Vitamin D and fish oil are among the supplements people take to protect their heart and lower their cancer risk. Asking what a randomized trial found is the fair test, and the largest such trial of both supplements is VITAL, which tested them in the same group of adults.
Vitamin D3: no effect on cancer or heart events
VITAL randomized 25,871 adults, men aged 50 and older and women aged 55 and older, to 2,000 IU of vitamin D3 a day or to placebo. During a median follow-up of 5.3 years, invasive cancer was diagnosed in 1,617 participants, 793 in the vitamin D group and 824 in the placebo group (hazard ratio 0.96, 95% CI 0.88 to 1.06). Major cardiovascular events occurred in 805 participants (hazard ratio 0.97, 95% CI 0.85 to 1.12) (Manson 2019).
The authors concluded that vitamin D did not lower the incidence of invasive cancer or cardiovascular events. Cancer deaths were lower on vitamin D, but not significantly (hazard ratio 0.83, 95% CI 0.67 to 1.02).
Omega-3: a smaller heart attack signal in the same trial
VITAL tested 1 g a day of marine omega-3 (EPA and DHA) in the same participants. Major cardiovascular events occurred in 386 on omega-3 and 419 on placebo (hazard ratio 0.92, 95% CI 0.80 to 1.06), which was not statistically significant (Manson 2019, omega-3).
Total myocardial infarction was lower (hazard ratio 0.72, 95% CI 0.59 to 0.90). Stroke and cancer were not lower (hazard ratios 1.04 and 1.03). A heart attack finding among several secondary endpoints needs confirmation in a trial designed to test it.
Prescription EPA and high-dose omega-3 gave different results
REDUCE-IT gave 8,179 adults with high triglycerides who were taking a statin either 4 g a day of icosapent ethyl, a prescription purified EPA, or placebo. The primary composite of cardiovascular death, heart attack, stroke, revascularization or unstable angina occurred in 17.2% on icosapent ethyl and 22.0% on placebo (hazard ratio 0.75, 95% CI 0.68 to 0.83) (Bhatt 2019).
STRENGTH gave 13,078 high-risk patients on statins 4 g a day of omega-3 carboxylic acids or corn oil. The interim analysis showed a low probability of benefit, so the trial was stopped early, and it found no significant reduction in major adverse cardiovascular events (Nicholls 2020).
The two trials differ in product, dose and population, and the difference is not settled. Neither tested an over-the-counter fish oil capsule.
Vitamin D testing: the blood level is the test
Vitamin D deficiency is diagnosed with a blood test for 25-hydroxyvitamin D. The Endocrine Society guideline recommends that test for people at risk of deficiency. It says there is not sufficient evidence to screen people who are not at risk, or to prescribe vitamin D for cardiovascular protection (Holick 2011).
The US Preventive Services Task Force concluded in 2021 that the evidence is insufficient to assess the balance of benefits and harms of screening asymptomatic adults for vitamin D deficiency (USPSTF 2021).
Vitamin D with vitamin K2
Some vitamin D products add vitamin K2. VITAL tested vitamin D3 alone, and the omega-3 trials tested omega-3 alone, so these trials say nothing about the combinations.
What this does not say
- VITAL enrolled adults who were generally healthy. It does not show what happens in people who are deficient or who already have heart disease.
- Hazard ratios are averages for groups. They are not predictions for one person.
- The cancer and heart attack subgroup results were secondary analyses, and several findings were not statistically significant.
- The omega-3 trial used 1 g a day of EPA and DHA. Our fish oil capsules are supplements, not the prescription EPA product tested in REDUCE-IT, and their doses differ.
How we use this
We do not present vitamin D or fish oil as protection against cancer or heart attacks. We check vitamin D levels when there is a reason to, and we recommend omega-3 only when the reason and the dose are clear.
If a supplement is part of your plan, we say what it is for, what the trials found, and when we will review it.
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- 1.Manson JE et al. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med. 2019;380:33-44. Manson JE et al., N Engl J Med, 2019
- 2.Manson JE et al. Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med. 2019;380:23-32. Manson JE et al., N Engl J Med, 2019
- 3.Bhatt DL et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380:11-22. Bhatt DL et al., N Engl J Med, 2019
- 4.Nicholls SJ et al. Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events: The STRENGTH Randomized Clinical Trial. JAMA. 2020;324:2268-2280. Nicholls SJ et al., JAMA, 2020
- 5.Holick MF et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911-1930. Holick MF et al., J Clin Endocrinol Metab, 2011
- 6.Vitamin D Deficiency: Screening recommendation statement. US Preventive Services Task Force, 2021. US Preventive Services Task Force, 2021