Phytosterols, red yeast rice, and lifestyle changes instead of statins: a randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Many patients who refuse or cannot tolerate statin drugs choose alternative therapies for lipid lowering. OBJECTIVES: This study aimed to determine the lipid-lowering effects of phytosterol tablets and lifestyle change (LC) on top of red yeast rice (RYR) therapy in patients with a history of statin refusal or statin-associated myalgias. DESIGN: A total of 187 participants (mean low-density lipoprotein cholesterol [LDL-C], 154 mg/dL) took RYR 1800 mg twice daily and were randomized to phytosterol tablets 900 mg twice daily or placebo. Participants were also randomized to a 12-week LC program or usual care (UC). Primary end point was change in LDL-C at 12, 24, and 52 weeks. Secondary end points were effect on other lipoproteins, high-sensitivity C-reactive protein, weight, and development of myalgia. RESULTS: Phytosterols did not significantly improve LDL-C at weeks 12 (P = .54), 24 (P = .67), or 52 (P = .76) compared with placebo. Compared with the UC group, the LC group had greater reductions in LDL-C at weeks 12 (-51 vs -42 mg/dL, P = .006) and 24 (-48 vs -40 mg/dL, P = .034) and was 2.3 times more likely to achieve an LDL-C <100 mg/dL (P = .004). The LC group lost more weight for 1 year (-2.3 vs -0.3 kg, P < .001). All participants took RYR and had significant decreases in LDL-C, total cholesterol, triglycerides, high-sensitivity C-reactive protein, and an increase in high-density lipoprotein cholesterol for 1 year when compared with baseline (P < .001). Four participants stopped supplements because of myalgia. CONCLUSIONS: The addition of phytosterol tablets to RYR did not result in further lowering of LDL-C levels. Participants in an LC program lost significantly more weight and were more likely to achieve an LDL-C <100 mg/dL compared with UC.

The role of red yeast rice for the physician.

Red yeast rice is an ancient Chinese dietary staple and medication used by millions of patients as an alternative therapy for hypercholesterolemia. In recent years, the use of red yeast rice has grown exponentially due to increased public interest in complementary and alternative medications and the publication of several randomized, controlled trials demonstrating its efficacy and safety in different populations. The most promising role for red yeast rice is as an alternative lipid-lowering therapy for patients who refuse to take statins because of philosophical reasons or patients who are unable to tolerate statin therapy due to statin-associated myalgias. However, there is limited government oversight of red yeast rice products, wide variability of active ingredients in available formulations, and the potential of toxic byproducts. Therefore, until red yeast rice products are regulated and standardized, physicians and patients should be cautious in recommending this promising alternative therapy for hyperlipidemia.

Marked variability of monacolin levels in commercial red yeast rice products: buyer beware!

BACKGROUND: Red yeast rice (RYR) is a widely available dietary supplement used by millions of patients as an alternative therapy for hyperlipidemia. It contains 14 active compounds called monacolins that inhibit hepatic cholesterol synthesis. Although studies have suggested that some formulations of RYR may be effective and safe for lipid lowering, monacolin levels are not standardized among marketed products and are generally not published on labels. We evaluated monacolin levels in 12 commercial RYR formulations and tested for citrinin, a mycotoxin that is nephrotoxic in animals. METHODS: Each formulation of RYR was labeled "600 mg/capsule" of active product. Analyses for monacolins and citrinin were performed between August 2006 and June 2008 using high-performance liquid chromatography with mass spectroscopy-mass spectroscopy detection. Laboratory analyses of RYR products were conducted by ConsumerLab.com, White Plains, New York. RESULTS: There was marked variability in the 12 RYR products in total monacolins (0.31-11.15 mg/capsule), monacolin K (lovastatin) (0.10-10.09 mg/capsule), and monacolin KA (0.00-2.30 mg/capsule). Four products had elevated levels of citrinin. CONCLUSIONS: We found striking variability in monacolin content in 12 proprietary RYR products and the presence of citrinin in one-third of the formulations tested. Although RYR may have potential as an alternative lipid-lowering agent, our findings suggest the need for improved standardization of RYR products and product labeling. Until this occurs, physicians should be cautious in recommending RYR to their patients for the treatment of hyperlipidemia and primary and secondary prevention of cardiovascular disease.

Tolerability of red yeast rice (2,400 mg twice daily) versus pravastatin (20 mg twice daily) in patients with previous statin intolerance.

