Nutritional modulators of sleep: A narrative review of vitamins, minerals, amino acids, and their neurobiological and chronoepigenetic mechanisms

This narrative review synthesizes evidence on how vitamins, minerals, and amino acids modulate sleep through neurobiological, circadian, and epigenetic pathways. B-group vitamins (B6, B12, folate) are cofactors in the synthesis of serotonin and gamma-aminobutyric acid (GABA). The lack of these factors increases the excitability of neurons and interferes with sleep. Vitamin D exerts its regulation through its nuclear receptor by controlling the key clock genes and melatonin secretion, and suppresses neuroinflammation. Magnesium and calcium modulate neuronal excitability and melatonin synthesis (enhancing GABAergic tone and enzyme activity) to promote slow-wave sleep. Iron and zinc affect the dopaminergic circuits; iron supplementation decreases restless-leg syndrome and sleep fragmentation. Tryptophan and other amino acids stimulate the formation of serotonin/melatonin to reduce sleep latency, and inhibitory amino acids (glycine, GABA) increase central nervous system inhibition to facilitate sleeping. Epigenetic mechanisms that operate on nutrient signals, especially methylation of clock genes using the vitamins folate and B12, are becoming appreciated. Taken together, these mechanisms affect the process of sleep latency, duration, and architecture. The review notes the prospect of more personalized nutritional interventions (possibly personalized by genotyping) in optimizing sleep, but notes that further research is necessary in the form of larger controlled trials.