Clinical trial NCT00065546: Human Requirements for the Nutrient Choline
Official title: Human Requirements for the Nutrient Choline
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postmenopausal Women
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2003-07-31
Enrollment: 43
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief 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.

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 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)

Primary outcomes:
measure: Evidence of liver or muscle dysfunction (based on elevations in CPK, AST, ALT), or increased liver fat (measured by liver MRI)
timeFrame: Labs measured every 3-4 days throughout 62-day trial. Liver MRI performed on study days 1, 10, 31, 52, 62.
Secondary outcomes:
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Steven H Zeisel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: Leslie M Fischer, PhD, MPH, RD
role: STUDY_DIRECTOR
References:
citation: da Costa KA, Corbin KD, Niculescu MD, Galanko JA, Zeisel SH. Identification of new genetic polymorphisms that alter the dietary requirement for choline and vary in their distribution across ethnic and racial groups. FASEB J. 2014 Jul;28(7):2970-8. doi: 10.1096/fj.14-249557. Epub 2014 Mar 26.
citation: da Costa KA, Sanders LM, Fischer LM, Zeisel SH. Docosahexaenoic acid in plasma phosphatidylcholine may be a potential marker for in vivo phosphatidylethanolamine N-methyltransferase activity in humans. Am J Clin Nutr. 2011 May;93(5):968-74. doi: 10.3945/ajcn.110.011064. Epub 2011 Mar 16.
citation: Fischer LM, da Costa KA, Kwock L, Galanko J, Zeisel SH. Dietary choline requirements of women: effects of estrogen and genetic variation. Am J Clin Nutr. 2010 Nov;92(5):1113-9. doi: 10.3945/ajcn.2010.30064. Epub 2010 Sep 22.