Dr UVB

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Also we tend to use high quality references from the last 5 years. Thus I have reverted your changes as the previous content was supported by never refs. Best Doc James (talk · contribs · email) 03:09, 11 June 2015 (UTC)

Have moved the discussion to the talk page and asked for further input Talk:Vitamin_D#Vitamin_D_and_Cancer Doc James (talk · contribs · email) 23:42, 11 June 2015 (UTC)

This is concerning. Rather than go with the best quality recent research you appear to be choosing old literature that you like. Doc James (talk · contribs · email) 23:48, 11 June 2015 (UTC)

Wikipedia Review

Dear Doc James, I've again reviewed the vitamin D and cancer topic in Wikipedia and found that the section still remains somewhat scant. The first reference is to a popular press article about sales of vitamins in general. The remainder seems to trivialize the 35 years or so of active scientific research in this topic area. Rather than citing any original articles, it relies on a single tendentious review. Since students use Wikipedia to learn about the progression of scientific investigations as well as the latest findings on a topic, I wondered if we might consider rewriting this section together to reflect both the historical advancements in the understanding of vitamin D and cancer, as well as results of the latest laboratory, observational, and large cohort studies. I would like to suggest that we set-up an editorial board of subject matter experts who would then together revise this section. We would then submit a final draft to you as the Wikipedia editor. I have several colleagues listed below that I think would likely be very interested and willing to undertake this project. If you are amendable to this suggestion, please respond to my office email. We can then begin circulating revisions to this section. Many thanks. Very respectfully, Ed

Edward Gorham, MPH, PhD Adjunct Professor Department of Family Medicine and Public Health School of Medicine University of California, San Diego (619) 990-3848 Email: edward.d.gorham2.civ@mail.mil Dr UVB (talk) 14:51, 6 July 2015 (UTC)

Proposed subject matter experts: University of California Riverside Anthony W. Norman, Ph.D. University of California San Diego Cedric F. Garland, Dr. P.H. Boston University School of Medicine Michael F. Holick, Ph.D., M.D. Creighton University Robert P. Heaney, M.D. Joan M. Lappe, Ph.D., R.N. Harvard School of Public Health Edward Giovannucci, M.D., ScD. Linus Pauling Institute Adrian F. Gombart, Ph.D. Medical University of Graz, Austria Stefan Pilz, M.D. Medical University of South Carolina Bruce W. Hollis, Ph.D. Carol L. Wagner, M.D. Roswell Park Cancer Institute Donald L. Trump, M.D. University of Auckland Robert Scragg, M.D., Ph.D. University of Saskatchewan Susan J. Whiting, Ph.D. University of Toronto, Mt Sinai Hospital Reinhold Vieth, Ph.D. Vienna Medical University Heidi S. Cross, Ph.D.

Are you referring to Vitamin_D#Cancer? It is supported by 5 review articles. We tend not to cite original articles but tend to use review articles such as meta analysis instead. Doc James (talk · contribs · email) 18:13, 6 July 2015 (UTC)

Agree these reviews are a reasonable standard, but there could be much more added reviewing associations between vitamin D and colorectal, prostate, breast and other cancers. Is there any support for a separate, more detailed entry on "Vitamin D and cancer"? Jrfw51 (talk) 19:43, 6 July 2015 (UTC)

The original message is in some ways wonderful. It would be great to get this kind of academic firepower behind articles. However, there is so much hype around nutrients and risk of getting cancer and the possibility of preventing cancer in the media and the literature, but in my view, in terms of actual medical knowledge there is almost nothing to say. The SELECT trial taught us all that the even the most solid-seeming hypotheses about nutrients and cancer turn out to be not only wrong, but 180 degrees wrong. I think the WEIGHT we give the topic of "Vitamin D and cancer" is perfect. Would be amazing if we could get this kind of effort around well-established topics like Hypertension and especially all our psych articles. Jytdog (talk) 20:08, 6 July 2015 (UTC)

Thank you, Jytdog and Jrfw51, Site specific cancer studies would, in my view, be an important addition to this section. Many dietary and serum studies have been carried out for both colon (1) and breast cancer (2), and for cancers of other sites. Nested case-control serum studies have certain advantages over dietary studies of vitamin D since it doesn't matter whether the vitamin D is dietary or sun-derived. 25(OH)D is relatively stable and an optimal biomarker for vitamin D status. Results from large cohort studies should not be discounted, such as the prospective EPIC study of serum 25 (OH)D and colon cancer in countries across Europe (1). These are important primary sources, and deserve their own citation. In vitro cell studies of antineoplastic effects of 25(OH)D and 1,25(OH)D in several tumor lines should at least be mentioned. These potent vitamin D metabolites act as hormones and influence tight junctions between cells, promote apoptosis, and down-regulate oncogenes. Vitamin D is not simply another nutrient when it comes to cancer. The review of supplement sales is overly broad, not particularly relevant to this section, and should be considered for deletion. The role of most nutrients in disease causation has been contentious since they were first identified (3). This should not discourage us from their study or fair reporting of results of these investigations. Very respectfully, Professor Gorham

