A comprehensive review of nutritional influences on the serotonergic system.

Abstract

Serotonin (5-hydroxytryptamine) is a critical monoamine neurotransmitter and hormone that orchestrates a vast array of physiological and psychological processes, including mood, sleep, appetite, and gastrointestinal motility. Its synthesis is dependent on the availability of its dietary precursor, the essential amino acid tryptophan (Trp), with impact on biochemical pathways that may be modulated by other nutrients. We conducted a literature review search to comprehensively examine the nutritional influences on the serotonergic system. Relevant original research, systematic reviews, meta-analyses, and clinical trial reports were retrieved from PubMed, Scopus, and Google Scholar, with additional articles identified from reference lists of published review papers. Key nutritional determinants of serotonergic function include macronutrients that influence tryptophan-to-large-neutral-amino-acid (Trp/LNAA) ratio, a regulator of brain Trp availability, and micronutrients such as B-vitamins, vitamin D, iron and magnesium that serve as essential cofactors in serotonin synthesis and metabolism. Emerging evidence also highlights the role of the gut microbiota, shaped by dietary components, prebiotics and probiotics, in modulating serotonergic function across both central and peripheral systems. Nutritional factors that affect serotonin have been increasingly linked to conditions such as depression, anxiety, sleep disturbances, disordered eating, obesity, and irritable bowel syndrome. Altogether, this review emphasizes the profound impact of nutrition on serotonergic regulation, and advocates for targeted dietary approaches as promising catalysts for optimizing human health. Key research gaps and future directions are outlined to help advance the translation of current evidence into precise nutritional guidelines and clinical applications, with the complexity of serotonin pathways as an important consideration. STATEMENT OF SIGNIFICANCE: Serotonin impacts many physiologic processes in the body yet the impact of nutrition in the regulation of serotonin-related outcomes has not been integrated. This review synthesizes emerging evidence on both macronutrient and micronutrient influences on serotonin pathways, connecting central and peripheral mechanisms including gut-brain interactions, presenting a new perspective on nutritional targets and translational potential for various serotonin-related diseases spanning mental, metabolic and gastrointestinal outcomes.