The Essential Role of Vitamin E and the Consequences of Its Deficiency

Vitamin E, discovered in 1922, has been recognized as an essential nutrient for human health since 1983. This fat-soluble antioxidant plays a crucial role in protecting cells from oxidative damage. The importance of vitamin E was initially observed in children with fat malabsorption syndromes, such as abetalipoproteinemia, cystic fibrosis, and cholestatic liver disease. These conditions impair the body’s ability to absorb dietary fats, leading to a deficiency in vitamin E.

Symptoms of vitamin E deficiency have also been reported in individuals suffering from protein-calorie malnutrition, though such cases are rare. In the general population, vitamin E deficiency is uncommon due to its wide availability in various foods like nuts, seeds, and vegetable oils. However, individuals with fat malabsorption disorders are particularly vulnerable to this deficiency. For these at-risk groups, supplementation is often recommended to prevent the onset of deficiency symptoms.

The absence of sufficient vitamin E in the body has significant consequences. One of the most severe effects is the destruction of red blood cells, a condition known as erythrocyte hemolysis. This occurs because vitamin E protects the polyunsaturated fatty acids in cell membranes from oxidative damage. Without this protection, the cells break open, spilling their contents and leading to anemia. Premature infants are particularly susceptible to erythrocyte hemolysis because they miss the critical transfer of vitamin E from the mother during the last weeks of pregnancy.

Vitamin E deficiency primarily manifests as peripheral neuropathy, a condition characterized by the degeneration of large axons in sensory neurons. This leads to symptoms such as numbness, tingling, and loss of coordination. Other neurological symptoms include spinocerebellar ataxia, skeletal myopathy, and pigmented retinopathy. In severe cases, prolonged deficiency can result in neuromuscular dysfunction affecting the spinal cord and retina, leading to irreversible damage.

Given the essential functions of vitamin E in maintaining cellular integrity and neurological health, ensuring adequate intake is vital, particularly for those at risk of deficiency.
The Essential Role of Vitamin E and the Consequences of Its Deficiency

Vitamin E Food Sources

Vitamin E Discovery

Vitamin E, first identified in 1922 by Evans and Bishop as an unidentified factor present in vegetable oils necessary for female rat reproduction, was initially denoted as 'factor X' and the 'antisterility factor.' Nevertheless, Evans proposed the adoption of the letter E for this factor to conform to the established naming convention used for vitamin D at that time.

In 1936, researchers successfully isolated an active vitamin E compound from wheat germ oil. This compound enabled animals to produce offspring, prompting the research group to name it alpha-tocopherol, derived from the Greek words 'tocos' (meaning childbirth) and 'ferein' (to bring forth), emphasizing its importance in rat fertility. The inclusion of the 'ol' suffix indicated the presence of an OH group in the molecule.

The correct structure of vitamin E was determined in 1938, and in the same year, P. Karrer successfully synthesized the substance.

During the 1940s, Canadian physicians discovered that vitamin E could provide protection against coronary heart disease in humans. Since then, the demand for vitamin E has rapidly increased, leading to a proliferation of product types available to the pharmaceutical, food, feed, and cosmetic industries.

In 1968, the Food and Nutrition Boards of the National Academy of Sciences officially recognized vitamin E as an essential nutrient.
Vitamin E Discovery

Vitamin E: Main functions in human body

Vitamin E is present in human tissues and it is necessary for normal metabolism. It is found to be widely distributed in foods. Vitamin E is the collective term given to a group of fat-soluble compounds first discovered in 1922 by Evans and Bishop; these compounds have distinct antioxidant activities essential for health.

Deficiency of vitamin E in man has not been reported and so there is no recommended daily intake. Vitamin E deficiency occurs only as a result of genetic abnormalities in α–tocopherol transfer protein, as a result of various fat malabsorption syndromes, or as a result of protein-energy malnutrition.

It has numerous important roles within the body because of its antioxidant activity. For example, vitamin E protecting substances such as unsaturated fatty acids, carotene and ascorbic acid, which are easily oxidized.

Vitamin E is an essentially naturally occurring fat-soluble nutrient that is involved in several biological processes such as immunity, protection against tissue damage (hear, nerve, etc) reproduction, growth and development.

Vitamin E helps to prevent arteries from clogging by blocking the conversion of cholesterol into the waxy fat deposits called ‘plaque’ that stick to blood vessel walls. Vitamin E also thins the blood, allowing it to flow more easily through arteries even when plaque is present.

One of the few generally recognized uses for vitamin E is in the treatment of hemolytic anemia in premature babies.

