Methodist Journal



The Burgeoning Field of Cardio-Oncology

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Barry H. Trachtenberg Leads Issue on Cardio-Oncology

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Heart Failure in Relation to Anthracyclines and Other Chemotherapies

Heart Failure in Relation to Tumor-Targeted Therapies and Immunotherapies

The Role of Cardiovascular Imaging and Serum Biomarkers in Identifying Cardiotoxicity Related to Cancer Therapeutics

Prevention and Treatment of Chemotherapy-Induced Cardiotoxicity

Cardiovascular Toxicities of Radiation Therapy

Electrophysiologic Complications in Cancer Patients

Vascular Toxicity in Patients with Cancer: Is There a Recipe to Clarify Treatment?

Future Directions in Cardio-Oncology


A Rare Case of Pancreatitis-Induced Thrombosis of the Aorta and Superior Mesenteric Artery

Anomalous Origin of the Right Coronary Artery from the Left Main Coronary Artery in the Setting of Critical Bicuspid Aortic Valve Stenosis

Simultaneous Transfemoral Mitral and Tricuspid Valve in Ring Implantation: First Case Report with Edwards Sapien 3 Valve

Uneventful Follow-Up 2 Years after Endovascular Treatment of a High Flow Iatrogenic Aortocaval Fistula Causing Pulmonary Hypertension and Right Heart Failure


Do Not Pass Flow: Microvascular Obstruction on Cardiac Magnetic Resonance After Reinfarction Following Primary Percutaneous Coronary Intervention



Cardio-Oncology, Then and Now: An Interview with Barry Trachtenberg


Onconephrology: An Evolving Field


Herbal Nephropathy


Rolling the Dice on Red Yeast Rice


Letter to the Editor in Response to “Cardiac Autonomic Neuropathy in Diabetes Mellitus”

Vol 15, Issue 3 (2019)

Article Full Text


Red Yeast Rice for Hypercholesterolemia

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Article Citation:

Cicero AFG, Fogacci F, Banach M. Red Yeast Rice for Hypercholesterolemia. Methodist DeBakey Cardiovasc J. 2019;15(3):192-9.


The extract of red yeast rice (RYR) is the most effective cholesterol-lowering nutraceutical on the market. In particular, its effectiveness is directly related to the amount of monacolin K within the extract (up to 10 mg/day). Consuming monacolin K on a daily basis reduces low-density lipoprotein (LDL) cholesterol plasma levels between 15% and 25% within 6 to 8 weeks. Certainly, the decrease in LDL-cholesterol is accompanied by a similar reduction in total cholesterol, non–high-density lipoprotein cholesterol, plasma apolipoprotein B, matrix metalloproteinases 2 and 9, and high-sensitivity C-reactive protein. Furthermore, the RYR lipid-lowering effect is associated with significant improvements in pulse wave velocity and endothelial function, which are validated and reliable biomarker tools able to detect vascular aging. Although it has a mechanism of action similar to statins, a daily consumption of between 3 and 10 mg monacolin K has only minimal associated risks, and mild myalgias are seen only in the frailest patients (those who also cannot tolerate minimal dosages of statin). The monacolin K  found in RYR is a safe and effective supplement for managing mild to moderate hypercholesterolemia in people with no additional cardiovascular risk factors.

red yeast rice , monacolin k , nutraceutical , lipid-lowering supplement


Among the modifiable cardiovascular (CV) risk factors, high levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are the most important for the development of coronary heart disease (CHD).1 The recent American Heart Association 2016 update on Heart Disease and Stroke Statistics once again verified that only 75.7% of US children and 46.6% of US adults present targeted TC levels (< 170 mg/dL for untreated children and < 200 mg/dL for untreated adults), a trend that is comparable to other Western countries.2,3Current treatment involves lifestyle changes such as diet and exercise and may include lipid-lowering therapy, depending on the severity of dyslipidemia and CV risk.4 Specific lifestyle interventions for hypercholesterolemia include a diet low in saturated fat (< 7% of total energy), such as the Mediterranean diet and DASH (Dietary Approaches to Stop Hypertension). These and other diets high in fruits, vegetables, whole grains, nuts, low-fat dairy products, poultry, and fish, with limited portions of lean red meat and sugary foods and beverages, are the most recommended.5 Other lifestyle changes include moderate- to high-intensity physical activity (? 150 min/week), weight loss of 5% to 10% for overweight or obese patients, and smoking cessation, including avoidance of passive tobacco smoke.6  If maintained over the long-term, these lifestyle modifications can reduce LDL-C and non–high-density lipoprotein cholesterol (HDL-C) levels by 5% to 15% and may even significantly reduce the risk of CVD.7 Patients unable to reach their target cholesterol goals through lifestyle interventions should consider using lipid-lowering nutraceuticals. These can be taken alone or in conjunction with pharmacological therapy, which is indicated for those with out-of-target lipid values or who are intolerant to statins.8 It is in this context that we review the available clinical evidence on the efficacy and safety of red yeast rice (RYR) extract, a widely used and effective nutraceutical with a lipid-lowering effect.9


