Targeted manipulation of dietary omega-3 and omega-6 fatty acids has previously been shown to decrease nontraumatic headaches in controlled trials. This study assessed the effects of a diet high in omega-3 fatty acids and low in omega-6 linoleic acid (H3L6 diet) on headache frequency and severity, headache impact, and plasma nociceptive mediators in a persistent post-traumatic headache (pPTH) population. One hundred and twenty-two participants with pPTH were randomized 1:1 to 12 weeks of either the H3L6 (n = 62) or a control (n = 60) diet. A priori primary end-points were the plasma levels of the antinociceptive docosahexaenoic acid (DHA) derivative 17-hydroxy-DHA and the Headache Impact Test (HIT-6) score. Secondary end-points included headache days/month and average daily headache pain intensity (0–10 scale). Statistical analyses followed intention-to-treat principles and were adjusted for baseline values. Relative to the control group, the H3L6 group significantly reduced headache days/month (−2.1, 95% confidence interval [CI]: −3.5 to −0.8, p = 0.002) and average headache intensity (−0.9, 95% CI: −1.2 to −0.5, p < 0.001) and increased circulating 17-hydroxy-DHA (nanograms/milliliter; difference 0.07, 95% CI: 0.02–0.11, p = 0.003), although it did not significantly improve HIT-6 scores (−1.6, 95% CI: −4.0 to 0.8, p = 0.18). In conclusion, the H3L6 diet reduced headache pain and increased antinociceptive mediators, supporting its potential as an adjunct nonpharmacological pPTH therapy.
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