REVIEW OF: Pawełczyk T et al, Schizophr Res 2021;230:61–68

TYPE OF STUDY: Randomized, double-blind, placebo-controlled trial

Patients with schizophrenia are at greater risk for metabolic syndrome, whether from lifestyle, antipsychotic side effects, or the illness itself. Omega-3 fatty acids have metabolic benefits in the general population, and levels of these “healthy fats” tend to be low in people with schizophrenia. Earlier research found that omega-3 supplementation improved negative symptoms in schizophrenia, and this study examined their metabolic effects in schizophrenia.

This was a randomized, double-blind, placebo-controlled trial of 71 adults with stable schizophrenia on antipsychotic medication. They were treated with either omega-3 fatty acids or a fish-flavored placebo for six months. Both the placebo and the active intervention contained 0.2% alpha-tocopherol (vitamin E) to prevent oxidation of fatty acids. The omega-3 intervention consisted of a 3:1 ratio of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids with a total daily dosage of 2,200 mg/day. Body composition and metabolic parameters associated with metabolic syndrome were assessed at baseline, then at eight and 26 weeks after study initiation. Both groups began the trial with similar metabolic parameters.

After eight weeks, the placebo group had a nonsignificant increase in metabolic syndrome (p = 0.083), and this increase was even greater at 26 weeks (p = 0.007). By contrast, the rate of metabolic syndrome decreased in the treatment group, although the effect was just marginally significant (p = 0.0408). Notably, the omega-3 group had significant reductions in fasting blood glucose (p = 0.045), total cholesterol (p = 0.037), and blood glucose levels (p = 0.034), but improvements in other metabolic parameters were not significant. Patients on olanzapine experienced the greatest metabolic benefits with omega-3s.

The investigators also found an association between triglyceride level and the psychopathology subscale of the Positive and Negative Syndrome Scale, suggesting that lower triglycerides are associated with improved symptoms of psychopathology (p = 0.0008).

Omega-3s were well tolerated in this study. They have a mild anticoagulant effect, but patients on anticoagulants may still be able to take omega-3s with approval from their prescribing physician. Omega-3 supplementation may deplete vitamin E, which notably was supplemented in this study.

The 3:1 EPA:DHA ratio used in this study can be difficult to find but is worth the search, as this is also the ratio that worked in studies of depression. We found three products with a similar ratio that were tested by independent labs: Viva Naturals (on Amazon), Member’s Mark (at Sam’s Club), and Kirkland Signature (at Costco) at a cost of 15–25 cents/day.

TCPR’s Take
This study is small and preliminary, but omega-3s have established benefits for metabolic health in various conditions and are worth considering in schizophrenia.