Dietary Supplementation to Increase Serum Choline Levels

University of Colorado Denver (CU Denver)

Status: Completed

Conditions: Healthy

Treatments: Dietary Supplement: Betaine (1000 mg BID); Dietary Supplement: Phosphatidylcholine; Dietary Supplement: Betaine (588 mg qam and 412 mg qpm)

Study type: Interventional

Funder types: Other

Identifiers

NCT02403804

14-1783

UL1TR001082 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The goal is to assess whether, in adult women during the luteal phase of their menstrual cycle, supplementing their diet with either phosphatidylcholine or betaine increases their serum choline levels.

Full description

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.

Enrollment: 8 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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8 participants in 1 patient group

All subjects

Other group

Description:

All 3 weeks will occur during luteal phase of menstrual cycle with a two-to-three week washout period between weeks. Week 1: Phosphatidylcholine 3600 mg qam and 2700 mg qpm Week 2: Betaine anhydrous 588 mg qam and 412 mg qpm Week 3: Betaine anhydrous 1000 mg BID

Treatment:

Dietary Supplement: Betaine (588 mg qam and 412 mg qpm)

Dietary Supplement: Phosphatidylcholine

Dietary Supplement: Betaine (1000 mg BID)