The results have been published from a massive clinical trail spanning five years investigating whether long-term omega-3 fish oil supplements improve mood or help prevent depression. No differences in any measure were detected between placebo and omega-3 groups.
Instead of looking at severe clinical depression or major depressive disorder (MDD), this clinical trial was more interested in generally investigating the long-term influence of omega-3 supplementation on mood. To generate any kind of meaningful data on such a heterogenous condition as depression a clinical trial needs a very large cohort. So the researchers recruited 18,353 participants aged over 50 with no clinical signs of depression at the time of recruitment.
"This study is a significant step,” explains lead investigator on the trial Olivia Okereke. “It requires many thousands of people to conduct this type of study of preventing depression in adults – something we call universal prevention – and the participants were taking randomized study pills for between five to seven years on average. So, it is rare to see a long-term randomized trial of this kind."
Half the cohort received a placebo, while the other half were given a marine-derived omega-3 supplement called Omacor (containing 465 mg of eicosapentaenoic acid (EPA) and 375 mg of docosahexaenoic acid (DHA)). All subjects were followed for at least five years. Depression was tracked using two measures, looking at clinically diagnosed episodes of depression and annual questionaries following self-reported long-term changes in mood.
The results were reasonably clear. Looking at mood scores over time the researchers detected no difference between placebo and omega-3 groups. The results unexpectedly showed a small but statistically significant increase in episodes of clinically relevant depressive symptoms in the omega-3 cohort compared to those taking the placebo.
Okereke is cautious to note this does not indicate omega-3 supplements were actually increasing a person’s risk of developing depression. She stresses the overall long-term mood scores remained stable, suggesting the effect of omega-3 supplements is more likely to be entirely neutral over an extended period of time.
No single piece of research will ever be definitive and the researchers do note a number of limitations in the trial to temper broad conclusions. Perhaps the biggest sticking point is the fact the trial utilized relatively small doses of a marine-derived combination of two omega-3 fatty acids: EPA and DHA.
Years of discordant omega-3 studies have led some researchers to hypothesize potential differences in outcomes between EPA and DHA supplementation. A meta-analysis published earlier this year looked at 38 randomized clinical trials on omega-3 and concluded EPA administered alone may be responsible for most of the beneficial health outcomes from these supplements. And that study even speculated DHA could blunt the benefits of EPA, meaning supplements that combine the two fatty acids may be ineffective.
So this big trial certainly may offer some pretty clear evidence that long-term supplementation with omega-3 combinations of EPA and DHA does not offer benefits to mood or prevention of depression, but that is all it can really say. A recent study from King’s College London, for example, found a mechanism to suggest very high doses of omega-3 fatty acids could reduce the neuroinflammation that has been associated with severe depression.
Senior author on the trial JoAnn Manson is clear in saying there are still plenty of reasons why a doctor may recommend someone take certain fish oil supplements, either for cardiovascular health or in cases of existing depression in high-risk patients. But these new findings do suggest casual supplementation of omega-3 fish oil may not do much to prevent general depression.
"... our findings indicate there is no reason for adults without depression in the general population to take fish oil supplements solely for the purpose of preventing depression or for maintaining a positive mood,” says Manson.
The new study was published in the journal JAMA.
Source: Massachusetts General Hospital