Dietary Supplementation to Increase Serum Choline Levels

NCT ID: NCT02403804

Last Updated: 2020-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2015-09-29

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.

Conditions

Healthy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

All subjects

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

Group Type: OTHER

Phosphatidylcholine

Intervention Type: DIETARY_SUPPLEMENT

Phosphatidylcholine 3600 mg qam and 2700 mg qpm

Betaine (588 mg qam and 412 mg qpm)

Intervention Type: DIETARY_SUPPLEMENT

Betaine anhydrous 588 mg qam and 412 mg qpm

Betaine (1000 mg BID)

Intervention Type: DIETARY_SUPPLEMENT

Betaine anhydrous 1000 mg BID

Interventions

Phosphatidylcholine

Phosphatidylcholine 3600 mg qam and 2700 mg qpm

Intervention Type: DIETARY_SUPPLEMENT

Betaine (588 mg qam and 412 mg qpm)

Betaine anhydrous 588 mg qam and 412 mg qpm

Intervention Type: DIETARY_SUPPLEMENT

Betaine (1000 mg BID)

Betaine anhydrous 1000 mg BID

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Trimethylglycine; Trimethylglycine

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Camille Hoffman, MD

Role: PRINCIPAL_INVESTIGATOR

Denver Health and Hospitals

Randal G Ross, MD

Role: STUDY_DIRECTOR

University of Colorado School of Medicine

Ann Olincy, MD

Role: STUDY_DIRECTOR

University of Colorado School of Medicine

Locations

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Countries

United States

Other Identifiers

UL1TR001082

Identifier Type: NIH

Identifier Source: secondary_id

View Link

14-1783

Identifier Type: -

Identifier Source: org_study_id