VitaminE is a collective name for all stereoisomers of tocopherols and tocotrienols.The most biologically active form is α-tocopherol, butβ-, γ-, δ-tocopherols,4 tocotrienols, and several stereoisomers may also have important biologicalactivity. Vitamin E acts as achain-breaking antioxidant and is an efficient free radical scavenger, to protect low-density lipoproteins (LDLs) and polyunsaturated fats in membranesfrom oxidation. A network of other antioxidants (e.g., vitamin C, glutathione)and enzymes maintain vitamin E in its reduced state.
Absorption and Metabolism
After absorption, vitamin E is taken up from chylomicrons by the liver, and a hepatic α-tocopherol transport protein mediates intracellular vitamin E transport and incorporation into very low-density lipoprotein (VLDL). The transportprotein has particular affinity for α-tocopherol; thus this natural isomer has the most biologicactivity.
VitaminE is widely distributed in the food supply and is particularly high insunflower oil, safflower oil, and wheat germ oil; γ tocotrienols are notably present in soybean and corn oils.Vitamin E is also found in meats, nuts, and cereal grains, and small amountsare present in fruits and vegetables. The RDA for vitamin E is 15 mg/d (34.9 μmol or22.5 IU) for all adults. Diets high in polyunsaturatedfats may necessitate a slightly higher requirement for vitamin E.
Functions of vitamin E
1) It acts as a lipid-soluble antioxidant in cell membranes, and is important inmaintaining the fluidity of cell membranes.
Antioxidant role of vitamin E
Reactive oxygen species (ROS) are molecular oxygen metabolites that arehighly reactive with lipids, proteins, and DNA, causing oxidative damage tothese cellular macromolecules. This damage, termed oxidative stress, accumulates over time and is thought tocontribute to both disease pathology and the aging process. Cellular mechanismsthat exist to counteract ROS include stabilization by enzymes such as superoxidedismutase and Catalase, and direct scavenging by antioxidant molecules such asglutathione (GSH) and a major extracellular antioxidant in plasma; vitamin E, a major lipidsoluble antioxidant; and ascorbate, a critical intracellular and extracellularantioxidant.
The main function of vitamin E is as a chain-breaking, free-radical trappingantioxidant in cell membranes and plasma lipoproteins.
By reacting with the lipid peroxide radicals formed byperoxidation of polyunsaturated fatty acids, it gets converted to tocopheroxyl radical.The resultant radical (Oxidized form) is relatively unreactive, and ultimatelyforms nonradical compounds. Commonly, the tocopheroxyl radical is reduced backto tocopherol by reaction with vitamin C from plasma. (See Figure)
Ascorbate (Vitamin C) is essential formaintaining vitamin E in its reduced, active form. Ascorbate is oxidized todehydroascorbate in plasma and that is recycled back to ascorbate by GSH aswell as by several enzyme systems in erythrocytes, neutrophils, endothelial cellsand hepatocytes (See figure).
GSH itself gets oxidized during this process andis converted back to its reduced form by Glutathione reductase utilizingNADPHas the reductant. GSH is also required bySelenium containing Glutathione Peroxidase enzyme for decomposing H2O2.
A synergism is observed between seleniumand vitamin E .The synergism is related to theprocessof antioxidation, wherein tocopherols tend to preventoxidativedamage to polyunsaturated fats in cell membranes,whereas selenium,as part of seleno-enzyme glutathione peroxidase,catalyzes thedestruction of lipid hydro peroxides. This explainshow these twonutrients play separate but interrelated rolesin the cellular defensesystem against oxidative damage. Vitamin E deficiency results in failure to scavengefree radicals and as a consequence there is membrane disruption especially ofred blood cells.(See the details below)
As an antioxidant, vitamin E plays a protective role inmany organs and systems. Vitamin E is necessary for maintaining a healthyimmune system, and it protects the thymus and circulating white blood cellsfrom oxidative damage. Also, it may work synergistically with vitamin C inenhancing immune function. Recent research evidence indicates that the combineduse of high doses of vitamin C and vitamin E helps prevent Alzheimer’s disease.In eyes, vitamin E is needed for the development of the retina and protectsagainst cataracts and macular degeneration.
