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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 α-tocopherol (AT), the predominant lipid-soluble antioxidant in LDL. There are scant data on the direct comparison ofRRR -AT and all-racemic (rac) -AT on LDL oxidizability. Hence, the aim of the present study was to examine the relative effects ofRRR -AT and all-rac -AT on plasma antioxidant levels and LDL oxidation in healthy persons in a dose-response study. The effect ofRRR -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 theRRR -AT and all-rac -AT groups compared with baseline. There were no significant differences in plasma, lipid-standardized, and LDL AT levels betweenRRR -AT and all-rac -AT supplementation at any dose comparison. The lag phases of oxidation were significantly prolonged with doses ≥400 IU/d ofRRR -AT and all-rac -AT, as measured by conjugated-dienes assay and at 400 IU/d ofRRR -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 forRRR -AT when compared with all-rac -AT. Also, there were no significant differences in LDL oxidation after in vitro enrichment of LDL withRRR -AT and all-rac -AT. Thus, supplementation with eitherRRR -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 ≥400 IU/d for both forms.

Dose-Response Comparison of RRR -α-Tocopherol and All-Racemic α-Tocopherol on LDL Oxidation