Delivery of orally supplemented α-tocotrienol to vital organs of rats and tocopherol-transport protein deficient mice

The natural vitamin E tocotrienol (TCT) possesses biological properties not shared by tocopherols (TCP). Nanomolar α-TCT, not α-TCP, is potently neuroprotective (JBC 275:13049; 278:43508). Tocopherol-transport protein (TTP) represents the primary mechanism for maintaining normal α-TCP concentrations in plasma and extrahepatic tissues. TTP primarily transports α-TCP and has low affinity for α-TCT. There are no studies that have investigated tissue delivery of α-TCT when orally gavaged on a long-term basis. A long-term study was conducted to examine the effects of α-TCT or α-TCP supplementation, either alone or in combination, on tissue levels. Rats were maintained on a vitamin E-deficient diet and gavaged with α-TCT or α-TCP alone or in combination. Five generations of rats were studied over 60 weeks. TTP-deficient mice were supplemented with TCT and bred to examine tissue delivery of oral α-TCT. Orally supplemented α-TCT was effectively delivered to most tissues over time. When co-supplemented, α-TCP outcompeted α-TCT for transport systems delivering vitamin E to tissues. To evaluate the significance of TTP in α-TCT delivery to tissues, tissue levels of α-TCT in supplemented TTP-deficient mice were studied. α-TCT was transported to several vital organs in TTP-deficient mice. α-TCT restored fertility in TTP-deficient mice. In sum, orally supplemented α-TCT was successfully delivered to several vital organs. The transport efficiency of α-TCT to tissues may be maximized by eliminating the co-presence of α-TCP in the oral supplement. Examination of whether α-TCT may benefit humans suffering from neurological disorders because of congenital TTP deficiency is warranted.