Nutrition and Health Implications of Vitamin E

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With publication of the Dietary Reference Intakes (DRI) for vitamin E by the Food and Nutrition Board, National Institute of Medicine (1), recommended intakes for vitamin E now are based on the 2R-stereoisomeric forms of —-tocopherol (—-T). Other forms including the 2S-stereoisomers present in synthetic all-rac-—-T preparations and other tocopherols and tocotrienols in foods do not contribute to the intake requirement. Although sound scientific evidence backs the decision of the Panel on Dietary Antioxidants and Related Compounds to consider only the 2R-stereoisomers when setting optimal human intake xrecommendations, scientists involved with food science aspects of vitamin E must take a broader view because of the general antioxidant actions of the tocopherols and tocotrienols in foods. Likewise, food chemists and nutritionists involved in nutrient databank operations must decide on proper presentation of food composition data on vitamin E. Use of the milligram —-tocopherol equivalent (mg —-TE) has been discontinued in presentation of the United States Department of Agriculture databank.


Several reviews completed since 1998 cover newer aspects of vitamin E nutrition.(1, 2, 3, 4) The in-depth and well-referenced DRI report (1) represents the best source for a current overview of factors affecting human requirements for vitamin E. Other highly informative publications include those by Traber (2), Frei and Traber (3), and Bramley et al. (4). All readers interested in vitamin E nutrition should access the chapter on vitamin E in the latest edition of Modern Nutrition in Health and Disease (2) written by Dr. Maret Traber. It is not the purpose of this chapter to cover all aspects of vitamin E nutrition; however, we do discuss various aspects of significance to those involved with food delivery systems. The immense body of scientific studies developed over the past decade shows that we are just beginning to understand the impact of vitamin E on human well-being.

2.2.1. Absorption, Transport, and Preferential Selectivity for —-Tocopherol

Quite recent knowledge about absorption and transport of vitamin E led to the decision by the Panel on Antioxidants and Related Compounds (1) to base the DRIs for vitamin E on the ¿^-stereoisomers of —-T. The absorption and transport processes for vitamin E follow the sequence outlined:

1. Natural and synthetic forms of the tocopherols and tocotrienols are equally absorbed from the intestinal lumen in the form of mixed micelles (1, 5-10). Micelle formation relies on proper fat digestion to yield free fatty acids and mono- and diglycerides that act as emulsifiers with the bile salts. Disturbances in pancreatic function or liver secretion of bile, therefore, decrease absorption of the tocopherols and tocotrienols (2).

2. After passage of the micelles into the intestinal mucosa, chylomicrons are synthesized from fatty acids, lysophospholipids, sn-2 mono-acylglycerides, cholesterol, and other fat-soluble substances including the tocopherols and tocotrienols (11). The chylomicrons are lipoproteins designed to transport dietary lipids and lipid-soluble substances from the intestinal mucosa through the lymphatic system to the circulatory system.

3. In the blood, triaclyglycerol components of the chylomicrons are hydrolyzed by lipoprotein lipase with the formation of lipid-depleted chylomicron remnants. At this point, some of the circulating tocopherols and tocotrienols are transferred to tissue and to high-density lipoproteins (HDLs). Transfer from the HDL to other circulating lipoproteins then occurs (2, 6, 11).

4. The chylomicron remnants, containing most of the absorbed tocopherols and tocotrienols (2), are taken up by the liver. Triacylglycerols are synthesized and together with other fat-soluble components are formed into very-low-density lipoproteins (VLDLs)

that mediate the transport of lipid from the liver to the peripheral tissue through the circulatory system (12).

5. In the liver, RRR-a-T is preferentially incorporated into nascent VLDL (13). After secretion of the VLDL into the circulatory system, a-T is transferred to HDL and to other lipoproteins after delipidation of the VLDLs. The process selectively enriches plasma and, thus, tissue with a-T. The overall process is depicted in Figure 2.1. Role of the Hepatic —-Tocopherol Transfer Protein. The preferential incorporation of a-T into nascent VLDL in the liver is accomplished by action of the a-tocopherol transfer protein (a-TTP), which has been identified, isolated, and characterized from rat and human liver cytosol (1418). In vitro, the purified a-TPP transfers a-T between liposomes and microsomes (15, 19). However, the transfer of a-T to nascent VLDL has not been demonstrated in vivo (2). Hosomi et al. (19) showed that the relative affinity of a-TTP was greatest for RRR-a-T when compared to other tocopherols, tocopheryl esters, and a-tocotrienol (a-T3). Calculated on the basis of degree of competition with RRR-a-T, the relative affinities were RRR-a-T=100, RRR-^-T=38, RRR- j-T=9, RRR-£T=2, a-tocopheryl acetate=2, a-tocopheryl quinone=2, SRR-a-T=11, and a-T3=12.

It is evident that a-TTP can discriminate between RRR-a-T and other forms of vitamin E, most likely on the basis of the number and position of the methyl groups on the chromanol ring (4) and the stereoisomerism at the 2 carbon of the chromanol ring of a-T. Hosomi et al. (19) concluded that the biological activity of various forms of vitamin E is dependent upon tissue delivery and that their affinities for a-TPP limit secretion into lipoproteins and ultimate delivery to tissues. Affinity for the a-TTP was, therefore, proposed as a major determinant of biological activity.

2.2.2. Biological Activity

Initial estimations of the biological activity of the tocopherols and some of the tocotrienols were established by the rat fetal resorption assay.(20, 21) The classical approach follows the ability of vitamin E-deficient rats to maintain pregnancy. If vitamin E is not provided during the first 10-15 days after conception, the embryos die and are resorbed (22). Feeding of known levels of various vitamin E compounds and observation of their effects on fetal survival established relative biological activities. It has been assumed that values of biological activity determined with test animals directly apply to humans (23). However, with recognition of the selectivity for 2-R isomers of a-T through action of the a-TTP, human requirements are now established by using only the 2-R isomeric forms of a-T (1). Since the Dietary Reference Intakes refer only to the 2-R isomers, confusion

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figure 2.1 Transport and delivery of vitamin E. LPL, lipoprotein lipase, a-TTP, —¡-tocopherol transport protein; LDL, low-density lipoprotein; HDL, high-density lipoprotein; VLDL, very-low-density lipoprotein. (Modified from Ref. 2.)

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