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OCR for page 218
TABLE 1 Dietary Reference Intakes for Choline by
Life Stage Group
DRI values (mg/day)
AIa,b ULc
males females
Life stage group
NDd
0 through 6 mo 125 125
7 through 12 mo 150 150 ND
1 through 3 y 200 200 1,000
4 through 8 y 250 250 1,000
9 through 13 y 375 375 2,000
14 through 18 y 550 400 3,000
19 through 30 y 550 425 3,500
31 through 50 y 550 425 3,500
51 through 70 y 550 425 3,500
> 70 y 550 425 3,500
Pregnancy
£ 18 y 450 3,000
19 through 50 y 450 3,500
Lactation
£ 18 y 550 3,000
19 through 50 y 550 3,500
a AI = Adequate Intake.
b Although AIs have been set for choline, there are few data to assess whether a
dietary supply of choline is needed at all stages of the life cycle. It may be that the
choline requirement can be met by endogenous synthesis at some of these stages.
c UL = Tolerable Upper Intake Level. Unless otherwise specified, the UL represents
total intake from food, water, and supplements.
d ND = Not determinable. This value is not determinable due to the lack of data of
adverse effects in this age group and concern regarding the lack of ability to handle
excess amounts. Source of intake should only be from food to prevent high levels of
intake.
OCR for page 219
PART III: CHOLINE 219
CHOLINE
C
holine is required for the structural integrity of cell membranes. It is
also involved in methyl metabolism, cholinergic neurotransmission,
transmembrane signaling, and lipid and cholesterol transport and
metabolism. Choline in the diet is available as free choline or is bound as
esters such as phosphocholine, glycerophosphocholine, sphingomyelin, or
phosphatidylcholine.
Since data were insufficient to set an Estimated Average Requirement (EAR)
and thus calculate a Recommended Dietary Allowance (RDA) for choline, an
Adequate Intake (AI) was instead developed. The AIs for choline are based on
the intake required to maintain liver function, as assessed by measuring serum
alanine aminotransferase levels. The Tolerable Upper Intake Level (UL) is based
on hypotension as the critical effect, with fishy body odor as the secondary
consideration.
Although AIs have been set for choline, there are few data to assess whether
a dietary supply of choline is needed at all stages of the life cycle. It may be that
the choline requirement can be met by endogenous synthesis at some of these
stages. DRI values are listed by life stage group in Table 1.
Foods rich in choline include milk, liver, eggs, and peanuts. Lecithin, a
food additive used as an emulsifying agent, also adds choline to the diet. Al-
though choline is clearly essential to life, few data exist on the effects of inad-
equate dietary intake in healthy people. The signs and symptoms associated
with excess choline intake are fishy body odor, sweating, vomiting, salivation,
hypotension, gastrointestinal effects, and liver toxicity.
CHOLINE AND THE BODY
Function
Choline is required for the structural integrity of cell membranes. It is also
involved in methyl metabolism, cholinergic neurotransmission, transmembrane
signaling, and lipid and cholesterol transport and metabolism. For example,
choline accelerates the synthesis and release of acetylcholine, an important
neurotransmitter involved in memory and muscle control. It is also a precur-
sor for the synthesis of phospholipids, including phosphatidylcholine (a mem-
brane constituent important for the structure and function of membranes), for
intracellular signaling and hepatic export of very low density lipoproteins.
Lecithin, a substance commonly added to foods as an emulsifying agent, is
OCR for page 220
DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS
220
rich in phosphatidylcholine. The term lecithin is often interchangeably used
with phosphatidylcholine.
Absorption, Metabolism, Storage, and Excretion
Dietary choline is absorbed in the small intestine. Before it can be absorbed
from the gut, some is metabolized by bacteria to form betaine, which may be
absorbed and used as a methyl donor, and methylamines, which are not methyl
donors.
Choline is found in foods as free choline and as esterified forms such as
phosphocholine, glycerophosphocholine, sphingomyelin, and phosphatidylcho-
line. Pancreatic enzymes can liberate choline from some of the latter to form
free choline. Free choline enters the portal circulation of the liver, whereas phos-
phatidylcholine may enter the lymph in chylomicrons. All tissues, including
the brain, liver, and kidneys, accumulate choline by diffusion and mediated
transport. Some choline is excreted in the urine unchanged but most is oxi-
dized in the kidneys to form betaine.
DETERMINING DRIS
Determining Requirements
Since data were not sufficient for deriving an EAR, and thus calculating an
RDA, an Adequate Intake (AI) was instead developed. The AIs for choline are
based on the prevention of liver damage, as assessed by measuring serum ala-
nine aminotransferase levels. The estimate is uncertain because it is based on a
single published study and may need revision when data are available. This
amount is influenced by the availability of methionine and folate in the diet (see
“Dietary Interactions”). It may also be influenced by gender, pregnancy, lacta-
tion, and stage of development. Although AIs are set for choline, it may be that
the requirement can be met by endogenous synthesis at some of these life stages.
