We present here current data on the distribution and metabolism of vitamin E analogs in vivo. There are eight different naturally occurring forms of vitamin E : four tocopherols (α-,β, γ- and δ-toc) and four tocotrienols (α-,β-,γ and δ-toc). With regard to the bioavailability of vitamin E, it has been established that the affinity of various vitamin E analogs for α–tocopherol transfer protein (α-TTP), which may determine their plasma levels, is a major determinant if their biological activity however, a novel function of toc-3 has been noted as a result of its unique distribution in the skin and the adipose tissue. In addition, following the discovery that the final metabolites of Toc and Toc-3 are in the form of carboxyethyl hydroxychroman, it is now possible to examine the intermediary metabolites of vitamin E analogs. The metabolites of vitamin E is known to be involved in the actions of drug metabolic enzymes (CYP3A, CYP4F2). However, the relationship between α –TTP and the metabolic enzymes that are responsible for the regulation of vitamin E metabolism has yet to be clarified. Future research will focus on the elucidation of the vitamin E metabolic regulation system.

Tocochromanols (tocopherols and tocotrienols), collectively known as vitamin E, are essential antioxidant components of both human and animal diets. Because of their potential health benefits, there is a considerable interest in plants with increased or customized vitamin E content. Here, we have explored a new strategy to reach this goal. In plants, phenylalanine is the precursor of a myriad of secondary compounds termed phenylpropanoids. In contrast, much less carbon is incorporated into tyrosine that provides p-hydroxyphenylpyruvate and homogentisate, the aromatic precursors of vitamin E. Therefore, we intended to increase the flux of these two compounds by deriving their synthesis directly at the level of prephenate. This was achieved by the expression of the yeast (Saccharomyces cerevisiae) prephenate dehydrogenase gene in tobacco (Nicotiana tabacum) plants that already overexpress the Arabidopsis p-hydroxyphenylpyruvate dioxygenase coding sequence. A massive accumulation of tocotrienols was observed in leaves. These molecules, which were undetectable in wild-type leaves, became the major forms of vitamin E in the leaves of the transgenic lines. An increased resistance of the transgenic plants toward the herbicidal p-hydroxyphenylpyruvate dioxygenase inhibitor diketonitril was also observed. This work demonstrates that the synthesis of p-hydroxyphenylpyruvate is a limiting step for the accumulation of vitamin E in plants.

Vitamins E and K share structurally related side chains and are degraded to similar final products. For vitamin E the mechanism has been elucidated as initial omega-hydroxylation and subsequent beta-oxidation. For vitamin K the same mechanism can be suggested analogously. omega-Hydroxylation of vitamin E is catalyzed by cytochrome p450 enzymes, which often are induced by their substrates themselves via the activation of the nuclear receptor PXR. Vitamin E is able to induce CYP3A-forms and to activate a PXR-driven reporter gene. It is shown here that K-type vitamins are also able to activate PXR. A ranking showed that compounds with an unsaturated side chain were most effective, as are tocotrienols and menaquinone-4 (vitamin K(2)), which activated the reporter gene 8-10-fold. Vitamers with a saturated side chain, like tocopherols and phylloquinone were less active (2-5-fold activation). From the fact that CYPs commonly responsible for the elimination of xenobiotics are involved in the metabolism of fat-soluble vitamins and the ability of the vitamins to activate PXR it can be concluded that supranutritional amounts of these vitamins might be considered as foreign.

BACKGROUND: Epidemiologic evidence suggests that the concentrations of antioxidant vitamins in human plasma may play an important role in numerous chronic diseases, such as cancer and cardiovascular disease. However, methods for simultaneous measurement of these antioxidants are scarce. We developed and validated a new HPLC method for simultaneous determination of these vitamers in human plasma that uses a novel column-switching approach.

METHODS: The new method uses liquid-liquid extraction and isocratic separation with two monomeric C(18) columns maintained at 35 and 4 degrees C coupled with ultraviolet-visible and fluorometric detection. This method could separate 14 vitamers and 3 internal standards within 27 min. No additional modifier was required; the mobile phase was acetonitrile-methanol (65:35 by volume), and the flow rate was 1 mL/min.

RESULTS: For photodiode array detection, the detection limits (signal-to-noise ratio >3) were 0.02 mg/L for beta-carotene, lutein, zeaxanthin, and canthaxanthin; 0.01 mg/L for all-trans-retinol, beta-cryptoxanthin, alpha-carotene, and lycopene; and 0.1 mg/L for all tocopherols and tocotrienols. The detection limit was at least 25-fold lower (0.004 mg/L) when fluorometry was used for measurement of delta-, gamma-, and alpha-tocotrienol and delta-tocopherol compared with ultraviolet detection. The recovery and imprecision of the assay were generally >90% and <10%, respectively.

