In 2000, the USA Institute of Medicine (IoM) noted that the amount of vitamin E necessary to maintain the correct metabolism of polyunsaturated fatty acids (PUFAs) in cell membranes is related to the intake of PUFAs. A recent review by Raederstorff et al. examines in detail the relationship between PUFA intake and vitamin E requirement. The basal metabolic requirement of 3 to 4 mg/day α-tocopherol needs to be increased to 12.5 to 20 mg/day, just to balance out typical intakes of PUFAs in the Western diet.
The key function of vitamin E in cell membranes is as an antioxidant. Whilst all isoforms of vitamin E have some antioxidant ability, it is the RRR α-tocopherol that has the highest in vivo bioactivity. It is also the only isoform to be bound by a specific transfer protein (α-TTP) which protects the molecule within the cell and prevents it from undergoing the fate of rapid degradation that befalls all the other isoforms. The antioxidant ability of vitamin E is due to the 6-hydroxy group on the chromanol ring which is the active site for scavenging free radicals. The tocopherol radical, once formed, is stable and unable to react further – which breaks the chain of oxidation events (otherwise the reaction would continue to propagate). This essential role of vitamin E has been recognized by the European Food Safety Authority (EFSA) who, after reviewing all available evidence, concluded that “vitamin E contributes to the protection of cell constituents from oxidative damage” (3).
Early animal studies in the 1960s revealed that the relative quantities of α-tocopherol necessary to protect one mole of LCPUFA with 1:2:3:4:5:6 double bonds were 0.3:2:3:4:5:6 respectively (2). The Elgin study conducted between 1953 and 1967 conducted human trials with vitamin E:PUFA ratios. They determined that humans have a basal metabolic requirement of 3 to 4 mg/day α-tocopherol if PUFAs are absent from their diet. A long term diet of 60 g/day corn oil required an increase of α-tocopherol to 30 mg/day to prevent a decrease in the erythrocyte hemolysis test values.
The incorporation of α-tocopherol into the cell membrane leads to a decrease in cell fluidity. α-tocopherol seems to accumulate in the unstructured areas (i.e., not the lipid rafts) which often have high concentrations of the highly unstable PUFA docosahexaenoic acid (DHA). High concentrations of α-tocopherol are also found on the cell membrane surface. Here, if it is in the α-tocopheroxy radical form, it is able to be regenerated by ascorbic acid at the hydrophilic/hydrophobic interface.
Taking into account current average PUFA intakes in the Westernized diet (specifically oleic acid, the omega-6 fatty acids: linoleic acid and arachidonic acid and the omega-3 fatty acids: α-linolenic acid, DHA and EPA), Raederstorff et al. (2) calculated a total daily requirement of α-tocopherol of between 12.5 and 20 mg vitamin E to account for the PUFA intake.