July 06, 2021
"This is the first moderate-sized, controlled trial showing that targeted changes in diet can decrease physical pain," study investigator Christopher Ramsden, MD, with the National Institute on Aging and the University of North Carolina at Chapel Hill, told Medscape Medical News.
"With additional study, it may ultimately be possible to design better diets and integrate targeted dietary changes alongside medications to improve the lives of patients with chronic pain," said Ramsden.
The study was published online June 30 in The BMJ.
Omega-3 and omega-6 fatty acids are precursors of oxylipins, which are involved in the regulation of pain and inflammation. Oxylipins derived from omega-3 fatty acids are associated with pain-reducing and anti-inflammatory effects, whereas oxylipins derived from omega-6 fatty acids worsen pain and provoke migraine in experimental models. Yet, prior studies of omega-3 fatty acid supplementation for migraine have been inconclusive.
For the study, the researchers evaluated the impact of altering dietary omega-3 and omega-6 fatty acids on migraine in 182 adults (mean age, 38 years; 88% women) with chronic migraine (5 to 20 migraine days per month).
All participants received meal kits that included fish, vegetables, hummus, salads, and breakfast items. They were randomly assigned to one of three diets (two intervention, one control) for 16 weeks.
One diet increased omega-3 intake (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) to 1.5 g/d and maintained linoleic acid (omega-6) at around 7% of energy intake.
A second diet increased EPA and DHA to 1.5 g/d and decreased linoleic acid to <1.8% of energy intake. The control diet maintained EPA and DHA at <150 mg/d and linoleic acid at around 7% of energy.
Both intervention diets increased serum levels of 17-hydroxydocosahexaenoic acid (17-HDHA), an antinociceptive derivative of omega-3 fatty acids, compared with the control diet, which "supports the biological plausibility" of this type of approach for pain reduction, said Ramsden.
Both intervention diets also led to improved scores on the six-item Headache Impact Test (HIT-6), compared with the control diet, but the difference was not statistically significant.
However, migraine frequency was statistically significantly decreased in both intervention groups.
The high omega-3 diet was associated with 1.3 fewer headache hours per day and two fewer headache days per month. The high omega-3 plus low omega-6 diet was associated with 1.7 fewer headache hours per day and four fewer headache days per month, suggesting additional benefit from lowering dietary omega-6, the investigators note.
The high omega-3 groups also reported shorter and less severe headaches compared with the control group.
On the basis of the results, "it is reasonable for patients to try dietary changes as an adjunct approach, under the supervision of their healthcare providers," said Ramsden.
Better Than Drugs?
Rebecca Burch, MD, with the Graham Headache Center at the Brigham and Women's Hospital, Boston, Massachusetts, agrees.
"These results support recommending a high omega-3 diet to patients in clinical practice," Burch writes in a linked editorial.
"Many people with migraine are highly motivated and interested in dietary changes, and clinicians might want to provide patients with information about the diets described in the study," she adds.
Birch noted that the magnitude of the response to the intervention diets is "notable," given that recently approved drugs for migraine prevention reduce headache days by 2 to 2.5 per month compared with placebo, "suggesting that a dietary intervention can be comparable or better."
Burch says these findings "take us one step closer to a goal long sought by headache patients and those who care for them: a migraine diet backed up by robust clinical trial results."
However, experts with the UK Science Media Center were more cautious.
In a statement, Alister McNeish, PharmD, University of Reading, Reading, United Kingdom, cautioned that individuals who are 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" (change in HIT-6) and "reasonable improvements in secondary outcomes," McNeish said.
"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," McNeish added.
He also pointed out that the level of 1.5 g/d of omega-3 (EPA/DHA) in these intervention diets is "largely in line with guidance for consumption in cardiovascular health (a minimum of about 1 g 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," McNeish said.
Also weighing in, Tom Sanders, DSc, PhD, professor emeritus of nutrition and dietetics, King's College London, United Kingdom, said: "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."
Major funding for the study was provided by the National Institutes of Health. Ramsden has disclosed no relevant financial relationships. Burch is on the board of directors of the American Headache Society and the Headache Cooperative of New England and receives a stipend for work as an associate editor for the journal Neurology. Sanders is a member of the science committee of the British Nutrition Foundation and Nutritional Director HEART UK. Sanders has disclosed no relevant financial relationships.