The researchers, who drew on data from the large-scale UK Biobank (UKBB) biomedical database, associated higher docosahexaenoic acid (DHA) blood levels with significant risk reductions for all-cause mortality and mortality due to cardiovascular disease (CVD), cancer and other causes.
“Besides showing that higher DHA levels were strongly and dose-dependently associated with lower risk for death (in all four categories), this paper also added these new data from the UKBB to our previous FORCE study on the same topic, strengthening the findings of the latter, making it crystal clear that people with higher omega-3 levels were ‘destined’ to live longer than those with lower levels,” said William Harris, PhD, a lead author on the study and president of the Fatty Acid Research Institute (FARI).
The research was supported in part by funding from the Richard I. Galamba Revocable Trust, the William H. Donner Foundation and grants from The National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH).
Building on FORCE
The study—which the research team called the largest ever to examine the relationship between DHA status and long-term mortality—analyzed data from 117,702 subjects with baseline plasma DHA levels and 12.7 years of follow-up between April 2007 and December 2021. Blood levels of EPA were not available in the database.
Associations with risk for mortality endpoints were analyzed categorically by quintile of DHA plasma levels, reporting that risk for death across all four outcomes was 21% lower in individuals with the highest DHA levels than in the lowest quintile. Of the participants with the highest levels, about half were taking an omega-3 supplement.
In a secondary analysis, the researchers merged the UKBB findings with an earlier pooled analysis of 17 studies in the Fatty Acids and Outcomes Research Consortium (FORCE), corroborating results in a cumulative sample population including 160,404 individuals and 24,342 deaths over an average 14-year follow-up.
“Here, comparing Q5 to Q1, risk for all-cause mortality was lower by 17%; for CVD death lower by 21%; for cancer death lower by 19%; and death from all other causes lower by 15%,” they reported.
The study suggested that the reduced mortality risk may be due to the cumulative effects of omega-3 on blood pressure, heart rate, vagal tone, telomeres, mTOR, skeletal muscle mass/strength, mitochondrial function, among other factors.
“If you’re less likely to die from CVD and cancer–the two major killers today–then your overall health must be better,” Dr. Harris added. “Any marker that 1) is linked with longer survival and 2) is modifiable should be optimized. People should strive to get their omega-3 levels up as early in life as possible and keep them there to obtain the most long-term benefit from these fatty acids.”
A word on higher omega-3 levels
In an editorial published in the same issue of the Mayo Clinic Proceedings, experts from University of Eastern Finland, the Global Organization for EPA and DHA Omega-3s (GOED) and the Ochsner Clinical School applauded the breadth of the undertaking. They highlighted the use of DHA blood level assessment as an accurate and objective marker.
“The recent Mayo Clinic Proceedings study provided additional evidence on the implementation of omega-3 fatty acids in a healthy diet in the prevention of CVD and other disease outcomes; thus, the inclusion of DHA (and combined EPA and DHA) in disease prevention strategies can definitely still be recommended,” the authors wrote.
The editorial also addressed the significant concerns surrounding the associations between higher doses of omega-3s and the risk of atrial fibrillation (AF).
“One of the greatest concerns among patients with AF is the increased risk of stroke,” they noted. “Although the study […] does not address the risk of stroke, the same group has recently found that higher omega-3 levels are associated with a lower risk of total and ischemic stroke.”
As to what might be next in this line of research, Dr. Harris said, “Any molecule, compound, nutrient that impacts total and cause-specific risk for death is doing something very deep in our cells, so learning what that might be should stimulate new research.”
Source: Mayo Clinic Proceedings
doi: 10.1016/j.mayocp.2023.11.026
“Circulating Docosahexaenoic Acid and Risk of All-Cause and Cause-Specific Mortality”
Authors: Evan L. O’Keefe et al.
