Human Requirements for the Nutrient Choline

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Steven Zeisel, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT00065546
First received: July 28, 2003
Last updated: January 5, 2012
Last verified: January 2012
  Purpose

The purpose of this study is to increase our understanding of how much choline humans need to get from their diet. Choline is an essential nutrient found in many foods, including eggs and milk. In addition to dietary sources, choline can be made in the liver. Choline is important in making membranes or wrappers for all the cells in the body and for making chemicals that allow nerve cells to work properly. In a previous study we found that the dietary requirement for choline varies greatly from person to person. This was caused, in part, by how much estrogen a person has and their genetic makeup. We are conducting this study to explore how estrogen levels and specific differences in genes influence choline requirements so that we can refine the dietary recommendations for this nutrient.


Condition Intervention
Postmenopausal Women
Other: Estrogen plus choline depletion diet
Other: Placebo plus choline depletion diet
Other: Pre-menopausal women with SNPs given a low choline diet

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Official Title: Human Requirements for the Nutrient Choline

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Evidence of liver or muscle dysfunction (based on elevations in CPK, AST, ALT), or increased liver fat (measured by liver MRI) [ Time Frame: Labs measured every 3-4 days throughout 62-day trial. Liver MRI performed on study days 1, 10, 31, 52, 62. ] [ Designated as safety issue: No ]

Enrollment: 43
Study Start Date: June 2007
Study Completion Date: January 2012
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Post-menopausal women randomized to receive estrogen replacement therapy.
Other: Estrogen plus choline depletion diet
Post-menopausal subjects receive estrogen and are then challenged with a low choline diet to determine if estrogen protects them from induction of choline deficiency.
Placebo Comparator: 2
Post-menopausal women randomized to receive a placebo.
Other: Placebo plus choline depletion diet
Post-menopausal women are randomized to receive a placebo and are then subjected to a low choline diet to determine if clinical signs of choline deficiency can be induced.
Experimental: 3
Pre-menopausal women with specific genetic variants.
Other: Pre-menopausal women with SNPs given a low choline diet
Pre-menopausal women with specific genetic polymorphisms in genes related to choline metabolism are placed on a choline depletion diet to determine if the SNPs increase or decrease the risk of diet-induced choline deficiency.

Detailed Description:

Choline is an essential nutrient essential used for the structural integrity and signaling functions of cell membranes, cholinergic neurotransmission, and lipid transport/metabolism. Choline is obtained from the diet and from endogenous biosynthesis catalyzed by the enzyme phosphatidylethanolamine N-methyltransferase (PEMT). The major premise for this proposal is that humans require a dietary source of choline and that this requirement has significant individual variation and is modulated by estrogen and common genetic polymorphisms. The promoter of the PEMT gene is estrogen responsive, and we hypothesize that estrogen status influences the dietary requirement for choline. We identified other common single nucleotide polymorphisms (SNPs) that increase or decrease the likelihood that a human will develop organ dysfunction when fed a low choline diet. Experiments are proposed that will refine our understanding of estrogen-mediated induction of the PEMT promoter; determine whether postmenopausal women treated with estrogen have a decreased susceptibility to developing organ dysfunction associated with choline deficiency; determine the prevalence of SNPs that increase susceptibility to choline deficiency in the population and examine dietary choline requirements in humans with these SNPs.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy
  • Non-smoker
  • BMI between 18 and 34
  • Normal mammogram in last 12 months (post-menopausal women only)

Exclusion Criteria:

  • Hormone or estrogen therapy
  • Allergic to soy, eggs, wheat
  • History of breast, uterine, or other estrogen-dependent cancer
  • Liver or kidney problems
  • History of circulation, bleeding, or blood-clotting disorder
  • Anemia or evidence of iron overload
  • Hyperthyroidism, neurological disorder, or autoimmune disease
  • Diabetes controlled by insulin
  • Positive serology for HIV or Hepatitis B or C
  • Alcohol or illegal drug misuse/abuse
  • Pacemaker, aneurysm clip, cardiac heart valve, mechanical devices/implants
  • Other metal in body (i.e. injured by a BB, shrapnel, or metallic object)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00065546

Locations
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Steven H Zeisel, MD, PhD University of North Carolina, Chapel Hill
Study Director: Leslie M Fischer, PhD, MPH, RD University of North Carolina, Chapel Hill
  More Information

No publications provided by University of North Carolina, Chapel Hill

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Steven Zeisel, Professor of Nutrition and Pediatrics, Director, UNC Nutrition Research Institute, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00065546     History of Changes
Other Study ID Numbers: DK55865, R01DK055865
Study First Received: July 28, 2003
Last Updated: January 5, 2012
Health Authority: United States: Federal Government
United States: Institutional Review Board

Additional relevant MeSH terms:
Choline
Estrogens
Lipotropic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses
Lipid Regulating Agents
Nootropic Agents
Central Nervous System Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2014