Clinical trial NCT02403804: Dietary Supplementation to Increase Serum Choline Levels
Official title: Dietary Supplementation to Increase Serum Choline Levels
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: Dietary supplements
serum choline
women
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2015-03-31
Enrollment: 8
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: change in serum choline
timeFrame: 4 hours post supplement.- baseline
Secondary outcomes:
measure: change in serum choline
timeFrame: 2 hours post supplementation.- baseline
measure: change in serum choline
timeFrame: 6 hours post supplementation.- baseline
measure: change in serum choline
timeFrame: 8 hours post supplementation.- baseline
measure: change in serum choline
timeFrame: 10 hours post supplementation.- baseline
measure: change in serum choline
timeFrame: 12 hours post supplementation - baseline
measure: change in serum choline
timeFrame: 1 week post supplementation - baseline
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
Study officials:
affiliation: Denver Health and Hospitals
name: Camille Hoffman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado School of Medicine
name: Randal G Ross, MD
role: STUDY_DIRECTOR
affiliation: University of Colorado School of Medicine
name: Ann Olincy, MD
role: STUDY_DIRECTOR
References: