Human Requirements for the Nutrient Choline

Postmenopausal Women Clinical Trial

Official title:

Human Requirements for the Nutrient Choline

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00065546
• Other study ID #: DK55865
• Secondary ID: R01DK055865
• Status: Completed
• Phase: N/A
• First received: July 28, 2003
• Last updated: January 5, 2012
• Start date: June 2007
• Est. completion date: January 2012

Study information

• Verified date: January 2012
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: January 2012
• Est. primary completion date: September 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 85 Years

Eligibility

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)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Postmenopausal Women

Intervention

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 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.
• 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.

Locations

Country	Name	City	State
United States	University of North Carolina	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evidence of liver or muscle dysfunction (based on elevations in CPK, AST, ALT), or increased liver fat (measured by liver MRI)		Labs measured every 3-4 days throughout 62-day trial. Liver MRI performed on study days 1, 10, 31, 52, 62.	No