Choline, a dietary component of many foods, is part of several major
phospholipids (including phosphatidylcholine - also called lecithin) that
are critical for normal membrane structure and function. The major
precursor of betaine, it is used by the kidney to maintain water balance
and by the liver as a source of methyl-groups for methionine formation.
Also, choline is used to produce the important neurotransmitter
acetylcholine. In the body choline is mainly found in phospholipids, such
as lecithin (phosphatidylcholine) and sphingomyelin. The outer leaflet of
plasma membrane is rich in these choline-phospholipids whereas the inner
leaflet is dominated by phosphatidylethanolamine, phosphatidylserine, and
phosphatidylinositol. Phosphatidylcholine, the predominant phospholipid
(>50%) in most mammalian membranes, not only contributes to the structure
of the membrane bilayer, but products of receptor-mediated lecithin
hydrolysis also serve as important second messengers in signal cascades
that control cell growth and gene expression. Disaturated
phosphatidylcholine is the primary active component of surfactant in the
lung; a deficiency of surfactant in the neonate leads to respiratory
distress syndrome in premature infants.
The metabolism of choline, methionine, and methyl-folate are closely
interrelated; the metabolic pathways intersect at the formation of
methionine from homocysteine. Some choline can be formed from methionine
(through the methylation of phosphatidylethanolamine by
phosphatidylethanolamine N-methyltransferase using S-adenosylmethionine as
the methyl donor). This can provide some of the choline required by
humans.
There are a number of mechanisms that ensure the developing fetus and
the infant receive adequate amounts of choline. Like other nutrients,
large amounts of choline are delivered to the fetus across the placenta.
This depletes maternal stores of choline. Human milk is an especially good
source of choline.
Deficiencies: Although each of the above functions is
absolutely vital for the maintenance of normal cellular and organ
functions, it has been difficult to identify choline-deficiency syndromes
in humans. The Institute of Medicine noted that "Healthy males with normal
folate and vitamin B12 status fed a choline deficient diet have diminished
plasma choline and phosphatidylcholine concentrations, and develop liver
damage. For these humans, de novo synthesis of choline was not adequate to
meet the demand for the nutrient." Patients fed by total parenteral
nutrition sometimes develop fatty liver, abnormal liver function tests,
and low plasma choline and phosphatidylcholine concentrations. This is in
part due to an impaired capacity to de novo synthesize choline. In some of
these patients, these abnormalities resolve when they are treated with a
dietary source of choline.
Diet recommendations: Based on the limited human data
that is currently available, the Institute of Medicine, National Academy
of Sciences USA, recommended that humans consume choline. They set an
adequate intake (AI) level for choline of 550 mg/day for men and 425
mg/day for women. For children, the AI was proportionately adjusted for
body size.
Food sources: Choline and choline esters can be found
in significant amounts in many foods consumed by humans; some of the
choline is added during processing (especially in the preparation of
infant formula). Little reference information exists on the relative
choline content of foods, but we estimate the average choline dietary
intake (as choline and choline esters) of the adult human to be more than
500 mg/day. Orally ingested choline (e.g., as hydrochloride salt) may be
degraded by intestinal bacteria and cause a fishy body odor; this does not
occur when lecithin is eaten.
Clinical uses: Amino acid-glucose solutions used in
total parenteral nutrition of humans lack choline. The lipid emulsions
that deliver extra calories and essential fatty acids during parenteral
nutrition contain choline in the form of lecithin (20% emulsion contains
13.2 mmol/L). Humans treated with parenteral nutrition required 1-1.7 mmol
of choline-containing phospholipid/day during the first week of parenteral
nutrition therapy to maintain plasma choline levels.
There are no established approaches to determine nutritional status for
choline. Plasma choline and phosphatidylcholine concentrations fall when
humans are fed a choline-deficient diet or after strenuous, prolonged
physical activity, such as running a marathon. Even in severe deficiency,
plasma choline concentrations do not fall below 50% of normal. Measurement
of serum alanine aminotransferase activity, which rises approximately 1
week after the feeding a choline-deficient diet, may prove beneficial in
assessment of choline nutritional status.
Toxicity: Large oral doses of choline or
phosphatidylcholine may be associated with hypotension, sweating,
salivation and diarrhea. Large doses of choline can cause a fishy body
odor. The Tolerable Upper Limit for adults has been set at 3.5 g/day of
choline.
