Abstract
Antioxidants may have a role in the prevention of atherosclerosis. In the present trial, we investigated the antioxidant properties of Palm Vitee, a γ-tocotrienol-, and α-tocopherol enriched fraction of palm oil, in patients with carotid atherosclerosis. Serum lipids, fatty acid peroxides, platelet aggregation, and carotid artery stenosis were measured over an 18-month period in fifty patients with cerebrovascular disease. Change in stenosis was measured with duplex ultrasonography. Ultrasound scans were done at six months, twelve months, and yearly thereafter. Bilateral duplex ultrasonography revealed apparent carotid atherosclerotic regression in seven and progression in two of the 25 tocotrienol patients, while none of the control group exhibited regression and ten of 25 showed progression (P<0.002). Serum thiobarbituric acid reactive substances, anex vivo indicator of maximal platelet peroxidation, decreased in the treatment group from 1.08±0.70 to 0.80±0.55 μM/L (P<0.05) after 12 mon, and in the placebo group, they increased nonsignificantly from 0.99±0.80 to 1.26±0.54 μM/L. Both tocotrienol and placebo groups displayed significantly attenuated collagen-induced platelet aggregation responses (P<0.05) as compared with entry values. Serum total cholesterol, low density lipoprotein cholesterol, and triglyceride values remained unchanged in both groups, as did the plasma high density lipoprotein cholesterol values. These findings suggest that antioxidants, such as tocotrienols, may influence the course of carotid atherosclerosis.
Similar content being viewed by others
Abbreviations
- HDL:
-
high density lipoprotein
- LDL:
-
low density lipoprotein
- TBARS:
-
thiobarbituric acid reactive substances
References
Salonen, J.T., Yla-Herttuala, S., Yamamoto, R., Butler, S., Korpella, H., Salonen, R., Nyyssonen, K., Palinski, W., and Witztum, J.L. (1992) Autoantibody Against Oxidized LDL and Progression of Carotid Atherosclerosis,Lancet 339, 883–887.
Witztum, J.L., and Steinberg, D. (1991) Role of Oxidized Low Density Lipoprotein in Atherogenesis,J. Clin. Invest. 88, 1785–1792.
Steinberg, D., and Workshop Participants (1992) Antioxidants in the Prevention of Atherosclerosis,Circulation 85, 2338–2344.
Esterbauer, H., Dieber-Rotheneder, M., Striegel, G., and Waeg, G. (1991) Role of Vitamin E in Preventing the Oxidation of Low-Density Lipoprotein,Am. J. Clin Nutr. 3, 314S-321S.
Carew, T.E., Schwenke, D.C., and Steinberg, D. (1987) Antiatherogenic Effect of Probucol Unrelated to Its Hypocholesterolemic Effect: Evidence That Antioxidantsin vivo Can Selectively Inhibit Low Density Lipoprotein Degradation in Macrophage-Rich Fatty Streaks Slowing the Progression of Atherosclerosis in the WHHL Rabbit,Proc. Natl. Acad. Sci. (USA) 84, 7725–7729.
Mao, S.J.T., Yates, M.T., Parker, R.A., Chi, E.M., and Jackson, R.L. (1991) Attenuation of Atherosclerosis in a Modified Strain of Hypercholesterolemic Watanabe Rabbit with Use of a Probucol Analogue (MD29,311) That Does Not Lower Serum Cholesterol,Arterioscl. and Thromb. 11, 1266–1275.
Rimm, E.B., Stampfer, M.J., Ascherio, A., Giovanucci, E., Colditz, G.A., and Willett, W.C. (1993) Vitamin E Consumption and the Risk of Coronary Heart Disease in Men,N. Engl. J. Med. 328, 1450–1456.
Stampfer, M.J., Hennekens, C.H., Manson, J.E., Colditz, G.A., Rosner, B., and Willett, W.C. (1993) Vitamin E and Risk of Coronary Disease in Women (1993),N. Eng. J. Med. 328, 1444–1449.
Gey, K.F. (1995) Ten-Year Retrospective on the Antioxidant Hypothesis of Arteriosclerosis,J. Nutr. Biochem. 6, 206–236.
Manson, J.E., Stampfer, M.J., Willett, W.C., Colditz, G.A., Speizer, F.E., and Hennekens, C.H. (1995) Antioxidant Vitamin Consumption and Incidence of Stroke in Women,New Engl. J. Med., 23, November, in press.
Pandey, D., Shekelle, R., Tangney, C., and Stamler, J. (1995) Vitamin C and β-Carotene and Risk of Death in Middle-Aged Men in the Western Electric Study,Am. J. Epidem., in press.
Kritchevsky, S.B., Shimakawa, T., Dennis, B., Eckfeldt, J., Carpenter, M., and Heiss, G. (1993) Dietary Antioxidants and Carotid Artery Wall Thickness: ARIC Study,Circulation 87, 3.
Delong, D.M., Delong, R., Wood, P.D., Lippel, K., and Rifkind, B.M. (1986) A Comparison of Methods for the Estimation of Plasma Low- and Very Low-Density Lipoprotein Cholesterol,J. Am. Med. Assoc. 256, 2372–2377.
