High Dosage Omega-3 Fatty Acids Outperform Existing Pharmacological Options for Migraine Prophylaxis: A Network Meta-Analysis

Ping-Tao Tseng¹, Bing-Yan Zeng², Jiann-Jy Chen³, Chun-Hsien Kuo⁴, Bing-Syuan Zeng⁵, John S Kuo⁶, Yu-Shian Cheng⁷, Cheuk-Kwan Sun⁸, Yi-Cheng Wu⁹, Yu-Kang Tu¹⁰, Brendon Stubbs¹¹, Andre F Carvalho¹², Chih-Sung Liang¹³, Tien-Yu Chen¹⁴, Chih-Wei Hsu¹⁵, Mein-Woei Suen¹⁶, Chun-Pai Yang¹⁷, Shih-Pin Hsu¹⁸, Yen-Wen Chen¹⁹, Yow-Ling Shiue²⁰, Chao-Ming Hung²¹, Kuan-Pin Su²², Pao-Yen Lin²³

Affiliations

¹ Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Psychology, Collage of Medical and Health Science, Taichung, Asia University, Taiwan; Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung City, Taiwan; Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung City, Taiwan.
² Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Internal Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan.
³ Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung City, Taiwan; Department of Otorhinolaryngology, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan.
⁴ Department of Psychology, Collage of Medical and Health Science, Taichung, Asia University, Taiwan.
⁵ Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan.
⁶ Neuroscience and Brain Disease Center and Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
⁷ Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Psychiatry, Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Taiwan.
⁸ Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; School of Medicine for International Students, College of Medicine, I-Shou University Kaohsiung, Taiwan.
⁹ Department of Sports Medicine, Landseed International Hospital, Taoyuan, Taiwan.
¹⁰ Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
¹¹ Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, United Kingdom; Positive Ageing Research Institute (PARI), Faculty of Health, Social Care Medicine and Education, Anglia Ruskin University, Chelmsford, United Kingdom.
¹² Innovation in Mental and Physical Health and Clinical Treatment (IMPACT) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia.
¹³ Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, Taipei, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
¹⁴ Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan; Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
¹⁵ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
¹⁶ Department of Psychology, Collage of Medical and Health Science, Taichung, Asia University, Taiwan; Gender Equality Education and Research Center, Asia University, Taichung, Taiwan; Department of Medical Research, Asia University Hospital, Asia University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
¹⁷ Department of Neurology, Kuang Tien General Hospital, Taichung, Taiwan; Department of Nutrition, Hungkuang University, Taichung, Taiwan.
¹⁸ Department of Neurology, E-Da hospital, I-Shou University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
¹⁹ Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung City, Taiwan.
²⁰ Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung City, Taiwan. Electronic address: shirley@imst.nsysu.edu.tw.
²¹ School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan; Division of General Surgery, Department of Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan. Electronic address: ed100647@edah.org.tw.
²² Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan; An-Nan Hospital, China Medical University, Tainan, Taiwan. Electronic address: cobol@cmu.edu.tw.
²³ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital. Electronic address: paoyenlin@gmail.com.

PMID: 38110000
PMCID: PMC10808921
DOI: 10.1016/j.advnut.2023.100163

Review

High Dosage Omega-3 Fatty Acids Outperform Existing Pharmacological Options for Migraine Prophylaxis: A Network Meta-Analysis

Ping-Tao Tseng et al. Adv Nutr. 2024 Feb.

. 2024 Feb;15(2):100163.

doi: 10.1016/j.advnut.2023.100163. Epub 2023 Dec 16.

