Choline (DB00122): A Comprehensive Monograph on its Biochemical, Pharmacological, and Clinical Profile

Executive Summary

Choline, identified by DrugBank accession number DB00122, is a small molecule that transcends its classification as a simple nutraceutical. It is a cornerstone of human physiology, fundamentally essential for the structural integrity of every cell, the functional capacity of the nervous system, and the regulation of hepatic lipid metabolism. Its biological importance is rooted in a tripartite role: as an indispensable precursor for the synthesis of major membrane phospholipids like phosphatidylcholine and sphingomyelin; as the direct antecedent to the neurotransmitter acetylcholine, which governs memory, muscle control, and autonomic function; and as the substrate for the production of the methyl-donor betaine, linking it inextricably to one-carbon metabolism and epigenetic regulation.

This monograph provides an exhaustive analysis of choline, from its fundamental chemical properties to its complex clinical profile. A central theme that emerges is the clinical paradox of choline. On one hand, dietary deficiency leads to severe and demonstrable organ dysfunction, most notably non-alcoholic fatty liver disease (NAFLD) and myopathy. On the other hand, its therapeutic application is not straightforward and requires a nuanced understanding of an individual's genetic makeup, hormonal status, and gut microbiome composition. The form in which choline is consumed—whether as a water-soluble salt or a lipid-soluble phospholipid—profoundly impacts its pharmacokinetic profile, bioavailability, and metabolic fate, particularly concerning the generation of trimethylamine N-oxide (TMAO), a metabolite implicated in cardiovascular disease.