UMIN000001396.

Lovastatin is clinically used to treat patients with hypercholesterolemia and successfully lowers cholesterol levels. The mechanism of action of lovastatin is inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an enzyme involved in the biosynthesis of cholesterol from acetyl-CoA. Inhibition of this enzyme could also inhibit the intrinsic biosynthesis of coenzyme Q10 (CoQ10), but there have not been definitive data on whether lovastatin reduces levels of CoQ10 as it does cholesterol. The clinical use of lovastatin is to reduce a risk of cardiac disease, and if lovastatin were to reduce levels of CoQ10, this reduction would constitute a new risk of cardiac disease, since it is established that CoQ10 is indispensable for cardiac function. We have conducted three related protocols to determine whether lovastatin does indeed inhibit the biosynthesis of CoQ10. One protocol was done on rats, and is reported in the preceding paper [Willis, R. A., Folkers, K., Tucker, J. L., Ye, C.-Q., Xia, L.-J. & Tamagawa, H. (1990) Proc. Natl. Acad. Sci. USA 87, 8928-8930]. The other two protocols are reported here. One involved patients in a hospital, and the other involved a volunteer who permitted extraordinary monitoring of CoQ10 and cholesterol levels and cardiac function. All data from the three protocols revealed that lovastatin does indeed lower levels of CoQ10. The five hospitalized patients, 43-72 years old, revealed increased cardiac disease from lovastatin, which was life-threatening for patients having class IV cardiomyopathy before lovastatin or after taking lovastatin. Oral administration of CoQ10 increased blood levels of CoQ10 and was generally accompanied by an improvement in cardiac function. Although a successful drug, lovastatin does have side effects, particularly including liver dysfunction, which presumably can be caused by the lovastatin-induced deficiency of CoQ10.

The present study investigated the association of lifestyles to periodontal health status of workers in a manufacturing company in Japan. In a annual health checkup, periodontal health status was assessed by using the Community Periodontal Index (CPI) criteria and analysed by modified Miller's CPI score. Lifestyle information was also obtained by a self-administered questionnaire. Bivariate and multivariate analyses were used to examine the relationship between lifestyle and oral health care variables and 2 indicators of periodontal health status. These were the modified Miller's CPI score and the probability of subjects in the upper 25th percentile of CPI distribution as an indicator of poor periodontal health. The modified Miller's CPI score was found to increase with age, but to vary according to the workers' lifestyles. In bivariate analyses, significant variables were age, smoking, alcohol consumption, toothbrushing frequency, toothbrushing method, and use of interdental cleaners. In multivariate analyses, age, smoking, and use of interdental cleaners had significantly independent effects. Amount of smoking or alcohol consumption was associated with periodontal health status. Excessive use of alcohol may contribute to the development of periodontal disease, although further investigations are required to confirm this finding. The data from this study indicate that lifestyles which include smoking and insufficient oral health care have an independent association with periodontal disease.

Lovastatin is used for the treatment of hypercholesterolemia. It functions by inhibiting the enzyme, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 1.1.1.34), that is required for the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonic acid. Since biosynthesis of both cholesterol and coenzyme Q (CoQ) requires mevalonic acid as a precursor, it was considered that lovastatin therapy would also result in a lowering of cellular CoQ levels. This study was conducted to determine whether lovastatin treatment does decrease CoQ levels and whether such decreases can be prevented by CoQ supplementation. Forty-five adult male Holtzman rats were randomly assigned to one of three treatment groups. Controls were fed ground laboratory rat chow ad libitum. The other two groups were fed ground laboratory rat chow containing 400 mg of lovastatin per kg of diet ad libitum. One of the lovastatin-fed groups received CoQ10 (15 mg per kg of body weight) daily via stomach intubation. After 4 weeks, samples of heart, liver, and blood were analyzed for CoQ concentrations. Results indicated that CoQ concentrations in all tissues analyzed were decreased in lovastatin-treated rats. Lovastatin-treated animals that were supplemented with CoQ10 had blood, heart, and liver CoQ10 CoQ10 (the subscript indicates the number of isoprene units in the side chain) is an important participant in electron transport in the respiratory chain in mammalian mitochondria (2-9). Evidence has been accumulating over the last two decades that this coenzyme may be important in a variety of clinical conditions. Essential hypertension, periodontal disease, lichen planus, doxorubicin-induced cardiotoxicity, cardiac output in heart patients, renal ischemia survival, and hepatic damage by antineoplastic drugs (mitomycin C and 5-fluorouracil dry syrup) have been reported to improve or be mitigated by CoQ10 treatment (10-24). It is likely and very important that some, if not most, of the side effects associated with the use of lovastatin in treatment of hypercholesterolemia are due to a decrease in CoQ10 levels.Known side effects of lovastatin include marked, persistent increases in serum transaminases, myalgia, myositis, increased creatine kinase levels, renal failure, and, in mice, tumors of liver, lung, and stomach (2). Therefore, it is plausible that many of the side effects associated with the use of lovastatin in treatment of hypercholesterolemia are due to a decrease in CoQ10 levels.This study in the rat model was undertaken to determine whether lovastatin treatment does indeed decrease CoQ levels and whether such decreases can be prevented by CoQ supplementation. METHODSForty-five adult male Holtzman rats were randomly assigned to one of three treatment groups (15 rats per group). Group I (controls) were fed ground laboratory rat chow (Purina) ad libitum. Groups II (lovastatin treatment group) and III (lovastatin plus CoQ treatment group) were fed ground laboratory rat chow containing 400 mg of lovastatin per kg of diet ad libitum. The lov...