186 Introduction to Human Nutrition
Biofl avonoids
The most studied fl avonoids are hesperitin and quer-
citin. Because they are biologically active, they are
commonly called biofl avonoids. Most fruits and green
leafy vegetables contain relatively large amounts of
fl avonoids; altogether some 2000 have been identi-
fi ed, and average intakes of fl avonoids from a mixed
diet are of the order of 1 g/day.
There is no evidence that biofl avonoids are dietary
essentials, but they have potentially useful antioxidant
actions. Oxidation of fl avonoids may serve to protect
susceptible nutrients from damage in foods and the
intestinal lumen, and they may also act as antioxi-
dants in plasma and tissues. Epidemiological evidence
suggests that the intake of fl avonoids is inversely cor-
related with mortality from coronary heart disease.
Carnitine
Carnitine has a central role in the transport of fatty
acids across the mitochondrial membrane. It is syn-
thesized in both liver and skeletal muscle by methyla-
tion of lysine, followed by two vitamin C-dependent
hydroxylations. In experimental animals, defi ciency
of lysine has little effect on plasma and tissue concen-
trations, but methionine defi ciency can lead to carni-
tine depletion, and carnitine has a methionine-sparing
effect in methionine-defi cient animals.
Defi ciency of vitamin C may result in impaired
synthesis of carnitine in species for which ascorbate
is a vitamin.
The administration of the anticonvulsant valproic
acid can lead to carnitine depletion. This results in
impaired β-oxidation of fatty acids and ketogenesis,
and hence a nonketotic hypoglycemia, with elevated
plasma nonesterifi ed fatty acids and triacylglycerols.
There may also be signs of liver dysfunction, with
hyperammonemia and encephalopathy. The admin-
istration of carnitine supplements in these conditions
has a benefi cial effect.
Although carnitine is not generally nutritionally
important, it may be required for premature infants,
since they have a limited capacity to synthesize it.
There is some evidence that full-term infants may also
have a greater requirement for carnitine than can
be met by endogenous synthesis; infants fed on
carnitine-free soya-milk formula have higher plasma
concentrations of nonesterifi ed fatty acids and triacyl-
glycerols than those receiving carnitine supplements.
Carnitine depletion, with disturbed lipid metabolism,
has also been reported in adults maintained for pro-
longed periods on total parenteral nutrition. There is
some evidence that supplements of carnitine may
increase the ability of muscle to oxidize fatty acids,
and so increase physical work capacity, although other
studies have shown no effect.Choline
Choline is important as a base in phospholipids: both
phosphatidylcholine (lecithin) in all cell membranes
and sphingomyelin in the nervous system. In addi-
tion, acetylcholine is a transmitter in the central and
parasympathetic nervous systems and at neuromus-
cular junctions. There is some evidence that the avail-
ability of choline may be limiting for the synthesis of
acetylcholine in the central nervous system under
some conditions. In animals, defi ciency of choline
results in fatty infi ltration of the liver, apparently as a
result of impairment of the export of lipoproteins
from hepatocytes; prolonged defi ciency may result in
cirrhosis. The kidney can also be affected, with tubular
necrosis and interstitial hemorrhage, probably as a
result of lysosomal membrane disruption.
There is no evidence that choline is a dietary essen-
tial for humans, and no condition similar to the
effects of choline defi ciency in experimental animals
has been reported. Since phosphatidylcholine is found
in all biological membranes, dietary defi ciency is
unlikely to occur except when people are maintained
on defi ned diets free from phospholipids. Plasma
concentrations fall during long-term total parenteral
nutrition, and it is possible that the impaired liver
function seen in such patients is partly the result of
choline depletion.Inositol
The main function of inositol is in phospholipids;
phosphatidylinositol constitutes some 5–10% of the
total membrane phospholipids. In addition to its
structural role in membranes, phosphatidylinositol
has a major function in the intracellular responses to
hormones and neurotransmitters, yielding two intra-
cellular second messengers, inositol trisphosphate,
and diacylglycerol.
There is no evidence that inositol is a dietary essen-
tial. Infants may have a higher requirement than can
be met by endogenous synthesis. Untreated diabetics
have high plasma concentrations of free inositol and
high urinary excretion of inositol, associated with
relatively low intracellular concentrations of inositol,
suggesting that elevated plasma glucose may inhibit