Omega-3-enriched diet cuts headache days

Consuming a diet enriched with the EPA and DHA* omega-3 fatty acids leads to less frequent and milder headache in patients with migraine, according to a double-blind, randomized study.

Participants in the three-arm, double-blind, parallel-group randomized trial were 182 adults (mean age 38 years, 88 percent women) who experienced migraines for 5–20 days per month (67 percent qualified as chronic migraine). [BMJ 2021;374:n1448]

They were randomized to one of the three diet interventions with varying proportions of EPA, DHA, and linoleic acid: (i) H3 diet (n=61), with EPA+DHA increased to 1.5 g/day and linoleic acid maintained at ~7 percent of energy intake; (ii) H3-L6 diet (n=61), comprising increased n-3 EPA+DHA levels to 1.5 g/day while linoleic acid was decreased to ≤1.8 percent of energy levels; or control diet (n=60), which maintained EPA+DHA at <150 mg/day and linoleic acid at 7 percent of energy intake.

Both the H3 and the H3-L6 groups experienced shortened duration of headache by 1.3 and 1.7 hours per day, respectively, compared with the control group. The duration of moderate-to-severe headache was also shorter by 0.7 to 0.8 hours a day, respectively, relative to control diet.

In particular, participants on the H3-L6 diet had less frequent headache per month than those on the H3 diet (headache days per month, -2.0, 95 confidence interval [CI], -3.2 to -0.8), indicating that participants derived more benefits from lowering dietary linoleic acid.

“n-3 and n-6 fatty acids are major components of tissues implicated in migraine pathogenesis and oxylipin derivatives have potent antinociceptive (pain-reducing) properties,” the researchers explained on the potential mechanisms mediating the benefits of the EPA- and DHA-enriched diets.

Consistent with the reduced frequency and duration of headache, both the H3 and the H3-L6 diets led to lower levels of pain-related lipids compared with the control diet, as indicated by increased levels of circulating 17-HDHA (baseline-adjusted mean difference 0.7 and 0.6 log ng/mL, respectively), a known precursor of antinociceptive oxylipins. 

“Both active diets altered blood levels of bioactive oxylipins implicated in headache pathogenesis in a manner consistent with a lowered nociceptive state, and did not alter classic mediators of headache pain [such as] prostaglandins and calcitonin gene-related peptide [CGRP],” the researchers explained.

While both diets led to lower scores on the headache impact test (HIT-6**), the difference did not reach statistical significance compared with the control diet.

“Although this is statistically a negative study with regard to the primary clinical endpoint, there are several factors that make the overall findings clinically meaningful,” wrote Dr Rebecca Burch from Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, US, in a linked editorial. [BMJ 2021;374:n1535]

The current findings, in particular, were notable for the extent of response. Given that the reductions in headache frequency were reported at magnitude of 2–2.5 fewer headache days per month with anti-CGRP monoclonal antibodies vs placebo, Burch stated that the current trial “suggests that a dietary intervention can be comparable or better. Dietary interventions combined with pharmacological treatments might have an additive benefit.”

*EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid

**a 6-item questionnaire assessing headache impact on quality of life