Nutrition and Calcitonin Gene Related Peptide (CGRP) in Migraine
by Michal Fila Nutrients 2023, 15(2), 289;
Targeting calcitonin gene-related peptide (CGRP) and its receptor by antibodies and antagonists was a breakthrough in migraine prevention and treatment. However, not all migraine patients respond to CGRP-based therapy and a fraction of those who respond complain of aliments mainly in the gastrointestinal tract. In addition, CGRP and migraine are associated with obesity and metabolic diseases, including diabetes. Therefore, CGRP may play an important role in the functioning of the gut-brain-microflora axis. CGRP secretion may be modulated by dietary compounds associated with the disruption of calcium signaling and upregulation of mitogen-activated kinase phosphatases 1 and 3.
CGRP may display anorexigenic properties through induction of anorexigenic neuropeptides, such as cholecystokinin and/or inhibit orexigenic neuropeptides, such as neuropeptide Y and melanin-concentrating hormone CH, resulting in the suppression of food intake, functionally coupled to the activation of the hypothalamic 3′,5′-cyclic adenosine monophosphate. The anorexigenic action of CGRP observed in animal studies may reflect its general potential to control appetite/satiety or general food intake.
Therefore, dietary nutrients may modulate CGRP, and CGRP may modulate their intake. Therefore, anti-CGRP therapy should consider this mutual dependence to increase the efficacy of the therapy and reduce its unwanted side effects. This narrative review presents information on molecular aspects of the interaction between dietary nutrients and CGRP and their reported and prospective use to improve anti-CGRP therapy in migraine.
Nutraceuticals, food or dietary supplements exerting beneficial health effects were studied in migraine prevention and therapy (reviewed in [16]). They are magnesium, coenzyme Q10, feverfew, riboflavin, phycocyanin, vitamin D and others. These studies do not always relate nutraceuticals action to CGRP concentration and suggest that such non-pharmacological treatment may be especially useful, but with modest efficacy, in headaches prevention in adolescents, pregnant or breastfeeding women, the elderly with complex drug therapy, patients who are inadvisable to pharmacological therapies. These non-pharmacological therapies are usually well-tolerated and safe. It was observed that women with migraine had lower plasma levels of Mg, Ca, Cu, and Zn than controls, but their dietary intake of Mg, Cu, and Fe was lower than recommended [42]. Therefore, patients with migraine may have lower plasma levels of minerals, and dietary intervention to ensure adequate mineral intake may be beneficial for them.
Those results showed that cocoa extract might repress stimulated CGRP release by a mechanism involving inhibition of calcium channels and suggest that diets rich in cocoa may suppress trigeminal sensory nerve activation. Subsequent studies showed that cocoa extract prevented inflammatory response in trigeminal ganglion neurons, which can be underlined by the upregulation of MKP-1 and MKP-3 [67] (Figure 2). These studies confirm the important role of MKP-1 in CGRP response to the intake of dietary nutrients.
