What is the evidence that vitamin D can help reduce the risk of cancer in people?

A number of epidemiologic studies have investigated whether people with higher vitamin D intakes or higher blood levels of vitamin D have lower risks of specific cancers. The results of these studies have been inconsistent, possibly because of the challenges in carrying out such studies. For example, dietary studies do not account for vitamin D made in the skin from sunlight exposure, and the level of vitamin D measured in the blood at a single point in time (as in most studies) may not reflect a person’s true vitamin D status. Also, it is possible that people with higher vitamin D intakes or blood levels are more likely to have other healthy behaviors. It may be one of these other behaviors, rather than vitamin D intake, that influences cancer risk.

Several randomized trials of vitamin D intake have been carried out, but these were designed to assess bone health or other non-cancer outcomes. Although some of these trials have yielded information on cancer incidence and mortality, the results need to be confirmed by additional research because the trials were not designed to study cancer specifically.

The cancers for which the most human data are available are colorectal, breast, prostate, and pancreatic cancer. Numerous epidemiologic studies have shown that higher intake or blood levels of vitamin D are associated with a reduced risk of colorectal cancer.7-10 In contrast, the Women’s Health Initiative randomized trial found that healthy women who took vitamin D and calcium supplements for an average of 7 years did not have a reduced incidence of colorectal cancer.11 Some scientists have pointed out that the relatively low level of vitamin D supplementation (10 μg, or 400 IU, once a day), the ability of participants to take additional vitamin D on their own, and the short duration of participant follow-up in this trial might explain why no reduction in colorectal cancer risk was found. Evidence on the association between vitamin D and the risks of all other malignancies studied is inconclusive.

How is vitamin D being studied now in clinical cancer research?

Taken together, the available data are not comprehensive enough to establish whether taking vitamin D can prevent cancer.12 To fully understand the effects of vitamin D on cancer and other health outcomes, new randomized trials need to be conducted.13 However, the appropriate dose of vitamin D to use in such trials is still not clear.14 Other remaining questions include when to start taking vitamin D, and for how long, to potentially see a benefit.

To begin addressing these issues, researchers are conducting two phase I trials to determine what dose of vitamin D may be useful for chemoprevention of prostate, colorectal, and lung cancers (trial descriptions here and here). In addition, larger randomized trials have been initiated to examine the potential role of vitamin D in the prevention of cancer. The Vitamin D/Calcium Polyp Prevention Study, which has finished recruiting approximately 2,200 participants, is testing whether vitamin D supplements, given alone or with calcium, can prevent the development of colorectal adenomas (precancerous growths) in patients who previously had an adenoma removed. The study’s estimated completion date is December 2017. The Vitamin D and Omega-3 Trial (VITAL) will examine whether vitamin D supplements can prevent the development of a variety of cancer types in healthy older men and women.15 The organizers of VITAL expect to recruit 20,000 participants and complete the trial by June 2016.

Researchers are also beginning to study vitamin D analogs—chemicals with structures similar to that of vitamin D—which may have the anticancer activity of vitamin D but not its ability to increase calcium levels.16

Selected References

1. Otten JJ, Hellwig JP, Meyers LD. Vitamin D. In: Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC: National Academies Press, 2006.

2. Institute of Medicine Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academies Press; 2011.

3. Thorne J, Campbell MJ. The vitamin D receptor in cancer. Proceedings of the Nutrition Society. 2008;67(2):115-127.

4. Moreno J, Krishnan AV, Feldman D. Molecular mechanisms mediating the antiproliferative effects of vitamin D in prostate cancer. Journal of Steroid Biochemistry and Molecular Biology 2005; 97(1–2):31–36.

5. Holt PR, Arber N, Halmos B, et al. Colonic epithelial cell proliferation decreases with increasing levels of serum 25-hydroxy vitamin D. Cancer Epidemiology, Biomarkers, and Prevention 2002; 11(1):113–119.

6. Deeb KK, Trump DL, Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nature Reviews Cancer. 2007;7(9):684-700.

7. Ma Y, Zhang P, Wang F, et al. Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies. Journal of Clinical Oncology. 2011;29(28):3775-3782.

8. Gandini S, Boniol M, Haukka J, et al. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. International Journal of Cancer. 2011;128(6):1414-1424.

9. Woolcott CG, Wilkens LR, Nomura AM, et al. Plasma 25-hydroxyvitamin D levels and the risk of colorectal cancer: the multiethnic cohort study. Cancer Epidemiology, Biomarkers & Prevention. 2010;19(1):130-134.

10. Jenab M, Bueno-de-Mesquita HB, Ferrari P, et al. Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control study. BMJ. 2010;340:b5500.

11. Wactawski-Wende J, Kotchen JM, Anderson GL, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. New England Journal of Medicine 2006; 354(7):684–696.

12. Chung M, Lee J, Terasawa T, et al. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force. Annals of Internal Medicine. 2011;155(12):827-838.

13. IARC Working Group on Vitamin D. Vitamin D and cancer: A report of the IARC Working Group on Vitamin D. IARC Working Group Reports. Lyon, France: International Agency for Research on Cancer, 2008.

14. Yetley EA, Brulé D, Cheney MC, et al. Dietary Reference Intakes for vitamin D: Justification for a review of the 1997 values. American Journal of Clinical Nutrition 2009; 89(3):719–727.

15. Manson JE, Bassuk SS, Lee IM, et al. The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemporary Clinical Trials. 2012;33(1):159-171.

16. Pereira F, Larriba MJ, Muñoz A. Vitamin D and colon cancer. Endocrine-Related Cancer. 2012;19(3):R51-71.