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Review Article | Open Access | Online First

Future of red yeast rice: a promising and safer natural approach for daily management of hypercholesterolemia

Guo-Dong Ma^{¹^,^†}, Xin-Ge Hu^{¹^,^†}, Jin-Hong Xu^², Fang Yang^³, Jian-Gang Chen^⁴(), Guo-Xun Chen^²()

1Department of Nutrition, University of Tennessee at Knoxville, Knoxville 37916, USA

2College of Food Science and Technology, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan 430070, China

3School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan 430065, China

4Department of Public Health, University of Tennessee at Knoxville, Knoxville 37916, USA

^†These authors contributed equally to this work.

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Highlights

(1) Red Yeast Rice and Treatment Options Lifestyle changes can lower LDL cholesterol levels without increasing the side effects caused by statins.

(2) Future modified red yeast products could be hydrophilic or hydrophobic, thus creating simple daily functional foods that can be adapted to lower blood lipids for a broader range of people.

(3) Contaminants caused by process defects and human error can lead to the mixing of impurities into the product. Which leads to additional risks, even fatal, in the use of red yeast rice, emphasizing the need for upgraded processes and strict quality control.

Graphical Abstract

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The graphical abstract illustrates how red yeast rice (RYR), containing Monacolin K (natural Lovastatin), competitively inhibits HMG-CoA reductase in the liver, blocking cholesterol synthesis and reducing hyperlipidemia. Future modified red yeast rice products could be hydrophilic or hydrophobic, affecting their audience and bioavailability. This product modification aims to create simple daily functional foods that lower blood lipids, reduce side effects like muscle pain, and enhance active ingredient bioavailability for superior effectiveness while minimizing unintended toxic side effects. The image shows RYR in various forms, from raw rice to supplements, emphasizing its potential as a natural cholesterol-lowering agent.

Abstract

Hypercholesterolemia is closely associated with the risk of cardiovascular diseases. Medicinal and dietary approaches are both used to combat it. Red yeast rice (RYR) is a traditional ingredient that has been used for a long time in food preparation. Interestingly, it shows activity to alleviate hypercholesterolemia as a food supplement due to the high content of lovastatin (also known as monacolin K), a statin drug. To gain a comprehensive understanding of RYR and its functions, we have reviewed the current literature from PubMed. This review summarizes the RYR historical use in traditional Chinese medicine and compares it with statins for controlling hypercholesterolemia. In addition, we have also included the side effects of RYR, its impacts on the heart, liver, and muscle, and the limitations of current research. The needs to reduce side effects while providing the same bioavailability and efficacy of RYR for the alleviation of hypercholesterolemia are important for its benefits in health. We believe that more research is needed to thoroughly investigate RYR and find novel compounds with activities to control hypercholesterolemia and help subjects who are sensitive to statin-mediated side effects.

Keywords

red yeast rice hyperlipidemia hypercholesterolemia statin monacolin K side effects

References

[1]

Fukami, H., Higa, Y., Hisano, T., et al., a review of red yeast rice, a traditional fermented food in Japan and East Asia: its characteristic ingredients and application in the maintenance and improvement of health in lipid metabolism and the circulatory system. Molecules, 2021 , 26: 1619. https://doi.org/10.3390/molecules26061619

Crossref

[2]

WHO TEAM Integrated Health Services, Complementary and Integrative Medicine, WHO traditional medicine strategy: 2014–2023. 2014-2023 ed. 2017, World Health Organization: World Health Organization Library, 76.

[3]

Wang, S., Chen, Y., Wang, R., et al., effectiveness of red yeast rice on carotid atherosclerosis: a systematic review and meta-analysis. Frontiers in Pharmacology, 2022 , 13: 937809. https://doi.org/10.3389/fphar.2022.937809

Crossref

[4]

Huang, Y. Z., Wang, L., Huang, Y. Y. Red yeast rice rich in monacolin k and preparation method of red yeast rice, in Fujian Agriculture and Forestry University, Administration, 2015 , China

[5]

Health. Red yeast rice: what you need to know. 2023. (cited 2023) Available from: https://www.nccih.nih.gov/health/red-yeast-rice

[6]

Klimek, M., Wang S., Ogunkanmi, A. Safety and efficacy of red yeast rice ( Monascus purpureus) as an alternative therapy for hyperlipidemia. Pharmacy and Therapeutics, 2009, 34: 313–327. https://doi.org/10.1111/j.1365-2710.2008.01010.x

Year	Study design	Outcomes	Group size	Gender	Group age	Time course	Drug and dosage	Reference
Note: GABA, γ-aminobutyric acid; MKA, monacolin K β-hydroxy acid; TC, total cholesterol.
2021	Randomized Controlled Trial	LDL and total cholesterol, apolipoprotein B, and blood pressure in the RYR group were significantly lower than that in the dietary control group. No serious side effects on muscle, liver, or kidney function were observed	18 patients without cardiovascular diseases and suboptimal control of LDL-C cholesterol ((3.96 ± 0.19) mmol/L) through dietary therapy alone	Both	Adults	8 weeks	Low-dose red yeast rice (200 mg/day) with 2 mg of monacolin K	[88]
2023	Randomized Controlled Trial	A daily low-dose statin lowered LDL-C significantly more than placebo, fish oil, cinnamon, garlic, turmeric, plant sterols, and RYR, which do not show any difference in cardiovascular benefit from the placebo	190 individuals,had an LDL-C of 70−189 mg/dL, without atherosclerotic cardiovascular diseases	Both	40−50 years for men or 50−60 years for women	28 days	Daily doses of rosuvastatin 5 mg, fish oil 2,400 mg, cinnamon 2,400 mg, garlic with 5,000 μg of allicin, turmeric curcumin with bioperine 4,500 mg, CholestOff Plus with 1,600 mg of plant sterols, or red yeast rice 2,400 mg	[34]
2022	Clinical TrialNCT03828006	LDL-C levels of patients in the intervention group decreased by 26.1 mg/dL and that in the placebo group increased by 4.5 mg/dL	100 participants enrolled in 2 patient groups, 88 assessed for eligibility, excluded 19 for not meeting the requirements, randomized 69 patients and enrolled. 35 patients in treatment group, 8 dropped out after 3-month visit. 4 of the placebo group subjects dropped out after baseline visit, and 5 dropped out after 3-month visit	46 female, 11 maleIn the treatment group	43-63 years old	3−6 months	A tablet containing 3.75 mg of monacolin K of RYR, 515 mg of berberine and 50 mg of coenzyme Q10 per tablet or a placebo daily	[61]
2022	Randomized Controlled Trial	Lifestyle changes and a low dose of MKA significantly improved lipid profile in patients. On average, LDL-C decreased by 15.6%, TC decreased by 15.3%, and non-HDL-C decreased by 35.4%	117 subjects with moderate to severe dyslipidemia and low cardiovascular risk; three groups with lifestyle and dosage level	Both, 26% are female	18−80 Years old range	60 days	3 g of RYR, 5 g of Folium Nelumbinis powder, and 2 g of Rhizoma Atractylodis Lanceae powder	[29]
2012 Apr	Clinical Trial	The combination of diet and exercise improve and RYR/phytosterols mix led to an average reduction of 20% and 28% in TC and LDL-C levels, respectively	18 patients with hyperlipidemia	22% male, 78% female	(57 ± 13) years	6 weeks	One 5 g serving scoop of powder containing 1,200 mg of RYR and 1,250 mg of phytosterol mix before breakfast and dinner	[94]
2019	Randomized Controlled Trial	A combination of RYR extract, guggulipid extract, and chromium picolinate reduced total cholesterol levels by 15.9% and LDL levels by 19.9% after 2 weeks. The reductions maintained throughout the 8-week study	80 subjects enrolled the study	38 males and 42 females	30–79 years old	4 weeks run-in period and 8 weeks treatment period	A nutraceutical product containing RYR extract, guggulipid extract, and chromium picolinate called NutraforChol	[95]
2013	Randomized Controlled Trial	RYR extract reduced LDL-C by 36 mg/dL (22%) and TC by 37 mg/dL (15%)	52 individuals with a total cholesterol level of above 200 mg/dL	Intervention: 19 males, 12 females.Placebo: 10 males, 11 females	44−66 years	8 weeks	2 capsules every evening, each capsule contains monacolin K 5.025 mg, Ubiquinone 30 mg, Procyanidins 20 mg and Lecithin 100 mg	[20]
2013	Randomized Controlled Trial	RYR significantly decreases LDL-C, TC, triglycerides, high-sensitivity C-reactive protein, and an increase in HDL-C compared to their baseline	187 subjects	66 females, 121 males	50−72 years old	12-weeks. primary end point was change in LDL-C at 12, 24, and 52 weeks	RYR 1,800 mg twice daily and randomized to phytosterol tablets 900 mg twice daily or placebo	[96]
2009	Randomized Controlled Trial	RYR led to significantly more reductions of LDL-C than the placebo group at both weeks 12 and 24	62 patients with dyslipidemia and a history of discontinuation of statin therapy due to myalgias	13 female, 49 male	59−70 years old	24 weeks	1,800 mg of red yeast rice, twice daily	[40]

