Vitamin E deficiency has been found to impair bone calcification. This study was done to determine the effects of vitamin E deficiency and supplementation on parathyroid hormone, i.e. the hormone involved in bone regulation. Female Sprague-Dawley rats were divided into 4 groups: 1) normal rat chow (RC), 2) vitamin E deficiency (VED), vitamin E deficient rats supplemented with 3) 60 mg/kg alpha-tocotrienol (ATT) and 4) 60 mg/kg (alpha-tocopherol (ATF). Treatment was carried out for 3 months. Vitamin E deficiency caused hypocalcaemia during the first month of the treatment period, increased the parathyroid hormone level in the second month and decreased the bone calcium content in the 4th lumbar bone at the end of the treatment. Vitamin E supplementation (ATT and ATF) failed to improve these conditions. The bone formation marker, osteocalcin, and the bone resorption marker, deoxypyridinoline did not change throughout the study period. In conclusion vitamin E deficiency impaired bone calcium homeostasis with subsequent secondary hyperparathyroidism and vertebral bone loss. Replacing the vitamin E with pure ATF or pure ATT alone failed to correct the changes seen.

We previously reported that tocotrienols acted as more potent inhibitors against selenium deficiency–induced cell death than the corresponding tocopherol isoforms (J. Biol. Chem. 2003;278:39428–39434). In the present study, we first compared the differences in the cellular uptake between α- tocopherol (α-Toc) and _-tocotrienol (α-Toc-3). The initial rate of cellular uptake of α-Toc-3 was 70-fold higher than that of α-Toc. Subcellular fractionation analysis of _-Toc-3 and α-Toc–fortified cells showed similar cellular distribution of these antioxidants, which was directly proportional to the lipid distribution. The cells containing similar amounts of α-Toc-3 and α-Toc showed similar resistance against the oxidative stress caused by peroxides.

These results suggest that the apparent higher cytoprotective effect of α-Toc-3 than α-Toc is primarily ascribed to its higher cellular uptake.