Vitamin E is the general term for all tocopherols and tocotrienols, of which alpha-tocopherol is the natural and biologically most active form. Although gamma-tocopherol makes a significant contribution to the vitamin E CONTENT in foods, it is less effective in animal and human tissues, where alpha-tocopherol is the most effective chain-breaking lipid-soluble antioxidant. The antioxidant function of vitamin E is critical for the prevention of oxidation of tissue PUFA. Animal experiments have shown that increasing the degree of dietary fatty acid unsaturation increases the peroxidizability of the lipids and reduces the time required to develop symptoms of vitamin E deficiency. From these experiments, relative amounts of vitamin E required to protect the various fatty acids from being peroxidized, could be estimated. Since systematic studies on the vitamin E requirement in relation to PUFA consumption have not been performed in man, recommendations for vitamin E intake are based on animal experiments and human food intake data. An intake of 0.6 mg alpha-tocopherol equivalents per gram linoleic acid is generally seen as adequate for human adults. The minimum vitamin E requirement at consumption of fatty acids with a higher degree of unsaturation can be calculated by a formula, which takes into account the peroxidizability of unsaturated fatty acids and is based on the results of animal experiments. There are, however, no clear data on the vitamin E requirement of humans consuming the more unsaturated fatty acids as for instance EPA (20:5, n-3) and DHA (22:6, n-3). Studies investigating the effects of EPA and DHA supplementation have shown an increase in lipid peroxidation, although amounts of vitamin E were present that are considered adequate in relation to the calculated oxidative potential of these fatty acids. Furthermore, a calculation of the vitamin E requirement, using recent nutritional intake data, shows that a reduction in total fat intake with a concomitant increase in PUFA consumption, including EPA and DHA, will result in an increased amount of vitamin E required. In addition, the methods used in previous studies investigating vitamin E requirement and PUFA consumption (for instance erythrocyte hemolysis), and the techniques used to assess lipid peroxidation (e.g. MDA analysis), may be unsuitable to establish a quantitative relation between vitamin E intake and consumption of highly unsaturated fatty acids. Therefore, further studies are required to establish the vitamin E requirement when the intake of longer-chain, more-unsaturated fatty acids is increased. For this purpose it is necessary to use functional techniques based on the measurement of lipid peroxidation in vivo. Until these data are available, the widely used ratio of at least 0.6 mg alpha-TE/g PUFA is suggested. Higher levels may be necessary, however, for fats that are rich in fatty acids containing more than two double bonds.

Vitamin E supplementation has been shown to contribute in immunoregulation, antibody production, and resistance to implanted tumors. Similarly beta-carotene has been shown to down-regulate growth factors which contribute towards proliferation of pre-malignant cells. We embarked upon a study to evaluate the effect of vitamin E and beta-carotene on natural killer (NK) cells, which perform tumor surveillance role in the mammalian body. Mouse splenocytes or human peripheral blood lymphocytes were used as NK cells with murine YAC-1 lymphoma or human K-562 lymphoma cells, respectively, as target cells. The NK cells were treated with vitamin E or beta-carotene while target cells were labeled with sodium 51chromate. Both cell types were then reacted for 4 hours. The NK cell tumorolytic activity was measured by the chromium release assay. Oral administration of alpha-tocopherol at a dose of 100 mg/d in mice showed a significant increase in NK cell activity. Similarly, treatment of NK cells with alpha-tocopherol in vitro at doses 0.5 mg/ml, 1-0 mg/ml, and 2.0 mg/ml increased the tumorolytic activity of NK cells. Tocotrienol showed a similar response at ten times lower dose. When NK cells were treated with varying concentrations of palm vitee (mixture of alpha-tocopherol and tocotrienol), maximum effect was observed at the dose mixture of 12 micrograms and 24 micrograms alpha-tocopherol and tocotrienol, respectively. When murine NK cells were treated in vitro with beta-carotene at doses ranging from 2 ng/mg to 200 ng/ml, a decrease in tumorolytic effect was observed. However, human NK cells after treatment with beta-carotene at doses ranging from 0.1 microgram/ml to 10 micrograms/ml showed a significant increase in tumorolytic function. NK cells were also obtained from mice that had been parenterally administered beta-carotene and alpha-tocopherol. These experiments showed no significant increase in the NK cell function.

