Recommended tocopherols

The recommended daily allowance for vitamin E ranges from 10 international units (1 lU = 1 mg all-rac-prevent vitamin E deficiency in humans. High levels enhance immune responses in both animals and humans. Requirements for animals vary from 3 USP units /kg diet for hamsters to 70 lU /kg diet for cats (13). The complete metaboHsm of vitamin E in animals or humans is not known. The primary excreted breakdown products of a-tocopherol in the body are gluconurides of tocopheronic acid (27) (Eig. 6). These are derived from the primary metaboUte a-tocopheryl quinone (9) (see Eig. 2) (44,45). 

Vitamin E is not recommended for the prevention of chronic disease, such as coronary heart disease or cancer. Clinical trials using vita min E supplementation have been uniformly disappointing. For example, subjects in the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study trial who received high doses of vitamin E, not only lacked cadiovascular benefit but also had an increased inci dence of stroke. 

There are numerous papers that refer to the quantification of tocopherols and tocotrienols using HPLC methods. Normal-phase HPLC methods with a silica column as well as reversed-phase HPLC methods with a C18 column are commonly used. A silica normal-phase column is able to separate all eight tocopherols and tocotrienols in a typical chromatographic procedure. Because plant tissues possess most forms of tocopherol and tocotrienol, it is recommended that the normal-phase HPLC method be applied to food samples from plants. In the reversed-phase HPLC method, [3- and y-tocopherol and (3-and y-tocotrienol are not usually completely separated. This method can be used in animal tissues, which either lack or have reduced levels of [3- and y-tocopherol and (3- and y-tocotrienol. The resolution of the normal-phase HPLC method is higher than that of reversed-phase HPLC method however, the reversed-phase HPLC column is more long-lasting than the normal-phase HPLC column (see Critical Parameters and Troubleshooting). 

Cereals and nuts are blended to fine particles before sample preparation. Saponification, heating, and liquid/liquid extraction are employed in the sample preparation to weaken sample matrix and eliminate interference compounds. Most cereals and nuts contain various forms of tocopherol and tocotrienol. The normal-phase HPLC method is recommended for these types of samples. 

In normal-phase HPLC on a silica column, separation is based on the number and position of methyl substituents on the chromanol ring. In reversed-phase HPLC on a Cl8 column, separation is based on the structure of the side chain and the number of methyl substituents. It is therefore difficult to completely separate [3-and y-tocopherol and (3- and y-tocotrienols by reversed-phase HPLC, because both have the same side-chain structure and number of methyl substituents on the chromanol ring. Only six peaks are usually found in the reversed-phase HPLC method. Thus, reversed-phase HPLC is recommended for samples from animal tissues, which contain little or no P and y vitamers. 

Antioxidants. To reduce oxidation reactions that could impact tocopherols and tocotrienols during saponification and extraction, an antioxidant, such as ascorbic acid or pyrogallol, is added to the sample solution. Also, it is recommended that the sample vessel be flushed with nitrogen and sealed before saponification. 

Research Council defined 1 mg of a-tocopherol as 1 unit of a-TE (mg x 1). The activities as a-TE of other vitamers were (3-tocopherol, mg x 0.5 y-tocopherol, mg xO. 1 8-tocopherol, mg x 0.03 a-tocotrienol, mg x 0.3 and (3-to-cotrienol, mg x 0.05. The activities of y- and 8-tocotrienol were undetectable. The Recommended Dietary Allowances (RDAs) are only based on intake of the 2R-stereoisomeric forms of a-tocopherol (RRR-, RSR-, RRS-, and RSS-tocopherol) from food, fortified food, and vitamin supplements (Food and Nutrition Board, 2000). The 2S-stereoisomeric forms of a-tocopherol and the other tocopherols ((3-, y-, and 5-tocopherol) and tocotrienols are not used to estimate the RDAs. 

In another study (Moriel et al., 2002), 11 patients with mild essential hypertension were compared with 11 healthy subjects for water- and lipid-soluble antioxidants and the concentrations of nitric oxide derivatives in the plasma. A significant reduction in plasma lycopene was observed in the hypertensive patients compared to the normal subjects. Similar reductions in ascorbate, urate, and (3-carotene were also observed in this study. However, there were no differences in the nitrous oxide derivatives between the two groups. Hypertension and lymphatic circulation impairment are associated with liver cirrhosis. When patients with liver cirrhosis were compared to healthy matched controls, a significant reduction in serum lycopene, other carotenoid antioxidants, retinol, and oc-tocopherol were observed in the cirrhotic patients. Based on these observations, the authors recommend thorough screening for the antioxidants and improved diet in the... 

Supplementation with the antioxidant vitamins ascorbic acid (250 mg) and mixed natural tocopherols (50 IU on alternate days) may be beneficial. Higher doses may vitiate the impact of lipid lowering therapy. Other naturally occurring antioxidants such as resveratrol, 3-catechin, selenium, and various carotenoids found in a variety of fruits and vegetables may provide additional antioxidant defense. Homocysteine, which initiates proatherogenic changes in endothelium, can be reduced in many patients by restriction of total protein intake to the amount required for amino acid replacement. Daily supplementation with up to 2 mg of folic acid plus other B vitamins is also recommended. 

