This diet was associated with significant reductions in symptom variability in patients with bipolar disorder.
CASE VIGNETTE
“Mr Truth” is a 35-year-old African-American man with a 15-year history of bipolar I disorder without psychotic features. He has been clinically stable and has had no psychiatric hospitalizations for 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. At a follow-up outpatient visit, Mr. Truth asks about the potential mental health benefits of fish oil supplementation for his bipolar disorder. How would you respond, as your psychiatrist?
Mood instability in Bipolar disorder is associated with relapse and disease severity.1 There is a need for non-pharmacological adjuvant treatments for this patient population. Dietary modifications, particularly n-3 and n-6 polyunsaturated fatty acids (PUFAs), represent one such potential target. PUFAs comprise more than a third of brain lipids and have been implicated in mood disorders.two There is conflicting evidence regarding the efficacy of n-3 PUFA supplementation in patients with bipolar disorder, and there is also evidence that some mood stabilizers may decrease metabolism of n-6 PUFAs.3 Therefore, Saunders et al.4 investigated a combined intervention to reduce 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 the mood instability (as measured by the ecological momentary assessment [EMA]) and general psychological distress in people with bipolar disorder. The primary clinical outcome was variability in mood and distress and general psychosocial functioning. The primary biochemical outcome was the change in n-6 AA, n-3 DHA, and their metabolites. The authors compared the diet high in n-3 EPA plus DHA (1500 mg daily) and low in n-6 LA (2% energy) (H3-L6) with a control diet (CD) standardized for the usual distribution of PUFA 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 years of age, had current hypomanic or depressive symptoms, and were receiving psychiatric treatment. They were excluded if they were currently hospitalized, had supported 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 physician based on the Mini International Neuropsychiatric Interview. The study authors gave participants Android smartphones programmed for the research 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 dietician to review dietary compliance and food records, receiving dietary advice, and collecting food supplies. A mood and stress survey was randomly administered twice daily in an EMA paradigm, in which patients rated their mood, energy, speed of thought, impulsiveness, anxiety, irritability, and pain on an analog scale. from 0 to 100. Blood samples for biochemical analyzes were collected at baseline and at weeks 4, 8, 12, and 48. The authors made comparisons between the diet groups using 2-sample t-tests or 2-sum Wilcoxon ranges and used linear mixed-effects models to analyze the continuous PUFA concentration results. Data was analyzed using an intention-to-treat approach.
The authors randomized 82 participants. The mean age was 43.5 years and 83% of the participants were women. Self-reported diet adherence 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 variability and impulsivity. Mean n-6 LA levels were slightly decreased and n-3 EPA and DHA levels increased over time in the H3-L6 group compared to the CD group. There were no changes in any other measured PUFAs and adverse events associated with the diet were minimal.
Study Conclusions
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 PUFA levels in patients with bipolar disorder over 12 weeks. It is noted that dietary trials, especially dietary intervention versus nutritional supplementation, are particularly difficult to conduct. Study strengths included the use of diet-based interventions provided by dieticians and the use of EMA for data collection. Study limitations included the relatively small sample size and female predominance.
The bottom line
Increased n-3 EPA and DHA and decreased n-6 LA through a dietary intervention improved daily variability in mood symptoms in patients with bipolar disorder. The findings warrant replication in future larger trials.
Do your patients ask about the use of fish oil supplements? Share your experiences with us on [email protected].
doctor miller is a professor in the Department of Psychiatry and Behavioral Health at Augusta University in Augusta, Georgia. He is on the editorial board and serves as head of the schizophrenia section of Psychiatric Times™. The author reports receiving research support from Augusta University, the National Institute of Mental Health, and Stanley Medical Research. Institute.
References
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(Suppl 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. Reconsideration of dietary polyunsaturated fatty acids in bipolar disorder: a translational picture. J Clin Psychiatry. 2016;77(10):e1342-e1347.
4. Saunders EFH, Mukherjee D, Myers T, et al. Adjunctive dietary intervention for bipolar disorder: a randomized, controlled, parallel-group, double-blind, modified trial of a high n-3 lower n-6 diet.. Bipolar disorder. 2022;24(2):171-184. ❒
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