Key Findings:
Omega-3 fatty acids may help stabilize mood by multiple mechanisms, including suppression of neuronal signaling, second messenger generation, calcium channel and protein kinase C activity, pro inflammatory cytokines, and kindling. This research showed that ALA in flax oil is efficacious in the pediatric bipolar population for reducing symptoms of mania and depression. Effects were seen in children and adolescents with bipolar I or bipolar II disorder taking flax oil at a dose of 10–12 capsules a day and for subjects who demonstrated an increase in EPA. Manic symptom severity correlated negatively with levels of free AA and free EPA.
ABSTRACT:
Objectives: This clinical trial evaluated whether supplementation with flax oil, containing the omega-3 fatty acid a-linolenic acid (a-LNA), safely reduced symptom severity in youth with bipolar disorder. Methods: Children and adolescents aged 6–17 years with symptomatic bipolar I or bipolar II disorder (n = 51), manic, hypomanic, mixed, or depressed, were randomized to either flax oil capsules containing 550 mg a-LNA per 1 gram or an olive oil placebo adjunctively or as monotherapy. Doses were titrated to 12 capsules per day as tolerated over 16 weeks. Primary outcomes included changes in the Young Mania Rating Scale, Child Depression Rating Scale-Revised, and Clinical Global Impressions- Bipolar ratings using Kaplan-Meier survival analyses. Results: There were no significant differences in primary outcome measures when compared by treatment assignment. However, clinician rated Global Symptom Severity was negatively correlated with final serum omega-3 fatty acid compositions: % a-LNA (r = 0.45, p < 0.007), % eicosapentaenoic acid (EPA) (r = 0.47, p < 0.005); and positively correlated with final arachidonic acid (AA) (r = 0.36, p < 0.05) and docosapentaenoic acid (DPA) n-6 (r = 0.48, p < 0.004). The mean duration of treatment for a-LNA was 11.8 weeks versus 8 weeks for placebo; however, the longer treatment duration for a-LNA was not significant after controlling for baseline variables. Subjects discontinued the study for continued depressive symptoms.
Conclusions: Studies of essential fatty acid supplementation are feasible and well tolerated in the pediatric population. Although flax oil may decrease severity of illness in children and adolescents with bipolar disorder who have meaningful increases in serum EPA percent levels and ⁄ or decreased AA and DPA n-6 levels, individual variations in conversion of a-LNA to EPA and docosahexaenoic acid as well as dosing burden favor the use of fish oil both for clinical trials and clinical practice. Additionally, future research should focus on adherence and analysis of outcome based on changes in essential fatty acid tissue compositions, as opposed to group randomization alone