Figure- showing the anti oxidant role of vitamin E, A synergism is observed between Vitamin E,C and G-SH dependent Glutathione peroxidase.
2) Other functions of vitamin E- It also has a (relatively poorly defined) role in cell signaling. Besides that, Vitamin Einhibits prostaglandin synthesis and theactivities of protein kinase C and Phospholipase A2.
3) In highconcentration, the tocopheroxyl free radical can penetrate further into cellsand, potentially, propagate a chain reaction. Therefore, vitamin E may, likeother antioxidants, also have pro-oxidantactions, especially at high concentrations. This explains the bleedingobserved in vitamin E toxicity.
Vitamin E Deficiency
Dietary vitamin E deficiency is common in developingcountries; deficiency among adults in developed countries is uncommon and is usuallydue to fat malabsorption. The mainsymptoms are hemolytic anemia and neurologic deficits.
Absorption of vitamin E depends on normalpancreatic biliary function, biliary secretion, micelle formation, andpenetration across intestinal membranes. Interference with any of theseprocesses could result in a deficiency state.
Indeveloping countries, the most common cause is inadequate intake of vitamin E.In developed countries, the most common causes are disorders that cause fat malabsorption, including Abetalipoproteinemia(genetic absence of Apo lipoprotein B), chronic cholestatic hepatobiliarydisease, pancreatitis, short bowel syndrome, and cystic fibrosis.
Vitamin E deficiency is seen in only severeand prolonged malabsorptive diseases, such as celiac disease, or aftersmall-intestinal resection. Children with cystic fibrosis or prolongedcholestasis may develop vitamin E deficiency characterized by areflexia andhemolytic anemia.
Children with Abetalipoproteinemia cannot absorb or transportvitamin E and become deficient quite rapidly.(Apo B48 is required for chylomicron formation and that is needed for transportation of vitamin E from gut to liver)
Isolated vitamin E deficiency syndrome – Developing in the absence of fat malabsorption, this syndrome iscaused by an autosomal-recessive genetic disorder. Neurologic findings developwithin the first decade of life. It is due to a defect in the α-tocopheroltransport protein.
The main symptoms are-
Mild hemolytic anemia and nonspecific neurological deficits
Biochemical basis of hemolytic anemia- Vitamin E deficiency results in oxidative damage to thered cell membrane, with the resultant altered permeability and osmolysis.(Seethe flowchart below)
Flow chart- showing the biochemical basis of hemolytic anemia observedin vitamin E deficiency
Bochemical basis of Ataxia and neurological symptoms- Vitamin E deficiency causes axonal degeneration of thelarge myelinated axons and results in posterior column and spinocerebellarsymptoms. Peripheral neuropathy is initially characterized by areflexia, withprogression to an ataxic gait, and by decreased vibration and positionsensations.
In adults with malabsorption, vitamin Edeficiency very rarely causes spinocerebellar ataxia because adults have largevitamin E stores in adipose tissue.
Low α-tocopherollevel or low ratio of plasma α-tocopherol to plasma lipids
Measuring the plasma α-tocopherollevel -is the most direct method of diagnosis. In adults, vitamin E deficiencyis suggested if the α-tocopherol level is < 5 μg/mL(< 11.6 µmol/L).
Because abnormal plasma lipid levels can affect vitamin E status, a low ratio of plasma α-tocopherol toplasma lipids (< 0.8 mg/g total lipid) is the most accurate indicator in adults with hyperlipidemia.
In children and adults with Abetalipoproteinemia, plasma α-tocopherollevels are usually undetectable.
Although premature neonates may require supplementation, human milk and commercialformulas have enough vitamin E for full-term neonates.
If malabsorption causes clinically evident deficiency, α-tocopherol15 to 25 mg/kg orally once/day should be given. However, larger doses given byinjection are required to treat neuropathy during its early stages or toovercome the defect of absorption and transport in Abetalipoproteinemia.
Vitamin E Toxicity
Many adults take relatively large amounts of vitamin E (α-tocopherol 400to 800 mg/day) for months to years without any apparent harm. Occasionally,muscle weakness, fatigue, nausea, and diarrhea occur. The most significant riskis bleeding. However, bleeding is uncommon unless the dose is > 1000 mg/day or the patient takes oral coumarin or warfarin.