Does Omega 3 Decrease Risk of Death But Not Disease?

The New England Journal of Medicine, a peer-reviewed scientific journal, had some interesting omega-3 studies this month. One was the VITAL study, which investigated a 1 g mixed omega-3 supplement and 2000 IU vitamin D supplement in people from the general United States population. The other was the REDUCE-IT study, which investigated a 4 g EPA omega-3 supplement in people around the world with high blood triglyceride levels and receiving statins. Both were rather large studies that lasted about 5 years. And their results were quite different.

The VITAL study was larger and more long term than most studies. It was funded by the National Institutes of Health. It included 25,781 participants in the United States including men over age 50 and women over age 55 for 5.3 years. They had no history of cancer (except non-melanoma skin cancer) or cardiovascular disease. Participants received an omega-3 supplement or placebo, or vitamin D or placebo. The reports were split into two publications, one focusing on the effect of the omega-3 supplement, and one focusing on the effect of the vitamin D supplement. The omega-3 supplement included 840 mg of omega-3 fatty acids (460 mg of EPA and 380 mg of DHA). The vitamin D supplement was 2,000 IU in the form of cholecalciferol.

Omega 3 may not decrease cardiac events but may decrease risk of dying by a heart attack. Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. While, overall, the study concluded that there was no general benefit from omega-3 supplementation, there were some interesting points. Among participants who supplemented while eating less than 1.5 servings of fish a week, there was a reduction in major cardiovascular events. The researchers pointed out that dietary fish intake is rarely considered as a modifier in omega-3 supplementation trials. It is usually controlled or ignored. And these results suggest that levels of fish intake may need more consideration. There was also a greater benefit of omega-3 supplementation to black participants. For all participants, the risk of myocardial infarction and death by myocardial infarction (heart attack) was decreased with supplementation. But there was not a decrease in stroke events or the sum of all cardiovascular events (stroke, infarction, procedures to unclog arteries, and death from cardiovascular causes). And there was no reduction in cancer risk while taking the omega-3 supplements.

Vitamin D may not decrease risk of cancer but may decrease risk of dying from cancer. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. There were no significant differences in the risk of cardiovascular events or invasive cancer with vitamin D supplementation. However, when looking only at the data after the first two years of supplementation (the longer term effect), the rate of death from cancer was significantly lower with vitamin D than with placebo. The researchers acknowledged that unmeasured factors such as outdoor physical activity or general nutritional status confounded such studies. Or perhaps the participants generally had blood levels of vitamin D that were high enough to provide protection from heart disease and cancer, so there was little/no benefit to the supplement in this population.

New England Journal of Medicine included editorials referring to the two parts of the VITAL study. The editorials focused on the lack of changes to cardiovascular events and the occurrence of cancer. However, no genetic data was discussed in these reports. And, for a person who is at increased risk for cancer based on genetic makeup, it seems that the decreased risk of death from cancer would be more relevant. For the person with genetic risk factors for stroke, non-related to heart disease, the supplement may have other effects on their risk for stroke but we cannot tell from this study. If the NIH did not have the funding to collect or analyze genetic material for all 25,781 participants, they could have collected the data from a subset or included questions about family medical history as a potential indicator of genetic risk. Even though the REDUCE-IT study does not include genetic data directly, the participants have several factors in common: their health measurements qualify them for statin use, and they still have high triglyceride levels while on statins. We have the technology to build a framework for personalized medicine, yet the NIH-funded VITAL study still focused on recommendations for the population as a homogenous unit.

Omega 3 may reduce the risk of cardiac events and cardiovascular death. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. For the REDUCE-IT study, researchers recruited 8,179 participants from around the world who were receiving statin therapy and who still had a fasting triglyceride level of 135 to 499 mg/dL (less than 100 mg/dL is considered optimal) and a low-density lipoprotein cholesterol level of 41 to 100 mg/dL. The participants received a placebo or 4 g EPA supplement (2 g twice daily) for 4.9 years. Triglycerides and non-HDL cholesterol decreased significantly in the supplement group. The risk of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, and unstable angina was 25% lower in the supplement group. The risk reduction of major adverse cardiovascular events occurred even if the triglyceride level remained about 150 mg/dL after treatment. The supplemented group did not see an increase in LDL levels, as often happens with DHA supplements. The researchers acknowledged that these results varied from many omega-3 supplement studies and pointed out that it may be due to the greater amount of EPA or the ratio of EPA to DHA.