rickets in children and osteomalacia in adults"

In the ref "Although rickets and osteomalacia are extreme examples of the effects of vitamin D deficiency, osteoporosis is an example of a long-term effect of calcium and vitamin D insufficiency "

Insufficiency might have osteoporosis as a long term effect but only deficiency causes rickets and osteomalacia. Saying vitamin D insufficiency can result in misshapen bones is misleading because mere insufficency can't give you rickets and osteomalacia. The more serious condition of deficiency is needed to develop rickets and osteomalacia. Overagainst (talk) 14:02, 14 April 2010 (UTC)

1. The lead is a faithful paraphrase of the Office of Dietary Supplements 2009 fact sheet. The author uses "insufficient" to include "deficient"; "deficiency" is a level of insufficiency, extreme insufficiency. I take your point, though. It doesn't make it clear that misshapen bones are the product of D3 levels lower than those that produce thin or brittle bones. That could be done in the body of the article. Anthony (talk) 15:07, 14 April 2010 (UTC)

UVB and D₃ synthesis

The article says

• Vitamin D3 is made in the skin when 7-dehydrocholesterol reacts with UVB ultraviolet light at wavelengths between 270–300 nm, with peak synthesis occurring between 295-297 nm.

But the first ref (Norman 1998) says "7-Dehydrocholesterol absorbs UV light most efficiently over the wavelengths of 270–290 nm and thus only UV light in this wavelength range has the capability to produce vitamin D3". and the second ref (MacLaughlin, Anderson & Holick 1982) says "The optimum wavelengths for the production of previtamin D₃ were determined to be between 295 and 300 nanometers." The paragraph's third ref (Holick 1995) says "solar ultraviolet B photons with energies between 290 and 315 nm penetrate the skin where they cause the photolysis of 7-dehydrocholesterol (provitamin D3) to precholecalciferol (previtamin D3)" and "when human skin is exposed to narrow band radiation (295-300 nm), “65% of the original 7-dehydrocholesterol content is converted to precholecalciferol."

The third ref (Holick 1995) is meant to support this

• These wavelengths are present in sunlight when the UV index is greater than 3. At this solar elevation, which occurs daily within the tropics, daily during the spring and summer seasons in temperate regions, and almost never within the arctic circles, vitamin D₃ can be made in the skin, with prolonged exposure to UVB rays an equilibrium is achieved in the skin, and excess vitamin D simply degrades as fast as it is generated.

It doesn't. These are old refs so perhaps the article is right. Does anyone have (preferably one} ref that supports the text's assertions? For now, I've replaced the ref's with . Anthony (talk) 03:06, 12 April 2010 (UTC)

"The action of sunlight (ultraviolet (UV) radiation of wavelength 290-310nm) on the skin converts 7-dehydrocholesterol to previtamin D3, which is then metabolized to vitamin D3 by isomerization. [...]Solar UV radiation varies with latitude, time of year and time of day. From mid-October to the beginning of April at latitudes of about 52° and above (the UK is at latitude 50-60° N) there is no UV radiation of appropriate wavelength for the cutaneous production of previtamin D3." [3]

The article says Vitamin D3 is made in the skin when 7-dehydrocholesterol reacts with UVB ultraviolet light at wavelengths between 270–300 nm

This seems to be wrong as little or no radiation below 290nm reaches the earth's surface and more importantly ultraviolet (UV) radiation of 220-290 nm is classified as UV-C, (UVC is not normally found in commercial sunbeds). "Accidental overexposure to UVC can cause corneal burns, commonly termed welders' flash, and snow blindness, a severe sunburn to the face. While UVC injury usually clears up in a day or two, it can be extremely painful". [4]. Overagainst (talk) 17:30, 15 April 2010 (UTC)

Health effects of mega doses

http://jama.ama-assn.org/cgi/content/full/303/18/1815 Doc James (talk · contribs · email) 14:30, 12 May 2010 (UTC)

The above study used a single annual dose of 500,000 IU of vitamin D to each patient which resulted in an increase of falls and fractures. This mega overdose was clearly toxic and says nothing about possible benefits from the same amount of vitamin D divided into daily doses over a full year (1370 IU per day). However, this study does establish a toxic single dose to be avoided and therefore should be mentioned in the article. Greensburger (talk) 15:03, 12 May 2010 (UTC)

Yes I agree and that is what they say in this study as well.Doc James (talk · contribs · email) 15:25, 12 May 2010 (UTC)

7-Dehydrocholesterol conversion to pre-vitamin D3

How does the concentration of 7-Dehydrocholesterol in human skin vary with age etc?

How fast does the conversion reaction to pre-vitamin D3 take place, when exposed to UVB? Minutes? Seconds? Faster? How brief of an exposure of human skin to UVB is succifient for the process to take place?

Is the conversion reaction proportional to UVB exposure, over a wide range? Or is there perhaps a threshold of UVB that must be exceeded for the reaction to take place? And is there an upper limit of UVB intensity, beyond which reaction efficiency is reduced?

How does all of this vary in different species?

What is the logic or evolutionary "reason" for requiring external UVB to produce the required Vit D? Do any species somehow synthesize Vit D without depending on external UVB? -71.174.180.139 (talk) 02:05, 4 June 2010 (UTC)

"7-dehydrocholesterol in the skin absorbs UVB photons with energies between 290 and 315 nm in its 5,7-diene region, forming previtamin D3. [1] This reaction is purely dependent on light, and takes place in all animals but is particularly important in vertebrates. If 7-DHC is placed in vitro (in quartz tubes), the reaction takes place in the same way. It is not dependent on enzymes or cells at all. [2][3] If this previtamin D3 remains in the skin, and is further exposed to light, it breaks down into inert bioproducts, lumisterol and tachysterol. [1] No more than 15% of 7-DHC in the skin can be transformed to previtamin D3 in humans, no matter how long the exposure to sunlight. [4] This may be the maximum in all systems as it is the maximum in vitro [2] [3] and the maximum in surgically obtained human skin [7]. This is a useful regulatory device, making it impossible for an animal to produce too much previtamin D3. If the stores of previtamin D3 are completely depleted, lumisterol and tachysterol then become able to be photo-isomerized to previtamin D3, so these compounds are useful storage devices. [5]" http://www.anapsid.org/uvbanne.html 1999 Anne Marsden

This source has additional interesting details. -71.174.180.139 (talk) 03:26, 4 June 2010 (UTC)

50,000 IU supplements

50,000 IU mega-dose pills seem common.

Doctors have a tradition of prescribing 50,000 IU weekly for 8 weeks. Why?

What are the pros and cons of taking so much weekly, vs. taking the same amount more evenly, on a daily basis? What are the pros and cons of spreading it out even more evenly, say 3 times a day?

If it is important to ingest fat at the same time, how much of what fats are required? -71.174.180.139 (talk) 02:45, 4 June 2010 (UTC)

Vitamin D Best Taken With Largest Meal of Day, Study Finds
www.drugs.com/news/vitamin-d-best-largest-meal-day-study-finds-24290.html
"boosted the level of vitamin D in their blood by an average of 56 percent"

50,000 IU Vit.D is very popular in research studies. The main reason seems to be "convenience". It may actually be more convenient (and cheap) for some consumers; but most might find a regular daily habit easier. Mostly large doses seem to be used because it is more convenient for institutions to administer/enforce, since fewer "treatments" are needed.

There are almost no studies comparing more vs. less frequent dosing of same over-all quantities. There was a crazy study giving thousands of old women 500,000 (ten 50,000 pills) once a year (because they were afraid the subjects were forgetting to take daily pills). It turned out quite badly. What a surprise. The women fell more and had more fractures; they can't figure out exactly why.

Once-A-Year Vitamin D Megadose Ups Fracture Risk: Study

www.drugs.com/news/once-year-vitamin-d-megadose-ups-fracture-risk-study-24382.html

-96.237.69.64 (talk) 02:16, 11 June 2010 (UTC)

The higher "Prescription" doses such as 50,000 are often D2 rather than D3. This is bad -- D3 is generally considered to be a better supplement than D2.

Taking Prescription Vitamin D? You Might Want to Think Twice…

blog.easy-immune-health.com/nutrients/vitamin-d/prescription-vitamin-d-not-suitable-for-supplementation/

-96.237.69.64 (talk) 13:28, 11 June 2010 (UTC)

cod liver oil

Modern cod liver oil does not have as much Vitamin D as it used to. It does contain a lot of Vitamin A in a form called Retinoic Acid. Vitamin A as retinoic acid prevents Vitamin D from being utilized. This source concludes that modern cod liver oil is a Bad Thing:

Cod Liver Oil Information That's Not for Your Grandma!

www.easy-immune-health.com/cod-liver-oil-information.html

-96.237.69.64 (talk) 13:36, 11 June 2010 (UTC)

not just kidneys

The article mostly reflects the simplistic traditional theory that only the kidneys produce activated 1,25-Vit D. But the kidneys only make a limited quantity regardless of how much 25-Vit D comes from the liver. Dr. Holick (The UV Advantage, Dr. Holick, 2004, p.23, p.103-104) claims to have published a study in 1998 proving that there are cells throughout the body that can produce their own local 1,25-Vit D as long as there is plenty of 25-Vit D around, with general anti-cancer benefits. Is this "true"? Please update the article to properly reflect. -96.237.69.64 (talk) 23:12, 22 June 2010 (UTC)

The surprising microgram

According to the International System of Units microgram can be written also as μg and the standard does not support other ways. According to Greensburger, "This is an English language article and vitamin labeling in the U.S. uses mcg not μg." However accurate his/her argument may be, this article is also international and serves all users and readers who speak English language, which is an official language in 53 countries and several international organizations. -Uikku (talk) 06:15, 5 July 2010 (UTC)

Ah, sure it is an international encyclopedia, with usual international conventions on basic measurement units reflected in MOS. (Conversions are Ok though). Materialscientist (talk) 06:22, 5 July 2010 (UTC)

Bogus links?

Is Vitamin D Council a legitimate site? - some of the content seems to ring alarm bells and it is listed as questionable on QuackWatch. Perhaps we should think twice before linking it as an external reference? —Preceding unsigned comment added by 125.238.88.20 (talk) 13:24, 10 July 2010 (UTC)

The website Vitamin D Council says "The Vitamin D Council is a group of concerned citizens who believe many humans are needlessly suffering and dying from Vitamin D Deficiency" and lists their directors that include two MDs and two PhDs. Members include numerous professors. Two of the directors have bio links which point to their hundreds of respectable publications.

Anti-vitamin crackpots libel anybody they disagree with, including other crackpots in addition to respectable MDs, scientists, professors, researchers, educators, etc. Greensburger (talk) 17:09, 10 July 2010 (UTC)

"Vitamin" confusion

According to the "Vitamin" article as currently displayed on Wikipedia:

"A vitamin is an organic compound required as a nutrient in tiny amounts by an organism.[1] In other words, an organic chemical compound (or related set of compounds) is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet."

