RRR-a-tocopherol

RRR)-a-tocopherol, (RRR)-a-tocopheryl acetate, all-rai -a-tocopherol, all-rai a-tocopheryl acetate, all-rai a-tocopheryl succiaate... 

The yield of the more active RRR-a-tocopherol can be improved by selective methylation of the other tocopherol isomers or by hydrogenation of a-tocotrienol (25,26). Methylation can be accompHshed by several processes, such as simultaneous halo alkylation and reduction with an aldehyde and a hydrogen haUde in the presence of staimous chloride (27), amino alkylation with ammonia or amines and an aldehyde such as paraformaldehyde followed by catalytic reduction (28), or via formylation with formaldehyde followed by catalytic reduction (29). 

Although apparendy not commercially important, fermentation (qv) processes have been reported for the production of tocopherols. yispergillus niger (30), iMctohacter (31), Eugknagracilis Z. (32,33), and Mjcohacterium (34) have been shown to produce (RRR)-a-tocopherol. In the case of Eug/ena, titers of 140—180 mg/L have been reported. 

AH formulations of vitamin E must show low acidity, and contain not more than 0.004% heavy metals (reported as Pb) and not more than 10 ppm Pb. Eormulations that contain RRR-a-tocopherol must have a specific rotation of +24 ° for the oxidation product with alkaline potassium ferricyanide. 

The term vitamin E describes a family of eight antioxidants, four tocopherols, alpha (a), beta ((3), gamma (y) and delta (8), and four tocotrienols (also a, (3, y, and 8). a-Tocopherol is present in nature in only one form, RRR a-tocopherol. The chemical synthesis of a-tocopherol results in eight different forms (SRR, SSR, SRS, SSS, RSR, RRS, RSS, RRR), only one of which is RRR a-tocopherol. These forms differ in that they can be right (R) or left (S) at three different places in the a-tocopherol molecule. RRR a-tocopherol is the only form of vitamin E that is actively maintained in the human body and is therefore the form of vitamin E found in the largest quantities in the blood and tissue. A protein synthesized in the liver (a-TTP alpha-tocopherol transfer protein) preferentially selects the natural form of vitamin E (RRR a-tocopherol) for distribution to the tissues. However, the mechanisms for the regulation of vitamin E in tissues are not known... 

Due to bleeding risk, individuals on anticoagulant therapy or individuals who are vitamin K-deficient should not take vitamin E supplementation without close medical supervision. Absent of that, vitamin E is a well-tolerated relatively non-toxic nutrient. A tolerable upper intake level of 1,000 mg daily of a-tocopherol of any form (equivalent to 1,500 IU of RRR a-tocopherol or 1,100 IU of all-rac-a-tocopherol) would be, according to the Food and Nutrition Board of the Institute of Medicine, the highest dose unlikely to result in haemorrhage in almost all adults. 

It should be noted that pharmacological vitamin E is not a free natural RRR-a-tocopherol or synthetic All rac a-tocopherol but its acetate ester. a-Tocopheryl acetate has the phenolic hydroxyl group blocked and therefore, is not a genuine antioxidant, but this compound is very rapidly hydrolyzed in vivo into a-tocopherol. It is interesting that the biological activity of a-tocopheryl acetate is the same as that of a-tocopherol in humans but significantly lower in rats [30]. ( A man is not a rat Professor KU Ingold.)... 

Vitamin E RRR- a-tocopherol all-rac- a-tocopherol HepG2 dose response No difference in EC50 or IC50 [17]... 

In the analysis of foods that contain significant amounts of both naturally occurring toco-pherols and supplemental a-tocopheryl acetate, saponification, by hydrolyzing the esterified vitamin E, allows the total a-tocopherol content to be measured as a single peak by HPLC. It should be noted that if totally synthetic all-rac-a-tocopheryl acetate is the supplemental form used, its hydrolysis product, all-rac-a-tocopherol, is less biologically active than is naturally occurring RRR-a-tocopherol, making it impossible to calculate a potency value for the total vitamin E. This problem does not arise if the supplement used is / / / -a-tocopheryl acetate. 

