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Red Yeast Rice

Medically reviewed by Drugs.com. Last updated on Dec 4, 2018.

Scientific Name(s): Monascus purpureus Went.
Common Name(s): Ang-khak, Beni-koji, Cholestin, Hon-Chi, Hongqu, Koji, Monascus, Red fermented rice, Red mold, Red rice koji, Red rice yeast, Red yeast, Red-koji, Rotschimmelreis, Xuezhikang, Zhibituo, Zhitai

Clinical Overview

Use

M. purpureus is a natural source of mevinolin, the active ingredient of the drug lovastatin, therefore, having beneficial effects in the treatment of hyperlipidemia. However, red yeast rice should not be used in place of lovastatin and regular medical care because of potential product safety concerns related to dietary supplements, and lack of patient monitoring. Evidence also exists for its antibacterial and anticancer effects, as well as its activity on glycemic metabolism.

Dosing

Red yeast rice is available commercially, primarily as a 600 mg capsule. Most manufacturers suggest an oral dosage of 2 capsules twice a day for a total dose of 2,400 mg/day. Commercial over-the-counter products often contain coenzyme Q10 to supplement low levels of this enzyme in patients with statin myopathy. Clinical trials have used dosages of 1,200 to 3,600 mg/day.

Contraindications

Hypersensitivity to any components of red yeast rice. Anaphylactic reactions in certain populations are documented. Because red yeast rice depletes tissue of coenzyme Q10, which may increase the risk of statin-induced myopathy, patients with muscle damage caused by statins should avoid its use.

Pregnancy/Lactation

Avoid use during pregnancy and lactation. One ingredient in red yeast rice is monacolin K, which is also known as mevinolin or lovastatin and has statin-like activity. Statins are potential teratogens based on theoretical considerations and small case studies. CNS and limb defects have been reported in newborns exposed to statins in utero.

Interactions

There are many possible drug interactions associated with red yeast rice. Consult a health care provider before using any dietary supplement.

Adverse Reactions

Meta-analysis of the efficacy of 3 red yeast rice preparations (Cholestin, Xuezhikang, and Zhibituo) from 93 randomized trials (9,625 patients) documented no serious adverse reactions. The most common adverse reactions included dizziness, decreased appetite, nausea, stomachache, abdominal distension, and diarrhea. A small number of patients experienced increased serum blood urea nitrogen (BUN) and ALT levels. A meta-analysis showed incidence of liver injury, kidney injury, and muscle symptoms with red yeast rice products was not significantly different compared to control.

Toxicology

The nephrotoxic mycotoxin citrinin has been isolated from some strains of M. purpureus and Monascus ruber. No severe toxicities at high doses have been reported. Not recommended for use in patients with liver or kidney disease.

Scientific Family

  • Aspergillaceae

History

The recorded use of red yeast rice dates back to the Chinese pharmacopoeia, Pen-ts'ao Kang-Mu (AD 1596), published during the Ming Dynasty.1 The red mold species M. purpureus may be cultivated on starch-containing substrates.2 The purported food and medicinal values of the species date back to 800 AD.3 In 1884, Dutch scientists studied the fungus Monascus after discovering its use by villagers in the colonial island of Java. It was classified and named by the French botanist Philippe Van Tieghem.4 Red yeast rice is derived from rice allowed to ferment with the yeast M. purpureus. In 1895, the M. purpureus species was isolated from red koji, named for the purple color of the culture.5, 6

Red yeast rice has been used in Chinese medicine to strengthen the spleen, promote or improve digestion, eliminate dampness and phlegm, promote or improve blood circulation, and remove blood stasis. During the Ming Dynasty, red yeast rice was described as "sweet in flavor and warm in property."7, 8 The genus Monascus has been used for centuries in Asia as a source of pigment for coloring traditional foods. The medicinal properties of red yeast rice are valued throughout Asia, and the species is also used to make rice wine and as a food preservative for maintaining the color and taste of fish and meat.7 Commercial food applications include coloration of sausage, hams, surimi, and tomato ketchup. The pigment has a long history of use as a food ingredient for Asian consumers, but not in Europe or the United States. However, a study documents the registration of numerous patents obtaining the use of Monascus as a food pigment in Japan, the United States, France, and Germany.9 Additionally, it has been used to enhance the flavor of food in Asian countries.10