As I understand it, Vitamin D only sometimes qualifies, depending on the location, time of year, and individual sun exposure. I think a mention of why it was originally and is still classified as a vitamin would help reduce confusion, as one of the few facts that most people know about it is usually that your skin makes it from sunlight, which makes definition as a vitamin somewhat confusing. Nightsmaiden (talk) 11:44, 30 July 2010 (UTC)

In response to your suggestion, I added a short paragraph explaining why vitamin D can be both a nutrient and also be made in the skin. Greensburger (talk) 06:48, 2 August 2010 (UTC)

The term "vital amines", the info on cod liver oil and vitamin A (including the work of Margarite Davis and David Mellanby), and the last statement of the paragraph do not appear to be supported by the cited source. Perhaps additional sources should be added for those parts of it. --Robert.Allen (talk) 10:07, 2 August 2010 (UTC)

I added a reference for "vital amines", cod liver oil, vitamin A, sick dogs, Davis, and Mellanby. Greensburger (talk) 07:56, 3 August 2010 (UTC)

Bold texthello my name is desray and i wanted to now a lttle information about vitamin D. and a little bit about what the vitamin is used for so when u get my question please can u answer it because i was just about to take on of the chewy vitamin D things and i asked my frend wat it vitamin d and she just suggested for me ro go on the internet and ask someone or somthing about wat it seems to be or wat it can do to the human body so thx for pactiently waiting for me to be done so that u can answer my easy question thx bye now!!!! =) :) if u help me then mabey i will like ur guyses website a little better then i do now so bye <3 —Preceding unsigned comment added by 24.21.200.78 (talk) 18:22, 13 September 2010 (UTC)

The structural formula of vitamin D

The structural formula of vitamin D contains errors. The methyl group at atom С-13 should be placed over a plane of rings C and D, and hydrogen at atom C-14 should be located under a plane of rings C and D.--Kibogo (talk) 08:01, 20 September 2010 (UTC)

Hi Kibogo and thank you for pointing that out. Can you provide the details (author, date, title and page number) of an English-language text book or peer-reviewed paper that confirms your observation? Anthony (talk) 08:15, 20 September 2010 (UTC)

The absolute configuration of cholesterol and vitamin D has been established in 1954-1956 [Absolute Configuration of Cholesterol/ Cornforth, J. W.; Youhotsky, Irene; Popják, G./ Nature, Volume 173, Issue 4403, pp. 536 (1954);

review in the book /Louis F Fieser,Mary Fieser. Steroids. Reihold Publishing Corp, New York, 1959: chapter 1, 4]. 

In the structural formula placed in article, the configuration of chiral centers at atoms C13,C14,C17 corresponds to a configuration these centers in the enantiomer cholesterol [. Scott D. Rychnovsky, Daniel E. Mickus;J. Org. Chem., 1992, 57 (9), pp 2732–2736].--195.91.230.32 (talk) 22:02, 20 September 2010 (UTC)--195.91.230.32 (talk) 22:07, 20 September 2010 (UTC) Is this enough? --Kibogo (talk) 22:19, 20 September 2010 (UTC)

Thanks Kibigo. I'm not a chemist. If the papers you refer to support the changes you propose, can you please make the changes in the article? Paste

<ref>Cornforth, JW., Youhotsky, I. & Popjak, G. (March 1954). "Absolute configuration of cholesterol" ''Nature'' '''173''' (4403): 536. PMID 13154371</ref>

and

<ref>Rychnovsky, SD & Mickus, DE (1992). {{plainlink|url=http://pubs.acs.org/doi/abs/10.1021/jo00035a036|name="Synthesis of ent-cholesterol, the unnatural enantiomer"}} ''The journal of organic chemistry'' '''57''' (9): 2732–2736.</ref>

and

<ref>Fieser, LF & Fieser, M (1959) ''Steroids'' New York: Reihold Publishing Corp.</ref>

into the article after the corrected text and it will appear as citation numbers like this,^[24][25][26] and the full citations will appear at the bottom of the page under References. If you need to change illustrations, let me know and I'll find an editor who can help with that. If you have any other questions, just ask. Anthony (talk) 10:17, 21 September 2010 (UTC)

Dear Anthony, the correct formula of vitamin D3 is resulted in article Cholecalciferol. I would be grateful to you if you can transfer the formula from article Cholecalciferol to this article. Vitamins D3 and D2, cholesterol and the majority of others sterols possess the same absolute configuration of a sterol nucleus. It seems to me therefore what more pertinently to cite the data about an absolute configuration of corresponding molecules in articles Cholecalciferol or Cholesterol, or Sterols. Thanks for the help --Kibogo (talk) 20:54, 21 September 2010 (UTC)

recommended among

I removed the statement "no established recommended intake by NIH" as the NIH website[[5]] cite the Food and Nutrition Board recommendations. Gerardw (talk) 22:34, 11 October 2010 (UTC)

Is the amount of vitamin D in 85g of catfish better expressed as the amount in 100g of catfish, as most of the rest of the natural sources are in that format? same with Sardines.

Eggs and fish liver oils seem to be in natural units - if 15ml is a serving spoon/tablespoon size worldwide. —Preceding unsigned comment added by Carawaystick (talk • contribs) 23:01, 17 November 2010 (UTC)

Editing References

I wanted to edit Reference 98 on this page: http://wiki.riteme.site/wiki/Vitamin_D

The link for Ref. 98 no longer works, and I hunted about and found the article free online here: http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0781.2010.00524.x/pdf

But when I tried to edit the References, I got taken here: http://wiki.riteme.site/w/index.php?title=Vitamin_D&action=edit&section=24 which is a blank page.

Is there no way to edit References? Perhaps it requires one to have a special status. And perhaps someone who is able to edit the References could check that what I've written above is correct and make the edit themselves.

Rainlightly (talk) 23:50, 12 December 2010 (UTC)

I fixed that reference for you. When you wish to change the reference, usually you need to edit the document itself and find it there. (There are several citation styles adopted for wikipedia article, but usually, the "reference list" which you tried to edit is merely an operator which collects references added in various places in the document). Materialscientist (talk) 23:56, 12 December 2010 (UTC)

A 2011 review of the evidence!

Institute of medicine report [6] Doc James (talk · contribs · email) 02:16, 8 January 2011 (UTC)

It's been updated. [7] --Anthonyhcole (talk) 04:55, 8 January 2011 (UTC)

The Institute of Medicine of the National Academies is to publish its Dietary Reference Intakes for Calcium and Vitamin D

IoM NYT article. The 14-member expert committee, convened by the Institute of Medicine, examined nearly 1,000 publications. They have determined that most people have adequate amounts of vitamin D, ie a level of 20 to nanograms of vitamin D per milliliter of blood. This all that anyone needs, (not over 30 nanograms of vitamin D per milliliter of blood which the committee says is at the top of the normal range). There is no support for claims that the higher levels which require supplements to attain are beneficial, a level of 20 to 30 nanograms is all that is needed for bone health and almost everyone is in that range. Not only is there no benefit in trying to attain attain still higher levels such as 40 to 50 nanograms the committee says there are now indications that such high concentrations are harmful. Most people have adequate amounts of vitamin D in their blood supplied by their diets and natural sources like sunshine. I think the article should be changed to reflect that.Overagainst (talk) 20:21, 1 December 2010 (UTC)

Vitamin D is required for much more than "bone health". --cheers, Michael C. Price ^talk 08:56, 7 December 2010 (UTC)

"This review found that information about the health benefits [of vitamin D] beyond bone health were from studies that provided often mixed and inconclusive results and could not be considered reliable," [8]. The recommendation that people need 600 international units a day (800 a day over age 70) assumes that they are not getting any vitamin D from skin synthesis( which is totally unrealistic for anyone in the real world unless they avout the sun and the shade) and warns that doses above 4,000 units a day may be harmful. The people who say that vitamin D has all these non bone benefits uniformly recommend levels over 20 to 30 nanograms per milliliter. For example What is the Dose‐Response Relationship between Vitamin D and Cancer Risk?says that 50% of the colon cancer incidence in north America could be prevented by maintainance of a serum 25(OH) D level of 34ng/ml. to prevent 50% of breast cancer - 52ng/ml. here is some information about one of the authors "Frank C. Garland, 60, the University of California at San Diego epidemiologist who, with his brother Cedric, was the first to demonstrate that vitamin D deficiencies play a role in cancer and other diseases, died Aug. 17 at UCSD Thornton Hospital. He had cancer of the esophageal junction" [9] Not exactly in the fullness of his years was he? And is it any wonder Plasma vitamin D and mortality in older men: a community-based prospective cohort study. "During follow-up (median: 12.7 y), 584 (49%) participants died. There was a U-shaped association between vitamin D concentrations and total mortality. An approximately 50% higher total mortality rate was observed among men in the lowest 10% (<46 nmol/L) and the highest 5% (>98 nmol/L) of plasma 25(OH)D concentrations compared with intermediate concentrations. So that's what exceeding the Institute of Medicine recommendations ( being over 39 ng/ml) is required for, it gives a 50% higher total mortality rate. Overagainst (talk) 14:10, 8 December 2010 (UTC)

Without reading the original paper and the supporting data we cannot know if greater mortality at higher 25(OH)D concentrations was because the subjects were older at the high end and therefore had more degenerative diseases and hence a higher mortality rate. And having more diseases, wouldn't those 80 year olds probably swallow greater amounts of vitamins, including vitamin D? Also, were the subjects tested for vitamin K? With adequate calcium and vitamin D, a deficiency in vitamin K can cause calcification of soft tissue such as heart valves, perhaps from taking anti-coagulants and/or insufficient colon bacteria producing vitamin K. If the study did not control for age, unreported vitamin D intake, and vitamin K in the blood, then there is nothing to be learned from the U-shaped curve. Greensburger (talk) 03:06, 9 December 2010 (UTC)

"The idea that high plasma vitamin D concentrations are related to overall cancer death can at first seem counterintuitive, because vitamin D has potent antiproliferative, pro differentiative, and immunomodulatory functions in a variety of cell types (10). Nevertheless, experimental studies have reported that excessive vitamin D activity could promote cancer (8) and accelerate aging (11). Cancer development may be promoted by the direct stimulatory effects of vitamin D on the oncogenic enzyme CYP24 (13) and insulin-like growth factor I (IGF-I) production (32, 33). Interestingly, vitamin D excess has also been shown to exacerbate premature aging phenotypes in mouse models of aging (11). These mice, however, can be rescued and their life span extended by suppressing IGF-I activities (11), restricting dietary intake of vitamin D, or by ablating the 1a-hydroxylase gene that is essential for biosynthesis of 1,25-dihydroxyvitamin D (32, 33). {...}Greatly increased enterohepatic cancer death rates were ob- served with both low and high plasma vitamin D concentrations. This is a particularly intriguing finding, because in addition to its classical role in mineral homeostasis, the vitamin D receptor (VDR) is evolutionarily and functionally linked to a distinct group of nuclear receptors that are involved in the elimination of toxic substances absorbed by the gut (19, 22). Low concentrations of vitamin D could contribute to increased enterohepatic carci- nogenesis by reduced detoxification of secondary toxic bile acids (19, 34). Activation of VDR by these bile acids or vitamin D induces expression in vivo of CYP3A, a cytochrome P450 en- zyme that detoxifies secondary bile acids in the liver and intestine (37). Secondary bile acids are formed in the intestine but enter the bile after enterohepatic circulation (19, 34). In contrast, high concentrations of vitamin D suppress the farnesoid X receptor that detoxifies carcinogenic bile acids (12, 20, 21), suggesting a mechanism for increased cancer risk with high vitamin D concentrations. In addition, vitamin D induces osteocalcin (26), which is expressed in pancreatic cancer cells and increases their growth, proliferation, and invasion (35). Also intriguing is the fact that the synthesis and excretion of bile acids were observed to be dramatically elevated in Klotho-deficient mice (36) that ex- hibit altered mineral homeostasis due to high vitamin D activity (11).{...} Major strengths of our study include the very precise and valid measurement technique used for 25(OH)D analysis (37, 38) and the detailed characterization of study participants regarding mortality risk factors in a prospective design with no loss to follow-up. Additional advantages are the setting in a single geographic area, the homogenous population, and the large number of deaths. Furthermore, the personal identity number provided to all Swedish citizens enables individual matching to registers, resulting in objective and complete information on mortality and morbidity (17). We could thus exclude men with prevalent cancers and cardiovascular diseases at baseline. The results were not explained by competing risks. Our results were also independent of a large number of mortality risk factors, including frailty indicators, lifestyle habits, and biomarkers re- lated to calcium homeostasis. Few participants reported use of vitamin D supplements, and these were not predominantly found among men with high vitamin D concentrations. Our results were also independent of the dietary intake of vitamin D. This is in agreement with previous studies in Sweden showing that vitamin D status in our population is only modestly determined by lyfestyle factors [...] A less detailed quantile analytic approach, such as an analysis of associations with 25(OH)D quartiles, has well-described shortcomings and would have obscured findings at the extremes of vitamin D status (40). Therefore, our analytic approach with the restricted cubic spline analysis together with the categori- zation of vitamin D by our percentiles and a contemporary method (27) is a further strength of our study (40)." Overagainst (talk) 10:56, 9 December 2010 (UTC) And here is the most recent one, it suggests the point at which 25(OH) D concentrations become dangerous is only 30ng/ml ( Hey! how about that, the 14-member expert committee knows what they are talking about). Circulating 25-Hydroxyvitamin D Levels and Frailty Status in Older Women "Conclusion: Lower (<20 ng/ml) and higher (30 ng/ml) levels of 25(OH)D among older women were moderately associated with a higher odds of frailty at baseline". Here's the Science Daily article a U-shaped relationship between vitamin D levels and frailty; older women with vitamin D levels higher than 30 ng/ml and those with levels lower than 20 ng/ml were more likely to be frail Overagainst (talk) 12:17, 9 December 2010 (UTC)

