Five out of six randomized controlled trials with eicosapentaenoic acid (fish) have shown positive effects in schizophrenia, and 4 of 6 were favorable in depression and bipolar disorders (J Nutr Biochem 2006 Apr 28). 

A high dietary intake for fish, especially fatty ocean fish like salmon, sardines, mackerel, or tuna has been linked to a significant decrease in deaths due to heart disease and to a lower rate of depression.  The American Heart Association now recommends that everyone eat fish at least once a week.  The research would suggest that one pound a week is more healthy level.  Since many people don't like fish or can't afford it, I recommend taking 2-3 fish oil capsules per day for everyone unless you are a big fish eater.  Fish sandwiches and fish sticks are actually unhealthy and should not be eaten.  Oily fish, such as tuna, salmon, mackerel, sardines, and herring are best.

Whether fish or fish oil helps schizophrenic conditions is uncertain.  The evidence is now fairly good that it helps decrease depression, but the evidence is less clear on schizophrenia.  Still, I strongly recommend fish (one pound per week) or fish oil (2-4 capsule per day) for general health and it might help schizophrenia in some patients.  EPA and DHA are the two omega-3 fatty acids in fish oil.  While the research suggests that EPA might have more benefit for schizophrenia than DHA, standard fish oil capsules contain both and there is certainly no harm to DHA.  The typical 1000 mg fish oil capsule contains 180 mg of EPA and 120 mg of DHA.  The schizophrenia studies suggest that a higher amount, e.g. 6 capsules twice a day, might be better, although perhaps a smaller number when taken all year long might work just as well.

Higher Fish Consumption by Nation Lowers Bipolar Disease, But Not Schizophrenia: A new study has shown that the more seafood consumed in a country, the lower the rates of bipolar disease. Below 50 pounds consumption of seafood per year seemed to be a threshold level below which risk of bipolar II and bipolar spectrum disorder increased.  Authors attribute the benefit to higher omega-3 fatty acid consumption. Cross-national comparisons of seafood consumption and rates of bipolar disorders. Noaghiul S, Hibbeln JR. Am J Psychiatry. 2003 Dec;160(12):2222-7

Lower Omega-3 in Schizophrenia May Be Lower Intake: Smoking schizophrenic patients had lower baseline omega-3 and lower intake in 12 week study of 3 g/day. NIMH. Smoking, gender, and dietary influences on erythrocyte essential fatty acid composition among patients with schizophrenia or schizoaffective disorder. Hibbeln JR, Makino KK, Martin CE, Dickerson F, Boronow J, Fenton WS. Biol Psychiatry 2003 Mar 1;53(5):431-41

Double-Blind Study says 2 g/d EPA Omega-3 Ideal: A 12 week PC DB study of persistent schizophrenic patients on atypicals comparing 0, 1, 2, and 4 g/d of ethyl-EPA concluded 2 g/d had maximum therapeutic effect. Clozapine patients had substantial benefit from the EPA. Peet M, Horrobin DF. A dose-ranging exploratory study of the effects of ethyl-EPA in patients with persistent schizophrenic symptoms. J Psychiatr Res 2002;36:7-18.

Fish oil + Vitamin C + Vitamin E Schizophrenic Patients Improved: In a poor quality trial of 34 stable chronic schizophrenic patients on traditional or atypical anti-psychotics, the authors gave 4-months EPA:DHA (360:240) with vitamin E 400 IU and vitamin C 500 mg bid. The average patient had a 25% reduction in psychotic scores which continued after supplement was discontinued. There is evidence of increased oxidative stress in schizophrenia and antioxidants protect membrane EPUFAs like DHA. Arvindakshan M, Ghate M, Ranjekar PK, et al. Supplementation with a combination of omega-3 fatty acids and antioxidants (vitamins E and C) improves the outcome of schizophrenia. Schizophr Res 2002.

Schizophrenic Patients Less Likely to have been Breast Fed so Less EPA-DHA: Brit J Psychiatry study lack of breast milk increases the risk of schizophrenia. More schizoid and schizotypal as well as lower IQ. Robin McCreadie, Scotland

EPA Helps in DB: Trial DB of an EFA supplement with schizophrenics with movement disorders. No benefit for dyskinesia but high significant improvements in total psychopathology scores and schizophrenia subscale and memory improvement., Vaddadi, West Sussex, Psychiatry Res 3/89 27:313-23

EPA no Benefit in Larger DB: Am J Psychiatry 2001 Dec;158(12):2071-4. 87 patients in a DB PC 16-week study of 3 g./day. NIMH

EPA Helps Schizophrenia in DB: 25% improvement in 3-month trial vs. DHA or placebo. Malcolm Peet, Sheffield, Eng (NY Reuters 9/3/98). Peet says depleted AA and DHA in RBC membr of schiz and and 1^st degree relatives and improvement in schiz and TD in 6 mo open trial increased n-3. Pts continued on previous psych meds. Peet, PLEFA 8/96;55:71

EPA Might Help in DB: Schizophr Res 2001 Apr 30;49(3):243-51. Peet. Two small studies both finding some evidence on benefit in DB.

