Introduction
The term vitamin E covers eight fat-soluble compounds found in nature. Four of them are called tocopherols and the other four tocotrienols. They are identified by the prefixes α, β, γ and δ. α-Tocopherol is the most common and biologically the most active of these naturally occurring forms of vitamin E. Natural tocopherols occur in RRR-configuration only (RRR-α-tocopherol was formerly designated as d-α-tocopherol). The chemical synthesis of α-tocopherol results in a mixture of eight different stereoisomeric forms which is called all-rac-α-tocopherol (or dl-α-tocopherol). The biological activity of the synthetic form is lower than that of the natural form.
The name tocopherol derives from the Greek words tocos, meaning childbirth, and pherein, meaning to bring forth. The name was coined to highlight its essential role in the reproduction of various animal species.
The ending -ol identifies the substance as being an alcohol.
The importance of vitamin E in humans was not accepted until fairly recently. Because its deficiency is not manifested by a well-recognised, widespread vitamin deficiency disease such as scurvy (vitamin C deficiency) or rickets (vitamin D deficiency), science only began to recognise the importance of vitamin E at a relatively late stage.
Functions
The major biological function of vitamin E is that of a lipid soluble antioxidant preventing the propagation of free-radical reactions. Free radicals are formed in normal metabolic processes and upon exposure to exogenous toxic agents (e.g. cigarette smoke, pollutants). Vitamin E is located within the cellular membranes. It protects polyunsaturated fatty acids (PUFAs) and other components of cellular membranes from oxidation by free radicals. Apart from maintaining the integrity of the cell membranes in the human body, it also protects low density lipoprotein (LDL) from oxidation.
Recently, non-antioxidant functions of α-tocopherol have been identified.
α-Tocopherol inhibits protein kinase C activity, which is involved in cell proliferation and differentiation. Vitamin E inhibits platelet aggregation and enhances vasodilation. Vitamin E enrichment of endothelial cells downregulates the expression of cell adhesion molecules, thereby decreasing the adhesion of blood cell components to the endothelium.
Main functions in a nutshell:
1.Major fat soluble antioxidant of the body
2.Non-antioxidant functions in cell signalling, gene expression and regulation of other cell functions
Dietary sources
Vegetable oils (olive, soya beans, palm, corn, safflower, sunflower, etc.), nuts, whole grains and wheat germ are the most important sources of vitamin E. Other sources are seeds and green leafy vegetables. The vitamin E content of vegetables, fruits, dairy products, fish and meat is relatively low.
The vitamin E content in foods is often reported as α-tocopherol equivalents (α-TE). This term was established to account for the differences in biological activity of the various forms of vitamin E. 1 mg of α-tocopherol is equivalent to 1 TE. Other tocopherols and tocotrienols in the diet are assigned the following values: 1 mg β-tocopherol = 0.5 TE; 1 mg γ-tocopherol = 0.1 TE; 1 mg δ-tocopherol = 0.03 TE; 1 mg α-tocotrienol = 0.3 TE; 1 mg β-tocotrienol = 0.05 TE.
Absorption and body stores
Vitamin E is absorbed together with lipids in the small intestine, depending on adequate pancreatic function and biliary secretion. Tocopherol esters which are present in food supplements and processed food are hydrolysed before absorption. Vitamin E is incorporated into chylomicrons and transported via the lymphatic system to the liver.
α-Tocopherol is the vitamin E form that predominates in blood and tissue. This is due to the action of a liver protein (α-tocopherol transfer protein) preferentially incorporating α-tocopherol into the lipoproteins which deliver it to the different tissues. Vitamin E is found in most human body tissues. The highest vitamin E contents are found in the adipose tissue, liver and muscles. The pool of vitamin E in the plasma, liver, kidneys and spleen turns over rapidly, whereas turnover of the content of adipose tissue is slow.
Measurement
Normal α-tocopherol concentrations in plasma measured by high performance liquid chromatography range from 12-45 μM (0.5-2 mg/100 ml). Plasma α-tocopherol concentrations of <11.6 μM, the level at which erythrocyte haemolyses occurs, indicate poor vitamin E nutritional status. Since plasma levels of α-tocopherol correlate with cholesterol levels, the α-tocopherol concentration is often indicated as α-tocopherol-cholesterol ratio.
Vitamin E content is generally expressed by biological activity, using the scale of International Units (IU). According to this system, 1 mg of RRR-α-tocopherol, biologically the most active of the naturally occurring forms of vitamin E, is equivalent to 1.49 IU vitamin E. The biological activity of 1 mg of all-rac-α-tocopheryl acetate, the synthesised form of vitamin E commonly used in food enrichment, is equivalent to 1 IU. Recently, the unit of α-tocopherol equivalent was established (see: Dietary sources).
Stability
Light, oxygen and heat, detrimental factors encountered in long storage of foodstuffs and food processing, lower the vitamin E content of food. In some foods it may decrease by as much as 50% after only two weeks’ storage at room temperature. To a large extent, frying destroys the vitamin E in vegetable oils.
Esters of α-tocopherol (α-tocopheryl acetate and α-tocopheryl succinate) are used for supplements because they are more resistant to oxidation during storage.
Interactions
Positive interactions
The presence of other antioxidants, such as vitamin C and beta-carotene, supports the antioxidative, protective action of vitamin E; the same is true of the mineral selenium.
