title: Studies of LDL oxidation following alpha-, gamma-, or delta-tocotrienyl acetate supplementation of hypercholesterolemic humans.
abstract: 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- (alpha-, gamma-, or delta-) 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), alpha- (n = 13), gamma- (n = 12), or delta- (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 alpha- and gamma-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: alpha-T3 0.98 +/- 0.80 micromol/l, gamma-T3 0.54 +/- 0.45 micromol/l, and delta-T3 0.09 +/- 0.07 micromol/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) alpha-T3 may be potent in decreasing LDL oxidizability.
authors.affiliation: Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: D
authors.initials: D
authors.lastname: O'Byrne
authors.forename: S
authors.initials: S
authors.lastname: Grundy
authors.forename: L
authors.initials: L
authors.lastname: Packer
authors.forename: S
authors.initials: S
authors.lastname: Devaraj
authors.forename: K
authors.initials: K
authors.lastname: Baldenius
authors.forename: P P
authors.initials: PP
authors.lastname: Hoppe
authors.forename: K
authors.initials: K
authors.lastname: Kraemer
authors.forename: I
authors.initials: I
authors.lastname: Jialal
authors.forename: M G
authors.initials: MG
authors.lastname: Traber
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D001055:Apolipoproteins B / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D014810:Vitamin E / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D000975:Antioxidants; D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D005609:Free Radicals; D008077:Lipoproteins, LDL; D014810:Vitamin E; D002784:Cholesterol