Although vitamin E has been known as an essential nutrient for reproduction since 1922, we are far from understanding the mechanisms of its physiological functions. Vitamin E is the term for a group of tocopherols and tocotrienols, of which alpha-tocopherol has the highest biological activity. Due to the potent antioxidant properties of tocopherols, the impact of alpha-tocopherol in the prevention of chronic diseases believed to be associated with oxidative stress has often been studied, and beneficial effects have been demonstrated. Recent observations that the alpha-tocopherol transfer protein in the liver specifically sorts out RRR-alpha-tocopherol from all incoming tocopherols for incorporation into plasma lipoproteins, and that alpha-tocopherol has signaling functions in vascular smooth muscle cells that cannot be exerted by other forms of tocopherol with similar antioxidative properties, have raised interest in the roles of vitamin E beyond its antioxidative function. Also, gamma-tocopherol might have functions apart from being an antioxidant. It is a nucleophile able to trap electrophilic mutagens in lipophilic compartments and generates a metabolite that facilitates natriuresis. The metabolism of vitamin E is equally unclear. Excess alpha-tocopherol is converted into alpha-CEHC and excreted in the urine. Other tocopherols, like gamma- and delta-tocopherol, are almost quantitatively degraded and excreted in the urine as the corresponding CEHCs. All rac alpha-tocopherol compared to RRR-alpha-tocopherol is preferentially degraded to alpha-CEHC. Thus, there must be a specific, molecular role of RRR-alpha-tocopherol that is regulated by a system that sorts, distributes, and degrades the different forms of vitamin E, but has not yet been identified. In this article we try to summarize current knowledge on the function of vitamin E, with emphasis on its antioxidant vs. other properties, the preference of the organism for RRR-alpha-tocopherol, and its metabolism to CEHCs.

http://tocofemax.com.br/site/artigos/1.pdf

Vitamin E: function and metabolism

Absorption, lipoprotein transport, and regulation of plasma concentrations of vitamin E in humans.

Natural vitamin E includes four tocopherols and four tocotrienols. RRR-α-tocopherol is the most abundant form in nature and has the highest biological activity. Although vitamin E is the main lipid-soluble antioxidant in the body, not all its properties can be assigned to this action. As antioxidant, vitamin E acts in cell membranes where prevents the propagation of free radical reactions, although it has been also shown to have pro-oxidant activity. Non-radical oxidation products are formed by the reaction between α-tocopheryl radical and other free radicals, which are conjugated to glucuronic acid and excreted through the bile or urine. Vitamin E is transported in plasma lipoproteins. After its intestinal absorption vitamin E is packaged into chylomicrons, which along the lymphatic pathway are secreted into the systemic circulation. By the action of lipoprotein lipase (LPL), part of the tocopherols transported in chylomicrons are taken up by extrahepatic tissues, and the remnant chylomicrons transport the remaining tocopherols to the liver. Here, by the action of the “α-tocopherol transfer protein”, a major proportion of α-tocopherol is incorporated into nascent very low density lipoproteins (VLDL), whereas the excess of α-tocopherol plus the other forms of vitamin E are excreted in bile. Once secreted into the circulation, VLDL are converted into IDL and LDL by the action of LPL, and the excess of surface components, including α-tocopherol, are transferred to HDL. Besides the LPL action, the delivery of α-tocopherol to tissues takes place by the uptake of lipoproteins by different tissues throughout their corresponding receptors. Although we have already a substantial information on the action, effects and metabolism of vitamin E, there are still several questions open. The most intriguing is its interaction with other antioxidants that may explain how foods containing small amounts of vitamin E provide greater benefits than larger doses of vitamin E alone.

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Vitamin e: action, metabolism and perspectives

Vitamin E: Emerging aspects and new directions.

Vitamin E is the term used for eight naturally occurring fat-soluble nutrients called tocopherols. alpha-Tocopherol is essential, has the highest biological activity and predominates in many species. In humans vitamin E is the most important lipid soluble antioxidant and deficiency may cause neurological dysfunction, myopathies and diminished erythrocyte life span. alpha-Tocopherol is absorbed via the lymphatic pathway and transported in association with chylomicrons. In plasma, alpha-tocopherol is found in all lipoprotein fractions but mostly is associated with apo B-containing lipoproteins. alpha-Tocopherol is associated with very-low-density lipoprotein when it is secreted from the liver. In the rat, about 90% of total body mass of alpha-tocopherol is recovered in the liver, skeletal muscle and adipose tissue. Most alpha-tocopherol is located in the mitochondrial fractions and in the endoplasmic reticulum, whereas little is found in cytosol and peroxisomes. New clinical evidence from heavy drinkers and from experimental work in rats suggests that alcohol may increase oxidation of alpha-tocopherol. Increased demand for vitamin E has also been observed in premature infants and patients with malabsorption, but there is little evidence that the healthy population requires supplementation of vitamin E to a well-balanced diet.

Absorption, transport and distribution of vitamin E.

We studied the effect of long-term correction of vitamin E deficiency on neurologic function in 14 children with chronic cholestasis. Vitamin E repletion was achieved in all, either by large oral doses (up to 120 IU per kilogram of body weight per day) or by intramuscular administration of dl-alpha-tocopherol (0.8 to 2.0 IU per kilogram per day). With early institution of therapy, neurologic function remained normal in two asymptomatic children below the age of three years after 15 and 18 months of therapy. Neurologic function became normal in three symptomatic children below age three after 18 to 32 months of therapy. Restitution of neurologic function was more limited in nine symptomatic children 5 to 17 1/2 years old after 18 to 48 months of therapy. We conclude that vitamin E repletion therapy should be initiated at an early age in children with chronic cholestasis complicated by vitamin E deficiency, to prevent irreversible neurologic injury.

Improved neurologic function after long-term correction of vitamin E deficiency in children with chronic cholestasis.

To determine the reversibility of neurologic abnormalities due to vitamin E (E) deficiency, we prospectively studied the effects of E repletion on 14 children with chronic cholestasis, well-documented E deficiency, and characteristic sural nerve or muscle lesions: Group A(n=2)- both age 20 mo., no neurologic signs; Group B(n=3)- age <3 yrs., with characteristic neurologic signs; Group C(n=9)- ages 5-17 yrs., with neurologic signs. E repletion was achieved by oral (n=4; 60 to 90 IU/kg/day) or intramuscular (n=10;1.0-1.5 IU/kg/day) dl-a-tocopherol. Child neurologists performed serial neurologic exams each 6-12 mo., assigning a neurologic score based on rating each of 12 neurologic signs from 0 (normal) to 3+ (severely abnormal). The mean neurologic scores for each group at 6 month time intervals were (Table):

/pdf/reversibility-of-vitamin-e-deficiency-neurologic-syndrome-3yud0hqobc.pdf

Susan T. Iannaccone

Papers

Improved neurologic function after long-term correction of vitamin E deficiency in children with chronic cholestasis.

Reversibility of vitamin e deficiency neurologic syndrome during chronic childhood cholestasis