Omega-3 supplements: not a silver bullet for depression

Numerous posts can be found on social media encouraging people to take omega-3 supplements to treat depression. Among some of the prominent examples we found was a video clip of Stanford neuroscientist and podcaster Andrew Huberman claiming that “omega-3 from fish oils is as effective at reducing depression as antidepressants” (YouTube and TikTok).

Another example we found showed naturopath Barbara O’Neill claiming that postmortem examination of suicide victims showed “no omega-3 in their brain”, implying a causal relationship between omega-3 levels and depression.

Claims about the benefits of omega-3 supplementation for mental health also circulate in other languages, including Spanish, Polish, and Portuguese.

How much truth is there to the claim that omega-3 supplements treat depression? In this Insight article, we take a look at the scientific evidence on the relationship between omega-3 fatty acids and depression. Our findings show that while omega-3 could be a promising intervention for some people with depression, we’re still a long way from establishing its effectiveness or showing that it can replace conventional treatments.

What is depression?

Depression is a fairly common mental health disorder. The World Health Organization estimates that 332 million people around the world are affected by depression; women are about 1.5 times more likely to be affected by the condition compared to men. Genes and environmental factors, such as continuous exposure to violence, neglect, abuse or poverty, influence the risk of depression.

Temporary feelings of sadness are a normal part of life, but depression as a medical condition involves low mood or sadness that persists for weeks or months. Other symptoms include a sense of hopelessness, sleep disturbances, changes in appetite, and suicidal ideation (thoughts of suicide). Untreated depression can severely disrupt a person’s life and relationships.

Major depressive disorder is likely the form of depression that most people are most familiar with, but there are also other types of depressive disorders that exist, such as postpartum depression which occurs before, during, or after childbirth, and premenstrual dysphoric disorder.

Treatment depends on the severity of depression and usually involves a combination of approaches. For example, people who have mild depression may be recommended exercise and talking therapy as treatment, while people with moderate to severe depression may be recommended to take antidepressant medication as well.

Selective serotonin reuptake inhibitors (SSRIs) are common antidepressants. They increase the level of a neurotransmitter called serotonin in the brain, which regulates mood and behavior. Having said that, depression is a complex condition that involves multiple factors; low serotonin levels alone don’t determine whether someone has depression, contrary to a popular misconception that Science Feedback examined in a previous review.

What are omega-3 fatty acids?

Omega-3 fatty acids are essential nutrients that play an important role in heart health, as well as hormone production and immune function. Rich sources of omega-3 include oily fish (like salmon, sardines, herring, and mackerel), nuts, and seeds. They come in three main forms: a-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA tends to be found in nuts and seeds, while EPA and DHA tend to be found in fish.

In general, there is no hard and fast rule on the amount of omega-3 fatty acids that we must consume, although recommendations to consume a certain amount of omega-3 exist in various countries. For example, the Heart Foundation in Australia recommends that people consume between 250 and 500 milligrams of omega-3 fatty acids, specifically in the forms of EPA and DHA, per day.

The British Heart Foundation states that “[t]here is no government recommendation in the UK of how much omega-3 we need. But UK government dietary advice recommends we eat two 140g (cooked weight) portions of fish a week with one of these being an oily fish”. This translates to about 450 milligrams per day of DHA and EPA. It also adds that people “do not need to take omega-3 supplements unless they’ve been prescribed by your doctor”.

Where does the idea that omega-3 supplementation treats depression come from?

This 2006 review in the American Journal of Psychiatry gives an overview of the origin of this hypothesis^[1]. Briefly, scientists noted increased rates of depression in Western societies, which they hypothesized might be connected with dietary changes. Specifically, people now eat less fish and plant-based foods, instead consuming more animal-based food and common vegetable oils. This shift in dietary pattern leads to a reduced intake of omega-3 fatty acids and an increased intake of the omega-6 fatty acid called arachidonic acid, which is thought to promote inflammation.

