146 Introduction to Human Nutrition
functions require adequate, but not excessive, vitamin
A status. A number of drugs, including barbiturates
and other anticonvulsants, induce cytochrome
P 450 , resulting in increased catabolism of calcidiol
(and retinol), and cause drug-induced osteomalacia.
The antituberculosis drug isoniazid inhibits cholecal-
ciferol 25-hydroxylase in the liver, and prolonged
administration can lead to the development of
osteomalacia.
Strontium is a potent inhibitor of the kidney 1-
hydroxylase, and strontium intoxication can lead to
the development of vitamin D-resistant rickets or
osteomalacia. Although there is normally little expo-
sure to potentially toxic intakes of strontium, its
salts are sometimes used to treat chronic lead
intoxication.
8.4 Vitamin E
Although vitamin E was identifi ed as a dietary essen-
tial for animals in the 1920s, it was not until 1983 that
it was clearly demonstrated to be a dietary essential
for human beings. Unlike other vitamins, no unequiv-
ocal physiological function for vitamin E has been
defi ned; it acts as a lipid-soluble antioxidant in cell
membranes, but many of its functions can be replaced
by synthetic antioxidants. There is epidemiological
evidence that high intakes of vitamin E are associated
with lower incidence of cardiovascular disease,
although in many intervention trials vitamin E
supplements have been associated with increased
all-cause mortality.
Vegetable oils are rich sources of vitamin E, but
signifi cant amounts are also found in nuts and seeds,
most green leafy vegetables, and a variety of fi sh.
Vitamers and units of activity
Vitamin E is the generic descriptor for two families of
compounds, the tocopherols and the tocotrienols
(Figure 8.5). The different vitamers have different
biological potency. The most active is α-tocopherol,
and it is usual to express vitamin E intake in terms of
mg α-tocopherol equivalents. This is the sum of mg
α-tocopherol + 0.5 × mg β-tocopherol + 0.1 × mg
γ-tocopherol + 0.3 × mg α-tocotrienol. The other
vitamers have negligible vitamin activity.
The obsolete international unit of vitamin E activ-
ity is still sometimes used: 1 IU = 0.67 mg α-
tocopherol equivalent; 1 mg α-tocopherol = 1.49 IU.
Synthetic α-tocopherol does not have the same
biological potency as the naturally occurring com-
pound. This is because the side-chain of tocopherol
has three centers of asymmetry and when it is synthe-
sized chemically the result is a mixture of the various
isomers. In the naturally occurring compound all
three centers of asymmetry have the R-confi guration,
and naturally occurring α-tocopherol is called all-R,
or RRR-α-tocopherol.Absorption and metabolism
Tocopherols and tocotrienols are absorbed unchanged
from the small intestine, in micelles with other dietary
lipids, and incorporated into chylomicrons. The
major route of excretion is in the bile, largely as gluc-
uronides and other conjugates.
There are two mechanisms for tissue uptake of
vitamin E. Lipoprotein lipase releases the vitamin by
hydrolyzing the triacylglycerols in chylomicrons and
VLDLs, while separately there is uptake of low-density
lipoprotein (LDL)-bound vitamin E by means of LDL
receptors. Retention within tissues depends on intra-
cellular binding proteins, and it is likely that the dif-
ferences in biological activity of the vitamers are due
to differences in the affi nity of these proteins for the
different vitamers.Metabolic functions of vitamin E
The main function of vitamin E is as a radical-
trapping antioxidant in cell membranes and plasma
lipoproteins. It is especially important in limiting
radical damage resulting from oxidation of PUFAs, by
reacting with the lipid peroxide radicals before they
can establish a chain reaction. The tocopheroxyl
radical formed from vitamin E is relatively unreactive
and persists long enough to undergo reaction to yield
non-radical products. Commonly, the vitamin E
radical in a membrane or lipoprotein is reduced back
to tocopherol by reaction with vitamin C in plasma.
The resultant monodehydroascorbate radical then
undergoes enzymic or non-enzymic reaction to yield
ascorbate and dehydroascorbate, neither of which is
a radical.
The stability of the tocopheroxyl radical means that
it can penetrate further into cells, or deeper into
plasma lipoproteins, and potentially propagate a
chain reaction. Therefore, although it is regarded
as an antioxidant, vitamin E may, like other
antioxidants, also have pro-oxidant actions at high