title: Dose-response comparison of RRR-alpha-tocopherol and all-racemic alpha-tocopherol on LDL oxidation.
abstract: Much data have accrued in support of the concept that oxidation of LDL is a key early step in atherogenesis. The most consistent data with respect to micronutrient antioxidants and atherosclerosis appear to relate to alpha-tocopherol (AT), the predominant lipid-soluble antioxidant in LDL. There are scant data on the direct comparison of RRR-AT and all-racemic (rac)-AT on LDL oxidizability. Hence, the aim of the present study was to examine the relative effects of RRR-AT and all-rac-AT on plasma antioxidant levels and LDL oxidation in healthy persons in a dose-response study. The effect of RRR-AT and all-rac-AT at doses of 100, 200, 400, and 800 IU/d on plasma and LDL AT levels and LDL oxidation was tested in a randomized, placebo-controlled study of 79 healthy subjects. Copper-catalyzed oxidation of LDL was monitored by measuring the formation of conjugated dienes and lipid peroxides over an 8-hour time course at baseline and again after 8 weeks. Plasma AT, lipid-standardized AT, and LDL AT levels rose in a dose-dependent fashion in both the RRR-AT and all-rac-AT groups compared with baseline. There were no significant differences in plasma, lipid-standardized, and LDL AT levels between RRR-AT and all-rac-AT supplementation at any dose comparison. The lag phases of oxidation were significantly prolonged with doses > or = 400 IU/d of RRR-AT and all-rac-AT, as measured by conjugated-dienes assay and at 400 IU/d of RRR-AT and 800 IU/d of both forms of AT by lipid peroxide assay. Again, there were no significant differences in the lag phase of oxidation at each dose for RRR-AT when compared with all-rac-AT. Also, there were no significant differences in LDL oxidation after in vitro enrichment of LDL with RRR-AT and all-rac-AT. Thus, supplementation with either RRR-AT or all-rac-AT resulted in similar increases in plasma and LDL AT levels at equivalent IU doses, and the degree of protection against copper-catalyzed LDL oxidation was only evident at doses > or = 400 IU/d for both forms.
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235-9072, USA.
authors.forename: S
authors.initials: S
authors.lastname: Devaraj
authors.forename: B
authors.initials: B
authors.lastname: Adams-Huet
authors.forename: C J
authors.initials: CJ
authors.lastname: Fuller
authors.forename: I
authors.initials: I
authors.lastname: Jialal
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013237:Stereoisomerism; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D014810:Vitamin E