Summary
Migraines severely impact one’s ability to function and can cause a decrease in quality of life. Common migraine symptoms include, but are not limited to: intense headaches, feelings of nausea and extreme sensitivity to sound and light. Current pharmacological treatment options can have intense side effects, limited efficacy and may not be suitable for everyone. Research has shown that omega-3 fatty acids EPA and DHA offer protection against prevalence, duration and severity of migraines in people suffering from this condition.
 
Introduction
Worldwide, 1 in 7 people experience at least one migraine episode per year, often causing severe pain and disablement. Common symptoms include headaches, nausea, vomiting and sensitivity to light and sound. Around one-third of migraines are preceded by an aura. This is a term for a signalling malfunction in the brain that results in disturbing sensory perceptions such as light flashes or a tingling sensation. Migraine symptoms can be so intense that they can severely disable a persons day-to-day functioning during an episode, which can last for days. Though pharmacological treatment options focused on symptom reduction or episode prevention (such as amitriptyline or non-steroidal anti-inflammatory drugs) are available, no cure currently exists. Furthermore, pharmacological treatment is often coupled with side effects and may not always be suitable for certain individuals, for example those suffering from heart or liver conditions. This emphasizes the need for other approaches to decrease the occurrence and burden of migraines for people suffering from this condition.

There are three main theories regarding the driving factor that causes migraines: the neuroinflammation, vasodilation, and trigemino-vascular theory. The neuroinflammation theory states that migraines are caused by inflammation in the brain, which is often coupled with widening of blood vessels (vasodilatation). Accordingly, non-steroidal anti-inflammatory drugs are commonly given for treatment of migraines. The vasodilatation theory explains migraine as a consequence of blood vessels in the brain widening. However various studies show conflicting results regarding the occurrence, severity and location of vasodilatation in the brains of migraine patients during an episode. According to the trigemino-vascular theory, a signalling hub that normally relays sensory input from our body to the brain becomes overactivated in migraines. This then results in sensation of pain and increased sensitivity to sensory input, such as sound, smell and light. It is likely that a combination of the factors mentioned above contribute to migraines, which may present themselves differently per individual.

Crucially, all of these proposed factors are relevant in the context of omega-3 fatty acids. Next to the well-known anti-inflammatory properties of omega-3 fatty acids and their metabolites, these compounds can have properties that inhibit the sensation of pain and counter vasodilatation as well. This has sparked interest in the therapeutic potential of omega-3 fatty acids in migraine, which has been intensively studied in clinical trials. 
 
Research findings
Soares and colleagues set out to investigate the effect of dietary levels of omega 3 fatty acids EPA and DHA in migraine patients receiving medicinal treatment for prevention of migraine episodes (Soares et al. 2018). For a period of 60 days, 27 migraine patients (men and women) received 800mg EPA and 700mg DHA per day in combination with amitriptyline, a medicine aimed at prevention of migraine episodes. The control group received a placebo (starch) during the same period. After 60 days, the effects were assessed by a second researcher. It was found that 66% of patients in the group taking omega-3 supplements had a reduction of more than 80% fewer days with headache symptoms per month. This percentage was significantly higher than the control group, where 33% had a reduction of more than 80% fewer days with headache symptoms per month. On basis of these results, the authors concluded that supplementation with omega-3 fatty acids can offer help in reducing the number of days per month with migraine symptoms.

Ramsden and collaborators set out to investigate the effects of dietary intake of omega-3 and omega-6 fatty acids on migraine (Ramsden et al. 2021). They set up a clinical trial where people suffering from migraines were given diets with controlled amounts of omega-3 fatty acids DHA + EPA and omega-6 fatty acid LA. Linoleic acid (LA) is commonly found in vegetable  oils and makes up for around 7% of dietary energy intake in a typical western diet, which is also characterized by insufficient levels of omega-3 fatty acids. By controlling the amount of dietary omega-3 and omega-6 fatty acids, the researchers of this study aimed to change the previously mentioned proposed driving factors of migraine in participants. The 182 study participants with a mean age of 38 years (160 women, 22 men) suffered from migraine for 5-20 days per month and were evenly divided into three groups. Participants were allowed to continue using medicine for prevention or treatment of migraines; around 60% of participants took preventative medicine. Each group received their controlled diet for a period of 16 weeks, after which the effects were assessed. Group 1 (61 individuals) received a diet with 1.5g of DHA + EPA and 7% of dietary energy from LA. Group 2 (61 individuals) received 1.5g of DHA + EPA per day and ≤1.8% of dietary energy from LA. Group 3 (60 individuals, control group) received less than 0.15g DHA + EPA per day and 7% of dietary energy from LA, typical of a western diet.
Compared with the control group, group 1 and 2 reported a decrease in moderate to severe headache hours, and a decrease in total headache hours per day and month. Furthermore, group 2 (enhanced omega-3 and decreased omega-6 dietary intake) had a greater decrease in headache days per month than group 1 (enhanced omega-3 and unchanged omega-6 dietary intake). Crucially, group 2 showed a decrease in use of acute headache related drugs compared to the control group. In addition, both group 1 and 2 showed a decrease in use of non-steroidal anti-inflammatory drugs and aspirin compared to the control group. These findings indicate that supplementation with DHA + EPA may be an effective way to decrease the frequency and severity of episodes for migraine patients. Reducing the dietary intake of omega-6 fatty acids in combination with increasing the dietary intake of omega-3 fatty acids enhances these effects. Overall, these results put forward dietary intake of omega-3 fatty acids DHA and EPA as effective ways to reduce headache duration and occurrence in adults suffering from migraine.

