The risk was between 15% and 33% lower for depression, and between 19% and 22% lower for anxiety, when the researchers statistically analyzed the data using quintiles.
Taking a fish oil supplement was associated with a “a 9%–10% lower risk for a history of depression and anxiety, respectively, and a 20% lower risk for recent anxiety,” wrote researchers at OmegaQuant Analytics and other institutions in the USA and Taiwan.
“Collectively, our findings provide compelling biological support for the protective role of ω-3 fatty acids, especially EPA, in the maintenance of mental health and the prevention of mood disorders,” they wrote in Nutritional Epidemiology.
Clarifying the relationship
Studies into omega-3 intake and depression or anxiety have yielded mixed results; the current researchers aimed to clarify the relationships using data from the United Kingdom Biobank (UKBB).
The UKBB is a population-based cohort of 502,411 individuals, aged 40–70 y, recruited in the United Kingdom between April 2007 and December 2010.
The researchers used a random sample of 258,354 participants with available plasma fatty acid data. The participants were mainly white, working or retired, with an average age of 56, and over half were female.
Some analyses used data from a sample of 468,145 people who were asked whether they used a fish oil supplement and how often. The researchers also used data from a food frequency questionnaire to assess dietary oily fish consumption.
The findings revealed that about 32% regularly used a fish oil supplement. The mean plasma omega-3 level was 4.97% in the supplement users and 4.12% in the nonusers.
“We found that all 3 ω-3 PUFA metrics were inversely associated with a history of both depression and anxiety,” the researchers wrote. For recent anxiety and depression, there were fewer associations with omega-3 measures, which the researchers noted could be due to “the lower prevalence (hence low power) of the recent conditions compared with a lifetime history.”
Oily fish consumption “was generally associated with lower risk for depression and anxiety, irrespective of FOS use, and vice versa,” they wrote, noting a lack of dose-response relationship, which perhaps “perhaps reflects the lack of precision in the dietary intake estimates”.
Proposed mechanisms
The researchers noted that the key findings are consistent with proposed mechanistic pathways in previous studies.
“ω-3 fatty acids, particularly EPA (a component of the non-DHA metric) is known to exert anti-inflammatory effects by reducing the production of proinflammatory cytokines and promoting the resolution of inflammation, which has increasingly been recognized as a key contributor to the pathophysiology of depression and anxiety,” they wrote.
Moreover, DHA, as the most abundant omega-3 in the brain, maintains cell membrane fluidity, supporting neurotransmitter signalling and, in turn, mood.
Previous research has indicated that omega-3 can modulate the synthesis of neurotransmitters such as serotonin and dopamine, potentially having antidepressant and anti-anxiety effects. EPA has been shown to modulate the hypothalamic-pituitary-adrenal axis and enhance key neurotransmitters.
“These mechanistic pathways may explain why stronger and more consistent associations were observed for non-DHA ω-3 PUFA and total ω-3 PUFA exposures compared with DHA alone,” the study noted.
While the current study utilized data from a large cohort, the researchers acknowledged the limitations of a historical study, calling for future prospective studies to explore omega-3, depression, and anxiety.
Source: The Journal of Nutrition, Volume 156, Issue 1, 101219 DOI: 10.1016/j.tjnut.2025.10.032, “Associations of Plasma Omega-3 Fatty Acid Levels and Reported Fish Oil Supplement Use with Depression and Anxiety: A Cross-Sectional Analysis from the United Kingdom Biobank.” Authors: W.S. Harris et al.
