|Abstract or Summary
- The primary goal of my study was to evaluate the effects of high dietary vitamin E on the rodent skeleton. The outcomes from my study assess the impact of high intakes of vitamin E and increased concentrations of its metabolite, carboxy ethyl hydroxy chromanol (CEHC), on bone turnover and skeletal pathology. These findings contribute to a better understanding of the potential skeletal consequences of high intakes of vitamin E. Our central hypothesis was that bone loss mediated by high dietary vitamin E is due to high extra-hepatic tissue concentrations of its metabolite, CEHC. Our study consisted of two specific aims:
In Aim 1, we evaluated the hypothesis that high dietary vitamin E induces bone loss in rodents. Sprague Dawley rats, 11-weeks-old, were fed for 18 weeks semi-purified diets containing adequate alpha-tocopherol (78 mg/kg diet), high alpha-tocopherol (518 mg/kg diet), or mixed-tocopherols and tocotrienols (234 mg/kg diet). Alterations in bone mineral density, bone mass, and microarchitecture were assessed using dual x-ray absorptiometry and micro-computed tomography, respectively. Serum osteocalcin, bone formation rates, and osteogenic gene expression were also examined using an osteocalcin immunoassay, histomorphometry and polymerase chain reaction (PCR) analyses, respectively. Cancellous bone volume fraction in proximal tibia and lumbar vertebra were unaffected by dietary treatments. Additionally, no significant differences between groups were detected for serum osteocalcin, osteogenic gene expression, or bone formation rates. Given these findings, we conclude that vitamin E added to otherwise adequate diets has no adverse effects on bone mass and bone turnover in young adult male rats.
In Aim 2, we evaluated the hypothesis that increased concentrations of the anti-inflammatory metabolite, CEHC, mediate bone loss in rodents. Using the study design from Aim 1, we measured serum and tissue concentrations of CEHC in each treatment group. Rats consuming diets containing high alpha-tocopherol had increased plasma, bone marrow, and liver alpha-CEHC concentrations, whereas rats consuming diets of mixed-tocopherols and tocotrienols had increased plasma gamma-CEHC compared with other treatment groups. Only plasma gamma-CEHC was correlated with serum osteocalcin, a marker of bone turnover, with the highest plasma gamma-CEHC and lowest serum osteocalcin concentrations from the mixed-tocopherols and tocotrienols group. Given these findings, we conclude that plasma gamma-CEHC may play a role in bone turnover, as evidenced by a correlation with lower serum osteocalcin.
In summary, my study has shown that high intakes of dietary vitamin E and its metabolite, CEHC, have no adverse effects on the rodent skeleton. Interestingly, plasma gamma-CEHC is correlated with low serum osteocalcin; however, the physiological significance of this relationship is unclear.