PUFAs: No Benefit for Anxiety, Depression Treatment, Prevention?

Megan Brooks

November 07, 2019

Increasing polyunsaturated fatty acid (PUFA) intake likely offers little or no benefit in preventing symptoms of anxiety or depression, results of a systematic review and meta-analysis show. However, at least one expert said the research has many limitations and flaws and cautioned against drawing any firm conclusions based on these findings.

"The most trustworthy studies consistently showed little or no effect" of long-chain omega-3 supplements, including fish oils, on depression or anxiety, "and they should not be encouraged as a treatment," study investigator Lee Hooper, PhD, from University of East Anglia (UEA) Norwich Medical School, United Kingdom, said in a statement.

"Oily fish can be a very nutritious food as part of a balanced diet. But we found that there is no demonstrable value in people taking omega-3 oil supplements for the prevention or treatment of depression and anxiety," coauthor Katherine Deane, PhD, also from UAE, added.

The study was published online October 24 in the British Journal of Psychiatry.

"Little or No Effect"

The analysis included 31 randomized controlled trials enrolling 41,470 adults with and without depression or anxiety. Only trials lasting at least 6 months were included in the analysis.

The studies compared higher vs lower omega-3, omega-6 and/or total PUFA intakes. The intervention could consist of advice, foodstuffs, or oral supplements (including oil, capsules or provided foodstuffs) that aimed to alter omega-3, omega-6, and/or total PUFA intake, or (if no specific aim was stated) achieved a change of at least 10% of baseline intake.

Results of the meta-analysis suggested "little or no effect" of increasing long-chain omega-3 on risk of depression symptoms (risk ratio 1.01, 95% confidence interval [CI], 0.92 - 1.10) or anxiety symptoms (standardized mean difference 0.15; 95% CI, 0.05 - 0.26) for those without depression or anxiety at baseline, the researchers report. They say the evidence was of "moderate-quality."

Evidence of effects on depression severity and remission in existing depression were unclear, with "very-low-quality evidence," the researchers report.

Results did not differ by risk of bias, omega-3 dose, duration, or nutrients replaced.

There was some suggestion that increasing alpha-linolenic acid by 2 g/d may increase risk of depression symptoms "very slightly" over 40 months; 1000 people would need to increase their alpha-linolenic acid intake for one additional person to develop depression symptoms, the researchers calculate.

Data on other outcomes and effects of increasing omega-6 and total PUFA were "missing or of very low quality."

The authors caution that the variety of methods used to assess depression and anxiety symptoms, and limited clinical diagnoses of depression/anxiety, may limit clinical interpretation of the results.

In addition, some of the studies lacked complete information on baseline levels of omega-3 intake, which could alter effectiveness of omega-3 supplementation.

Major Concerns

Kuan-Pin Su, MD, PhD, chief of the Department of General Psychiatry, China Medical University, Taichung, Taiwan, has major concerns about the analysis.

"The main reasons of inconsistent results from this and many other meta-analyses in omega-3 trials are due to common methodological flaws, such as pooling heterogeneous clinical trials, applying nonstandardized diagnostic procedures and unreliable outcome measurements, and implementing improper intervention methods," Su told Medscape Medical News.

This analysis included "many problematic" omega-3 clinical trials to investigate the topic of depression and anxiety, said Su. For example, participants could have a current or previous diagnosis of clinical depression or anxiety, but this was not necessary. In fact, most participants had no proper assessment for clinical depression/anxiety, Su noted.

"Obviously, the methodological flaws undermine the possibility to detect the small signals in clinical trials for omega-3's antidepressant and anxiolytic effects. In other words, if the included data is a mess (heterogeneous), the results will be a mess (inconsistent)," said Su.

Su is a strong proponent of "nutritional psychiatry" and a founding member of the International Society for Nutritional Psychiatry Research (ISNPR), which recently published a clinical practice guideline recommending omega-3 PUFAs as adjunctive therapy for major depressive disorder.

Concerns Addressed

Medscape Medical News reached out to the investigators for response to Su's concerns but received no response by press time. However, lead investigator Hooper subsequently responded, noting her team specifically assessed the effects of omega-3 on anxiety "in a more general population, not just in those who are ill."

"What we see in these long trials (at least 6 months duration) is the suggestion that taking omega-3 capsules worsens anxiety symptoms. However this effect is very small and not clinically important — so we conclude that there is little or no effect," said Hooper.

Hooper also countered that the results "are not heterogeneous. We pooled longer-term trials in general populations of adults that assessed anxiety levels. The I2 test (which assesses heterogeneity) for anxiety in our review was 0%, suggesting almost no heterogeneity between the results of the trials in adults that we included."

This research was funded by the World Health Organization Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health (via the University of East Anglia). The authors have disclosed no relevant financial relationships. Su is a founding committee member of the ISNPR, the board director of the International Society for the Study of Fatty Acids, and an associate editor of the journal Brain, Behavior, and Immunity.

Br J Psychiatry. Published online October 24, 2019. Abstract

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