More on arachidonic acid and omega-6 in general

Arachidonic acid, an omega-6 fatty acid, has been maligned by critics of seed oils due to its role as a precursor to pro-inflammatory molecules like prostaglandins. However, this is a simplistic understanding of the biological role of arachidonic acid. In fact, arachidonic acid is also a precursor for making molecules that are anti-inflammatory, such as lipoxins.

The bottom line: omega-6 fatty acids like arachidonic acid aren’t inherently bad and are in fact beneficial when consumed in moderation.

On top of that, some studies noted an association between frequent seafood consumption, particularly fish, and the prevalence of depression in cross-country and national comparisons^[2,3]. In addition, some studies noted that people with depression tended to have lower levels of omega-3 fatty acids in the blood than people who didn’t have the condition^[4,5].

Taken together, these findings suggest that low omega-3 fatty acid level is linked to depression and raising it could help. These associations don’t establish a causal relationship, but they provide the groundwork and justification for further research that can demonstrate causality, especially clinical studies in humans. We discuss some of this research below.

Evidence for benefits of omega-3 in depression is mixed

The evidence indicating that omega-3 plays a role in the biology of depression comes from several types of studies. These include studies in cell cultures (cells growing in the laboratory) that shed light on the molecular mechanisms mediated by omega-3, as well as randomized clinical trials in people. 

One study conducted both in vitro experiments and a randomized trial in 22 people diagnosed with major depression^[6]. It found that EPA and DHA protected neurons (nerve cells) growing in cell cultures from inflammatory damage, preserving the growth of new neurons and blocking cell death. Furthermore, in the randomized trial, EPA or DHA supplementation for 12 weeks was correlated with improvements in depressive symptoms.

In his comments to Science Media Centre, Michael Bloomfield, head of the translational psychiatry research group at University College London, called this research “fascinating”, adding that it “sheds light on some of the potential mechanisms that may underlie response to omega oils”. This information could help scientists identify new treatment targets and recognize who is likely to respond to omega-3 supplementation, he said.

However, the study also contains important caveats. Kevin McConway, emeritus professor of applied statistics at the Open University, pointed out that there was no control group in the trial, meaning it was impossible to determine if improvements were due to the fish oil supplements or just part of the natural course of disease:

“The study did find that, on average, the depression was less severe, on the measurement scale that was used, at the end of the twelve weeks. But perhaps the score would have improved in that way, over that timescale, even if the patients have not been given the omega-3 acids.  We just can’t tell, since every patient got omega-3 fatty acids.”

When it comes to determining the safety and effectiveness of a medical intervention, randomized controlled trials still remain the gold standard.

One trial which looked at whether omega-3 supplementation could prevent depression was conducted across four European countries^[7]. The study included about 680 people with overweight and subclinical depression. It found that omega-3 levels were higher in participants who received supplementation. However, the higher omega-3 level wasn’t associated with a change in depressive symptoms.

Other trials looked at whether omega-3 supplementation could treat an existing depressive disorder instead of preventing it. One such trial was conducted in Canada and included more than 400 adult participants with major depression. It reported that omega-3 supplementation for eight weeks improved symptoms in a subset of participants, specifically those who did not have anxiety—but not in others.

The study’s results are also difficult to interpret because the study population wasn’t uniform in terms of the treatment that participants were receiving. About 40% of participants were on antidepressants while receiving supplementation, making it difficult to determine what effects were due to omega-3 supplementation.

Preliminary results from a randomized trial in the U.S. showed that omega-3 supplementation over 12 weeks could mitigate cognitive impairment, a symptom of depression^[8]. More specifically, it improved motivational symptoms which affect interest and energy. However, the sample size of the study was quite small, with just 45 participants completing the trial to an adequate degree.

The researchers noted that the effect of supplementation wasn’t equal in all participants and that “it was those with more severe immune dysfunction who benefited most”. They added that the sample population was “unlikely” to be representative of people with depression as a whole and called for larger studies to validate these findings.

Another trial looked at the effect of omega-3 supplementation in children and adolescents with moderate to severe depression^[9]. The study included more than 250 participants and lasted for 36 weeks. In this trial, supplementation provided no meaningful benefit over placebo in terms of depression severity, quality of life or antidepressant use.

