When fish oils are given to the general public, there was not a reduction of major cardiovascular events. Among subgroups, differences were noted.
Information surrounding fish oils has been conflicting. A recent study, the VITamin D and OmegA-3 TriaL, or VITAL, took another look at omega-3s and cardiovascular disease.
VITAL researchers note that it is the largest and longest randomized trial of daily high-dose vitamin D (vitamin D3 [cholecalciferol], 2000 IU) and omega-3 fatty acid supplementation (Omacor® fish oil, 1 gram) for the prevention of cancer and cardiovascular disease in generally healthy men and women without these conditions at baseline. The trial included 25,871 adults—12,786 men aged 50 years and older and 13,085 women aged 55 and older—who were followed for an average of 5.3 years. This study is really several studies in one since 3 interventions were conducted and looked at 3 types of outcomes.
Looking at the fish oil-only intervention, 1 gram of prescription grade fish oil, equal parts of EPA/DHA were given once a day to 12,933 people over the age of 50. They were followed for more than 5 years (5.3 years to be exact). The goal of this portion of the study was to answer the question: do fish oils work in the general public to reduce the onset of heart disease? That means the primary outcome was primary prevention of major cardiovascular events, which was a composite of myocardial infarction, stroke, or death from cardiovascular causes were recorded. Secondary endpoints included coronary revascularization procedures and other incidental findings that showed people were developing heart disease.
After more than 5 years, the study results were published in The New England Journal of Medicine. A total of 12,933 participants received active omega-3 vs 12,938 who received placebo. Of these, 386 of the former and 419 of the latter experienced a major CVD event, which was not significantly different (HR, 0.92; 95% CI, 0.80-1.06) To summarize these results: fish oils did not change the primary outcomes compared to the placebos, statistically speaking.
Among subgroups, however, there was a 40% reduction in risk for total MI among the omega-3 group members who consumed fewer than 4.5-6 ounces of fish per week (P=.048) and a 19% reduction in major CVD events. It would make sense that if a diet is lacking in a specific nutrient, providing that nutrient in a pill form would improve health. As time goes by, we are finding that healthy oils are certainly necessary for good health. Perhaps in the setting of a fish free diet, low fish diet, or a diet lacking in healthy oils, fish oils do make a difference.
In addition, the HR for total MI was 0.23 for people with African ancestry taking omega-3 compared with placebo (number of events, 9 vs 39, respectively; P=.001). That is a 77% reduction in MI risk. What was the cause of the good results in the African lineage population? More studies are needed to reveal what is really going on. But it was noted that the benefits from fish oils were irrelevant of how much fish these participants ate during the week, and the baseline blood levels of EPA and DHA in this subgroup was similar to the others.
Thinking about the mechanism of action of fish oils with respect to cardiovascular health makes me wonder how it worked in this subpopulation. According to the authors of this study, the MOA for fish oil is antithrombotic, hypotriglyceridemic, blood-pressure—lowering, and antiinflammatory effects; impeded growth of atherosclerotic plaques; slowing of heart rate; reduced susceptibility to cardiac arrhythmias; and the promotion of nitric oxide–induced endothelial relaxation whereby n−3 fatty acids may reduce risk. Epigenetics and pharmacogenomics are new sciences about genetic variations. The medical information seems to be getting more and more detailed.
To make sense of the fish oil results between studies of the past and understand why we are getting conflicting results we must pay special attention to confounding factors such as:
It is only through examining all these differences that will we be able to find out who exactly is benefiting from fish oil supplementation. We already know that everyone benefits for a healthy diet of whole foods, and healthy oils, but when do fish oil pills improve health? The answers are slowly coming in.
Manson J, Cook NR, Lee IM, et al. Marine n−3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J. Med. 2018; DOI: 10.1056/NEJMoa1811403