CHINESE RED RICE DEPLETES MUSCLE COENZYME Q10 AND MAINTAINS MUSCLE DAMAGE AFTER DISCONTINUATION OF STATIN TREATMENT

To the Editor: Hyperlipidemia is a well-known risk factor for atherosclerosis, and its control is crucial in the prevention of cardiovascular diseases, especially when other risk factors, such as diabetes mellitus, hypertension, obesity, family history, or smoking, are present. In Western countries, the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) inhibitors, or statins, are used to decrease total cholesterol levels in hyperlipidemic subjects.1 They appear safe and well tolerated, but they can have muscle side effects, ranging from myalgias and cramps to muscle weakness and even myoglobinuria.2,3 The real incidence and the pathogenetic mechanisms of statin-induced myopathy, as well as its duration after discontinuation of the drug, are a matter of discussion.4 In the presence of adverse effects, alternative measures to control blood lipid levels include the use of so-called natural products. A 76-year-old man with type II diabetes mellitus had been taking statins at low dosage (20 mg/d) since the age of 72 (first simvastatin for 2 years, then atorvastatin for 2 years). Six months before referral, he began to complain of generalized muscle weakness. Laboratory analyses revealed a significant increase in serum creatine kinase (CK), peaking at 3,000 U/L, and the atorvastatin was discontinued. Although he reported a slight improvement in strength, hyperCKemia was 3,700 U/L after a drug-free period of 6 months, and the patient was referred to the Paolo Peirolo Center for Neuromuscular Diseases at the University of Turin. Family history was negative for neuromuscular disorders. Clinical examination was normal. Thyroid function, serum lactic acid, and immunological and rheumatological assays were normal. Electromyography was unremarkable. Open quadriceps muscle biopsy (Figure 1) demonstrated moderate fiber size variability and several atrophic and angular fibers with predominance of type II fibers. Oxidative enzyme activities, glycogen, and lipids were normally distributed. Immunohistochemical analysis and immunoblotting excluded alterations of dystrophin, sarcoglycans, merosin, emerin, caveolin, calpain, and dysferlin. Spectrophotometric assay disclosed no alterations of mitochondrial enzyme activities. Coenzyme Q10 levels determined in muscle homogenates were low (10.7 μg/g; controls 25±4.5 μg/g). Finally, the patient admitted that 3 months after discontinuing statins, he had replaced them with a Chinese product naturally derived from rice fermented with red yeast (Monascus purpureus). Three months after its withdrawal, the patient's symptoms definitively improved, and CK fell to 1,000 U/L. A. Hematoxylin and eosin stain demonstrates moderate size variability with atrophic and angular fibers (× 350).B. The ATPase reaction stain shows predominance of type II fibers (pH 4.55, × 150). Chinese red rice is an herbal preparation used in Chinese medicine that contains mevalonic acid and monacolin K. Like statins, it reduces cholesterol biosynthesis through direct inhibition of the hepatic HMG-CoA reductase. Currently, the United States Food and Drug Administration classifies it as a dietary supplement; in Italy it is marketed as a "natural statin" and sold over the counter. Because it has the same structure and activity as lovastatin, it should not be considered as an alternative hypocholesterolemic drug in patients with statin-induced muscle damage. Two cases of muscle damage directly related to red yeast rice have reported: one with rhabdomyolysis5 and another with hyperCKemia, pain and muscle weakness.6 The pathological mechanisms leading to muscle damage could be the same associated with statin myotoxicity; the decrease of Coenzyme Q10 (CoQ10-ubiquinone) could play an important role, with consequent dysfunction of the mitochondrial respiratory chain. Very low CoQ10 has been found in patients with statin myopathy (7 and unpublished data). In rodents, high doses of red yeast rice have been found to suppress hepatic and cardiac CoQ10.8 In this patient, CoQ10 in muscle tissue was low, confirming its possible role in determining muscle damage. Patients with statin-induced muscle damage should not be prescribed "natural" medications such as red yeast rice. Financial Disclosure: None. Author Contributions: Liliana Vercelli: participated in design of the study, search of relevant research papers, evaluation and elaboration of the results, and writing of the manuscript, and saw and approved the final version. Laura Palmucci: participated in design of the study, evaluation and elaboration of the results, and writing of the manuscript, and saw and approved the final version. Tiziana Mongini: participated in the design of the study, evaluation of muscle biopsy, and discussion of the manuscript, and saw and approved the final version. Nadia Olivero: participated in the research of relevant papers and the work-up of muscle biopsy and saw and approved the final version. Carmelo Rodolico: participated in the biochemical determination of CoQ10 and relevant research papers and saw and approved the final version. Olimpia Musumeci: performed the biochemical determination of CoQ10 in the patient, participated in the revision of the manuscript, and saw and approved the final version. Sponsor's Role: This study was partially supported by Grant ex-60% MIUR, but the sponsor had no role in the study.