Potential Hazards

Excessive intake of vitamin D (more than 100 μg/d) can lead to hypercalcemia and calcinosis of the kidneys, heart and lungs. Because of the association between UV exposure and skin cancer risk, the Institute of Medicine advises against increasing vitamin D levels through sun exposure or tanning. Nor are the long-term health effects, including risks, known for high-dose vitamin D supplementation.

Evidence in Favor

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There is limited evidence countenancing vitamin D supplementation’s protective effect against cancer or beneficial effects on outcomes among patients with cancer. Several meta-analyses have suggested, however, that cancer outcomes might be linked to circulating 25(OH)D.

A recent meta-analysis of data pooled from 64 published studies found that higher circulating levels of 25(OH)D are associated with better progression-free (PFS) and overall survival among patients diagnosed with cancers.5 The authors noted that functional variants of genes in the vitamin D pathway were also associated with outcomes, which represents evidence of “a causal link” between vitamin D and cancer survival. They called for new clinical trials that assess vitamin D’s influence on cancer outcomes in genotype-stratified study-participant populations.

The authors of a 2014 meta-analysis of data pooled from 73 cohort studies and 22 randomized controlled trials found that when they compared the lowest and highest thirds of study participants’ circulating 25(OH)D from primary prevention studies, there was a modestly higher risk of death from cancer among patients with lowest circulating 25(OH)D (pooled relative risk [RR] 1.14; 95% CI: 1.01-1.29).6

Similarly, authors of a 2014 Cochrane systematic review and pooled analysis concluded that circulating cholecalciferol (D3) was significantly associated with reduced cancer mortality (RR 0.88; 95% CI: 0.78-0.98; P = .02).7

Yet both of these 2014 studies’ findings derived from studies of all-causes of mortality, which were not specifically designed to assess cancer or cancer risk mortalities and might suffer from confounding and statistical bias.2 Studies of vitamin D and specific types of cancer indicate that the association might also vary importantly between different kinds of cancer.

Higher estimated 25(OH)D levels in the Nurses’ Health Study and Health Professionals Follow-up Study found that after a follow-up of 20 years, pancreatic cancer risk was significantly and inversely related with vitamin D levels (RR 0.65; 95% CI: 0.50-0.86; P = .001).8

The Pathways Study found that serum 25(OH)D concentrations independently predict disease prognosis and overall survival among patients with breast cancer “most prominently” among premenopausal women.9 In multivariate analyses comparing the highest and lowest thirds of patient 25(OH)D levels, OS hazard ratio (HR) was 0.72 (95% CI: 0.54-0.09) overall and 0.45 among premenopausal women (95% CI: 0.21-0.96) .9

The exact nature of these associations is not, however, yet clear. There is some evidence that serum 25(OH)D levels are associated with the risk of different breast cancer subtypes, for example.10