Fish Oil Helps in DB: Am J Psychiatry 2002 Sep;159(9):1596-8. 40 patients, 12 weeks as add-on. 3 g/d E-EPA (1.5g BID). Decrease in both positive and negative symptoms (76 to 66 with EPA (13%), 74 to 71 with placebo (4%)). Dyskinesia also decreased. Randomized, placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia. Emsley R, Myburgh C, Oosthuizen P, van Rensburg SJ. Department of Psychiatry, University of Stellenbosch, Tygerberg, Cape Town, South Africa. [email protected]

Fish Oil May Help: membrane phospholipid metabolism is abnormal in schizophrenic patients. Marked depletion of essential fatty acids, particularly arachidonic acid and docosahexanoic acid, in red blood cell membranes from schizophrenic patients. Similar abnormalities are present in first degree relatives of schizophrenic patients. Changes in diet, which modify membrane levels of fatty acids, can have significant effects upon symptoms of schizophrenia and tardive dyskinesia (TD). We have found that schizophrenic patients who eat more (n-3) fatty acids in their normal diet have less severe symptoms. In a pilot study of (n-3) fatty acid supplementation we observed significant improvement in both schizophrenic symptoms and tardive dyskinesia over a 6 week period. Prostaglandins Leukot Essent Fatty Acids 1996 Aug;55(1-2):71-5

Fish Oil May Help Schizophrenia: Laugharne of Sheffield found 10 caps of MaxEPA fish oil/d x 6weeks led to significant improvement mental function and schizophrenic symptoms. RBC deficiency in both n-3 and n-6 especially DHA and arachidonic acid. No deficiency in diets although individuals with higher n-3 in diet not as severe. Lipids 1996 Mar;31 Suppl:S163-5 Sheffield, UK

Omega-3 Helps Schizophrenia: DB study reported at Int Congress on Schiz Res 4/97 that adding n-3 to Rx results in improvement. Peet, Laugharne.

Negative Symptoms Improve in Schizophrenia: Chronic schiz with negative flush test found increased flush after 6 mo. EFA supplementation and improvement in affective symptoms. Glen, UK, Prostagl Leuko EFA 8/96;55:9. Pts without flush had low DHA and AA.

Diet in 8 Countries, Animal Fat Bad, Fish OK: Study found that 97% of the variance in patient recovery between countries could be attributed to dietary variations with high total fat intake and high intake of land animal and bird fat especially (p=.0002). There is a favorable recovery linkage, tho not as strong, linked to a higher intake of fats from fish, seafood, and vegetables (p>.10). Used data from 8 national centers participating in WHO international 2-year f/u study. Incidence of schiz similar in all countries. Christiansen, Denmark, Acta Psychia Scand 88;78:587

Schizophrenia Skin Fibroblasts Abnormal: S. Mahadik in Prostagl Leukot EFA 55:65-70 ’96 and Psychiatry Res 63:133-42 notes earlier reports of defectin utilization of Essential PUFAs by RBCs. Cultured skin fibroblasts. Uptake and incorp of both LA and ALA were normal. The utilization of EPA into DHA was significantly lower in 1^st-episode psychotic patients (96 vs 161 nmoles/mg) indicating delta 6- and delta 5-desaturase may be normal but delta 4 may be lower in fibroblasts from 1^st episode patients. Ramchand & Peet in 55:59-64 say abn decr tyrosine transport has been documented in two studies of schiz fibroblast cultures and that it has been shown that tyrosine transport into the brain is also decreased. They say they have also found a decr for tyrosine transport in schiz fibroblasts and that the inhibition is uncompetitive. They suggest a cell membrane problem, one that could be due to altered metabolism of phospholipids such as AA and DHA

DHA Low in Schizophrenia RBCs: Significantly reduced docosahexaenoic and docosapentaenoic acid concentrations in erythrocyte membranes from schizophrenic patients compared with a carefully matched control group. Assies J, Lieverse R, Vreken P, Wanders RJ, Dingemans PM, Linszen DH. Biol Psychiatry 2001 Mar 15;49(6):510-22

Schizophrenia with Abnormal RBC Membranes: 40 Schizophrenic patients were tested and found increased frequency of dihomogamma-linolenic acid but no abnormal phospholipase-A2 allele. Doris, UK Schiz Res 5/98 31:185. Vaddadi in Schiz Res 7/96;20:287 also found incr in RBC dihomogamma-linolenic and also a decr in linoleic in 72 schiz. No relationship to TD. Horrobin ’96 Prostag Leuk EFA 55:3-7 says schiz is disorder of membrane phospholipid metab assoc with loss of highly polyunsat f.a. from membrane due to enhanced activity of a phospholipase A2. M

Increased Omega-3 Membrane Loss in Schizophrenia: Evidence for enhanced phospholipase A2 activity causing a loss of EPA and DHA from membranes. Horrobin, Nova Scotia, Med Hypotheses 12/95;45:605

Helps Schizophrenia in Case Report: Notes inverse relationship betw schiz and some inflam disorders. Increased risk assoc with maternal malnutrition during fetal development. Differences is severity and prognosis in different countries (Horrobin Schiz Res ’94;13:195. Notes studies find in membr def of AA and DHA from excess activity of phospholipase A2. Clozapine assoc with dramatic rise in RBC membr PUFAs. EPA a PLA2 inhibitor. Rx 2g/d EPA. Dramatic improvement esp betw 1^st and 2^nd month with continuing good rate betw 2^nd and 3^rd month and slow continuing improvement through 6^th month where symptoms 80% gone. Contining improvement in second 6 months. Excessive activity of cytosolic PLA2 leads to depletion of AA and DHA. Basan Puri, London

Less Oxidative Damage with Anti-Psychotics: Sheffield study showing less oxidative damage to RBCs of schiz pts medicated with anti-psychotics suggesting a protective role and that the EFA deficits in schiz RBC are not due to Rx but to schiz process. PLEFA 8/96;55:27

Failing Niacin Flush=Deficit AA and DHA: Schizophrenic patients found that after 6 mo EPA treatment, the flush test improved. Glen, Vaddadi, Horrobin, Inverness, PLEFA 8/96

High Dose Phenothiazine/thioxanthene Lower EPA/DHA: Study of thrombocyte of low and high dose treatment of schizophrenia and control found marked decreases in AA, EPA, DHA, and ALA in high dose and AA in low dose. Fischer, U Munich, Biochem Pharmacol 2/92;44:317