Negative interactions
When taken at the same time, iron reduces the availability of vitamin E to the body; this is especially critical in the case of anaemic newborns.
The requirement for vitamin E is related to the amount of polyunsaturated fatty acids consumed in the diet. The higher the amount of PUFAs, the more vitamin E is required.
Vitamin K deficiency may be exacerbated by vitamin E, thereby affecting blood coagulation.
Various medications decrease absorption of vitamin E (e.g., cholestyramine, colestipol, isoniazid).
Deficiency
Because depletion of vitamin E tissue stores takes a very long time, no overt clinical deficiency symptoms have been noted in otherwise healthy adults. Symptoms of vitamin E deficiency are seen in patients with fat malabsorption syndromes or liver disease, in individuals with genetic defects affecting the α-tocopherol transfer protein and in newborn infants, particularly premature infants.
Vitamin E deficiency results in neurological symptoms (neuropathy), myopathy (muscle weakness) and pigmented retinopathy. Early diagnostic signs are leakage of muscle enzymes, increased plasma levels of lipid peroxidation products and increased haemolysis of erythrocytes (red blood cells). In premature infants, vitamin E deficiency is associated with haemolytic anaemia, intraventricular haemorrhage and retrolental fibroplasia.
Disease prevention and therapeutic use
Research studies suggest that vitamin E has numerous health benefits. Vitamin E is thought to play a role in preventing atherosclerosis and cardiovascular diseases (heart disease and stroke) due to its effects on a number of steps in the development of atherosclerosis (e.g. inhibition of LDL oxidation, inhibition of smooth muscle cell proliferation, inhibition of platelet adhesion, aggregation and platelet release reaction).
Recent studies suggest that vitamin E enhances immunity in the elderly, and that supplementation with vitamin E lowers the risk of contracting an upper respiratory tract infection, particularly the common cold.
Researchers are investigating the prophylactic role of vitamin E in protecting against exogenous pollutants and lowering the risk of cancer and of cataracts.
Vitamin E in combination with vitamin C may protect the body from oxidative stress caused by extreme sports (e.g. ultra marathon running).
A role of vitamin E supplementation in the treatment of neurodegenerative diseases (Alzheimer′s disease, amyotrophic lateral sclerosis) is also under investigation.
Recommended Dietary Allowance (RDA)
The recommended daily intake of vitamin E varies according to age, sex and criteria applied in individual countries. In the USA, the RDA for adults is 15 mg RRR-α-tocopherol/day (FNB, 2000). In Europe, adult recommendations range from 4 to 15 mg α-TE/day for men and from 3 to 12 mg α-TE/day for women.
The RDA for vitamin E of 15 mg cannot easily be acquired even with the best nutritional intentions, yet most research studies show that optimal intake levels associated with health benefits tend to be high. Vitamin E intake should also be adapted to that of PUFA, which influences the requirement for this vitamin. The EC Scientific Committee on Foods (SCF) has suggested a consumption ratio of 0.4 mg α-TE per gram of PUFA.
Safety
Vitamin E has low toxicity. After reviewing more than 300 scientific studies, the US-based Institute of Medicine (IOM) concluded that vitamin E is safe for chronic use even at doses of up to 1000 mg per day. A recently published meta-analysis suggested that taking more than 400 IU of vitamin E per day brought a weekly increase in the risk of all-cause mortality. However, much of the research was done in patients at high risk of a chronic disease and these findings may not be generalisable to healthy adults. Many human long-term studies with higher doses of vitamin E have not reported any adverse effects, and it has been concluded that vitamin E intakes of up to 1600 IU (1073 mg RRR-α-tocopherol) are safe for most adults.
The Antioxidant Panel of the Food and Nutrition Board (FNB, 2000) has set the UL (tolerable upper intake level) for adults at 1000 mg/day of any form of supplemental α-tocopherol. In 2003 the EC Scientific Committee on Foods (SCF) established the UL of 300 mg α-TE for adults. Also in 2003, the UK Expert group on Vitamins and Minerals (EVM; 2003) set the UL at 540 mg α-TE for supplemental vitamin E.
Pharmacologic doses of vitamin E may increase the risk of bleeding in patients treated with anticoagulants. Patients on anticoagulant therapy or those anticipating surgery should avoid high levels of vitamin E.
Supplements, food fortifications and other applications
Vitamin E is available in soft gelatine capsules, or as chewable or effervescent tablets, and is found in most multivitamin supplements.
The most common fortified foods are soft drinks and cereals.
The all-rac-α-tocopherol form of vitamin E is widely used as an antioxidant in stabilising edible oils, fats and fat-containing food products.
Research has shown that vitamin E in combination with vitamin C reduces the formation of nitrosamines (a proven carcinogen in animals) in bacon more effectively than vitamin C alone.
Vitamin E has been used topically as an anti-inflammatory agent, to enhance skin moisturisation and to prevent cell damage by UV light.
In pharmaceutical products tocopherol is used, for example, to stabilise syrups, aromatic components, and vitamin A or provitamin A components.
α-Tocopherol is used as an antioxidant in plastics, technical oils and greases, and in the purified, so-called white oils, employed in cosmetics and pharmaceuticals.
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