Phytosterols, Red Yeast Rice, and Lifestyle Changes Instead of Statins

A Randomized, Double-Blinded, Placebo-Controlled Trial

David J. Becker, MD; Benjamin French, PhD; Patti B. Morris, RD; Erin Silvent, BA; Ram Y. Gordon, MD


Am Heart J. 2013;166(1):187-196. 

In This Article

Abstract and Introduction


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.


Statins (3-hydroxy-3-methyl-glutaryl coenzyme-A reductase inhibitors) are the most effective lipid-lowering medications for prevention of coronary artery disease.[1,2] They are generally well tolerated, but up to 40% of patients discontinue therapy within 1 year.[3,4] Reasons include fear of adverse effects, cost, and reluctance to take prescription medications. Despite physician recommendations, patients often adopt alternative therapies to manage their hypercholesterolemia.

Two popular lipid-lowering supplements are phytosterols and red yeast rice (RYR). Phytosterols, which include stanols and sterols, are present in plant-based foods and reduce low-density lipoprotein cholesterol (LDL-C) by decreasing intestinal absorption of cholesterol.[5] The average Western diet provides only 20 to 50 mg of phytosterols per day, but they are widely available in higher doses in tablet or capsule form and in "functional foods" such as margarine and yogurt. Phytosterols, in doses of 1600 to 3000 mg/d, may lower LDL-C by 4.1% to 15% compared with placebo.[6]

Red yeast rice is made by culturing a yeast, Monascus purpureus on rice. This produces compounds called monacolins that inhibit 3-hydroxy-3-methyl-glutaryl coenzyme-A reductase, the rate-limiting step in hepatic cholesterol synthesis. Studies have demonstrated the safety and efficacy of RYR, with LDL-C reductions of 22% to 28%.[7–9] Red yeast rice may also have a therapeutic role in patients with statin-associated myalgias (SAMs), described as muscle pain or weakness.[7,8]

Another important method to lower cholesterol is lifestyle modification. The combination of diet, exercise, and weight loss reduces LDL-C by 5% to 15%.[10]

We previously demonstrated that RYR combined with lifestyle change lowered LDL-C by 25%, but only 30% of participants achieved an LDL-C <100 mg/dL.[7] Evidence suggests that phytosterols significantly lower LDL-C when combined with statin therapy.[11] Because RYR has statin-like properties, in this trial, we added phytosterols to RYR and lifestyle changes to evaluate a nonprescription approach to lipid lowering in patients who refused statin therapy or had a history of statin intolerance.