Dietary Supplementation to Increase Serum Choline Levels

Elevated maternal serum free choline has the potential to improve fetal brain development . However, in humans, choline can be metabolized by gut flora into two metabolites with adverse outcomes: trimethylurea (which causes body odor) and Trimethylamine (TMA) which is then, once absorbed, metabolized into Trimethylamine-N-Oxide (TMAO). There is some concern that TMAO may be atherogenic and thus, if elevated over an extended period of time, may increase risk for cardiac disease. Thus, while maternal choline supplementation may improve fetal brain development, there is a potential for maternal adverse effects.

However, humans have an active choline metabolic pathway, and other components of the choline metabolic pathway (e.g. phosphatidylcholine and betaine) may be interchangeable with choline post absorption but are resistant to gut bacteria metabolism (i.e. serum TMA does not increase). Thus, these other compounds would be expected to increase serum but with no impact on TMA or trimethylurea levels. An initial study of phosphatidylcholine supplementation in pregnant women was consistent with this hypothesis; infant offspring demonstrated improved cerebral inhibition; while no adverse events were identified for either mother or infant.

Unfortunately, because of the lipid groups incorporated into phosphatidylcholine, its molecular weight is high and reasonable doses require consuming several large capsules a day. The study represents the first attempt to determine if betaine, an alternative compound within the same metabolic pathway but with a much lower molecular weight, also increases serum choline levels. As the first step, this proposal seeks to address this in non-pregnant women. Specifically, the goals are to (a) assess whether changes in serum choline levels in response to molar equivalent supplementation of phosphatidylcholine versus betaine are similar, and (b) whether, for betaine, there is a dose response relationship between supplementation dose and serum choline levels.