RRR-a-tocopheryl acetate

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

Property i7//-n7iva-Tocopherol RRR-a-T ocopherol all-rac-d-T ocopheryl Acetate RRR-a-Tocopheryl -Acetate... 

RRR-a-Tocopheryl Acetate occurs as a colorless to yellow, clear, viscous oil. It is a form of vitamin E obtained by the vacuum steam distillation and acetylation of edible vegetable oil products. It may solidify on standing, and melts at about 25°. It is unstable in the presence of alkalies. It is insoluble in water freely soluble in alcohol and miscible with acetone, with chloroform, with ether, and with vegetable oils. 

Labeling All label claims that are in terms of International Units (IU) should be based on the following 1 mg of RRR-a-Tocopheryl Acetate = 1.36 IU. 

Procedure Chromatograph 2 to 5 p.L of the Assay Preparation as described under Calibration. Measure the areas under the major peaks occurring at relative retention times of approximately 0.60 (a-tocopheryl acetate) and 1.00 (hexadecyl hexadecanoate), and record the values as ay and aj, respectively. Calculate the weight, in milligrams, of RRR-a-Tocopheryl Acetate in the sample by the formula... 

Assay Determine as directed in the monograph for RRR-a-Tocopheryl Acetate, using the following as the Assay Preparation. Dissolve an accurately weighed amount of sample, equivalent to about 30 mg of all-rac-a-tocopheryl acetate, in 10.0 mL of the Internal Standard Solution. 

Acidity Determine as directed in the monograph for RRR-a-Tocopheryl Acetate. 

RRR-a-Tocopheryl Acetate Concentrate occurs as a light brown to light yellow, clear, viscous oil. It is a form of vitamin... 

Gum Arabic Ammonia Solution All-rac-a-Tocopherol RRR-a -T ocopherol RRR-Tocopherols Concentrate, Mixed RRR-a-Tocopheryl Acetate All-rac-a-Tocopheryl Acetate RRR-a-Tocopheryl Acetate Concentrate RRR-a-Tocopheryl Acid Succinate... 

Fuller, C-, Chandalia, M., Garg, A., Grundy, S., and Jialal, 1. (1996). RRR-a-tocopheryl acetate supplementation at pharmacologic doses decreases low-density-lipoproiein oxidative susceptibility but not protein glycation in patients with diabetes mellitus. Am. 

As a measure of their biological activity, all E vitamers can be assigned a potency, determined in a bioassay. One international unit (lU) is defined as the activity of 1 mg of flZZ-rac-a-tocopheryl acetate. Accordingly, the biopotencies of RRR-a-tocopheryl acetate, RRR-a-tocopherol and a/Z-rac-a-tocopherol have been calculated to be 1.36, 1.49, and 1.10 lU, respectively. The chirality of the C-2 atom is crucial to the activity, the 2-epimers having only one-third of the potency of the 2R forms. Biopotencies of tocopherols and tocotrienols can be expressed relative to that of a-tocopherol. Reported values (in %) are 100 (a-tocopherol), 40 (p-tocopherol), 8 (y-tocopherol), 1 (8-tocopherol), 21 (a-tocotrie-nol), and 4 (p-tocotrienol). This order parallels that of the relative antioxidant activity of the various vitamers (see B). 

The biological activity of various vitamin E forms was estabUshed by the fetal resorption assay ia tats and is assumed to be appHcable to humans. The results of some human studies may iadicate that the ratio of 1.36 underestimates the biological activity of the RRR form relative to the all-rac form of a-tocopheryl acetate (10—12). 

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.)... 

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. 

Commercially available vitamin E consists of either a mixture of namrally occurring tocopherols and tocotriraiols (from natural sources), RRR-a-tocopherol (formerly called d-a-tocopherol), synthetic a-tocopherol, consisting of the eight possible side-chain stereoisomers at eqnal amonnts (all roc-a-tocopherol, formerly called dl-a-tocopherol), or their esters (a-tocophrayl succinate, a-tocopheryl acetate, a-toco-... 

DL-a Tocopherol. See Tocopherol (R,R,R)-a-Tocopherol. See,D-a-Tocopherol RRR-y-Tocopherol. See (+)-y-Tocopherol d,l-a-Tocopherol acetate ( )-o-Tocopherol acetate. See dl-a-Tocopheryl acetate a-Tocopherol acid succinate. See Tocopheryl succinate... 

