In a study published in the journal Advances in Nutrition, the authors suggest that taking >1.5 grams/day of EPA/DHA significantly reduces migraine frequency and severity compared with placebo. ~ Dr. Broussard
High-Dosage Omega-3 Fatty Acids Outperform Existing Pharmacological Options for Migraine Prophylaxis
April 04, 2024
Advances in Nutrition
TAKE-HOME MESSAGE
- This network meta-analysis compared the efficacy and acceptability of various dosages of EPA/DHA with those of guideline-recommended or FDA-approved prophylactic pharmacologic interventions for migraine. Compared with other treatments, high-dosage EPA/DHA supplementation was associated with the highest reduction in migraine frequency as well as severity and showed the most favorable acceptability rates.
- This study provides evidence that EPA/DHA supplementation can be considered as a first-choice treatment for migraine prophylaxis. Large-scale randomized controlled trials are needed to determine the optimal dosing of polyunsaturated fatty acids in this patient population.
Clinical question
How effective and acceptable are various dosages of EPA/DHA compared with current pharmacological interventions for migraine prevention?
Key points
Despite the conclusion of this article, there is still only preliminary evidence of the benefit of supplemental omega-3 fatty acids for migraine. The authors of the review looked at relatively few, mostly small (N~50) omega-3 trials, and concluded that:
Author’s conclusions
“This study provides compelling evidence that high-dosage EPA/DHA supplementation can be considered a first-choice treatment for migraine prophylaxis because this treatment displayed the highest efficacy and highest acceptability of all studied treatments.”
Relevance
Migraine affects more than 40 million Americans, and, while a host of preventive medications exist, studies have shown that long-term compliance can be less than 50%, especially among people with chronic migraine.1,2,3 Even with the introduction of CGRP modulators, which promise better compliance, issues regarding access to this medication continue to demand additional patient-friendly prevention options. Although omega-3 fatty acids have shown potential in the setting of migraine due to their neuro–anti-inflammatory actions, previous trials on supplements have had methodological limitations, which have limited consistent findings.4,5 Currently, we know that an increased intake of omega-3 fatty acids through the diet with a concomitant decrease in omega-6 fatty acids has strong evidence in the prevention of migraine based on the work of NIH researcher Chris Ramsden as published in The BMJ.6
Details of the trial
Setting: A comprehensive network meta-analysis evaluating randomized controlled trials (RCTs) of medications and various dosages of omega-3 fatty acids for migraine prevention. A total of 6616 individuals from 40 RCTs (but only 4 for omega-3 fatty acids, 1 for amitriptyline + omega-3 fatty acids, and 35 for prescription treatment). Participants were predominantly female (78.9%), with a mean age of 35 years, and had episodic or chronic migraine.
In total, 78 articles were considered for full-text review, of which 38 were excluded for various reasons including non-oral treatments and use in acute treatment.
The few omega-3 trials were categorized into low-, medium-, and high-dose EPA/DHA levels:
Preventive drugs evaluated were: Topiramate, valproate, propranolol, timolol, amitriptyline, venlafaxine, lisinopril, frovatriptan, and candesartan.
Treatments: High, medium, and low dosages of EPA/DHA were compared with FDA-approved or guideline-recommended migraine prophylactic medications.
Endpoints: Primary outcomes included changes in migraine frequency and acceptability (dropout rates). Secondary outcomes included response rates, changes in migraine severity, rate of rescue medication usage, and incidence of adverse events.
Limitations: Unfortunately, numerous limitations in this analysis make its stated conclusions not ready for prime time, including:
Incorporation into practice
Omega-3 fatty acids are an intriguing potential for the prevention of migraines. At this point, the evidence is strongest for an increase in dietary omega-3 fatty acids with a concomitant reduction in omega-6 fatty acids, which can be achieved through a reduction in the intake of packaged foods that use omega-6 fatty acid as a preservative as well as a switch to less omega-6–predominant cooking oils, such as extra virgin olive oil. The choice of dietary omega-3 fatty acid should be based on sustainable and low-toxin sources with sites like the Monterey Bay Aquarium’s Seafood Watch to help with the choice.
At this point, supplemental omega-3 fatty acids have relatively preliminary evidence for preventing migraines and need additional evidence to support their use. Meanwhile, the strongest use case for supplemental omega-3 fatty acids is for individuals on other preventive drugs such as amitriptyline and those who may not consume omega-3 fatty acids in their diet and who wish to turn to dietary supplementation. Similar to dietary omega-3 fatty acids, testing sources like USP, NSF, and ConsumerLab should be referenced to confirm the safety testing of the supplement being considered.
Remaining questions: Future supplemental omega-3 fatty acid trials should optimally examine factors including:
References
Abstract
Migraine is a highly prevalent neurologic disorder with prevalence rates ranging from 9% to 18% worldwide. Current pharmacologic prophylactic strategies for migraine have limited efficacy and acceptability, with relatively low response rates of 40% to 50% and limited safety profiles. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are considered promising therapeutic agents for migraine prophylaxis. The aim of this network meta-analysis (NMA) was to compare the efficacy and acceptability of various dosages of EPA/DHA and other current Food and Drug Administration-approved or guideline-recommended prophylactic pharmacologic interventions for migraine. Randomized controlled trials (RCTs) were eligible for inclusion if they enrolled participants with a diagnosis of either episodic or chronic migraine. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed were 1) changes in migraine frequency and 2) acceptability (i.e., dropout for any reason). Secondary outcomes included response rates, changes in migraine severity, changes in the frequency of using rescue medications, and frequency of any adverse events. Forty RCTs were included (N = 6616; mean age = 35.0 y; 78.9% women). Our analysis showed that supplementation with high dosage EPA/DHA yields the highest decrease in migraine frequency [standardized mean difference (SMD): -1.36; 95% confidence interval (CI): -2.32, -0.39 compared with placebo] and the largest decrease in migraine severity (SMD: -2.23; 95% CI: -3.17, -1.30 compared with placebo) in all studied interventions. Furthermore, supplementation with high dosage EPA/DHA showed the most favorable acceptability rates (odds ratio: 1.00; 95% CI: 0.06, 17.41 compared with placebo) of all examined prophylactic treatments. This study provides compelling evidence that high dosage EPA/DHA supplementation can be considered a first-choice treatment of migraine prophylaxis because this treatment displayed the highest efficacy and highest acceptability of all studied treatments. This study was registered in PROSPERO as CRD42022319577.
Journal Abstract