2017	Randomized Controlled Trial	RYR-olive extract supplement reduced Lp-PLA2 by 7%. Reductions of 20% in Oxidized cholesterol (OxLDL) and 7% in Lp-PLA2 were correlated with each other	50 metabolic syndrome (MetS) patients	Female and male waist circumference >88 cm and 102 cm, respectively	Adults	20 weeks	The Cholesfytolplus capsules contained 82.9 mg monacolin and 32.8 mg hydroxytyrosol	[97]
Jan 2021	Randomized Controlled Trial	Correlations were found between plate numbers and biomarkers of cardiovascular risk in subjects with moderate hypercholesterolemia	33 subjects	16 male and 14 female	18−70 years	12 weeks	Bifidobacterium longum BB536, red yeast rice extract (10 mg/dose monacolin K)	[98]
Feb2019	Randomized Controlled Trial	A combination of Bifidobacterium longum BB12 and RYR extracts reduced TC by 7.25%, and LDL-C by 7.24%, compared to the placebo group	33 subjects,17 of them used placebo, 1 drop out	16 males and 17 females	Mean = 57, 48−63 years old	12 weeks	RYR extract contains monacolin K 10 mg, niacin 16 mg, coenzyme Q10 20 mg	[63]
Aug 2013	Randomized Controlled Trial	RYR nutraceuticals containing 10 mg monacolin can safely reduce cholesterol levels, hs-CRP, and markers of vascular remodeling in patients	25 subjects	19 males, 12 females	Mean = 52,45–61 years old	4 weeks of diet and physical activity; 4 weeks of treatment	10 mg of monacolins from Monascus purpureus and 10 mg of coenzyme Q10	[99]
Apr 2016	Randomized Controlled Trial	Monacolin treatment decreases LDL-C by 26.3% and improves endothelial reactivity	40 non-smokers moderately hypercholesterolemic subjects	26 males, 14 females	Mean = 50, 39−61 years old	6 months of testing. After 4 weeks of diet and physical activity	10 mg monacolins and 30 mg coenzyme Q10	[92]
Mar 2015	Randomized Controlled Trial	The intervention decreases LDL-C by 24%, TC by 17%, apolipoprotein by 15%, TG by 9%, oxidized LDL by 20%, systolic by 10 mmHg pressure and diastolic pressure 7 mmHg, respectively	50 subjects with metabolic syndrome	30 females, 20 males.	Adults	8 weeks	10.82 mg of monacolins and 9.32 mg of hydroxytyrosol per capsule	[20]
Aug 2017	Randomized Controlled Trial	RYR decrease diastolic blood pressure by 2.67 mmHg after 12 weeks	60 subjects with primary hyperlipidemia	43 males, 17 females.	Mean = 47, 34−58 years old	8 weeks	RYR with Lactobacillus casei or placebo	[100]
Feb 1999	Clinical Trial	RYR decreases TC and LDL-C after 8 weeks	46 men and 37 women	Male and female	34−78 years old	12 weeks	RYR 2.4 g or placebo daily and a diet with less than 10% fat, 300 mg of saturated fat, and 300 mg of cholesterol	[101]