In a large meta-analysis of randomized controlled trials, Tseng and colleagues compared the effects of EPA & DHA supplementation to preventative medicine in the treatment of migraine (Tseng et al. 2024). They analysed grouped data from 40 randomized controlled trials with a total of 6616 adult chronic or episodic migraine patients (men and women) with a mean age of 35. In supplementation trials, EPA + DHA was given in various concentrations in order to investigate their effect on migraine frequency, severity, adverse effects. This was then compared with randomized controlled trials where the efficacy of preventative medicine for migraines was tested, such as amitriptyline, topiramate or valproate. The network meta-analysis showed that of all analysed treatments, supplementation with high dosage of EPA + DHA resulted in the highest decrease of migraine frequency and severity compared to placebo treatment. Moreover, the supplementation with EPA + DHA had the highest acceptability rate of all analysed treatments, meaning that this preventative treatment was the best tolerated amongst participants.
 
Conclusion
The studies described above have shown that omega-3 fatty acids EPA and DHA offer protection against severity, duration and occurrence of migraines. In migraine patients taking amitriptyline (medication to prevent episodes), supplementation with DHA + EPA is shown to further decrease the amount of headache days per month. Dietary intervention with enhanced intake of EPA + DHA is shown to reduce episode prevalence and severity, and decreases the usage of acute headache related drugs in migraine patients. The latter effect is enhanced when dietary omega-6 intake is decreased in addition to enhancement of omega-3 intake. Finally, a large meta-analysis comparing efficacy of EPA + DHA supplementation to certain pharmacological migraine treatments showed that EPA + DHA supplementation results in the biggest decrease of migraine frequency and severity compared to placebo. Importantly, supplementation with EPA + DHA had the highest acceptability rate of treatments as well. Although future research will have to determine the individual effects of EPA and DHA against migraines, robust evidence shows that these omega-3 fatty acids can offer a decrease of migraine burden.
 
References
Ramsden, Christopher E., Daisy Zamora, Keturah R. Faurot, Beth MacIntosh, Mark Horowitz, Gregory S. Keyes, Zhi-Xin Yuan, et al. 2021. ‘Dietary Alteration of N-3 and n-6 Fatty Acids for Headache Reduction in Adults with Migraine: Randomized Controlled Trial’. BMJ 374 (July): n1448. https://doi.org/10.1136/bmj.n1448.

Soares, Adriana De Almeida, Polyanna Mendes Camarço Louçana, Ema Pereira Nasi, Kamila Maria De Holanda Sousa, Odara Maria De Sousa Sá, and Raimundo Pereira Silva-Néto. 2018. ‘A Double- Blind, Randomized, and Placebo-Controlled Clinical Trial with Omega-3 Polyunsaturated Fatty Acids (OPFA ɷ-3) for the Prevention of Migraine in Chronic Migraine Patients Using Amitriptyline’. Nutritional Neuroscience 21 (3): 219–23. https://doi.org/10.1080/1028415X.2016.1266133.

Tseng, Ping-Tao, Bing-Yan Zeng, Jiann-Jy Chen, Chun-Hsien Kuo, Bing-Syuan Zeng, John S Kuo, Yu-Shian Cheng, et al. 2024. ‘High Dosage Omega-3 Fatty Acids Outperform Existing Pharmacological Options for Migraine Prophylaxis: A Network Meta-Analysis’. Advances in Nutrition 15 (2): 100163. https://doi.org/10.1016/j.advnut.2023.100163.