Vitamin E (Tocopherols and Tocotrienols)

Mechanism

Chemical structure and biological affinities

Vitamin E compounds are classified into four tocopherols (α, β, γ, δ) and four tocotrienols (α, β, γ, δ). However, only α-tocopherol is actively retained by the human body due to the specificity of the hepatic transporter, which gives it the highest biological potency measured in tocopherol equivalents.

Mechanism of Action: Inhibition of Lipid Peroxidation

Polyunsaturated fatty acids (PUFAs) integrated into cellular lipid membranes are highly vulnerable to oxidation by oxygen free radicals (R^). The destructive process occurs in three phases:

1. Initiation: A free radical subtracts a hydrogen atom from a carbon neighboring a double bond in the PUFA, generating a carbon-centered lipid radical (L^).
2. Propagation: The lipid radical reacts rapidly with molecular oxygen to form a lipid peroxyl radical (LOO^), which attacks another adjacent PUFA to form a lipid hydroperoxide (LOOH) and a new carbon radical, perpetuating the chain reaction.
3. Termination by Vitamin E: α-Tocopherol (Toc-OH) interrupts the propagation by rapidly giving up a hydrogen atom to the lipid peroxyl radical, neutralizing it to inert lipid hydroperoxide: LOO^ + Knock-OH LOOH + Knock-O^ The resulting tocopheryl free radical (Toc-O^) is stable and does not attack lipid membranes. Subsequently, it is reduced back to its original form of active tocopherol at the membrane interface by the synergistic action of Vitamin C and reduced glutathione.

Pharmacokinetics

Pharmacokinetics

• Absorption: Passive jejunal absorption, absolutely requiring the presence of bile salts and the incorporation of dietary lipids to form insoluble micelles. Its bioavailability rate varies between 20% and 50%.
• Hepatic Distribution and Transport: It is secreted from the enterocyte into the lymphatic system packaged in chylomicrons. Chylomicron remnants transport vitamin E to the liver, where hepatocytes internalize the complex. Hepatic α-Tocopherol Transfer Protein (α-TTP) selectively selects and loads α-tocopherol into very low density lipoproteins (VLDL) for export into the general circulation. The other forms of vitamin E (γ-tocopherol) are not recognized by α-TTP and are eliminated via the bile.
• Storage: It is deposited mainly in the lipid droplets of adipose tissue, in skeletal muscle and in the lipid cell membranes of all organs.

Security

Indications, Contraindications and Adverse Effects

• Indications for Use: Treatment of deficiency secondary to chronic malabsorption syndromes (such as abetalipoproteinemia, extensive ileal resection, childhood hepatic cholestasis or cystic fibrosis). Treatment of non-alcoholic steatohepatitis (NASH) in non-diabetic adults under close monitoring.
• Contraindications: Known hypersensitivity. Patients undergoing treatment with oral anticoagulants or at risk of active bleeding.
• AMR and Toxicity: Generally non-toxic at low doses. However, megadoses of vitamin E (>800 IU/day) antagonize the action of vitamin K in the coagulation cascade, inhibiting the carboxylation of vitamin K-dependent coagulation factors, which increases the risk of severe bleeding (including hemorrhagic stroke).