Melatonin supplementation has become ubiquitous in sleep medicine, yet many users overlook a critical biochemical reality: the body synthesizes melatonin nightly through a four-step enzymatic cascade that demands specific micronutrient cofactors. Iron, folate, vitamin B6, zinc, and magnesium are not optional—they are essential raw materials in the tryptophan-to-melatonin pathway.
Without adequate levels of these micronutrients, exogenous melatonin supplementation may fail to restore normal sleep architecture. This biochemical dependence explains why some patients experience minimal benefit from supplements despite adequate dosing. Healthcare providers should consider comprehensive micronutrient assessment alongside melatonin therapy, particularly in populations at risk for nutritional deficiencies.
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