# Vitamin D and omega-3 supplementation

Source: https://onco.cc/technologies/vitamin-d-omega3-supplementation/  
OnCo record `vitamin-d-omega3-supplementation` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Technology
- Status: phase-3
- Last checked: 2026-09-08
- Principle: 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

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Vitamin_D
- VITAL (NEJM 2019): https://doi.org/10.1056/NEJMoa1809944
- SUNSHINE (JAMA 2019): https://doi.org/10.1001/jama.2019.2402

## Connected records

- ideas: [A biomarker-directed trial of vitamin D after surgery for digestive tract cancers](https://onco.cc/ideas/idea-reg-vitamin-d-digestive-cancer-biomarker-trial/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- fronts: [Diet, Exercise & Lifestyle](https://onco.cc/fronts/nutrition-lifestyle/), [Prevention & Risk](https://onco.cc/fronts/prevention/)
- technologies: [Bone loss caused by cancer treatment, and what rebuilds it](https://onco.cc/technologies/cancer-treatment-bone-loss/), [Chemoprevention & risk-reducing surgery](https://onco.cc/technologies/chemoprevention/)
- drugs: [Bevacizumab](https://onco.cc/drugs/bevacizumab/), [FOLFOX (5-FU, leucovorin, oxaliplatin)](https://onco.cc/drugs/folfox/)
- terms: [Unproven diet claims (alkaline, juice, 'anti-cancer' diets)](https://onco.cc/terms/unproven-diet-claims/)
- trials: [VITAL (VITamin D and OmegA-3 TriaL)](https://onco.cc/trials/vital/)
- bottlenecks: [Failures are hidden](https://onco.cc/bottlenecks/b-negative-results/), [Misinformation and unproven therapies](https://onco.cc/bottlenecks/b-misinformation/)
- key papers: [Effect of High-Dose vs Standard-Dose Vitamin D3 Supplementation on Progression-Free Survival Among Patients With Advanced or Metastatic Colorectal Cancer: The SUNSHINE Randomized Clinical Trial](https://onco.cc/key-papers/paper-ng-jama/), [Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease](https://onco.cc/key-papers/paper-manson-n-engl-j-med/)
- roadmaps: [Diet, exercise and lifestyle roadmap: causes established → interventions that disappointed → exercise proven as treatment](https://onco.cc/roadmaps/nutrition-lifestyle-roadmap/)

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