Food and Behaviour Research

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Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: a randomized trial.

Ramsden C, Faurot K, Zamora D, Suchindran C, Macintosh B, Gaylord S, Ringel A, Hibbeln J, Feldstein A, Mori T, Barden A, Lynch C, Coble R, Mas E, Palsson O, Barrow D, Mann J (2013) Pain 154(11) 2441-2451. DOI: 10.1016/j.pain.2013.07.028 

Web URL: Read this and related articles on PubMed here


Omega-3 and n-6 fatty acids are biosynthetic precursors to lipid mediators with antinociceptive and pronociceptive properties. We conducted a randomized, single-blinded, parallel-group clinical trial to assess clinical and biochemical effects of targeted alteration in dietary n-3 and n-6 fatty acids for treatment of chronic headaches.

After a 4-week preintervention phase, ambulatory patients with chronic daily headache undergoing usual care were randomized to 1 of 2 intensive, food-based 12-week dietary interventions: a high n-3 plus low n-6 (H3-L6) intervention, or a low n-6 (L6) intervention. Clinical outcomes included the Headache Impact Test (HIT-6, primary clinical outcome), Headache Days per month, and Headache Hours per day. Biochemical outcomes included the erythrocyte n-6 in highly unsaturated fatty acids (HUFA) score (primary biochemical outcome) and bioactive n-3 and n-6 derivatives.

Fifty-six of 67 patients completed the intervention. Both groups achieved targeted intakes of n-3 and n-6 fatty acids. In intention-to-treat analysis, the H3-L6 intervention produced significantly greater improvement in the HIT-6 score (-7.5 vs -2.1; P<0.001) and the number of Headache Days per month (-8.8 vs -4.0; P=0.02), compared to the L6 group.

The H3-L6 intervention also produced significantly greater reductions in Headache Hours per day (-4.6 vs -1.2; P=0.01) and the n-6 in HUFA score (-21.0 vs -4.0%; P<0.001), and greater increases in antinociceptive n-3 pathway markers 18-hydroxy-eicosapentaenoic acid (+118.4 vs +61.1%; P<0.001) and 17-hydroxy-docosahexaenoic acid (+170.2 vs +27.2; P<0.001).

A dietary intervention increasing n-3 and reducing n-6 fatty acids reduced headache pain, altered antinociceptive lipid mediators, and improved quality-of-life in this population.


Chronic daily headaches were significantly reduced by consuming more long-chain omega-3 fats (EPA and DHA, found in fish and seafood) and reducing intake of omega-6 fats (found in all vegetable oils).

This was a randomised controlled clinical trial - the kind of study design that provides the highest level of evidence for causal effects.

The findings support what is already known about the effects of omega-3 EPA/DHA - as susbtances made from them help to reduce inflammation and pain, while a diet rich in omega-6 fats generally has the opposite effect, promoting both nflammation and pain signalling.

What is novel about this trial is that that the changes in omega-3/6 balance were achieved by dietary changes, rather than via supplementation with EPA/DHA.

These results show that dietary changes can be an effective way to improve the management of serious headache pain. More such trials are now needed to confirm these results - and importantly, to find out if this approach may also be of benefit in other chronic pain conditions.

UPDATE 2015: For further findings from this trial, providing information on both additional effects and potential mechanisms, please see:

UPDATE 2021:  A new, larger clinical trial involving patients with migraine has now confirmed and extended these findings. See: