A secondary analysis depicted that in patients with chronic daily headaches, reducing dietary linoleic acid (LA) levels for 12 weeks, with or without increasing intake of omega-3 polyunsaturated fatty acids (PUFAs), led to elevated levels of free docosahexaenoic acid (DHA)-epoxides in their plasma. These changes correlated with improved headache control, enhanced physical and mental health, and reduced interference of headaches in daily activities.

Qing Shen et al. aimed to examine the potential association between the clinical benefits of low LA/high n-3 PUFA dietary intervention [H3-L6] diet and alterations in plasma unesterified PUFA-derived lipid mediators (plasma lipid mediators), specifically those implicated in nociception, such as prostanoids. Using ultra-high-pressure liquid chromatography plus tandem mass-spectrometry, the measurement of lipid mediators was done.

The findings indicated that reducing linoleic acid in the diet, with or without additional omega-3 fatty acids, did not result in changes to unesterified n-6 PUFA-derived lipid mediators in comparison to the baseline. However, arachidonic acid, di-homo-gamma-linolenic acid, and linoleic acid-derived lipid species were positively correlated with mental health burden, headache intensity, and frequency.

There was a correlation between metabolites derived from alpha-linolenic acid (ALA) and an increase in both headache frequency and intensity, despite no observable changes in these metabolites between the dietary groups compared to the baseline. On the other hand, DHA-derived epoxides showed significantly higher levels in the H3-L6 group as opposed to the L6 group.  The rise in plasma DHA-epoxides resulting from dietary modifications was linked to an enhanced quality of life, improved mental and physical health, and a decrease in the frequency of headaches.

Prostanoids, except prostaglandin F2 (PGF2)-alpha, were not detected, and there were no associations found with any outcomes. Diet-induced alterations in DHA-epoxides were related to a reduction in pain for individuals suffering from chronic headaches, whereas metabolites of ALA and n-6 PUFA were associated with nociception. Associations between lipid mediators and mental health, as well as the quality of life, align with the outcomes of pain management in this particular population. The results suggest that there is a network of various lipid mediator targets, influenced by diet, that can be explored for effective pain management in individuals with chronic daily headaches.

The findings from this study offer valuable insights into the network of diet-modifiable lipid mediator targets for pain management in individuals with chronic daily headaches. By understanding the specific changes in lipid mediators associated with pain reduction, researchers hope to develop targeted interventions and personalized dietary plans to alleviate the burden of chronic headaches and improve the overall well-being of affected individuals.