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Omega-3 supplementation lowers inflammation and anxiety in medical students: A randomized controlled trial
Open accessAbstract
Observational studies have linked lower omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and higher omega-6 (n-6) PUFAs with inflammation and depression, but randomized controlled trial (RCT) data have been mixed. To determine whether n-3 decreases proinflammatory cytokine production and depressive and anxiety symptoms in healthy young adults, this parallel group, placebo-controlled, double-blind 12-week RCT compared n-3 supplementation with placebo. The participants, 68 medical students, provided serial blood samples during lower-stress periods as well as on days before an exam. The students received either n-3 (2.5 g/d, 2085 mg eicosapentaenoic acid and 348 mg docosahexanoic acid) or placebo capsules that mirrored the proportions of fatty acids in the typical American diet. Compared to controls, those students who received n-3 showed a 14% decrease in lipopolysaccharide (LPS) stimulated interleukin 6 (IL-6) production and a 20% reduction in anxiety symptoms, without significant change in depressive symptoms. Individuals differ in absorption and metabolism of n-3 PUFA supplements, as well as in adherence; accordingly, planned secondary analyses that used the plasma n-6:n-3 ratio in place of treatment group showed that decreasing n-6:n-3 ratios led to lower anxiety and reductions in stimulated IL-6 and tumor necrosis factor alpha (TNF-α) production, as well as marginal differences in serum TNF-α. These data suggest that n-3 supplementation can reduce inflammation and anxiety even among healthy young adults. The reduction in anxiety symptoms associated with n-3 supplementation provides the first evidence that n-3 may have potential anxiolytic benefits for individuals without an anxiety disorder diagnosis. ClinicalTrials.gov identifier: NCT00519779.
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“Although omega-3 supplementation was unrelated to changes in depression in this study”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Kiecolt-Glaser, Belury, Andridge, Malarkey, & Glaser, 2011
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“medical students who received omega-3 supplementation exhibited a 14% reduction in LPS-stimulated IL-6 production and a 20% reduction in anxiety symptoms compared to those in the control group”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Kiecolt-Glaser, Belury, Andridge, Malarkey, & Glaser, 2011
In the citing paper
“various RCTs have shown that omega-3 fatty acid supplementation reduces inflammation142–144 and may thus have health-promoting effects141–144”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [142]
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Chronic inflammation in the etiology of disease across the life span
Furman, D., Campisi, J., Verdin, E., Carrera-Bastos, P., Targ, S., Franceschi, C., Ferrucci, L., Gilroy, D. W., Fasano, A., Miller, G. W., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0675-0 · Cited by 4,915
Slavich, G. M., & Irwin, M. R. (2014) · Psychological Bulletin · doi:10.1037/a0035302 · Cited by 2,206
Polyunsaturated fatty acids and their metabolites in brain function and disease
Bazinet, R. P., & Layé, S. (2014) · Nature reviews. Neuroscience · doi:10.1038/nrn3820 · Cited by 1,703
Iddir, M., Alex Brito, O., Dingeo, G., Sosa, S., Samouda, H., Frano, M. R. L., & Bohn, T. (2020) · Nutrients · doi:10.3390/nu12061562 · Cited by 825
Mental health comorbidity in patients with atopic dermatitis
Yaghmaie, P., Koudelka, C. W., & Simpson, E. L. (2013) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2012.10.041 · Cited by 449
Metadata
- Authors
- Kiecolt-Glaser, J. K., Belury, M. A., Andridge, R., Malarkey, W. B., & Glaser, R.
- Affiliations
- The Ohio State University (US)
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 25
- Issue
- 8
- Pages
- 1725-1734
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC3191260
- OpenAlex
- W2140758044
- Cited by
- 340
- References
- 70
- Citations by year
- 2026: 19 · 2025: 18 · 2024: 30 · 2023: 24 · 2022: 31 · 2021: 32 · 2020: 24 · 2019: 28 · 2018: 18 · 2017: 21 · 2016: 13 · 2015: 24 · 2014: 26 · 2013: 15 · 2012: 17
- FWCI
- 17.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Ohio State University
- National Institutes of Health (UL1TR000090)
- National Cancer Institute (CA16058, P30CA016058)
- National Center for Complementary and Alternative Medicine
- National Center for Research Resources (UL1RR025755)
- NIH Clinical Center
- National Center for Advancing Translational Sciences
- National Center for Complementary and Integrative Health (R21AT003912, AT003912)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Keywords
- omega-3 fatty acids, n-6/n-3 ratio, inflammation, anxiety, depression, medical students, eicosapentaenoic acid, docosahexaenoic acid, interleukin-6, TNF-α, lipopolysaccharide stimulation, exam stress, young adults
- MeSH terms
- Adult, Affect, Anxiety, Depression, Diet, Double-Blind Method, Fatty Acids, Female, Humans, Inflammation, Male, Neutrophils, Patient Compliance, Stress, Psychological, Health Behavior, Exercise, Fatty Acids, Omega-3, Cytokines, Sample Size, Dietary Supplements, Young Adult
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