CONCLUSIONS: This new method separates a wide range of fat-soluble antioxidant vitamins in human plasma, including six carotenoids, three isoforms of tocotrienols and tocopherols (delta-, gamma-, and alpha-), and all-trans-retinol. The overall findings suggest that our method is faster, more sensitive, and more comprehensive than existing methods.

Vitamins E and K share structurally related side chains and are degraded to similar final products. For vitamin E the mechanism has been elucidated as initial omega-hydroxylation and subsequent beta-oxidation. For vitamin K the same mechanism can be suggested analogously. omega-Hydroxylation of vitamin E is catalyzed by cytochrome p450 enzymes, which often are induced by their substrates themselves via the activation of the nuclear receptor PXR. Vitamin E is able to induce CYP3A-forms and to activate a PXR-driven reporter gene. It is shown here that K-type vitamins are also able to activate PXR. A ranking showed that compounds with an unsaturated side chain were most effective, as are tocotrienols and menaquinone-4 (vitamin K(2)), which activated the reporter gene 8-10-fold. Vitamers with a saturated side chain, like tocopherols and phylloquinone were less active (2-5-fold activation). From the fact that CYPs commonly responsible for the elimination of xenobiotics are involved in the metabolism of fat-soluble vitamins and the ability of the vitamins to activate PXR it can be concluded that supranutritional amounts of these vitamins might be considered as foreign.

The oil palm (Elaeis guineensis) is native to many West African countries, where local populations have used its oil for culinary and other purposes. Large-scale plantations, established principally in tropical regions (Asia, Africa and Latin America), are mostly aimed at the production of oil, which is extracted from the fleshy mesocarp of the palm fruit, and endosperm or kernel oil. Palm oil is different from other plant and animal oils in that it contains 50% saturated fatty acids, 40% unsaturated fatty acids, and 10% polyunsaturated fatty acids. The fruit also contains components that can endow the oil with nutritional and health beneficial properties. These phytonutrients include carotenoids (alpha-,beta-,and gamma-carotenes), vitamin E (tocopherols and tocotrienols), sterols (sitosterol, stigmasterol and campesterol), phospholipids, glycolipids and squalene. In addition, it is recently reported that certain water-soluble powerful antioxidants, phenolic acids and flavonoids, can be recovered from palm oil mill effluent. Owing to its high content of phytonutrients with antioxidant properties, the possibility exists that palm fruit offers some health advantages by reducing lipid oxidation, oxidative stress and free radical damage. Accordingly, use of palm fruit or its phytonutrient-rich fractions, particularly water-soluble antioxidants, may confer some protection against a number of disorders or diseases including cardiovascular disease, cancers, cataracts and macular degeneration, cognitive impairment and Alzheimer’s disease. However, whilst prevention of disease through use of these phytonutrients as in either food ingredients or nutraceuticals may be a worthwhile objective, dose response data are required to evaluate their pharmacologic and toxicologic effects. In addition, one area of concern about use of antioxidant phytonutrients is how much suppression of oxidation may be compatible with good health, as toxic free radicals are required for defence mechanisms. These food-health concepts would probably spur the large-scale oil palm (and monoculture) plantations, which are already seen to be a major cause of deforestation and replacement of diverse ecosystems in many countries. However, the environmental advantages of palm phytonutrients are that they are prepared from the readily available raw material from palm oil milling processes. Palm fruit, one of only a few fatty fruits, is likely to have an increasingly substantiated place in human health, not only through the provision of acceptable dietary fats, but also its characteristic protective phytonutrients.

The palm fruit (Elaies guineensis) yields palm oil, a palmitic-oleic rich semi solid fat and the fat-soluble minor components, vitamin E (tocopherols,tocotrienols), carotenoids and phytosterols. A recent innovation has led to the recovery and concentration of water-soluble antioxidants from palm oil milling waste, characterized by its high content of phenolic acids and flavonoids. These natural ingredients pose both challenges and opportunities for the food and nutraceutical industries. Palm oil’s rich content of saturated and monounsaturated fatty acids has actually been turned into an asset in view of current dietary recommendations aimed at zero trans content in solid fats such as margarine, shortenings and frying fats. Using palm oil in combination with other oils and fats facilitates the development of a new generation of fat products that can be tailored to meet most current dietary recommendations. The wide range of natural palm oil fractions, differing in their physico-chemical characteristics, the most notable of which is the carotenoid-rich red palm oil further assists this. Palm vitamin E (30% tocopherols, 70% tocotrienols) has been extensively researched for its nutritional and health properties, including antioxidant activities, cholesterol lowering, anti-cancer effects and protection against atherosclerosis. These are attributed largely to its tocotrienol content. A relatively new output from the oil palm fruit is the water-soluble phenolic-flavonoid-rich antioxidant complex. This has potent antioxidant properties coupled with beneficial effects against skin, breast and other cancers. Enabled by its water solubility, this is currently being tested for use as nutraceuticals and in cosmetics with potential benefits against skin aging. A further challenge would be to package all these palm ingredients into a single functional food for better nutrition and health.