The article currently says "Levels of 25-hydroxy-vitamin D that are consistently above 200 ng/mL (500 nmol/L) are thought to be potentially toxic" Such an extreme understatement amounts to incorrect medical advice IMO.Overagainst (talk) 22:29, 6 December 2010 (UTC)

The threshold at whgich hypercalcemia starts is not well known, the 500 nmol/L is a conservative limit. A recent animal experiments suggests that the point where toxicity stars lies well above 1000 nmol/L as no toxicity was aboserved at this level. People who have become ill from Vit. D overdose had levels way higher than 1000 nmol/L. Count Iblis (talk) 03:51, 14 December 2010 (UTC)

Your assertions seem to derive from a paper by R.Vieth Vitamin D Toxicity, Policy, and Science. Toxicity is the degree to which a substance can damage an organism. The article currently says "Levels of 25-hydroxy-vitamin D that are consistently above 200 ng/mL (500 nmol/L) are thought to be potentially toxic" This is virtually saying (and will be taken as meaning) that levels under 200ng/mL are not potentialy toxic, (I.E. have no potential for detectable toxic effects). The Institute of Medicine of the National Academies in fact cautions that there are indications concentrations of 40 to 50 ng/mL are harmful, as their report is is the gold standard for medical claims it ought to be made clear in the article that there is a potential for toxicity far below 200ng/mL.Overagainst (talk) 16:51, 14 December 2010 (UTC)

Hmmm, that would mean that there is a potential for toxicity without using supplements, which is a bit strange... Count Iblis (talk) 23:49, 17 January 2011 (UTC)

Very few people go as high as 40 or 50 ng/mL from sun exposure, those who do are usually white sun worshippers living in places like Hawaii. Maintaining such high vitamin D levels year round is unnatural, unusual and, as The Institute of Medicine of the National Academies cautions, has the potential to cause harm. Whites have evolved to cope with a greater annual range of vitamin D levels under much less intense UV only present for part of the year. Dark skinned people of tropical ancestry who are naturally adapted to have the optimal level of vitamin D under conditions of year round intense UV do not have high vitamin D levels. They certainly don't average anything like 40 or 50 ng/mL as I could cite from many studies of Africans or south Indians Overagainst (talk) 17:58, 11 February 2011 (UTC)

I see, but surely a net intake of 10,000 IU per day year round is natural? Hunter gatherers in Africa spend hours per day outside looking for food and this is how Homo Sapiens has lived for almost all its history. Using this webtool I find that in Namibia with 70% body exposure to the Sun around midday, it only takes 5 minutes for someone with skin type 6 to get 1000 IU on this day. Now the Bushmen I saw in a recent documentary were outside for hours, searching for animal tracks during midday. They were actually moving at slow jogging speed for hours during the afternoon heat. Vitamin d levels will saturate at somewhere between 10,000 and 20,000 IU, so that should be the ammount they are getting.

I've also read that taking showers some hours after sun exposure will interfere with vitamin D production in the skin. Perhaps this limits vitamin D levels in modern people to low levels? Count Iblis (talk) 23:03, 11 February 2011 (UTC)

Source in supplements?

What is the source of vitamin D in currently available supplements as tablets, capsules, sprays or lotions? Plant or animal origin or synthetic from culture, and if so, what source? --Zefr (talk) 19:11, 7 February 2011 (UTC)

I feel this should be discussed in the article, as it relates to information about sources consumers may prefer, vegan vs. fish vs. industrial culture preparations, if applicable. --Zefr (talk) 19:43, 7 February 2011 (UTC)

I added a small section on industrial production --User:juliakbird (talk) 16:35, 10 February 2011

Thanks for the research and editing. Fascinating use of raw materials! --Zefr (talk) 00:54, 11 February 2011 (UTC)

animal carcass hides are widely used as the raw material I beleiveOveragainst (talk)

Ingestion of vitamin D

From the article -"[W]hole-body exposure to one minimal erythemal dose [a dose that would just begin to produce sunburn in a given individual] of simulated solar ultraviolet radiation is comparable with taking an oral dose of between 250 and 625 micrograms (10 000 and 25 000 IU) vitamin D."[14]

The similar effect of supplementation and whole body exposure to one erythemal dose prompted a researcher [85] to suggest 250 micrograms/day (10,000 IU) in healthy adults should be adopted as the tolerable upper limit.[85] Supplements and skin synthesis have a different effect on serum 25(OH)D concentrations;[86] endogenously synthesized vitamin D3 travels in plasma almost exclusively on vitamin D-binding protein (VDBP), providing for a slower hepatic delivery of the vitamin D and the more sustained increase in plasma 25-hydroxycholecalciferol. Orally administered vitamin D produces swift hepatic delivery and increases in plasma 25-hydroxycholecalciferol. The richest food source of vitamin D — wild salmon — would require 35 ounces a day to provide 10,000IU.[87] Recommending supplementation, when those supposedly in need of it are labeled healthy, has proved contentious, and doubt exists concerning long term effects of attaining and maintaining serum 25(OH)D of at least 80nmol/L by supplementation.[88]

A Toronto study concluded, "skin pigmentation, assessed by measuring skin melanin content, showed an inverse relationship with serum 25(OH)D." The uniform occurrence of low serum 25(OH)D in Indians living in India[89] and Chinese in China,[90] does not support the hypothesis that the low levels seen in the more pigmented are due to lack of synthesis from the sun at higher latitudes; the leader of the study has urged dark-skinned immigrants to take vitamin D supplements nonetheless, saying, "I see no risk, no downside, there's only a potential benefit."[91][92] Whether the toxicity of oral intake of vitamin D is due to that route being unnatural, as suggested by Fraser,[86] is not known, but there is evidence to suggest dietary vitamin D may be carried by lipoprotein particles[93] into cells of the artery wall and atherosclerotic plaque, where it may be converted to active form by monocyte-macrophages.[94] These findings raise questions regarding the effects of vitamin D intake on atherosclerotic calcification and cardiovascular risk.

Calcifediol (25-hydroxy-vitamin D) is implicated in the etiology of atherosclerosis, especially in non-Caucasians.[86][88][137][138] Freedman et al. (2010) found that serum vitamin D correlates in African Americans, but not in Euro-Americans, with calcified atheroscleratic plaque. "Higher levels of 25-hydroxyvitamin D seem to be positively correlated with aorta and carotid CP in African Americans but not with coronary CP. These results contradict what is observed in individuals of European descent."[88][119][120][138][139] One study found an elevated risk of ischaemic heart disease in Southern India in individuals whose vitamin D levels were above 89 ng/mL.[137] A review of vitamin D status in India concluded that studies uniformly point to low 25(OH)D levels in Indians despite abundant sunshine, and suggested a public health need to fortify Indian foods with vitamin D might exist.[89] However the levels found in India are consistent with many other studies of tropical populations which have found that even an extreme amount of sun exposure, such as incurred by rural Indians,[140] does not raise 25(OH)D levels to the levels typically found in Europeans"

So you see there is not a optimum Vitamin D level for all humans, it varies by ethnicity. Nor is it desirable to try and reach the astronomically high levels called normal and recommended by (supplement company owner) Vieth or his followers. In fact it's most unwise. Trying to reach those levels by injesting vitamin D suplements is especially likely to prove harmful.Overagainst (talk) 22:24, 17 February 2011 (UTC)

I'm not conviced by the suggested possible side effects of vitamin D supplements. I take 10,000 IU per day in Winter and 5,000 IU per day in summer, so that the total intake from supplements plus sun is about 10,000 IU per day year round. To me it doesn't make any sense why animals would have evolved to use vitamin D to regulate the uptake of calcium from foods if this is all that vitamin D does. It is simply crazy to make this process dependent on the maximum solar elevation. So, clearly there is more to it and it is not difficult to simply guess what is going on here. Obviously, it has to be something along these lines. Thsi then explains why you can't get from foods the dose you can get from the Sun. While it is not natural to get such amounts of vitamin D by ingestion, one also has to consider that it would also be natural for the body to adapt to Winter and vitamin D shortage has a natural role to play here. Of course, we don't want this so we shoud take unnatural measures to porevent this. Count Iblis (talk) 02:03, 21 February 2011 (UTC)

Vitamin D deficiency is widely prevalent in over 80 per cent of the population of India

http://www.thehindubusinessline.com/industry-and-economy/article1474770.ece?homepage=true

Even at a conservative reading, the deficiency is widely prevalent in over 80 per cent of the population, says Dr Tandon. Whether it is children, adults, lactating mothers, elderly or new-borns, the deficiency is there, he adds.

The reason for such prevalence, include among other things, early morning and late evening walks that avoid the sun, glasses that protect from exposure to ultra-violet (UV) rays, pollution, too much time indoors or in vehicles, traditional clothing that limits exposure to sunlight and the increasing use of sun-block in urban India.

Count Iblis (talk) 01:50, 21 February 2011 (UTC)

Wording challenges

"The photosynthesis of vitamin D evolved over 750 million years ago; the phytoplankton coccolithophor Emeliani huxleii is an early example. Vitamin D played a critical role in the maintenance of a calcified skeleton in vertebrates as they left their calcium-rich ocean environment for land over 350 million years ago. "Because vitamin D can only be synthesized via a photochemical process, early vertebrates that ventured onto land either had to ingest foods that contained vitamin D or had to be exposed to sunlight to photosynthesize vitamin D in their skin to satisfy their body’s vitamin D requirement."[11]"

This bothers me because of the certainty in which it is said. Couldn't it be said in a better way like, "Scientists believe Vitamin D evolved over 750 million years ago." Considering you can't necessarily say it absolutely did evolve then, considering what you find in fossil records is only a small percentage of what there really was. — Preceding unsigned comment added by Crazyhistory (talk • contribs) 02:04, 10 January 2011 (UTC)

In Production In the Skin, the paragraph about the layers skin seems to unintentionally imply that Vitamin D is produced only in the skin of the palms and the soles. Not clear why the palms and the soles are mentioned in this context; are two vitamin producing strata not be present in all skin? —Preceding unsigned comment added by 24.238.37.99 (talk) 16:22, 23 April 2011 (UTC)

Large Doses of Vitamin D Needed to Cut Disease Risk

See here

To dramatically cut the risk of breast cancer and multiple sclerosis, people need to consume far more vitamin D than researchers expected, according to a new study.