To resolve all eight stereoisomers, the systems based on PTMA silica or Chiralcel OD for the separation of a-tocopheryl acetates have been combined with GC (145,149,168). First, the LC separation of the acetates is carried out to yield four fractions. Collected peaks are pooled in an LC-A fraction, containing ali 2R stereoisomers (peaks 1 + 2) and an LC-B fraction composed of the 2S stereoisomers (peaks 3 + 4). Both LC-A and LC-B are then further resolved by GC, after conversion of the acetate to methyl ether derivatives, into the eight individual components. Application of this method to biological samples of rats revealed that, after administration of fl//-rac-a-tocopheryl acetate the 2R stereoisomers accumulated preferentially (70% to 80%) in plasma and tissues, as opposed to their 2S counterparts, which represented a minor (14% to 30% of total) fraction (149). The four 2R stereoisomers, including the natural RRR form, were equally enriched. 

RV Acuff, SS Thedford, NN Hidiroglou, AM Papas, TA Odom Jr. Relative bioavailability of RRR- and all-rac-a-tocopheryl acetate in humans studies using deu-terated compounds. Am J Clin Nutr 60, 397-402, 1994. 

The amount of vitamin E required by the body depends upon its size and the amount of polyunsaturated fats in the diet, as vitamin E is needed to protect these fats from oxidation. The requirement for vitamin E depends upon intake of refined oils, fried foods, or rancid oils. Supplemental estrogen or estrogen imbalance in women increases the need for vitamin E, as does air pollution. The recommended dietary allowance (RDA) for vitamin E is really quite low, many people do not consume this in their diet alone. Table 19.1 lists the RDAs and tolerable upper intake levels (ULs) for vitamin E. The new recommendations for vitamin E are expressed as milligrams of RRR-a-tocopherol equivalents. Dietary supplements of vitamin E are labeled in terms of international units (lU). 1 mg of synthetic vitamin E (a//-rac-a-tocopheryl acetate is equivalent to 1 lU vitamin E, but only 0.45 mg RRR-a-tocopherol. 1 mg of natural vitamin E (RRR-a-tocopherol) provides 1.5 lU. For the LIE, the Food and Nutrition Board recommended 1000 mg of any a-tocopherol form, which is equivalent to 1500 lU RRR- or 100 lEI all-rac-a-tocopherol (Food and Nutrition Board, 2000 Hathcock et al., 2005 Combs, 2008). 

The chemical synthesis of a-tocopherol results in an equal mixture of eight different stereoisomers (RRR, RSR, RRS, RSS, SRR, SSR, SRS, SSS) or, more formally, 2,5,7,8-tetramethyl-2RS-(4 RS,8 RS,12 trimethyltridecyl)-6-chromanol. To indicate that synthetic a-tocopherol is a racemic mixture, it is called d //-rac-a-tocopherol, or on labels, factors used to convert international units (lU) to milligrams. For example, if a vitamin E supplement is labeled 400 lU and it is d/-a-tocopheryl acetate, then 400 times 0.45 equals 180mg2R-a-tocopherol, but if it is labeled d-a-tocopheryl acetate, then 400 times 0.67 equals 268 mg2R-a-tocopherol. 

Most vitamin E supplements and food fortificants contain all rac-a-tocopherol, but can contain mixtures of tocopherols or tocotrienols. Supplements often are sold as esters, which protect a-tocopherol from oxidation. These can be acetates, succinates, or nicotinates of a-tocopherol. Either the natural stereoisomer (RRR-a-tocopherol) or the synthetic all rac-a-tocopherol) can be sold as an ester, e.g., d- or d/-a-tocopheryl acetate, respectively. 

According to the US Pharmacopoeia (USP), IIU of vitamin E equals Img all rac a-tocopheryl acetate, 0.67mg RRR-a-tocopherol, or 0.74 mg RRR-a-toco-pheryl acetate. These conversions were estimated on the relative biologic activities of the various forms when tested in the rat assay for vitamin E deficiency, the fetal resorption assay. These USP lUs are currently used in labeling vitamin E supplements and food for-tificants. It should be noted that the current RDA does not use vitamin E USP units but rather the recommendation for adults is set at 15 mg of RRR-a-tocopherol or IR-a-tocopherols. Most foods contain RRR-a-tocopherol naturally, but foods that have been fortified with vitamin E contain the synthetic form, e.g., fortified breakfast cereals. If the amount of vitamin E on the label is given in international units, then this must be multiplied by the factors given in Table 2 to obtain the amount of 2R-/3-tocopherol. 

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