Common Genetic Variants Alter Metabolism and Influence Dietary Choline Requirements

Abstract

Nutrient needs, including those of the essential nutrient choline, are a population wide distribution. Adequate Intake (AI) recommendations for dietary choline (put forth by the National Academies of Medicine to aid individuals and groups in dietary assessment and planning) are grouped to account for the recognized unique needs associated with age, biological sex, and reproductive status (i.e., pregnancy or lactation). Established and emerging evidence supports the notion that common genetic variants are additional factors that substantially influence nutrient requirements. This review summarizes the genetic factors that influence choline requirements and metabolism in conditions of nutrient deprivation, as well as conditions of nutrient adequacy, across biological sexes and reproductive states. Overall, consistent and strong associative evidence demonstrates that common genetic variants in choline and folate pathway enzymes impact the metabolic handling of choline and the risk of nutrient inadequacy across varied dietary contexts. The studies characterized in this review also highlight the substantial promise of incorporating common genetic variants into choline intake recommendations to more precisely target the unique nutrient needs of these subgroups within the broader population. Additional studies are warranted to facilitate the translation of this evidence to nutrigenetics-based dietary approaches.

Choline, Neurological Development and Brain Function: A Systematic Review Focusing on the First 1000 Days

“…It is also important to use clearly defined endpoints to assess neurological development and brain function so that study comparisons can be made effectively and future meta-analytical work undertaken. As mentioned, SNPs could also influence the choline requirements of pregnant women and should be considered when designing future studies and compiling public health guidance [26,27].…”

“…It should be recognized that single nucleotide polymorphisms (SNP) in choline metabolizing genes can alter: (1) the use of choline as a methyl donor, (2) the partitioning of dietary choline between betaine and phosphatidylcholine synthesis, and (3) the distribution of dietary choline between cytidine diphosphate-choline and PEMT pathways, which could influence the choline requirements of pregnant women [26,27]. Mechanistically, other work [28] shows enhanced use of choline for phosphatidylcholine production via both the cytidine diphosphate-choline and PEMT pathways, further indicating substantial demands for choline in late pregnancy.…”

“…For exclusive lactation, an intake of 520 mg/day have been set by EFSA, which provides an additional 120 mg/day on top of adult recommendations, that is, the estimated average amount of choline secreted in human milk daily [21]. Common genetic variants (such as those found in the PEMT and methylenetetrahydrofolate dehydrogenase (MTHFD1) genes) can also interact with choline metabolism and can impact on choline requirements [26].…”

Choline

“…Common genetic variants in choline and folate metabolic enzymes influence the risk of choline inadequacy and the metabolic fate of dietary choline across different life stages and nutrient intakes (7,19,20). Single nucleotide polymorphisms, such as rs12325817 and rs4646343 in the PEMT gene and rs2236225 in the MTHFD1 gene, influence the risk of choline deficiency and the partitioning of choline towards oxidation or phosphatidylcholine production (19,21).…”

Neuroprotective Effects of Choline and Other Methyl Donors

“…Despite this recommendation, some individuals do not meet their daily choline requirement and other individuals increase their intake above the recommended value. AI varies from one individual to another and this variation is influenced by several factors such as age, sex, genetic and environmental factors [33][34][35]. For example, an elevated intake of choline is required for pregnant women to support fetal growth and development and improve neurocognitive functions of offspring later in life [12,32].…”