Vitamin E

Vitamin E refers to a group of eight fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings. α-Tocopherol, the most biologically active form of vitamin E, is the second most common form of vitamin E in the North American diet. This variant of vitamin E can be found most abundantly in wheat germ oil, sunflower, and safflower oils. It is a fat-soluble antioxidant that stops the production of reactive oxygen species formed when fat undergoes oxidation.

Health effects
While it was initially hoped that vitamin E supplementation would have a positive effect on health, research has not supported these conclusions. Vitamin E does not decrease mortality in adults, even at large doses, and may slightly increase it. It does not improve blood sugar control in an unselected group of people with diabetes mellitus or decrease the risk of stroke. Daily supplementation of vitamin E does not decrease the risk of prostate cancer and may increase it. Studies on its role in age related macular degeneration are ongoing as, even though it is of a combination of dietary antioxidants used to treat the condition, it may increase the risk. A Japanese study in 2012 found that vitamin E may contribute to osteoporosis.

Deficiency
Vitamin E deficiency can cause:
 * spinocerebellar ataxia
 * myopathies
 * peripheral neuropathy
 * ataxia
 * skeletal myopathy
 * retinopathy
 * impairment of the immune response
 * erythrocyte hemolysis

Functions
Vitamin E has many biological functions; the antioxidant function being the most important and/or best known. Other functions include enzymatic activities, gene expression and neurological function(s). It's also been suggested that the most important function of vitamin E is in cell signaling (and, that it may not have a significant role in antioxidant metabolism).


 * As an antioxidant, vitamin E acts as a peroxyl radical scavenger, preventing the propagation of free radicals in tissues, by reacting with them to form a tocopheryl radical which will then be oxidized by a hydrogen donor (such as Vitamin C) and thus return to its reduced state. As it is fat-soluble, it is incorporated into cell membranes, which protects them from oxidative damage.


 * As an enzymatic activity regulator, for instance, protein kinase C (PKC), which plays a role in smooth muscle growth, can be inhibited by α-tocopherol. α-Tocopherol has a stimulatory effect on the dephosphorylation enzyme, protein phosphatase 2A, which in turn, cleaves phosphate groups from PKC leading to its deactivation, bringing the smooth muscle growth to a halt.


 * Vitamin E also has an effect on gene expression. Macrophages rich in cholesterol are found in the atherogenetic tissue. Scavenger receptor CD36 is a class B scavenger receptor found to be up-regulated by oxidized low density lipoprotein (LDL) and binds it. Treatment with alpha tocopherol was found to downregulate the expression of the CD36 scavenger receptor gene and the scavenger receptor class A (SR-A) and modulates expression of the connective tissue growth factor (CTGF). CTGF gene, when expressed, is responsible for the repair of wounds and regeneration of the extracellular tissue that is lost or damaged during atherosclerosis.


 * Vitamin E also plays a role in neurological functions, and inhibition of platelet aggregation.


 * Vitamin E also protects lipids and prevents the oxidation of polyunsaturated fatty acids (PUFAs.)

So far, most human supplementation studies about vitamin E have used only alpha-tocopherol. This can affect levels of other forms of vitamin E, e.g. reducing serum gamma- and delta-tocopherol concentrations. Moreover, a 2007 clinical study involving alpha-tocopherol concluded that supplementation did not reduce the risk of major cardiovascular events in middle aged and older men.

Dietary sources

 * {| class=wikitable style="text-align:center;"

! colspan=2 rowspan=1 | mg/(100 g) || colspan=1 rowspan=2 |Some foods with vitamin E content ! low||high beet, collard, and dandelion greens
 * colspan=2|150 ||align=left | Wheat germ oil
 * colspan=2| 41||align=left | Sunflower oil
 * colspan=2|34||align=left | Safflower oil
 * 15||26||align=left | Nuts and nut oils, like almonds and hazelnuts
 * colspan=2|15||align=left | Palm oil
 * 1.5||3.4||align=left | High-value green, leafy vegetables: spinach, turnip,
 * 15||26||align=left | Nuts and nut oils, like almonds and hazelnuts
 * colspan=2|15||align=left | Palm oil
 * 1.5||3.4||align=left | High-value green, leafy vegetables: spinach, turnip,
 * colspan=2|15||align=left | Palm oil
 * 1.5||3.4||align=left | High-value green, leafy vegetables: spinach, turnip,
 * 1.5||3.4||align=left | High-value green, leafy vegetables: spinach, turnip,
 * colspan=2|2.1||align=left | Avocados
 * 1.1||1.5||align=left | Asparagus
 * colspan=2|1.5||align=left | Kiwifruit (green)
 * 0.78||1.5||align=left | Broccoli
 * 0.8||1||align=left | Pumpkin
 * 0.26||0.94||align=left | Sweet potato
 * colspan=2 |0.9||align=left | Mangoes
 * 0.54||0.56||align=left | Tomatoes
 * 0.36||0.44||align=left | Rockfish
 * colspan=2 |0.3||align=left | Papayas
 * 0.13||0.22||align=left | Low-value green, leafy vegetables: lettuce
 * }
 * colspan=2 |0.9||align=left | Mangoes
 * 0.54||0.56||align=left | Tomatoes
 * 0.36||0.44||align=left | Rockfish
 * colspan=2 |0.3||align=left | Papayas
 * 0.13||0.22||align=left | Low-value green, leafy vegetables: lettuce
 * }
 * colspan=2 |0.3||align=left | Papayas
 * 0.13||0.22||align=left | Low-value green, leafy vegetables: lettuce
 * }
 * 0.13||0.22||align=left | Low-value green, leafy vegetables: lettuce
 * }

