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.

Inclusion Criteria:

1. premenopausal

2. No nicotine use

3. No marijuana use

4. No illicit substance use

5. Weight >= 90 pounds

Exclusion Criteria:

1. self-reported body odor of unknown etiology

2. personal or family history of cystathionine beta synthase deficiency (homocystinuria)

3. personal or family history of trimethylaminuria, renal or liver disease, Parkinson's
disease