BACKGROUND AND PURPOSE:

• n-3 and n-6 fatty acids (obtained through diet) are implicated in migraine pathogenesis
  • n-6 fatty acid derivatives (oxylipins) have pain-promoting properties, while n-3 fatty acid derivatives have pain-reducing properties
  • Previous pilot studies suggest reducing n-6 fatty acid intake, while increasing n-3 fatty acids, may result in fewer headache days per month
• Ramsden et al. (BMJ, 2021) assessed whether fatty acid dietary interventions decrease headache in adults with migraine

METHODS:

• Three arm, parallel group, randomized, modified double blind, controlled trial
• Participants
  • Individuals with migraines 5 to 20 days per month
  • With or without aura
  • Minimum 2 years
• Interventions
  • H3 diet
    • Increase n-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to 1.5 g/day and maintain n-6 linoleic acid at around 7% of energy
  • H3-L6 diet
    • Increase n-3 EPA+DHA to 1.5 g/day and decrease n-6 linoleic acid to ≤1.8% of energy
  • Control diet
    • Maintain n-3 EPA+DHA at <150 mg/day and n-6 linoleic acid at around 7% of energy
• Study design
  • All participants received foods accounting for two-thirds of daily food energy | Otherwise, continued usual care
  • Headache frequencies were assessed daily with an electronic diary
  • Diets detailed in supplementary material in the study
    • N-3 increased using high fat fish diet
    • N-6 controls given blend of corn oil and extra virgin olive oil and a blend of butter and corn oil | N-6 linoleic acid reduced diet consisted of a blend of macadamia nut oil and extra virgin olive oil and regular butter
  • Analysis was by intention to treat
• Primary outcome (at 16 weeks)
  • Antinociceptive mediator 17-hydroxydocosahexaenoic acid (17-HDHA) blood levels
  • Headache impact test (HIT-6) | 6 item questionnaire assessing headache impact on quality of life

RESULTS:

• H3: 61 participants | H3-L6: 61 participants | control: 60 participants
  • 88% women; mean age 38 years
  • Criteria met for chronic migraine: 67% of participants
• The H3-L6 and H3 diets increased circulating 17-HDHA (log ng/mL) compared to the control diet
  • H3-L6: baseline-adjusted mean difference 0.6 (95% CI, 0.2 to 0.9)
  • H3: baseline-adjusted mean difference 0.7 (95% CI, 0.4 to 1.1)
• There was an improvement in HIT-6 scores in the H3-L6 and H3 groups, but this was not statistically significant
  • H3-L6: baseline-adjusted MD −1.6 (95% CI, −4.2 to 1.0)
  • H3: baseline-adjusted MD −1.5 (95% CI, −4.2 to 1.2)
• Compared with the control diet, the H3-L6 and H3 diets decreased
  • Total headache hours per day
    • H3-L6: baseline-adjusted MD −1.7 (95% CI, −2.5 to −0.9)
    • H3: baseline-adjusted MD −1.3 (95% CI, −2.1 to −0.5)
  • Moderate to severe headache hours per day
    • H3-L6: baseline-adjusted MD −0.8 (95% CI, −1.2 to −0.4)
    • H3: baseline-adjusted MD −0.7 (95% CI, −1.1 to −0.3)
  • Headache days per month
    • H3-L6: baseline-adjusted MD −4.0 (95% CI, −5.2 to −2.7)
    • H3: baseline-adjusted MD −2.0 (95% CI, −3.3 to −0.7)
• The H3-L6 diet decreased headache days per month more than the H3 diet
  • Baseline-adjusted MD −2.0 (95% CI, −3.2 to −0.8)

Nociceptive Markers

• The H3-L6 and H3 diets altered n-3 and n-6 fatty acids and several of their nociceptive oxylipin derivatives in plasma, serum, erythrocytes or immune cells
• H3-L6 and H3 diets did not alter classic headache mediators calcitonin gene related peptide and prostaglandin E2

CONCLUSION:

• High omega 3 and low omega 6 fatty acid diet ( linoleic acid) decreased the number of migraine headache hours per day and the number of headache days per month
  • However, patient-reported quality of life was not improved
• An editorial provides a more optimistic viewpoint and states

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

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

These results support recommending a high omega 3 diet to patients in clinical practice 

Learn More – Primary Sources:

Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial

Editorial: Dietary omega 3 fatty acids for migraine

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