Jun 2013	Clinical Trial	RYR decreases TC and LDL-C levels after 8 weeks	30 patients, 28 completed	19 males, 9 females	Mean = 45.6,33–58 years old	8 week first and follow up for 4 weeks	RYR capsules 600 mg twice a day	[102]
Dec 2017	Controlled Clinical Trial	A combination of RYR and olive extract attenuates blood lipid levels in patients with hypercholesterolemia	642 hypercholesterolemic patients	289 males, 353 females	Mean = 59 years old	2 months	RYR and olive extract (5 mg hydroxytyrosol equivalent)	[80]
Feb 2012	Randomized Controlled Trial	RYR, bitter melon, chlorella, soy protein, and licorice extracts are effective in reducing TC, LDL-C, TG, waist circumference, blood pressure and other metabolic syndrome symptoms	228 subjects, 92 completed, 52 in plant-based treatment, 44 in placebo	44 males, 48 females	Mean = 52, 41−62 years old. Health adults, quit smoking a year ago, not pregnant	12 weeks	Mixing RYR0.37 g, bitter gourd 40 g, chlorella 1.5 g, soy protein 1.1 g, and licorice 2.2 g and divided into 1 g tablet once daily	[79]
Jun 2011	Randomized Controlled Trial	RYR extract reduces total cholesterol by 18.5%, LDL-C by 25.1%, and apolipoprotein B by 25.3% in patients with hypercholesterolemia	40 child patients, 24 subject affected by heterozygous Familial hypercholesterolemia and 16 subject affected by Familial combined hyperlipidemia	21 males,19 females	Children aged 8−16 years	4 weeks week-in; 8 weeks of treatment; 4 weeks washout	RYR extract 200 mg with 3 mg of monacolins, and 10 mg policosanols once daily	[71]
Mar 2019	Randomized Controlled Trial	Monacolin K reduces blood TC and LDL-C levels significantly compared to other groups in a 3-month study	52 total subjects. 16 in monacolin K-rich group, 17 in GABA-rich group, 17 in placebo groups	22 males,30 females	Mean = 43; 29−64 years in all groups	3 months	RYR 400 mg with 8 mg of monacolin K or 0.14 mg of GABA daily	[77]
Jul 2017	Randomized Controlled Trial	After 12 weeks, the compounds effectively reduced LDL-C by 20% and non-HDL-C by 15%	39 subjects	54% females	age (52 ± 11) years	12 weeks	Berberine 200 mg, monacolin K 3 mg, chitosan 10 mg and coenzyme Q 10 mg	[103]
Apr 2014	Randomized Controlled Trial	The nutraceutical combination significantly decreased TC, LDL-C, TG and all adipocytokines levels compared to baseline	134 dislipidemic patients, 132 finished after 3 months	67 males, 65 females	Mean = 54, 46−64 years old	3 months	1 tablet/day, a combination of RYR 200 mg, Silybum marianum 300 mg, Monascus putpureus 3 mg, Guggul (Commiphora mukul) 100 mg, Guggulipidi 10 mg, Saccharumqfficinartun 31.7 mg, policosanols 30 mg, octacosanol18.4 mg	[64]