The nutraceutical RYR is created by fermenting yeast (eg, Monascus purpureus, M. pilosus, M. floridanus, M. ruber and, more recently, Pleurotus ostreatus) in red rice (Oryza sativa); the typical red coloration is due to the presence of pigments produced by secondary fermentation.

Figure 1. Main cholesterol-lowering mechanism of action of red yeast rice.

Red yeast rice contains 25% to 73% sugars (starch in particular), 14% to 31% proteins, 2% to 7% water, 1% to 5% fatty acids, sterols, isoflavones, pigments such as rubropunctamine and monascorubramine, and polyketides.10 The fermentation of yeast and rice produces a complex of substances called monacolins that have recognized lipid-lowering qualities. The concentration of monacolins in the most commonly used RYR nutraceuticals usually reaches up to 1.9%.11 Several types of monacolins have been identified based on the strain of yeast used and the fermentation conditions. One of these subtypes is monacolin K, which was first isolated by Professor Akira Endo and found to be structurally identical to lovastatin.12 Its primary mechanism of action is to inhibit 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, the rate-controlling enzyme of the cholesterol synthesis pathway (Figure 1).

Although monacolin K and lovastatin have the same structure, their pharmacokinetic profiles and bioavailability are different. Lovastatin is administered as a single active ingredient with 31% bioavailability in humans, whereas monacolin K is only one of several RYR components that can change the pharmacokinetic profile of lovastatin. The chemical structure of monacolin K also highlights the possible differences in pharmacokinetics and efficacy compared to lovastatin since there are strong variations in the lactone-to-acid ratio. In particular, the better-absorbed acid form ranges from 5% to 100% of total monacolin K—depending on the product—and greatly influences the molecule’s bioavailability. The lactone ring opening can occur under alkaline conditions or can be enzymatically hydrolyzed in the small intestine and by the liver cytochrome P450 (CYP450) 3A family.13


Several meta-analyses of randomized controlled clinical trials (RCTs) have verified the lipid-lowering effects of RYR. The most recent, by Gerard et al., included 20 studies with RYR doses varying between 1,200 mg and 4,800 mg/day and containing from 4.8 mg to 24 mg of monacolin K. The meta-analysis demonstrated that RYR reduced LDL-C by an average of 1.02 mmol/L (39.4 mg/dL) after 2 to 24 months of treatment compared to placebo. This effect on LDL lowering was not different from moderate-intensity statins (0.03 mmol/L) such as pravastatin 40 mg and lovastatin 20 mg. The authors also found a small increase in HDL-C (0.07 mmol/L) and a decrease in triglycerides (TG) of 0.26 mmol/L compared to placebo.14

Red yeast rice has also been shown to improve endothelial function in humans. In a clinical trial by Zhao and colleagues, 50 patients with CHD were randomized to 1,200 mg/day of RYR (containing 11.4 mg monacolin K) or placebo for 6 weeks and were monitored for lipid levels, high sensitivity C-reactive protein (hsCRP), and flow-mediated dilation (FMD) after consuming high-fat meals (50 g). At 6 weeks follow-up, those receiving RYR showed reductions in hsCRP and in the total area under the TG curve (TG-AUC) (P < .001 for both) as well as improved post- and pre-prandial FMD (P < .001), whereas the placebo group showed no significant changes in serum lipids and FMD.15 However, significant improvements in endothelial reactivity (measured as pulse volume displacement) and arterial stiffness have been documented by adding 30 mg coenzyme Q10 (CoQ10) or a mix of other antioxidants such as 100 mg green tea dry extract, 20 mg CoQ10, and 20 mg resveratrol to RYR extract.16,17

