References

1. Pearce, B. C., R. A. Parker, M. E. Deason, A. A. Qureshi, and J. J. Wright. 1992. Hypocholesterolemic activity of synthetic and natural tocotrienols. J Med Chem 35:3595-606.

2. Parker, R. A., B. C. Pearce, R. W. Clark, D. A. Gordon, and J. J. Wright. 1993. Tocotrienols regulate cholesterol production in mammalian cells by post- transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. J Biol Chem 268:11230-8.

3. Song, B. L., and R. A. DeBose-Boyd. 2006. Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase stimulated by delta- and gamma-tocotrienols. J Biol Chem 281:25054-61.

4. Palozza, P., S. Verdecchia, L. Avanzi, S. Vertuani, S. Serini, A. Iannone, S. Manfredini. 2006. Comparative antioxidant activity of tocotrienols and the novelchromanyl-polyisoprenyl molecule FeAox-6 in isolated membranes and intact cells. Mol Cell Biochem 287(1-2):21-32.

5. Tan, B. 2005. Appropriate spectrum vitamin E and new perspectives on desmethyl tocopherols and tocotrienols. JANA 8:35-42.

6. Qureshi, A. A., H. Mo, L. Packer, and D.M. Peterson. 2000. Isolation and structural identification of novel tocotrienols from rice bran with hypocholesterolemic, antioxidant and antitumor properties. J Agric Food Chem48 (8):3130-3140.

7. Qureshi, A. A., B. C. Pearce, R. M. Nor, A. Gapor, D. M. Peterson, and C. E. Elson. 1996. Dietary alpha-tocopherol attenuates the impact of gamma- tocotrienol on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in chickens. J Nutr 126:389-94.

8. Mensink, R. P., A. C. van Houwelingen, D. Kromhout, and G. Hornstra. 1999. A vitamin E concentrate rich in tocotrienols had no effect on serum lipids, lipoproteins, or platelet function in men with mildly elevated serum lipid concentrations. Am J Clin Nutr 69:213-9.

9. Mustad, V. A., C. A. Smith, P. P. Ruey, N. K. Edens, and S. J. DeMichele. 2002. Supplementation with 3 compositionally different tocotrienol supplements does not improve cardiovascular disease risk factors in men and women with hypercholesterolemia. Am J Clin Nutr 76:1237-43.

10. Qureshi, A. A., S. A. Sami, W. A. Salser, and F. A. Khan. 2002. Dose- dependent suppression of serum cholesterol by tocotrienol-rich fraction (TRF25) of rice bran in hypercholesterolemic humans. Atherosclerosis 161:199-207.

11. Tan, D. T., H. T. Khor, W. H. Low, A. Ali, and A. Gapor. 1991. Effect of a palm-oil-vitamin E concentrate on the serum and lipoprotein lipids in humans. Am J Clin Nutr 53:1027S-1030S.

12. Schaffer, S., W. E. Muller, and G. P. Eckert. 2005. Tocotrienols: constitutional effects in aging and disease. J Nutr 135:151-4.

13. Yu, S.G., A.M. Thomas, A. Gapor, B. Tan, N. Qureshi, and A.A. Qureshi. Dose-response impact of various tocotrienols on serum lipid parameters in 5- week-old female chickens. 2006. Lipids 41 (5): 453-461.

14. Qureshi, A.A., and N. Qureshi. 1993. Tocotrienols: Novel hypocholesterolemic agents with antioxidant properties. In L. Packer and J. Fuchs (ed.), Vitamin E in Health and Disease. Marcel Dekker, New York.

15. Theriault, A., J. T. Chao, and A. Gapor. 2002. Tocotrienol is the most effective vitamin E for reducing endothelial expression of adhesion molecules and adhesion to monocytes. Atherosclerosis 160:21-30.

16. Chao, J. T., A. Gapor, and A. Theriault. 2002. Inhibitory effect of delta-tocotrienol, a HMG CoA reductase inhibitor, on monocyte-endothelial cell adhesion. J Nutr Sci Vitaminol (Tokyo) 48:332-7.

17. Naito, Y., M. Shimozawa, M. Kuroda, N. Nakabe, H. Manabe, K. Katada, S. Kokura, H. Ichikawa, N. Yoshida, N. Noguchi, and T. Yoshikawa. 2005. Tocotrienols reduce 25-hydroxycholesterol-induced monocyte-endothelial cell interaction by inhibiting the surface expression of adhesion molecules. Atherosclerosis 180:19-25.

18. Holub, B. 1989. Inhibition of Platelet Aggregation by Tocotrienols. University of Guelph, Ontario, Canada. Internal Publication.

19. Newaz, M. A., and N. N. Nawal. 1999. Effect of gamma-tocotrienol on blood pressure, lipid peroxidation and total antioxidant status in spontaneously hypertensive rats (SHR). Clin Exp Hypertens 21:1297-313.

20. Newaz, M. A., Z. Yousefipour, N. Nawal, and N. Adeeb. 2003. Nitric oxide synthase activity in blood vessels of spontaneously hypertensive rats: antioxidant protection by gamma-tocotrienol. J Physiol Pharmacol 54:319-27.

