Adjunctive dietary intervention for bipolar disorder: a randomized, controlled, parallel-group, modified double-blinded trial of a high n-3 plus low n-6 diet

Abstract

Objective: To investigate the preliminary efficacy of a high n-3 plus low n-6 (H3-L6) dietary intervention in improving mood stability in Bipolar Disorder (BD) when compared to dietary intervention with usual U.S. levels of n-6 and n-3 polyunsaturated fatty acid (PUFA) intakes (control diet, CD).

Methods: This 2-arm, parallel-group, randomized, modified double-blind, controlled 48-week study of 12-week intensive diet intervention in subjects with BD was conducted at a single suburban-rural site in the mid-Atlantic region. Participants with DSM-IV TR BD I or II with hypomanic or depressive symptoms were randomized, stratified on gender (N = 82). The intervention included the provision of group-specific study foods and dietary counseling. Variability of mood symptoms was measured by a twice-daily, 12-week ecological momentary analysis (EMA) paradigm, and group differences were analyzed using multilevel models. Circulating n-3 and n-6 fatty acids were measured at baseline and after 4, 8, and 12 weeks of diet exposure.

Results: All 82 randomized participants were included in biochemical analyses. Seventy participants completed at least 2 EMA surveys and were included in primary EMA analyses. Variability in mood, energy, irritability, and pain as measured using EMA was reduced in the H3-L6 group compared to the CD group. No significant differences in mean ratings of mood symptoms, or any other symptom measures, were detected. The dietary intervention effect on target PUFAs significantly differed by the group over time.

Conclusions: A dietary intervention adjunctive to usual care showed preliminary efficacy in improving variability in mood symptoms in participants with BD.

Trial registration: ClinicalTrials.Gov NCT02272010.

Keywords: bipolar disorder; depression; diet; fatty acids; food; omega-3; omega-6; unsaturated.

Conflict of interest statement

CONFLICT OF INTEREST

ES reports having received a stipend for work as an associate editor from the Journal of Clinical Psychiatry and past participation in an advisory board for Myriad Neuroscience. The other authors report no financial relationships with commercial interests.

© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Figures

FIGURE 1

CONSORT study diagram

FIGURE 2

Percent change in outcome variability in H3-L6 group, compared to control diet group. *p<0.004. Calculated as 1-eβ, where β is reported in Table 4 as the estimate of the diet intervention effect on within-person variability for each outcome measure

FIGURE 3

Plotted mixed model geometric mean estimates for eicosapentaenoic acid, docasahexaenoic acid, arachidonic acid, and linoleic acid concentrations as percent of total fatty acid concentration over the duration of Phase 1 intensive dietary intervention with corresponding 95% confidence intervals, adjusted for gender. Perc, percent; FA, fatty acid. X-axis table delineates the number of samples analyzed at each time point by diet group (study week visit number), where week 0 represents the Baseline visit (participants were randomized to their dietary intervention group at week 0) and week 12 was the last Phase 1 study visit for the intensive dietary intervention phase