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A critical review of Vitamin D and cancer: A report of the IARC Working Group on vitamin D William B. Grant Dermato-Endocrinology. Volume 1, Issue 1 January/February 2009 Pages: 25 - 33 The International Agency for Research on Cancer (IARC) released a report, Vitamin D and Cancer, on November 25, 2008. The report focused on the current state of knowledge and level of evidence of a causal association between vitamin D status and cancer risk. Although presenting and evaluating evidence for the beneficial role of UVB and vitamin D in reducing the risk of cancer, it discounted or omitted important evidence in support of the efficacy of vitamin D. The report largely dismissed or ignored ecological studies on the grounds that confounding factors might have affected the findings. The report accepted a preventive role of vitamin D in colorectal cancer but not for breast cancer.

Vitamin D and Cancer - PDFs online - IARC Working Group Reports IARC Publications PDFs online - IARC Working Group Reports Vitamin D and Cancer "

Incidence of reported cold/influenza symptoms according to season. The 104 subjects in the placebo group (light shade) reported cold and flu symptoms year around with the most symptoms in the winter. While on 800 IU per day (intermediate shade) the 104 test subjects were as likely to get sick in the summer as the winter. Only one of the 104 test subjects had cold/influenza symptoms during the final year of the trial, when they took 2,000 IU of vitamin D per day (dark shading). Adapted from: Aloia JF, Li-Ng M: Epidemic influenza and vitamin D. Epidemiol Infect 2007; 135: 1095-1096

Hypercalcemia due to Hypervitaminosis D: Report of Seven Patients. Joshi R. J Trop Pediatr. 2009 Apr 1. [Epub ahead of print] PMID: 19339514

"IARC Publications PDFs online - IARC Working Group Reports Vitamin D and Cancer "

The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the literature. Köstner K, Denzer N, Müller CS, Klein R, Tilgen W, Reichrath J. Anticancer Res. 2009 Sep;29(9):3511-36. Review. PMID: 19667145 CONCLUSION: Significant associations with VDR polymorphisms have been reported in cancer of the breast (Fok1, Bsm1, Taq1, Apa1, poly (A)), prostate (Fok1, Bsm1, Taq1, poly (A)), skin (Fok1, Bsm1, A-1210), colorectum (Fok1, Bsm1), ovary (Fok1, Apa1) and bladder (Fok1), and in renal cell carcinoma (Taq1, Apa1). However, conflicting data have been reported for most malignancies. After careful evaluation of the actual literature, it can be summarized that data indicating an association of VDR polymorphisms and cancer risk are strongest for breast cancer (Bsm1, Fok1), prostate cancer (Fok1) and malignant melanoma (MM) (Fok1). Data indicating an association of VDR polymorphisms and cancer prognosis are strongest for prostate cancer (Fok1), breast cancer (Bsm1, Taq1), MM (Bsm1) and renal cell carcinoma (Taq1).

In the last post, we talked about the new report on vitamin D and cancer from the International Agency for Research into Cancer (IARC). In this one, we'll summarise what the report has to say on the balance between getting enough vitamin D through sun exposure and reducing the risk of skin cancer by being SunSmart. IARC calls for more trials to really pin down the effects of vitamin D supplements - either positive or negative - depending on how much vitamin D people already have in their system. Until then, they feel that there is no solid basis for changing any existing recommendations about vitamin D.

Vitamin D supplementation. Eveleigh B. Can Fam Physician. 2007 Sep;53(9):1435; author reply 1435. PMID: 17872869 My concern regarding vitamin D2 is that it is a synthetic analogue and might interact with the vitamin D receptor differently in various cell systems. It has been reported that vitamin D3 might improve glycemic control.7 Vitamin D2 has been reported to cause worsening of glycemic control in people of East Indian descent.8 Is this because of vitamin D receptor polymorphism, or because of enhanced 24-hydroxylase enzyme activation, or is it due to how vitamin D2 interacts with the receptor? Until this has been sorted out, I feel safest using vitamin D3. There are about 2000 synthetic analogues of vitamin D. The search is on for one that can cross the blood-brain barrier to treat certain types of brain cancers without causing hypercalcemia.9 But then again, what other effects would this compound have? There are still so many unknowns

