Effects of nutrition on mood variability in bipolar disorder

This diet has been associated with significant reductions in symptom variability in patients with bipolar disorder.


“Mr Truth” is a 35-year-old African-American male with a 15-year history of Bipolar I Disorder without psychotic features. He has been clinically stable and has had no psychiatric hospitalizations in the past 5 years on a regimen of lithium 900 mg daily and hydroxyzine 25 mg 3 times daily as needed for anxiety. He works full time as an insurance salesman. During an outpatient follow-up visit, Mr. Truth asks about the potential mental health benefits of fish oil supplementation for his bipolar disorder. How would you react, as a psychiatrist?

Mood instability in bipolar disorder is associated with relapse and disease severity.1 There is a need for non-pharmacological adjunctive treatments for this patient population. Dietary modifications, in particular n-3 and n-6 ​​polyunsaturated fatty acids (PUFAs), represent one of these potential targets. PUFAs make up more than a third of brain lipids and have been implicated in mood disorders.2 There is conflicting evidence regarding the effectiveness of n-3 PUFA supplementation in patients with bipolar disorder, and there is also evidence that some mood stabilizers may decrease n-6 PUFA metabolism.3 Therefore, Saunders et al4 studied a combination intervention lowering dietary n-6 PUFAs (arachidonic acid [AA] and linoleic acid [LA]) and increased dietary n-3 PUFAs (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) in patients with bipolar disorder.

The current study

The authors hypothesized that this dietary intervention would reduce mood swing (as measured by Momentary Ecological Rating [EMA]) and general psychological distress in people with bipolar disorder. The primary clinical outcome was mood variability and general psychosocial distress and functioning. The primary biochemical outcome was the change in n-6 AA, n-3 DHA and their metabolites. The authors compared the diet rich in n-3 EPA plus DHA (1500 mg per day) and low in n-6 LA (2% energy) (H3-L6) with a control diet (CD) standardized according to the usual distribution of PUFAs in America ( n-3 EPA + DHA [150 mg daily] and low n-6 LA [7% energy]).

Participants with bipolar disorder were included if they were over 18, had hypomanic or depressive symptoms, and were currently undergoing psychiatric treatment. They were excluded if they were currently hospitalized, endorsed suicidal or homicidal ideation, had an active substance use or eating disorder, or had a history of specific food allergies (eg, fish, gluten, dairy). A diagnosis of bipolar disorder was confirmed by a clinician based on the Mini International Neuropsychiatric Interview. Study authors gave participants research-programmed Android smartphones to collect daily self-report surveys.

After a 2-week baseline period, the authors randomly assigned participants 1:1 to H3-L6 or CD for 12 weeks, with in-person assessments every 2 weeks. These included meeting with a dietitian to review diet adherence and food records, receiving dietary advice and collecting food. A mood and stress survey was randomly performed twice daily in an EMA paradigm, in which patients rated their mood, energy, speed of thought, impulsivity, anxiety, irritability, and pain on a visual analogue scale from 0 to 100. Blood samples for biochemical analyzes were taken at baseline and at weeks 4, 8, 12, and 48. The authors made comparisons between diet groups using 2-sample t-tests or Wilcoxon rank-sum tests and used linear mixed-effects models to analyze continuous PUFA concentration outcomes. Data were analyzed using an intention-to-treat approach.

The authors randomly assigned 82 participants. The average age was 43.5 years and 83% of the participants were women. Self-reported dietary compliance was approximately 85% in each group. The H3-L6 diet group had significant reductions in mood variability, energy, speed of thought, anxiety, and pain. In contrast, the CD group had significant reductions in energy and impulsivity variability. Mean AL n-6 levels were slightly reduced and EPA and DHA n-3 levels increased over time in the H3-L6 group compared to the CD group. There were no changes in the other PUFAs measured, and diet-related adverse events were minimal.

Conclusions of the study

The study authors concluded that a diet high in n-3 PUFAs and low in n-6 PUFAs was associated with significant reductions in symptom variability and modulation of blood levels of PUFAs in patients with bipolar disorder for 12 weeks. Dietary trials, especially dietary interventions versus nutritional supplementation, are particularly difficult to conduct. Study strengths included the use of diet-focused interventions delivered by dietitians and the use of EMA for data collection. Limitations of the study included the relatively small sample size and the female predominance.

The essential

Increasing EPA and DHA n-3 and decreasing AL n-6 with dietary intervention improved the daily variability of mood symptoms in patients with bipolar disorder. The results warrant replication in larger future trials.

Do your patients have questions about using fish oil supplements? Share your experiences with us at PTEditor@mmhgroup.com.

Dr. Miller is a professor in the Department of Psychiatry and Health Behavior at Augusta University in Augusta, Georgia. He is on the editorial board and is chief of the schizophrenia section for Psychiatric Times™. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and Stanley Medical Research Institute.


1. Bauer M, Glenn T, Alda M, et al. Comparison of pre-episode and pre-remission states using mood ratings of patients with bipolar disorder. Pharmacopsychiatry. 2011;44(supplement 1):S49-53.

2. Liu JJ, Green P, John Mann J, et al. Polyunsaturated fatty acid utilization pathways: implications for brain function in neuropsychiatric health and disease. Brain Res. 2015;1597:220-246.

3. Saunders EFH, Ramsden CE, Sherazy MS, Gelenberg AJ. Reconsidering dietary polyunsaturated fatty acids in bipolar disorder: a translational picture. J Clin Psychiatry. 2016;77(10):e1342-e1347.

[ PubMed ]4. Saunders EFH, Mukherjee D, Myers T, et al. Dietary adjunctive intervention for bipolar disorder: a randomized, controlled, parallel-group, double-blind modified trial of a diet high in n-3 and low in n-6. Bipolar disorder. 2022;24(2):171-184. ❒

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