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

Abstract

ObjectiveTo determine whether dietary interventions that increase n-3 fatty acids with and without reduction in n-6 linoleic acid can alter circulating lipid mediators implicated in headache pathogenesis, and decrease headache in adults with migraine.DesignThree arm, parallel group, randomized, modified double blind, controlled trial.SettingAmbulatory, academic medical center in the United States over 16 weeks.Participants182 participants (88% women, mean age 38 years) with migraines on 5-20 days per month (67% met criteria for chronic migraine).InterventionsThree diets designed with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and linoleic acid altered as controlled variables: 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 and continued usual care.Main outcome measuresThe 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. Headache frequency was assessed daily with an electronic diary.ResultsIn intention-to-treat analyses (n=182), 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% confidence interval 0.2 to 0.9; 0.7, 0.4 to 1.1, respectively). The observed improvement in HIT-6 scores in the H3-L6 and H3 groups was not statistically significant (−1.6, −4.2 to 1.0, and −1.5, −4.2 to 1.2, respectively). Compared with the control diet, the H3-L6 and H3 diets decreased total headache hours per day (−1.7, −2.5 to −0.9, and −1.3, −2.1 to −0.5, respectively), moderate to severe headache hours per day (−0.8, −1.2 to −0.4, and −0.7, −1.1 to −0.3, respectively), and headache days per month (−4.0, −5.2 to −2.7, and −2.0, −3.3 to −0.7, respectively). The H3-L6 diet decreased headache days per month more than the H3 diet (−2.0, −3.2 to −0.8), suggesting additional benefit from lowering dietary linoleic acid. 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, but did not alter classic headache mediators calcitonin gene related peptide and prostaglandin E2.ConclusionsThe H3-L6 and H3 interventions altered bioactive mediators implicated in headache pathogenesis and decreased frequency and severity of headaches, but did not significantly improve quality of life.Trial registrationClinicalTrials.gov NCT02012790

Leukocyte inflammatory phenotype and function in migraine patients compared with matched non-migraine volunteers: A pilot study

“…For example, since CD16 + monocytes express CXCR7 on cell surface; using CXCR7 antagonist might help reduce the non-classical monocytes transmigration across the BBB [46]. This study also provides additional evidence for the use of targeted alterations in dietary linolenic acid and n-3 EPA + DHA in migraineurs [28,29].…”

“…Broad expression of CD36 on different cells suggests this multi-functional receptor could be involved in a broad spectrum of diseases [23,[50][51][52]. The effects of high dietary omega-3 and low omega-6 targeted alteration to treat migraine in the parent randomized clinical trial suggested that the binding of long chain fatty acid to CD36 might play vital roles in chronic headache [28] and possibly for migraine [29]. Indeed, predominant monocytes and platelets gene up-regulations are characteristic for migraine [10].…”

“…Coburn et al demonstrated that long chain fatty acid uptake and utilization have been defective in CD36 knockout mice [27]. Our team reported that a dietary intervention with increased omega-3 fatty acids helped to reduce headache pain [28,29], and it has been known that omega-3 could induce the CD36 mRNA expression in an animal model [30,31]. Because of its essential role in lipid metabolism, CD36 MFI expression levels in migraineurs should be studied further.…”

Changes in Plasma Lipid Levels Following Cortical Spreading Depolarization in a Transgenic Mouse Model of Familial Hemiplegic Migraine

“…Another study in which migraine GWAS data were investigated with respect to genetically associated blood metabolic traits, DHA and DPA were identified as fatty acids that were genetically associated with a higher risk for migraine [ 56 ]. Of note, lower dietary intake of DHA and EPA are associated with a higher attack frequency in migraine patients [ 18 ]; vice versa, increasing dietary intake of EPA and DHA in chronic and episodic migraine patients resulted in a reduction in headache frequency and severity [ 57 ] and physical pain [ 58 ], underscoring the involvement of these lipids in migraine pathophysiology. Our findings suggest that DPAn-3, DHA, ALA, and EPA might have potential as biomarkers of an anti-inflammatory response (when levels are elevated), or a neuroinflammatory response (in case of an absence of elevated levels) in the context of an aura and hemiplegic migraine.…”

The Inverse Correlation of Isoflavone Dietary Intake and Headache in Peri- and Post-Menopausal Women

“…Studies have shown that specific diets, such as a low-calorie diet, carbohydrate-restricted diet, and weight-loss diets for obese patients, can improve headaches [ 5 ]. In a randomized controlled trial of 182 patients, high n-3 fatty acid diets ameliorated the frequency and severity of headache compared to the control diet [ 6 ].…”