Sexual dimorphism in the prevalence of
migraine (70% women 30% men) suggests the involvement of reproductive
hormones in a women's life. Excessive
estrogen during menstruation directly stimulate
estrogen receptor alpha thickly populated in trigeminal ganglia and periaqueductal gray which manifest as menstrual
migraine. In contrast increased
progesterone during pregnancy evokes
progesterone receptors A/B, which coexist with ERs, providing complete remission from
migraine episodes. Moreover,
estrogen also increases nociception through extracellularly signal-regulated
kinase (ERK) stimulation and down-regulating antinociceptive
GABA, IL-R1 and Zn-fingers.
Hormones may provoke
migraine indirectly by disrupting
mineral homeostasis.
Estrogen enhances the absorption and half-life of
copper which in turn inhibits the absorption of
zinc.
Zinc is required for the synthesis of
melatonin and
CoQ10 essential for growing women. Excess of
copper exacerbates the deficiency of
zinc,
melatonin and
CoQ10 typically low in migraineurs.
Melatonin is an
antioxidant,
free radical scavenger and activates
antioxidant enzymes like CuZn-
superoxide dismutase,
catalase,
glutathione peroxidase (a Se-
enzyme) and
glutathione reductase.
Zinc deficiency reduces activity of CuZn-SOD.
Magnesium and
vitamin B6 modulates the level of NO in the cell, both of which are deficient in migraineurs.
Magnesium is essential for the removal of trapped NO from within the cell which does not occur under low
magnesium levels, which reacts with
superoxide generating dangerous
peroxynitrite.
Iron stimulates
nitric oxide synthase producing more NO which is inhibited by
zinc, thus, antagonizing
peroxynitrite generation. Female
hormones lowers
magnesium but increase
calcium levels which enhance
migraine ubiquitousness. Accumulation of
copper and
iron in deep areas of brain and peripheral nerves typically catalyses the oxidation of
catecholamines and generate
free radicals involved in lipid-peroxidation,
demyelination, denudation of axons and neurodegeneration in specific areas exposing hyperalgesic axons provoking
Classical migraine. Furthermore,
zinc is an essential component of Zn-fingers (Krox20 and Krox24) which play a pivotal role in the differentiation of Schwann cells-the mainstay for the myelination/remyelination of peripheral nerves. Taken together, conceptually and logically, 30 migraineurs were administered 75 mg of
zinc sulfate orally in water daily for 6 weeks+one
capsule of
vitamin B-complex+one
capsule of
vitamin A or E (first 10 days) which almost cured all of them. Placebo controlled trials with incremental doses of
zinc sulfate along with
magnesium and
selenium are proposed to augment recovery involving large population of migraineurs. Monitoring of hair and blood
mineral analysis for rational
therapy is recommended.