Metabolomics reveals reasons for the efficacy of acupuncture in migraine patients: The role of anaerobic glycolysis and mitochondrial citrate in migraine relief

Acupuncture is used worldwide to treat migraine, but its scientific mechanism remains unclear. Here, we report a 1H NMR metabolomics study involving 40 migraine patients and 10 healthy people randomly receiving acupuncture or sham acupuncture, followed by machine learning techniques and functional analysis. We found that acupuncture at acupoints particularly enhanced anaerobic glycolysis and modified mitochondrial function by adjusting the levels of plasma pyruvic acid (P = 0.012), lactic acid (P = 0.031) and citrate (P = 0.00079) at a Bonferroni-corrected level of significance compared to the pre-treatment level of these three metabolites in migraine patients. Therefore, acupuncture supplies energy to migraine patients and relieves migraine attacks. In contrast, we observed that sham acupuncture may partially supply energy to migraine patients through lipid metabolism by changing the levels of plasma lipid (P = 0.0012), glycerine (P = 0.021), and pyruvic acid (P = 0.047) at a Bonferroni-corrected level of significance. The functional network analysis further indicates this different way of supplying energy contributes to the different effects of acupuncture and sham acupuncture. Our findings reveal novel metabolic evidence for the specific effect of acupuncture in relation to sham acupuncture. This metabolic evidence could enlighten a brand new direction into acupuncture analgesia mechanism, which in turn would pose fresh challenges for future acupuncture research.