Vitamin E deficiency

Vitamin E deficiency disorders

Oxidative stress plays a role in the pathogenesis of complicationsof several conditions for which it has therefore been reasonable to suggest that, in such conditions, vitamin E status may be a determinant of risk. Several such conditions have been found to be associated with relatively low vitamin E intake or status; however, in general, vitamin E intervention trials have failed to demonstrate benefits.

Vitamin E deficiency

Neurodegenerative Disorders

Neural tissues conserve vitamin E, apparently by maintaining a relatively larger portion in the less labile cellular pool. In fact, vitamin E appears to be redistributed to neural tissues under conditions of nutritional deficiency.73 Several facts make it reasonable to expect neuronal tissue to be susceptible to oxidative stress: neurons contain large amounts of both PUFAs and iron, but do not have extensive antioxidant defense systems; neurons are terminally differentiated and do not replicate when damaged; redox cycling drugs (that generate ROS) can cause Parkinson like neural damage in animal models; dopamine metabolism in dopaminergic neurons generates ROS; exposure to hyperbaric oxygen can cause seizures; defects in α-TTP are manifest as ataxia (e.g., AVED); vitamin E deficiency is manifest by neurological signs. There is no question that vitamin E is essential for neurologic function.


In comparison with controls, diabetic erythrocytes have significantly more lipid peroxidation78 which, by altering membrane fluidity, is thought to render erythrocytes hypercoagulable and more ready to adhere to endothelial cells. Membrane lipid peroxidation correlates with erythrocyte contents of glycated hemoglobin (HbA1c), and supplementation of non-insulin-dependent (type 2) diabetics with high levels of vitamin E has been found to reduce hemoglobin damage. Oxidative stress is also known to alter cellular serine/threonine kinase activities, resulting in the phosporylation of insulin receptor substrate-1, which reduces insulin signaling. However, insulin sensitivity also appears to be affected through translational regulatory functions of vitamin E. Supranutritional levels of either α- and γ-tocopherols have been shown to upregulate an endogenous ligand involved in activating PPARγ, which plays a role in insulin sensitivity by upregulating adiponectin, an adipokin that increases insulin sensitivity.


Cataracts result from the accumulation in the lens of damaged proteins that aggregate and precipitate, resulting in opacification of the lens.81 Much of this damage involves oxidations characterized by the loss of sulfhydryls, the formation of disulfide and non-disulfide covalent linkages, and the oxidation of tryptophan residues. Several epidemiological studies have found circulating α-tocopherol level or vitamin E intake to be inversely associated with cataract risk. Vitamin E has been shown in animal models to reduce or delay cataracts induced by galactose or aminotriazol treatment, and to reduce the photoperoxidation of lens lipids. These effects are thought to involve its direct action as an antioxidant or its indirect antioxidant effect in maintaining lens glutathione in the reduced state. Nevertheless, large scale, randomized controlled trials have not found α-tocopherol supplementation at supranutritional levels (50–500 mg/day) to reduce risk of cataracts.

Lung Health

The lungs are continuously exposed to relatively high concentrations of O2 as well as environmental oxidants and irritants. The first line of defense of the respiratory epithelium organ is the respiratory tract lining fluid, which contains a variety of antioxidants, including vitamin E, as well as relatively high concentrations of vitamin C, urate, reduced glutathione, extracellular superoxide dismutase, catalase, and glutathione peroxidase. Nevertheless, a metaanalysis of observational studies found no relationship of estimated dietary intake of vitamins E, C or β-carotene on risk of asthma.

Skin Health

The skin is subject to the oxidizing effects resulting from exposure to ultraviolet light, which is known to generate ROS from the photolysis of intracellular water. Studies with animal models have shown that the tocopherol content of dermal tissues decreases with UV irradiation, presumably as a result of that oxidative stress. Vitamin E in skin is found in greatest concentrations in the lower levels of the strateum corneum, where it is released by sebum.

Topical treatment with vitamin E may increase the hydration of the strateum corneum, and confer protection against UV-induced skin damage, as measured by reduced erythemal responses and delayed onset of tumorigenesis. One study reported that regular topical application of vitamin E reduced wrinkle amplitude and skin roughness in about half of cases. For these reasons, α-tocopherol and α-tocopheryl acetate are widely used in skin creams and cosmetics.


Rheumatoid arthritis is thought to be caused by antigenic triggering, in the articular joints, of an inappropriate immune response that leads to chronic inflammation. Indirect evidence suggests that the inflammatory production of ROS leads to the oxidation of lipids in the synovial fluid, which increases the viscosity of that fluid. Studies with animal models have found that vitamin E supplementation can reduce joint swelling, and randomized controlled trials have shown high-level supplementation with the vitamin (100–600 IU/day) to relieve pain and be anti-inflammatory; however, α-tocopherol supplements have not been found effective in reducing rheumatoid arthritis risk.

Cardiovascular Health

Observational epidemiologic studies have consistently demonstrated benefits of vitamin E on cardiovascular disease



Vitamin E deficiency can result from insufficient dietary intake or impaired absorption of the vitamin. Several other dietary factors affect the need for vitamin E. Two are most important in this regard: selenium and PUFAs.

Selenium spares the need for vitamin E; accordingly, animals fed low-selenium diets generally require more vitamin E than animals fed the same diets supplemented with an available source of selenium. In contrast, the dietary intake of PUFAs directly affects the need for vitamin E; animals fed high-PUFA diets require more vitamin E than those fed low-PUFA diets. Other factors that can be expected to increase vitamin E needs are deficiencies of sulfur-containing amino acids;103 deficiencies of copper, zinc, and/or manganese;104 and deficiency of riboflavin.

Alternatively, vitamin E can be replaced by several lipidsoluble synthetic antioxidants106 (e.g., BHT,107 BHA,108 DPPD109) and, possibly, by vitamin C. Conditions involving the malabsorption of lipids can also lead to vitamin E deficiency (Table 7.17). Such conditions include those resulting in loss of pancreatic exocrine function (e.g., pancreatitis, pancreatic tumor, nutritional pancreatic atrophy in severe selenium deficiency), those involving a lumenal deficiency of bile (e.g., biliary stasis due to mycotoxicosis, biliary atresia), and those due to defects in lipoprotein metabolism (e.g., abetalipoproteinemia). Premature infants, who are typically impaired in their ability to utilize dietary fats, are also at risk of vitamin E deficiency.


Vitamin E has been viewed as one of the least toxic of the vitamins. Both animals and humans appear to be able to tolerate rather high levels. For animals, doses at least two orders of magnitude above nutritional requirements (e.g., to 1,000–2000 IU/kg) are without untoward effects. For humans, daily doses as high as 400 IU have been considered to be harmless, and large oral doses, as great as 3,200 IU, have not been found to have consistent ill effects.



The Vitamins

Fourth Edition

Gerald F. Combs, Jr

Professor Emeritus

Cornell University

Ithaca, NY


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