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Original Investigation
November 8, 2018

Monthly High-Dose Vitamin D Supplementation and Cancer Risk: A Post Hoc Analysis of the Vitamin D Assessment Randomized Clinical Trial

Author Affiliations
  • 1School of Population Health, University of Auckland, Auckland, New Zealand
  • 2Department of Public Health, University of Cambridge, Cambridge, United Kingdom
  • 3Department of Public Health & General Practice, University of Otago, Christchurch, New Zealand
  • 4Department of Nutrition, Harvard TH Chan School of Public Health, Boston, Massachusetts
  • 5Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts
  • 6Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston
JAMA Oncol. 2018;4(11):e182178. doi:10.1001/jamaoncol.2018.2178
Key Points

Question  Is monthly high-dose vitamin D supplementation associated with cancer prevention?

Findings  In this post hoc analysis of Vitamin D Assessment (ViDA) randomized clinical trial that included 5108 community adults in New Zealand, the cumulative incidence of cancer for a median follow-up period of 3.3 years was 6.5% among participants receiving 100 000 IU of vitamin D3 monthly and 6.4% among participants receiving placebo.

Meaning  Monthly high-dose vitamin D supplementation may not be associated with cancer prevention and should not be used for this purpose.


Importance  Previous randomized clinical trials have reported inconsistent results on the effect of vitamin D supplementation on cancer incidence.

Objective  To examine whether high-dose vitamin D supplementation received monthly, without calcium, is associated with a reduction in cancer incidence and cancer mortality in the general population.

Design, Setting, and Participants  This is a post hoc analysis of data from the Vitamin D Assessment (ViDA) study, a randomized, double-blind, placebo-controlled trial that recruited participants from family practices and community groups in Auckland, New Zealand, from April 5, 2011, through November 6, 2012, with follow-up completed December 31, 2015. Participants were adult community residents aged 50 to 84 years. Of 47 905 adults invited from family practices and 163 from community groups, 5110 participants were randomized to receive vitamin D3 (n = 2558) or placebo (n = 2552). Two participants withdrew consent, and all others (n = 5108) were included in the primary analysis. Data analysis was by intention to treat.

Interventions  Oral vitamin D3, in an initial bolus dose of 200 000 IU and followed by monthly doses of 100 000 IU, or placebo for a median of 3.3 years (range, 2.5-4.2 years).

Main Outcomes and Measures  Post hoc primary outcome was the number of all primary invasive and in situ malignant neoplasms (excluding nonmelanoma skin cancers) diagnosed from randomization until the study medication was discontinued on July 31, 2015.

Results  Of the 5108 participants included in the analysis, the mean (SD) age was 65.9 (8.3) years, 58.1% were male, and 4253 (83.3%) were of European or another race/ethnicity, with the remainder being Polynesian or South Asian. Mean (SD) baseline deseasonalized 25-hydroxyvitamin D concentration was 26.5 (9.0) ng/mL. In a random sample of 438 participants, the mean follow-up 25-hydroxyvitamin D concentration consistently was greater than 20 ng/mL higher in the vitamin D group than in the placebo group. The primary outcome of cancer comprised 328 total cases of cancer (259 invasive and 69 in situ malignant neoplasms) and occurred in 165 of 2558 participants (6.5%) in the vitamin D group and 163 of 2550 (6.4%) in the placebo group, yielding an adjusted hazard ratio of 1.01 (95% CI, 0.81-1.25; P = .95).

Conclusions and Relevance  High-dose vitamin D supplementation prescribed monthly for up to 4 years without calcium may not prevent cancer. This study suggests that daily or weekly dosing for a longer period may require further study.

Trial Registration  anzctr.org.au Identifier: ACTRN12611000402943