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Vitamin D and omega-3 supplementation

The largest trial of vitamin D and fish-oil pills found they did not prevent cancer. A possible reduction in cancer deaths, and hints of benefit after a digestive cancer diagnosis, keep the question alive.

VITAL (NEJM 2019) randomised 25,871 US adults to vitamin D3 2000 IU/day and/or omega-3 fatty acids 1 g/day for a median 5.3 years: invasive cancer incidence was unchanged (HR 0.96 for vitamin D, 1.03 for omega-3). Total cancer mortality was numerically lower with vitamin D, reaching significance only in analyses excluding the first two years (HR 0.75), an exploratory finding, and a pooled meta-analysis of vitamin D trials suggests a 10-15% reduction in cancer death but not incidence. In patients already diagnosed, the Japanese AMATERASU (digestive tract cancers) and SUNSHINE (metastatic colorectal, high-dose vitamin D with chemotherapy) trials were null on their primary endpoints with subgroup hints; the phase 3 SOLARIS trial of high-dose vitamin D with FOLFOX-bevacizumab in metastatic colorectal cancer was negative (2025). Omega-3 supplements have no consistent cancer prevention effect; in cachexia they preserve weight in some trials but not function. The defensible summary: correct deficiency, do not expect prevention from supplements.

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How it works

Vitamin D acts through the vitamin D receptor on cell differentiation, proliferation and immune modulation; omega-3 fatty acids reduce pro-inflammatory eicosanoids. Neither has translated into reduced cancer incidence in randomised trials.

Strengths
  • Definitive randomised evidence on incidence
  • Cheap and safe at tested doses
  • Mortality signal worth a purpose-designed trial
Limitations
  • Primary prevention endpoints null
  • Secondary and subgroup findings drive continued hype
  • Baseline deficiency rarely stratified

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