Vitamin E comprises of eight compounds that share the biological effects of α‑tocopherol. These include three other tocopherol analogues (β-, γ-, δ) as well as four tocotrienol analogues (α-, β-, γ-, δ). Both tocopherols and tocotrienols have a chromanol ring structure attached to a side chain. Tocotrienols differ in their chemical structure to the tocopherols in that instead of a saturated side chain, they possess double bonds in the chain at the 3’, 7’ and 11’ positions. Vitamin E is considered to be an effective in vivo antioxidant, as the molecules are able to donate hydrogen atoms to free radicals. This allows quenching of propagation reactions that are thought to be involved in the development of disease and may be responsible for aging. Vitamin E is most effective as an antioxidant in lipid membranes because it is a hydrophobic molecule.
Tocotrienols are thought to show better antioxidant effects in vivo than tocopherols, although this is controversial. Tocotrienols have slightly different membrane positioning to tocopherols, and appear to have a disordering effect on membranes perhaps because their side chain structure is not straight as a result of the double bonds. Tocopherols and tocotrieonols are absorbed in humans and plasma levels rise with increased intake in food. Much of the investigation into the absorption and metabolism of tocotrienols has been performed in animal models, but it is known that tocotrienol plasma level may reach around 1 µmol/L in humans. Once absorbed, tocotrienols are distributed in a number of tissues in animals including adipose tissue, skin, lungs and brains. Research suggests that tocotrienols undergo ω-oxidation followed by β-oxidation of their side chain, followed by excretion in the bile.
Tocotrienols have a number of biological effects in vivo that appear to be protective of disease. One of the ways that tocotrienols might protect from cardiovascular disease is because they have an ability to lower cholesterol levels. Whereas the statin drugs are able to inhibit the rate limiting enzyme involved in cholesterol synthesis (HMG-CoA reductase), tocotrienols appear to lower cholesterol because they increase degradation of HMG-CoA reductase as well as decrease the translation of HMG-CoA reductase mRNA. Tocotrienols also show a protective effect from cancer because they are able to decrease cell proliferation. The effects of tocotrienols on cell proliferation is likely due to their ability to inhibit cell signalling of cAMP-dependent protein kinases from epidermal growth factor receptors. Tocotrienols therefore appear to have clear inhibitory effects on cancer and cardiovascular disease above and beyond their general antioxidant function.
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