Tocopherol requirements/recommendations

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). 

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. 

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. 

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... 

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. 

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%. 

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... 

As regards the use of vitamins in cancer prevention, as distinct from cancer treatment, there is no evidence that a vitamin intake above that required for normal nutrition provides extra protection. However, since vegetables contain /5-carotene, tocopherols, ascorbic acid and also considerable amounts of fibre, all of which are credited with beneficial effects, a high vegetable diet would seem to have much to recommend it. A list of some of the dietary factors currently believed to have either cancer-preventing or cancer-promoting effects is given in Table 12.2. 

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). 

Vitamin E is the most potent fat-soluble antioxidant in human plasma. Although vitamin E was first discovered in 1922, its metabolic function remains an enigma. There are eight different molecular forms with vitamin E antioxidant activity, yet the body preferentially retains a-tocopherol. This preference for a-tocopherol has led the Eood and Nutrition Board in its 2000 Dietary Reference Intakes (DRIs) for vitamin E to recommend that only a-tocopherol, not the other forms, meets human requirements for vitamin E. Moreover, only a-tocopherol is recognized by the hepatic a-tocopherol transfer protein (a-lT P). This protein regulates plasma a-tocopherol concentrations and genetic abnormalities in the protein (or its absence) leads to vitamin E deficiency in humans. 

Table 1 Estimated average requirements (EARs), recommended dietary allowances (RDAs), and average intakes (Als) (mgday ) for a-tocopherol in adults and children...

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