Studies of LDL oxidation following α-, γ-, or δ-tocotrienyl acetate supplementation of hypercholesterolemic humans

D. O'Byrne, Scott M Grundy, L. Packer, S. Devaraj, K. Baldenius, P. P. Hoppe, K. Kraemer, I. Jialal, M. G. Traber

Research output: Contribution to journalArticlepeer-review

116 Scopus citations


In vitro tocotrienols (T3s) have potent vitamin E antioxidant activity, but unlike tocopherols can inhibit cholesterol synthesis by suppressing 3-hydroxy-3-methyl-glutarylCoA (HMG-CoA) reductase. Because hypercholesterolemia is a major risk factor for coronary artery disease and oxidative modification of low-density lipoprotein (LDL) may be involved in atherogenesis, we investigated whether daily supplements of placebo, or alpha-, gamma-, or delta- (α-, γ-, or δ-) tocotrienyl acetates would alter serum cholesterol or LDL oxidative resistance in hypercholesterolemics in a double-blind placebo controlled study. Subjects were randomly assigned to receive placebo (n = 13), α- (n = 13), γ- (n = 12), or δ- (n = 13) tocotrienyl acetate supplements (250 mg/d). All subjects followed a low-fat diet for 4 weeks, then took supplements with dinner for the following 8 weeks while still continuing diet restrictions. Plasma α- and γ-tocopherols were unchanged by supplementation. Plasma T3s were undetectable initially and always in the placebo group. Following supplementation in the respective groups plasma concentrations were: α-T3 0.98 ± 0.80 μmol/l, γ-T3 0.54 ± 0.45 μmol/l, and δ-T3 0.09 ± 0.07 μmol/l. Alpha-T3 increased in vitro LDL oxidative resistance (+22%, p < .001) and decreased its rate of oxidation (p < .01). Neither serum or LDL cholesterol nor apolipoprotein B were significantly decreased by tocotrienyl acetate supplements. This study demonstrates that: (i) tocotrienyl acetate supplements are hydrolyzed, absorbed, and detectable in human plasma; (ii) tocotrienyl acetate supplements do not lower cholesterol in hypercholesterolemic subjects on low-fat diets; and (iii) α-T3 may be potent in decreasing LDL oxidizability. Copyright (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)834-845
Number of pages12
JournalFree Radical Biology and Medicine
Issue number9
StatePublished - Nov 1 2000


  • Antioxidant
  • Cholesterol
  • Free radicals
  • HMG CoA reductase
  • Low-density lipoprotein oxidation
  • Tocopherol
  • Tocotrienol
  • Vitamin E

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


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