21. Qureshi, A. A., W. A. Salser, R. Parmar, and E. E. Emeson. 2001. Novel tocotrienols of rice bran inhibit atherosclerotic lesions in C57BL/6 ApoE- deficient mice. J Nutr 131:2606-18.

22. Suarna, C., B. J. Wu, K. Choy, T. Mori, K. Croft, O. Cynshi, and R. Stocker. 2006. Protective effect of vitamin E supplements on experimental atherosclerosis is modest and depends on preexisting vitamin E deficiency. Free Radic Biol Med 41:722-30.

23. Tomeo, A. C., M. Geller, T. R. Watkins, A. Gapor, and M. L. Bierenbaum. 1995. Antioxidant effects of tocotrienols in patients with hyperlipidemia and carotid stenosis. Lipids 30:1179-83.

24. Kooyenga, D.K., T.R. Watson, M. Geller, M. L. Bierenbaum. 2001. Micronutrients and Health: Antioxidants modulate the course of carotid atherosclerosis: A four-year report. Nesaretnam, K., L. Packer (Eds). Illinois: AOCS Press. 366-375.

25. Watkins, T. R., M. Geller, D. K. Kooyenga, and M. Bierenbaum. 1999. Hypocholesterolemic and antioxidant effect of rice bran oil non-saponifiables in hypercholesterolemic subjects. Env & Nutr Int 3:115-122.

26. American Heart Association. 2006.

27. Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. 2001. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285:2486-2497.

28. World Health Organization. 1999. Definition, diagnosis, and classification of diabetes mellitus and its complications: report of a WHO consultation. Geneva, World Health Organization.

29. Wan Nazaimoon, W. M., and B. A. Khalid. 2002. Tocotrienols-rich diet decreases advanced glycosylation end-products in non-diabetic rats and improves glycemic control in streptozotocin-induced diabetic rats. Malays J Pathol 24:77- 82.

30. Chen, C.W., and H.H. Cheng. 2006. A rice bran oil diet increases LDL-receptor and HMG-CoA reductase mRNA expressions and insulin sensitivity in rats with streptozotocin/nicotinamide-induced type 2 diabetes. J Nutr 136(6):1472-6.

31. Qureshi, A. A., S. A. Sami, and F. A. Khan. 2002. Effects of stabilized rice bran, its soluble and fiber fractions on blood glucose levels and serum lipid parameters in humans with diabetes mellitus Types I and II. J Nutr Biochem 13:175-187.

32. Montonen, J., P. Knekt, R. Jarvinen, and A. Reunanen. 2004. Dietary antioxidant intake and risk of type 2 diabetes. Diabetes Care 27:362-6.

33. Baliarsingh, S., Z. H. Beg, and J. Ahmad. 2005. The therapeutic impacts of tocotrienols in type 2 diabetic patients with hyperlipidemia. Atherosclerosis 182:367-74.

34. Theriault, A., J. T. Chao, Q. Wang, A. Gapor, and K. Adeli. 1999. Tocotrienol: a review of its therapeutic potential. Clin Biochem 32:309-19.

35. Elson, C. E. 1995. Suppression of mevalonate pathway activities by dietary isoprenoids: protective roles in cancer and cardiovascular disease. J Nutr 125:1666S-1672S.

36. Sylvester, P. W., and A. Theriault. 2003. Role of tocotrienols in the prevention of cardiovascular disease and breast cancer. Curr Top Nutr Res 1:121- 136.

37. Nakagawa, K., T. Eitsuka, H. Inokuchi, and T. Miyazawa. 2004. DNA chip analysis of comprehensive food function: inhibition of angiogenesis and telomerase activity with unsaturated vitamin E, tocotrienol. Biofactors 21:5-10.

38. Yano, Y., H. Satoh, K. Fukumoto, I. Kumadaki, T. Ichikawa, K. Yamada, K. Hagiwara, and T. Yano. 2005. Induction of cytotoxicity in human lung adenocarcinoma cells by 6-O-carboxypropyl-alpha-tocotrienol, a redox-silent derivative of alpha-tocotrienol. Int J Cancer115:839-46.

39. Wada, S., Y. Satomi, M. Murakoshi, N. Noguchi, T. Yoshikawa, and H. Nishino. 2005. Tumor suppressive effects of tocotrienol in vivo and in vitro. Cancer Lett 229:181-91.

40. Kline, K., W. Yu, and B. G. Sanders. 2001. Vitamin E: mechanisms of action as tumor cell growth inhibitors. J Nutr 131:161S-163S.

41. Sakai, M., M. Okabe, H. Tachibana, K. Yamada. 2006. Apoptosis induction by gamma-tocotrienol in human hepatoma Hep3B cells. J Nutr Biochem 17(10):672-6.

42. Elson, C. E., D. M. Peffley, P. Hentosh, and H. Mo. 1999. Isoprenoid- mediated inhibition of mevalonate synthesis: potential application to cancer. Proc Soc Exp Biol Med 221:294-311.