Chemistry

Red yeast rice forms naturally occurring hydroxymethylglutaryl-CoA reductase (HMG-CoA) inhibitors,11 a family of natural substances known as monacolins. The major ingredient in red yeast rice is monacolin K, which is also known as mevinolin or lovastatin. Monacolin K is found in some commercial red yeast–related products.8 One chemical study using high-performance liquid chromatography with photodiode array detection documented a total of 14 monacolin compounds, including monacolin K, J, L, M, and X with their corresponding hydroxyl acid forms, as well as dehydromonacolin K, dihydromonacolin L, compactin, and 3-hydroxy-3,5-dihydromonacolin L. Starch is the most abundant ingredient, accounting for 73% of the bulk, while crude protein accounts for 15%.8 Trace elements, magnesium and sodium, are the most abundant metal elements. The total monacolin content is usually 0.4% weight/weight rice.8 Red yeast rice also contains sterols, such as beta-sitosterol and campesterol, that may block cholesterol absorption in the intestines. Unsaturated fatty acids (eg, oleic, linoleic, linolenic acids) and B complex vitamins (eg, niacin) have been isolated and may further help reduce cholesterol.1

Monascus produces several secondary metabolites, such as pigments, monacolins, gamma-aminobutyric acid (GABA), and dimerumic acid.7, 8, 9, 11, 12 A total of 8 pigments called azaphilones are produced by Monascus and include yellow (monascin, ankaflavin, yellow II, and xanthomonascin A), orange (monascorubrin and rubropunctatin), and reddish-purple (monascorubramine and rubropunctamine), each of which may have biological activity.5, 9, 13, 14 Commercial utilization of agro−industrial residues for pigment and enzyme production from M. purpureus is documented.9, 15 The natural pigment of Monascus also improves the organoleptic characteristics of various cheeses.16

Monascidin A, another constituent of Monascus, has been characterized as citrinin by qualitative methods, mass spectra, and nuclear magnetic resonance.17 Citrinin is a myotoxin that is especially toxic to liver and kidney tissues, and is suspected of being a renal carcinogen leading to renal tumors.18 Monacolin K and citrinin are both polyketide derivatives. Chemical methods are available to remove citrinin and retain monacolin K in red yeast rice.18

Uses and Pharmacology

Most research focuses on M. purpureus as a natural source of lovastatin, therefore, having beneficial effects in the treatment of hyperlipidemia. Evidence also exists for its antibacterial and anticancer effects, as well as its activity on glycemic metabolism.19

Alzheimer disease

Red mold rice and its metabolites may be beneficial in Alzheimer disease by inhibiting Abeta-induced neurocytotoxicity, Abeta deposition in the brain, and Abeta synthesis pathway as well as by promoting the neuroprotective factor, soluble amyloid precursor protein alpha.52

Antibacterial activity

The activity of Monascus derivatives depends on the hydrophobicity of pigment derivatives and on the amount of pigment absorbed to the cell surface.13

Animal/In vitro data

Antibacterial activity was found against gram-positive and gram-negative species.1, 20, 21 Orange Monascus pigments have been reported to have weak antibacterial activity, while the red pigment has little to no activity.13 Orange pigments had antimicrobial activities against Bacillus subtilis, Escherichia coli, some filamentous fungi, and yeasts.20 Monascidin A inhibited bacteria from the genera Bacillus, Streptococcus, and Pseudomonas. Two yellow pigments had bacteriostatic activity against B. subtilis and inhibitory activity against Staphylococcus aureus.1

Clinical data

No clinical data exists regarding the use of red yeast rice for its antibacterial effects.

Antioxidant effects

In an in vitro study, polysaccharides derived from red mold rice and red mold dioscorea fermented with M. purpureus were found to exert antioxidant activities such as scavenging of radicals, chelating, and inhibiting linoleic acid peroxidation. Additionally, these polysaccharides were found to possess immunomodulatory effects such as enhanced cell proliferation, phagocytosis, and production of cytokines and nitric oxide.53

Bone formation

Statins may reduce the risk of bone fractures, as well as increase bone formation and bone mass. Red yeast rice stimulated bone formation in rats.43

Cancer

The mechanism of action may involve monacolin K and red yeast pigment fraction inhibiting de novo cholesterogenesis that is required for tumor growth.6 Monacolin K is an effective anticancer agent that blocks the mevalonate biosynthesis pathway, inducing suppression of cancer growth.22

Animal/In vitro data

Red yeast rice inhibited proliferation and stimulated apoptosis, perhaps through caspases4, 9, 11 and poly(ADP-ribose) polymerase cleavage in human colon adenocarcinoma cell lines.6 Proteomic studies found monacolin K to inhibit cell proliferation through multiple protein expressions (a total of 20 proteins), including peroxiredoxins, cytoskeleton proteins, chaperone proteins, and energy-producing enzymes. Monacolin K may also alter the expression of some redox-related enzymes.22, 23 Three active components of Monascus fermented red yeast rice (monacolin K, monascorubrin, and ankaflavin) have documented antiproliferative effects against tumor cells.22 Red mold rice extract was found to induce cell cycle arrest and apoptosis in MCF-7 breast cancer cells.24 Additionally, M. purpureus fermented products were found to be beneficial in the prevention and treatment of oral cancer. Specifically, treatment was associated with a reduction in the number of tumors, mean tumor volume, and tumor burden.5 Red yeast rice was also found to reduce the volume of prostate tumors in mice with a greater effect noted with red yeast compared with lovastatin.25

Oral administration or topical application of monascorubrin pigment inhibited skin cancer development in mice.6, 26, 27

Rubropunctatin, derived from Monascus, was found to inhibit the growth of the human gastric cancer cell line SH-SY5Y, BCG-823, AGS, and MKN45.28

Clinical data

No clinical data exists for the use of red yeast rice in cancer.

Diabetes

The postulated mechanism of action involves the release of acetylcholine from nerve terminals, which in turn stimulates muscarinic receptors in pancreatic cells, increasing insulin release and resulting in lower plasma glucose.29 Additionally, monascin has been found to act as a peroxisome proliferator–activated receptor (PPAR)-gamma agonist to improve insulin sensitivity.10, 30

Animal/In vitro data

Hon-Chi (red yeast rice fermented with Monascus pilous and M. purpureus) decreased plasma glucose in a dose-dependent manner in rats.29 An increase in plasma insulin or C-peptide was also observed, and similar results were documented in streptozotocin-induced diabetic rats.31 Another study found that Hon-Chi improved insulin sensitivity in rats and delayed development of insulin resistance.2 In a study of rats, monascin administration was found to exert PPAR-gamma agonist activity, as well as increase Nrf2 activation.30 Red mold dioscorea was found to improve glycemic control, exert antioxidant and anti-inflammatory effects, and protect beta-cells in the pancreas.32

Clinical data

No clinical data exists for using red yeast rice for its effects on glycemic control.

Hepatic disease

A murine study of alcoholic liver disease found that treatment with Monascus-fermented red mold rice attenuated elevations in liver function tests (ASTs/ALTs) as well as hepatic triglycerides and total cholesterol accumulation. It was also found to exert antioxidant effects and reduce cytokine levels.47

Orange pigment derivatives of Monascus have been found to exert activity against hepatitis C.48

Hyperlipidemia

Monacolin K competitively inhibits HMG-CoA reductase, the enzyme that catalyzes HMG-CoA to mevalonate and then to cholesterol, which results in decreased very low density lipoprotein cholesterol (VLDL-C) and plasma triglycerides, as well as LDL-C.

Animal/In vitro data

In the late 1970s, it was discovered that Monascus metabolites inhibited HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis.33 Zhitai (0.25% HMG-CoA reductase inhibitors) and Xuezhikang (the ethanolic extract containing 1.1% HMG-CoA reductase inhibitors) have both been extensively studied in China and both contain Monascus.34 In 3 separate animal studies, Xuezhikang was effective in reducing serum cholesterol levels, similar to the effect of lovastatin. Xuezhikang was also found to suppress aortic atherosclerotic plaque formation and lipid accumulation in animal livers. The dose of 0.4 and 0.8 g/kg in 1 report reduced serum cholesterol levels by 44% and 59%, respectively.35

Clinical data

The 2013 American College of Cardiology/American Heart Association Guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular (ASCVD) risk in adults did not make a recommendation regarding the use of Xuezhikang (extract of red yeast Chinese rice), because only a single ASCVD outcomes trial was documented and was not available in the United States during the timeframe for evidence review.248

A 2012 published review of literature from 2005 to 2010 consisting of clinical trials involving human patients and focusing on dyslipidemia found red yeast rice to reduce total and LDL-C when compared with placebo. Additionally, when red yeast rice was combined with lifestyle changes or other alternative therapies (eg, niacin, fish oil, octacosanol) and compared with statins, there was no difference between regimens containing red yeast rice or statin therapy on total cholesterol and LDL-C levels.42 Similar results in efficacy were demonstrated in a trial that documented a significantly better side effect profile of red yeast rice (1.2 g/day) compared to simvastatin (20 mg/day) in 60 patients with hyperlipidemia and moderate to low cardiovascular risk. The changes in fatigue scores and physical activity levels from baseline were significantly worse with simvastatin over the 4-week study period (P<0.001 each), whereas they remained unchanged from baseline with red yeast rice. The difference between groups was also statistically significant (P<0.01 and P<0.001, respectively).260 In a randomized trial, red yeast rice (1,800 mg twice daily) compared to placebo in statin intolerant patients resulted in significant reductions in LDL-C.261

Many Chinese studies evaluating Monascus are available. One major, randomized, multicenter trial involved 446 hyperlipidemic patients with total cholesterol levels greater than 230 mg/dL. At the end of an 8-week treatment, total serum cholesterol was reduced by an average of 23%, triglycerides were reduced by 37%, LDL-C was reduced by 29%, and high-density lipoprotein cholesterol (HDL-C) levels were increased by 20%.36 Red yeast rice reduced lipid ratios including LDL-C levels, total cholesterol/HDL-C, LDL-C/HDL-C, and apolipoprotein B/apolipoprotein A-I in hypercholesterolemic patients.37 Similar results were found in a phase 2 multicenter, double-blind, paralle-group, randomized, placebo-controlled trial conducted in the United States and China that enrolled 116 dyslipidemic patients without coronary artery disease in which 1,200 and 2,400 mg/day of Xuezhikang significantly reduced non-HDL-C by approximately 24% and LDL-C by approximately 27% from baseline to treatment week 12 (P < 0.001 each vs baseline and vs placebo). Treatment was well tolerated. No differences in lipid efficacy end points were observed between American and Chinese participants.255 A meta-analysis reviewed the efficacy of 3 red yeast rice preparations (Cholestin, Xuezhikang, and Zhibituo) from 93 randomized trials (9,625 patients). When compared with placebo, red yeast rice treatment reduced serum total cholesterol, triglycerides, and LDL-C levels, and increased HDL-C levels. Although there were no clinical studies at the time that directly compared red yeast rice with any statin, the efficacy of red yeast rice on lipid modification was comparable with that of the prescription drugs pravastatin, simvastatin, lovastatin, atorvastatin, or fluvastatin. When compared with nonstatin drug therapy, red yeast rice was superior to nicotinate and fish oils, but not to fenofibrate and gemfibrozil. No difference was found between Xuezhikang and Zhibituo in lipid profiles.38, 39 Additionally, a double-blind, crossover, randomized clinical trial in 25 moderately hypercholesterolemic (LDL-C 130 to 190 mg/dL) Italian men found that 4 weeks of monacolins treatment, in combination with Mediterranean dietary advice, resulted in a more favorable change in total cholesterol (−12.45%), LDL-C (−21.99%), and non-HDL-C (−14.67%). The red yeast rice extract product contained 10 mg monacolins and 10 mg coenzyme Q10.249

A systematic review and meta-analysis of 20 randomized studies (N = 6,663) published through November 2014 that evaluated the effect on LDL cholesterol of red yeast rice products with a known content of monacolin K, found the effect of red yeast rice 10 mg/day for 2 months to 3.5 years to be no different from pravastatin 40 mg, simvastatin 10 mg, or lovastatin 20 mg therapy (1.02 mmol/L reduction). In the study that compared red yeast rice with gemfibrozil, red yeast rice was beneficial on all lipid parameters; however, gemfibrozil provided a greater improvement in triglycerides. Additionally, it was more effective than placebo. No difference was found in incidence of kidney or liver injury between intervention and control groups; however, methods for evaluating adverse effects across studies was unclear with a high risk of bias.254 A systematic review of all randomized controlled trials published through May 2015 comparing single preparation red yeast rice with simvastatin in participants with primary hyperlipidemia were assessed to determine efficacy and safety. Data on changes in triglycerides, HDL- and LDL-cholesterol, and total cholesterol were pooled and analyzed. A total of 10 trials (N = 905) were eligible for inclusion and all were conducted in China except for 1 in which the location was not specified. Total daily doses of red yeast rice ranged from 1.2 to 3.6 g given for 4 to 12 weeks; simvastatin doses ranged from 10 mg/day to 20 mg/day and 1 study also included pravastatin as a comparator. Risk of bias was unclear for all trials; most had low risk for addressing incomplete outcome data (70%) and high risk of bias for selective reporting (70%). No significant difference was found between red yeast rice and simvastatin for reduction in triglycerides, total cholesterol, or LDL- or HDL-cholesterol. However, 2 trials showed a significant improvement in LDL-cholesterol favoring red yeast rice and HDL-cholesterol favoring simvastatin. No significant difference in adverse events was reported between groups.256

When combined with policosanols, artichoke leaf extracts, garlic, and pine bark extract, red yeast rice was found to be effective in reducing LDL-C when given for 16 weeks to patients with moderate hypercholesterolemia. Total cholesterol and apolipoprotein B100 were reduced after 4 weeks of supplementation and either stabilized or slightly increased by week 16.40 In another randomized, double-blind, placebo-controlled trial, lifestyle changes combined with the use of red yeast rice in participants yielded a larger reduction in LDL-C levels at weeks 12 and 24 as compared with that of participants receiving red yeast rice and usual care. The addition of phytosterol to red yeast rice therapy did not result in any further reductions in lipid parameters. There were no differences at week 52. Additionally, those receiving red yeast rice with lifestyle changes were more likely to achieve an LDL-C goal of less than 100 mg/dL.41

Italian investigators evaluated a combination product containing berberine, red yeast rice, folic acid, and coenzyme Q10 in statin intolerant patients older than 75 years (n = 80) with total cholesterol higher than 200 mg/dl or LDL-C higher than 160 mg/dl in a 12-month, randomized, single-blind study. There were significant reductions in total cholesterol (−20%), and LDL-C (−31%) (P < 0.05 for both results). No significant changes compared with baseline were seen for liver enzymes or creatine kinase (CK) levels.251 Similar results were seen with a commercially available combination product of 1.5% (5.025 mg) red yeast rice that also contained 30 mg coenzyme Q10, 20 mg procyanidins from grape seed, and 100 mg lecithin. Data from 52 participants with a total fasting cholesterol of higher than 200 mg/dL and triglycerides less than 400 mg/dL revealed that 2 capsules taken twice daily for 8 weeks produced a 22% reduction in LDL cholesterol in 20% of the intervention group and a 15% reduction in total cholesterol (P < 0.001); magnitude of effect on LDL was high and ranged from −8% to 40.5%. No significant differences in creatine-kinase elevation or side effects were noted between treatment and placebo, although muscle aches tended to be more prevalent in the intervention group.253 Extending on data published in a 2014 meta-analysis, studies conducted between 2013 and 2016 were evaluated in a meta-analysis to assess safety and efficacy in treating dyslipidemic adults. An additional 13 studies, 11 of which were randomized controlled trials, and 2 meta-analyses were identified that included 1,246 and 7,467 participants, respectively. The majority of trials used tested multi-ingredient formulations with monacolin K being the most common red yeast rice element used. Other ingredients included artichoke leaf, garlic, pine bark, green tea, ubiquinol, astaxanthin, resveratrol, quercetin, Silybum marianum, octasonol, grapeseed, black pepper seed, guggulsterols, and various vitamins. All 13 studies reported significant decreases in LDL cholesterol compared to placebo, other nutraceuticals, or diet and exercise. No significant differences were noted for HDL, and results regarding total cholesterol and triglycerides were equivocal. No changes in liver or renal function were noted in any of the studies and 10 studies noted no changes in creatine kinase. Other side effects were minimal and included mostly GI effects, such as heartburn, nausea, and abdominal pain.259

Another Italian study evaluated red yeast rice extract in pediatric patients (n = 40; 8 to 16 years of age) with familial hypercholesterolemia (n = 24) and familial combined hyperlipidemia. This randomized, placebo-controlled crossover trial used 200 mg of red yeast rice extract (monacolins 3 mg, policosanols 10 mg) or matching placebo daily for 8 weeks, with a 4-week washout period between treatments. Active treatment was performed similarly in the 2 disease groups, with pooled results showing significant reductions in total cholesterol (−18.5%) and LDL-C (−25.1%) (P < 0.001 for both results). No significant changes were seen in HDL-C, apolipoprotein A-1, liver enzymes or CK levels.252

Statin-naïve adults (n=191) in India with newly diagnosed hyperlipidemia and no evidence of cardiovascular disease experienced a significant improvement in lipid parameters, which was evident in both the placebo and treatment groups. All patients were advised about a healthy lifestyle and diet modifications and then assigned to placebo or a proprietary nutritional supplement (PreLipid) that contained red yeast rice (400 mg), grapeseed, niacin, folic acid, and black pepper. In total, 4 of 5 lipid parameters (total cholesterol, LDL, HDL, and non-HDL cholesterol) were improved significantly in the placebo group and all 5 measures were significantly improved in the supplement group with triglycerides being the 5th measure improved. The improvements seen with the red yeast rice formula were significantly better than those seen by diet and lifestyle (placebo) alone. The supplement was well tolerated but resulted in a significant decrease in ALT compared to placebo. The study was an industry-funded 12-week multicenter, double-blind, randomized controlled trial.258

Hypertension

An aqueous extract of M. purpureus prevented and reversed fructose-induced hypertension in rats and did not affect blood pressure levels in normotensive rats fed a regular diet. The effect is believed to be associated with the GABA contents.3 In another study of hypertensive rats, red mold dioscorea 150 mg/kg as a single dose was found to reduce systolic and diastolic blood pressure values 8 hours after administration. This effect was not noted with red mold rice administration. Higher amounts of GABA, yellow pigments, and higher angiotensin I−converting enzyme activity were noted with red mold dioscorea compared with red mold rice.44

Men's health conditions

In a murine study, Monascus cursory extraction was found to suppress baldness in male mice, decrease prostate-specific antigen levels, reduce tumor volume and incidence in testosterone-induced prostate cancer, and decrease dihydrotestosterone, but not testosterone levels. Further studies are warranted to determine the role of Monascus in alopecia, benign prostatic hyperplasia, and prostate cancer.49

Other cardiovascular effects

In a study of rats infused with angiotensin II, those given 200 mg/kg/day of red yeast rice extract 7 days before the infusion and continued for 28 days were found to have reduced atherosclerotic lesions in the intima of the aorta, as well as suppressed angiotensin II expression. The incidence of abdominal aortic aneurysm was reduced with red yeast rice therapy. Additionally, total cholesterol levels were lower with red yeast rice administration.45

In a randomized, double-blind, placebo-controlled study, 4,870 Chinese patients with coronary heart disease having a history of myocardial infarction (MI) were randomized to receive Xuezhikang 0.6 g twice daily or placebo in addition to conventional therapy. After 4 years, nonfatal MI and deaths from coronary heart disease were 5.72% in the Xuezhikang group compared with 10.41% in the control group (45% relative risk reduction). Secondary end points of stroke, tumor, and percutaneous coronary intervention/coronary artery bypass grafting were significantly reduced with treatment compared with placebo (6.92% vs 10.04%, respectively, P = 0.097).46 The effect of a combination of red yeast rice plus ubiquinone on endothelial function and arterial stiffness was investigated in a double-blind, randomized, placebo-controlled trial in pharmacologically untreated hypercholesterolemic adults (n=40). Total and LDL-C levels improved significantly, starting after 2 months of administration, in patients randomized to treatment (10 mg monacolins from Monascus purpureus and 30 mg emulsioned coenzyme Q10) compared to placebo (P<0.05). Significant improvements were also seen in the vascular parameters; endothelial reactivity improved +6% with treatment and changed −0.3% with placebo (P<0.05). Additionally, a significant benefit was observed in arterial stiffness measurements with red yeast rice-coenzyme Q10 (P<0.05). No significant changes were documented between groups in triglycerides, HDL-C, glucose, transaminases, creatine, or creatine phosphokinase.257

Pulmonary disease

Monascus daily supplementation given to rats was found to decrease cigarette smoke–induced lung injuries through reducing oxidative stress and maintaining antioxidant mechanisms.50 Ankaflavin was found to act as an Nrf2 activator in both lung cancer cells and ovalbumin-challenged mice, attenuating airway inflammation and improving lung injury.51

Dosing

Red yeast rice is available commercially, primarily in 600 mg capsule form. Most manufacturers suggest an oral dosage of 2 capsules twice a day for a total dose of 2,400 mg/day. Commercial OTC products often contain coenzyme Q10 to supplement low levels of this enzyme in patients with statin myopathy.54 Clinical trials have used dosages of 1,200 to 3,600 mg/day for 4 to 12 weeks 55, 56, 256

Pregnancy / Lactation

Avoid use during pregnancy and lactation. The major ingredient in red yeast rice is monacolin K, which is also known as mevinolin or lovastatin and has statin-like activity. Statins have been identified as potential teratogens based on theoretical considerations and in small case studies.57 CNS and limb defects have been reported in newborns exposed to statins in utero.58

Interactions

The clinical importance of these interactions has not been determined for consumption of red yeast rice, but caution is warranted.

Amiodarone: May decrease the metabolism of HMG-CoA Reductase Inhibitors. Consider therapy modification.59, 60, 61, 62, 63, 64, 65

Antacids: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy.66, 67, 68, 69

Bezafibrate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Bezafibrate may increase the serum concentration of HMG-CoA Reductase Inhibitors. More specifically, bezafibrate may increase the serum concentration of fluvastatin. Consider therapy modification.70, 71, 72, 73, 74, 75, 76, 77, 78

Bosentan: May increase the metabolism of HMG-CoA Reductase Inhibitors. Monitor therapy.79, 80

Calcium Channel Blockers (Nondihydropyridine): May increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin (and possibly other related compounds) may be increased. Monitor therapy.81, 82, 83, 84, 85

Colchicine: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification.86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin and related compounds found in Red Yeast Rice may be increased. Avoid combination.99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109

Cyproterone: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification.110, 111

Danazol: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification.109, 112, 113, 114

DAPTOmycin: HMG-CoA Reductase Inhibitors may enhance the adverse/toxic effect of DAPTOmycin. Specifically, the risk of skeletal muscle toxicity may be increased. Consider therapy modification.115, 116, 117, 118, 119, 120

Dronedarone: May increase the serum concentration of Red Yeast Rice. In particular, concentrations of the lovastatin-like components may be increased. Monitor therapy.121, 122

Etravirine: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. This applies to atorvastatin, lovastatin and simvastatin. Conversely, levels of fluvastatin may be increased. Monitor therapy.123

Fenofibrate: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy.74, 124, 125, 126, 127, 128, 129, 130

Fenofibric Acid: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy.74, 124, 125, 126, 127, 128, 129, 130, 131

Fluconazole: May increase the serum concentration of Red Yeast Rice. Specifically, concentrations of lovastatin and related compounds found in Red Yeast Rice may be increased. Monitor therapy.104, 105, 106, 107, 108, 132, 133, 134, 135, 136

Fosphenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification.137, 138

Fusidic Acid: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Specifically, the risk for muscle toxicities, including rhabdomyolysis may be significantly increased. Avoid combination.139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156

Grapefruit Juice: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification.113, 114, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171

HMG-CoA Reductase Inhibitors: Red Yeast Rice may enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Avoid combination.75, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182

Lanthanum: HMG-CoA Reductase Inhibitors may decrease the serum concentration of Lanthanum. Consider therapy modification.67, 68, 183

Macrolide Antibiotics: May decrease the metabolism of HMG-CoA Reductase Inhibitors. Consider therapy modification.99, 130, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202

Niacin: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Consider therapy modification.203, 204, 205, 206, 207, 208, 209

Niacinamide: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy.204, 206, 207, 208, 209, 210

Pazopanib: HMG-CoA Reductase Inhibitors may enhance the hepatotoxic effect of Pazopanib. Specifically, the risk for increased serum transaminase concentrations may be increased. Monitor therapy.211

Phenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification.137, 138

Proton Pump Inhibitors: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy.188, 191, 212, 213, 214, 215, 216, 217, 218, 219

Rifamycin Derivatives: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification.138, 220, 221

Sildenafil: May decrease the metabolism of HMG-CoA Reductase Inhibitors. Consider therapy modification.113, 222

St. John's wort: May increase the metabolism of HMG-CoA Reductase Inhibitors. Monitor therapy.223

Trabectedin: HMG-CoA Reductase Inhibitors may enhance the myopathic (rhabdomyolysis) effect of Trabectedin. Monitor therapy.224, 225, 226, 227, 228

Vitamin K Antagonists: HMG-CoA Reductase Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy.229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242

Adverse Reactions

Use of red yeast rice should be avoided with hypersensitivity to any of its components. Anaphylactic reactions have been reported.243, 244 Because red yeast rice decreases tissue levels of coenzyme Q10, which may increase the risk of statin-induced myopathy, patients with muscle damage caused by statins should avoid its use.54, 245

Meta-analysis of the efficacy of 3 red yeast rice preparations (Cholestin, Xuezhikang, and Zhibituo) from 93 randomized trials (9,625 patients) documented no serious adverse reactions. The most common adverse reactions included dizziness, decreased appetite, nausea, stomachache, abdominal distension, and diarrhea. A small number of patients experienced increased serum BUN and ALT levels.39

A meta-analysis showed incidence of liver injury, kidney injury, and muscle symptoms with red yeast rice products was not significantly different compared to control; however methods for evaluating adverse effects across studies was unclear with a high risk of bias.254

A case report describes a possible association between red yeast rice and peripheral neuropathy. A 60-year-old man developed peripheral neuropathy while receiving imatinib for a metastatic GI tumor, in addition to red yeast rice supplement. Upon discontinuation of red yeast rice, his symptoms abated. He continued imatinib therapy for at least 2 years with no further concerns.246

Toxicology

The nephrotoxic mycotoxin, citrinin, has been isolated from some strains of M. purpureus and M. ruber.12, 246

Studies on Monascus have shown no toxicity at doses much greater than typical dosing in both long- and short-term therapy. In rats fed Monascus at 50 times the human dose, no abnormalities in behavior or in blood and urine testing were seen. One percent to 2% of HMG-CoA reductase (ie, statin) users, in general, experience hepatotoxicity and myopathy.34 Monascus is not recommended for use in patients with liver or kidney disease.247

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