A daily vitamin D intake of 4,000 to 8,000 international units (IU) is needed for adults to maintain blood levels high enough to halve their risks of breast and colon cancers, multiple sclerosis and Type 1 diabetes, said study researcher Cedric Garland, professor of family and preventive medicine at University of California, San Diego.

Count Iblis (talk) 23:06, 23 February 2011 (UTC)

I'd think twice before taking the 'expert' advice of the Garland brothers if I were you. Look above in the section 'The Institute of Medicine of the National Academies is to publish its Dietary Reference Intakes for Calcium and Vitamin D' [10] "Frank C. Garland, 60, the University of California at San Diego epidemiologist who, with his brother Cedric, was the first to demonstrate that vitamin D deficiencies play a role in cancer and other diseases, died Aug. 17 at UCSD Thornton Hospital. He had cancer of the esophageal junction" [3] Not exactly in the fullness of his years was he?" Read the except from the paper about the increased mortality which results from the Garlands' minimum recomended level.The Institute of Medicine of the National Academies advice is the gold standard and you would be wise to accept it.

So this study isn't fit for this article? BE——Critical_{__Talk} 22:45, 28 February 2011 (UTC)

The IOM committee has looked at all the evidence (including that of Garland and Co). The IOM concluded that the recommended minimum daily intake of 600 IU/day will prevent deficiency diseases, that over 20 nanograms/millileter is adequate for bone health and nearly everyone is in that range. In your link Heaney and Garland are not providing any new research but re-stating their position that 40 to 60 ng/ml is the optimum concentration of 25-vitamin D in the blood. They are saying that it is necessary to ingest 4000-8000 IU a day to maintain that level. If ingesting 600IU a day puts your blood vitamin D to 20 ng/ml why is it necessary to ingest over ten times more to double the blood level to 40ng/ml eh? I'll tell you why, it's because the body resists a vitamin D level that high because it is harmful. Look at the work of Heaney's main authority Vieth, he says HERE that "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 (40 ng/ml), a total vitamin D supply of 100 μg (4000 IU)/d is required". If 40 ng/ml is the optimum level then the blood should be hoovering the stuff up until that level is reached. But it doesn't. Plasma vitamin D and mortality in older men: a community-based prospective cohort study. (a very sophisticated study) has found that being over 39 ng/ml gives a 50% higher total mortality rate. Overagainst (talk) 11:55, 1 March 2011 (UTC)

Well, that might be true. However, the body isn't built to resits the diseases of aging, such as cancer. Thus, what you say might be true for something like sugar levels, but it would not be true for what amounts to an anti-cancer drug. If D is basically a very benign form of chemotherapy, for which you would have to weight the risks and benefits. This study was published February 21 in the journal Anticancer Research, so I'm not sure how they could have already been reviewed and found lacking? BE——Critical_{__Talk} 18:36, 1 March 2011 (UTC)

There is no optimal level in this sense. If vitamin D levels are low, then the body assumes that hard times are coming, as explained here in detail. For optimal health, you need to make sure you get 10,000 IU per day, do hard physical exercise (e.g. fast running) at least 30 minutes per day, 5 times per week and sleep 9 hours per day. This is exactly how Homo Sapiens has lived since 200,000 years ago right until a few centuries ago. Vitamin D is part of a healthy lifestyle, it promotes muscle strength, fitness etc. etc. It may well be the case that 10,000 IU per day for a couch potato who sleeps 5 hours per day is not so good... Count Iblis (talk) 01:05, 2 March 2011 (UTC)

Right, but my impression is that native societies do not run very much, but rather do a significant amount of walking. They usually run only where that is necessary to catch game. But anyway, why is it we can't mention the study above? I'm not an expert on MEDRS. It just looked like an RS for other kinds of articles. BE——Critical_{__Talk} 02:28, 2 March 2011 (UTC)

I would be happy to mention that study, however, we need the consensus here to do so. Also, I'm a mere stupid theoretical physicsts with little indepth knowledge of medicine, so I tend to defer to the medical experts here, even if I don't 100% agree with them. We could ask for comments on this issue from other Wikipedians to see if it is appropriate to add this and some tother studies.... Count Iblis (talk) 15:54, 2 March 2011 (UTC)

It seems like an RS, but it's too new to have been reviewed except by peer review. So it's not the ideal medical source. But at the same time, this is an ongoing controversy. I would think the article would have a section on the ongoing debate specifically. And this source, by the same author (Cedric Garland) is already used (if the "C" stands for Cedric). BE——Critical_{__Talk} 18:10, 2 March 2011 (UTC)

I think "high levels" of vitamin D are wildly understated , I have personally used therapeutic levels of 1 000 000 IU daily for up to 3 weeks to reverse psoriasis with no ill effects except enhanced thirstiness . These levels were well documented in 1930's or so to work for the auto immune conditions, you can google old newspaper articles which is how I found out about it. Maybe it would be useful to link this or this — Preceding unsigned comment added by Vlado1979 (talk • contribs) 02:24, 3 March 2011 (UTC)

Becritical - "However, the body isn't built to resist the diseases of aging, such as cancer" Nonsense, men can father children well into their seventies so the system of vitamin D regulation (like all the other systems in the body) is optimized to keep them in top shape till that age at least. It's called natural selection. The actual study which Garland is staking the generalizations he made in the 2011 paper on is 3 years old, hence it has been gone into by The Institute of Medicine of the National Academies' committee (which is made up of acknowledged experts in the field). They have found that when the Garlands' conclusions are looked at the evidence just doesn't stand up. Mortality Overagainst (talk) 19:15, 3 March 2011 (UTC)

Dr. Michael Holick another scholar known for his studies indicating that vitamin D is related to far more than bone health, and his recommendations for levels of supplemental vitamin D are as high as 10,000 IU (250μg)/d (116)—particularly in regions where exposure to sun is relatively low (150). My professor reminded me that in 2000, Michael Holick chaired the Federal panel that set the daily value at 400 IU, and still he has changed his position and is rallying for exponentially higher doses. In 1999, intake of equal to or greater than 40,000 IU (1000μg)/d was the toxic concentration level for 25(OH)D serum; however intake above 1000 IU (25μg)/d was avoided even though it was considered at least five times lower than adverse levels of intake (151). In 2007 however, the Council for Responsible Nutrition published a review of the upper limit for Vitamin D, raising it from 2000 IU to 10,000 IU based on current research indicating the many health benefits produced by adequate levels of vitamin D (http://www.ajcn.org/content/89/3/719.abstract). This year, the IOM recommended 600 IU for all adults; it seems prudent however to consider further research into the benefits of higher daily values in light of the myriad health risks and concerns associated with Vitamin D deficiency. Continued research into the risks and efficacy of high supplement intake levels is currently underway to futher elucidate how much vitamin D is not only necessary for good health, but what levels will prevent cancers, bone conditions and other immune diseases and what levels can harm the body (151). Atticus591 (talk) 04:08, 27 April 2011 (UTC)

Inaccuracies in relating 25-hydroxyvitamin D to ischemic heart disease.

http://www.ncbi.nlm.nih.gov/pubmed/12889694

Count Iblis (talk) 16:39, 27 March 2011 (UTC)

This was not a prospective study that began with only healthy subjects. And it did not control for dietary variables such as use of polyunsaturated vegetable oils that are known to cause ischemic heart disease. Instead the patients were selected because they already had heart disease that could have been caused by rancid oil, while the healthy controls may have been healthy because they avoided vegetable oils and hence had less heart disease. This study is junk science having no validity. Greensburger (talk) 17:41, 27 March 2011 (UTC)

Indeed, and therefore we should remove the mention of this unreliable result in the Wiki-article. Count Iblis (talk) 15:03, 31 March 2011 (UTC)

Freedman et al. (2010) found that serum vitamin D correlates in African Americans, but not in Euro-Americans, with calcified atheroscleratic plaque. "Higher levels of 25-hydroxyvitamin D seem to be positively correlated with aorta and carotid CP in African Americans." His comments here - "Doctors frequently prescribe supplemental vitamin D," Freedman said. "However, we do not know all of its effects and how they may differ between the races. The bottom line is that racial differences in calcium handling are seen and black and white patients have differing risk for bone and heart disease. We should more clearly determine the effects of supplementing vitamin D in black patients with low levels based on existing criteria and should not assume that the effects of supplementation will be the same between the races." Freedman's study is state of the art, it supports the Indian one). (Note that Vieth recommends extra vitamin D for those with darker skin. Overagainst (talk) 12:15, 5 April 2011 (UTC)

Strong opposition to IOM report

See here. If there are so much objections from experts on Vitamin D on the IOM report, then this Wiki artcle should not put so much weight on that report. Count Iblis (talk) 15:06, 31 March 2011 (UTC)

We are back to the group headed by (supplement company owner's spouse) Prof. Vieth again, his assertion that ingesting 10,000IU a day is harmless is not shared by an expert committee convened by The Institute of Medicine of the National Academy of Sciences. Maybe The Institute of Medicine of the National Academy of Sciences should have picked some supplement company owners' husbands to decide whether we should all be taking huge doses of vitamin D. The opposition comes from someone with an apparent conflict of interest (Vieth), the surviving Garland brother, and Robert P. Heaney. Does Heaney look healthy to you ? Overagainst (talk) 11:34, 5 April 2011 (UTC)

I have read that the IOM members who wrote the report were mostly not experts in the field. Perhaps this is a good thing as you can then get a more independent review of what the vitamin D experts have come up with, but in this case this didn't work out well. The IOM report had been postoned because of strong disagreements between the few experts in the panel on the one hand, and the people who are not experts in vit. D specifically. I think that such strong disagreements in the scientific community should be mentioned in the article.

Also, I don't think there is an obvious issue with some people being involved in the vitamin D suplement business. Where I live, the legal limit for supplements is 400 IU. But one 400 IU pill costs just a little less as a 4000 IU pill that I can order from the US.... Count Iblis (talk) 14:20, 5 April 2011 (UTC)

Lack of vitamin D may stiffen arteries

http://www.upi.com/Health_News/2011/04/04/Lack-of-vitamin-D-may-stiffen-arteries/UPI-37601301897490/

A lack of Vitamin D can lead to stiffer arteries and an inability of blood vessels to relax, making a heart attack more likely, U.S. researchers say.

Dr. Ibhar Al Mheid of Emory University School of Medicine and Dr. Arshed Quyyumi, a professor of medicine and director of the Emory Cardiovascular Research Institute, obtained data from 554 Emory or Georgia Tech employees -- average age 47 and generally healthy -- who took part in the Center for Health Discovery and Well Being program.

The researchers say the average level of 25-hydroxyvitamin D -- a form of the vitamin reflecting diet as well as production in the skin -- in participants' blood was 31.8 nanograms per milliliter. In this group, 14 percent had 25-hydroxyvitamin D levels of less than 20 nanograms per milliliter -- considered deficient -- and 33 percent had less than 30 nanograms per milliliter levels -- considered insufficient.