1) Jenab M, Bueno-de-Mesquita HB, Ferrari P, van Duijnhoven FJ, Norat T, Pischon T, Jansen EH, et al. Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations: a nested case–control study. BMJ 340:b5500, 2011. PMID 20093284

2) Abbas S, Linseisen J, Slanger T, Kropp S, Mutschelknauss EJ, Flesch-Janys D, Chang-Claude J. Serum 25-hydroxyvitamin D and risk of post-menopausal breast cancer: results of a large case-control study. Carcinogenesis. 2008;29:93–9 PMID 17974532

3) Heaney RP. Nutrients, endpoints, and the problem of proof. J Nutr. 2008 Sep;138(9):1591-5. PMID 18716155

Dr UVB (talk) 18:27, 8 July 2015 (UTC)

I added PMIDs to the 1st 2 refs and fleshed out the 3rd. Thanks for replying. I agree that the science is important (there are so, so many things that we still need to understand better in terms of human biology in health and disease). But it seems to me that the argument you are trying to make is that the two big studies you cite - that show correlation only - are somehow important for health. We can show studies like that all day, and in vitro studies showing mechanisms too, but nobody has ever been ever able to show that an intervention with supplemention does a darn thing, outside of the very clear nutritional deficiencies like scurvy, rickets, etc., folate in pregnancy (although that is being questioned now, apparently) and a few others. On the flipide, as I mentioned above, with these claims flying around all over the place, that we can somehow prevent cancer or other diseases by trying to micromanage our diets/nutrients/"chemical" exposure, the organic food, dietary supplement, and fad diet industries make piles of money and people walk around full of anxiety. The recent review on Vitamin D, PMID 26071820, nails it from my perspective - there is almost nothing to say, healthwise. But I'll stop soapboxing and let others respond. Jytdog (talk) 18:51, 8 July 2015 (UTC)

Thank you again, Jytdog, for your thoughtful response. Controversy is an inevitable part of scientific progress. EV McCollum himself, who first isolated vitamin D, was widely derided for the idea that it might prevent rickets. The proof of vitamin D in rickets prevention was based on observational and animal studies. Dr. Taylor's commentary represents a certain point of view, but there are many others who would not be so quick to dismiss the importance of vitamin D in public health. I'm attaching a link to another commentary, just for interest. There is incidentally a randomized controlled trial by Lappe et al that meets this highest level of medical evidence which is unfortunately omitted in Dr. Taylor's commentary, but included below. The temporal sequence, consistency across study designs, strength of association, and the dose-response findings each help address the causality issues you question. These factors should be noted in Wikipedia. The important thing in my view is to establish a balanced panel of subject matter experts who could improve this section of Wikipedia, as I've suggested above. Very respectfully, Professor Gorham

Dr UVB (talk) 00:10, 9 July 2015 (UTC)

Dr UVB (talk) 00:10, 9 July 2015 (UTC)

What would show benefit would be a placebo controlled RCT of supplementation. As cancer is common showing benefit should not be that hard if a meaningful benefit exists.

The impact factor of the journal in which the article you link is published is 1.6 [2] This is low.

The impact factor of this journal is 9.1 [3]. Other forms of research are just typically hypothesis generating. Doc James (talk · contribs · email) 03:37, 9 July 2015 (UTC)

I think we are confusing Health effects of supplementation with another topic: Associations of vitamin D with human disease. We all recognize that the reviews of prospective supplementation studies show uncertain benefits. There is much more to this topic than whether supplements are effective or not. I do not find elsewhere on this page any clear review of the multiple and varying associations with different cancers or discussion of the controversies around causation, association and prevention. Jrfw51 (talk) 17:30, 9 July 2015 (UTC)

Yes there are associations between vit D levels and health but the question is is that relationship causal and the only thing that can show that is RCTs. Doc James (talk · contribs · email) 17:43, 9 July 2015 (UTC)

Thank you for this message, Doc James. You may have an interest in the results of a seminal nested case-control study published in Lancet (impact rating?) indicating more than a 75% reduction in colon cancer risk in the third and fourth highest quintiles of serum 25(OH)D. This prospective nested case-control study conducted by myself and colleagues at Johns Hopkins led to numerous others, most with remarkably consistent results. These studies culminated in the EPIC cohort study referenced above.

Incidentally, a randomized controlled trail does exist (abstract also provided below) which found exactly the level of evidence you are seeking. In fact, these investigators observed a 60% reduction in incidence of cancers of all sites in the vitamin D and calcium treatment arm of this trial.

