Vitamin ESlides prepared by Dr. Ashok Mosesfor Franco-Indian PharmaceuticalsLtd.
Vitamin E• Vitamin E refers to a group of eight fat-solublecompounds that include both tocopherols andtocotrienols. Of the many different forms of vitaminE, γ-tocopherol is the most common in the NorthAmerican diet. γ-Tocopherol can be found in cornoil, soybean oil, margarine, and dressings. In theNorth American diet, α-tocopherol, the mostbiologically active form of vitamin E, is the second-most common form of vitamin E. This variant can befound most abundantly in wheat germ oil, sunflower,and safflower oils. As a fat-soluble antioxidant, itstops the production of reactive oxygen species formedwhen fat undergoes oxidation.
FunctionsVitamin E has many biological functions, the antioxidantfunction being the most important and/or best known.Other functions include enzymatic activities, gene expression,and neurological function(s). The most important function ofvitamin E has been suggested to be in cell signaling (and itmay not have a significant role in antioxidantmetabolism).• As an antioxidant, vitamin E acts as a peroxyl radicalscavenger, preventing the propagation of free radicals intissues, by reacting with them to form a tocopheryl radical,which will then be reduced by a hydrogen donor (such asvitamin C) and thus return to its reduced state. As it isfat-soluble, it is incorporated into cell membranes, whichprotects them from oxidative damage.
Functions• As an enzymatic activity regulator, forinstance, protein kinase C (PKC), which plays arole in smooth muscle growth, can beinhibited by α-tocopherol. α-Tocopherol has astimulatory effect on the dephosphorylationenzyme, protein phosphatase 2A, which inturn, cleaves phosphate groups from PKC,leading to its deactivation, bringing thesmooth muscle growth to a halt.
Functions• Vitamin E also has an effect on gene expression.Macrophages rich in cholesterol are found in theatherogenetic tissue. Scavenger receptor CD36 is aclass B scavenger receptor found to be up-regulated byoxidized low density lipoprotein (LDL) and binds it.Treatment with α-tocopherol was found todownregulate the expression of the CD36 scavengerreceptor gene and the scavenger receptor class A (SR-A) and modulates expression of the connectivetissue growth factor (CTGF). The CTGF gene,when expressed, is responsible for the repair ofwounds and regeneration of the extracellular tissuelost or damaged during atherosclerosis.
Functions• Vitamin E also plays a role in neurological functions,and inhibition of platelet aggregation.• Vitamin E also protects lipids and prevents the oxidation ofpolyunsaturated fatty acids.So far, most human supplementation studies about vitamin Ehave used only α-tocopherol. This can affect levels of otherforms of vitamin E, e.g. reducing serum γ- and δ-tocopherolconcentrations. Moreover, a 2007 clinical study involving α-tocopherol concluded supplementation did not reduce therisk of major cardiovascular events in middle-aged and oldermen.
DeficiencyVitamin E deficiency can cause:• Spino-cerebellar ataxia• Myopathies• Peripheral neuropathy• Ataxia• Skeletal myopathy• Retinopathy• Impairment of the immune response• Red blood cell destruction
Recommended daily intakeThe Food and Nutrition Board at the Institute of Medicine (IOM) of the US National Academy ofSciences reported the following dietary reference intakes for vitamin E:mg/day AgeInfants• 4 0 to 6 months• 5 7 to 12 monthsChildren• 6 1 to 3 years• 7 4 to 8 years• 11 9 to 13 yearsAdolescents and adults• 15 14 and olderOne IU of vitamin E is defined as equivalent to either: 0.67 mg of the natural form, RRR-α-tocopherol, also known as d-α-tocopherol; or 0.45 mg of the synthetic form, all-rac-α-tocopherol, also known as dl-α-tocopherol.
History• The first use for vitamin E as a therapeutic agent wasconducted in 1938 by Widenbauer, who used wheatgerm oil supplement on 17 premature newborn infantssuffering from growth failure. Eleven of the original 17patients recovered and were able to resume normalgrowth rates.• In 1945, Drs. Evan V. Shute and Wilfred E. Shute,siblings from Ontario, Canada, published the firstmonograph arguing that megadoses of vitamin E canslow down and even reverse the development ofatherosclerosis. Peer-reviewed publications soonfollowed.
History• The same research team also demonstrated, in1946, that α-tocopherol improved impairedcapillary permeability and low platelet counts inexperimental and clinical thrombocytopenicpurpura.• Later, in 1948, while conducting experiments onalloxan effects on rats, Gyorge and Rose notedrats receiving tocopherol supplements sufferedfrom less hemolysis than those that did notreceive tocopherol.
History• In 1949, Gerloczy administered all-rac-α-tocopheryl acetate to prevent and cureedema. Methods of administration usedwere both oral, that showed positive response,and intramuscular, which did not show aresponse. This early investigative work on thebenefits of vitamin E supplementation was thegateway to curing the vitamin E deficiency-causedhemolytic anemia described during the 1960s.Since then, supplementation of infant formulaswith vitamin E has eradicated this vitamin’sdeficiency as a cause for hemolytic anemia.
FormsThe eight forms of vitamin E are divided intotwo groups; four are tocopherols and four aretocotrienols. They are identified by prefixesalpha- (α-), beta- (β-), gamma- (γ-), and delta-(δ-). Natural tocopherols occur in the RRR-configuration only. The synthetic form containseight different stereoisomers and is called all-rac-α-tocopherol.
Forms• α-Tocopherol α-Tocopherol is an important lipid-soluble antioxidant. It performs itsfunctions as antioxidant in the glutathione peroxidase pathway,and itprotects cell membranes from oxidation by reacting with lipid radicalsproduced in the lipid peroxidation chain reaction. This would removethe free radical intermediates and prevent the oxidation reaction fromcontinuing. The oxidized α-tocopheroxyl radicals produced in thisprocess may be recycled back to the active reduced form throughreduction by other antioxidants, such as ascorbate,retinol or ubiquinolHowever, the importance of the antioxidant properties of this molecule atthe concentrations present in the body are not clear and the reasonvitamin E is required in the diet is possibly unrelated to its ability to actas an antioxidant. Other forms of vitamin E have their own uniqueproperties; for example, γ-tocopherol is a nucleophile that can reactwith electrophilic mutagens.
Forms• TocotrienolsCompared with tocopherols, tocotrienols are sparsely studied. Lessthan 1% of PubMed papers on vitamin E relate to tocotrienols. The currentresearch direction is starting to give more prominence to the tocotrienols, thelesser known but more potent antioxidants in the vitamin E family. Some studieshave suggested that tocotrienols have specialized roles inprotecting neurons from damage and cholesterol reduction by inhibitingthe activity of HMG-CoA reductase; δ-tocotrienol blocks processing of sterolregulatory 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 outon the other forms of vitamin E, conclusions relating to the other forms ofvitamin E, based on trials studying only the efficacy of α-tocopherol, may bepremature.