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expert reaction to a study looking at diets rich in omega 3 fatty acids and headache in adults with migraine

A U.S. study published in the BMJ looks at diets rich in omega 3 fatty acids and frequency of headaches in patients with migraine.


Dr Alister McNeish, Associate Professor in Cardiovascular Pharmacology, University of Reading, said:

“Overall it seems the study is well conducted with an appropriate control group and two high omega-3 diets – one with low omega 6 content that could potentially provide nuance if it were increase in omega-3 or decrease in omega -6 that may have a potential effect. The results in the primary outcome (reduction in HIT-6 score) were not significant indicating that patients felt no benefit to their overall quality of life. Interestingly the secondary outcomes of headache frequency and severity were meaningfully reduced in both omega-3 enriched diets. Perhaps indicating that dietary interventions to increase omega-3 have the potential to have a beneficial effect as migraine treatment. Patients in all groups continued their normal medication as per the experimental design to ascertain if diet could have an effect in combination with treatment.

“This study adds to the literature and provides nuance but like the literature overall there is conflicting information in that the primary outcome was not met but secondary outcomes were met, I think this study strengthens the evidence that omega -3 could have a role in headache management but does not fully answer the question.

“One limitation of the study is that the effect of other omega-3 fatty acids such as ALA (mainly sourced form plants) was not assessed.

“The implications for the real world is that there is potential that refining dietary interventions could have an overall positive effect and reduction in frequency and intensity of headaches demonstrates this has potential to improve treatment.

“The authors speculated on a mechanism which reflects high omega-3 reducing levels of pain causing oxylipins but it did not affect other pain causing chemicals with more established links to headache such as CGRP and Certain Prostaglandins (PGE2). There are also a plethora of other pathways in the body that can be affected by changes in dietary fatty  acid consumption so is hard to be eliminate these as potential contributors to any effects seen.

“People prone to headaches should not start taking omega 3 fatty acid supplements due to this study. This was a controlled dietary intervention which increased levels of both DHA and EPA that found no overall significant effect on the primary outcome and reasonable improvements in secondary outcomes. Supplementation would not necessarily reflect the levels of omega 3 here and other elements of diet would not be controlled; supplements of omega-3 fatty acids vary in their purity, composition, and strength so would be hard to precisely match the foods supplied in this study.

“The level of 1.5g of omega-3 (EPA/DHA) in these diets are largely in line with guidance for consumption in cardiovascular health (a minimum of about 1g per day is recommended by the American heart association) and for a healthy well balanced diet many people consume far under this amount. Therefore following current guidance for following a healthy well balanced diet has a role to play in general good health – including in headache . The role of other omega-3 fatty acids particularly those gained from a plant based diet (ALA) were not assessed in this studied.”


Prof Vimal Karani, Professor in Nutrigenetics & Nutrigenomics, University of Reading, said:

“Firstly, migraine is a complex trait with a strong genetic component where heritability has been estimated to range from 30 – 60%. As demonstrated by the authors, diet rich in omega-3 fatty acids might reduce the symptoms of migraine; however, given the differences in the genetic susceptibility across people, the finding cannot be generalised. Furthermore, studies have also identified monogenic migraine disorder which is caused due to a pathogenic genetic variant in a single gene. It is possible that there might be individuals with the genetic variants which can influence the ability of omega-3 fatty acids in reducing the symptoms of migraine.

“Secondly, several studies have reported differences in the prevalence of migraine across ethnic groups. Even though the RCT has included blacks and whites, the sample size of the cohort is small to identify ethnic-specific differences in the effect of omega-3 fatty acids on migraine. In addition, the study did not adjust for ethnicity as a confounder in their statistical analysis. Hence, genetic factors and race/ ethnicity are likely to confound the observed associations, and these could be some of the reasons why the study did not see a significant improvement in the quality of life. Further large RCTs involving multiple ethnic groups are required to confirm or refute the findings.”


  1. Sutherland et al, The Journal of Headache and Pain, 2019.
  2. Siewert et al, International Journal of Epidemiology, 2020.
  3. Loder et al, The Journal of Headache and Pain, 2015.
  4. Abu-Arafeh et al. Dev Med Child Neurol, 2010.
  5. Stewart et al. Neurology, 1996.


