Coenzyme Q10 & Magnesium for Migraine

Coenzyme Q10

There are other arguments supporting the idea of ​​mitochondrial damage in the pathophysiology of migraines: monoamine oxidase, succinate dehydrogenase, NADH dehydrogenase (which works together with coenzyme Q10), cyclooxygenase and citrate synthetase. are all Krebs cycle enzymes, found in reduced quantities in migraine sufferers compared to healthy patients (Sangiorgi et al. 1994). Also, it was shown in a study of 1550 children and adolescents with migraine (Hershey et al. 2007) that thirty percent of them had a lowered plasma coenzyme Q10 level. Interestingly, all of these enzymes are encoded from mitochondrial DNA, which is more vulnerable to oxidative stress than nuclear DNA, and which is transmitted only by maternal inheritance.

Magnesium (Mg2 ⁺ )

Another important element in metabolism, magnesium (Mg ²⁺ ), a cofactor in more than 300 biochemical reactions, participates in all reactions involving the formation or use of ATP. Its role in migraine was mentioned by Welch in 1995 as a blocker of neuro-inflammation, NMDA receptors, glutamate and NO synthesis (Welch et al. 1995). Neurogenic inflammation is mainly relayed by two neuropeptides, CGRP and substance P. The latter is indirectly under the influence of Mg ²⁺ via its degradation protein, neutral endopeptidase. However, at the intestinal and cardiac level, it has been shown that hypomagnesemia reduces the expression of this coenzyme, thus promoting the inflammatory response (Weglicki et al., 2009). Mg ²⁺ also influences vascular tone, its absence causing spasm of the cerebral arteries and vasoconstriction (Agarwal et al. 2014), while its excess tends to reduce the tone of the arteries.

Mg ²⁺ deficiency initiates platelet aggregation and glutamate release, leading to serotonin release (Dolati et al. 2019). The influence of Mg ²⁺ in neuronal functioning is also related to NMDA receptors, activated by glutamate and glycine under physiological conditions. Initially, the receptor is blocked by Mg ²⁺ , preventing the calcium channel from opening. To activate the channel, the membrane potential must first be depolarized, thereby removing Mg ²⁺ from the receptor. Conversely, a Mg ²⁺ deficiency leads to abnormal functioning of NMDA receptors and allows a toxic intracellular entry of Ca ²⁺ . This intrusion tends to release free radicals, such as oxygen or NO derivatives (Goadsby et al. 2017). NO, as well as the other free radicals produced, are dependent on the Mg ²⁺ /Ca ²⁺ ratio.

During a massive release of glutamate, there is a significant entry of Ca ²⁺ into the cell and more particularly into its mitochondria, this independently of the presence of NMDA receptors. This chain reaction can hypothetically participate in the appearance of the DCE. Studies have shown that Mg ²⁺ deficiency associated with NO exposure in the hippocampus of rats was sufficient to trigger DCE (Horiguchi et al. 2005).