Both frequency and intensity dropped with more EPA and DHA intake

A diet rich in omega-3 (n-3) fatty acids reduced the frequency and intensity of headaches in migraine patients compared with a diet with normal intake of omega-3 and omega-6 (n-6) fatty acids, a randomized trial found.

Adults with chronic and episodic migraine were randomized to one of three diets that varied intake of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and linoleic acid: the H3 diet, which increased EPA and DHA; the H3-L6 diet, which increased EPA and DHA and reduced linoleic acid; or a control diet, which mimicked the average U.S. intake of n-3 and n-6 fatty acids.

“While the benefit of the H3 and H3-L6 diets on quality of life was inconclusive, the reduction in headaches was robust, particularly for the H3-L6 diet,” wrote Christopher Ramsden, MD, of the National Institute on Aging in Baltimore, Maryland, and co-authors in The BMJ.

Omega-3 derivatives have anti-nociceptive and anti-inflammatory effects. Oxylipins derived from omega-6 fatty acids worsen pain and can provoke migraine.

In this trial, the primary clinical endpoint was 1.5 point improvement at 16 weeks on the six-item headache impact test, HIT-6, a patient-reported headache-affected quality of life indicator (range 38-76; higher scores indicate worse quality of life). The H3-L6 and H3 diets reduced mean scores by 1.6 and 1.5, respectively, but were not statistically significant.

The study’s other primary endpoint was the anti-nociceptive mediator 17-hydroxydocosahexaenoic acid (17-HDHA) in blood. The H3-L6 and H3 diets increased circulating 17-HDHA (log ng/mL) compared with the control diet (baseline-adjusted mean difference 0.6, 95% CI 0.2-0.9; 0.7, 95% 0.4-1.1, respectively).

“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 (prostaglandins, calcitonin gene related peptide),” Ramsden and colleagues noted.

Secondary outcomes based on headache diary data showed (P≤0.001 for all):

  • The interventions reduced total headache hours daily by 1.7 for the H3-L6 group and 1.3 for the H-3 group, compared with controls.
  • The interventions reduced moderate-to-severe headache hours daily, by 0.8 for the H3-L6 group and 0.7 for the H3 group, compared with controls.
  • The H3-L6 group had 4 fewer headache days per month compared versus controls and 2 fewer headache days per month versus the H3 group.

“Mean reductions of 1.7 headache hours per day and 4.0 headache days per month in the H3-L6 group versus the control group are comparable to those recently reported for botulinum toxin injections (−2.4 migraine days per month) and monoclonal antibodies targeting calcitonin gene related peptide (−1.8 to −2.1 days per month with a composite headache endpoint),” the researchers pointed out. “These findings suggest that the intervention might be an efficacious adjunct approach for managing headache.”

In an accompanying editorial, Rebecca Burch, MD, of Brigham and Women’s Hospital in Boston, noted that the trial’s results “take us one step closer to a goal long sought by headache patients and those who care for them: a migraine diet backed up by robust clinical trial results.”

“International Headache Society guidelines and regulatory standards specify the use of headache or migraine frequency as the preferred outcome measure for trials of preventive interventions for migraine,” Burch stated. “Interpretation of this study’s findings is therefore complex: the study was negative according to the prespecified primary outcome, but would have been positive if judged by more guideline adherent endpoints.”

Headache frequency and intensity outcomes in the trial “are even more remarkable because roughly two-thirds of the study population met the criteria for chronic migraine (>15 headache days per month) and a little over half met the criteria for drug overuse headache, populations which are typically more refractory to treatment,” she added.

A 2020 review of studies exploring omega-3 fatty acid supplementation for migraine included 10 studies from January 2000 until February 2020, and reported variable methodology and moderate evidence for a therapeutic role of omega-3 fatty acids as migraine therapy, she noted.

In the present study, 182 participants were randomized to H3-L6 (n=61), H3 (n=61), or control (n=60) diets and included in intention-to-treat analysis. The cohort had a mean age of 38.3 and 88% were women. Participants had a baseline mean HIT-6 score of 62.7, indicating severe effect of headaches on quality of life. Chronic migraine was present in 67%, and 56% of participants met criteria for acute drug overuse.

On average, participants had 16.3 headache days a month at baseline, with a mean 5.4 headache hours per day. Theytook an average of 4.3 headache-related drugs per person.

The choice to use the HIT-6 as a primary outcome was a limitation of the study, Ramsden and co-authors said. “The International Headache Society recommends the use of headache diary data for primary endpoints when assessing efficacy in chronic migraine populations,” they wrote. “Unfortunately, we were not aware of these guidelines when the study was designed.”

The trial also studied mainly women under age 40; results may not apply to men, or to older or younger people.

  1. A diet rich in omega-3 (n-3) fatty acids reduced the frequency and intensity of headaches in migraine patients compared with a diet with normal intake of omega-3 and omega-6 (n-6) fatty acids, a randomized trial found.

  2. An omega-3 diet also altered blood levels of bioactive oxylipins implicated in headache pathogenesis.

Paul Smyth, MD, Contributing Writer, BreakingMED™

This project was funded by the National Center for Complementary and Integrative Health (NCCIH), National Institutes of Health (NIH; main funding source). Additional support was provided by the intramural programs of the National Institute on Aging (NIA) and the National Institute on Alcohol Abuse and Alcoholism, NCCIH T32 Research Fellowship Program, the Mayday Fund, and the UNC Nutrition Obesity Research Center, CHAI Core, and the National Institute of Diabetes and Digestive and Kidney Diseases.

The NIA has claimed intellectual property related to stable analogs of oxidized lipid mediators with Ramsden and another co-author named as inventors.

Burch is on the board of directors of the American Headache Society and the Headache Cooperative of New England, and receives a stipend for work as an associate editor for the journal Neurology.

Cat ID: 35

Topic ID: 82,35,730,35,192,925