Ohishi, N., Ohkawa, H., Miike, A., Tatano, T., and Yagi, K. (1985) A New Assay Method for Lipid Peroxides Using a Methylene Blue Derivative,Biochem. Intl. 10, 205–211.
Mihara, M., Uchiyama, M., and Fukuzawa, K. (1980) Thiobarbituric Acid Value on Fresh Homogenate of Rat as a Parameter of Lipid Peroxidation in Aging; CCl4 Intoxication and Vitamin E Deficiency,Biochem. Med. 23, 302–311.
Bieri, J.G., Tolliver, T.J., and Catigniani, C.L. (1979) Simultaneous Determination of α-Tocopherol and Retinol in Plasma and Red Cells by High Pressure Liquid Chromatography,Am. J. Clin. Nutri. 32, 2143–2149.
Galvez, A., Badimon, L., Badimon, J., and Fuster, V. (1986) Electrical Aggregometry in Whole Blood from Human, Pig, and Rabbit,Thromb. and Hem. 56, 128–132.
Salonen, J.T., Nyssonen, K., Parviainen, M., Kantola, M., Kantola, M., Korpela, H., and Solonen, R. (1993) Low Plasma β-Carotene, Vitamin E and Selenium Levels Associated with Accelerated Carotid Atherogenesis in Hypercholesterolemic Finnish Men,Circulation 87, 2.
Bierenbaum, M.L., Reichstein, R.P., Bhagavan, H.N., and Watkins, T.R. (1992) Relationship Between Serum Lipid Peroxidation Products in Hypercholesterolemic Subjects and Vitamin E Status,Biochem. Int. 28, 57–66.
Qureshi, A.A., Qureshi, N., Hasler-Rapacz, J.O., Weber, F.E., Chaudhary, V., Crenshaw, T.D., Gapor, A., Ong, A.S.H., Chong, Y.H., Peterson, D., and Rapacz, J. (1991) Dietary Tocotrienols Reduce Concentrations of Plasma Cholesterol, Apolipoprotein B, Thromboxane B2 and Platelet Factor 4 in Pigs with Inherited Hyperlipidemias,Am. J. Clin. Nutr. 53, 1042S-1049S.
Qureshi, A.A., Qureshi, N., Wright, J.J.K., Shen, Z., Kramer, G., Gapor, A., Chong, Y.H., Dewitt, G., Ong, A.S.H., Peterson, D.M., and Bradlow, B.A. (1991) Lowering of Serum Cholesterol in Hypercholesterolemic Humans by Palmvitee,Am. J. Clin. Nutr. 53, 1021S-1026S.
Wahlquist, M., Krivokuca-Bogetic, Z., Lo, C.S., Hoge, B., Smith, R., and Lukito, W. (1992) Differential Serum Responses of Tocopherols and Tocotrienols During Vitamin Supplementation in Hypercholesterolemic Individuals Without Change in Coronary Risk Factors,Nutr. Res. 12, S181-S201.
Watkins, T.R., Lenz, P., Gapor, A., Struck, M., Tomeo, A., and Bierenbaum, M.L. (1993) γ-Tocotrienol as a Hypocholesterolemic and Antioxidant Agent in Rats Fed Atherogenic Diets,Lipids 28, 1113–1118.
Bierenbaum, M.L., Fleischman, A.I., Raichelson, R.I., Hayton, T., and Watson, P.B. (1973) Ten-Year Experience of Modified-Fat Diets on Younger Men with Coronary Heart Disease,Lancet 2, 1404–1407.
Miettinen, T.A., Huttunen, J.K., Naukkaunien, V., Strandberg, T., and Vanhanen, H. (1986) Long-Term Use of Probucol in the Multifactorial Primary Prevention of Vascular Disease,Am. J. Card. 57, 49H-54H.
Bocan, T.M.A., Mazur, M.J., Mueller, S.B., Charlton, G., Kieft, K.A., and Krause, B.R. (1994) Atherosclerotic Lesion Development in Hypercholesterolemic Japanese Quail Following Probucol Treatment: A Biochemical and Morphological Evaluation,Pharmacol. Res. 29, 65–76.
Johansson, J., Olsson, A., Bergstrand, L., Elinder, L.S., Nilsson, S., Erikson, U., Molgaard, J., Holme, I., and Waldius, G. (1995) Lowering of HDL2b by Probucol Partly Explains the Failure of the Drug to Affect Femoral Atherosclerosis in Subjects with Hypercholesterolemia,Arterio. Vasc. Biol. 15, 1049–1056.
Atkins, D., Psaty, B.M., Koepsell, T.D., Longstreth, W.T., and Larson, E.B. (1993) Cholesterol Reduction and the Risk of Stroke in Men. A Meta-Analysis of Randomized, Controlled Trials,Ann. Intern. Med. 119, 136–145.
Herbert, P.R., Gaziano, J.M., and Hennekens, C.H. (1995) An Overview of Trials of Cholesterol Lowering and Risk of Stroke,Arch. Int. Med. 155, 50–55.
Author information
Authors and Affiliations
About this article
Cite this article
Tomeo, A.C., Geller, M., Watkins, T.R. et al. Antioxidant effects of tocotrienols in patients with hyperlipidemia and carotid stenosis. Lipids 30, 1179–1183 (1995). https://doi.org/10.1007/BF02536621
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02536621