Dietary Supplementation to Increase Serum Choline Levels

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: Phosphatidylcholine; Dietary supplement: Betaine (588 mg qam and 412 mg qpm); Dietary supplement: Betaine (1000 mg BID)

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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	Dietary supplement: Phosphatidylcholine; Phosphatidylcholine 3600 mg qam and 2700 mg qpm; Dietary supplement: Betaine (588 mg qam and 412 mg qpm); Betaine anhydrous 588 mg qam and 412 mg qpm; Other Names: Trimethylglycine; Dietary supplement: Betaine (1000 mg BID); Betaine anhydrous 1000 mg BID; Other Names: Trimethylglycine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
change in serum choline	4 hours post supplement.- baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
change in serum choline	2 hours post supplementation.- baseline
change in serum choline	6 hours post supplementation.- baseline
change in serum choline	8 hours post supplementation.- baseline
change in serum choline	10 hours post supplementation.- baseline
change in serum choline	12 hours post supplementation - baseline
change in serum choline	1 week post supplementation - baseline

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Camille Hoffman, MD, Denver Health and Hospitals; Study Director: Randal G Ross, MD, University of Colorado School of Medicine; Study Director: Ann Olincy, MD, University of Colorado School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): September 29, 2015
• Study Completion (Actual): September 29, 2015

Study Registration Dates

• First Submitted: February 3, 2015
• First Submitted That Met QC Criteria: March 25, 2015
• First Posted (Estimate): March 31, 2015

Study Record Updates

• Last Update Posted (Actual): September 2, 2020
• Last Update Submitted That Met QC Criteria: August 31, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: women; Dietary supplements; serum choline
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antimetabolites; Gastrointestinal Agents; Hypolipidemic Agents; Lipid Regulating Agents; Lipotropic Agents; Betaine
• Other Study ID Numbers: 14-1783; UL1TR001082 (U.S. NIH Grant/Contract)