Gamma‐tocopherol and gamma‐tocotrienol are primarily metabolized to conjugated CEHC and sulfated long‐chain carboxychromanols in rats

Vitamin E is known to be metabolized to the terminal urinary‐excreted metabolite, 2‐(â ‐carboxyethyl)‐6‐hydroxychroman (CEHC). We recently showed that sulfated long‐chain carboxychromanols are generated from the metabolism of tocopherols. Here we identified similar sulfated long‐chain carboxychromanols by electrospray mass spectrometry from human A549 cells incubated with gamma‐tocotrienol (g‐TE). Sulfation was confirmed by sulfatase digestion which converted sulfated carboxychromanols to carboxychromanols. In the culture media, more than 90% long‐chain carboxychromanols from g‐TE, but less than 45% from tocopherols were sulfated. In rats, six hours after administration of g‐TE or g‐tocopherol (g‐T), the plasma had increased levels of sulfated 9′‐, 11′‐, 13′‐carboxychromanol and 13′‐carboxychromanol. Sulfatase digestion revealed that conjugated CEHC is by far the most abundant metabolite, accounting for >75% of total metabolites, whereas free CEHC is a minor metabolite. Total metabolites from g‐TE were significantly (P<0.05) higher than those from g‐T, while g‐TE was significantly (P<0.05) lower than g‐T in the plasma. These results demonstrate that in rats, sulfation is quantitatively important to vitamin E metabolism, g‐TE is more extensively metabolized than g‐T, and sulfation likely occurs parallel to â‐oxidation. (Supported by NIH R01AT001821)