Future Directions in Choline: From Neurodevelopment to Cardiometabolic Health

Although choline was established as an essential nutrient over three decades ago, critical questions remain about how choline regulates brain, liver, and cardiometabolic health across the lifespan. This Perspective summarizes emerging insights presented at the <i>Future Directions in Choline Symposium: A Tribute to Steven H. Zeisel</i>, which outlined three converging areas of research: (i) choline-dependent mechanisms in neurodevelopment and cognition, (ii) the link between choline metabolism and obesity, and (iii) the role of trimethylamine N-oxide (TMAO) in cardiovascular disease. Evidence from clinical and preclinical studies confirms that maternal choline intake is critical for neurogenesis, cognition, and visual system development, and that higher choline availability buffers the fetal brain against environmental and psychosocial stressors. Choline supplementation improves cognitive outcomes in fetal alcohol spectrum disorder and mitigates neurodegenerative pathology in Alzheimer's models. In cardiometabolic health, recent data challenge the interpretation of TMAO as a causal toxin, positioning it instead as a marker of renal function. Moving forward, the field must develop validated biomarkers of choline adequacy in free-living populations, harmonize intervention protocols, and define context-specific requirements across obesity, pregnancy, and glucagon-like peptide-1 (GLP-1)-based therapy use. These efforts will refine dietary recommendations and solidify choline's role in lifelong brain and metabolic health.