Tocopherol, or vitamin E, is a fat-soluble vitamin in eight forms that is an important antioxidant. Vitamin E is often used in skin creams and lotions because it is claimed by the manufacturers to play a role in encouraging skin healing and reducing scarring after injuries such as burns.
Natural vitamin E exists in eight different forms or isomers, four tocopherols and four tocotrienols. All isomers have a chromanol ring, with a hydroxyl group which can donate a hydrogen atom to reduce free radicals and a hydrophobic side chain which allows for penetration into biological membranes. There is an alpha, beta, gamma and delta form of both the tocopherols and tocotrienols, determined by the number of methyl groups on the chromanol ring. Each form has its own biological activity, the measure of potency or functional use in the body.
Forms of vitamin E
Alpha-tocopherol is traditionally recognized as the most active form of vitamin E in humans, and is a powerful biological antioxidant. The measurement of "vitamin E" activity in international units (IU) was based on fertility enhancement by the prevention of spontaneous abortions in pregnant rats relative to alpha tocopherol. It increases naturally to about 150% of normal in the maternal circulation during human pregnancies. 1 IU of vitamin E is defined as the biological equivalent of 0.667 milligrams of RRR-alpha-tocopherol (formerly named d-alpha-tocopherol, or of 1 milligram of all-rac-alpha-tocopheryl acetate (commercially called dl-alpha-tocopheryl acetate, the original d,l- synthetic molecular mix, properly named 2-ambo-alpha-tocopherol, is no longer manufactured). The other R,R,R tocopherol vitamers are slowly being recognized as research begins to elucidate their additional roles in the human body. Many naturopathic and orthomolecular medicine advocates suggest that vitamin E supplements contain at least 20% by weight of the other natural vitamin E isomers. Commercially available blends of natural vitamin E include "mixed tocopherols" and "high gamma tocopherol" formulas.
Tocotrienols, with four d- isomers, also belong to the vitamin E family. The four tocotrienols have structures corresponding to the four tocopherols, except with an unsaturated bond in each of the three isoprene units that form the hydrocarbon tail. Tocopherols have a saturated phytyl tail.
Antioxidants such as vitamin E act to protect cells against the effects of free radicals, which are potentially damaging by-products of the body's metabolism. Free radicals can cause cell damage that may contribute to the development of cardiovascular disease and cancer. Vitamin C and other anti-oxidants recycle vitamin E end-products back into effective suppressors of free radicals. Studies are underway to determine whether vitamin E might help prevent or delay the development of those chronic diseases.
Commercial vitamin E supplements can be classified into several distinct categories: fully synthetic vitamin E, "d,l-alpha-tocopherol", the most inexpensive, most commonly sold supplement form usually as the acetate ester; semisynthetic "natural source" vitamin E esters, the "natural source" forms used in tablets and multiple vitamins; highly fractionated natural d-alpha tocopherol; less fractionated "natural mixed tocopherols"; high gamma-tocopherol fraction supplements; and tocotrienol supplements.
Synthetic vitamin E is now manufactured as all-racemic alpha tocopheryl acetate with three chiral centers, with only one alpha tocopherol molecule (moiety) in 8 molecules as actual R,R,R-alpha tocopherol. Synthetic all-rac vitamin E is usually marked as d,l-tocopherol or d,l-tocopheryl acetate, with 50% d-alpha tocopherol moiety and 50% l-alpha-tocopherol moiety, as synthesized by an earlier process with only one chiral center. The synthetic form is not as active as the natural alpha tocopherol form. The 1950's thalidomide disaster with numerous severe birth defects is a common example of d- vs l- epimer forms type problem with synthesized racemic mixtures. Information on any side effects of the synthetic vitamin E epimers is not readily available. Naturopathic and orthomolecular medicine advocates have long considered the synthetic vitamin E forms to be with little or no merit for cancer, circulatory and heart diseases.
Semisynthetic "natural source" vitamin E, manufacturers convert the common natural beta, gamma and delta tocopherol isomers into esters using acetic or succinic acid and add methyl groups to yield d-alpha tocopheryl esters such as d-alpha tocopheryl acetate or d-alpha tocopheryl succinate. These tocopheryl esters are more stable and are easy to use in tablets and multiple vitamin pills. Because only alpha tocopherols were officially counted as "vitamin E" in supplements, refiners and manufacturers faced enormous economic pressure to esterify and methylate the other natural tocopherol isomers, d-beta-, d-gamma- and d-delta-tocopherol into d-alpha tocopheryl acetate or succinate. However these alpha tocopheryl esters have been shown to be variably and less efficiently absorbed in humans than in the original normative tests using rats. Tocopheryl nicotinate and tocopheryl linolate esters are used in cosmetics and some pharmaceuticals. In the healthy human body, the semisynthetic forms are easily de-esterified over several days, primarily in the liver, but not for common problems in premature babies, aged or ill patients.
"Mixed tocopherols" in the US contain at least 20% w/w other natural R,R,R- tocopherols, i.e. R,R,R-alpha-tocopherol content plus at least 25% R,R,R-beta-, R,R,R-gamma-, R,R,R-delta-tocopherols. Some premium brands may contain 200% w/w or more of the other tocopherols and measurable tocotrienols. Some mixed tocopherols with higher gamma-tocopherol content are marketed as "High Gamma-Tocopherol". The label should report each component in milligrams, except R,R,R-alpha-tocopherol may still be reported in IU. THE END.