ATBC 2C 501U (ART) 64 yrs 904 M Not recommended the use of a-tocopherol in men with previous myocardial infarction. 130... 

Based on the plasma concentration of a-tocopherol to prevent significant hemolysis in vitro (14 to 16 /xmol per L), the U.S./Canadian estimated average requirement is 12 mg per day, giving a Recommended Dietary Amount (RDA) of 15 mg per day (Institute of Medicine, 2000) - a 50% increase on the previous RDA (National Research Council, 1989). This increase arose partly as a result of considering only the 2R isomers in dietary intake (Section 4.1). Average intakes are of the order of 8 to 12 mg of a -tocopherol equivalent per day it would be difficult meet this reference intake without significant changes in diet or use of supplements. 

There was a statistically significant increase in the risk of retinal hemorrhage with parenteral vitamin E in premature infants (28). This has led some researchers to conclude that tocopherol should not be recommended for the prevention of retinopathy in prematurity (29), particularly in infants with birth weights of less than 1 kg. 

Premature neonates are reported to have a relative deficiency of vitamin E at birth, which has been associated with hemolytic anemia (16). Since there was an increased incidence of necrotizing enterocolitis when oral tocopherol was given to such infants (7,8,17,18), parenteral tocopherol was for a while recommended for use in very ill neonates (19,20). 

The optimal dietary requirements of vitamin E for humans are not yet known, especially with the emergence of new paradigms regarding adequate levels of dietary micronutrients (Chalem, 1999). Recommendations in the United States and Canada have been reevaluated, and a new concept of Dietary Reference Intake (DRI, 2000) was issued for vitamin E and other antioxidants. The DRI recommendation should prevent specific deficiency disorders, support health in general ways and minimize the risk of toxicity, which carries more tasks than the previous recommendations (DRI, 2000). Accordingly, the recommendations for intakes were set to higher levels than previously. Estimated Average Requirements (EAR) for adults, both men and women, were set to 12 mg a-tocopherol/day, RDA to 15 mg/day and Tolerable Upper Intake Level (UL) to 1000 mg/day. Moreover, the EAR and RDA are based only on the 2R-stereoisomeric forms of a-tocopherol, because the other vitamers... 

AOCS. 1990. Official Method Ce 8-89. Determination of Tocopherols and Tocotrienols in Vegetable Oils and Fats by HPLC, in Official Methods and Recommended Practices of the Am. Oil Chem. Soc. Sampling and Analysis of Commercial Fats and Oils. 4th ed. Champaign, IL Am. Oil Chem. Soc. Press, 5 pp. 

RDA for vitamin E was increased in the year 2000 by 50% from 10 to 15 mg/day for adults by the U.S. Food and Nutrition Board.Most European reference intakes are related to the polyunsaturated fatty acid intake. The changes in the United States were accompanied by some debate, critics arguing that this amount could not be met by the usual North American diet. For infants up to 6 months, an AI of 4mg/day was proposed, for infants 7 to 12 months an AI of 5mg/day and the RDA for children 1 to 18 years was set at 6 to 15 mg/day, dependent upon age. Another departure in the newer recommendations was that the daily requirement he met by RRR-a-tocopherol alone as the other forms of vitamin E are not converted to a-tocopherol and are poorly recognized by the a-tocopherol transfer protein in the liver. 

The recommended amount of vitamin E to be supplied intravenously to adults is 10 mg as a-tocopherol. This is rather lower than the oral provision, but takes into account the fact that it is completely delivered into the blood stream. 

These observations on the pro-oxidant behavior of the antioxidant (normally) a-Toc in micelles and lipid membranes provide some insight into the remarkable pro-oxidant activity of a-Toc in low density lipoprotein, LDL, under in vitro conditions. The radical initiated oxidation of LDL is of great interest because it is implicated in heart disease. The tocopherol-mediated peroxidation (TMP) of LDL was reported on in detail by Bowry and Stocker and is also the subject of timely, detailed reviews . This interesting story will not be reviewed again here, but these articles are highly recommended since they provide important insight into the unique behavior of a-Toc. 

Since oxidation is one of the major factors in protein degradation, the use of specific antioxidants may be required. Ascorbic acid, monothio-glycerol, and alpha tocopherols have been used for this purpose. A recommended antioxidant dose14 would range from 0.05 to 0.1%. 

Table 8.4 Factors for Converting International Units of Vitamin E to a-Tocopherol (mg) to Meet Recommended Intake ...

There is reason to conclude that vitamin deficiency might contribute to arteriosclerosis. There is a correlation between elevated homocysteine levels and incidence of cardiovascular disease (59). There is debate as to whether homocysteine contributesto the dam e of cells on the interior of blood vessel or whether homocysteine is a marker of intensive cell repair and formation of replacement cells. Nevertheless, administration of pyridoxine, folic acid, and (yanocobalamin are being recommended along with the two antioxidant vitamins, a-tocopherol and ascorbic acid for arteriosclerosis. Vitamin Bg is required for two of the steps in the catabolism of homocysteine to succinyl CoA (Fig. 8.52). Note in Fig. 8.52 (bottom) that biotin and a coenzyme form of cobalamin also are required for... 

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