Vitamin D: Beyond Bone Health?
The work of Budhathoki et al. is methodologically robust and their findings make an important contribution to the current literature (1). However it is prematrue and indeed a non-sequitur to conclude that vitamin D has an oncoprotective effect.
Their study shows a strong inverse correlation between serum vitamin D and the risk of a host of cancers. However, in contrast with this finding, the body of evidence from the most recent 2014 Cochrane review and randomised controlled trials shows that vitamin D supplementation does not reduce the risk of cancer (2,3,4). One must conclude that vitamin D is a surrogate or proxy for an oncoprotector, given that its putative protective effect against cancer is not reproduced by vitamin D supplementation.
The authors correctly identify that their study population do not consume significant quantities of food fortified with vitamin D, hence the majority of their vitamin is photogenerated. UV light itself may be the oncoprotector. UV light produces nascent tumour cells in the skin, with generic tumour antigens involved in tumorigenesis and metastases. These cells are eradicated by the host immmunity, resulting in some acquired immunity to future tumour antigens and cancer. This is solar vaccination. Vitamin D levels are a surrogate marker for UV exposure, hence the associations observed by the authors. Thus UV light may be the oncoprotector rather than vitamin D.
One of the most telling pieces of evidence is that of Dimitrakopoulou, published in this journal (5). They uncouple vitamin D levels from UV exposure, to see if there is a veritable link with vitamin D and cancer risk. The authors look at inviduals with low vitamin D levels due to genetic polymorphisms. However, these individuals had no increased risk of 7 cancer types. Similar results have been reported in the context of individual cancers such as prostate cancer (6,7). These studies conclude that the a causal link can not explain any relationship between vitamin D and tumour risk. Hence the evidence does not appear to support the authors' conclusion in this present study that the inverse association of serum vitamin D levels with cancer risk is suggestive of an anti-tumour effect of vitamin D.
(1) Budhathoki SS, Hidaka A, Yamaji T, Sawada N, Tanaka-Mizuno S, Kuchiba A, Charvat H, Goto A, Kojima S, Sudo N, Shimazu T, Sasazuki S, Inoue M, Tsugane S, Iwasaki M; Japan Public Health Center-based Prospective Study Group. Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: large case-cohort study within Japan Public Health Center-based Prospective Study cohort. BMJ. 2018 Mar 7;360:k671
(2) Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Krstic G, Wetterslev J, Gluud C.Vitamin D supplementation for prevention of cancer in adults. Cochrane Database Syst Rev. 2014 Jun 23;(6):CD007469
(3) Manson JE, Bassuk SS, Buring JE.Vitamin D, Calcium, and Cancer: Approaching Daylight? JAMA. 2017 Mar 28;317(12):1217-1218
(4) Lappe J, Watson P, Travers-Gustafson D, Recker R, Garland C, Gorham E, Baggerly K, McDonnell SL.Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial. JAMA. 2017 Mar 28;317(12):1234-1243.
(5) Dimitrakopoulou VI, Tsilidis KK, Haycock PC, et al. Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study. BMJ2017;359:j4761
(6) Trummer O, Langsenlehner U, Krenn-Pilko S, Pieber TR, Obermayer-Pietsch B, Gerger A, Renner W, Langsenlehner T.Vitamin D and prostate cancer prognosis: a Mendelian randomization study. World J Urol. 2016 Apr;34(4):607-11. doi: 10.1007/s00345-015-1646-9. Epub 2015 Jul 25.
(7) Mondul AM, Shui IM, Yu K, Travis RC, Stevens VL, Campa D, Schumacher FR, Ziegler RG, Bueno-de-Mesquita HB, Berndt S, Crawford ED, Gapstur SM, Gaziano JM, Giovannucci E, Haiman CA, Henderson BE, Hunter DJ, Johansson M, Key TJ, Le Marchand L, Lindström S, McCullough ML, Navarro C, Overvad K, Palli D, Purdue M, Stampfer MJ, Weinstein SJ, Willett WC, Yeager M, Chanock SJ, Trichopoulos D, Kolonel LN, Kraft P, Albanes D.Genetic variation in the vitamin d pathway in relation to risk of prostate cancer--results from the breast and prostate cancer cohort consortium. Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):688-96
Competing interests: No competing interests