Tocopherols and tocotrienols are being increasingly recognized to have an important role in the prevention of atherosclerosis. It has been reported that they protect low-density lipoprotein (LDL) and tissues from oxidative stress and that tocotrienols can reduce plasma cholesterol levels. Two isocratic high-performance liquid chromatography (HPLC) methods for simultaneous analysis of tocopherols, tocotrienols, and cholesterol in muscle tissue were developed. Method A involves basic saponification of the sample, but causes losses of the gamma- and delta-homologs of vitamin E. Method B does not involve saponification, thereby protecting the more sensitive homologs. Both permit rapid analysis of multiple samples and neither requires specialized equipment. These methods may provide techniques useful in simultaneous assessment of oxidative stress status (OSS) and cholesterol levels.

A simple high-performance liquid chromatographic method using fluorescence detection was developed for the determination of vitamin E especially delta-, gamma- and alpha-tocotrienols in human plasma. The method entailed direct injection of plasma sample after deproteinization using a 3:2 mixture of acetonitrile-tetrahydrofuran. The mobile phase comprised 0.5% (v/v) of distilled water in methanol. Analyses were run at a flow-rate of 1.5 ml/min with the detector operating at an excitation wavelength of 296 nm and emission wavelength of 330 nm. This method is specific and sensitive, with a quantification limit of approximately 40, 34 and 16 ng/ml for alpha-, gamma- and delta-tocotrienol, respectively. The mean absolute recovery values were about 98% while the within-day and between-day relative standard deviation and percent error values of the assay method were all less than 12.0% for alpha-, gamma- and delta-tocotrienol. The calibration curve was linear over a concentration range of 40-2500, 30-4000 and 16-1000 ng/ml for alpha-, gamma- and delta-tocotrienol, respectively. Application of the method in a bioavailability study for determination of the above compounds was also demonstrated.

This article reviews compounds of botanical origin which are capable of lowering plasma levels of glucose and cholesterol and blood pressure, as well as compounds inhibiting atherosclerosis and thrombosis. Hypoglycemic natural products comprise flavonoids, xanthones, triterpenoids, alkaloids, glycosides, alkyldisulfides, aminobutyric acid derivatives, guanidine, polysaccharides and peptides. Hypotensive compounds include flavonoids, diterpenes, alkaloids, glycosides, polysaccharides and proteins. Among natural products with hypocholesterolemic activity are beta-carotene, lycopene, cycloartenol, beta-sitosterol, sitostanol, saponin, soybean protein, indoles, dietary fiber, propionate, mevinolin (beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor) and polysaccharides. Heparins, flavonoids, tocotrienols, beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors (statins), garlic compounds and fungal proteases exert antithrombotic action. Statins and garlic compounds also possess antiatherosclerotic activity.

The immunoregulatory effects of dietary alpha-tocopherol (Toc) and tocotrienols (T-3) on humoral and cell-mediated immunity and cytokine productions were examined in Brown Norway rats. We found that the IgA and IgG productivity of spleen and mesenteric lymph node (MLN) lymphocytes was significantly enhanced in the rats fed on Toc or T-3, irrespective of concanavalin A (Con A) stimulation of the lymphocytes. On the contrary, the IgE productivity of lymphocytes from the rats fed on Toc or T-3 was less without Con A stimulation, but was greater in the presence of Con A, especially in the T-3 group. Toc or T-3 feeding significantly decreased the proportion of CD4+ T cells and the ratio of CD4+/CD8+ in both spleen and MLN lymphocytes of the rats fed on Toc or T-3. The interferon-gamma productivity of MLN lymphocytes was higher in the rats fed on Toc or T-3 than in those fed on a control diet in the presence of Con A, while that of spleen lymphocytes was lower in the rats fed on Toc or T-3. In addition, T-3 feeding decreased the productivity of tumor necrosis factor-alpha of spleen lymphocytes, while it enhanced the productivity of MLN lymphocytes. These results suggest that oral administration of Toc and T-3 affects the proliferation and function of spleen and MLN lymphocytes.

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