43. Mo, H., and C. E. Elson. 1999. Apoptosis and cell-cycle arrest in human and murine tumor cells are initiated by isoprenoids. J Nutr 129:804-13.

44. He, L., H. Mo, S. Hadisusilo, A. A. Qureshi, and C. E. Elson. 1997. Isoprenoids suppress the growth of murine B16 melanomas in vitro and in vivo. J Nutr 127:668-74.

45. Mizushina, Y., K. Nakagawa, A. Shibata, Y. Awata, I. Kuriyama, N. Shimazaki, O. Koiwai, Y. Uchiyama, K. Sakaguchi, T. Miyazawa, and H. Yoshida. 2006. Inhibitory effect of tocotrienol on eukaryotic DNA polymerase lambda and angiogenesis. Biochem Biophys Res Commun 339:949-55.

46. Nesaretnam, K., N. Guthrie, A. F. Chambers, and K. K. Carroll. 1995. Effect of tocotrienols on the growth of a human breast cancer cell line in culture. Lipids 30:1139-43.

47. Nesaretnam, K., R. Stephen, R. Dils, and P. Darbre. 1998. Tocotrienols inhibit the growth of human breast cancer cells irrespective of estrogen receptor status. Lipids 33:461-9.

48. Schwenke, D. C. 2002. Does lack of tocopherols and tocotrienols put women at increased risk of breast cancer? J Nutr Biochem 13:2-20.

49. Shun, M. C., W. Yu, A. Gapor, R. Parsons, J. Atkinson, B. G. Sanders, and K. Kline. 2004. Pro-apoptotic mechanisms of action of a novel vitamin E analog (alpha-TEA) and naturally occurring form of vitamin E (delta- tocotrienol) in MDA-MB-435 human breast cancer cells. Nutr Cancer 48:95-105.

50. Palapattu, G. S., S. Sutcliffe, P. J. Bastian, E. A. Platz, A. M. De Marzo, W. B. Isaacs, and W. G. Nelson. 2005. Prostate carcinogenesis and inflammation: emerging insights. Carcinogenesis 26:1170-81.

51. Conte, C., A. Floridi, C. Aisa, M. Piroddi, A. Floridi, and F. Galli. 2004. Gamma-tocotrienol metabolism and antiproliferative effect in prostate cancer cells. Ann N Y Acad Sci 1031:391-4.

52. Narimah, A. H. H., A. M. Y. Permeen, A. Gapor, B. A. K. Khalid, and W. Z. Wan Ngah. 1998. Effect of palm oil g-tocotrienol on the proliferation of normal splenic lymphocytes and cervical cancer (CaSki) cells. Mal J Biochem Mol Biol 3:8-11.

53. Traber, M. G., M. Podda, C. Weber, J. J. Thiele, M. Rallis, and L. Packer. 1997. Diet-derived and topically applied tocotrienols accumulate in skin and protect the tissue against ultraviolet light-induced oxidative stress. Asia Pac J Clin Nutr 6:63-67.

54. Kamat, J. P., H. D. Sarma, T. P. Devasagayam, K. Nesaretnam, and Y. Basiron. 1997. Tocotrienols from palm oil as effective inhibitors of protein oxidation and lipid peroxidation in rat liver microsomes. Mol Cell Biochem 170:131-7.

55. Mutalib, M.S.A., H. Khaza’ai, and K.W.J. Wahle. 2003. Palm-tocotrienol- rich fraction (TRF) is a more effective inhibitor of LDL oxidation and endothelial cell lipid peroxidation than alpha-tocopherol in vitro. Food Res Intl 36:405-413.

56. Weber, C., M. Podda, M. Rallis, J. J. Thiele, M. G. Traber, and L. Packer. 1997. Efficacy of topically applied tocopherols and tocotrienols in protection of murine skin from oxidative damage induced by UV-irradiation. Free Radic Biol Med 22:761-9.

57. Traber, M. G., M. Rallis, M. Podda, C. Weber, H. I. Maibach, and L. Packer. 1998. Penetration and distribution of alpha-tocopherol, alpha- or gamma- tocotrienols applied individually onto murine skin. Lipids 33:87-91.

58. Packer, L., S.U. Weber, G. Rimbach. 2001. Molecular aspects of alpha- tocotrienol antioxidant action and cell signaling. J Nutr 131:369S-373S.

59. McAnally J.A., J. Gupta, S. Sodhani, L. Bravo, H. Mo. Apr. 2007. Tocotrienols potentiate lovastating-mediated growth suppression in vitro and in vivo. Exp Biol Med 232(4):523-31.

60. Tan, B., A. Mueller. Tocotrienols: Vitamin E beyond Tocopherols. Tocotrienols in Cardiometabolic Diseases. Ed. Ron Watson. AOCS Press: Champaign, IL, 2008.

61. Malafa, M.P., and S.M. Sebti. H. Delta-Tocotrienol Treatment and Prevention of Pancreatic Cancer Lee Moffitt Cancer Center & Research Institute, University of South Florida (Tampa). USPTO US2008/0004233. 1/3/08.