148 Introduction to Human Nutrition
concentrations. This may explain why, although epi-
demiological studies have shown a clear association
between high blood concentrations of vitamin E and
lower incidence of atherosclerosis, the results of inter-
vention trials have generally been disappointing. In
many trials there has been increased all-cause mortal-
ity among those taking vitamin E and other antioxi-
dant supplements.
The tocotrienols have lower vitamin activity than
tocopherols, and indeed it is conventional to consider
only γ-tocotrienol as a signifi cant part of vitamin E
intake. However, because of their unsaturated side-
chain, the tocotrienols also have a hypocholesterol-
emic action not shared by the tocopherols. They act
to reduce the activity of 3-hydroxy-3-methylglutaryl-
coenzyme A (HMG CoA) reductase, the rate-limiting
enzyme in the pathway for synthesis of cholesterol, by
repressing synthesis of the enzyme.
Vitamin E defi ciency
In experimental animals vitamin E defi ciency results
in a number of different conditions.
● Defi cient female animals suffer the death and reab-
sorption of the fetuses. This provided the basis of
the original biological assay of vitamin E.
● In male animals defi ciency results in testicular
atrophy and degeneration of the germinal epithe-
lium of the seminiferous tubules.
● Both skeletal and cardiac muscle are affected in
defi cient animals. This necrotizing myopathy is
sometimes called nutritional muscular dystrophy –
an unfortunate term, since there is no evidence that
human muscular dystrophy is related to vitamin E
defi ciency.
● The integrity of blood vessel walls is affected, with
leakage of blood plasma into subcutaneous tissues
and accumulation under the skin of a green fl uid:
exudative diathesis.
● The nervous system is affected, with the develop-
ment of central nervous system necrosis and axonal
dystrophy. This is exacerbated by feeding diets rich
in PUFAs.
Dietary defi ciency of vitamin E in human beings is
unknown, although patients with severe fat malab-
sorption, cystic fi brosis, some forms of chronic liver
disease or (very rare) congenital lack of plasma β-
lipoprotein suffer defi ciency because they are unable
to absorb the vitamin or transport it around the body.
They suffer from severe damage to nerve and muscle
membranes.
Premature infants are at risk of vitamin E defi -
ciency, since they are often born with inadequate
reserves of the vitamin. The red blood cell membranes
of defi cient infants are abnormally fragile, as a result
of unchecked oxidative radical attack. This may lead
to hemolytic anemia if they are not given supple-
ments of the vitamin.
Experimental animals that are depleted of vitamin
E become sterile. However, there is no evidence that
vitamin E nutritional status is in any way associated
with human fertility, and there is certainly no evi-
dence that vitamin E supplements increase sexual
potency, prowess, or vigor.Vitamin E requirements
It is diffi cult to establish vitamin E requirements,
partly because defi ciency is more or less unknown,
but also because the requirement depends on the
intake of PUFAs. It is generally accepted, albeit with
little experimental evidence, that an acceptable intake
of vitamin E is 0.4 mg α-tocopherol equivalent/g
dietary PUFA.Indices of vitamin E status
The plasma concentration of α-tocopherol is used to
assess vitamin E status; since most vitamin E is trans-
ported in plasma lipoproteins, it is the concentration
per gram total plasma lipid, or better per mole
cholesterol, that is useful, rather than the simple
concentration.
Erythrocytes are incapable of de novo lipid synthe-
sis, so peroxidative damage resulting from oxygen
stress has a serious effect, shortening red cell life and
possibly precipitating hemolytic anemia in vitamin E
defi ciency. This has been exploited as a method of
assessing status by measuring the hemolysis of red
cells induced by dilute hydrogen peroxide relative to
that observed on incubation in water. This gives a
means of assessing the functional adequacy of vitamin
E intake, albeit one that will be affected by other, unre-
lated, factors. Plasma concentrations of α-tocopherol
below 2.2 mmol/mol cholesterol or 1.1 μmol/g total
plasma lipid are associated with increased susceptibil-
ity of erythrocytes to induced hemolysis in vitro.
An alternative method of assessing functional anti-
oxidant status, again one that is affected by both
vitamin E and other antioxidants, is by measuring the