Red yeast rice is a rare example of a nutraceutical that has been evaluated in some long-term studies for its effect on CV outcomes. In a trial from China involving 1,445 patients aged 65 to 75 years, all with a history of myocardial infarction, those receiving RYR supplementation over a 4-year period had a reduced risk of CHD (31%), all-cause mortality (31.9%), stroke (44.1%), the need for coronary artery bypass graft or a percutaneous coronary intervention (48.6%), and malignancies (51.4%) compared to placebo. Death from coronary heart disease was 6.4% in those receving RYR and 9% in those receiving placebo, indicating that RYR significantly decreased the risk of CHD death by 29.2%; however, no long-term studies have specifically evaluated the effect of RYR on CVD mortality as a primary end point. The same study also estimated that 18, 33, and 23 elderly patients ? 65 years old or 23, 82, and 51 adults would need to be treated with RYR supplementation over those 4 years to prevent one coronary event, one coronary death, and one all-cause death, respectively.18


As recently suggested by the International Lipid Expert Panel, consuming combinations of nutraceuticals with different lipid-lowering actions, especially in conjunction with a healthy lifestyle, could be a valid alternative for preventing CHD in patients with moderate hypercholesterolemia and, in some cases, with statin intolerance.19,20 In particular, the interaction between RYR and natural products with different mechanisms of action may have a synergetic effect. For example, RYR inhibiting the HMG-CoA reductase enzyme might be advantageously coupled with other nutraceuticals to increase lipid excretion in the bowel (plant sterols, soluble fibers, probiotics, glucomannan), enhance the hepatic uptake of cholesterol (soybean proteins, berberine), or induce LDL-C excretion (chlorogenic acid, soy proteins, berberine).21

Red Yeast Rice and Policosanols

Several studies have evaluated the efficacy and safety of RYR in combination with policosanols, a mixture of aliphatic alcohols derived from purified sugar cane.22 Cicero et al. administered RYR extract (340 mg containing 5 mg of monacolin K) combined with octacosanols (10 mg) to 111 patients with normal/borderline triglyceridemia, moderate hypercholesterolemia, and low risk for CVD (< 20% by Framingham Risk Score). After 2 months of treatment, LDL-C was reduced by an average of 20% without any serious safety concerns, a result similar to that seen in patients treated with pravastatin 20 mg/day.23

In a different placebo-controlled clinical study, 240 patients with an overall coronary risk < 20% and primary-moderate hypercholesterolemia were treated with RYR extract (200 mg, corresponding to 3 mg of monacolin K) combined with linear aliphatic alcohols (10 mg). At 4 months of follow-up, patients had experienced a 29% reduction in LDL-C and 26% reduction in non–HDL-C.24

Red yeast rice (200 mg, corresponding to 3 mg of monacolin K) combined with policosanol (10 mg) was also evaluated in 1,665 adult and 743 elderly patients in a large, single-blind, randomized, multicenter study that compared the metabolic effect of nutraceuticals plus diet versus diet alone. At 16-week follow-up, patients had experienced a 21% reduction in LDL-C and 13% improvement in HDL-C with no significant change in TG levels.25

Beneficial results were also obtained in 40 children affected by heterozygous familial hypercholesterolemia or familial combined hyperlipidemia. In a randomized, double-blind, placebo-controlled, cross-over trial, patients received either placebo or a dietary supplement of RYR extract (200 mg, corresponding to 3 mg of monacolins) and policosanols (10 mg). After 8 weeks, the treatment was determined to be effective, safe, and well tolerated, with those receiving the RYR combination showing an 18.5% reduction in total cholesterol, a 25.1% reduction in LDL-C, and a 25.3% reduction in apolipoprotein B.26

Red Yeast Rice, Policosanols, and Berberine

The lipid-lowering properties of RYR (3 mg monacolin K) combined with policosanols (10 mg) and berberine (500 mg) is the most-studied association and the one for which meta-analyses of RCTs are available. Data from a recent meta-analysis of 14 RCTs involving 3,159 subjects indicated that the RYR-policosanol-berberine association can improve LDL-C by 23.6 mg/dL, HDL-C by 2.71 mg/dL, TG by 14.2 mg/dL, and glucose by 2.52 mg/dL—with improvements in lipid and glucose profiles maintained in the long-term.27 This combination was also found to be safe and well tolerated in 80% of adult and elderly patients who were previously intolerant to statin treatment.28

De Castro-Orós et al. investigated the genetic variants of LDL receptor (LDLR) and proprotein convertase subtilsin-kexin type 9 (PCSK9) and their role in the variations of responses to this RYR-policosanol-berberine supplement and determined that they may be linked to three polymorphisms in the 3’ UTR region of LDLR and two at the 5’ UTR region of PCSK9. These results may explain the variable responses among patients with moderate hypercholesterolemia and may be useful in identifying subjects who could potentially benefit the most from this supplementation.29 Other studies of this nutraceutical combination found that it improved endothelial function and pulse wave velocity in dyslipidemic patients30 and was as effective as moderate-dose statins in lowering LDL-C in patients with primary hypercholesterolemia and a history of statin intolerance or refusal of statin treatment.31

Red Yeast Rice and Plant Sterols

In a study by Feuerstein and Bjerke, 18 patients with hypercholesterolemia received a nutraceutical product of RYR 1,200 mg (titration in monacolin K not reported) and phytosterols 1,250 mg daily and showed a 33% reduction of LDL-C after 6 weeks of treatment.32 This effect was confirmed in a double-blind, placebo-controlled RCT evaluating a similar RYR-phytosterol combination in 90 hypercholesterolemic subjects, showing 27% and 19% reductions in LDL-C and apolipoprotein B, respectively.

Red Yeast Rice and Artichoke

Some clinical trials have evaluated the combination of RYR (166.67 mg, 0.4% monacolin K), artichoke leaf extracts (200 mg, 5%-6% chlorogenic acid) and sugarcane-derived policosanols (3.70 mg, 90% policosanols; 60% octacosanol) taken 3 times daily and its effect on lipid and inflammatory parameters. In a randomized, double-blind, controlled study involving 39 mildly hypercholesterolemic patients, there was a 21.4% reduction in LDL-C  and a 12.2% reduction in TG after 16 weeks.34 In a similar study of 100 patients, the authors reported a 14.3% reduction in LDL-C and improvements in total cholesterol, apoB100, and apoB100/apoA-I ratio without any effect on safety.35 Although there were no safety concerns when the authors conducted another study that doubled the dose, the higher dosage did not result in additional benefit.36

The association of RYR (200 mg, containing monacolin K 10 mg), artichoke extract (500 mg), and banaba extract (50 mg) was recently evaluated for primary prevention of CVD in a trial involving 30 adults with suboptimal LDL-C levels. Patients were treated for 6 weeks with the tested nutraceutical compound or placebo and assigned to the second sequence of the study after 2 weeks of wash out. The treatment led to improvements in LDL-C (-18.2%), non–HDL-C (-15%), glutamic oxaloacetic transaminase (-10%), glutamate-pyruvate transaminase (-30.9%), and hs-CRP (-18.2%) compared to placebo, while no changes were observed in the other investigated parameters.37


A double-blind, placebo-controlled trial involving 134 low-risk dislipidemic patients studied the effects of RYR (334 mg, 10 mg monacolin), policosanol (30 mg), and silymarin (150 mg) on lipid profile and endothelial and inflammatory parameters. After 3 months of treatment, LDL-C in the treated group decreased compared with baseline (P = .041) and placebo (P = .037) while triglycerides decreased compared with baseline (P = .039) but not with placebo (P = .061). All tested inflammatory parameters (ie, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-selectin, MMP-2 and -9, hs-CRP, IL-6 and TNF-alpha) decreased in the treated group.38

The same nutraceutical compound was tested by another research group in an 8-week randomized clinical trial of 80 hypercholesterolemic patients. Compared to placebo, those receiving the active treatment experienced significant improvements in LDL-C (-23.3%), hs-CRP (-2.4%), and endothelial function (pulse volume displacement vs baseline: +17%) but no significant differences in TG, HDL-C, and safety parameters.39


Cicero et al. tested the efficacy of RYR (5 mg monacolin K) and omega-3 polyunsaturated fatty acids (183 mg EPA, 122 mg DHA) for primary prevention of CVD in 107 untreated patients with polygenic hypercholesterolemia and metabolic syndrome. Patients experienced significant decreases in LDL-C (-22% ± 3%), TG (-9% ± 5%), and non–HDL-C (-21% ± 3%) and a significant increase in HDL-C (+1.5% ± 0.5%) after 8 weeks of treatment, with no changes in safety parameters. Furthermore, 75% of patients achieved an LDL-C target < 160 mg/dL and 25% < 130 mg/dL. The study highlighted a greater decrease in serum TG levels only in patients with baseline TG > 150 mg/dL, who reached 11% reduction, compared to participants with baseline TG < 150 mg/dL.40


Inducers or inhibitors of CYP450 may alter plasma concentrations of monacolin K. For this reason, the simultaneous use of nutraceuticals with certain foods or drugs that are CYP450 inhibitors (eg, grapefruit juice, cyclosporine, HIV protease inhibitors, fibrates, niacin, coumarin, nefazodone, macrolides, antifungals) may increase the myotoxicity risk and, although rarely, cause rhabdomyolysis.41-43 Even if chronic use of monacolins could cause mild to moderately severe side effects, they are usually safe and well tolerated. The one exception is citrinin, which is a mycotoxin metabolite derived from Monascus fermentation.44 In several animal studies, chronic use of citrinin is nephrotoxic and gradually leads to hyperplasia of the renal tubular epithelium, renal adenomas, and sometimes to renal tumors (ie, a dose of 50 mg/kg causes tumors in 100% of the tested animals). Furthermore, citrinin causes reproductive toxicity, malformations, and certain embryo toxicity (even in vitro).45,46 The European Food Safety Agency (EFSA) has determined that the maximum dose of citrinin that can be ingested in humans without experiencing nephrotoxicity is 20 µg/kg per day.47 However, neither genotoxic nor carcinogenic effects can be excluded with certainty. Certain RYR supplements labeled “600 mg/capsule” have been detected with citrinin levels that exceed 114 µg/capsule, so that the recommended dosage of four capsules per day would significantly exceed the EFSA recommended level.11

Recent concerns have been voiced regarding the safety of RYR after publication of case reports that claimed toxicity.48 However, according to a recent meta-analysis of 53 RCTs with a total of 8,535 patients (4,437 in the RYR treatment arm and 4,303 in the control arm), use of monacolin K is not associated with an increased risk of muscular adverse events (OR 0.94, 95% CI, 0.53-1.65).49 Furthermore, the study demonstrated a reduced risk of nonmuscular adverse events (OR 0.59, 95% CI, 0.50-0.69) and serious adverse events (OR  0.54, 95% CI, 0.46-0.64) compared to the control group. The high tolerability profile of RYR was confirmed by the subgroup analyses. In addition, increasing daily doses of monacolin K was associated with a reduced risk of nonmusculoskeletal adverse events (slope: -0.10; 95% CI, -0.17 to -0.03; two-tailed P < .01).49 Thus, RYR seems to be an overall tolerable and safe lipid-lowering dietary supplement, even in patients previously intolerant to statin treatment, especially when they are adequately monitored and contain low monacolin K content (3 mg/day).20


Several meta-analyes and clinical trials have shown the correlation between decreased LDL-C levels and reduction of the relative risk for CVD.50 A meta-analysis performed by the Cholesterol Treatment Trialists’ (CTT) Collaboration group that included data from 14 RCTs and 90,056 individuals showed that a greater decrease in LDL-C serum concentrations correlated with a greater reduction in vascular and coronary events.51 Another meta-analysis by the CTT Collaboration involving > 170,000 patients showed that for every 1 mmol/L (~40 mg/dL) reduction in LDL-C, the risk of coronary artery disease, revascularization, and ischemic stroke decreased by just over one-fifth, suggesting that a 3.2 mmol/L (125 mg/dL) reduction in LDL-C could result in a 40% to 50% decrease in risk without affecting deaths due to cancer, stroke, or other nonvascular events.52 A reduction of 1 mmol/L is achievable through lipid-lowering nutraceuticals. The Heart Protection Study Collaborative Group determined that every 1% reduction in LDL-C levels correlates with a > 1% reduction in the relative risk of CV events.53 This reduction could be achieved by therapeutic lifestyle interventions and daily use of RYR. The positive effect of RYR on laboratory parameters other than LDL-C and on instrumental biomarkers of vascular aging (Table 1) supports its use in patients with moderately elevated LDL-C, especially in primary prevention.54

Table 1. Positive effects of red yeast rice in humans.

In light of the evidential data, the EFSA provided a scientific opinion substantiating the health claims related to RYR administration and plasma LDL-C levels, specifying that the relationship is possible when ingesting a dose of RYR that contains between 3 and 10 mg of monacolin K.55 However, some European national regulatory agencies have suggested using a lower dose of monacolin K due to safety concerns. In particular, specific attention should be given when prescribing full-dosed RYR for statin-intolerant patients.


  • Red yeast rice (RYR) extract is the most effective nutraceutical for lowering cholesterol.
  • RYR efficacy is proportional to its content of monacolin K.
  • The combination of RYR and other natural products with different mechanisms of action has a supposed synergic effect that can be functional in the treatment of hypercholesterolemia.
  • Recent studies confirm the high tolerability profile of RYR.
Conflict of Interest Disclosure

Dr. Banach conducts research on behalf of Sanofi and Valeant and is a consultant for Abbott/Mylan, Abbott Vascular, Actavis Generics, Akcea Therapeutics, Amgen, Biofarm, KRKA, MSD Pharma, Sanofi-Aventis, Valeant, Daiichi Sankyo, Esperion Therapeutics, Eli Lilly, and Resverlogix Corp.; Dr. Cicero is a consultant for Amgen, Menarini Group, Mylan, and Sanofi; and Dr. Fogacci is a consultant for Mylan.

  1. Colantonio LD, Bittner V, Reynolds K, et al. Association of Serum Lipids and Coronary Heart Disease in Contemporary Observational Studies. Circulation. 2016;133(3):256-64.
  2. Writing Group Members, Mozaffarian D, Benjamin EJ, et al.; American Heart Association Statistics Committee; Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. 2016;133(4):e38-360.
  3. NCD Risk Factor Collaboration (NCD-RisC). Trends in total cholesterol and lipid fractions in 22 Western and Asian countries. Lancet. 2019 (in press).
  4. Booth JN 3rd, Colantonio LD, Howard G, et al. Healthy lifestyle factors and incident heart disease and mortality in candidates for primary prevention with statin therapy. Int J Cardiol. 2016;207:196-202.
  5. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Sep 10;140(11):e596-e646.
  6. Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts): Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur J Prev Cardiol. 2016;23(11):NP1-NP96.
  7. Poli A, Barbagallo CM, Cicero AFG, et al. Nutraceuticals and functional foods for the control of plasma cholesterol levels. An intersociety position paper. Pharmacol Res. 2018;134:51-60.
  8. Patti AM, Toth PP, Giglio RV, et al. Nutraceuticals as an Important Part of Combination Therapy in Dyslipidaemia. Curr Pharm Des. 2017;23(17):2496-2503.
  9. Cicero AFG, Colletti A, Bajraktari G, et al. Lipid-lowering nutraceuticals in clinical practice: position paper froman International Lipid Expert Panel. Nutr Rev. 2017 Sep 1;75(9):731-767.
  10. Ma J, Li Y, Ye Q, et al. Constituents of red yeast rice, a traditional Chinese food and medicine. J Agric Food Chem. 2000;48(11):5220-5.
  11. Gordon RY, Cooperman T, Obermeyer W, Becker DJ. Marked variability of monacolin levels in commercial red yeast rice products: buyer beware! Arch Intern Med. 2010;170(19):1722-7.
  12. Endo A. Monacolin K, a new hypocholesterolemic agent produced by a Monascus species. J Antibiot (Tokyo). 1979 Aug;32(8):852-4.
  13. Li YG, Zhang F, Wang ZT, Hu ZB. Identification and chemical profiling of monacolins in red yeast rice using high-performance liquid chromatography with photodiode array detector and mass spectrometry. J Pharm Biomed Anal. 2004;35(5):1101-12.
  14. Gerards MC, Terlou RJ, Yu H, Koks CH, Gerdes VE. Traditional Chinese lipid-lowering agent red yeast rice results in significant LDL reduction but safety is uncertain – a systematic review and meta-analysis. Atherosclerosis. 2015;240(2):415-23.
  15. Zhao SP, Liu L, Cheng YC, et al. Xuezhikang, an extract of cholestin, protects endothelial function through antiinflammatory and lipid-lowering mechanisms in patients with coronary heart disease. Circulation. 2004;110(8):915-20.
  16. Cicero AF, Morbini M, Parini A, et al. Effect of red yeast rice combined with antioxidants on lipid pattern, hs-CRP level, and endothelial function in moderately hypercholesterolemic subjects. Ther Clin Risk Manag. 2016;12:281-6.
  17. Cicero AF, Morbini M, Rosticci M, D”Addato S, Grandi E, Borghi C. Middle-Term Dietary Supplementation with Red Yeast Rice Plus Coenzyme Q10 Improves Lipid Pattern, Endothelial Reactivity and Arterial Stiffness in Moderately Hypercholesterolemic Subjects. Ann Nutr Metab. 2016;68(3):213-9.
  18. Li JJ, Lu ZL, Kou WR, et al.; Chinese Coronary Secondary Prevention Study Group. Beneficial impact of Xuezhikang on cardiovascular events and mortality in elderly hypertensive patients with previous myocardial infarction from the China Coronary Secondary Prevention Study (CCSPS). J Clin Pharmacol. 2009;49(8):947-56.
  19. Cicero AF, Colletti A. Combinations of phytomedicines with different lipid lowering activity for dyslipidemia management: The available clinical data. Phytomedicine. 2016;23(11):1113-8.
  20. Banach M, Patti AM, Giglio RV, et al.; International Lipid Expert Panel (ILEP). The Role of Nutraceuticals in Statin Intolerant Patients. J Am Coll Cardiol. 2018 Jul 3;72(1):96-118.
  21. Cicero AF, Parini A, Rosticci M. Nutraceuticals and cholesterol-lowering action. Int J Cardiol Med Endocr. 2015;6:1-4.
  22. Varady KA, Wang Y, Jones PJ. Role of policosanols in the prevention and treatment of cardiovascular disease. Nutr Rev. 2003 Nov;61(11):376-83.
  23. Cicero AF, Brancaleoni M, Laghi L, Donati F, Mino M. Antihyperlipidaemic effect of a Monascus purpureus brand dietary supplement on a large sample of subjects at low risk for cardiovascular disease: a pilot study. Complement Ther Med. 2005;13(4):273-8.
  24. Stefanutti C, Mazza F, Vivenzio A, et al. Combined treatment with Dif1stat and diet reduce plasma lipid indicators of moderate hypercholesterolemia more effectively than diet alone: a randomized trial in parallel groups. Lipids. 2009;44(12):1141-8.
  25. Cicero AF, Benvenuti C, AR Moweb study Group. Efficacy of a red yeast rice based nutraceutical in large subgroups of hypercholesterolemic subjects in every day clinical practice. Med J Nutr Metab. 2010;3:239-46.
  26. Guardamagna O, Abello F, Baracco V, Stasiowska B, Martino F. The treatment of hypercholesterolemic children: efficacy and safety of a combination of red yeast rice extract and policosanols. Nutr Metab Cardiovasc Dis. 2011;21(6):424-9.
  27. Pirro M, Mannarino MR, Bianconi V, et al. The effects of a nutraceutical combination on plasma lipids and glucose: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 2016;110:76-88.
  28. Marazzi G, Cacciotti L, Pelliccia F, et al. Long-term effects of nutraceuticals (berberine, red yeast rice, policosanol) in elderly hypercholesterolemic patients. Adv Ther. 2011;28(12):1105-13.
  29. De Castro-Orós I, Solà R, Valls RM, et al. Genetic Variants of LDLR and PCSK9 Associated with Variations in Response to Antihypercholesterolemic Effects of Armolipid Plus with Berberine. PLoS One. 2016;11(3):e0150785.
  30. Cicero AF, Parini A, Rosticci M, et al. Effect of a lipid-lowering nutraceutical on pulse-wave-velocity in hypercholesterolemic patients with or without chronic kidney disease. Open Hypertens J. 2013;5(1):18-22.
  31. Pisciotta L, Bellocchio A, Bertolini S. Nutraceutical pill containing berberine versus ezetimibe on plasma lipid pattern in hypercholesterolemic subjects and its additive effect in patients with familial hypercholesterolemia on stable cholesterol-lowering treatment. Lipids Health Dis. 2012;11:123.
  32. Feuerstein JS, Bjerke WS. Powdered red yeast rice and plant stanols and sterols to lower cholesterol. J Diet Suppl. 2012;9(2):110-5.
  33. Cicero AF, Fogacci F, Rosticci M, et al. Effect of a short-term dietary supplementation with phytosterols, red yeast rice or both on lipid pattern in moderately hypercholesterolemic subjects: a three-arm, double-blind, randomized clinical trial. Nutr Metab. 2017;14:61.
  34. Ogier N, Amiot MJ, Georgé S, et al. LDL-cholesterol-lowering effect of a dietary supplement with plant extracts in subjects with moderate hypercholesterolemia. Eur J Nutr. 2013;52(2):547-57.
  35. Barrat E, Zaïr Y, Ogier N, et al. A combined natural supplement lowers LDL cholesterol in subjects with moderate untreated hypercholesterolemia: a randomized placebo-controlled trial. Int J Food Sci Nutr. 2013;64(7):882-9.
  36. Barrat E, Zaïr Y, Sirvent P, et al. Effect on LDL-cholesterol of a large dose of a dietary supplement with plant extracts in subjects with untreated moderate hypercholesterolaemia: a randomised, double-blind, placebo-controlled study. Eur J Nutr. 2013;52(8):1843-52.
  37. Cicero AF, Colletti A, Fogacci F, Bove M, Rosticci M, Borghi C. Effects of a Combined Nutraceutical on Lipid Pattern, Glucose Metabolism and Inflammatory Parameters in Moderately Hypercholesterolemic Subjects: A Double-blind, Cross-over, Randomized Clinical Trial. High Blood Press Cardiovasc Prev. 2017;24(1):13-18.
  38. Derosa G, Bonaventura A, Bianchi L, et al. A randomized, placebo-controlled study on the effects of a nutraceutical combination of red yeast rice, silybum marianum and octasonol on lipid profile, endothelial and inflammatory parameters. J Biol Regul Homeost Agents. 2014;28(2):317-24.
  39. Cicero AF, Colletti A, Rosticci M, Grandi E, Borghi C. Efficacy and tolerability of a combined lipid-lowering nutraceutical on cholesterolemia, hs-CRP level and endothelial function in moderately hypercholesterolemic subjects. J Biol Regul Homeost Agents. 2016;30(2):593-8.
  40. Cicero AF, Derosa G, Pisciotta L, Barbagallo C; SISA-PUFACOL Study Group. Testing the Short-Term Efficacy of a Lipid-Lowering Nutraceutical in the Setting of Clinical Practice: A Multicenter Study. J Med Food. 2015;18(11):1270-3.
  41. Kantola T, Kivistö KT, Neuvonen PJ. Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther. 1998;63(4):397-402.
  42. DFG Permanent Senate Commission on Food Safety. Toxicological evaluation of red mould rice: An update [Internet]. Kaiserslautern, Germany: DFG-Senate Commission on Food Safety; 2013 Nov 13 [cited 2019 Jun 11]. 26 p. Available from:
  43. Prasad GV, Wong T, Meliton G, Bhaloo S. Rhabdomyolysis due to red yeast rice (Monascus purpureus) in a renal transplant recipient. Transplantation. 2002;74(8):1200-1.
  44. Rasheva TV, Nedeva TS, Hallet JN, Kujumdzieva AV. Characterization of a non-pigment producing Monascus purpureus mutant strain. Antonie Van Leeuwenhoek. 2003;83(4):333-40.
  45. Arai M, Hibino T. Tumorigenicity of citrinin in male F344 rats. Cancer Lett. 1983;17(3):281-7.
  46. Singh ND, Sharma AK, Dwivedi P, Patil RD, Kumar M. Experimentally induced citrinin and endosulfan toxicity in pregnant Wistar rats: histopathological alterations in liver and kidneys of fetuses. J Appl Toxicol. 2008;28(7):901-7.
  47. EFSA Panel on Contaminants in the Food Chain (CONTAM). Scientific Opinion on the risks for public and animal health related to the presence of citrinin in food and feed. EFSA Journal. 2012;10(3):2605.
  48. EFSA Panel on Food Additives and Nutrient Sources Added to Food. Scientific opinion on the safety of monacolins in red yeast rice. EFSA Journal. 2018;16(8):5368.
  49. Fogacci F, Banach M, Mikhailidis DP, et al; Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group; International Lipid Expert Panel (ILEP). Safety of red yeast rice supplementation: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 2019;143:1-16.
  50. Hobbs FD, Banach M, Mikhailidis DP, Malhotra A, Capewell S. Is statin-modified reduction in lipids the most important preventive therapy for cardiovascular disease? A pro/con debate. BMC Med. 2016;14:4.
  51. Baigent C, Keech A, Kearney PM, et al; Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267-78.
  52. Baigent C, Blackwell L, Emberson J, et al; Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-81.
  53. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7-22.
  54. Cicero AF, Colletti A, Bajraktari G, et al. Lipid lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel. Arch Med Sci. 2017;13(5):965-1005.
  55. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on the substantiation of health claims related to monacolin K from red yeast rice and maintenance of normal blood LDL-cholesterol concentrations (ID 1648, 1700) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA Journal. 2011;9(7):2304.

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