Omega-3 Supplements No Mood Booster in Older Age

Among older adults, omega-3 supplements yielded no benefit for mental health outcomes, the VITAL-DEP trial found.

Among more than 18,000 adults ages 50 and older, marine omega-3 fatty acids supplements -- 1 g daily, comprised of 465 mg of eicosapentaenoic acid and 375 mg of docosahexaenoic acid -- didn't reduce the risk of depressive symptoms, Olivia Okereke, MD, of Massachusetts General Hospital in Boston, and colleagues reported in JAMA.

In fact, these adults who were free of clinically-relevant depressive symptoms at baseline saw a small but statistically significantly higher risk for depressive symptoms while taking omega-3s versus placebo in an adjusted model (651 vs 583 events; HR 1.13, 95% CI 1.01-1.26, P=0.03).

This co-primary outcome included the total of both incident and recurrent cases of clinically-relevant depressive symptoms.

However, when looking instead at longitudinal mood scores -- the trial's other coprimary endpoint -- there were no significant difference between the omega-3 group and the placebo group. This was marked by only a 0.03-point (95% CI -0.01 to 0.07, P=0.19) mean difference between treatment groups in the change in the eight-item Patient Health Questionnaire depression scale. Average mood score between the groups was also never significantly different at any point during the trial.

"In this study, we gave equal attention to the risk of developing a clinical depression at any point and to overall mood scores for the duration of follow-up," Okereke told MedPage Today in an email. "While a small increase in risk of a depression was inside the statistical margin of significance, there was no harmful or beneficial effect of omega-3 on the overall course of mood during the roughly 5 to 7 years of follow-up."

But despite these findings, this doesn't mean that there aren't other clinical benefits to omega-3s, taken under a healthcare provider's guidance, she argued.

"These supplements increasingly have been found to have benefits for cardiac disease prevention and treatment of inflammatory conditions, in addition to being used for management of existing depressive disorders in some high-risk patients," she said.

In prevention of cardiovascular disease, results have been mixed in randomized trials: Prescription omega-3 icosapent ethyl (Vascepa, containing only eicosapentaenoic acid without docosahexaenoic acid) reduced major adverse cardiovascular events on top of a statin in primary or secondary cardiovascular disease prevention, but a mix of the two omega-3 fatty acids in prescription omega-3 carboxylic acids (Epanova) held no such benefits among people with high triglycerides and actually caused atrial fibrillation. Lower-dose, mixed omega-3 supplements also flopped in a recent cardiovascular prevention trial in diabetes.

Okereke's group originally wished to tackle omega-3s in mental health because many experts have for years recommended the supplements for reducing the recurrence of depression in some high-risk patients.

"However, there are no guidelines related to the use of omega-3 supplements for preventing depression in the general population," Okereke said. And, "the results of our study indicate there is no reason for people in the general population to take omega-3 fish oil supplements solely for the purpose of preventing depression or for maintaining a positive mood."

Her group referenced some prior meta-analyses and large observational studies that yielded opposing findings, sometimes linking omega-3 fatty acids supplements and dietary fish intake with significant relative risk reductions in depressive symptoms. However, the somewhat lower dose of omega-3 used in her study -- 1 g per day -- was lower than what some previous trials found to be effective. More specifically, prior data suggested a dose of 1.5 g per day or higher might be the magic threshold for reducing depressive symptoms.

Dubbed the Vitamin D and Omega-3 Trial–Depression Endpoint Prevention (VITAL-DEP) study, this analysis was an ancillary study to the VITAL parent trial, which honed in on the effects of vitamin D3 and marine omega-3 fatty acids on prevention of incident cancer and cardiovascular disease. With a median follow-up of about 5 years, this cohort included a total of 9,171 adults who were randomized to received omega-3 pills and 9,182 randomized to placebo.

Among the entire cohort, the most common adverse events reported were major cardiovascular events (2.7% with supplements vs 2.9% for placebo), all-cause mortality (3.3% vs 3.1%), gastrointestinal bleeding (2.6% vs 2.7%), easy bruising (24.8% vs 25.1%), and stomach upset or pain (35.2% vs 35.1%).

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