Effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system in individuals at ultra-high risk of psychosis

• Omega-3 PUFA with alpha-tocopherol have a weak (at a trend level) influence on the vitamin E and the glutathione AODS.
• Our findings in terms of the vitamin E AODS suggest direct support of the antioxidative defense at membrane level.
• This mechanism could underlay the clinical effectiveness of the verum condition.

BackgroundOxidative stress and impaired antioxidant defenses are reported in schizophrenia and are associated with disturbed neurodevelopment, brain structural alterations, glutamatergic imbalance, increased negative symptoms, and cognitive impairment. There is evidence that oxidative stress predates the onset of acute psychotic illness. Here, we investigate the effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system (AODS).MethodIn 64 help-seeking UHR-individuals (13–25 years of age), vitamin E levels and glutathione were investigated before and after 12 weeks of treatment with either 1.2 g/d omega-3 (PUFA-E) or saturated fatty acids (SFA-E), with each condition also containing 30.4 mg/d alpha-tocopherol to ensure absorption without additional oxidative risk.ResultsIn multivariate tests, the effects on the AODS (alpha-tocopherol, total glutathione) were not significantly different (p=0.13, p=0.11, respectively) between treatment conditions. According to univariate findings, only PUFA-E caused a significant alpha-tocopherol increase, while PUFA-E and SFA-E caused a significant gamma- and delta-tocopherol decrease. Total glutathione (GSHt) was decreased by PUFA-E supplementation.ConclusionEffects of the PUFA-E condition on the vitamin E and glutathione AODS could be mechanisms underlying its clinical effectiveness. In terms of the vitamin E protection system, PUFA-E seems to directly support the antioxidative defense at membrane level. The effect of PUFA-E on GSHt is not yet fully understood, but could reflect antioxidative effects, resulting in decreased demand for glutathione. It is still necessary to further clarify which type of PUFA/antioxidant combination, and in which dose, is effective at each stage of psychotic illness.