Omega-3 VITAL study results “better than expected” despite negative primary findings, GOED says

Photo © Shutterstock.com/Africa Studio

The long-awaited, large-scale VITAL trial on omega-3 and vitamin D supplementation for cardiovascular health is now published in The New England Journal of Medicine¹. Researchers from VITAL (the VITamin and OmegA-3 TriaL) also presented the results during November’s 2018 American Heart Association Scientific Sessions held November 10-12 in Chicago. While researchers did not find a lower incidence of major cardiovascular events or cancer due to supplementation (the study’s primary endpoint), the study did reveal some positive, statistically significant benefits, says omega-3 association the Global Organization for EPA and DHA Omega-3 (GOED; Salt Lake City, UT).

A total 25,871 subjects were randomized at the start of the placebo-controlled trial (a two-by-two factorial design), including 5,106 African American subjects. During the study, 15,535 subjects ultimately had blood samples that could be analyzed in the study. Subjects were age 50+. The mean age of participants was 67.1-years-old. Subjects who underwent supplementation were given vitamin D (2000 IU/day; from Pharmavite) and a fish oil supplement (1 g/day, including 460 mg EPA and 380 mg DHA omega-3 fatty acids) in the form of the omega-3 drug Omacor from Pronova/BASF. This omega-3 dose is recommended by the American Heart Association for cardioprotection, the researchers said.

The primary endpoint was the prevention of cardiovascular events and cancer in men 50 years of age or older and in women 55 years of age or older in the U.S. The primary cardiovascular event endpoint included, collectively, myocardial infarction, stroke, or death from CVD. The cancer endpoint included “invasive cancer of any type.” The researchers also looked at secondary endpoints, including how those individual cardiovascular endpoints (myocardial infarction, stroke, death, etc.) fared individually, as well as site-specific cancers (e.g., colorectal, breast, and prostate cancer).

Subjects were followed for 5.3 years. Blood samples were taken at baseline (from 16,956 participants), of whom 15,535 had blood samples that could ultimately be analyzed. During follow-up among the groups, researchers found no significant difference in overall major cardiovascular events; they found 805 major cardiovascular events total (386 in the omega-3 group and 419 in the placebo group). The researchers also found no significant difference in the risk of cancer between the omega-3 and the placebo groups.

“Supplementation with omega-3 fatty acids did not result in lower incidence of major cardiovascular events or cancer than placebo,” the researchers concluded.

However, in a news release, GOED pointed to some statistically significant results in the study showing that omega-3 supplemention did provide benefits. These statistically significant results include:

• Total myocardial infarction: a 28% risk reduction in the omega-3 group compared to placebo (145 events in the omega-3 group versus 200 events in the placebo group)
• Total coronary heart disease: a 17% risk reduction in the omega-3 group compared to placebo (308 events in the omega-3 group versus 370 events in the placebo group)
• Fatal myocardial infarction: a 50% risk reduction in the omega-3 group versus placebo (13 events in the omega-3 group versus 26 in the placebo group)

In a news release, GOED added: “The greatest reductions were demonstrated in those with low dietary fish intake and in African Americans.” It added that more “scrutiny of the data is required to better understand these findings.”

The association said: “Overall, GOED’s view is that the VITAL results on omega-3s were more positive than we expected. Additionally, the presentation of VITAL by the study authors [at the American Heart Association event] was also positive in tone.”

While this study includes positive takeaways, GOED warned that media coverage so far has often been negative, highlighting the fact that the study’s primary endpoint of reducing overall major CVD events and cancer was not met.

Trade association the Council for Responsible Nutrition (CRN: Washington, DC) also highlighted VITAL's positive findings. In a press statement, Duffy MacKay, ND, CRN's vice president, scientific and regulatory affairs, stated:

"While early news coverage has focused on topline results, CRN is encouraged by several very positive findings showing benefits of omega-3 and vitamin D supplementation in additional analyses:

• Almost a 30% reduction in heart attacks in the fish oil group compared with placebo.
• A 40% reduction of heart attacks in fish oil groups who had less than 1.5 servings of fish per week, with even more dramatic impacts among African-Americans.
• Reduction in the rate of cancer deaths two or more years later in people who took vitamin D.

The study reaffirms the safety of both vitamin D and omega-3 fatty acids, and does not change decades of research showing how critical vitamin D and omega-3 supplementation are for overall health:

• Vitamin D, a nutrient of public health concern, plays an important role in bone health, immune function, and maintaining cardiovascular health in adults.
• Omega-3 is essential to cardiovascular health, prenatal health, and cognitive health.

These findings are promising, and CRN looks forward to ancillary studies that are expected to be published from this impressive data collected on over 25,000 participants."

More Results from REDUCE-IT Trial

At the American Heart Association event, researchers from another large-scale omega-3 drug trial, the REDUCE-IT trial, discussed their study on Amarin’s Vascepa drug. The study showed that the drug achieved a statistically significant risk reduction of 25% in the first occurrence of major cardiovascular events. Read more here. At the American Heart Association event, the researchers shared further details from the REDUCE-IT study, finding numerous benefits with the omega-3 intervention. GOED shared these findings:

• Key secondary composite of cardiovascular death, myocardial infarction, or stroke: 26% risk reduction
• Cardiovascular death or nonfatal myocardial infarction: 25% risk reduction
• Fatal or nonfatal myocardial Infarction: 31% risk reduction
• Urgent or emergent revascularization: 35% risk reduction
• Cardiovascular death: 20% risk reduction
• Hospitalization or unstable angina: 32% risk reduction
• Fatal or nonfatal stroke: 28% risk reduction
• Total mortality, nonfatal myocardial infarction, or nonfatal stroke: 23% risk reduction

Story updated 11/14/18 11:00 AM PDT to include comments from Council for Responsible Nutrition

References:

1. Manson JE et al. “Marine n-3 fatty acids and prevention of cardiovascular disease and cancer.” The New England Journal of Medicine. Published online November 10, 2018.