Supplemental Choline and Brain Development in Humans
Condition: Healthy
Study type: Interventional

Summary: 
      Studies have shown that choline is a necessary part of the human diet. Choline is important
      in making membranes for all the cells in the body, and for making chemicals that are
      responsible for nerve function. Studies have also shown that choline improves memory of rats
      when they are given choline at early stages in their lives. The purpose of this study is to
      find out whether choline supplementation (provided as a choline dietary supplement) in
      pregnant women will improve memory function of their babies after they are born.

      In this study, we hypothesize that high dietary choline consumption during pregnancy and
      lactation will:

        1. Increase maternal choline concentration in plasma

        2. Increase breast milk choline concentration

        3. Enhance memory performance in the children born of supplemented mothers
    

Detailed description: 
      The development of brain during critical periods in embryogenesis is vulnerable to changes in
      diet, specifically changes in choline intake. Babies born of mothers eating more choline are
      smarter on memory testing. These effects of dietary choline have been repeatedly demonstrated
      in rodent models in a series of studies funded by the NIH during the last eight years.
      Specifically, prenatal choline supplementation in rats facilitates cognitive function and
      visuospatial memory, whereas choline deficiency impairs divided attention and accelerates the
      age-related decline in temporal processing. There are two sensitive periods in rat brain
      development during which treatment with choline produces long-lasting enhancement of spatial
      memory that is lifelong. The first occurs during embryonic days 12-17 (rats give birth on day
      21) and the second, during postnatal days 16-30. Choline supplementation during these
      critical periods elicits a major improvement in memory performance at all stages of training
      on a 12-arm radial maze. These changes in memory are correlated with decreases in the
      threshold for induction of long-term potentiation and with biochemical changes. Choline
      supplementation in pregnant rats decreases choline acetyltransferase activity and increases
      phospholipase D (PLD) activity in the hippocampus of offspring. Also, it increases the size
      of the cell body of cholinergic neurons. In contrast choline deficiency increases the
      activity of cholinergic system, but does not affect the basal level of PLD activity in
      hippocampus. These long-lasting functional, anatomical, and biochemical alterations may be
      related to the changes in neurogenesis and differentiation in fetal hippocampus and septum,
      areas of brain that are important for normal spatial learning and memory.

      It is not known if these findings in rodents are likely to be true in humans, as human and
      rat brains mature at different rates. Moreover, rat brain is comparatively more mature at
      birth than is the human brain, but in humans hippocampal development may start around 20
      weeks gestation and continue for months after birth. However, everything we know about brain
      development tells us that the processes seen in rodents are the same as those that occur in
      the developing human brain. For this reason, it is extremely likely that the robust effects
      we observe for choline in rodent brain have importance in the human. The research is the
      first major study in humans to determine whether maternal diet and diet during the baby's
      first year influences brain function.
    

Intervention name(s): Phosphatidylcholine; Corn oil placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 850 mg per day from 18 weeks pregnancy through 90 days postpartum; Placebo capsules containing corn oil given from 18 weeks pregnancy through 90 days postpartum
Other intervention name(s): PhosChol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)