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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:687-696.)
© 1996 American Heart Association, Inc.

Articles

Cosupplementation With Coenzyme Q Prevents the Prooxidant Effect of -Tocopherol and Increases the Resistance of LDL to Transition Metal–Dependent Oxidation Initiation

Shane R. Thomas; Jií Neuil; Roland Stocker

From the Biochemistry Group, the Heart Research Institute, 145 Missenden Rd, Camperdown, Sydney, NSW, 2050, Australia.

Correspondence to Dr Roland Stocker, The Heart Research Institute, 145 Missenden Rd, Camperdown, Sydney, NSW 2050, Australia. E-mail r.stocker@hri.edu.au.

Abstract There is considerable interest in the ability of antioxidant supplementation, in particular with vitamin E, to attenuate LDL oxidation, a process implicated in atherogenesis. Since vitamin E can also promote LDL lipid peroxidation, we investigated the effects of supplementation with vitamin E alone or in combination with coenzyme Q on the early stages of the oxidation of isolated LDL. Isolated LDL was obtained from healthy subjects before and after in vitro enrichment with vitamin E (D--tocopherol, -TOH) or dietary supplementation with D--TOH (1 g/d) and/or coenzyme Q (100 mg/d). LDL oxidation initiation was assessed by measurement of the consumption of -TOH and cholesteryl esters containing polyunsaturated fatty acids and the accumulation of cholesteryl ester hydroperoxides during incubation of LDL in the transition metal–containing Ham's F-10 medium in the absence and presence of human monocyte-derived macrophages (MDMs). Native LDL contained 8.5±2 molecules of -TOH and 0.5 to 0.8 molecules of ubiquinol-10 (CoQ₁₀H₂, the reduced form of coenzyme Q) per lipoprotein particle. Incubation of this LDL in Ham's F-10 medium resulted in a time-dependent loss of -TOH with concomitant stoichiometric conversion of the major cholesteryl esters to their respective hydroperoxides. MDMs enhanced this process. LDL lipid peroxidation occurred via a radical chain reaction in the presence of -TOH, and the rate of this oxidation decreased on -TOH depletion. In vitro enrichment of LDL with -TOH resulted in an LDL particle containing sixfold to sevenfold more -TOH, and such enriched LDL was more readily oxidized in the absence and presence of MDMs compared with native LDL. In vivo -TOH–deficient LDL, isolated from a patient with familial isolated vitamin E deficiency, was highly resistant to Ham's F-10–initiated oxidation, whereas dietary supplementation with vitamin E restored the oxidizability of the patient's LDL. Oral supplementation of healthy individuals for 5 days with either -TOH or coenzyme Q increased the LDL levels of -TOH and CoQ₁₀H₂ by two to three or three to four times, respectively. -TOH–supplemented LDL was significantly more prone to oxidation, whereas CoQ₁₀H₂-enriched LDL was more resistant to oxidation initiation by Ham's F-10 medium than native LDL. Cosupplementation with both -TOH and coenzyme Q resulted in LDL with increased levels of -TOH and CoQ₁₀H₂, and such LDL was markedly more resistant to initiation of oxidation than native or -TOH–enriched LDL. These results demonstrate that oral supplementation with -TOH alone results in LDL that is more prone to oxidation initiation, whereas cosupplementation with coenzyme Q not only prevents this prooxidant activity of vitamin E but also provides the lipoprotein with increased resistance to oxidation.

Key Words: atherosclerosis • lipid hydroperoxides • macrophage • ubiquinone • vitamin E

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