Evidence Against

Epidemiological studies yielded mixed evidence about vitamin D intake, vitamin D blood levels, and cancer risk. Overall, while there is emerging evidence that vitamin D levels in the bloodstream might correlate with lower risks and improved survival in certain cancers, it is not yet clear that dietary supplementation is an effective chemopreventive or cancer-treatment intervention.

Common potential confounds and limitations in this research literature include studies failing to account for sunlight exposure (and skin pigmentation) and/or calcium supplementation, determination of blood levels at only 1 point in time (which might not accurately reflect individuals’ baseline vitamin D levels), relatively low vitamin D supplementation goals (eg, 10 μg/d), and short follow-up times. Weight and alcohol consumption levels might modulate the potential association between vitamin D and breast cancer risk, as might VDR genotypes and other genomic factors in breast and other cancer types.11


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A prospective cohort analysis found no association between dietary vitamin D intake or plasma 25(OH)D levels and endometrial cancer risk, but the authors noted that study participants exhibited a “low and narrow” range of vitamin D.12

At least 5 randomized clinical trials of vitamin D supplementation and cancer mortality have been published.13-17 These studies found that vitamin D supplementation can reduce bone fracture among patients with cancer but that supplementation was not associated with improved cancer incidence or survival outcomes.

The most recent of the randomized clinical trials published to date was the phase 3 Clinical Trial of Vitamin D3 to Reduce Cancer Risk in Postmenopausal Women (CAPS), published in March 2017. This randomized, 4-year, double-blind, placebo-controlled study of 2303 health postmenopausal women found that daily high-dose (50 μg; 2000 IU) vitamin D3 plus calcium (1500 mg) supplementation was not associated with reduced cancer risk (3.9% vs 5.6%; P = .06), narrowly missing significance.17

Conclusions and Ongoing Phase 3 Randomized Clinical Trials

There is growing evidence that higher circulating levels of vitamin D are associated with lower risks of at least some types of cancer and improved cancer outcomes. There is, however, not enough evidence to conclude that dietary supplements are an effective intervention for reducing cancer risk or improving cancer outcomes.

A larger, randomized, controlled clinical trial that is nearing completion should allow clearer determination of vitamin D’s potential value in preventing or treating cancers among other adults in the general population: the Vitamin D and Omega-3 Trial (VITAL) cancer prevention trial, which was designed to determine the effects of vitamin D and omega-3 fatty acid dietary supplementation on cancer and cardiovascular disease risk among adults aged at least 50 years (men) or 55 years (women).18

Another randomized clinical trial that is active but no longer recruiting patients is the Vitamin D/Calcium Polyp Prevention Study, which was designed to determine if vitamin D dietary supplements, with or without calcium, can reduce the risk of precancerous colorectal adenoma recurrence after adenoma removal.19

References

  1. Vitamin D and cancer prevention. National Cancer Institute website. https://www.cancer.gov/about-cancer/causes-prevention/risk/diet/vitamin-d-fact-sheet. Accessed April, 2017.
  2. Tagliabue E, Raimondi S, Gandini S. Vitamin D, cancer risk, and mortality. Advanc Food and Nutr Res. 2015;75:1-52. doi: 10.1016/bs.afnr.2015.06.003
  3. U.S. 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. http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Vitamin%20D%20and%20Calcium%202010%20Report%20Brief.pdf
  4. Ross AC, Manson JE, Abrams SA. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53-8. doi: 10.1210/jc.2010-2704
  5. Vaughan-Shaw PG, O’Sullivan F, Farrington SM, et al. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. Br J Cancer. 2017 Mar 16. doi: 10.1038/bjc.2017.44 [Epub ahead of print]
  6. Chowdhury R, Kunutsor S, Vitezova A, et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ. 2014;348:g1903. doi: 10.1136/bmj.g1903
  7. Bjelakovic G, Gluud LL, Nikolova D, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2014;1:CD007470. doi: 10.1002/14651857.CD007470.pub3
  8. Bao Y, Ng Y, Wolpin BM, Michaud DS, Giovannucci E, Fuchs CS. Predicted vitamin D status and pancreatic cancer risk in two prospective cohort studies. Br J Cancer. 2010;102(9):1422-7. doi: 10.1038/sj.bjc.6605658
  9. Yao S, Kwan ML, Ergas IJ, et al. Association of serum level of vitamin D at diagnosis with breast cancer survival: a case-cohort analysis in the Pathways study. JAMA Oncol. 2017;3(3):351-7. doi: 10.1001/jamaoncol.2016.4188
  10. Shirazi L, Almquist M, Borgquist S, Malm J, Manjer J. Serum vitamin D (25OHD3) levels and the risk of different subtypes of breast cancer: a nested cast-control study. Breast. 2016;28:184-90. doi: 10.1016/j.breast.2016.06.002
  11. Deschasaux M, Souberbielle JC, Latino-Martel P, et al. Weight status and alcohol intake modify the association between vitamin D and breast cancer risk. J Nutr. 2016;146(3):576-85. doi: 10.2945/jn.115.221481
  12. Liu JJ, Bertrand KA, Karageorgi S, et al. Prospective analysis of vitamin D and endometrial cancer risk. Ann Oncol. 2013;24(3):687-92. doi: 10.1093/annonc/mds509.
  13. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2012;85(6):1586-91.
  14. Avenell A, MacLennan GS, Jenkinson DL, et al. Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium (RECORD trial). J Clin Endocrinol Metabol. 2012;97(2):614-22.
  15. Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: Randomised double blind controlled trial. BMJ (Clinical Research Ed.). 2003;326(7387):469. doi: 10.1136/bmj.326.7387.469
  16. Wactawski-Wende J, Kotchen JM, Anderson GL, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. New Engl J Med. 2006;354(7):684-96.
  17. Lappe J, Watson P, Travers-Gustafson D, et al. Effect of vitamin D and calcium supplementation on cancer incidence in older women: a randomized clinical trial. JAMA. 2017;317(12):1234-43. doi: 10.1001/jama.2017.2115
  18. 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. Contemp Clin Trials. 2012;33:159-71. doi: 10.1016/j.cct.2011.09.009
  19. Clinicaltrials.gov. Vitamin D/calcium polyp prevention study. NCT00153816. https://clinicaltrials.gov/ct2/show/NCT00153816. Accessed April, 2017.