Because of its antioxidant action, vitamin E may help protect against clouding of the lens of the eye (cataracts) and a progressive deterioration in the retina, the back part of the eye (age-related macular degeneration, AMD).

There were also studies indicate that vitamin E may slow the aging process and prevent premature aging by prolonging the useful life of human cells, thus maintaining the function of human organs.

Vitamin E is found in various foods and oils. Nuts, seeds and vegetable oils contain high amounts of α-tocopherol, and significant amounts are also available in green leafy vegetables and fortified cereals.
Vitamin E: Main functions in human body

Food sources of vitamin E

Vitamin E was discovered in 1922 but it was not until 40 years later that the vitamin was established as essential to human nutrition. Vitamin E is a fat-soluble vitamin and its main function is as an antioxidant, helping to protect cells from the damage caused by free radicals. People are also exposed to free radicals in the environment from cigarette smoke, air pollution, and ultraviolet light from the sun.

Since vitamin E is synthesized only in plants, the vitamin is an essential nutrient in the diet of animals and man.

Vitamin E is present in human tissues and it is necessary for normal metabolism. It is found to be widely distributed in foods.

Vitamin E is synthesized only by plants and, therefore, is found primarily in plant products, the richest sources being vegetable oils and products made from them, such as margarine and salad dressings.

Among vegetable oils, the content of vitamin E isomers differs vastly. Some vegetable oils such as olive, safflower and sunflower are rich in alpha-tocopherol, while other oils such as sesame seed, and rapeseed oil are rich in gamma-tocopherol. Corn and soybean oils also rich in gamma-tocopherol.

The dietary sources of tocotrienols are palm oil, rice bran oil, and the bran and germ portions of cereals such as oat, barley and rice.

Wheat germ oil is especially rich in vitamin E. While major sources of vitamin E in Japan are fish and shellfish.

Nuts (such as peanuts, hazelnuts, and, especially, almonds) and seeds (like sunflower seeds) are also among the best sources of vitamin E. Avocadoes are another good sources of vitamin E.
Food sources of vitamin E

Selenium deficiency and low vitamin E

Selenium is a micronutrient that is essential for the proper functioning of all organisms. Selenium, in the form of selenoproteins, carries out various functions in normal health and metabolism. This element is a cofactor of many enzymes, for example, glutathione peroxidase or thioredoxin reductase.

Selenium plays a role in the immune system functioning and the progression of HIV to AIDS. Selenium deficiency has been implicated in cardiovascular disease, infertility, myodegenerative diseases, and cognitive decline.

Selenium exhibits synergy with vitamin E. In metabolic processes, sulfur amino acids such

as cystine and methionine are closely associated with it. The combined interaction of selenium and

tocopherol gives the best results in the protection of organs against the destructive effects of free radicals. Combined administration of selenium and vitamin E results in an immunostimulatory effect.

Selenium deficiency occurs when there is inadequate dietary intake of selenium, typically due to a scarcity of selenium sources in a given region. Interestingly, low vitamin E intake may enhance the effect of selenium deficiency, which is associated with increased risk of fatal cancer.

Individuals whose blood (serum) selenium level is low with deficiencies of vitamin E accompanied are at the increased risk of developing cancer. In healthy individuals, the level of this element in blood is higher by several percent in comparison with those who suffer from cancer.
Selenium deficiency and low vitamin E

Vitamin E is good for heart

Vitamin E is a fat-soluble nutrient found in many foods. In the body, it acts as an antioxidant, helping to protect cells from the damage caused by free radicals. Free radicals are compounds formed when human bodies convert the food eaten into energy. Vitamin E was discovered more than 80 years ago as an essential micronutrient for reproduction in rats.

Vitamin E is a group of eight lipophilic molecules, four of which are tocopherols and four of which are tocotrienols. It is mostly found in nuts and various vegetable oils. γ-Tocopherol is the most abundant form of vitamin E in Western diet, while α tocopherol is the most abundant form of vitamin E in plasma, and is most biologically active.

Vitamin E is an antioxidant that some believe may help prevent diseases associated with oxidative stress. Research and the clinical experiences of physician show beyond a doubt that vitamin E is good for the heart. The role of vitamin E as a heart protector has been building for decades.

Cardiovascular disease, defined as coronary artery disease, hypertensive heart disease, congestive heart failure, peripheral vascular disease, and atherosclerosis including cerebral artery disease and strokes, is the leading cause of death in the United States.

Basic research has provided credible mechanisms by which vitamin E might exert cardiovascular benefit, including inhibition of oxidation of low-density lipoprotein (LDL) cholesterol in plasma.

