VITAL trial considers omega-3 fatty acids, vitamin D in CV protection and cancer mortality

Marine omega-3 fatty acids may provide a cardioprotective role, while vitamin D3 supplementation appears to benefit cancer mortality, according to principal results from the National Institutes of Health-funded VITamin D and OmegA-3 TriaL.

Results of the more than five-year large clinical trial were presented by JoAnn E. Manson, MD, DrPH, in the Late-Breaking Clinical Trial session, “The VITamin D and OmegA-3 TriaL (VITAL): Principal Results for Vitamin D and Omega-3 Fatty Acid Supplementation in the Primary Prevention of Cardiovascular Disease and Cancer.” It was funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute.

VITAL is one of only two large, randomized clinical trials of vitamin D for the prevention of cancer, heart disease and stroke — and the only such trial in a racially and ethnically diverse study population. Similarly, it’s the only large trial of fish oil supplements in a generally healthy population.

“This was a look at both the independent and joint effects of the intervention,” said Manson, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital and a Michael and Lee Bell Professor of Women’s Health at Harvard Medical School in Boston.

The study involved 25,871 U.S. adults (men age ≥50 and women age ≥55) who didn’t have a history of heart disease, cancer or stroke. Participants took daily dietary supplements of vitamin D3 (2000 IU daily) or marine omega-3 fatty acids (Omacor® fish oil, one gram daily). The trial was administered by Brigham and Women’s Hospital.

VITAL, which was a 2×2 factorial randomized, double-blind, placebo-controlled study, examined both the benefits and risks of the dietary supplements given to participants.

The omega-3 fatty acid component of the trial studied the primary endpoints of major CVD events, a composite of myocardial infarction, stroke and CVD mortality, as well as total invasive cancer, Manson said. Secondary endpoints included individual components of major CVD, other vascular events, site-specific cancers and cancer mortality.

During a median 5.3 years of treatment, the one gram of omega-3 daily supplementation participants received was associated with a significant 28 percent reduction in total MI, as well as significant reductions in fatal MI, percutaneous coronary intervention and total coronary heart disease. There was no significant reduction in stroke or CVD mortality.

Also, MI was 40 percent lower in participants who ate less than one-and-a-half servings of fish per week and 53 percent lower in those eating fish less than once per month. African-Americans experienced the greatest risk reduction in the study, regardless of dietary fish intake or cardiovascular risk factor status.

“The reduction in total MI was of a comparable or greater magnitude than that for aspirin or statins in primary prevention,” Manson said. “This supports a possible cardioprotective role for n-3 fatty acids in a usual-risk setting, especially among those with cardiovascular risk factors or low fish intake and in African-Americans.”

Manson said further research is needed to determine the people who may be most likely to derive a net benefit from supplementation.

Conversely, while vitamin D3 supplementation didn’t significantly reduce cardiovascular events or incidence of total cancer, Manson said it appeared to have benefits for cancer mortality. Findings include:

  • Total cancer mortality dropped 17 percent, which became a significant 25 percent reduction in preplanned analyses after exclusion of early follow-up.
  • In subgroup analyses, normal-weight participants experienced 24 percent and 42 percent treatment-associated reductions in cancer incidence and mortality, respectively.
  • Overweight and obese participants didn’t benefit.
  • Vitamin D didn’t significantly reduce all-cause mortality. A two-year, post-intervention follow-up is ongoing to capture latency effects of the study agents and increase statistical power to assess endpoints.

“The findings indicate that high-dose vitamin D does not lower the risk of developing cancer or cardiovascular disease in generally healthy men and women, although it suggests that it may lower the risk of cancer death,” Manson said. “Although our study shows that a vitamin D dose of 2000 IU per day is well tolerated, with few if any side effects, the results do not strongly support the initiation of high-dose vitamin D for prevention of cancer or cardiovascular disease in healthy patients who already meet vitamin D requirements for bone health.”

Despite widespread reports of quality control in the dietary supplement industry, the vitamin D and fish oil supplements used in the VITAL study underwent extensive quality control testing to ensure that they contained the correct nutrients in the correct doses,
were free from contaminants, arrived fresh to participants and remained shelf-stable for at least 18 months thereafter, Manson said.