Vitamin C, vitamin E and the carotenoids are important antioxidants in human tissues, that may have beneficial effects against a number of lifestyle diseases including cardiovascular disease and cancer. A wide variety of antioxidants in the diet may provide better protection against oxidative stress than isolated nutrients because reducing agents act synergistically in vivo, and high intakes of single antioxidants may actually produce a pro-oxidant effect. In addition, antioxidants can be both lipophilic and lipophobic, and so different antioxidants are preferentially found in different compartments of the cell. This provides complete cellular protective mechanisms that are further enhanced by the ability of some antioxidants to recycle others from their oxidised to reduced form. This cooperative recycling action has been particularly well reported between vitamin C and vitamin E, but evidence suggests that interactions between vitamin E and β-carotene are also possible.
Vitamin C is a potent water soluble antioxidant and as a result it is found mainly in the aqueous compartments of the cellular cytoplasm and the extracellular fluid. In contrast, vitamin E and carotenoids are lipid soluble antioxidants and are incorporated into the phosopholipid membranes of cells. However, differences exist between the location of the vitamin E and carotenoids within the membrane. For example, researchers1 have performed in vitro experiments and incorporated both β-carotene and α-tocopherol into dimyristoyl phosphatidylcholine liposomal membranes and generated free radicals to assess antioxidant protection. The results showed that the β-carotene was consumed faster when free radicals were generated within the liposomes, but α-tocopherol was consumed faster when free radicals were generated within the aqueous phase. This suggests that β-carotene is located mainly in the interior of the lipophilic membrane, while vitamin E is located on the membrane surface.
It is known that vitamin E and vitamin C interact to prevent oxidative damage in vivo, because ascorbate is able to reduce the tocopheroxyl radical back to tocopherol, this preventing pro-oxidant effects from vitamin E. High doses of vitamin E in the absence of adequate cellular vitamin C may have pro-oxidant effects. In the process of recycling oxidised vitamin E to its reduced form, vitamin C itself becomes oxidised to dehydroascorbate. The cell deals with dehydroascorbate by reaction with glutathione, which results in the formation of ascorbate and oxidised glutathione. Oxidised glutathione is then subsequently reduced via hydrogen donation from the electron carrier NADPH, which is maintained at high cellular concentrations via the pentose phosphate pathway. This demonstrates the complexity of cellular antioxidant defences, which also involve other compounds including endogenous compounds such as alpha lipoic acid and coenzyme Q-10 as well as exogenous compounds such as phenolics.
The interaction between carotenoids and vitamin E is not well understood, but addition of both antioxidants to lipid membranes produces a synergistic effect at reducing oxidative damage when compared to their individual contributions. This synergistic effect might occur because β-carotene and α-tocopherol work in different parts of the membrane. In addition β-carotene does not scavenge free radicals by donation of hydrogen atoms, as with α-tocopherol. Instead, β-carotene scavenges free radicals by energy transfer and creation of a double bond to form a conjugated polyene carbon-centred radical which is resonance-stabilised. Reaction of this carbon-centred radical with molecular oxygen then produces the peroxyl radical that is not stable and capable of producing cellular oxidation. Vitamin E may add synergism to β-carotene by scavenging this peroxyl radical before it causes oxidation. This pro-oxidant effect is illustrated in studies showing increased rates of cancer with supplementation of β-carotene in isolation.
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