A history of vitamin E.

Vitamin E (α-tocopherol) was discovered nearly 100 years ago because it was required to prevent fetal resorption in pregnant, vitamin E-deficient rats fed lard-containing diets that were easily oxidizable. The human diet contains eight different vitamin E-related molecules synthesized by plants; despite the fact that all of these molecules are peroxyl radical scavengers, the human body prefers α-tocopherol. The biological activity of vitamin E is highly dependent upon regulatory mechanisms that serve to retain α-tocopherol and excrete the non-α-tocopherol forms. This preference is dependent upon the combination of the function of α-tocopherol transfer protein (α-TTP) to enrich the plasma with α-tocopherol and the metabolism of non-α-tocopherols. α-TTP is critical for human health because mutations in this protein lead to severe vitamin E deficiency characterized by neurologic abnormalities, especially ataxia and eventually death if vitamin E is not provided in large quantities to overcome the lack of α-TTP. α-Tocopherol serves as a peroxyl radical scavenger that protects polyunsaturated fatty acids in membranes and lipoproteins. Although specific pathways and specific molecular targets have been sought in a variety of studies, the most likely explanation as to why humans require vitamin E is that it is a fat-soluble antioxidant.