Published in the journal JAMA, the team found a course of omega-3 supplements yielded mixed results, with a small but statistically significant increase in depression risk or symptoms but no difference in mood scores.
“Our findings indicate there is no reason for adults without depression in the general population to take fish oil supplements solely for the purpose of preventing depression or for maintaining a positive mood,” says senior author JoAnn Manson, Professor of Medicine at Harvard Medical School.
“There are still health reasons for some people to take omega-3 fish oil supplements. These supplements increasingly have been found to have benefits for cardiac disease prevention and treatment of inflammatory conditions, in addition to being used for management of existing depressive disorders in some high-risk patients.”
Meanwhile, Karolinska Institutet scientists discovered the receptor GPR32 that is activated by omega-3 fatty acids and plays a role in preventing inflammation in blood vessels and reducing atherosclerosis.
“We've found that this receptor is dysregulated in atherosclerosis, indicating a disruption in the body's natural healing processes," says the study's first author Hildur Arnardottir, Assistant Professor at the Department of Medicine, Solna, Karolinska Institutet.
"This discovery can pave the way for new strategies for preventing atherosclerosis by arresting inflammation in the blood vessels, while also turning on the body's healing processes with the help of omega-3 fatty acids."
Harvard Med School research
The JAMA study enrolled 18,353 adults aged 50 years or older without depression randomised to receive vitamin D and/or omega-3 supplements or matching placebos for a median of 5.3 years.
These interventions were specifically a randomised 2 × 2 factorial assignment to vitamin D3 (2000 IU/d), marine omega-3 fatty acids (1 gram per day (g/d) of fish oil (465 milligrams (mg) of eicosapentaenoic acid and 375mg of docosahexaenoic acid).
The placebo involved 9171 individuals randomised to omega-3 and 9182 randomised to matching placebo.
Among the participants who were randomised, the test for interaction between the omega-3 and the vitamin D agents was not significant.
Depression risk was significantly higher comparing omega-3 (651 events, 13.9 per 1000 person-years) with placebo (583 events, 12.3 per 1000 person-years).
While a small increase in risk of a depression was inside the statistical margin of significance, lead study author Olivia Okereke, an Associate Professor of psychiatry at Harvard Medical School says, “there was no harmful or beneficial effect of omega-3 on overall course of mood during the roughly 5 to 7 years of follow-up.”
Resolving resolvin’s role
The Karolinska Institutet team, writing in the Journal of Clinical Investigation, drew on previous work on atherosclerotic plaques and created a new experimental model with an over-expressed GPR32 receptor.
The GPR32 receptor counteracted atherosclerosis and inflammation in the blood vessels, and resolvins, formed from omega-3 fatty acids that activate the GPR32, enhanced these effects.
“GPR32 signalling attenuates atherosclerosis and mediates proresolving leukocyte responses in vivo,” the study notes.
“We provide evidence for the in vivo role of the receptor GPR32 in atheroprotection by means of promoting proresolving leukocyte responses, enhancing phagocytosis, and reducing oxLDL uptake, with implications for atherosclerotic lesion size, necrotic core formation, and aortic inflammation.
“Stimulating GPR32 may represent a potential therapeutic strategy for reducing atherosclerotic cardiovascular diseases by means of stimulating resolution of inflammation.
The study's last author Magnus Bäck, Senior Consultant Cardiologist and Professor at the Department of Medicine, Solna, Karolinska Institutet adds, "We'll now be studying the mechanisms behind the failed management of inflammation in the blood vessels and how omega-3 mediated stop signals can be used to treat atherosclerosis."
Source: Journal of Clinical Investigation
Published online: DOI: 10.1172/JCI142883
“The resolvin D1 receptor GPR32 transduces inflammation resolution and atheroprotection.”
Authors: Hildur Arnardottir et al
Published online: doi:10.1001/jama.2021.21187
“Effect of Long-term Supplementation With Marine Omega-3 Fatty Acids vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores”
Authors: Olivia Okereke et al