section 38.1
Fat-Soluble Vitamins
913
particularly wheat germ and salad oils. Green vegeta-
bles, beef liver, butter, milk, and eggs contain apprecia-
ble amounts. Animals presumably obtain vitamin E from
plants in their diet. Fish liver oils, although rich in vitamins
A and D, are devoid of vitamin E.
The RDA depends on age and increases as the amount
of polyunsaturated fatty acid (PUFA) in the diet increases.
However, foods that are rich in PUFA are also rich in
vitamin E.
Absorption, Transport, and Metabolism
Vitamin E is absorbed as free tocopherol, along with
other fat-soluble vitamins and dietary lipids. Tocopheryl
acetate, the form commonly used for dietary supplemen-
tation, is hydrolyzed before absorption. Uptake requires
bile salts. A selective impairment of vitamin E absorption
without malabsorption of other fat-soluble vitamins has
been identified; it was corrected after a large oral intake of
the vitamin. Patients with chronic fat malabsorption and
abetalipoproteinemia (Chapter 20) may develop vitamin
E deficiency.
About 75% of the absorbed vitamin E enters the lym-
phatics in chylomicrons, and the rest in other lipoproteins.
In plasma, vitamin E is carried by lipoproteins and erythro-
cytes. In humans, vitamin E is present in greatest amounts
in adipose tissue, liver, and muscle. Its principal excretory
route is the feces, probably by way of bile.
Function
The function most consistent with symptoms of vitamin
E deficiency in animals is that of a general, membrane-
localized antioxidant, which protects cellular and sub-
cellular membranes from attack by endogenous and ex-
ogenous free radicals. In membranes, vitamin E may
be located near enzyme complexes that produce free
radicals, such as NADPH-dependent oxidase systems.
Selenium alleviates some symptoms of vitamin E defi-
ciency, probably through its role as a cofactor for glu-
tathione peroxidase, which reduces peroxides generated
within cells, thereby preventing formation of free rad-
icals. Vitamin E in the plasma membrane may act as
a first line of defense against free radicals, while glu-
tathione peroxidase may be a second line of defense.
Most enzymes affected by vitamin E deficiency are mem-
brane bound or are involved in the glutathione-peroxidase
system.
Vitamin E may also possess antiatherogenic properties.
In vitro, studies have shown that oxidized low-density
lipoproteins (LDL) are proatherogenic (Chapter 20) and
vitamin E retards LDL oxidation. Thus, it is thought
vitamin E supplementation might reduce the morbidity
and mortality from coronary artery disease. Nonantioxi-
dant functions of vitamin E may involve several cellular
signaling pathways (e.g., protein kinase C initiated path-
ways). The signaling pathways cause inhibition of proli-
feration of smooth muscle cells, platelet adhesion, and
aggregation and function of adhesion molecules. Vita-
min E also may attenuate the synthesis of leukotrienes and
increase synthesis of prostacyclin by upregulating phos-
pholipase A
2
and cyclooxygenase. All of these actions of
vitamin E may contribute toward its protective properties
against the development of atherosclerosis. In elucidating
the various biological functions of vitamin E complex, the
specific roles played by each of the four species of to-
copherols and four of trienols are not understood. Some
studies have suggested that tocotrienols may be superior
to tocopherols in their cardiovascular related effects.
Hypo- and Hypervitaminosis E
Characteristic lesions of vitamin E deficiency in ani-
mals include necrotizing myopathy (inaccurately referred
to as nutritional muscular dystrophy), exudative diathesis,
nutritional encephalomalacia, irreversible degeneration of
testicular tissue, fetal death and resorption, hepatic necro-
sis, and anemia. Several of these conditions are directly re-
lated to peroxidation of unsaturated lipids in the absence
of vitamin E, and others can be prevented by synthetic
antioxidants or vitamin E.
It is difficult to produce vitamin E deficiency in adult
humans. Adult males who were depleted of vitamin E for
6
years showed no symptoms, although serum tocopherol
concentrations became very low. However, their erythro-
cytes lysed more readily than normal when exposed to
hydrogen peroxide or other oxidizing agents
in vitro.
This
finding led to the use of low-plasma vitamin E and in-
creased susceptibility of erythrocytes to oxidative hemol-
ysis as criteria for vitamin E deficiency.
Premature infants and children with chronic cholestasis
may develop spontaneous vitamin E deficiency. In prema-
ture infants, the deficiency manifests itself as increased
red cell fragility and mild hemolytic anemia. It has been
claimed, but not established, that these infants respond
to administration of vitamin E. The anemia is not pre-
vented by vitamin E, and only small improvements in
red cell indices follow vitamin E treatment. A role has
been claimed for vitamin E in prophylaxis of
retrolental
fibroplasia
and
bronchopulmonary dysplasia,
two types
of oxygen-induced tissue injury that occur in premature
infants treated aggressively with oxygen.
Children with chronic cholestasis may exhibit a neuro-
muscular disorder that responds to treatment with vitamin
E given parenterally or in large oral doses. Some patients
