Human Requirements for the Nutrient Choline - Full Text View

Sponsor:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:	NCT00065546

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
Healthy	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:	Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment
Official Title:	Human Requirements for the Nutrient Choline

Resource links provided by NLM:

MedlinePlus related topics: Diets Menopause

Drug Information available for: Choline Choline chloride Choline dihydrogen citrate Choline bitartrate Choline salicylate

U.S. FDA Resources

Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

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 ]

Estimated Enrollment:	60
Study Start Date:	June 2007
Estimated Study Completion Date:	November 2011
Estimated Primary Completion Date:	November 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator 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.
2: Placebo Comparator 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.
3: Experimental 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

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

Locations

United States, North Carolina
University of North Carolina	Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Brigitte Stephenson, MPH, RD 919-408-3320 ext 32 bjstep@unc.edu
Contact: Leslie M Fischer, PhD, MPH, RD 919 408-3320 ext 31 lfischer@email.unc.edu
Principal Investigator: Steven H Zeisel, MD, PhD

Sponsors and Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

Principal Investigator:	Steven H Zeisel, MD, PhD	The University of North Carolina, Chapel Hill
Study Director:	Leslie M Fischer, PhD, MPH, RD	The University of North Carolina, Chapel Hill

More Information

No publications provided

Responsible Party:	University of North Carolina at Chapel Hill ( Steven H. Zeisel, MD, PhD - Professor of Nutrition and Pediatrics, Director, UNC Clinical Nutrition Research Center )
Study ID Numbers:	HRNUT (DK55865)
Study First Received:	July 28, 2003
Last Updated:	October 5, 2009
ClinicalTrials.gov Identifier:	NCT00065546 History of Changes
Health Authority:	United States: Federal Government

Additional relevant MeSH terms:

Antimetabolites
Lipotropic Agents
Nootropic Agents
Choline
Estrogens
Molecular Mechanisms of Pharmacological Action
Antilipemic Agents

Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Hormones
Pharmacologic Actions
Therapeutic Uses
Central Nervous System Agents

ClinicalTrials.gov processed this record on November 27, 2009