In a recent publication in BMJ, Ramsden et al conducted a three-arm, parallel-group, randomized, modified double-blind, controlled trial to ascertain whether dietary interventions that increase omega-3 (n-3) fatty acids with and without reduction in omega (n-6) linoleic acid can modify circulating lipid mediators implicated in headache pathogenesis and decrease headache in adults with migraine.

The study involved 182 participants at the University of North Carolina (UNC) (88% female; average age 38 years) with migraine headaches on 5 to 20 days per month (67% met criteria for chronic migraine) who were randomly assigned to one of three diets for 16 weeks. All participants received meal kits that included fish, vegetables, hummus, salads, and breakfast items. Three diets designed with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and linoleic acid altered as controlled variables were used: H3 diet (n = 61)—increase EPA+DHA to 1.5 g/day and maintain linoleic acid at around 7% of energy; H3-L6 diet (n = 61)—increase n-3 EPA+DHA to 1.5 g/day and decrease linoleic acid to ≤1.8% of energy; control diet (n = 60)—maintain EPA+DHA at <150 mg/day and linoleic acid at around 7% of energy.

All participants received foods accounting for two-thirds of daily food energy; they continued usual care and were also given an electronic diary to record how many hours each day they had headache pain. The primary endpoints (Week 16) were the antinociceptive mediator 17-hydroxydocosahexaenoic acid (17-HDHA) in blood and the headache impact test (HIT-6), a six-item questionnaire assessing headache impact on quality of life. The authors noted that both intervention diets increased serum levels of 17-HDHA compared with the control diet, which "supports the biological plausibility" of this type of approach for pain reduction.

Both intervention diets led to improved scores on the HIT-6 compared with the control diet, but the difference was not statistically significant. However, the results indicated that migraine frequency was significantly diminished in both intervention groups. The researchers also discovered that the high–n-3 diet was associated with 1.3 fewer headache hours per day and 2 fewer headache days per month.

The researchers noted that the high–n-3 plus low–n-6 diet was correlated with 1.7 fewer headache hours per day and four fewer headache days per month, indicating additional benefit from lowering dietary n-6. The high–n-3 groups also reported shorter, less-severe headaches compared with the control group. In addition, the authors observed that participants reported fewer days per month with headaches, and some were able to decrease the amount of medication needed for their pain. However, participants did not report a change in quality of life. The researchers concluded that increasing dietary n-3, regardless of a change in n-6, decreases headache frequency and severity and that their findings demonstrate that dietary adjustments can be used to alleviate pain in humans, possibly encouraging investigators to explore additional research.

In an interview, co-first author Daisy Zamora, PhD, assistant professor in the Department of Psychiatry, UNC School of Medicine, stated, "I think this modification in diet could be impactful. The effect we saw for the reduction of headaches is similar to what we see with some medications. The caveat is that even though participants did report fewer headaches, some people did not change their perception of how headaches affected them." Dr. Zamora also indicated that the biochemical hypothesis of how certain fatty acids affect pain applies to a wide variety of chronic pain. She and her colleagues are currently working on a new study to test diet modification in other pain syndromes.

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