Differences in vitamin D status between countries in young adults and the elderly. McKenna MJ. Am J Med. 1992 Jul;93(1):69-77. PMID: 1385673 PURPOSE: To compare vitamin D status between countries in young adults and in the elderly. MATERIALS AND METHODS: Reports on vitamin D status (as assessed by serum 25-hydroxyvitamin D) from 1971 to 1990 were reviewed. Studies were grouped according to geographic regions: North America (including Canada and the United States); Scandinavia (including Denmark, Finland, Norway, and Sweden); and Central and Western Europe (including Belgium, France, Germany, Ireland, The Netherlands, Switzerland, and the United Kingdom). RESULTS: Vitamin D status varies with the season in young adults and in the elderly, and is lower during the winter in Europe than in both North America and Scandinavia. Oral vitamin D intake is lower in Europe than in both North America and Scandinavia. Hypovitaminosis D and related abnormalities in bone chemistry are most common in elderly residents in Europe but are reported in all elderly populations. CONCLUSIONS: The vitamin D status in young adults and the elderly varies widely with the country of residence. Adequate exposure to summer sunlight is the essential means to ample supply, but oral intake augmented by both fortification and supplementation is necessary to maintain baseline stores. All countries should adopt a fortification policy. It seems likely that the elderly would benefit additionally from a daily supplement of 10 micrograms of vitamin D.

Towards an adequate intake of vitamin D. An advisory report of the Health Council of the Netherlands R M Weggemans, G Schaafsma and D Kromhout Eur J Clin Nutr advance online publication, July 22, 2009; doi:10.1038/ejcn.2009.67

Vieth R, Fraser D. Vitamin D insufficiency: no recommended dietary allowance exists for this nutrient. CMAJ. 2002 Jun 11;166(12):1541-2. PMID: 12074121 In fact, current recommendations for vitamin D are not designed to ensure anything. They are simply based on the old, default strategy for setting a nutritional guideline, which is to recommend an amount of nutrient similar to what healthy people are eating. This approach underlies the circular logic behind a familiar refrain about nutrition: "If you eat a good diet, you won't need supplements." By this logic, the answer to the question, "How much nutrient do you need?" is, "Whatever healthy people happen to be eating." The essential point, lost in the confusing terminology of modern nutrient recommendations, is that a recommended daily allowance (RDA) does not yet exist for vitamin D. Instead, the recommendations for it are referred to as "adequate intake" (AI).12,13 The AI for young adults (5 µg or 200 IU) was chosen to approximate twice the average vitamin D intake reported by 52 young women in a questionnaire-based study reported from Omaha, Neb., in 1997.13,14 Because the available evidence was acknowledged as weak, the Food and Nutrition Board of the US Institute of Medicine called its recommendation an AI.

Concentrations of vitamin D3 and 25-hydroxyvitamin D3 in raw and cooked New Zealand beef and lamb. Roger Purchas, Maggie Zoua, Philip Pearcea and Felicity Jackson- Journal of Food Composition and Analysis Volume 20, Issue 2, March 2007, Pages 90-98 For lamb, the highest levels of vitamin D3 were in the shoulder chop both before and after cooking, while levels were lowest in the rack muscle. Similar cut differences were shown for 25OHD3 concentrations. For beef there were no significant differences between the cuts for vitamin D3, but concentrations of 25OHD3 were lower in the striploin before and after cooking, Vitamin D3 levels tended to be higher in beef cuts than in lamb cuts, but the opposite held for 25OHD3. Concentrations of vitamin D3 were similar to those in other reports, but the 25OHD3 levels were at the high end of reported ranges. With 25OHD3 being more potent than vitamin D3, it is concluded that meat can make a useful contribution of this vitamin to the human diet.

"If you're running low on vitamin D - as an estimated 70 percent of the U.S. population is - your immune system may not be functioning as well as it should. As a result, you may be more vulnerable to infectious diseases than you would if your vitamin D levels were optimal. Worse, you could be at higher than normal risk of a long list of diseases including heart disease and several kinds of cancer. A report recently published journal, Future Microbiology, highlighted research at the Linus Pauling Institute at Oregon State University, which has shown that vitamin D induces expression of an antimicrobial peptide gene called cathelicidin that is the "first line of defense" in the immune system's response to minor wounds, cuts and bacterial and viral infections. The regulation of cathelicidin by vitamin D could help explain its vital role in immune function. The report noted that vitamin D is a key cofactor in reducing inflammation, in blood pressure control and helping to protect against heart disease. Author Adrian Gombart explains that there is still much to explore about D's mechanisms of action, the potential use of synthetic analogs of it in new treatments, and its duty in fighting infection."

ncident invasive breast cancer, geographic location of residence, and reported average time spent outside. Millen AE, Pettinger M, Freudenheim JL, Langer RD, Rosenberg CA, Mossavar-Rahmani Y, Duffy CM, Lane DS, McTiernan A, Kuller LH, Lopez AM, Wactawski-Wende J. Cancer Epidemiol Biomarkers Prev. 2009 Feb;18(2):495-507. Epub 2009 Feb 3. PMID: 19190147 doi: 10.1158/1055-9965.EPI-08-0652 In conclusion, region of residence and geographic solar irradiance are not consistently related to risk of breast cancer and may not be sufficient proxy measures for sunlight/vitamin D exposure. The observed association between time spent outside and breast cancer risk support the hypothesis that vitamin D may protect against breast cancer.

