Modification of low-density lipoprotein (LDL) particles is an integral part of atherogenesis. It may take place enzymatically or through an oxidation cascade, which leads to oxidative modification of the LDL particle and its accumulation into monocyte-derived macrophages in the arterial intima. Alpha-tocopherol (á TOH) behaves as antioxidant during an attack with plenty of free radicals but pro-oxidatively during low radical flux. Ubiquinol is the first line antioxidant in the outer surface layer of LDL. It can be regenerated from its oxidised form ubiquinone. It is synthesised via the same pathway as cholesterol. Hence, the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) not only decrease plasma cholesterol but also the level of ubiquinol in LDL particles.

Altogether 104 patients with coronary heart disease participated and completed at least one study concentrating on the effects of different treatments on the susceptibility of LDL to oxidation. Effects of preventive group education, lovastatin, and ubiquinone supplementation were analysed.

On the average of three years after coronary bypass grafting, 72 patients participated in a controlled parallel study with a follow-up of one year. The effect of preventive group education was investigated by LDL TRAP (Total Radical Antiperoxiding capacity in LDL), a method using the azo compound 2,2-azobis(2,4-dimethylvaleronitrile) (AMVN) as a radical generator. A significant although transient increase was observed in the resistance of LDL against oxidation. Eight months after preventive education, the difference between the intervention group and the control group was 25% reflecting an almost parallel change in leisure time physical activity. However, LDL TRAP did not differ between the groups after one year. There was a significant difference of 1.2 kg in the body weight in favour of the intervention group after one year. Also circulating white blood cell count decreased in the intervention group, possibly suggesting lower degree of inflammation compared to controls. No clinically significant changes were observed in dietary habits or lipid values.

In a methodological study with 10 patients, LDL TRAP was compared with the lag time to the propagated formation of conjugated dienes, a measurement generally used to study the resistance of LDL against copper-mediated oxidation. Both methods revealed an evident improvement in the antioxidative capacity of LDL during á TOH supplementation, but the results after lovastatin therapy were incoherent.

In all 32 men participated in two double-blind, placebo-controlled cross-over studies, where effects of lovastatin (20 mg three times daily) therapy were studied with or without á TOH supplementation. Mean LDL cholesterol level in serum decreased significantly by 44%, apolipoprotein B-100 by 33%, triglycerides by 30%, while HDL cholesterol and apolipoprotein A-1 increased by 16% and 7%, respectively. Lovastatin shortened the consumption time of both ubiquinol and á TOH during oxidation induced by AMVN in average by 17% and 41%, respectively. According to the copper-mediated oxidation assay, the lag time shortened statistically significantly by 7%. The maximal amount of conjugated dienes tended to be decreased by lovastatin. Hence, lovastatin had both anti- and pro-oxidative effects on the resistance of LDL against oxidation.

The effect of ubiquinone supplementation during lovastatin therapy was assessed in a doubleblind, placebo-controlled cross-over study with 19 male subjects. Dietary ubiquinone (60 mg three times daily) prolonged the depletion time of LDL ubiquinol significantly but not that of á TOH during oxidation induced by AMVN. In copper-mediated oxidation of LDL, ubiquinone supplementation was followed by a prolongation of the lag time.

In conclusion, preventive education may improve the resistance of LDL against oxidation through life style changes. Because of the scarce effect of education on the lipid values, initiation of statin therapy should not be delayed while waiting for results of repeated preventive counselling. Lovastatin therapy had both anti- and pro-oxidative effects on LDL, and dietary ubiquinone improved the resistance of LDL against the early phase of oxidation during statin therapy. At the moment, routine ubiquinone supplementation has yet no prognostic indication for patients on statin therapy.