Most major nutrition surveys in the United States and Canada do not re-
port choline intake. The choline content of foods is also not included in major
nutrient databases.
Criteria for Determining Choline Requirements,
by Life Stage Group
Life stage group Criterion
0 through 6 mo Human milk content
7 through 12 mo Extrapolation from infants or from adults
1 through 3 y Extrapolation from adults
4 through >70 y Serum alanine aminotransferase levels
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PART III: CHOLINE 221
Pregnancy
£ 18 y through 50 y Age-specific + fetal and placental accumulation of choline
Lactation
£ 18 y through 50 y Age-specific + choline secreted in human milk
The UL
The Tolerable Upper Intake Level (UL) is the highest level of daily nutrient
intake that is likely to pose no risk of adverse effects for almost all people.
Members of the general population should not routinely consume more than
the UL. The UL for choline represents total intake from food, water, and supple-
ments. Hypotension was selected as the critical effect in deriving a UL for cho-
line, with fishy body odor selected as the secondary consideration.
Because there is no information from national surveys on choline intakes
or on supplement usage, the risk of adverse effects within the United States or
Canada cannot be characterized.
Special Considerations
Individuals susceptible to adverse effects: People with fish odor syndrome
(trimethylaminuria), renal disease, liver disease, depression, and Parkinson’s
disease may have an increased susceptibility to the adverse effects of choline
intakes at the UL.
DIETARY SOURCES
Foods
Most choline in foods is in the form of phophatidylcholine in membranes. Foods
that are especially rich in choline include milk, liver, eggs, and peanuts. It is
possible for usual dietary intakes to provide as much as 1,000 mg/day of cho-
line. Lecithin added during food processing may increase the average daily per-
capita consumption of phosphatidylcholine by 1.5 mg/kg of body weight for
adults.
Dietary Supplements
Choline is available as a dietary supplement as choline chloride or choline bi-
tartrate and as lecithin, which usually contains approximately 25 percent phos-
phatidylcholine or 3–4 percent choline by weight. There are no reliable esti-
mates of the frequency of use or the amount of these supplements consumed by
individuals in the United States and Canada.
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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS
222
Bioavailability
This information was not provided at the time the DRI values for this nutrient
were set.
Dietary Interactions
Choline, methionine, and folate metabolism interact at the point that homocys-
teine is converted into methionine. Disturbing the metabolism of one of these
methyl donors can affect the metabolism of the others.
INADEQUATE INTAKE AND DEFICIENCY
Although choline is clearly essential to life, few data exist on the effects of inad-
equate dietary intake in healthy people. Based on one study examining the
effects of artificially induced choline deficiency in healthy men who consumed
an otherwise adequate diet, liver damage occurred, resulting in elevated levels
of alanine aminotransferase in the blood. Fatty infiltration of the liver has also
been shown to occur in individuals fed with total parenteral nutrition (TPN)
solutions devoid of choline.
EXCESS INTAKE
Choline doses that are in orders of magnitude greater than estimated intake
from food have been associated with fishy body odor (trimethylaminuria), sweat-
ing, salivation, hypotension, and hepatotoxicity in humans. There are no indi-
cations in the literature that excess choline intake produces any additional ad-
verse effects in humans. Fishy body odor results from the excretion of excessive
amounts of trimethylamine, a choline metabolite, as the result of bacterial ac-
tion. Lecithin does not present a risk of fishy body odor.
OCR for page 223
PART III: CHOLINE 223
KEY POINTS FOR CHOLINE
Choline is required for the structural integrity of cell
3
membranes. It is also involved in methyl metabolism,
cholinergic neurotransmission, transmembrane signaling, and
lipid and cholesterol transport and metabolism.
Since data were insufficient to set an EAR and thus calculate
3
an RDA for choline, an AI was instead developed.
The AIs for choline are based on the prevention of liver
3
damage, as assessed by measuring serum alanine
aminotransferase levels.
Although AIs have been set for choline, there are few data to
3
assess whether a dietary supply of choline is needed at all
stages of the life cycle. It may be that the requirement can be
met by endogenous synthesis at some of these stages.
The UL is based on hypotension as the critical effect, with fishy
3
body odor as the secondary consideration.
People with fish odor syndrome (trimethylaminuria), renal
3
disease, liver disease, depression, and Parkinson’s disease
may have an increased susceptibility to the adverse effects of
choline intakes at the UL.
Foods rich in choline include milk, liver, eggs, and peanuts.
3
Lecithin, a food additive used as an emulsifying agent, also
adds choline to the diet.
Although choline is clearly essential to life, few data exist on
3
the effects of inadequate dietary intake in healthy people.
Based on one study examining the effects of induced
inadequate dietary intake in healthy men who consumed an
otherwise adequate diet, liver damage occurred.
Choline doses that are in orders of magnitude greater than
3
estimated intake from food have been associated with fishy
body odor (trimethylaminuria), sweating, salivation,
hypotension, and hepatotoxicity in humans. There are no
indications in the literature that excess choline intake produces
any additional adverse effects in humans.
