Vitamin D fights 13 cancers – review of 35 meta-analyses – Oct 2020

Vitamin D and clinical cancer outcomes: a review of meta analyses

John D Sluyter1, JoAnn E Manson2 3, Robert Scragg1

• 1 School of Population Health, University of Auckland, Private Bag，Auckland, New Zealand.
• 2 department of Medicine, Brigham and Womens Hospital, and Harvard Medical School, Boston, MA, USA.
• 3 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA USA
  • Correspondence: Dr John Sluyter, School of Population Health, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand. i.sluvter at auckland.ac.nz

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Intervention

The relationship between vitamin D status or supplementation and cancer outcomes has been examined in several meta-analyses. To address remaining knowledge gaps, we conducted a systematic overview and critical appraisal of pertinent meta-analyses. For meta-analyses of trials, we assessed their quality using AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews), strength of associations using umbrella review methodology and credibility of evidence using GRADE (Grading of Recommendations, Assessment, Development and Evaluation) criteria. Meta-analyses of observational studies reported inverse associations of 25-hydroxyvitamin D with risk of cancer incidence and cancer mortality and, particularly for colorectal cancer, fulfilled some of Bradford-HilFs causation criteria. In meta-analyses of trials, vitamin D supplementation did not affect cancer incidence. However, we found credible evidence that vitamin D supplementation reduced total cancer mortality risk, with 5 out of 6 meta-analyses reporting a relative risk (RR) reduction of up to 16%: RR=0.84 (95% confidence interval: 0.74-0.95). The strength of the association, however, was classified as weak. This was true among meta-analyses of high, moderate and lower quality (AMSTAR-2-rated). Trials did not include large numbers of vitamin D-deficient participants, many tested relatively low doses and lacked sufficiently powered data on site- specific cancers. In conclusion, meta-analyses show that, while observational evidence indicates that low vitamin D status is associated with a higher risk of cancer outcomes, randomized trials demonstrate that vitamin D supplementation reduces total cancer mortality but not cancer incidence. However, trials with larger proportions of vitamin D-insufficient participants and longer durations of follow-up, plus adequately powered data on site-specific common cancers, would provide further insight into the evidence base