Limited evidence supports a hypothesis suggesting that schizophrenic symptoms may be the result of altered neuronal membrane structure and metabolism. The structure and metabolism is dependent on blood plasma levels of certain essential fatty acids and their metabolites.
To review the effects of polyunsaturated fatty acids for people with schizophrenia.
We have updated the initial searches of 1998 and 2002 (Cochrane Schizophrenia Group's Register, July 2005), and where necessary, we contacted authors and relevant pharmaceutical companies.
We included all randomised clinical trials of polyunsaturated fatty acid treatment for schizophrenia.
Working independently, we selected studies for quality assessment and extracted relevant data. We analysed on an intention-to-treat basis. Where possible and appropriate we calculated the Relative Risk (RR) and their 95% confidence intervals (CI) and estimated the number needed to treat (NNT). For continuous data we calculated weighted mean differences (WMD) and their 95% confidence intervals. We also inspected the data for heterogeneity.
When any dose omega-3 (E-EPA or EPA) is compared with placebo, small short trials suggest that the need for neuroleptics appears to be reduced for people allocated omega-3 supplementation (n=30, 1 RCT, RR 0.73 CI 0.54 to 1.00) and mental state may improve (n=30, 1 RCT, RR not gaining 25% change in PANSS scores 0.54 CI 0.30 to 0.96, NNT3 CI 2-29). There are no differences in the number of people leaving the study early (n=271, 4 RCTs, RR 0.91 CI 0.36 to 2.33). There are few data on the comparison of any dose omega-6 (GLA) with placebo. For movement disorder outcomes, the only small study we found does not show any difference for average short-term endpoint AIMS score (n=16, 1 RCT, MD 1.30 CI -1.96 to 4.56). When any dose omega 3 (E-EPA or EPA) is compared with any dose omega-3 (DHA) there is no clear difference for mental state outcome of not gaining 25% change in PANSS scores (n=31, 1 RCT, RR 0.66 CI 0.39 to 1.11). When different doses of omega-3 (E-EPA) are compared with placebo there are no differences in measures of global and mental state between the studies. For the outcome of 'experiencing at least one adverse effect' no differences between groups are found for any dose (1g/day E-EPA vs placebo n=63 1 RCT, RR 0.97 CI 0.60 to 1.56; 2g/day E-EPA vs placebo n=63 1 RCT, RR 0.67 CI 0.37 to 1.20; 4g/day E-EPA vs placebo n=58, 1 RCT, RR 1.15 CI 0.72 to 1.82).
Two updates of this review have resulted in more included studies but relatively little useful additional data. The results remain inconclusive. The new trials all compare the omega-3 polyunsaturated fatty acids, in particular eicosapentaenoic acid and its ester, ethyl-eicosapentaenoic acid. The use of omega-3 polyunsaturated fatty acids for schizophrenia still remains experimental and this review highlights the need for large well designed, conducted and reported studies.
[Show abstract][Hide abstract] ABSTRACT: This study aimed to investigate polyunsaturated (PUFA) and trans isomeric fatty acid status in schizophrenia patients. Fatty acid composition of plasma phospholipids (PL) and triacylglycerols (TG) was analyzed by gas chromatography in 29 schizophrenia patients and 15 healthy controls. We found no difference in PL n-3 fatty acid status between the two groups, while the values of 22:5n-6 were significantly higher in patients with schizophrenia than in controls. In TG, values of docosatrienoic acid (20:3n-3) and docosapentaenoic acid (20:5n-3) were significantly higher in schizophrenia patients than in controls. We found no difference in the trans fatty acid status between patients and controls. In smoking schizophrenia patients significant negative correlations were detected between Wechsler adult full-scale intelligence quotients and values of total trans fatty acids in PL lipids, whereas no such correlation was seen either in non-smoking schizophrenia patients, or in healthy controls. While data obtained in the present study fail to furnish evidence for n-3 PUFA supplementation to the diet of patients with schizophrenia, they indicate that in smoking schizophrenia patients high dietary exposure to trans fatty acids is associated with lower intelligence quotients.
"In humans, a number of adverse health and behavioral outcomes are associated with low intake of n-3 PUFAs including cardiovascular disease (Mori and Woodman, 2006), inflammatory disease (De Caterina and Basta, 2001) and many neurodevelopmental and psychiatric conditions such as attention deficit hyperactivity disorder (ADHD), dyslexia, depression, schizophrenia and dementia (Bourre, 2005). N-3 PUFA intervention trials have, however, provided inconsistent results as regards symptom reduction or behavioral measures (reviewed in Appleton et al., 2008; Fotuhi et al., 2009; Freeman et al., 2006; Joy et al., 2006; Lim et al., 2006; Turnbull et al., 2008). More recently, the issue of cognitive and mood enhancement via n-3 PUFA supplementation has been explored in healthy volunteers. "
[Show abstract][Hide abstract] ABSTRACT: A number of recent studies have assessed the impact of dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) on behavioral outcomes; however, very little attention has been given to their impact upon brain function in physiological terms. Sixty-five healthy adults aged 18-29yrs took part in this double-blind, placebo-controlled study assessing the effects of 12 weeks daily dietary supplementation with docosahexaenoic acid-rich fish oil (1g, 2g) or placebo (olive oil). Relative changes in the concentration of oxyhemoglobin and deoxyhemoglobin were assessed in the prefrontal cortex using near-infrared spectroscopy during performance of nine computerized cognitive tasks. Supplementation with both doses of fish oil, in comparison with placebo, resulted in significantly increased concentrations of oxyhemoglobin and total levels of hemoglobin, indicative of increased cerebral blood flow, during the cognitive tasks. Changes in hemodynamic response to tasks were not accompanied by consistent changes in cognitive performance.
"The findings to date from studies of O3FA treatment in schizophrenia have generally been encouraging . Studies with positive results have utilized EPA rather than DHA, which has not yielded positive results . "
[Show abstract][Hide abstract] ABSTRACT: Patients with schizophrenia have significant cognitive deficits, generally resistant to conventional treatment. This preliminary study examined the effects of ethyl-eicosapentanoate (EPA) on an executive function in early course patients.
Patients with schizophrenia were given, after an informed consent, 2 g of an EPA daily for 24 weeks, in an open-label study. The Wisconsin Card Sort Test (WCST) was administered at baseline, weeks 4, 12 and 24.
The 27 patients, with a mean duration of illness of 4.2 years, were all receiving atypical antipsychotics; treatment remained unchanged for the study. Perseverative errors - the key measure derived from WCST - were significantly reduced from the baseline mean of 28.2 to 18.4 errors at week 24. Positive symptoms also improved significantly. There were no correlations between EPA levels and any clinical or other neuropsychological measures.
These findings suggest that an EPA has procognitive effects for patients with schizophrenia, but controlled trials are required.
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