Marine omega-3 fatty acid metabolites shown to reduce chronic pain

Recent work by Ramsden et al (1) at the NIH in Bethesda, MD, USA has demonstrated that a dietary intervention rich in marine omega-3 fatty acids but low in omega-6 fatty acids can provide an effective, complementary approach for managing chronic pain and related conditions. The beneficial effects were found to be due to specific endocannabinoids derived from docosahexaenoic acid (DHA).

Prior to the current study, Ramsden et al. had established that a diet rich in marine omega-3 fatty acids but low in omega-6 fatty acids when given to patients suffering from chronic daily headaches (CDH) resulted in reduction in intensity and frequency of headaches, reduced psychological stress and generally enhanced the quality of life (2, 3). The current study involved a cohort of 55 patients suffering CDH. An intervention diet rich in marine omega-3 fatty acids, but low in omega-6 fatty acids, was given for 12 weeks (1). Both the clinical and biochemical affects were assessed. All the participants had suffered chronic headaches for at least four hours a day and 15 days a month for a period of at least three months before the trial.

The intervention arm experienced considerable clinical improvements. The improvements were shown to be due to endocannabinoids directly derived from docosahexaenoic acid (DHA). Endocannabinioids from Arachidonic Acid (ARA) had no effect. Two relevant DHA-derived endocannabinoids were found, but which had different clinical effects. For each standard deviation, 2-DHG (2-docosahexaenoylglcyerol) provided a 10% reduction in the number of headaches per month and a 40% reduction in the number of severe headache hours a day. In addition there were improvements in the measures of psychological distress and mental health composite scores. For each standard deviation in DHA-EA (docosahexaenoylethanolamine) there was a 7% reduction in the number of headaches per month and a 30% reduction in the number of severe headache hours, but no other psychological effects. The levels of 2-DHG and DHA-EA had increased in plasma by 65% and 99% respectively over the 12 week intervention. This study provided the first known evidence that 2-DHG could be modified by diet. It was known that 2-DHG was found in relatively high concentrations in brain tissue.

The mechanism by which 2-DHG and DHA-EA achieve a reduction in headaches is unknown. 2-DHG, though very similar in structure to the ARA derived endocannabinoid 2-AG, has a low affinity for cannabinoid receptors. DHA-EA does have established anti-inflammatory and neurogenic properties. Ramsden et al conclude that a dietary intervention rich in DHA could “provide an effective, complementary approach for managing chronic pain and related conditions” (1).

1. Ramsden CE, Zamora D et al., Diet-induced changes in n-3 and n-6 endocannabinoids and reduction in headache pain and psychological distress, Journal of Pain, 2015, doi 10.1016/j.jpain.2015.04.007
2. Ramsden CE, Faurot KR et al., Targeted alteration in dietary n-3 and n-6 fatty acids improve life functioning and reduce psychological distress among patients with chronic headache : a secondary analysis of a randomized trial, 2015, Pain 156 :587–596.
3. Ramsden CE, Faurot KR et al., Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches : a randomized trial, Pain 2015, 154 : 2441–2451.