A study of depressed older women in a nursing home setting showed that after taking high-dose omega-3 fatty acids for eight weeks (2,500 mg once daily consisting of 1,670 mg EPA and 830 mg DHA), 40.9% had a remission of depression compared to 16.7% of those taking placebo. This study also found a statistically significant improvement in the self-assessed quality of life and that the fish oil treatment was well tolerated. In another study, the combination of EPA plus the prescription antidepressant fluoxetine (Prozac) was better than either EPA or fluoxetine alone for treating major depression in a short-term (8-week) study of 60 people. However, a study of people with congestive heart failure and depression failed to show any additional benefit from EPA (930 mg) and DHA (750 mg) daily when added to treatment with the prescription antidepressant sertraline (Zoloft).
The best evidence for omega-3's has been in cases of major and moderate depression, but not mild depression, and one group of researchers has concluded that the antidepressant benefit is strongly dependent upon the EPA content of the supplement. After pooling and reviewing studies using a total of 1,000 mg to 6,000 mg of EPA and DHA, those in which EPA was 60% or more of the total showed a highly significant improvement, whereas those that were less than 60% EPA did not. An analysis of eight clinical studies which investigated the effects of taking EPA and/or DHA from fish oil with various anti-depressants (including SSRI drugs such as fluoxetine and sertraline and tricyclic drugs such as amitriptyline) found that, overall, there appeared to be additive benefit, especially from EPA in doses of about 1,000 mg — 2,000 mg per day, concluding, "EPA-rich omega-3 fish oil may be recommended for the adjunctive treatment of major depressive disorder." Other researchers, however, believe that any benefit is, at best, small to negligible. Nevertheless, further analysis of blood samples from the study (above) found that elderly depression is characterized by very low levels of omega-3s, in particular EPA, in red blood cell membranes compared to those in healthy individuals and that EPA-rich supplementation restored EPA concentrations to normal values. Interestingly, an earlier study using 1,000 mg, 2,000 mg, or 4,000 mg of EPA found that only the group receiving 1,000 mg had a significantly better outcome than a group receiving placebo.
A small study among young adults (average age 20) with mild to moderate depression but not taking antidepressant medication, found that those who took two fish oil capsules (providing a total of 1000 mg EPA and 400 mg of DHA ) daily for 21 days had significantly improved self-reported depression scores compared to those who took a placebo. At the end of the study, 67% of those who took EPA and DHA were no longer clinically depressed, compared to 20% in the placebo group. It's worth noting that the amount of EPA given and ratio to DHA are consistent with those suggested by earlier research for treating depression.
A possible explanation for moderate improvements in depression among those who respond to fish oil, is that fish oil increases white matter (myelinated fibers that connect brain cells) in areas of the brain which can be compromised in depression. A small study of 16 acutely depressed adults with major depression found that among the 5 whose depression improved over the 6-week period of taking 4 grams of fish oil daily (OmegaLife-3, Unicity International, Inc., providing 1,600 mg of EPA and 800 mg DHA), 80% had increases in white matter in key brain regions, compared to only 45% of those whose depression did not improve.
An analysis of blood samples from 1,600 military personnel showed those who committed suicide had, prior to suicide, significantly lower blood levels of DHA than personnel who did not commit suicide. The population studied was predominantly male and the risk of suicide was found to be 62% greater among men with levels of serum DHA below 1.75% (% of total serum fatty acids) compared to those with higher levels. There was no such relationship with EPA levels. The researchers note that omega-3 fatty acid levels were generally low across the military personnel in the study, much lower than in the general population, and suggested that even greater risk reductions could be possible with higher serum levels of DHA.
A study of U.S. medical students showed, over 12 weeks, that those who received high-dose omega-3 fatty acids (2,496 mg once daily providing 2,085 mg EPA and 348 mg DHA), had a 20% reduction in anxiety symptoms compared to those receiving placebo treatment. Treated students also had a 14% decrease in a marker of inflammation (stimulated IL-6 production). The study intentionally used an extremely concentrated fish oil (supplied by OmegaBrite) high in EPA due to evidence that EPA has relatively stronger anti-inflammatory and antidepressant effects than DHA.
Fish oil may slightly blunt some responses to mental stress, according to a study of young men and women given a large amount of fish oil (9 grams daily providing 1,600 mg EPA and 1,100 mg DHA) for eight weeks. When the participants were asked perform math calculations as quickly as possible for 5 minutes (a mental stress test), the mean heart rate increased by 3 beats less per minute after fish oil therapy than when the test had been taken at the beginning of the study, before therapy. The increase in total nervous activity (measured by nerve activity in the leg) was also significantly less after fish oil therapy. A control group, given olive oil instead of fish oil, did not have these reductions in heart rate and nervous activity.
A year-long study in adolescents and young adults (ages 13 to 25) identified as at risk for developing psychosis or schizophrenia found those who took 700 mg EPA plus 480 DHA from fish oil daily for 3 months were much less likely to develop a psychotic disorder in the nine months following treatment compared to those who had taken a placebo: Among those who took the EPA and DHA, 4.9% developed psychosis compared to 27.5% of those in the placebo group. In a follow-up study approximately 7 years after the original treatment with EPA and DHA, only 10% had developed psychosis, compared to 40% among the placebo group. Those who took the fish oil had significantly higher measures of psychosocial functioning and required less medication than those who took the placebo. The researchers speculated that omega-3 supplementation may be especially effective during adolescence, when the brain is still undergoing significant development.
A study in Poland among first-episode schizophrenia patients (ages 16 to 35) found a small to moderate benefit from taking fish oil in addition to regular medication. During 26 weeks of taking 4 capsules daily of concentrated fish oil (providing a daily total of 1,320 mg of EPA and 880 mg of DHA) rather than a placebo containing olive oil, 69.4% experienced at least a 50% improvement in symptom severity while only 40% of those given the placebo experienced this level of improvement. The greatest improvements were in depressive symptoms. The researchers noted that studies of fish oil in people with chronic (long-term) schizophrenia have shown mixed results, suggesting that fish oil may be more effective at early stages of the disease.
Source : Swallownest Court Hospital, Doncaster and South Humber Healthcare NHS Trust, Sheffield, UK.
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