Choline and Brain Functioning in Postmenopausal Women

This study will use a randomized placebo-controlled trial to examine a single oral dose of 1650 mg choline influences brain functioning as measured by fMRI.

Study Overview

• Status: Completed
• Conditions: Menopause
• Intervention / Treatment: Dietary supplement: Choline; Dietary supplement: Placebo

Detailed Description

Choline is an essential nutrient that, in addition to its role in the brain, has a number of critical structural and physiologic roles throughout the body, including providing structural integrity and signaling function for cell membranes, facilitating lipid transport from the liver, and acting as the major source of methyl groups through diet. Aside from dietary intake, the only source of choline in the body is de novo synthesis of phosphatidylcholine, catalyzed by phosphatdylethanolamine-N-methyltransferase (PEMT). The PEMT gene has several estrogen-responsive components in its promoter region and is induced by estrogen. Post-menopausal (hypo-estrogenic) women with loss of function mutations in PEMT have been found to exhibit end-organ damage typical of choline deficiency.

Choline is also involved in the synthesis of acetylcholine, a major neurotransmitter and the central and peripheral nervous systems. The relationship between brain effects of the normal functioning of the cholinergic system and hormone changes after menopause has been demonstrated in preclinical studies in rat models and in experimentally in human studies. While the preclinical and clinical experiment studies have many similar findings regarding the influence of estrogen on cholinergic functioning, what is not clear from this research is how individual differences arise in the effects of the hormone withdrawal after menopause on brain functioning in middle aged women. It is possible that the estrogen control of the transcription of the PEMT gene may influence the availability of choline.

This study will examine the effects of a single oral dose of oral dose of 1650 mg choline versus placebo in 20 healthy postmenopausal women aged 50-65 years. Choline or placebo will be administered three hours before an MRI session where subjects undergo functional MRI scans.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Women aged 50-65 years
• Postmenopausal: Women who are postmenopausal will have not had a period in the last 12 months, have FSH>30 IU/L, and estradiol (E2) <50 pg/ml.
• Nonsmokers
• Not taking hormone therapy, SSRIs, phytoestrogens, SERMS, or antiestrogen medications and will be at least one year without such treatment
• Physically healthy
• No cardiovascular disease other than mild hypertension. Subjects will also not have current untreated or unremitted Axis I or II psychiatric or cognitive disorders (see screening below).
• IQ in the normal range >80
• Normal neuropsychological test performance

Exclusion Criteria:

• MCI or dementia - Montreal Cognitive Assessment <26, Mattis Dementia Rating Scale <130, and Global Deterioration Scale >2
• History of cancer treatment with cytotoxic and/or ongoing (current) maintenance targeted chemotherapy
• Blood pressure > 160/100 (untreated)
• Untreated thyroid disease
• Significant cardiovascular disease
• Asthma or COPD
• Active peptic ulcer
• Hyperthyroidism
• Epilepsy
• Current untreated or unremitted Axis I psychiatric disorders
• Use of medications on the Prohibited medications (see list)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Choline; Each subject completes two study days with choline and placebo.	Dietary supplement: Choline; Each subject gets one 1650 mg oral choline dose or placebo on each of two study days.
Experimental: Placebo; Each subject completes two study days with choline and placebo.	Dietary supplement: Placebo; Each subject gets one 1650 mg oral choline dose or placebo on each of two study days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BOLD Signal during fMRI working memory task	fMRI BOLD signal during a working memory task	Measured on each of the two study days

Collaborators and Investigators

• Sponsor: University of Vermont
• Collaborators: Balchem Corporation
• Investigators: Principal Investigator: Julie A Dumas, PhD, University of Vermont

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2022
• Primary Completion (Actual): December 20, 2022
• Study Completion (Actual): March 1, 2025

Study Registration Dates

• First Submitted: September 10, 2025
• First Submitted That Met QC Criteria: December 1, 2025
• First Posted (Estimated): December 4, 2025

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: cognition; fMRI; working memory; choline
• Additional Relevant MeSH Terms: Organic Chemicals; Amines; Alcohols; Amino Alcohols; Ethanolamines; Quaternary Ammonium Compounds; Onium Compounds; Trimethyl Ammonium Compounds; Choline
• Other Study ID Numbers: STU1720

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After data are published, deidentified data will be made available to those who request access.
• IPD Sharing Time Frame: 10/2025 until 9/2030
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No