Year of study	Study design	Outcomes	Group size	Researched gender	Group age	Time course	Drug and dosage	Reference
Note: ASCOT-LLA, Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm; HPS, Heart Protection Study; JUPITER, Justification for the Use of Statin in Prevention: An Intervention Trial Evaluating Rosuvastatin; WOSCOPS, The West of Scotland Coronary Prevention Study; LIPID, Long-term Intervention with Pravastatin in Ischaemic Disease; CORONA, Controlled rosuvastatin multinational study in heart failure; PROSPER, PROspective study of pravastatin in the elderly at risk; MEGA, Primary prevention of cardiovascular disease with pravastatin in Japan; AFCAPS/texCAPS, Air Force/Texas Coronary Atherosclerosis Prevention Study; 4S, Scandinavian Simvastatin Survival Study; ALLHAT-LLT, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial; GISSI-HF, Gruppo Italiano per lo Studio della Sopravvivenza nell\'Infarto Miocardico-Prevenzione-chronic heart failure; GISSI-Prevenzione, Gruppo Italiano per lo Studio della Sopravvivenza nell\'Infarto Miocardico-Prevenzione.
2010	Cohort study	Statins increased risk for incident diabetes by 9%	13 statin trials with 91,140 participants	Both	Adults, age group are 55−76 years old	4 years	13 different kinds of standard care-controlled statin trials.ASCOT-LLA (Atorvastatin10 mg), HPS (Simvastatin40 mg), JUPITER (Rosuvastatin20 mg), WOSCOPS (Pravastatin40 mg), LIPIDS (Pravastatin40 mg), CORONA (Rosuvastatin20 mg), PROSPER (Pravastatin40 mg). MEGA (Pravastatin10–20 mg), ADCAPS TexCAPS (Lovastatin20–40 mg), 4S (Simvastatin20–40 mg), ALLHAT-LLT (Pravastatin 40 mg), GISSI-HF (Rosuvastatin 10 mg), GISSI-PREVENZIONE (Pravastatin 20 mg)	[91]
2012	Cohort study	Statin use linked to increased risk of diabetes in postmenopausal women	161,808, 7.04% of them are using statin during the study	Females	50−79 years old	1, 3, 6, 9 years	Statins	[53]
2013	Cohort study	Atorvastatin, rosuvastatin, and simvastatin were associated with an increased risk of developing diabetes compared with pravastatin. Fluvastatin and lovastatin did not present a significant risk	All Ontario adults >65 years and taking statins	Both	66 and older	Up to 5 years	Statins:fluvastatin, lovastatin, pravastatin at all doses; high: atorvastatin ≥80 mg and rosuvastatin ≥40 mg; moderate: atorvastatin 20−<80 mg, rosuvastatin 10 mg−<40 mg, and simvastatin ≥80 mg; low: atorvastatin <20 mg; rosuvastatin <10 mg, simvastatin <80 mg	[43]
2014	Cohort study	Risk of new-onset diabetes increases with increased statin therapy adherence	115,709	Both	(62.3 ± 9.4) years	6−7 years	For high potency ones, rosuvastatin ≥10 mg, atorvastatin ≥20 mg, and simvastatin ≥40 mg. All others were defined as low potency	[104]
2020	Cohort study	In diabetic patients, the Ejection Fraction and the proportion of heart failure admissions of the hydrophilic statin group were significantly lower than that of the lipophilic group	1,752	Both	(64.4 ± 10.9) years	14 years (April 1998 to September, 2012)	The hydrophilic statins, pravastatin rosuvastatin and lipophilic statins, simvastatin, atorvastatin, pravastatin, fluvastatin	[23]
2020	Cohort study	People prescribed red yeast rice may have a lower risk of diabetes than people using the synthetic drug lovastatin	34,504	Both, 19,178 females, 15,326 males.	Adults, 20 years or older	2010−2014	Lovastatin and red yeast rice	[105]
2001	Cohort study	pravastatin therapy resulted in a 30% reduction (P = 0.042) in the hazard of becoming diabetic	5,974	Males	45−64 years	6 months	Pravastatin	[66]