Systematic reviews and meta-analyses, which look at multiple published studies, provide a more comprehensive view of the scientific evidence.

One meta-analysis published in 2019 analyzed 26 trials^[10]. It reported that omega-3 supplementation could produce improvements in depression. However, these improvements ranged from “small to modest”, and results varied widely from study to study. The authors concluded that more studies are needed to study how supplementation worked for different subsets of patients with depression, as well as what doses produced a response.

A Cochrane review published in 2021 examined 35 studies: 34 looked at the effect of omega-3 supplementation compared to placebo; just one study looked at the effect of supplementation compared to antidepressant treatment^[11].

Its conclusions were similar to those of the meta-analysis described above, as the authors reported “a small-to-modest positive effect of n-3PUFAs compared to placebo” in adults with major depressive disorder. The evidence was considered to be “of low or very low certainty, with many differences between studies”. Overall, the authors considered that “[a]t present, we do not have enough high quality evidence to determine the effects of n-3PUFAs as a treatment for MDD”.

In summary, while more investigations into omega-3 and depression are warranted, the claim that omega-3 is as effective as antidepressant medication made by Huberman is unsubstantiated by current evidence. We reached out to Huberman for comment, but did not receive a response.

Do benefits outweigh the risks?

In an article for Harvard Health Publishing, professor of psychiatry David Mischoulon, wrote that omega-3 supplements are “generally safe and well tolerated”. However, caution is needed when these supplements are taken by people with bipolar depression “to prevent cycling to mania”. He called omega-3 fatty acids “promising natural treatments for mood disorders”, but that more research about their effectiveness and long-term safety is still needed before omega-3 could be recommended to people with mental health disorders.

There are also other factors to consider. For instance, supplements aren’t typically regulated, unlike medications, and could contain impurities that pose a risk to health. On top of that, they cost money. In short, taking them when there’s no evidence they work simply exposes a person to unnecessary health risks and a waste of financial resources in exchange for no proven benefit.

Conclusion

Glowing recommendations of omega-3 supplements for depression on social media gloss over the current state of scientific evidence for their benefits. Although some studies suggest that omega-3 supplementation can help people with depression, it’s also evident that not everyone will benefit equally from it and we still don’t fully understand what factors determine a person’s response to omega-3 supplementation. Therefore, sweeping statements recommending omega-3 supplementation for treating depression aren’t substantiated by the current evidence.

Claims that omega-3 supplementation works as well as antidepressants aren’t supported by the evidence either, and can be harmful if people choose to replace their medication with supplements. More work needs to be done to determine which patients are most likely to benefit from supplementation and what doses will be effective.

References

1. Parker et al. (2006) Omega-3 Fatty Acids and Mood Disorders. American Journal of Psychiatry.
2. Hibbeln JR. (1998) Fish consumption and major depression. The Lancet.
3. Tanskanen et al. (2001) Fish Consumption and Depressive Symptoms in the General Population in Finland. Psychiatry Services.
4. Henning et al. (2003) Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam Study. American Journal of Clinical Nutrition.
5. Maes et al. (1996) Fatty acid composition in major depression: decreased ω3 fractions in cholesteryl esters and increased ratio in cholesteryl esters and phospholipids. Journal of Affective Disorders.
6. Borsini et al. (2021) Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: relevance for major depression and for human hippocampal neurogenesis. Molecular Psychiatry.
7. Thesing et al. (2020) Supplementation-induced increase in circulating omega-3 serum levels is not associated with a reduction in depressive symptoms: Results from the MooDFOOD depression prevention trial. Depression and Anxiety.
8. Berger et al. (2026) ω-3 Fatty Acids in Pediatric Major Depressive Disorder: A Randomized Clinical Trial. JAMA Network Open.
9. Liao et al. (2019) Efficacy of omega-3 PUFAs in depression: A meta-analysis. Translational Psychiatry.
10. Appleton et al. (2021) Omega‐3 fatty acids for depression in adults. Cochrane Database of Systematic Reviews.