Immunomodulatory Properties of Choline and its Dietary Forms throughout the Lifespan

Choline is involved in a broad range of critical physiological functions across all stages of the life cycle. Although choline's essentiality for neurotransmitter synthesis, cell membrane integrity, lipid transport, and one-carbon metabolism has been extensively studied, evidence shows that choline plays an underexplored role in immune function and inflammation. This narrative review synthesizes evidence from preclinical and clinical studies, systematically examining choline's impact on immune development and regulation. Key findings reveal that adequate intake of choline-particularly lipid-soluble forms of choline, such as phosphatidylcholine (PC) and sphingomyelin (SM)-supports immune cell signaling, membrane integrity, and gut barrier function. Early-life choline exposure (both maternal and postnatal) programs immune development, resulting in enhanced T-cell function and cytokine balance. Choline supplementation, specifically lipid-soluble forms, has also been shown to mitigate immune dysfunction and/or inflammation associated with obesity and chronic diseases (e.g., inflammatory bowel disease, arthritis). Observational data link higher choline intake to reduced systemic inflammation (e.g., lower C-reactive protein, interleukin-6), although the results are inconclusive, and human trials remain limited. Critically, the form of choline in the diet matters. A mixture of both lipid-soluble forms (PC, SM) and water-soluble forms (free choline, glycerophosphocholine, and phosphocholine) enhances immune development and function over diets containing solely water-soluble forms.