Authors

Affiliations

¹ Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Psychology, Collage of Medical and Health Science, Taichung, Asia University, Taiwan; Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung City, Taiwan; Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung City, Taiwan.
² Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Internal Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan.
³ Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung City, Taiwan; Department of Otorhinolaryngology, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan.
⁴ Department of Psychology, Collage of Medical and Health Science, Taichung, Asia University, Taiwan.
⁵ Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan.
⁶ Neuroscience and Brain Disease Center and Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
⁷ Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Psychiatry, Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Taiwan.
⁸ Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; School of Medicine for International Students, College of Medicine, I-Shou University Kaohsiung, Taiwan.
⁹ Department of Sports Medicine, Landseed International Hospital, Taoyuan, Taiwan.
¹⁰ Institute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
¹¹ Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, United Kingdom; Positive Ageing Research Institute (PARI), Faculty of Health, Social Care Medicine and Education, Anglia Ruskin University, Chelmsford, United Kingdom.
¹² Innovation in Mental and Physical Health and Clinical Treatment (IMPACT) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia.
¹³ Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, Taipei, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
¹⁴ Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan; Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
¹⁵ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
¹⁶ Department of Psychology, Collage of Medical and Health Science, Taichung, Asia University, Taiwan; Gender Equality Education and Research Center, Asia University, Taichung, Taiwan; Department of Medical Research, Asia University Hospital, Asia University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
¹⁷ Department of Neurology, Kuang Tien General Hospital, Taichung, Taiwan; Department of Nutrition, Hungkuang University, Taichung, Taiwan.
¹⁸ Department of Neurology, E-Da hospital, I-Shou University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
¹⁹ Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung City, Taiwan.
²⁰ Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung City, Taiwan. Electronic address: shirley@imst.nsysu.edu.tw.
²¹ School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan; Division of General Surgery, Department of Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan. Electronic address: ed100647@edah.org.tw.
²² Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan; An-Nan Hospital, China Medical University, Tainan, Taiwan. Electronic address: cobol@cmu.edu.tw.
²³ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital. Electronic address: paoyenlin@gmail.com.

PMID: 38110000
PMCID: PMC10808921
DOI: 10.1016/j.advnut.2023.100163

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.

Keywords: DHA; EPA; migraine; network meta-analysis; polyunsaturated fatty acid; prevention.

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Figures

**FIGURE 1**
Flowchart of the current network meta-analysis.

**FIGURE 2**
Network structure of the primary outcomes: (A) changes in migraine frequency and (B) acceptability in dropout rate. The lines between nodes represent direct comparisons in various trials, and the size of each circle is proportional to the size of the population involved in each specific treatment. The thickness of the lines is proportional to the number of trials connected to the network. Ami, amitriptyline; AmLowPUFA, low dosage n-3 PUFA + amitriptyline; Can, candesartan; Cyc, cyclandelate; HighPUFA, high dosage n-3 PUFA; Lam, lamotrigine; Lis, lisinopril; Max, Maxepa (ω-3 polyunsaturated fatty acids, eicosapentaenoic acid/docosahexaenoic acid: 180 mg/120 mg × 6 pills); MedPUFA, medium dosage n-3 PUFA; Nor, nortriptyline; Pla, Placebo; Pro, propranolol; PUFA, polyunsaturated fatty acid; ToN, topiramate + nortriptyline; Top, topiramate; TPr, topiramate + propranolol; Val, valproate; VaLowPUFA, low dosage n-3 PUFA + valproate; Ven, venlafaxine

**FIGURE 3**
Forest plot of the primary outcomes with reference to placebo: (A) changes in migraine frequency and (B) acceptability in dropout rate. Specific treatments were associated with (A) better improvement in migraine frequency than the placebo if the standardized mean difference was <0 or (B) better acceptability in dropout rate than the placebo if the odds ratio was < 1. Ami, amitriptyline; AmLowPUFA, low dosage n-3 PUFA + amitriptyline; Can, candesartan; Cyc, cyclandelate; HighPUFA, high dosage n-3 PUFA; Lam, lamotrigine; Lis, lisinopril; Max, Maxepa (ω-3 polyunsaturated fatty acids, eicosapentaenoic acid/docosahexaenoic acid: 180 mg/120 mg × 6 pills); MedPUFA, medium dosage n-3 PUFA; Nor, nortriptyline; Pla, Placebo; Pro, propranolol; PUFA, polyunsaturated fatty acid; ToN, topiramate + nortriptyline; Top, topiramate; TPr, topiramate + propranolol; Val, valproate; VaLowPUFA, low dosage n-3 PUFA + valproate; Ven, venlafaxine.

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References

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High Dosage Omega-3 Fatty Acids Outperform Existing Pharmacological Options for Migraine Prophylaxis: A Network Meta-Analysis

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High Dosage Omega-3 Fatty Acids Outperform Existing Pharmacological Options for Migraine Prophylaxis: A Network Meta-Analysis

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