Food and Behaviour Research

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Eicosapentaenoic acid and arachidonic acid: collaboration and not antagonism is the key to biological understanding.

Horrobin DF, Jenkins K, Bennett CN, Christie WW. (2002) Prostaglandins Leukot Essent Fatty Acids.  2002 Jan; 66(1) 83-90 PMID: 12051959 DOI: 10.1054/plef.2001.0338

Web URL: View this and related abstract via PubMed here.


Much of the literature on omega-3 and omega-6 fatty acids suggests that desirable effects of omega-3 fatty acids are in part related to depletion of arachidonic acid (AA). However, in rats and humans, we have found that low doses of EPA actually elevate membrane AA phospholipid concentrations.

In patients with schizophrenia, treatment with eicosapentaenoic acid (EPA) produced clinical improvement, but that improvement was greater at a dose of 2 g/day than at 4 g/day. The improvement was not significantly correlated with changes in either EPA or docosahexaenoic acid (DHA) but was highly significantly positively correlated with rises in red cell membrane AA. We suggest that elevation of concentrations of both AA and EPA in cell membranes may be important for health.


Omega-3 and Omega-6 fatty acids are essential nutrients, and both are needed in the right balance for physical and mental health. It is the longer-chain forms of each that are the most biologically important - omega-3 EPA and DHA, and omega-6 AA, and DGLA.

Numerous regulatory substances (including prostaglandins, leukotrienes and other cytokines, and thromboxins among many others) are made from these fatty acids, and these 'lipid mediators' play key roles in influencing immune function, blood flow, hormonal balance and many other aspects of cell signalling.

Broadly speaking, substances made from omega-3 EPA and omega-6 AA tend to have opposing effects. For example, AA's derivatives promote inflammation and blood clotting, while EPA's derivatives generally have anti-inflammatory, and anti-coagulant actions.

Relative omega-3 deficiencies have been consistently reported in patients with schizophrenia and many other mental health conditions, and both case studies and randomised controlled trials have shown that dietary supplemetation with EPA in particular can reduce schizophrenia symptoms.

However, blood data show that many patients lack both EPA and AA - and furthermore, supplementation with omega-3 EPA alone has been found to increase not only EPA (and DHA), but also blood concentrations of omega-6, AA, as this review emphasises (and see Richardson et al 2000).

The benefits of EPA supplementation for schizophrenia therefore do not appear to operate by reducing omega-6 AA and its derivatives. In fact, as reported here, analyses of blood data from clinical trials indicare that it is blood AA levels that correlate best with improvements in schizophrenia symptoms. 

Thus both omega-3 EPA and omega-6 AA appear to have important - and complementary - actions in relation to schizophrenia symptoms. The mechanisms underlying these actions are not yet understood, but clearly merit further study.
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