It is hypothesized that antioxidant nutrients, such as vitamin E, may be beneficial in retarding atherosclerosis. Observational cohort studies have supported vitamin E supplementation in preventing cardiovascular disease. Experimentally, it has been shown that dietary vitamin E can ameliorate the development of spontaneous atherosclerosis in nutritional models of cardiovascular disease.
Vitamin E is good for heart

Mechanism of vitamin E as antioxidant

Antioxidants such as vitamin E act to protect body cells against the effects of free radicals, which are potentially damaging by-products of the body's metabolism. Vitamin E serves as one of the body’s chief defenses against damage by free radicals.

Vitamin E occurs in nature in at least eight different isoforms: α, β, γ -and 𝛿 -tocopherols and α, β, γ- and 𝛿 -tocotrienols. Tocotrienols differ from the corresponding tocopherols only in their aliphatic tail. Free radical scavenging reactions of α tocopherol take place via the α -tocopheroxyl radical as an intermediate.

Tocopherol isomers are chain-breaking antioxidants. α-tocopherol, the most biologically active and abundant form of vitamin E in vivo, efficiently transfers a hydrogen atom to a lipid free radical, such as peroxyl, alkoxyl, and carbon~centered radicals, giving the corresponding non-radical product of the lipid and an α -tocopheroxyl radical.

Most notably, vitamin E prevents the oxidation of the polyunsaturated fatty acids, but is protects other lipids and related components (e.g. vitamin A) as well. It therefore occupies a unique position in the arsenal of natural antioxidants providing protection against various diseases.
Mechanism of vitamin E as antioxidant

Antioxidant activity of vitamin E

Vitamin E is a fat-soluble vitamin that exists in eight different forms. Each form has its own biological activity, the measure of potency or functional use in the body.

Vitamin E was first discovered in 1922 as a substance necessary for reproduction. Following this discovery, vitamin E was extensively studied, and it has become widely known as a powerful lipid-soluble antioxidant.

 It is actually two sets of four compounds each, the tocopherols (alpha, beta, gamma and delta) and the chemically related tocotrienols (alpha, beta, gamma and delta).

Vitamin E compounds (tocopherols and tocotrienols) are well recognized for their effective inhibition of lipid peroxidation in foods and living cells. Vitamin E is synthesized only by plants: therefore it is a very important dietary nutrient for humans and animals.

α-tocopherol is the most active form of vitamin E in humans, and is a powerful biological antioxidant. It is the major lipid soluble found in cells.

The antioxidative activity of the tocopherols is related to scavenging the free radicals of unsaturated lipids. α -Tocopherol, the most biologically active and abundant form of vitamin E in vivo, efficiently transfers a hydrogen atom to a lipid free radical, such as peroxyl, alkoxyl, and carbon~centered radicals, giving the corresponding non-radical product of the lipid and an α-tocopheroxyl radical.

Free-radical mediated pathology has been implicated in the development of degenerative diseases, conditions and also aging process.
Antioxidant activity of vitamin E

Functional use of vitamin E in human body

Vitamin E is the collective term given to a group of fat-soluble compounds first discovered in 1922 by Evans and Bishop.

Vitamin E consists of two families of compounds, the tocopherols and tocotrienols, characterized by a 6-chromanol ring and an isoprenoid side chain. The members of each family are designated alpha((α)-, beta(β)-, gamma(γ)-, or delta(δ)- according to the position of methyl groups attached to the chroman nucleus.

Vitamin E functions as a chain-breaking antioxidant that prevents the propagation of free radical reactions. It is primarily located in the cell and organelle membranes where it can exert its maximum protective effect, even when its concentration ratio may be only one molecule for every 2,000 phospholipid molecules. It acts as the first line of defense against lipid peroxidation, protecting the cell membranes from free radical attack.

It has been found that alpha-tocopherol mainly inhibits the production of new free radicals, while gamma-tocopherol traps and neutralises the existing free radicals. Oxidation has been linked to numerous possible conditions/diseases including: cancer, ageing, arthritis and cataracts.

The vitamin is a peroxyl radical scavenger and especially protects polyunsaturated fatty acids (PUFAs) within membrane phospholipids and in plasma lipoproteins.

Vitamin E increases the orderliness of the membrane lipid packaging, thus allowing for a tighter packing of the membrane and, in turn, greater stability to the cell. In 2011, study showed that vitamin E is necessary for maintaining proper skeletal muscle homeostasis and that the supplementation of cultured myocytes with α -tocopherol promotes plasma membrane repair.

