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: D O'Byrne, S Grundy, L Packer, S Devaraj, K Baldenius, P P Hoppe, K Kraemer, I Jialal, M G Traber
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 29 Issue 9 Pg. 834-45 (Nov 01 2000) ISSN: 0891-5849 [Print] United States
• PMID: 11063909 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antioxidants
• Apolipoproteins B
• Cholesterol, LDL
• Free Radicals
• Lipoproteins, LDL
• Vitamin E
• Cholesterol

Topics

• Adult
• Antioxidants (therapeutic use)
• Apolipoproteins B (blood)
• Cholesterol (blood)
• Cholesterol, LDL (blood)
• Double-Blind Method
• Female
• Free Radicals (metabolism)
• Humans
• Hypercholesterolemia (blood, drug therapy, metabolism)
• In Vitro Techniques
• Lipoproteins, LDL (metabolism)
• Male
• Middle Aged
• Oxidation-Reduction
• Vitamin E (analogs & derivatives, blood)