This month, the authoritative International Agency for Research into Cancer (IARC) have weighed in on the issue. By gathering a group of expert scientists, they have looked at all the available evidence and published a detailed report on vitamin D and cancer. The massive tome weighs in at 465 pages, but we'll take a look at the key points in the first of two posts looking at the vitamin D debate. It is impossible for us to get more than about five percent of the vitamin D we need from our diet - unless, like Eskimos, we eat oily fish three times a day.

Vitamin D replacement in Asians with diabetes may increase insulin resistance. Taylor AV, Wise PH. Postgrad Med J. 1998 Jun;74(872):365-6. PMID: 9799895 We report three cases of vitamin D replacement in British Asians with vitamin D deficiency and non-insulin-dependent diabetes mellitus. In all cases, replacement resulted in an increase in insulin resistance and a deterioration of glycaemic control

Wintertime vitamin D insufficiency is common in young Canadian women, and their vitamin D intake does not prevent it. Vieth R, Cole DE, Hawker GA, Trang HM, Rubin LA. Eur J Clin Nutr. 2001 Dec;55(12):1091-7. PMID: 11781676 INTERPRETATION: The self-reported vitamin D intake from milk and/or multivitamins does not relate to prevention of low vitamin D nutritional status of young women in winter. Recommended vitamin D intakes are too small to prevent insufficiency. Vitamin D nutrition can only be assessed by measuring serum 25(OH)D concentration.

Baseline serum 25-hydroxy vitamin d is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990-2000. Forouhi NG, Luan J, Cooper A, Boucher BJ, Wareham NJ. Diabetes. 2008 Oct;57(10):2619-25. Epub 2008 Jun 30. PMID: 18591391 doi: 10.2337/db08-0593 CONCLUSIONS: This prospective study reports inverse associations between baseline serum 25(OH)D and future glycemia and insulin resistance. These associations are potentially important in understanding the etiology of abnormal glucose metabolism and warrant investigation in larger, specifically designed prospective studies and randomized controlled trials of supplementation.

Vitamin D and skin physiology: a D-lightful story. Holick MF, Chen TC, Lu Z, Sauter E. J Bone Miner Res. 2007 Dec;22 Suppl 2:V28-33. PMID: 18290718 doi: 10.1359/jbmr.07s211 Very few foods naturally contain vitamin D, and those that do have a very variable vitamin D content. Recently it was observed that wild caught salmon had between 75% and 90% more vitamin D(3) compared with farmed salmon. The associations regarding increased risk of common deadly cancers, autoimmune diseases, infectious diseases, and cardiovascular disease with living at higher latitudes and being prone to vitamin D deficiency should alert all health care professionals about the importance of vitamin D for overall health and well being. Humans have depended on sunlight for their vitamin D requirement. The impact of season, time of day, and latitude on vitamin D synthesis is well documented.(2,3) We now report that altitude also has a dramatic influence on vitamin D3 production and that living at altitudes above 3500 m permits previtamin D3 production at a time when very little is produced at latitudes below 3400 m. It was surprising that, at 27° N in Agra (169 M), little previtamin D3 production was observed. However, there was significant air pollution that caused a haze over the city. It is likely the ozone and other UVB-absorbing pollutants in the air prevented the solar UVB photons from reaching the earth's surface to produce previtamin D3.

Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Hyppönen E, Power C. Am J Clin Nutr. 2007 Mar;85(3):860-8. PMID: 17344510 Conclusion: Prevalence of hypovitaminosis D in the general population was alarmingly high during the winter and spring, which warrants action at a population level rather than at a risk group level. Data from the 1958 birth cohort suggest that, at different cutoffs for hypovitaminosis D, a substantial public health problem exists in British whites. Obese participants and those living in Scotland were at the highest risk of hypovitaminosis D. However, the prevalence in the general population was very high during the winter and spring, which suggests that, to improve the situation, action is required at a population level rather than at a risk-group level. In the United States, calls have gone out for an increase in vitamin D fortification of foods (11), and the data from the current study suggest that such action is also warranted in the United Kingdom. Vitamin D is currently available without prescription as a dietary supplement only as part of cod liver oil or multivitamin products; hence, a need clearly exists to consider increased availability of over-the-counter supplements. Hypovitaminosis D has been implicated in the development of serious conditions, including diabetes, various types of cancer, and cardiovascular diseases, in addition to its essential role in maintaining bone health (1, 2). The high rates of hypovitaminosis D reported in this study suggest that immediate action is needed to improve the vitamin D status of the British population.