α-tocopherol appears unique in regulating phosphorylation cascades. Such a role may be important in heart disease where cell adhesion, proliferation, and oxidant production may all be modified through vitamin E-sensitive pathways.
Functional use of vitamin E in human body

Biological activity of vitamin E

Vitamin E, the most important lipid-soluble antioxidant, was discovered at the University of California at Berkeley in 1922 in the laboratory of Herbert M. Evans. At least eight vitamin E isoforms with biological activity have been isolated from plant sources.

Vitamin E is a naturally occurring free radical scavenger and its most widely accepted biological function is its antioxidant property. Vitamin E inhibits the free radical chain peroxidation of polyunsaturated lipids in membranes and lipoprotein.

The polyunsaturated linoleic, arachidonic and docosahexaenoic acids are examples of lipids sensitive to peroxidation. All natural forms and synthetic stereoisomers of vitamin E exhibit to varying degrees the ability to inhibit lipid peroxidation as chain-breaking antioxidants.

α-tocopherol

Tocopherols and tocotrienols are part of an interlinking set of antioxidant cycles, which has been termed the antioxidant network. Although the antioxidant activity of tocotrienols is higher than that of tocopherols, tocotrienols have a lower bioavailability after oral ingestion. Tocotrienols penetrate rapidly through skin and efficiently combat oxidative stress induced by UV or ozone.

Vitamin E (α-tocopherol) has the highest biological activity and reverses vitamin E deficiency symptoms in humans. α-tocopherol is a required nutrient for humans because it is needed 20 for prevention of vitamin E deficiency symptoms including neuropathy and hemolytic anemia.
Biological activity of vitamin E

Food sources of tocopherol

All eight forms of vitamin E (α-, β-, γ- and δ-tocopherols and tocotrienols) occurs naturally in foods, but relatively few foods have a high α-tocopherol concentration.

Generally, the richest sources are vegetables oils. Wheat germ oil, safflower oil, and sunflower oil contain predominantly α-tocopherol, while soy and corn oils have mainly γ-tocopherol.

Major sources of α-tocopherol in the American diet include vegetable oils, nuts, whole grains and green leafy vegetables.

Note that vegetable oils are also the richest sources of polyunsaturated fatty acids, which α-tocopherol protects.

Tocopherols exert their greatest effect in protection of animals fats (such as tallow) carotenoids, and vitamin A.

Tocopherols also functions as antioxidants in bacon, baked goods, butterfat, lard, margarine, rapeseed oil, safflower oil, and sunflower seed oil.

In United States, the average intake of α-tocopherol from food is approximately 8 mg daily for men and 6 mg daily for women, these levels are well below the RDA of 15 mg/day of RRR- α-tocopherol.
Food sources of tocopherol

Why is vitamin E important?

Vitamin E was discovered and characterized as a fat soluble nutritional factor during reproductive studies with rats. This observation was published in1922 by Herbert McLean Evans and Katharine Scott Bishop. 

That supplement, vitamin E (alpha-tocopherol), was eventually isolated from wheat germ oil in 1936. There are four different forms of tocopherol. The tocopherols have the same name except with the prefix alpha-, beta-, gamma-, and delta- (the first four letters of the Greek alphabet).

The four compounds are closely related, with some difference in the molecular weight and in the position and number of certain molecular constituents.

Vegetable oils and lipid rich plants products (e.g. nuts, seeds, grains) are the main dietary sources of vitamin E.

In Western diets, vitamin E intakes derives mainly from fats and oils contained in margarine, mayonnaise, salad dressing and desserts and also from fortified food such as breakfast cereals, milk and fruit juices. 

Function of Vitamin E
The vitamin is an antioxidant that serves to prevent the oxidation of some body components, such as unsaturated fatty acids, and is necessary for reproduction. This vitamin involved in several biological processes such as immunity, protection against tissue damage such as heart and nerve, reproduction, growth and development.

Vitamin E also slows the aging process, probably delaying the onset of such conditions as cataracts and wrinkles. And it helps heal or alleviated many minor health complaints – including everything from burns to menopausal hot flashes.

Vitamin E deficiency 
A primary deficiency of vitamin E is rare; deficiency is usually associated with diseases of fat malabsorption such as cystic fibrosis.

Without vitamin E, the red blood cells break open and spill their contents, probably due to oxidation of the polyunsaturated fatty acids in their membranes.

Muscular dystrophy is another equally important consequence of vitamin E deficiency. Skeletal, cardiac and smooth muscles and peripheral vascular system need vitamin E for their functioning.
Why is vitamin E important?