The term vitamin E refers to a class of
plant-derived, lipid-soluble compounds which possess a substituted
chromanol ring attached to a long phytyl side chain.1-3,12,13
The ring structure is necessary to confer vitamin E activity. The human
diet includes eight vitamin E compounds: the a-, ß-, ?-, and
d-tocopherals and the a-, ß-, ?-, and d-tocotrienols.1-3,13 Mammals do not interconvert the tocopherol(TC) isoforms.13 ?-TC is found in corn and soybean oil as well as walnuts, pecans, pistachios, and sesame seeds.20
The main sources of ß-TC and d-TC are corn, corn oil, and rapeseed oil.
Other good sources of d-TC are tomato seeds, rice germ, and soybean
oil.14 a-TC is found predominantly in peanuts, almonds, and sunflower seeds.
a-TC is the only form of vitamin E that is actively retained by the body.1 The TCs are extremely hydrophobic molecules.3
Consequently, the delivery of a-TC into target tissues and cells
requires the presence of a specific enzyme, a-TC transfer protein
(a-TTP).3-5 a-TTP also facilitates the intracellular
trafficking of a-TC from lysosomes to the plasma membrane and from
hepatocytes to circulating lipoproteins.4,13 The critical
role of this protein and its ligand are revealed by the debilitating
pathologies that characterize individuals with mutations in the a-TTP
gene.3,4 Heritable mutations in this protein lead to severe
vitamin E deficiency characterized by progressive neurodegeneration,
ataxia and eventually death if vitamin E is not provided in large
quantities to overcome the lack of a-TTP.2 Due to lack of
specific transfer mechanisms, other tocopherols and tocotrienols are not
efficiently retained by the liver, and are instead metabolized, and
predominantly eliminated.21 As a result, tissue levels of a-TCs are 10-fold higher than the levels of other TCs.4,13
a-TC acts as a lipid-soluble peroxyl radical scavenger that disrupts the chain reaction by which lipid peroxidation propagates.3,6
During lipid oxidation, oxidized tocopheroxyl radicals are produced
that can be recycled back to the active, reduced form through reduction
by vitamin C.13 This process prevents oxidative damage to
long-chain polyunsaturated fatty acids in cell membranes during times of
oxidative stress.1,2,3,6 Consequently, vitamin E adequacy is
critical for numerous physiologic functions that rely on bilayer
integrity such as cell permeability and adhesion.6 a-TC is also thought to play a role in controlling the expression of several genes.7
Symptomatic dietary vitamin E deficiency is rare.3
The main manifestation of deficiency is peripheral neuropathy
associated with the degeneration of the large-caliber axons of sensory
neurons.10 Clinical features include dysarthria, clumsiness
of the hands, loss of proprioception, areflexia, dysdiadochokinesia,
decreased visual acuity, and positive Babinski sign. Primary deficiency
is seen in cases of the autosomal recessive disorder ataxia due to
heritable mutations in a-TTP.3 Primary deficiency is associated by very low plasma vitamin E levels.3 Secondary deficiency occurs in disorders of lipid absorption or lipoprotein metabolism and transport.3
Compromised intestinal fat absorption diseases including cholestatic
liver disease, short bowl syndrome, Crohn's disease, and
abetalipoproteinemia can cause secondary vitamin E deficiency.3
Cystic fibrosis associated fat malabsorption can also cause deficiency
in fat-soluble vitamins, including vitamin E. Diseases caused by
molecular defects that affect lipid transport and trafficking, including
Niemann-Pick disease-type C and Tangier disease are also associated
with vitamin E deficiency. Vitamin E deficiency is also seen in some
hematological disorders including, beta-thalassemia major, sickle-cell
anemia, and glucose-6-phosphate dehydrogenase deficiency.1
A
number of animal studies, observational human studies, and clinical
trials have investigated the possibility that vitamin E may have a
cardioprotective effect.8 a-TC has been shown to increase
oxidative resistance in vitro and to reduce atherosclerotic plaque
formation in mouse models. In addition, a-TC inhibits oxidation of low-
density lipoprotein cholesterol and modulates expression of proteins
involved in the uptake, transport, and degradation of atherogenic
lipids.14 Consumption of foods rich in a-TC has been
associated with decreased risk of coronary heart disease in middle-aged
to older men and women. While some reports have been encouraging, the
majority of clinical studies have not demonstrated a benefit of vitamin E
supplementation in the primary and secondary prevention of
cardiovascular disease.8,14
Animal studies have reported preventive effects of vitamin E on Alzheimer's disease neuropathology.26
A recent study found that a-TC was effective in slowing the functional
decline of mild to moderate Alzheimer disease and was also effective in
reducing caregiver time in assisting patients.15 However, the therapeutic effect seen was modest and related to disease symptoms and not to the reversal of the disease process.16 Vitamin E isoforms may also have a role in the production and clearance of amyloid beta.23
Until
recently, most research on vitamin E has focused on a-TC, because it is
the predominant form of vitamin E in tissues and low intake of a-TC is
associated with clinical manifestations including peripheral neuropathy
and ataxia.14 However, there is accumulating evidence for a role for another member of the vitamin E family, ?-TC in health and disease.14,20 ?-TC is the major form of vitamin E in the corn and soybean oils that are a major staple of the American diet.14 ?-TC is low in other oils such as sunflower and olive oil that are more prevalent in European diets.13,17
The average serum concentrations of a-TC are similar among these
populations while serum ?-TC levels in United States are 2- to 6-fold
higher than levels in Europeans.13,18 It has been suggested
that the conflicting outcomes of a number of vitamin E studies performed
in different countries may, in part, reflect differences in the serum
levels of ?-TC in foods and supplements administered.14,18
Reactive oxygen species (ROS) are produced as byproducts of the aerobic cellular metabolism and lipid oxidation.14 a- and ?-TC have similar capacity to scavenge these ROS.13,19,20 This process produces oxidized TC radicals that are recycled back to their active, reduced forms via reduction by vitamin C.13
ROS accumulation beyond the body's ability to scavenge them results in
"oxidative stress," which has been implicated in the pathophysiology of
numerous diseases.14,19,22 Unlike a-TC, ?-TC also reacts with reactive nitrogen species (RNS) that are produced by neutrophilic inflammation.13,18,20 It has been suggested that the ?-TC's ability to scavenge RNS may reduce inflammation.18,19
Recent
studies reveal disparate effects from supplementation with a- ?- and TC
in clinical studies of asthma and atherosclerosis.13,17,18,20
It has been suggested that excess a-TC taken in supplements causes a
reduction of ?-TC concentration in plasma due to more rapid metabolism
of ?-TC.24 Reports indicate that allergic inflammation is
inhibited by supplementation with a-TC but elevated by supplementation
with ?-TC.13 Studies suggest that ?-TC elevates inflammation
in experimental asthma and ablates the anti-inflammatory benefit of a-TC
treatment.17 A recent clinical study found that a-TC
supplementation produced improved spirometric parameters while
?-tocopherol produced a negative effect on spirometric parameters.18
Another recent study revealed a positive association between dietary
vitamin E intake and lung function, and evidence of an inverse
relationship between serum levels of ?-tocopherol and lung function.25
