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Dietary -Tocopherol Attenuates the Impact of -Tocotrienol on Hepatic 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Activity in Chickens^1,2,

Asaf A. Qureshi^*,3, Bradley C. Pearce, Rosnah M. Nor^**, A. Gapor^**, David M. Peterson and Charles E. Elson

^* Advanced Medical Research, Madison, WI 53719 Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492 ^** Palm Oil Research Institute, Kuala Lumpur, Malaysia Cereal Crops Research, Agriculture Research Service, U.S. Department of Agriculture, Madison, WI 53705 Department of Nutritional Sciences, University of Wisconsin, Madison, WI 53706

The concentration-dependent impact of -tocotrienol on serum cholesterol can be traced to the posttranscriptional down-regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. -Tocotrienol also suppresses tumor growth. Palmvitee, the tocopherol and tocotrienol-rich fraction of palm oil, is the sole commercial source of -tocotrienol. Contrary to the universal findings of the efficacy of -tocotrienol there are conflicting reports of the impact of Palmvitee on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, serum cholesterol concentrations and tumor development. These conflicting reports led us to examine the impact of -tocopherol on the cholesterol-suppressive action of -tocotrienol. Control and experimental diets were fed to groups of White Leghorn chickens (n = 10) for 26 d. The control diet was supplemented with 21 nmol -tocopherol/g. All experimental diets provided 141 nmol of blended tocols/g diet. The -tocopherol and -tocotrienol concentrations of the experimental diets ranged from 21 to 141 and 0 to 120 nmol/g, respectively. We now report that including -tocopherol in tocol blends containing adequate -tocotrienol to suppress 3-hydroxy-3-methylglutaryl coenzyme A reductase activity results in an attenuation of the tocotrienol action (P < 0.001). A summary of results from studies utilizing different Palmvitee preparations shows that effective preparations consist of 15–20% -tocopherol and 60% - (and -) tocotrienol, whereas less effective preparations consist of 30% -tocopherol and 45% - (and -) tocotrienol.

KEY WORDS: • -tocotrienol • -tocopherol • 3-hydroxy-3-methylglutaryl coenzyme A reductase • cholesterol • chickens

¹ In part supported by Bristol-Myers Squibb Pharmaceutical Research Institute and the College of Agricultural and Life Sciences, University of Wisconsin, Madison, WI.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence should be addressed.

Manuscript received 17 May 1995. Revision accepted 17 October 1995.

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