Omega-3 Fatty Acid Plasma Levels Before and After Supplementation: Correlations with Mood and Clinical Outcomes in the Omega-3 and Therapy Studies

Abstract

Objective: To examine fatty acid profiles, their response to omega-3 fatty acid (Ω3) supplementation, and associations with clinical status and treatment response in youth with mood disorders.

Methods: In a placebo-controlled 2X2 design, 7-14 year-olds (N = 95) in parallel pilot trials (depression N = 72; bipolar N = 23) were randomly assigned to 12 weeks of Ω3 supplementation (1.4 g eicosapentaenoic acid [EPA], 0.2 g docosahexaenoic acid [DHA], and 0.27 g other Ω3 per day); psychoeducational psychotherapy (PEP); their combination; or placebo (mainly oleic and linoleic acid) alone. Blood was drawn at baseline (N = 90) and endpoint (n = 65). Fatty acid levels were expressed as percent of total plasma fatty acids. Correlational and moderator/mediator analyses were done with SPSS Statistics 23.

Results: At baseline: (1) DHA correlated negatively with alpha-linolenic acid (ALA) (r = -0.23, p = 0.029); (2) Arachidonic acid (AA, Ω6) correlated negatively with global functioning (r = -0.24, p = 0.022); (3) Total Ω3 correlated negatively with age (r = -0.22, p = 0.036) and diastolic blood pressure (r = -0.31, p = 0.006). Moderation: Baseline ALA moderated response to Ω3 supplementation: ALA levels above the sample mean (lower DHA) predicted significantly better placebo-controlled response (p = 0.04). Supplementation effects: Compared to placebo, 2 g Ω3 per day increased EPA blood levels sevenfold and DHA levels by half (both p < 0.001). Body weight correlated inversely with increased EPA (r = -0.52, p = 0.004) and DHA (r = -0.54, p = 0.003) and positively with clinical mood response. Mediation: EPA increase baseline-to-endpoint mediated placebo-controlled global function and depression improvement: the greater the EPA increase, the less the placebo-controlled Ω3 improvement.

Conclusion: Ω3 supplementation at 2 g/day increases blood levels substantially, more so in smaller children. A possible U-shaped response curve should be explored.

Keywords: mediation; moderation; mood disorders; omega-3 fatty acids; plasma levels; supplementation as treatment.

FIG. 1.

Baseline fatty acid Moderation of response to Ω3 versus Placebo. Lower score is better. (a) Moderation of depression response by baseline alpha-linolenic acid in the full sample (N = 90, p = 0.040). At 1 SD below the sample mean, both group slopes (Ω3: b = −0.8, SE = 0.2; placebo: b = −1.0, SE = 0.1) were significantly different from zero (p < 0.001), but not significantly different from each other; at 1 SD above the mean, although trajectories for Ω3 (b = −1.1, SE = 0.1) and placebo (b = −0.7, SE = 0.2) were again both significantly different from zero (p < 0.001), Ω3 demonstrated a more favorable trajectory relative to placebo (p = 0.031). (b) Marginal moderation of manic symptom response by EPA in the bipolar subgroup (n = 23, p = 0.052); at 1 SD below the subgroup mean, slope of Ω3 group was NS; placebo b = −0.7 (SE = 0.3, p = 0.011), difference in slopes was NS; at 1 SD above the mean, Ω3 b = −1.0, SE = 0.3, p = 0.002, placebo b = −0.5, SE = 0.3, p = 0.085; difference in slopes was NS. EPA, eicosapentaenoic acid.

FIG. 2.

Moderation of clinical response by BMI. Children's Depression Rating Scale (CDRS); lower score is better. On the left, improvement was almost identical for omega-3 and placebo in underweight and typical BMI children. On the right, improvement was significantly better for omega-3 than placebo in the overweight and obese subgroup, who had a lower mg/kg dose. BMI, body mass index.

FIG. 3.

Response on the Children's Global Assessment Scale by mg/kg doses of Ω3 within the supplemented participants. (Although higher mg/kg dose correlated with less improvement, only one supplemented youth declined in global function.)