Recommended daily intake
The Food and Nutrition Board at the Institute of Medicine (IOM) of the U.S. National Academy of Sciences report the following dietary reference intakes for vitamin E:


 * {| class=wikitable style="text-align:left;"

! align=center|mg/day||Age !colspan=2 |Infants !colspan=2 |Children !colspan=2 |Adolescents and Adults
 * align=center |4||0 to 6 months
 * align=center|5||7 to 12 months
 * align=center|5||7 to 12 months
 * align=center|5||7 to 12 months
 * align=center|6||1 to 3 years
 * align=center|7||4 to 8 years
 * align=center|11||9 to 13 years
 * align=center|7||4 to 8 years
 * align=center|11||9 to 13 years
 * align=center|11||9 to 13 years
 * align=center|15||14 and older
 * }
 * }

One IU of vitamin E is defined as equivalent to either: 0.67 mg of the natural form, RRR-alpha-tocopherol, also known as d-alpha-tocopherol; or 0.45 mg of the synthetic form, all-rac-alpha-tocopherol, also known as dl-alpha-tocopherol.

History
The first use for vitamin E as a therapeutic agent was conducted in 1938 by Widenbauer. Widenbauer used wheat germ oil supplement on 17 premature newborn infants suffering from growth failure. 11 out of the original 17 patients recovered and were able to resume normal growth rates. Later on, in 1948, while conducting experiments on alloxan effects on rats, Gyorge and Rose noted that the rats receiving tocopherol supplements suffered from less hemolysis than those that did not receive tocopherol. In 1949, Gerloczy administered all-rac-α-tocopheryl acetate to prevent and cure edema. Methods of administration used were both oral, that showed positive response, and intramuscular, which did not show a response. This early investigative work on the benefits of vitamin E supplementation was the gateway to curing the vitamin E deficiency caused hemolytic anemia described during the 1960s. Since then, supplementation of infant formulas with vitamin E has eradicated this vitamin’s deficiency as a cause for hemolytic anemia.

Forms
The eight forms of vitamin E are divided into two groups; four are tocopherols and four are tocotrienols. They are identified by prefixes alpha-, beta-, gamma-, and delta-. Natural tocopherols occur in the RRR-configuration only. The synthetic form contains eight different stereoisomers and is called all-rac-α-tocopherol.

α-Tocopherol
α-Tocopherol is an important lipid-soluble antioxidant. It performs its functions as antioxidant in what is known by the glutathione peroxidase pathway and it protects cell membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction. This would remove the free radical intermediates and prevent the oxidation reaction from continuing. The oxidized α-tocopheroxyl radicals produced in this process may be recycled back to the active reduced form through reduction by other antioxidants, such as ascorbate, retinol or ubiquinol. However, the importance of the antioxidant properties of this molecule at the concentrations present in the body are not clear and it is possible that the reason why vitamin E is required in the diet is unrelated to its ability to act as an antioxidant. Other forms of vitamin E have their own unique properties; for example, gamma-tocopherol is a nucleophile that can react with electrophilic mutagens.

Tocotrienols
Compared with tocopherols, tocotrienols are sparsely studied. Less than 1% of PubMed papers on vitamin E relate to tocotrienols. The current research direction is starting to give more prominence to the tocotrienols, the lesser known but more potent antioxidants in the vitamin E family. Some studies have suggested that tocotrienols have specialized roles in protecting neurons from damage and cholesterol reduction by inhibiting the activity of HMG-CoA reductase; delta-tocotrienol blocks processing of sterol regulatory element‐binding proteins (SREBPs).

Oral consumption of tocotrienols is also thought to protect against stroke-associated brain damage in vivo. Until further research has been carried out on the other forms of vitamin E, conclusions relating to the other forms of vitamin E, based on trials studying only the efficacy of alpha-tocopherol, may be premature.