"We found that people with vitamin D deficiency had vascular dysfunction comparable to those with diabetes or hypertension," Al Mheid says.

The findings were presented at the annual American College of Cardiology meeting in New Orleans.

Count Iblis (talk) 15:39, 4 April 2011 (UTC)

Freedman et al. (2010) suggests otherwise "Calcium can deposit in blood vessel walls forming a bone-like material called "calcified atherosclerotic plaque" and this plaque can be detected by computed tomography (CT) scans. Calcified atherosclerotic plaque is a reliable predictor of risk for heart attack and stroke". More d = 'Calcium deposits in blood vessel walls'. Overagainst (talk) 12:20, 5 April 2011 (UTC)

I see, but I also read that they used people suffering from diabetes in this study. It is also not clear what the relation between Vit. D use and the risk of atherosclerotic plaque is, because they failed to ask the patients what they were using. I would be more convinced if people taking supplements who, apart from vit. D deficiency, are healthy to begin with, would die more frequently from cardiovacular problems. Count Iblis (talk) 14:53, 5 April 2011 (UTC)

Although Freedman et al state that "there is no a priori reason to expect differences in this relationship based on the presence of diabetes".

It's generally not worth trying to make anything out of two contradictory news releases, as they tend to be low-value for medical claims. If there is a medical claim worth including in our encyclopedia, it will be analysed in a literature review published in a peer-reviewed journal. We waste our time by trying to perform our own amateur analysis on primary sources or press releases. --RexxS (talk) 03:47, 7 April 2011 (UTC)

Yes, we obviously cannot do our own OR here. However, it is still good to think what the consclusions are based on as described in the papers themselves. One result can be more tentative than another (e.g. a double blind test with a highly significant result should be given a higher weight than some vague correlation that may contradict the result of the double blind study when making some assumptions). Count Iblis (talk) 16:20, 12 April 2011 (UTC)

Actually, no. A double-blind test is still merely a single primary source and has no weight whatsoever against a secondary source such as a systematic review. This is where the editors have thoroughly examined the current literature on a particular topic and made judgements on that literature, drawing conclusions and resulting in a overview of the topic which is then published in a reputable scholarly journal. That then has the authority of expert review, peer review, and editorial oversight, and is the strongest sourcing available to us. I'd strongly recommend reading WP:MEDRS as it demands a very high quality of sourcing for medical claims, and gives guidance on selecting the best sources in order to avoid making these sort of OR judgements ourselves. --RexxS (talk) 23:33, 12 April 2011 (UTC)

Double blind study results confirm that vitamin D helps bloodvessles to relax. Count Iblis (talk) 16:29, 12 April 2011 (UTC)

Quoting or sourcing

In the section Cardiovascular disease, there is a rather odd quote:

• "Higher levels of 25-hydroxyvitamin D seem to be positively correlated with aorta and carotid CP in African Americans but not with coronary CP. These results contradict what is observed in individuals of European descent."

This seems to directly attributed to no-one, but indirectly attributed to no less than 5 distinct sources, according to the list of refs that follow it. It's not a direct quote from Freedman (2010) although it has similarities. Nor can I find those precise words anywhere except in our article and its mirrors.

These two sentences either need to be directly quoted and attributed to a single source; or re-written to summarise multiple findings, not quoted. In either case, the existence of five references is an indication that something is amiss. If CP is 'calcified atheroscleratic plaque' then it needs to be explained. We should not be expecting our general readers to be making guesses at acronyms, particularly for jargon. --RexxS (talk) 15:36, 5 April 2011 (UTC)

Further: I found the source to be a misquotation of Freedman (2010). It's now corrected as an accurate quotation, and attributed solely to Freedman et al. I've removed the four redundant cites, but one of them is now unused:

• Creemers, PC; Du Toit, ED; Kriel, J (1995). "DBP (vitamin D binding protein) and BF (properdin factor B) allele distribution in Namibian San and Khoi and in other South African populations". Gene geography. 9 (3): 185–9. PMID 8740896.

So I've dropped it here in case somebody can figure out why it was being used to support a quotation in another source. Either a source is good enough to quote, or it's not; it's a mistake to try to bolster sources by tacking on more sources, and that rapidly becomes a recipe for SYNTH. I've re-written the awkward phrasing of the previous sentence, so the only questions left are: (1) Why does this paragraph make the same point twice? (2) Are there no secondary sources that discuss the relationship between 25(OH)D and CP per WP:MEDRS? (3) If not, are these primary studies significant enough to warrant this much attention in the article? --RexxS (talk) 03:29, 7 April 2011 (UTC)

Now that we have the Institute of Medicine of the National Academies Dietary Reference Intake for Vitamin D we can dispense with most of the references to non-tertiary sources. Claims (explicit and implied) that vitamin D supplements will improve health and prevent disease ought to be removed from the article IMO. Re. sources & quotation. What are the issues with intellectual property rights in regard to direct quoting of studies and/or press releases ? Overagainst (talk) 20:16, 10 April 2011 (UTC)

No problems with quoting as long as you cite it carefully. We don't want a whole list of quotes, then this wouldn't be much of an encyclopedia! If what you're suggesting is highly technical, then it's better that we write it. If it's clear, then quote. Vitamin D does prevent some diseases, just not what the mega-vitamin pushers thinks it does. We should keep that. Otherwise, make changes, just make sure they're supported. OrangeMarlin ^{Talk• Contributions} 20:20, 10 April 2011 (UTC)

"Vitamin D does prevent some diseases" Reference please! (A tertiary source preferably.) Overagainst (talk) 20:45, 10 April 2011 (UTC)

Rickets? I am pretty sure that Orangmarlin was not saying that a daily vitamin D pill would be a magic shield against all disease or anything like that. 2over0 public (talk) 21:18, 10 April 2011 (UTC)

I think we have to be careful here. It is quit clear that you have a significant degree of polarization among the experts and you now have an IOM report that has come down to one side of the dispute. This is completely different from what you e.g. see in the controversy on Global Warming. There the scientific community is united with only a few out of the thousands of experts who disagree with the consensus view. The controversy there is mostly present outside of the climate science arena.

Take e.g. people like Dr. Vieth. They do claim that the so-called "megadoses" can protect against many illnesses. These people are not maverick scientists (like e.g. Pielke and Lindzen are in climate science). They do have hundreds of publications and quite a few of these are cited many hundreds of times.

Criticisms of the IoM report from reputable sources should thus be included in the article. E.g., this looks reasonably represntative of what expert critics are saying, although one has to find an acceptable source to cite from. Count Iblis (talk) 01:43, 11 April 2011 (UTC)

If you read the Institute of Medicine of the National Academies report it acknowledges that there are scientific claims for vitamin D being beneficial at higher intakes than the IOM's Dietary Reference Intake for Vitamin D (which the Institute Medicine of the National Academies thoroughly investigated and found to be groundless). So by giving an account of the IOM's findings it would be made clear that some scientists disagree with the IOM. What is the point of presenting information referenced to tertiary sources (like the IoM) if it is followed by a series of apparently countervailing points sourced to selected primary and secondary sources? Readers should be left with the correct understanding; that the findings of the Institute of Medicine of the National Academies are the authoritative scientific view. Overagainst (talk) 19:21, 11 April 2011 (UTC)

I think the issue is more that way the IOM has evaluated the existing results on vitamin D is rejected by quite a few experts. Also the IOM is one national health organization, other countries have drawn different conclusions based on the same body of scientific research (I think Canada still recommends 2000 IU per day for dark skinned people). Count Iblis (talk) 22:37, 11 April 2011 (UTC)

The recent report from the Institute of Medicine of the National Academies is the authoritative tertiary source on Vitamin D and it represents the expert scientific consensus. Accordingly, those scientists who disagree with the recent report from the Institute of Medicine of the National Academies are disagreeing with the scientific consensus among the recognized experts in the field. See Identifying reliable sources (medicine). Does the AIDS article give Professor Peter Duesberg's ideas equal time ? Overagainst (talk) 17:24, 12 April 2011 (UTC)

Well, perhaps medicine is a field in which "authority" plays a far more important role than in the hard sciences (e.g. physics) that I'm more familiar with. I can understand that this may be necessary, because you need to have certain standards for treatment, legal requirements for supplements etc. even when the science is not clear. But we then can't call this a "scientific consensus" if there is no consensus in the scientific community. You have a small number of IOM members taking an authoritative decision, it's perhaps best compared to the US Supreme Court making a ruling. Such a ruling may have been on a contriversial topic for which there was no consensus. While the Court will have taken into account all arguments, that typically won't end the controversy. Count Iblis (talk) 18:10, 12 April 2011 (UTC)

It's probably a mistake to consider Medicine as any less a hard science than Physics. Evidence-based medicine is a younger science, but is almost certainly no less rigorous. Here's what we say about scientific consensus (from WP:MEDSCI):

• "Wikipedia policies on the neutral point of view and not using original research demand that we present the prevailing medical or scientific consensus, which can be found in recent, authoritative review articles or textbooks and some forms of monographs. Although significant-minority views are welcome in Wikipedia, such views must be presented in the context of their acceptance by experts in the field. Additionally, the views of tiny minorities need not be reported."

I'd suggest that the concept of scientific consensus expressed in that is no different from that encountered in Physics. --RexxS (talk) 23:47, 12 April 2011 (UTC)

Well, if I with my physics background e.g read this article, then this doesn't give me any faith whatsoever that medicine is a science can be considered to be on an equal footing as physics. If you see this level of disputes going on in scientific papers, see the accusations of incompetence made the scientific paper itself about bad papers that are not filtered out in authoritative tertiary reviews, then clearly things are seriously wrong.

One thing that surprised me a lot about this field is that while the experts do research, write primary research articles and they also write secondary review articles, it are scientists from slightly different fields who write authoritative tertiary reports and that you then get big disputes in which the expert thrash the tertiary reports. Count Iblis (talk) 01:35, 13 April 2011 (UTC)

Oh, we physicists can still devolve into name-calling and bickering, it's just easier to prove someone wrong. (Although not perhaps right!) My biggest complaint with medical articles is the absolutely 'orrible statistics they all use. Rknight (talk) 07:25, 13 April 2011 (UTC)

@Count: Well, if with my physics background I look at the whole issue of Cold fusion – or even the brouhaha surrounding Brew's take on the speed of light – I can be pretty certain that Physics is just as susceptible to fringe advocacy as Medicine. The article you quote is merely an opinion-piece and I still don't understand why you don't bother to read WP:MEDRS which is very clear about the sources we should be using. There's no need to even look at Hollis & Wagner, because the only thing they have to say is this: "As was recently pointed out in a Cochrane review, the topic of maternal vitamin D requirements during pregnancy has been poorly studied. The reality is that we do not know what the actual vitamin D requirement during pregnancy is." You simply need to start from:

• Mahomed K, Gulmezoglu AM. Vitamin D supplementation in pregnancy [Cochrane review]. Cochrane Database Syst Rev 2000;(2):CD000228. PMID 10796185

and look on PubMed for later reviews on the same topic. There really is very little controversy about these findings; it doesn't take much reading to see that the scientific consensus is that more studies are needed to draw any reliable conclusions about the level of "maternal vitamin D requirements during pregnancy". So that's what our article should be stating as its principal point. If multiple differing views among published experts are actually a notable dispute among reliable sources, then that will be reported in an independent reliable source, just like any other fact that we include in our encyclopedia. It is a gross mistake to synthesise a dispute by juxtaposing different primary sources, unless that comparison has already been made in a secondary source; and it is an even bigger mistake to devote more of our article space to minority topics than we do to the mainstream view. --RexxS (talk) 15:02, 13 April 2011 (UTC)

You won't find any controversy/polemics about cold fusion, nor the speed of light in the peer reviewed physics articles. Hollis & Wagner wrote in that peer reviewed paper that a study which is known to be completely flawed by experts, was used for many years by authoritative institutions to set the safe upper level. To me this sounds rather extraordinary and this then casts doubt on the reliability of such "authoritative" reports like the IOM report (that are themselves not peer reviewed). So, the issue is not the amount of vitamin D mothers should use, rather the other statements made in that article which points to an unhealthy amount of disputes that exists in this field. That complicates the way we can use sources, i.m.o.

