Human Requirements for the Nutrient Choline
Condition: Postmenopausal Women
Study type: Interventional

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.
    

Intervention name(s): Estrogen plus choline depletion diet; Placebo plus choline depletion diet; Pre-menopausal women with SNPs given a low choline diet
Intervention type(s): Other; Other; Other
Intervention description(s): 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.; 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 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.
Intervention MeSH terms: Choline; Estrogens
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)