‘Top-tier evidence’: Major Australian meta-review backs EPA for improving mental health

By Tingmin Koe contact

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An Australia meta‐review of meta‐analyses of randomised controlled trials found that EPA has the most evidence for improving mental health. ©Getty Images
An Australia meta‐review of meta‐analyses of randomised controlled trials found that EPA has the most evidence for improving mental health. ©Getty Images

Related tags: Epa, Omega-3 fatty acid, Australia

Polyunsaturated fatty acids (PUFAs), and in particular eicosapentaenoic acid (EPA), has shown the strongest evidence for improving cognitive disorders, such as depression, according to a meta-review.

The meta-review, led by researchers from Sydney’s NICM Health Research Institute at Western Sydney University, was published in World Psychiatry​.

They evaluated existing studies that studied the relationship between nutrient intake and mental health improvement.

Examining 33 meta-analyses of placebo-controlled RCTs, the researchers said they studied “top tier evidence”​ involving a total of 10,951 subjects.

These subjects were at risk or are suffering from common and severe mental disorders.

Through the review, they said that PUFAs, in particular, EPA, displayed the strongest evidence as a useful adjunctive treatment for depression.

The majority of other nutritional supplements, such as vitamins, however, did not show ample evidence for improving mental health, they claimed,

For PUFAs, early findings also suggested that it could be beneficial for attention-deficit or hyperactivity disorder. No evidence was found for schizophrenia.

On the other hand, there were emerging evidence for N-acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia.

Here are their findings on the impact of different nutrients on mental health:

1.     PUFA​ 

The meta-review showed that omega-3 as an adjunctive treatment alongside antidepressants “appeared to be of the greatest benefit” ​when it had high-EPA content.

As a monotherapy intervention, the data becomes less compelling, and DHA or DHA‐predominant formulas do not appear to show any obvious benefit in major depressive disorders (MDDs).

Data from the RCTs further indicated that omega‐3 might be most beneficial for patients with raised inflammatory markers.

The researchers said that more research is needed concerning the efficacy of omega‐3 supplements in other mental health conditions.

An example is to further study the benefits of high EPA formula omega‐3 for children with ADHD, which at present, has already showed some emerging evidence.

2.     Folate

Using folate‐based supplements as an adjunctive treatment was found to significantly reduce symptoms of MDD and negative symptoms in schizophrenia. 

However, based on the Assessing the Methodological Quality of Systematic Reviews (AMSTAR-2) ratings, there was low confidence in the review findings.

Also, the positive overall effects of folate-based supplements were driven largely by RCTs of high‐dose (15 mg/day) methylfolate. 

Methylfolate, the active form of folate, is readily absorbed, and could  cross over the blood‐brain barrier.

Researchers said that further research on methylfolate as an adjunctive treatment for mental disorders was required.

3.      Vitamins

There is a lack of compelling evidence which shows the efficacy of vitamins and minerals, such as zinc and magnesium in improving any mental disorder.

The researchers have however noted that there were emerging evidence on the positive effects that vitamin D has for major depression.

 4.     Amino acid N-acetylcysteine

Findings show that N-acetylcysteine as an adjunctive treatment at doses of 2,000mg per day or higher, was potentially effective for reducing depressive symptoms.

N-acetylcysteine is the nutraceutical form of amino acid cysteine and is found in abundance in high protein foods.

Researchers said that significant reductions in total symptoms of schizophrenia have been observed when using N‐acetylcysteine as an adjunctive treatment.

However, there was substantial heterogeneity between studies, especially in study length. Notably, N‐acetylcysteine also has a delayed onset of action of about 6 months.

5.       Pre and probiotics  

From a recent meta-analysis that evaluated the pooled effect of probiotic interventions on depressive symptoms, it was found that probiotics may be beneficial for those with a clinical diagnosis of depression rather than subclinical symptoms.

In groups of individuals with mild to moderate depression as determined by thresholds on clinically validated scales, probiotic treatments of varying strains and doses also reduced depressive symptoms.

The researchers said that additional trials were required to replicate the results and also to evaluate the long‐term safety of probiotic interventions.

Research into the optimal dosing regimen and the most effective prebiotic and probiotic strains are also required.

A word of caution

Researchers cautioned that nutrient supplements should not be intended to replace dietary improvement.

At present, there are a number of scientific research which shows the link between dietary intake and mental health.

For instance, data from large scale studies showed that psychotic and mood disorders are associated with reduced serum levels of essential nutrients, such as zinc, folate, and vitamins.

For example, vitamin E occurs naturally in eight forms, but nutrient supplements may only provide one form.

The researchers added that more well‐designed studies are needed to confirm the mental health benefits of dietary interventions for people with diagnosed psychiatric conditions.


Source: World Psychiatry

The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta‐review of meta‐analyses of randomised controlled trials


Authors: Joseph Firth, et al

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