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Vitamin E

  • A fat soluble vitamin
  • Also called Anti infertility vitamin
  • Vitamin E acts as a chain-breaking antioxidant and is an efficient free radical scavenger.
  • It protects low-density lipoproteins (LDLs) and polyunsaturated fats in membranes from oxidation.
  • A network of other antioxidants (e.g., vitamin C, glutathione) and enzymes maintains vitamin E in its reduced state.

Structure of vitamin E

  • Vitamin E derivatives have a chromane ring (tocol) system.
  • An isoprenoid side chain is attached to the chromane ring (Figure-1)
  • There are eight naturally occurring tocopherols
  • Vitamin E is a collective name for all stereoisomers of tocopherols and tocotrienols.
  • The most biologically active is α-tocopherols, but β-, γ-, δ-tocopherols, 4 tocotrienols, and several stereoisomers may also have important biological activity.

 Structure of vitamin E










Figure-1- Alpha tocopherol- 5,7,8-trimethyl tocol

Absorption and Metabolism

  • Absorption requires the presence of bile salts
  • After absorption, vitamin E is taken up by chylomicrons to the liver
  • A hepatic α -tocopherol transport protein mediates intracellular vitamin E transport and incorporation into very low-density lipoprotein (VLDL).
  • The transport protein has particular affinity for α -tocopherol; thus this natural isomer has the most biologic activity.


  • Vitamin E is widely distributed in the food supply and is particularly high in sunflower 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 amounts are present in fruits and vegetables.
  • The RDA for vitamin E is 15 mg/d (34.9 μmol or 22.5 IU) for all adults.
  • Diets high in polyunsaturated fats 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 in maintaining the fluidity of cell membranes.

Antioxidant role of vitamin E

  • Reactive oxygen species (ROS) are molecular oxygen metabolites that are highly reactive with lipids, proteins, and DNA, causing oxidative damage to these cellular macromolecules.
  • This damage, termed oxidative stress, accumulates over time and is thought to contribute to both disease pathology and the aging process
  • Cellular mechanisms that exist to counteract ROS include stabilization by enzymes such as superoxide dismutase and Catalase,
  • Direct scavenging by antioxidant molecules such as glutathione (GSH), a major intracellular antioxidant; cysteine, a precursor of GSH and a major extracellular antioxidant in plasma
  • Vitamin E, is a major lipid soluble antioxidant; and
  • Ascorbate, is an intracellular and extracellular antioxidant.

The main function of vitamin E is as a chain-breaking, free-radical trapping antioxidant in cell membranes and plasma lipoproteins.

  • By reacting with the lipid peroxide radicals formed by peroxidation of polyunsaturated fatty acids, it gets converted to tocopheroxyl radical.
  • The resultant radical (oxidized form) is relatively unreactive, and ultimately forms nonradical compounds.
  • Commonly, the tocopheroxyl radical is reduced back to tocopherol by reaction with vitamin C from plasma. (See Figure-2)

Synergism between vitamin E, C, Selenium and Glutathione

  • Ascorbate (Vitamin C) is essential for maintaining vitamin E in its reduced, active form.
  • Ascorbate is oxidized to dehydroascorbate in plasma and that is recycled back to ascorbate by GSH as well as by several enzyme systems in erythrocytes, neutrophils, endothelial cells and hepatocytes (See figure-2).
  • GSH itself gets oxidized during this process and is converted back to its reduced form by Glutathione reductase utilizing NADPH as the reductant.
  • GSH is also required by Selenium containing Glutathione Peroxidase enzyme for decomposing H2O2.
  • A synergism is observed between selenium and vitamin E .
  • The synergism is  related to the process of antioxidation, wherein tocopherols tend to prevent oxidative damage to polyunsaturated fats in cell membranes, selenium, as part of seleno-enzyme glutathione peroxidase,catalyzed the destruction of lipid hydro peroxides.
  • This explains how these two nutrients play separate but interrelated role sin the cellular defense system against oxidative damage.
  • In high concentration, the tocopheroxyl free radical can penetrate further into cells and, potentially, propagate a chain reaction.
  • Therefore, vitamin E may also have pro-oxidant actions, especially at high concentrations. This explains the bleeding observed in vitamin E toxicity


 Synergism between vitamin C, E and Selenium











Figure- 2- A synergism is observed between Vitamin E, C and G-SH dependent Glutathione peroxidase. Vitamin E during the process of breaking the lipid peroxidation chain gets converted to oxidized form (tocopheroxyl ) that is reconverted back to reduced form by ascorbic acid (vitamin C), which in turn  itself gets converted to oxidized or dehydroascorbate form. The regeneration of reduced form takes place by reduced glutathione(G-SH), and  that gets oxidized  during this process and converted back to reduced form by glutathione reductase using NADPH as the hydrogen donor. Free radicals can also be quenched by Glutathione peroxidase, a Se containing Metalloenzymes, that requires the presence of reduced G-SH. Adequate activity of glutathione peroxidase reduces the amount of Vitamin E in diet and similarly adequate concentration of vitamin E in diet reduces the requirement of selenium.

2) Other functions of vitamin E

  • It also has a (relatively poorly defined) role in cell signaling.  
  • Vitamin E also inhibits prostaglandin synthesis
  • As an antioxidant, vitamin E plays a protective role in many organs and systems.
  • Vitamin E is necessary for maintaining a healthy immune system, and it protects the thymus and circulating white blood cells from oxidative damage.
  • Also, it may work synergistically with vitamin C in enhancing immune function.
  • Recent research evidence indicates that the combined use 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 protects against cataracts and macular degeneration.
  • In experimental animals vitamin E deficiency causes infertility

Vitamin E Deficiency

  • Dietary vitamin E deficiency is common in developing countries;
  • deficiency among adults in developed countries is uncommon and is usually due to fat malabsorption.
  • Absorption of vitamin E depends on normal pancreatic biliary function, biliary secretion, micelle formation, and penetration across intestinal membranes. Interference with any of these processes could result in a deficiency state.
  • The main symptoms are hemolytic anemia and neurologic deficits.
  • Vitamin E deficiency causes fragility of RBCs and degeneration of neurons, particularly peripheral axons and posterior column neurons.


  • Low α-tocopherol level or low ratio of plasma α-tocopherol to plasma lipids
  • Measuring the plasma α-tocopherol level is the most direct method of diagnosis.
  • In adults, vitamin E deficiency is 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 to plasma lipids (< 0.8 mg/g total lipid) is the most accurate indicator in adults with hyperlipidemia.


Supplemental α-tocopherol

  • If malabsorption causes clinically evident deficiency, α-tocopherol 15 to 25 mg/kg orally once/day should be given.
  • However, larger doses given by injection are required to treat neuropathy during its early stages or to overcome the defect of absorption


Although premature neonates may require supplementation, human milk and commercial formulas have enough vitamin E for full-term neonates.

Vitamin E Toxicity

  • Large amounts of vitamin E for months to years may not cause apparent harm.
  • Occasionally, muscle weakness, fatigue, nausea, and diarrhea occur.
  • The most significant risk is bleeding.
  • However, bleeding is uncommon unless the dose is > 1000 mg/day.


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