Currently, no consensus has been reached regarding the management of hyperlipidemia in patients who develop statin-associated myalgia (SAM). Many statin-intolerant patients use alternative lipid-lowering therapies, including red yeast rice. The present trial evaluated the tolerability of red yeast rice versus pravastatin in patients unable to tolerate other statins because of myalgia. The study was conducted in a community-based setting in Philadelphia, Pennsylvania. A total of 43 adults with dyslipidemia and a history of statin discontinuation because of myalgia were randomly assigned to red yeast rice 2,400 mg twice daily or pravastatin 20 mg twice daily for 12 weeks. All subjects were concomitantly enrolled in a 12-week therapeutic lifestyle change program. The primary outcomes included the incidence of treatment discontinuation because of myalgia and a daily pain severity score. The secondary outcomes were muscle strength and plasma lipids. The incidence of withdrawal from medication owing to myalgia was 5% (1 of 21) in the red yeast rice group and 9% (2 of 22) in the pravastatin group (p = 0.99). The mean pain severity did not differ significantly between the 2 groups. No difference was found in muscle strength between the 2 groups at week 4 (p = 0.61), week 8 (p = 0.81), or week 12 (p = 0.82). The low-density lipoprotein cholesterol level decreased 30% in the red yeast rice group and 27% in the pravastatin group. In conclusion, red yeast rice was tolerated as well as pravastatin and achieved a comparable reduction of low-density lipoprotein cholesterol in a population previously intolerant to statins.

Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized trial.

BACKGROUND: Red yeast rice is an herbal supplement that decreases low-density lipoprotein (LDL) cholesterol level. OBJECTIVE: To evaluate the effectiveness and tolerability of red yeast rice and therapeutic lifestyle change to treat dyslipidemia in patients who cannot tolerate statin therapy. DESIGN: Randomized, controlled trial. SETTING: Community-based cardiology practice. PATIENTS: 62 patients with dyslipidemia and history of discontinuation of statin therapy due to myalgias. INTERVENTION: Patients were assigned by random allocation software to receive red yeast rice, 1800 mg (31 patients), or placebo (31 patients) twice daily for 24 weeks. All patients were concomitantly enrolled in a 12-week therapeutic lifestyle change program. MEASUREMENTS: Primary outcome was LDL cholesterol level, measured at baseline, week 12, and week 24. Secondary outcomes included total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, liver enzyme, and creatinine phosphokinase (CPK) levels; weight; and Brief Pain Inventory score. RESULTS: In the red yeast rice group, LDL cholesterol decreased by 1.11 mmol/L (43 mg/dL) from baseline at week 12 and by 0.90 mmol/L (35 mg/dL) at week 24. In the placebo group, LDL cholesterol decreased by 0.28 mmol/L (11 mg/dL) at week 12 and by 0.39 mmol/L (15 mg/dL) at week 24. Low-density lipoprotein cholesterol level was significantly lower in the red yeast rice group than in the placebo group at both weeks 12 (P < 0.001) and 24 (P = 0.011). Significant treatment effects were also observed for total cholesterol level at weeks 12 (P < 0.001) and 24 (P = 0.016). Levels of HDL cholesterol, triglyceride, liver enzyme, or CPK; weight loss; and pain severity scores did not significantly differ between groups at either week 12 or week 24. LIMITATION: The study was small, was single-site, was of short duration, and focused on laboratory measures. CONCLUSION: Red yeast rice and therapeutic lifestyle change decrease LDL cholesterol level without increasing CPK or pain levels and may be a treatment option for dyslipidemic patients who cannot tolerate statin therapy.

Simvastatin vs therapeutic lifestyle changes and supplements: randomized primary prevention trial.

OBJECTIVE: To compare the lipid-lowering effects of an alternative regimen (lifestyle changes, red yeast rice, and fish oil) with a standard dose of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin). PATIENTS AND METHODS: This randomized trial enrolled 74 patients with hypercholesterolemia who met Adult Treatment Panel III criteria for primary prevention using statin therapy. All participants were randomized to an alternative treatment group (AG) or to receive simvastatin (40 mg/d) in this open-label trial conducted between April 1, 2006, and June 30, 2006. The alternative treatment included therapeutic lifestyle changes, ingestion of red yeast rice, and fish oil supplements for 12 weeks. The simvastatin group received medication and traditional counseling. The primary outcome measure was the percentage change in low-density lipoprotein cholesterol (LDL-C). Secondary measures were changes in other lipoproteins and weight loss. RESULTS: There was a statistically significant reduction in LDL-C levels in both the AG (-42.4%+/-15%) (P<.001) and the simvastatin group (-39.6%+/-20%) (P<.001). No significant differences were noted between groups. The AG also demonstrated significant reductions in triglycerides (-29% vs -9.3%; 95% confidence interval, -61 to -11.7; P=.003) and weight (-5.5% vs -0.4%; 95% confidence interval, -5.5 to -3.4; P<.001) compared with the simvastatin group. CONCLUSION: Lifestyle changes combined with ingestion of red yeast rice and fish oil reduced LDL-C in proportions similar to standard therapy with simvastatin. Pending confirmation in larger trials, this multifactorial, alternative approach to lipid lowering has promise for a subset of patients unwilling or unable to take statins.