Of course, we cannot write the Wiki article based on our own analysis here, we have to stick to the rules for sourcing. However, I think it is important to discuss things on the talk page, because one has to be able to judge precisely how we use tertiary reports here within the general framework of WP:MEDRS. But note that I don't plan to contribute to much to this article, I'm just pointing out certain things here on he talk page that I feel are relevant to the article. Count Iblis (talk) 17:13, 13 April 2011 (UTC)

Look at string theory! I'm keeping my eye on you, string theory! (A joke, I don't have the mathematical background to begin to understand the damn thing.) For the non-physicists, string theory is what we call an 'elegant theory', simply because it's relatively simple, and seems to explain things very nicely. It's just that there has yet to be experimental (or observational cosmological) data to verify it. That's why we experimentalists kinda just nod and pat the heads of the string theorists who get so excited.

Anyway, we can deal with uncertainty. We should officially recommend the Cochrane position; mention the (narrow) conclusions of other reviews; suggest at the conclusions of large, well-designed studies; and really equivocate at in vitro papers that suggest something as-yet unsupported by human studies. Anything further, case reports, J. Med. Hyp., etc., should probably not be mentioned at all in an encyclopedia. We might have to have some arguments over the large epidemiological studies, though. Rknight (talk) 18:09, 13 April 2011 (UTC)

The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine is the work of a 14 member expert committee which looked at 1000 scientific papers. "For extraskeletal outcomes, including cancer, cardiovascular disease, diabetes, and autoimmune disorders, the evidence was inconsistent, inconclusive as to causality, and insufficient to inform nutritional requirements". There can be arguments about the authority of this IoM report; it represents the scientific consensus which the article must reflect. This talk page is for discussing changes to the article to keep it in line with the scientific consensus. Your heterodox personal opinions are of no value Count Iblis. Overagainst (talk) 20:57, 13 April 2011 (UTC)

The leader of the expert committee explains in this interview how they reached their conclusions. To me this is very strange, for a number of reasons. First, why would a (rigorously proven) reduction in cancer risk (or for that matter any disease at all) be relevant for the RDA? The RDA for vegetables is not set in this way, so why set the RDA for vitamin D by looking at disease? The issue here is that if we don't know precisely what vitamin D really does, why choose some lower limit instead of the more natural higher limit of 10,000 IU/day which you would get from solar exposure if you lived like hunter gatherers in Africa?

Other reasons to be alarmed about the IOM recommendations are given here. So, there does exist valid criticism against the criteria the IOM has used to evaluate the existing results. Of course, what goes into this Wiki-article has to be based on good sources, be consistent with WP:MEDRS. But I don't see how that would a priori shield the IOM report from any criticisms published by reputable scientists in reputable peer reviewed journals. I don't know if any such criticism has appeared in the peer reviewed literature yet, though. So, this is something for the near future when the critique by Vieth. et al. appears in The Lancet. Count Iblis (talk) 22:54, 13 April 2011 (UTC)

For the last time. This talk page is for discussing changes to the article to keep it in line with the scientific consensus. The Institute of Medicine of the National Academies report on vitamin D is a tertiary source which represents the scientific consensus among experts. Overagainst (talk) 17:15, 15 April 2011 (UTC)

HIV and Tuberculosis

In this new section are the following sentences:

"HIV-1-infected individuals have lower levels of both the 25(OH)D form and the hormonally active form of vitamin D3, 1,25(OH)2D than uninfected individuals with the lowest concentrations found in persons with AIDS... Interestingly, oral consumption of foods rich in 25(OH)D, the inactive precursor for 1,25(OH)2D, increases CD4+ T cell counts in HIV-1-infected individuals, which normally decrease in number with progression to AIDS."

Similarly with TB. This suggests that HIV and TB are D3-deficiency diseases, in addition to being viral/bacterial infections. Do any of the references suggest that? Greensburger (talk) 02:18, 8 April 2011 (UTC)

I just did a revision of the section, reviewing each of the articles. Whomever wrote this section massively (but not always) misinterpreted the citations. Moreover, without looking very hard, I found a few articles that actually showed the opposite. For example, a fairly well designed clinical trial showed that it had no effect on tuberculosis, except in a subset of individuals that have a very specific vitamin D receptor genotype. I'm still reading the AIDS articles, but so far, the best citations are in vitro, which is a long way to human clinicals. I'm still considering deleting the whole section, except for the tuberculosis stuff. I might drop a note to the IP editor about WP:MEDRS and the such. But I'm doing some more investigation. So, you should not even come close to concluding that Vitamin D3 deficiency leads to TB or HIV susceptibility.OrangeMarlin ^{Talk• Contributions} 03:19, 8 April 2011 (UTC)

Whether D3 deficiency leads to TB or HIV susceptibility, is a separate issue than whether D3 therapy can mitigate or reverse preexisting TB or HIV. Ideally, a prospective study would make that distinction. Greensburger (talk) 05:16, 8 April 2011 (UTC)

Right, and one of the articles mentioned that it needed to be done before any definitive conclusions can be made. This is what's troubling me about the section, the anonymous IP editor is giving undue weight to something that hasn't been shown yet. OrangeMarlin ^{Talk• Contributions} 05:32, 8 April 2011 (UTC)

Orangemarlin edited mostly well, but misplaced a few of the references, I moved them to the right places and he reverted me. Why? He left a HIV reference in the TB section, why did he revert my correction? Also, Vitamin D3 has been shown, in vitro, to inhibit TB, why does he keep removing this section? --98.155.75.155 (talk) 05:32, 8 April 2011 (UTC)

First of all, you are conflating correlation with causation. I see this all the time. Second, I was ploughing through a lot of odd references, so I obviously made an error. Life goes on. I'm still going to remove your implication that Vitamin D does anything with either disease. It has not been proven, and you're making a conclusion not mentioned in the citations. OrangeMarlin ^{Talk• Contributions} 05:40, 8 April 2011 (UTC)

Vitamin D levels have been observed in these two diseases for many years now. I made no implication that either TB or HIV was a vitamin D driven disease. Only that, in vitro, vitamin D has been shown to have an effect on both HIV and TB. I have provided references. Do you disagree that vitamin D inhibits HIV or TB in vitro? --98.155.75.155 (talk) 05:43, 8 April 2011 (UTC)

Maybe something else could be added regarding the effect of the antiretrovirals, nevirapine and efavirenz on vitamin D homeostasis? --98.155.75.155 (talk) 05:54, 8 April 2011 (UTC)

Vitamin D has antimycobacterial activity in vitro

1,25(OH)₂D, has been shown to have antimycobacterial activity in vitro,

What part of those two references do you not agree with? --98.155.75.155 (talk) 05:16, 8 April 2011 (UTC)

First, stop edit warring. Second, discuss it on the talk page of the article, so all can participate. Your initial edits made it sound like Vitamin D cures tuberculosis and AIDS. It doesn't. I'm moving this discussion there. OrangeMarlin ^{Talk• Contributions} 05:28, 8 April 2011 (UTC)

I am not edit warring, you made some mistakes with your edits that I corrected. You left a HIV article as a reference to a statement that it had nothing to do with. Similarly you left TB references in the HIV section. I was just correcting your mistakes. --98.155.75.155 (talk) 05:40, 8 April 2011 (UTC)

Possible external link

An IP spammed the following link into both See also and References:

• Faustino R. Pérez-López.University of Zaragoza

It's not a reference, and 'see also' is for internal links, but it's possible that the external page may be useful either as a source of references to expand this article, or perhaps as an external link?

The IP geolocates to Torrevieja, Spain, so there's a possibility that Prof. Pérez-López himself may be the source of the edits. I'll drop an explanatory note on the IP's talk page. In any case, perhaps the regular editors here can have a look and see if we can make any use of the link. --RexxS (talk) 15:57, 10 April 2011 (UTC)

AAAS workshop on vitamin D

See here. Athletic performance and autism are apparently also related to vitamin D intake. Count Iblis (talk) 22:50, 11 April 2011 (UTC)

I think pretty much anyone can sign up to host an AAAS workshop. There is no actual citable information here. Certainly most of Cannell's claims aren't peer-reviewed, and don't merit mention in wikipedia. Rknight (talk) 07:38, 13 April 2011 (UTC)

There are peer reviewed articles, but no rigorous results on either autism or athletic performance. There is a double blind study on the relation between autism and vitamin D underway right now (pregnant women are given high doses of vitamin D or placebos). I see no harm in mentioning these facts in Wikipedia (in a NPOV without taking any position). It's similar to the LHC searching for the Higgs boson. That fact is mentioned in the relevant Wiki-articles too, we don't wait until it has been found.

An argument against mentioning these thing could be that it is not notable enough at this time. I don't really care much about whether or not one should have something in the article now. But it would certainly be a good for the editors here who live in California to attend the workshop  :) Count Iblis (talk) 22:07, 13 April 2011 (UTC)

No, it's the complete opposite of the LHC searching for the Higgs boson. The Higgs boson is predicted by a theory which has had fairly universal acceptance for well over 30 years. The studies searching for correlations between vitamin D and <insert condition here> are fishing expeditions with no basis in theory or fact, but are purely manifestations of wishful thinking. --RexxS (talk) 01:24, 14 April 2011 (UTC)

I agree that things are not as well motivated as in physics. However, consider this. Dr. Cannell and others postulated that vitamin D plays a role in the immune system based on epidemiological data many years ago (I think way back in the 1980s), and they were ridiculed for making too much of that. Not so long ago, someone published an article (I'll try to dig up the ref) in which it was mentioned that because vitamin D plays a role in bone health, it would be unlikely that it could do anything else in the body. But Cannell&co's basic point (forget the detailed claims) was rigorously proved correct recently. But then that doesn't stop people ridiculing him, so it seems to me that people have taken entrenched positions. This is similar to e.g. global warming, the sceptics will always continue to ridicule climate scientists, no matter what happens. Count Iblis (talk) 02:08, 14 April 2011 (UTC)

If, RexxS,

" The studies searching for correlations between vitamin D and <insert condition here> are fishing expeditions with no basis in theory or fact, but are purely manifestations of wishful thinking."

then why have so many correlations been found? In fact the theory is quite simple: we - clothed modern humans in temperate climes - are vitamin D deficient without supplementation. Since vitamin D is required for calcium signalling you would expect that correcting this deficiency to have widespread and multiple benefits. And that's what the data (i.e. the facts) is showing. -- cheers, Michael C. Price ^talk 09:53, 14 April 2011 (UTC)

Yes, the speculative theory is that simple. But as the proponents have not demonstrated that the exposures achieved by clothed modern humans in temperate climes are insufficient to generate the 25(OH)D needed for normal body function (particularly when combined with normal dietary intake), then it remains just speculation. The effects of vitamin D levels in the body are obviously far more complex than that, otherwise we'd expect all Inuits to suffer from rickets every winter, wouldn't we? --RexxS (talk) 13:52, 14 April 2011 (UTC)

