July 16, 2021
There has been much interest in omega-3 Polyunsaturated fatty acids (PUFAs) as treatments for ADHD. Humans are unable to synthesize the omega-3 PUFA alpha-linolenic acid (ALA)and the omega-6 PUFA linoleic acid (LA), and must therefore obtain these through food, which is why they are known as essential fatty acids. Because cells in the brain need omega-3 PUFAs, they have been studied as a treatment for ADHD by many researchers. Several meta-analyses are available.
A 2014 meta-analysis by Elizabeth Haw key and Joel Niggcombined nine studies involving 586 participants. It found mean blood levels of omega-3 PUFAs in persons with ADHD to be lower than in controls. The standardized mean difference (SMD) effect size was medium (SMD = .42, 95% CI = .26-.59), with less than a one in one thousand probability of such a result being obtained by chance alone. Adjusting for publication bias reduced the effect size slightly to .36 with a 95% CI of .21-.51, in the small-to-medium range. The authors then examined whether omega-3 supplementation could help alleviate ADHD symptoms. Combining 16 studies with 1,408 participants, they found improvements, but this time with a small effect size (SMD = .26, 95% CI =.15-.37), again with less than a one in a thousand probability of such a result being observed by chance. Adjusting for publication bias reduced the effect size to .16 with a 95% CI of .03-.28. For comparison, the SMD for stimulants is about 0.9.
Another meta-analysis conducted in the same year by BasantPuri and Julian Martins combined 18 PUFA supplementation studies involving1,640 participants. They also found a small effect size for reduced ADHD symptoms (SMD = .19, 95% CI = .09-.30, p<.001). Adjusting for publication bias further reduced the effect size to a paltry and statistically insignificant level (SMD = .12, 95% CI = -.01-.25). It should be noted that while16 of the studies involved omega-3 supplementation, two involved only omega-6supplementation. Yet the results for the latter did not differ noticeably from the former. When the authors limited the analysis to the 11 studies specifically including both the omega-6GLAand the omega-3 EPA, the effect size for reducing inattention symptoms was a bit higher(SMD = .31, 95% CI = .16-.46, p<.0001). But the results were not significantly different from those for the studies without the GLA+ALA combination (.012; 95% CI: .161-.137; p=.875). Publication bias was not addressed, and the hunt for a highly specific subset with positive results may have produced a false-positive finding. The authors conceded, "Weaknesses of this study include the following: although the pooled effect was statistically significant, only two studies showed a significant effect by themselves; the funnel plot showed evidence of publication bias; there was evidence of reporting bias; few studies were formally registered; study methodological quality was variable, and the placebo used across studies varied."
A 2016 meta-analysis by Laura Lachance et al. tried looking for differences in the ratio of omega-6 to omega-3 PUFAs, and more specifically, AA to EPA, in the blood of persons with ADHD versus normally developing persons. Pooling five studies with485 participants, it found the omega-6 to omega-3 ratio to be significantly higher in persons with ADHD, and pooling three studies with 279 participants, it likewise found the AA to EPA ratio significantly higher.
A 2017 meta-analysis by Jane Pei-Chen Chang et al. Reexamined comparative levels of omega-3 PUFAs in ADHD patients versus normally developing controls. Combining six studies with 396 participants, ADHD patients had lower levels in blood and mouth tissue, with a medium effect size (SMD =.38) that was not statistically significant (p=.14). Omega-6 levels were indistinguishable (SMD =.03) in the two groups. AA (SMD = .18, p=.33) and EPA (SMD = .25, p=.17) levels were slightly lower, but once again statistically not significant. DHA levels were lower as well, this time with a medium effect size (SMD = .56), but at the outer margin of significance (p=.05). Only by dropping one study were the authors able to claim significance for EPA, AA, and omega-3 differences.
Chang et al. also performed a meta-analysis of supplementation studies. Combining seven studies with 534 participants, they found a small to medium reduction in ADHD symptoms with omega-3 supplementation(SMD = .38, 95% CI = .2-.56, p<.0001). Corrections for publication bias were not reported. The authors also reported large reductions in both omission errors (SMD = 1.09, 95% CI = .43-.1.75, p<.001) and commission errors (SMD =2.14, 95% CI = 1.24-3.03, p<.00001) on a neuropsychological test of attention. But the former involved only 3 studies with 214 participants, and the latter only two studies with 85 participants.
Also in 2017, Pelsser et al. published a systematic review that identified only two meta-analyses of double-blind, placebo-controlled trials of PUFA supplementation. One of those, a 2012meta-analysis by Gillies et al., found no statistically significant declines in either parent-rated ADHD symptoms (five trials, 413 participants, SMD = -.17,95% CI = -.38-.03) or teacher-rated ADHD symptoms (four trials, 324participants, SMD = .05, 95% CI = -.18-.27). The other, a 2013 meta-analysis by Sonuga-Barke et al., found only a slight and barely statistically significant reduction in symptoms (11 trials, 827 participants, SMD = .16, 95% CI =.01-.31). Pelsser et al. concluded, "Considering the small average ESs [effect sizes] PUFA supplementation is unlikely to provide a tangible contribution to ADHD treatment."
Putting all of this together, there are indications that individuals with ADHD may have lower levels of omega-3 PUFAs, and that omega-3 supplementation may slightly reduce symptoms of ADHD, but the evidence remains inconclusive, with at best small effect sizes. It is possible, but not yet demonstrated, that omega-3 PUFAs might produce good outcomes in a small subset of patients.
Jane Pei-Chen Chang, Kuan-Pin Su, Valeria Mondelli, and carmine M Pariante, "Omega-3 Polyunsaturated Fatty Acids in Youths with Attention Deficit Hyperactivity Disorder: a Systematic Review and Meta-Analysis of Clinical Trials and Biological Studies," Neuropsychopharmacology (2017),43(3): 534-545.
Donna Gillies, John KH Sinn, Sagar S Lad, Matthew J Leach, MelissaJ Ross, "Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents," Cochrane Database of Systematic Reviews (2012), DOI:10.1002/14651858.CD007986.pub2.
Elizabeth Hawkey and Joel T. Negg, "Omega-3 fatty acid and ADHD: Blood level analysis and meta-analytic extension of supplementation trials," Clinical Psychology Review(2014), 34(6), 496-505.
Laura LaChance, Kwame McKenzie, Valerie H. Taylor, and Simone N. Vigod, "Omega-6 to Omega-3 Fatty Acid Ratio in Patients with ADHD: AMeta-Analysis," Journal of the Canadian Academy of Child and AdolescentPsychiatry (2016), 25(2), 87-96.
Lidy M. Pelsser, Klaas Frankena, Jan Toorman, Rob Rodrigues Pereira, "Diet and ADHD, Reviewing the Evidence: A Systematic Review of meta-Analyses of Double-Blind Placebo-Controlled Trials Evaluating the Efficacy of Diet Interventions on the Behavior of Children with ADHD," PLOS ONE (January 25, 2017), 1-25.
Basant K. Puri and Julian G. Martins, "Which polyunsaturated fatty acids are active in children with attention-deficit hyperactivity disorder receiving PUFA supplementation? A fatty acid validated meta-regression analysis of randomized controlled trials," Prostaglandins, Leukotrienes and Essential Fatty Acids (2014), 90, 179-189.
Edmund J.S. Sonuga-Barke et al., "NonpharmacologicalInterventions for ADHD: Systematic Review and Meta-Analyses of RandomizedControlled Trials of Dietary and Psychological Treatments," American Journal of Psychiatry (2013),170:275-289.