The Vitamins 149exhalation of pentane arising from the catabolism of
the products of peroxidation of n-6 PUFAs or ethane
arising from n-3 PUFAs.
Higher levels of intake
There is good epidemiological evidence that intakes
of vitamin E are associated with a lower risk of ath-
erosclerosis and ischemic heart disease. High concen-
trations of vitamin E will inhibit the oxidation of
PUFAs in plasma lipoproteins, and it is this oxidation
that is responsible for the development of atheroscle-
rosis. The plasma concentrations of α-tocopherol
that appear to be benefi cial would require an intake
of 17–40 mg/day, which is above what could be
achieved by eating normal diets. Individual interven-
tion trials of vitamin E supplements have generally
been disappointing, and metaanalysis shows a signifi -
cant increase in all-cause mortality among people
taking vitamin E (and other antioxidant) supple-
ments. This presumably refl ects the fact that the stable
tocopheroxyl radical can penetrate deeper into tissues
and plasma lipoproteins, and increase radical damage.
However, it is also possible that the plasma concentra-
tion of α-tocopherol is a surrogate marker for some
other protective factor in the diet.
Interactions with other nutrients
Vitamin C in plasma and extracellular fl uid is impor-
tant in reducing the tocopheroxyl radical in cell
membranes and plasma lipoproteins back to tocoph-
erol. There is also evidence that a variety of lipid-
soluble antioxidants may be important in the
antioxidant action of vitamin E in membranes and
lipoproteins, including ubiquinone and synthetic
antioxidants used in food processing, such as butyl-
ated hydroxytoluene and butylated hydroxyanisole.
Synthetic antioxidants will prevent or cure a number
of the signs of vitamin E defi ciency in experimental
animals.
There is a considerable overlap between the func-
tions of vitamin E and selenium. Vitamin E reduces
lipid peroxide radicals to unreactive fatty acids; the
selenium-dependent enzyme glutathione peroxidase
reduces hydrogen peroxide to water, thus lowering the
intracellular concentration of potentially lipid-dam-
aging peroxide. A membrane-specifi c isoenzyme of
glutathione peroxidase will also reduce the tocopher-
oxyl radical back to tocopherol. Thus, vitamin E acts
to remove the products of lipid peroxidation, whereas
selenium acts both to remove the cause of lipid per-
oxidation and to recycle vitamin E.8.5 Vitamin K
Vitamin K was discovered as a result of investigations
into the cause of a bleeding disorder (hemorrhagic
disease) of cattle fed on silage made from sweet clover
and of chickens fed on a fat-free diet. The missing
factor in the diet of the chickens was identifi ed as
vitamin K, whereas the problem in the cattle was that
the feed contained dicumarol, an antagonist of the
vitamin.
Since the effect of an excessive intake of dicumarol
was severely impaired blood clotting, it was isolated
and tested in low doses as an anticoagulant, for use in
patients at risk of thrombosis. Although it was effec-
tive, it had unwanted side-effects, and synthetic
vitamin K antagonists were developed for clinical use
as anticoagulants. The most commonly used of these
is warfarin, which is also used, in larger amounts, to
kill rodents.Vitamers
Three compounds have the biological activity of
vitamin K (Figure 8.6):
● phylloquinone, the normal dietary source, found in
green leafy vegetables;
● menaquinones, a family of related compounds syn-
thesized by intestinal bacteria, with differing lengths
of the side-chain;
● menadiol and menadiol diacetate, synthetic com-
pounds that can be metabolized to phylloquinone.Dietary sources, bacterial synthesis
and metabolism
Phylloquinone has a role in photosynthesis, and
therefore it is found in all green leafy vegetables; the
richest sources are spring (collard) greens, spinach,
and Brussels sprouts. In addition, soybean, rapeseed,
cottonseed, and olive oils are relatively rich in vitamin
K, although other oils are not.
About 80% of dietary phylloquinone is normally
absorbed into the lymphatic system in chylomicrons,
and is then taken up by the liver from chylomicron
remnants and released into the circulation in VLDLs.
Intestinal bacteria synthesize a variety of menaqui-
nones, which are absorbed to a limited extent from