Thanks for admitting that your statement "no basis in theory" is incorrect. Theories, BTW, are allowed to be speculative; that's why we collect data. Also, I should add, that what is not speculative is that clothed modern humans in temperate climes generate way below the amount we would generate if naked in Africa (even if pigmented). And no, Inuit do not disprove anything, because they were one of the few people to eat huge amounts of fish (cod liver oil, anyone?) -- cheers, Michael C. Price ^talk 14:28, 14 April 2011 (UTC)

Also, if we were to determine the RDA for vegetables this way, the recommendation would be that we eat just a little, because only in case of the most severe defiency diseases can a link be established rigorously. The evidence that eating 200 grams per day really prevents diseases like cancer is not rigorously established, but there are plenty of indications that there is a link. The same is true for the amount of exercise we should get, the amount of sleep etc. etc. Count Iblis (talk) 14:37, 14 April 2011 (UTC)

@Micheal: Indeed theories are allowed to be speculative, and those falling under the heading of "vitamin D and <insert condition here>" are precisely that: speculative. I could say it is speculative that "clothed modern humans in temperate climes generate way below the amount we would generate if naked in Africa", because I have adduced exactly the same quantity of evidence to support that opinion as you have for yours. You know as well as I do that the relationship between exposure and vitamin D levels is NOT linear, and varies from person to person. The Inuit actually do prove something: the claim that "we - clothed modern humans in temperate climes - are vitamin D deficient without supplementation" is so oversimplified as to be risible. The Inuit don't need to pop down to the local pharmacy or order tablets online to maintain their vitamin D levels. And yet you're still looking for support for your blanket claim that supplementation is necessary. Why? The scientific consensus is that supplementation is generally not necessary, and that's what our article should be saying, despite the joy that stating otherwise would bring to many pharmaceutical companies who would like to sell everybody on the planet at least 10,000 IU of vitamin D per day. Now if you wanted to sell me vitamin C, that would be another story ... Cheers, --RexxS (talk) 16:01, 14 April 2011 (UTC)

This statement is absolute nonsense: "The scientific consensus is that supplementation is generally not necessary", so this Wiki article should not be saying this. What is true is that authoritative institutions that set the RDA have said this. But then, they have been saying that Vitamin D intake above 2000 IU per day is potentially unsafe for many years, without a shred of evidence for that. Count Iblis (talk) 16:11, 14 April 2011 (UTC)

And what makes your opinion so special that we should accept it over that of reliable sources? I've told you that the only people who think that most people are vitamin D deficient are cranks or representatives of pharmaceutical companies. Which one are you? --RexxS (talk) 16:22, 14 April 2011 (UTC)

You can't get that from the reliable sources themselves. What you have to do is take the IOM report as gospel (which actually now does say that 600 IU per day supplementation is adviced and even that small amount is difficult to get from food), and dismiss all peer reviewed articles that don't agree with this. And what exactly makes e.g. Dr. Rienhold Vieth a "crank"? Is it because if he isn't a crank, you would have to take his publications, some of which are cited more than 700 times (by his fellow colleague canks, I presume) more serious? Count Iblis (talk) 16:37, 14 April 2011 (UTC)

Dr. Rienhold Vieth's wife owns a Vitamin D supplement company and as science journalist Steven Strauss commented that's not a apparent conflict of interest - it's a real one. Funnily enough Mrs. Vieth's Vitamin D product is the very same one which the FDA issued a warning about. You see mothers will tend to think more is better and give their baby a bit extra. There were many cases of severe vitamin D poisoning in Britain when vitamin D was added to powdered milk because mothers reasoned that 'more is better'. The report represents the scientific consensus among experts: Americans need no more than 600 IU (800 if > 70) of vitamin D a day and as they are already obtaining that there is no need for supplementation. The peer reviewed articles you refer to were not ignored [11]"Studies on these nonskeletal outcomes were taken into account, said JoAnn Manson, Elizabeth F. Brigham Professor of Women’s Health at Harvard Medical School, one of the IOM report’s 14 committee members. But in the end they were regarded as “inconsistent and nonconclusive,” she said. {...}.Vitamin D blood levels of 30 {ng/ml} or more are not reliably safe and would be inappropriate for a broad public health recommendation, said panelist Patsy Brannon, a Cornell University nutritionist and IOM committee member". Overagainst (talk) 17:28, 14 April 2011 (UTC)

I guess RexxS hasn't noticed how the "recommended" levels of vitamin D have been steadily rising in the last few years, nor that most people don't have a traditional Inuit diet (including most Inuit, BTW). But hey, don't let that stop you making your non-sequiturs. -- cheers, Michael C. Price ^talk 17:52, 14 April 2011 (UTC)

The IoM recommends vitamin D blood levels of 20 ng/ml and virtually everyone is at that level so supplementation not recommended by the IoM. People like Cedric Garland and his brother Frank (deceased) recommended 40 - 60ng/ml reasoning that as humans are from Africa the natural level of vitamin D in all humans is extremely high. The highest they could find in the US was Brinkley's Hawaiian lifeguards and they assumed the vitamin D level that goes with this freakish level of sun exposure must be the optimum one for good health. The trouble is that the only people who have vitamin D levels which average that high are Brinkley's subjects and their sun exposure is an order of magnitude greater than the average person, but - and this is a central point - their vitamin D levels are not 10X greater. So the dose response suggests that far from requiring these high vitamin D levels (as Vieth, Garland and Co. are claiming) the body resists them - whether from the sun or from supplements ( see previous comment Here). Many of the indigenous peoples of northern Canada, Alaska, and northern Asia are not Inuit and they lived on food poor in vitamin D (Caribou) while retaining brown skin. Finally, equatorial Africans do not have high vitamin D levels but it's not because of their skin color 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." 'And diet', think through the implications of that please. Overagainst (talk) 18:57, 14 April 2011 (UTC)

Folate and vitamin D synthesis are antagonistic. I suggest you think through the implications of that. -- cheers, Michael C. Price ^talk 21:46, 14 April 2011 (UTC)

Hehe - it seems we're all almost on the same wavelength at last. As you can see, we can all do our own OR, and come up with unsourced 'theories' that would support any given view. So here's what I'm driving at: The only reliable sources usable to make medical claims are secondary ones that are published in quality peer-reviewed journals. Our job is to find those sources and dispassionately report on what they say. If we rely on our own amateur analysis of secondaries, or attempt to use primary sources to 'debunk' the conclusions of reliable secondaries, then we breach our responsibilities to NPOV. When you get your pet theory published in Lancet and included in the Cochrane review, we can start giving it a place in this article. Until then, let's stick to WP:MEDRS please. --RexxS (talk) 23:47, 14 April 2011 (UTC)

Not my "pet theory", BTW: [12], [13]. -- cheers, Michael C. Price ^talk 05:03, 15 April 2011 (UTC)

You obviously didn't bother thinking through the implications. Allow me to elucidate, if their darker skin (for folic acid protection from UV) was inhibiting vitamin D synthesis it would explain why African ancestry reduces the effect of sun on vitamin D levels, but how could it also reduce the effect of diet ? Obviously it couldn't so that "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." suggests that Africans have evolved to resist the higher vitamin D levels which Vieth & Co are claiming were normal for our African ancestors and all other humans. Hence that effect of "sunlight and diet" on raising Vitamin D levels is reduced by African ancestry is highly significant.

"Folate and vitamin D synthesis are antagonistic" Not true. 5-Methyltetrahydrofolate inhibits photosensitization reactions and strand breaks in DNA "We demonstrate that 5-methyltetrahydrofolate (5-MTHF, the predominant folate in plasma) is also a potent, near diffusion limited, scavenger of singlet oxygen and quencher of excited photosensitizers. Both pathways result in decomposition of 5-MTHF, although ascorbate can protect against this loss. In the absence of photosensitizers, 5-MTHF is directly decomposed only very slowly by UVA or UVB. Although synthetic folic acid can promote DNA damage by UVA, submicromolar 5-MTHF inhibits photosensitization-induced strand breaks. These observations suggest a new role for reduced folate in protection from ultraviolet damage and have bearing on the hypothesis that folate photodegradation influenced the evolution of human skin color".—

Effects of UVA irradiation on the concentration of folate in human blood "These results suggest that UVA exposure destroyed PGA but not 5-methyltetrahydrofolate in human blood in vivo."

Re. folate supplementation "Treatment with folic acid plus vitamin B12 was associated with increased cancer outcomes and all-cause mortality

White skinned women have been intensively sunbathing and using sunbeds for decades,Folic acid deficiency would have caused pregnancy problems among heavily tanned women and been noticed by now. Furthermore the Bushmen who are basal to other populations in Africa and are adapted to the extremely powerful UV of the Kalahari are not dark skinned. Melanin may not filter out enough UV-B to make much of a difference anyway The value of melanin as a sunscreen . "Here we find that epidermal melanin is not a neutral density filter providing no or minimal protection for the induction of erythema at 295 and 315 nm and some protection at 305 and 365 nm." Overagainst (talk) 16:26, 15 April 2011 (UTC)

If you'd thought for a nanosecond before posting you would have done us all a favour:

suggests that their [African ancestry] is resisting higher vitamin d levels

No, it also suggests that the non-Africans have better dietary absorption mechanisms, since they're under greater evolutionary pressure to correct their deficiency. [note that the recent refactoring of the quote does not invalidate this rebuttal]

"Folate and vitamin D synthesis are antagonistic" Not true. 5-Methyltetrahydrofolate inhibits photosensitization reactions and strand breaks in DNA

An in vitro study, i.e. worthless. Sorry.

Effects of UVA irradiation on the concentration of folate in human blood "These results suggest that UVA exposure destroyed PGA but not 5-methyltetrahydrofolate in human blood in vivo."

Which is contradicted by The evolution of human skin coloration. Also please explain why there is a gradient of the MTHFR 677TT genotype.

Re. folate supplementation "Treatment with folic acid plus vitamin B12 was associated with increased cancer outcomes and all-cause mortality

What about longer term studies (15+ yrs) that show a near 5-fold reduction in colon cancer? e.g. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study.

Anyway, this is irrelevant since I assume you accept folate deficiency will cause neural tube defects?

White skinned women have been intensively sunbathing and using sunbeds for decades,Folic acid deficiency would have caused pregnancy problems among heavily tanned women and been noticed by now.

Who's been looking?