Prof Kevin McConway, Emeritus Professor of Applied Statistics, The Open University, said:

“This does look like a useful trial. But one note of caution. The participants in the trial were all people with migraine, who had headaches on between 5 and 20 days a month. So it can’t directly tell us about whether these diets can reduce headaches in people who don’t have migraine, but have some different type of headaches instead. The researchers do mention in the paper that further research could look at whether the same approach might help in other populations with chronic pain, but this particular study can’t directly say whether it would help or not, except in relation to migraine.”


Prof Tom Sanders, Professor Emeritus of Nutrition and Dietetics, King’s College London, said:

“This trial compares headache frequency and severity in patients given dietary advice to eat salmon to increase their intake of omega-3 fatty acids compared with patients on a typical American diet. The patients allocated to salmon in addition received advice to use blends of vegetable oils to either lower or maintain the intake of the omega-6 fatty acid linoleic acid compared with the control group.

“It was predicted that the level of a metabolite 17-HDHA would increase in the patients given dietary advice to eat salmon and as expected, this was the case. However, there was no significant difference in a composite score of headache severity and frequency which was the primary endpoint. However, in secondary analyses the patients appeared to suffer fewer severe headache. Consequently, these could arise by play of chance and are in need replicating in another study. 

“Much of the discussion focuses on the hypothetical link between the intake of omega-6 fatty acids and headache inducing metabolites and the potential of metabolites derived from omega-3 fatty acids to oppose these effects. The study failed to show any effect of altering the ratio of omega-6/omega-3 fatty acids. The major limitation of this study is the dietary intervention which was complex because the diets differed in respect of several minor components. For example, increasing the intake of salmon also increases the intake of several other micronutrients such as vitamin D and selenium as well as the intake of long-chain omega-3 fatty acids.

“Importantly, the study does not provide any evidence to show that dietary supplements of omega-3 fatty acid provide benefit. However, advice to eat moderate amounts (1-2 serving a week) of salmon would be consistent with current healthy eating advice.”


Dr Duane Mellor, Registered dietitian and Lead for nutrition and evidence based medicine, Aston Medical School, Aston University, said:

“This was a well conducted research clinical trial, which went to great lengths to try to hide from participants which study diet they were being asked to eat, something called blinding. This is important as it can reduce an individual’s expectation of what might happen in a study and reduce potential bias.

“This study of relatively young mostly female participants with migraine looked to show both how omega 3 fatty acids (found in oily fish such as mackerel, sardines and salmon and which are known to moderate inflammation) are involved in the causation of migraines and whether eating them can reduce symptoms of migraine. This study showed that over a four month period those on the diets rich in omega 3 fatty acids had higher levels of a blood marker (17-HDHA) which is associated with reduced pain, however the other main outcome measure of reported the Headache Impact Test (HIT-6) did not significantly improve in those who consumed more omega-3 fatty acids. So, although the study did not meet all its outcomes successfully, it did show reductions in number and severity of headaches and reduced use of some medication.

“So, this study helps provide an understanding of how diet may decrease risk of someone having a migraine, but perhaps due to the length of the study it was not able to fully show that diets rich in omega 3 fatty acids cause a reduction in migraines. The study looked at mainly young adult women, so this may not work in children, men or older adults. We need to know how this might benefit the groups not included in the study and if other sources of omega-3 fatty acids are effective, so non-fish consumers and those worried about sustainability and fish stocks can also benefit from the findings of this study. This is an interesting study which highlights another potential benefit of a Mediterranean healthy diet including oily fish.”



‘Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial’ by Ramsden et al was published at 00:01 UK time on Thursday 1st July 2021.

DOI: 10.1136/bmj.n1448



Declared interests

Prof Vimal Karani: “None.”

Prof Kevin McConway: “I am a Trustee of the SMC and a member of its Advisory Committee.  My quote above is in my capacity as an independent professional statistician.”

Prof Tom Sanders: “Member of Science Committee, British Nutrition Foundation, Nutritional Director HEART UK.”

Dr Duane Mellor: “No conflicts of interest.”

None others received.

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