In the VITAL study, investigators found that supplementation with omega-3s and vitamin D did not meet the primary endpoint of significantly reducing major cardiovascular events or total invasive cancer.
JoAnn Manson, MD, MPH
Higher intake of omega-3 fatty acids and supplementation with vitamin D have been associated with reduced risks of cardiovascular disease and cancer in observational studies, but the causational effects have been widely unknown.
However, new data from one of the largest randomized, placebo-controlled trials indicate that neither omega-3s nor vitamin D significantly reduced major cardiovascular disease events or total invasive cancers.
In the VITamin D and OmegA-3 TriaL (VITAL) study, a team of investigators led by JoAnn Manson, MD, DrPH, FAHA, set out to determine whether vitamin D3 and/or omega-3 fatty acids reduce the risk of a major cardiovascular event and total invasive cancer in a population of healthy adults.
The study enrolled 25,871 adults (men aged >50, women aged >55) and featured a 2-by-2 factorial design of to 1 of 4 supplement groups: vitamin D3 (cholecalciferol; 2000 IU daily) and marine omega-3 fatty acids1 g daily, ratio of EPA to DHA = 1.3:1); vitamin D and omega-3 placebo; vitamin D placebo and omega-3 fatty acids; or both placebos.
The primary endpoints of the study were occurrence of any major cardiovascular events including myocardial infarction, stroke, or death from cardiovascular causes and invasive cancer of any type.
During a median follow-up of 5.3 years, a major cardiovascular event occurred in 386 of the 12,933 participants in the omega-3 group and in 419 of the 12,938 patients in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P=0.24). Additionally, Invasive cancer was diagnosed in 820 participants in the omega-3 group and in 797 in the placebo group (hazard ratio, 1.03; 95% CI, 0.93 to 1.13; P=0.56).
The authors indicate that “In the analyses of key secondary endpoints, the hazard ratios were as follows: for the expanded composite end point of cardiovascular events, 0.93 (95% CI, 0.82 to 1.04); for total myocardial infarction, 0.72 (95% CI, 0.59 to 0.90); for total stroke, 1.04 (95% CI, 0.83 to 1.31); for death from cardiovascular causes, 0.96 (95% CI, 0.76 to 1.21); and for death from cancer (341 deaths from cancer), 0.97 (95% CI, 0.79 to 1.20). In the analysis of death from any cause (978 deaths overall), the hazard ratio was 1.02 (95% CI, 0.90 to 1.15). No excess risks of bleeding or other serious adverse events were observed.”
In the median follow up of 5.3 years, cancer was diagnosed in 793 of 12,927 participants in the vitamin D group and 824 of 12,944 participants in the placebo group (hazard ratio, 0.96; 95% confidence interval [CI], 0.88 to 1.06; P=0.47). Additionally, a major cardiovascular event occurred in 396 in the vitamin D group and 409 in the placebo group (hazard ratio, 0.97; 95% CI, 0.85 to 1.12; P=0.69).
The authors indicate that “in the analyses of secondary endpoints, the hazard ratios were as follows: for death from cancer (341 deaths), 0.83 (95% CI, 0.67 to 1.02); for breast cancer, 1.02 (95% CI, 0.79 to 1.31); for prostate cancer, 0.88 (95% CI, 0.72 to 1.07); for colorectal cancer, 1.09 (95% CI, 0.73 to 1.62); for the expanded composite endpoint of major cardiovascular events plus coronary revascularization, 0.96 (95% CI, 0.86 to 1.08); for myocardial infarction, 0.96 (95% CI, 0.78 to 1.19); for stroke, 0.95 (95% CI, 0.76 to 1.20); and for death from cardiovascular causes, 1.11 (95% CI, 0.88 to 1.40). In the analysis of death from any cause (978 deaths), the hazard ratio was 0.99 (95% CI, 0.87 to 1.12). No excess risks of hypercalcemia or other adverse events were identified.”
Other observations from the study include that there were no significant side effects observed in either agent nor were gastrointestinal symptoms increased. There was also no increased risk of hypercalcemia in the vitamin D participants, nor an increased risk of bleeding in the omega-3 patients.
Omega-3s reduced total myocardial infarction by 28%, with the greatest reductions in low dietary fish intake and in African Americans while also reducing percutaneous coronary intervention, fatal myocardial infarction, total congenital heart disease. Additionally, vitamin D reduced total cancer mortality in analyses with the exception of early follow up.
But in the end, supplementation with omega-3s and vitamin D did not meet the primary endpoint of significantly reducing major cardiovascular events or total invasive cancer.
The results of the VITAL study were presented in a late breaker session at the American Heart Association Scientific Sessions on November 10, 2018, in Chicago, Illinois. Additionally, articles about the vitamin D and omega-3 supplementations were published in the New England Journal of Medicine.