-- cheers, Michael C. Price ^talk 17:24, 15 April 2011 (UTC)

"No, it also suggests that the non-Africans have better dietary absorption mechanisms, since they're under greater evolutionary pressure to correct their deficiency." I don't follow you, by my way of thinking the study's results are not open to the interpretation that Africans have better dietary absorption mechanisms. Look at what the study says "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{...}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" Here

An in vitro study perhaps but it was by Bruce Ames.The evolution of human skin coloration. is staking its generalizations about UV on Branda and Eaton's paper but that was studying treatment for psoriasis which involves the use of methoxalen or other photosensitizers in plasma. Ames hints that Branda and Eaton were studying an unnatural situation. Juzeniene says 5-Methyltetrahydrofolate can be photodegraded by endogenous photosensitizers but conjugated bilirubin protects it. Natural selection has found found a way round the problem anyway Serum folate levels after UVA exposure: a two-group parallel randomised controlled trial "We did not observed significant differences of folate levels between UVA exposed and non-exposed volunteers" The gradient of the MTHFR 677TT genotype. is due to sexual selection. Doctors have have been looking for problems, there have been warnings against sunbathing and using sunbeds when pregnant, here. Overagainst (talk) 18:21, 15 April 2011 (UTC)

In the study's results are not open to the interpretation that Africans have better dietary absorption mechanisms. you mean non-Africans, I take it? BTW sexual selection normally kicks off in an adaptive direction. -- cheers, Michael C. Price ^talk 18:44, 15 April 2011 (UTC)

My mistake, I got a bit mixed about what you were saying there, sorry. Taking the study by itself "non-Africans have better dietary absorption mechanisms, since they're under greater evolutionary pressure to correct their deficiency" is a rather good interpretation for your line of argument. However as I ask above 'If ingesting 600IU a day puts your blood vitamin D to 20 ng/ml why is it necessary to ingest ten times more to double the blood level to 40ng/ml eh?" Does that dose response suggest that the whites have evolved to maximize vitamin D absorption? In The Pharmacology of Vitamin D Vieth himself remarks on the way humans handle vitamin D calling it "a system better designed to cope with an abundance of supply, not a lack of it" - "remarkably inefficient" -"no way to correct for deficiency".

"If one looks at the system of vitamin D metabolism in Figure 2 from the perspective of a system designed to control something, it becomes clear that this is a system better designed to cope with an abundance of supply, not a lack of it. The flow of vitamin D toward 25(OH)D is remarkably inefficient, with most bypassing it. Furthermore, there is no way to correct for deficiency of vitamin D, other than to redirect utilization of 25(OH)D toward 1,25(OH)2D production, which is the pathway most acutely important for life. That is, when supplies of vitamin D are severely restricted, its metabolism is directed only toward the maintenance of calcium homeostasis. To expand on the point that the system of vitamin D metabolism is effectively a designed for adjusting for higher inputs, not lower inputs, I offer the example of an air-conditioner system. Air conditioners are designed to compensate for excessive heat, but they are a useless way to compensate for a cold environment."

Vieth does not explain how this system has managed to survive natural selection for a 1,000 generations of Europeans. So 30,000 years after entering northern Europe we are expected to believe that natural selection has left people with mechanisms designed for Equatorial Africa which result in them not absorbing vitamin D from the diet or from skin synthesis. It is true that Africans vitamin D levels are raised even less than whites by sun or diet but neither whites or Africans show any sign of maximizing vitamin D levels. The assumption that Europeans evolved white skin to maximize vitamin D production from the sun because vitamin D from the sun is in short supply in northern Europe must be wrong: natural selection improves functioning and it would not have lightened skin color to make extra vitamin D but left an extremely wasteful and maladaptive system of handling vitamin D in place. Is a person wearing clothes able to get plenty of vitamin D from the sun in northern Europe ? Interdependence between body surface area and ultraviolet B dose in vitamin D production: a randomized controlled trial "Notably, a very small UVB dose of 0·75 SED (∼8 min of sun exposure on a clear day around the summer solstice in Denmark, 56°N) and a small body surface area of 12% resulted in significant 25(OH)D production." Overagainst (talk) 20:21, 16 April 2011 (UTC)

To take your last point first, it depends what they mean by "significant". If they mean "sufficient to prevent rickets", well yes, a short UVB exposure is enough. If they mean optimal for cancer prevention, well perhaps not. Cancer is mostly a disease of old age, and hence not so heavily selected against (esp when average lifespans were much shorter) as, say, bone development/strength. This also partly addresses the question of whether a 1000 generations enough to optimize vitamin D synthesis.

Also, we are full of systems that seem (or are) maladaptive because we do not understand the trade-offs involved. (Folate is just one possible example; there may be hundreds more we have no idea about at the present.)

The point about being designed to cope with abundance rather than scarcity passes me by. Doesn't that just indicate that we experienced higher levels in the past?

Finally you ask why we do not have a linear serum response to dietary intake. There may be a million reasons. One possibility is that as we absorb more we process more, so that average "hanging around" time decreases. Hence a non-linear sera response. -- cheers, Michael C. Price ^talk 20:53, 16 April 2011

Here is something I find helpful in thinking about these issuesA New Germ Theory, It's an excerpt from a big article

To illustrate his thinking about infectiousness and disease, Cochran not long ago gave me a tour of his conceptual bins, into which he sorts afflictions according to their fitness impact. Remember that fitness can be defined as the evolutionary success of one organism relative to competing organisms. Only one thing counts: getting one's genes into the future. Any disease that kills host organisms before they can reproduce reduces fitness to zero. Obviously, fitness takes a major hit whenever the reproductive system itself is involved, as in the case of venereal chlamydia. Consider a disease with a fitness cost of one percent - that is, a disease that takes a toll on survival or reproduction such that people who have it end up with one percent fewer offspring, on average, than the general population. That small amount adds up. If you have an inherited disease with a one percent fitness cost, in the next generation there will be 99 percent of the original number in the gene pool. Eventually the number of people with the disease will dwindle to close to zero - or, more precisely, to the rate produced by random genetic mutations: about one in 50,000 to one in 100,000.But what about something like atherosclerosis? I asked. Leaving aside the evidence concerning C. pneumoniae, it is not apparent why a genetic cause for atherosclerosis should be dismissed out of hand on evolutionary grounds. If it hits people in midlife or later, after they have launched their genes, how could it possibly affect' fitness? Cochran's response illustrates some of the intricacies of evolutionary thinking. "Well, obviously, it's not as bad as a disease that kills you before puberty, but A think it does have a fitness cost. First of all, it's really common. Second, people think that all you have to do to pass your genes along is have children, but that's not true. You still need to raise the offspring to adulthood. In a hunter-gatherer or subsistence-farming culture, the fitness impact of dying in midlife might be considerable, especially during bad times, like famines. You've got to feed your family. Also, cardiovascular disease is a leading cause of impotence, and any disease that makes males impotent at age forty-five has got to affect reproduction somewhat." But fifty-year-olds? Sixty-year olds? Grandmothers do a large proportion of the food-gathering in some tribal cultures, according to recent anthropological reports. "They aren't hampered by babies anymore, and they don't have to go around chucking spears like the men," says George C. Williams, a professor emeritus of ecology and evolution at the State University of New York at Stonybrook, and one of the pillars of modern evolutionary biology. "They contribute. substantially to the family diet." If long-lived elders historically have made a difference by fostering the survival of their descendants, and therefore their genes, Cochran figures, then a disease that kills sixty-year-olds could have a fitness impact of around one percent."

So every tiny advantage counts in evolution and you cannot say that a maladaptive system being left alone is not an anomaly; those who carried it would have died out and been totally replaced by now.

At a small dailly intake of vitamin C - up to about 150mg - the concentration in the blood is nearly proportional to the intake. 5mg per litre for an intake of 50 mg, 10mg for an intake of 50mg, 10mg per litre for an intake of 1000mg Above an intake of 150mg a day the concentration in the blood increases much less with increasing intake , reaching about 30mg per litre for an intake of 10 GRAMS a day. Compare Vieth's data on D, the dose response is significant.

"Two studies showed that in response to a given set of ultraviolet light treatment sessions, the absolute rise in serum 25(OH)D concentration was inversely related to the basal 25(OH)D concentration. In the study by Mawer et al (34), the increase in 25(OH)D in subjects with initial 25(OH)D concentrations <25 nmol/L was double the increase seen in subjects with initial concentrations >50 nmol/L. Snell et al (27) showed that in subjects with initial 25(OH)D concentrations <10 nmol/L, ultraviolet treatments increased 25(OH)D by 30 nmol/L, but in those with initial 25(OH)D concentrations approaching 50 nmol/L, the increase was negligible."(Vieth 99)

Plasma vitamin D and mortality in older men: a community-based prospective cohort study Vitamin D levels are optimized for good health. Our body's systems are never maladaptive. Overagainst (talk) 22:23, 16 April 2011 (UTC)

They are maladaptive if environmental conditions have changed. And even then it takes awhile for changes to spread (e.g. lactose intolerance). But my main problem is that things may seem maladaptive because we don't see the whole picture - it's just too complex (e.g. what are we sacrificing by diverting resources to synthesize vitamin D?). And so we should just go with the data, which is showing benefits of high doses of vitamin D. -- cheers, Michael C. Price ^talk 22:50, 16 April 2011 (UTC)

It does take a while for lactose tolerance to spread but lactose intolerance is a good example of the timescale for an advantageous genetic change

Conversation: Evolution Overdrive"What are the biggest evolutionary changes in humans over the last 50,000 years?

Well, there have been lots of trends. During the past 20,000 years and particularly the past 10,000, body size shrank a little bit, brain size shrank quite a lot, and tooth size reduced. The European and Asian genes that lighten skin color are pretty recent. Digestive things have changed, like the ability for adults to consume milk. You mean the genes that control lactose intolerance?

Yeah, this is a great example because it is really well known that Europeans, as well as some west and central Asians have a really high lactose digestion capacity as adults. Those places each have separate mutations that are new within the past 10,000 years, and the rest of the world didn't get those mutations, so that explains the difference.

But it's also a great example because people have probed 5,000-year-old Neolithic skeletons from Germany, and the lactase-digesting allele isn't there. That's around 90% in Germany today; in the Neolithic it's not there at all. That means that not only is this a very recent change but it is a recent change that we can document skeletally in the archaeological record."

So if a change is beneficial 10,000 years is more than enough time for it to happen. By the way European Skin Turned Pale Only Recently,Gene Suggests the date for skin lightening is 20,000 years after humans entered Europe so it is most unlikely that skin lightened because of simple lack of UV in the north. Interdependence between body surface area and ultraviolet B dose in vitamin D production: a randomized controlled trial"Accordingly, our study shows (Table 3) that given the same baseline 25(OH)D level (31·4 nmol L−1) and a UVI of 3, a sufficient level of vitamin D (> 50 nmol L−1) would be reached by four exposures of either 15 min sun exposure (0·75 SED) to ∼24% of the body surface area or 30 min sun exposure (1·5 SED) to only ∼6% of the body surface area." It should be remembered that vitamin D synthesis switches off after about 20 minutes, if Europeans have evolved white skin to maximize vitamin D synthesis why have they retained a mechanism which switches synthesis off after A BRIEF period in the sun? I think it is obvious that people in Europe wearing clothing have always been able to make and store all the vitamin D they need (and then some) in the course of their normal outdoor activities during the sunny months.

The data you are going with are open to other interpretations.

Weighing the Evidence Linking UVB Irradiance, Vitamin D, and Cancer Risk– "We agree with Dr Grant that evidence from ecological studies suggests that vitamin D may reduce cancer risk. Increasing distance from the equator is associated with increased risk of several cancers at a population level. However, one of the major limitations of ecological studies is referred to as the ecological fallacy, which is the error of making inferences at an individual level on the basis of aggregate population level data. It is entirely possible that a disease association found by comparing populations is absent, or even in the opposite direction, when individual level data are examined. Individuals in the population who develop cancer may not be those with low vitamin D status. In the case of ecological studies involving international cancer registries, many low-income countries are close to the equator and their cancer registries may be limited by the fact that many cancers are undiagnosed and underreported, resulting in a high likelihood of an ascertainment bias.1 Ecological studies are useful for generating hypotheses, but experimental studies and individual level data are necessary to ascertain causality. The association of reduced sunlight exposure at higher latitudes with increased cancer risk does not indicate that low vitamin D status causes increased cancer risk. Many confounding environmental and population variables are associated with both latitude and vitamin D exposure that can affect disease risk"