E-GEL 200 IU SOFT CAPSULES

Indications

• Vitamin E deficiency
• Prevention of oxidative stress-related conditions
• Adjunct therapy in chronic diseases such as coronary heart disease
• Potential protective role against certain cancers

Dosage

Children: Refer to BNF for Children for appropriate dosing in pediatric populations.

Adults: Refer to specific BNF guidelines for adult dosing of vitamin E.

Mechanism of action

Vitamin E functions primarily as an antioxidant, preventing free radical reactions with cell membranes. It terminates lipid peroxidation by reacting with unstable lipid radicals to form stable lipids and a relatively stable vitamin E radical. This radical can be regenerated back to its active form by ascorbate or glutathione. Additionally, vitamin E may have effects on inflammation and cancer progression through its influence on NF-kappaB signaling pathways.

Pharmacodynamics

Vitamin E protects cells from oxidative stress by neutralizing free radicals, thus preventing cellular damage. It is particularly important for the protection of lipids and fat-soluble vitamins, such as vitamins A and B, from oxidative degradation. Vitamin E deficiency can lead to increased susceptibility to oxidative damage, contributing to conditions such as coronary heart disease and certain types of cancer.

Pharmacokinetics

Vitamin E is absorbed in the intestine and transported via lipoproteins in the bloodstream. It is stored primarily in adipose tissue and the liver. The metabolism of vitamin E involves its conversion to various metabolites, which can be excreted in urine. Bioavailability may be affected by dietary fat intake, as it is a fat-soluble vitamin.

Adverse effects

• Nausea
• Diarrhea
• Fatigue
• Abdominal cramps
• Headache

Interactions

• Anticoagulants may have increased effects
• Cholestyramine may decrease absorption of vitamin E
• Certain chemotherapy agents may interact

Precautions

• Monitor for bleeding if on anticoagulants
• Caution in patients with liver disease
• Assess for vitamin E deficiency in at-risk populations

Pregnancy

Vitamin E is generally considered safe during pregnancy when taken in recommended amounts; however, excessive doses should be avoided.

Breast-feeding

Vitamin E is excreted in breast milk; usual dietary intake is generally considered safe while breastfeeding.

Storage

Store in a cool, dry place away from light. Keep container tightly closed.

Formulations

• Capsules
• Softgels
• Tablets
• Oil solutions

Mechanism of action

The mechanism of action for most of vitamin E's effects are still unknown. Vitamin E is an antioxidant, preventing free radical reactions with cell membranes. Though in some cases vitamin E has been shown to have pro-oxidant activity. One mechanism of vitamin E's antioxidant effect is in the termination of lipid peroxidation. Vitamin E reacts with unstable lipid radicals, producing stable lipids and a relatively stable vitamin E radical. The vitamin E radical is then reduced back to stable vitamin E by reaction with ascorbate or glutathione. Cancer development and progression are closely associated with inflammation. NF-kappaB (nuclear factor kappaB) provides a mechanistic link between inflammation and cancer, and is a major factor controlling the ability of malignant cells to resist tumor surveillance mechanisms. NF-kappaB might also regulate tumor angiogenesis and invasiveness and the signalling pathways that mediate its activation provide attractive targets for new chemopreventive and chemotherapeutic approaches. ROS (reactive oxygen species) initiate inflammation by up-regulation of pro-inflammatory cytokines and therefore antioxidants provide a major defence against inflammation. alpha-Tocopherol is a lipid-soluble antioxidant. In addition to decreasing lipid peroxidation, alpha-tocopherol may exert intracellular effects. Hence, the aim of this study was to test the effect of alpha-tocopherol supplementation in cancer prevention via suppression of NF-kappaB-mediated pro-inflammatory cytokines. alpha-Tocopherol treatment significantly down-regulates expression, synthesis as well as secretion of pro-inflammatory cytokine IL-6 (interleukin-6) in cancerous mice. It also suppresses NF-kappaB binding to IL-6 promoter in liver leading to decreased secretion of IL-6 in serum. The regulation of the signalling pathway by alpha-tocopherol is found apart from its antioxidant capacity to reduce lipid peroxidation. Thus, the present study provides evidence for the hypothesis that besides the powerful free radical scavenging effects, alpha-tocopherol has genomic effects in down-regulation of pro-inflammatory cytokine and cancer prevention via the NF-kappaB-dependent pathway. Mitocans are drugs selectively killing cancer cells by destabilizing mitochondria and many induce apoptosis via generation of reactive oxygen species (ROS). However, the molecular events by which ROS production leads to apoptosis has not been clearly defined. In this study with the mitocan alpha-tocopheryl succinate (alpha-TOS) the role of the Bcl-2 family proteins in the mechanism of malignant cell apoptosis has been determined. Exposure of several different cancer cell lines to alpha-TOS increased expression of the Noxa protein, but none of the other proteins of the Bcl-2 family, an event that was independent of the cellular p53 status. alpha-TOS caused a profound conformational change in the pro-apoptotic protein, Bak, involving oligomerization in all cell types, and this also applied to the Bax protein, but only in non-small cell lung cancer cells. Immunoprecipitation studies indicated that alpha-TOS activates the two BH1-3 proteins, Bak or Bax, to form high molecular weight complexes in the mitochondria. RNAi knockdown revealed that Noxa and Bak are required for alpha-TOS-induced apoptosis, and the role of Bak was confirmed using Bak- and/or Bax-deficient cells. We conclude that the major events induced by alpha-TOS in cancer cells downstream of ROS production leading to mitochondrial apoptosis involve the Noxa-Bak axis. It is proposed that this represents a common mechanism for mitochondrial destabilization activated by a variety of mitocans that induce accumulation of ROS in the early phases of apoptosis. /alpha-Tocopheryl succinate/

Pharmacodynamics

Vitamin E is a collective term used to describe 8 separate fat soluble antioxidants, most commonly alpha-tocopherol. Vitamin E acts to protect cells against the effects of free radicals, which are potentially damaging by-products of the body's metabolism. Vitamin E deficiency is seen in persons with abetalipoproteinemia, premature, very low birth weight infants (birth weights less than 1500 grams, or 3½ pounds), cystic fibrosis, and cholestasis and severe liver disease. Preliminary research suggests vitamin E may help prevent or delay coronary heart disease and protect against the damaging effects of free radicals, which may contribute to the development of chronic diseases such as cancer. It also protects other fat-soluble vitamins (A and B group vitamins) from destruction by oxygen. Low levels of vitamin E have been linked to increased incidence of breast and colon cancer.