Introduction
Vitamin E Requirements in Parenteral Nutrition

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Patients with parenteral nutrition depend on an adequate supply of micronutrients, in particular, antioxidant vitamins and cofactors such as selenium. In cases of oxidative stress (eg, chronic inflammation, sepsis, lung distress syndrome, and organ failure), there is a higher need for antioxidants. One of the most important antioxidant vitamins is vitamin E. For very low birth weight infants the plasma level is an indicator for adequate supply and for safety. Safe and effective blood levels are between 23 and 46 μmol/L, maintained with a dose of 2.8 IU/kg body weight (1–2 mg/day). For safety reasons a plasma level of 80 μmol/L should not be exceeded. For adults, 10 IU/day (9.1 mg/day) are recommended. Whether this dose is sufficient to ensure body stores and sufficient antioxidant activity is controversial. If parenteral lipid emulsions are supplied there is an additional need for vitamin E to protect the lipids (polyunsaturated fatty acids) from lipid peroxidation and to deliver additional vitamin E. Dietary guidelines for healthy adults recommend an intake of polyunsaturated fatty acids equal to 10% of total energy and an intake of α-tocopherol greater than 0.4 mg/g of polyunsaturated fatty acids. Randomized clinical trials are performed using special formulations of vitamin E solutions because vitamin E is available only in lipid emulsions to protect lipids, but not in an isolated solution for parenteral supply.

Section snippets

Vitamin E: Chemistry and Metabolism

α-Tocopherol is the naturally occurring compound with the highest vitamin E activity. It has 3 chiral centers (at 2′, 4′, and 8′ in Figure 1) at which the methyl groups are in the R-configuration but can exist as 7 other isomers. According to International Union of Pure and Applied Chemistry (IUPAC), the correct name is therefore 2R, 4R, and 8R-α-tocopherol. It usually is accompanied by small amounts of β-, γ-, and δ-tocopherol, which differ by the number and positions of the methyl groups

Infants and Children

A severe vitamin E deficiency with typical clinical signs is rare. Ataxia with isolated vitamin E deficiency is a rare autosomal-recessive neurodegenerative disease caused by mutation in the α-tocopherol transfer protein. As a consequence, the transfer of vitamin E into VLDL within the liver is impaired and low plasma levels (<3 mg/dL) of vitamin E are the consequence despite adequate intake. Clinical signs are gait and limb ataxia, dysarthria, lower-limb areflexia, loss of vibration and

Preterm Infants

Preterm infants may be more susceptible to liver damage from high intakes of vitamin E. A parenteral supply of 25–100 mg α-tocopherol-acetate (E-ferol Aqueous solution; Carter Glogau Labs, Inc, Glendale, AZ) to very low birthweight infants for as little as 1 week resulted in coagulopathy with liver failure. However, it is not clear whether this truly was caused by the vitamin E32, 33 or by the solubilizer polysorbate.

Vitamin E Toxicity in Adults

In general, toxic effects from high doses of vitamin E are quite rare even

Stability Issues

Vitamin E can be degraded by photooxidation in parenteral solutions. The mechanism of degradation involves a photocatalyzed reaction with oxygen. Consequently, factors influencing the availability of oxygen (the filling process or permeation through the bag) will influence the rate and degree of degradation. Because of the lower antioxidant activity of the synthetic vitamin E formulation (all-RAC-α-tocopheryl-acetate) frequently used in parenteral products, natural vitamin E (RRR-α-tocopherol)

Infants

Brion43 discussed the appropriate intravenous dose of vitamin E for very low birth weight infants. Based on the reported toxic side effects of high doses in preterm infants it is recommended not to go beyond a plasma level of 3.5 mg/dL (80 μmol/L). This level was confirmed in a recent Cochrane analysis.44 The American Academy of Pediatric Committee on Nutrition has suggested that safe and effective blood levels are between 23 and 46 μmol/L (1 and 2 mg/dL). This plasma level can be maintained

Parenteral Supply of Vitamin E: Experimental Studies

The endothelium is one of the primary targets of oxidative stress during ischemia/reperfusion. Consequently, a high content of vitamin E in the endothelium may help to prevent reperfusion-induced lipid peroxidation and subsequent membrane damage. Keaney et al56 have shown that the content of vitamin E in the blood vessel walls correlated with vessel resistance to endothelial dysfunction after incubation with oxidized LDL in hypercholesterolemic rats.

The availability of vitamin E for endothelial

Newborn

Vitamin E supplementation of very low birth weight infants has been recommended to reduce the risk of retinopathy of premature infants, intracranial hemorrhage, and chronic lung disease. Furthermore, the addition of vitamin E to fat emulsions prevents lipid peroxidation in vitro and subsequent increased oxidative stress in vivo.65, 66, 67

Göbel et al68 evaluated the safety and efficacy of a new lipid emulsion with reduced linoleic acid and α-linolenic acid content and a higher antioxidant

Conclusions

In certain disease stages it is essential to administer vitamin E in sufficient amounts. This is because the most efficient antioxidative capacity is related strongly to the degree of integration of the vitamin E molecule into cell membranes, where it reacts in a nonenzymatic fast manner. Based on recent data sufficient dietary supply with vitamin E is not achieved in the majority of the US population. As a consequence, vitamin E status should be monitored on the basis of plasma or cellular

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