Tocopherols and Tocotrienols Are Bioavailable in Rats and Primarily Excreted in Feces as the Intact Forms and 13'-Carboxychromanol Metabolites

Abstract

Vitamin E α-, γ-, or δ-tocopherol (αT, γT, δT) and γ- or δ-tocotrienol (γTE, δTE) are metabolized to hydroxychromanols and carboxychromanols including 13'-carboxychromanol (13'-COOH), 11'-COOH, and carboxyethyl hydroxychroman (CEHC), some of which have unique bioactivities compared with the vitamers. However, the bioavailability of these metabolites has not been well characterized. We investigated the pharmacokinetics (PK) of vitamin E forms and metabolites in rats. Six-week-old male Wistar rats received 1-time gavage of γT-rich tocopherols (50 mg/kg) containing γT/δT/αT (57.7%, 21.9%, and 10.9%, respectively) or δTE-rich tocotrienols (35 mg/kg) containing δTE/γTE (8:1). We quantified the time course of vitamin E forms and metabolites in the plasma and their 24-h excretion to the urine and feces. The general linear model repeated measure was used for analyses of the PK data. In the rats' plasma, Cmax of γT or δTE was 25.6±9.1 μM (Tmax=4 h) or 16.0±2.3 μM (Tmax=2 h), respectively, and sulfated CEHCs and sulfated 11'-COOHs were the predominant metabolites with Cmax of 0.4-0.5 μM (Tmax ∼5-7 h) or ∼0.3 μM (Tmax at 4.7 h), respectively. In 24-h urine, 2.7% of γT and 0.7% of δTE were excreted as conjugated CEHCs. In the feces, 17-45% of supplemented vitamers were excreted as unmetabolized forms and 4.9-9.2% as unconjugated carboxychromanols, among which 13'-COOHs constituted ∼50% of total metabolites and the amount of δTE-derived 13'-COOHs was double that of 13'-COOH derived from γT. PK data of vitamin E forms in rats reveal that γT, δT, γTE, and δTE are bioavailable in the plasma and are mainly excreted as unmetabolized forms and long-chain metabolites including 13'-COOHs in feces, with more metabolites from tocotrienols than from tocopherols.