These and many similar results are overlooked in the review by Taylor, et al. This is a drawback of relying solely on reviews. Elevation of this section of Wikipedia to an external panel of experts, such as those suggested above, could, in my opinion, improve this section of Wikipedia substantially. By almost any objective measure, it is currently lacking, both scientifically and factually. If you will not approve, may I request that we elevate to a higher echelon in the Wikipedia review process. Sincerely yours, Prof. Gorham

Lancet. 1989 Nov 18;2(8673):1176-8. Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Garland CF, Comstock GW, Garland FC, Helsing KJ, Shaw EK, Gorham ED.

Abstract Blood samples taken in 1974 in Washington County, Maryland, from 25 620 volunteers were used to investigate the relation of serum 25-hydroxyvitamin D (25-OHD) with subsequent risk of getting colon cancer. 34 cases of colon cancer diagnosed between August, 1975, and January, 1983, were matched to 67 controls by age, race, sex, and month blood was taken. Risk of colon cancer was reduced by 75% in the third quintile (27-32 ng/ml) and by 80% in the fourth quintile (33-41 ng/ml) of serum 25-OHD. Risk of getting colon cancer decreased three-fold in people with a serum 25-OHD concentration of 20 ng/ml or more. The results are consistent with a protective effect of serum 25-OHD on colon cancer.

Am J Clin Nutr. 2007 Jun;85(6):1586-91. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP.

Abstract Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers. However, interventional studies to test this effect are lacking. The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk of all types. This was a 4-y, population-based, double-blind, randomized placebo-controlled trial. The primary outcome was fracture incidence, and the principal secondary outcome was cancer incidence. The subjects were 1179 community-dwelling women randomly selected from the population of healthy postmenopausal women aged >55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were randomly assigned to receive 1400-1500 mg supplemental calcium/d alone (Ca-only), supplemental calcium plus 1100 IU vitamin D3/d (Ca + D), or placebo. When analyzed by intention to treat, cancer incidence was lower in the Ca + D women than in the placebo control subjects (P < 0.03). With the use of logistic regression, the unadjusted relative risks (RR) of incident cancer in the Ca + D and Ca-only groups were 0.402 (P = 0.01) and 0.532 (P = 0.06), respectively. When analysis was confined to cancers diagnosed after the first 12 mo, RR for the Ca + D group fell to 0.232 (CI: 0.09, 0.60; P < 0.005) but did not change significantly for the Ca-only group. In multiple logistic regression models, both treatment and serum 25-hydroxyvitamin D concentrations were significant, independent predictors of cancer risk. Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00352170. Dr UVB (talk) 20:58, 9 July 2015 (UTC)

I have given the Cochrane review greater weight in the section in question. It found a small benefit. Doc James (talk · contribs · email) 21:25, 9 July 2015 (UTC)

Cochrane excludes all observational epidemiologic studies including prospective cohort studies, nested case-control studies, and of course, case-control studies, and ecological studies. I don't want to turn this into a discussion of Cochrane, but public health advances linking cigarettes to lung cancer, lack of sunlight and vitamin D to rickets, passive smoking to heart disease, and numerous other medical advances would never have occurred if held to Cochrane criteria. John Snow, to his undying credit, did not randomly allocate people to drink or not drink cholera-tainted water from London's Broad Street pump. We have an opportunity to improve this section of Wikipedia substantially by admitting much published, peer-reviewed evidence approved medical journal editors and excluded by Cochrane. Koch's postulates of causality don't depend on Cochrane. If Cochrane is the current Wiki standard, the result will be to arbitrarily exclude all the lines of epidemiologic evidence described above. I would respectfully request an appeal of that decision, and a repeal of that standard. To whom should I address this request? V/r, Prof. Gorham

Dr UVB (talk) 22:20, 9 July 2015 (UTC)

Toxicity is very different from treatment. One can study treatment in a blinded fashion. One cannot do the same with toxicity. RCTs are thus not appropriate for toxicity but are for treatment due to the issues of multiple confounders. We do not have the same precautionary principles when doing something like taking a pill that we have when not doing something like smoking or improving air quality.

Additionally we do not just use Cochrane but they are a major position in medicine. We also use the IOM and other systematic reviews. By the way what content are you interested in adding? And are you willing to base the content on recent high quality secondary sources? Doc James (talk · contribs · email) 22:28, 9 July 2015 (UTC)

Excellent! So observational epidemiologic studies including prospective cohort studies, nested case-control studies, and of course, case-control studies, and ecological studies are admissible. Our panel will review and submit these for inclusion. Thank you, Dr. James. We'll get started on this right away. I'm not sure I completely follow your statements regarding toxicity. It is rarely an issue in vitamin D until serum levels of 25(OH)D exceed at least 100 ng/ml. This would be the approximate equivalent of a daily oral intake of 10,000 IU per day for several weeks. 50,000 IU per week is the prescribed replenishment dose for treating deficiency, or approximately 7,000 IU per day. I hope this is helpful. V/r, Prof. Gorham

Dr UVB (talk) 22:54, 9 July 2015 (UTC)