Under the denomination of vitamin E are collected eight different isomers that are present in nature and particularly in oils commonly used as food, The synthetic vitamin E is the all racemic a-tocopherol (ART), whereas the natural vitamin E is the RRR a-tocopherol (RRRT). 

Table 6 Clinical/epidemioloqical studies with Vitamin E as all racemic a-tocopherol (ART), or as RRR-a tocopherol (RRRT)...

Since vitamin E is very sensitive to oxidation, stable esters have mainly been used for topical formulations and are considered to be safe.64 As had previously been shown for skin of hairless mice,65 but not for human skin,66 the bioconversion of vitamin E acetate by esterases to vitamin E with its known antioxidant effects has recently also been demonstrated in human skin.48 When supplemented orally a-tocopherol acetate or a-tocopherol succinate get readily hydrolyzed to a-tocopherol in the gut47 with the natural single stereoisomeric form (RRR-a-tocopherol) appearing to have about twice the systemic availability of the synthetic form (all-rac-a-tocopherol)67... 

RRR-a-Tocopherol Concentrate occurs as a brown-red to light yellow, clear, viscous oil. It is a form of vitamin E obtained by the vacuum steam distillation of edible vegetable oil products, comprising a concentrated form of RRR-a-tocopherol. It oxidizes and darkens slowly in air and on exposure to light. It may contain an edible vegetable oil added to adjust the required amount of total tocopherols, and the content of RRR-a-tocopherol may be adjusted by suitable physical and chemical means. It is insoluble in water soluble in alcohol and miscible with acetone, with chloroform, with ether, and with vegetable oils. 

Labeling Indicate the milligrams per gram of RRR-a-to-copherol present. All label claims that are in terms of International Units (IU) should be based on the following 1 mg of RRR-a-tocopherol = 1.49 IU. 

Assay Not less than 40.0% of total tocopherols, of which not less than 95.0% consists of RRR-a-tocopherol (C29H50O2). Acidity Passes test. 

The high-alpha type contains a relatively high proportion of RRR-a-tocopherol and is recognized as a form of vitamin E and also as an antioxidant. The low-alpha type contains a relatively high proportion of d-(3-, D-y-, and D-S-tocopherols, with a minor level of RRR-a-tocopherol, and thus is not considered to be a form of vitamin E, but rather an antioxidant. Both types may contain an edible vegetable oil added to adjust... 

Assay High-Alpha Type Not less than 50.0% of total tocopherols, of which not less than 50.0% consists of RRR-a-tocopherol (C29H50O2) and not less than 20.0% consists of d-3- plus D-y- (C28H48O2) plus D-S-tocopherols (C27H46O2). Low-Alpha Type Not less than 50.0% of total tocopherols, of which not less than 80.0% consists of d-(3- plus D-y- plus D-S-tocopherols. 

Retention within tissues depends on intracellular binding proteins which, like the liver a-tocopherol transfer protein, have the highest affinity for RRR-a-tocopherol. The retention of a-tocopherol in tissues varies. In the lungs the vitamin has a half-life of 7.6 days, in liver 9.8 days, in skin 23.4 days, in brain 29.4 days, and in the spinal cord 76.3 days (Ingold et al., 1987). 

Tocopherols and tocotrienols form pale yellow and viscous liquids at room temperature that are soluble in lipids and lipophilic solvents but are insoluble in water. In agreement with the substitution pattern, the hydrophobic properties of tocopherols decrease in the order of a- > 0- > y- > 8-tocopherol (Sliwiok and Kocjan, 1992). The melting point of RRR-a-tocopherol is ca 3°C, while that of RRR-y-tocopherol is at -3° to -2°C (Schudel et al., 1972). The ultraviolet absorption spectra of tocopherols and tocotrienols in ethanol show maxima in the range of 290-298 nm (Schudel et al., 1972 Diplock, 1985). The pure tocopherols isolated from natural sources exhibit relatively small optical rotations tocopherols are dextrorotatory in ethanol, while they are levorotatory in benzene. The free phenolic hydroxyl group of tocopherol molecules mainly determines their chemical properties (Schudel et al., 1972). 

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