, Volume 30, Issue 12, pp 1179–1183 | Cite as

Antioxidant effects of tocotrienols in patients with hyperlipidemia and carotid stenosis

  • A. C. Tomeo
  • M. Geller
  • T. R. Watkins
  • A. Gapor
  • M. L. Bierenbaum


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.


Carotid Stenosis Probucol Carotid Atherosclerosis Carotid Artery Stenosis Tocotrienols 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



high density lipoprotein


low density lipoprotein


thiobarbituric acid reactive substances


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  1. 1.
    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.PubMedCrossRefGoogle Scholar
  2. 2.
    Witztum, J.L., and Steinberg, D. (1991) Role of Oxidized Low Density Lipoprotein in Atherogenesis,J. Clin. Invest. 88, 1785–1792.PubMedCrossRefGoogle Scholar
  3. 3.
    Steinberg, D., and Workshop Participants (1992) Antioxidants in the Prevention of Atherosclerosis,Circulation 85, 2338–2344.Google Scholar
  4. 4.
    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.Google Scholar
  5. 5.
    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.CrossRefGoogle Scholar
  6. 6.
    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.Google Scholar
  7. 7.
    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.PubMedCrossRefGoogle Scholar
  8. 8.
    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.CrossRefGoogle Scholar
  9. 9.
    Gey, K.F. (1995) Ten-Year Retrospective on the Antioxidant Hypothesis of Arteriosclerosis,J. Nutr. Biochem. 6, 206–236.CrossRefGoogle Scholar
  10. 10.
    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.Google Scholar
  11. 11.
    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.Google Scholar
  12. 12.
    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.Google Scholar
  13. 13.
    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.CrossRefGoogle Scholar
  14. 14.
    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.Google Scholar
  15. 15.
    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.PubMedCrossRefGoogle Scholar
  16. 16.
    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.Google Scholar
  17. 17.
    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.Google Scholar
  18. 18.
    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.Google Scholar
  19. 19.
    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.PubMedGoogle Scholar
  20. 20.
    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.PubMedGoogle Scholar
  21. 21.
    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.PubMedGoogle Scholar
  22. 22.
    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.CrossRefGoogle Scholar
  23. 23.
    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.PubMedCrossRefGoogle Scholar
  24. 24.
    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.CrossRefGoogle Scholar
  25. 25.
    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.PubMedCrossRefGoogle Scholar
  26. 26.
    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.PubMedCrossRefGoogle Scholar
  27. 27.
    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.Google Scholar
  28. 28.
    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.PubMedGoogle Scholar
  29. 29.
    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.CrossRefGoogle Scholar

Copyright information

© American Oil Chemists’ Society 1995

Authors and Affiliations

  • A. C. Tomeo
    • 1
  • M. Geller
    • 2
  • T. R. Watkins
    • 1
  • A. Gapor
    • 3
  • M. L. Bierenbaum
    • 1
  1. 1.Kenneth L. Jordan Research GroupMontclair
  2. 2.Elmhurst Medical CenterQueens
  3. 3.Palm Oil Research Institute of MalaysiaKuala LumpurMalaysia

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