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Osteoporosis, a degenerative bone disease, is characterized by low bone mass and microstructural deterioration of bone tissue resulting in aggravated bone fragility and susceptibility to fractures. The trend of extended life expectancy is accompanied by a rise in the prevalence of osteoporosis and concomitant complications in the elderly population. Epidemiological evidence has shown an association between vitamin E consumption and the prevention of age-related bone loss in elderly women and men. Animal studies show that ingestion of vitamin E, especially tocotrienols, may benefit bone health in terms of maintaining higher bone mineral density and improving bone microstructure and quality. The beneficial effects of tocotrienols on bone health appear to be mediated via antioxidant/anti-inflammatory pathways and/or 3-hydroxy-3-methylglutaryl coenzyme A mechanisms. We discuss (1) an overview of the prevalence and etiology of osteoporosis, (2) types of vitamin E (tocopherols versus tocotrienols), (3) findings of tocotrienols and bone health from published in vitro and animal studies, (4) possible mechanisms involved in bone protection, and (5) challenges and future direction for research. [ABSTRACT FROM AUTHOR]

Diets supplemented (1 mmol/kg) with thymol, carvacrol, and β-ionone significantly decreased the serum cholesterol levels of cockerels. These mevalonate-derived end products of plant secondary metabolism (isoprenoids) had no impact on two cytosolic prenyl alcohol (and ethanol) dehydrogenase activities; each treatment increased microsomal geranyl pyrophosphate pyrophosphatase activity by greater than twofold. The structural diversity of the isoprenoids which suppress cholesterol synthesis may be reconciled by their ability to increase pyrophosphatase activity, thus leading to the production of the endogenous, post-transcriptional regulator of 3-hydroxy-3-methyglutaryl coenzyme A reductase activity. [ABSTRACT FROM AUTHOR]

3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase provides mevalonate-derived intermediates for the prenylation or dolichylation of growth proteins including lamins, Ras and growth factor receptors. Competitive inhibitors of reductase, the statins, and downregulators of reductase, geraniol and farnesol, suppress pancreatic tumor growth, d-δ-Tocotrienol with a farnesol moiety suppresses tumor growth in vitro and in vivo. These considerations led to an in vitro evaluation of the impact of d-δ-tocotrienol on the proliferation of human MIA PaCa-2 and PANC-1 pancreas carcinoma cells and BxPC-3 pancreas adenocarcinoma cells, d-δ-Tocotrienol induced dose-dependent suppression of the 72-h proliferation of all cells cultured in 96-well plates, with IC50s of 28 ± 8 µmol/L (MIA PaCa-2), 45 ± 12 µmol/L (PANC-1) and 40 ± 7 pmol/L (BxPC-3), respectively, d-δ-Tocotrienol-mediated morphological changes resemble those occurring in apoptotic cells. Flow cytometric analysis employing Guava NexinTM Kit revealed d-δ-tocotrienol-induced apoptosis in PANC-1 cells. A blend of lovastatin (4 µmol/L) and d-δ-tocotrienol (10 µmol/L) suppressed the proliferation of MIA PaCa-2 cells by 71%, far exceeding the sum of the effects of lovastatin (149%) and d-5-tocotrienol (2%). d-δ-Tocotrienol as a reductase down-regulator may have potential in pancreatic cancer chemoprevention. TDA, TWU REP & Summer Stipend Award. [ABSTRACT FROM AUTHOR]