Young Ju, Ph.D.

Red yeast rice (RYR), also called Went yeast or red koji, has been used as a medicinal food for thousands of years in East Asian countries such as China, Japan, Korea, and Thailand. Research studies have reported numerous health benefits of RYR, including hypolipidemic (cholesterol-lowering), anti-atherosclerotic, anti-cancer, neuroprotective, hepatoprotective, anti-osteoporotic, anti-fatigue, anti-diabetic, anti-obesity, immunomodulatory, anti-inflammatory, anti-hypertensive, and antimicrobial activities. The purpose of this article is to provide you with more information about how taking RYR can affect blood cholesterol levels.

RYR is produced by the fermentation of rice with Monascus yeast (most commonly with Monascus purpureus strain) (1). This yeast is added to steamed rice and fermented in a controlled environment. During the fermentation process, the yeast enriches the rice with many fermentation byproducts, and the rice turns red.

Monacolin K in RYR (1),  one of many fermentation byproducts in RYR, is the key substance responsible for lowering cholesterol. Monacolin K is chemically identical to the prescription drug, lovastatin (Mevacor®). Lovastatin is a medicine in the statin class, which is the most common cholesterol-lowering drug class. Like other statins, lovastatin helps inhibit the production of cholesterol in the liver. Pharmaceutical doses of lovastatin ranges from 10 mg to 80 mg per day.  Approximately 10% of statin users may experience side effects. The most common side effects of lovastatin include structural, functional, and/or metabolic damage to muscle, liver, and kidney. Monacolin K content in RYR products varies from one product to another due to fermentation conditions, e.g., temperature, humidity, and duration.

During the fermentation process, a fungal toxin, citrinin, can also be produced. Citrinin can cause kidney damage. Some RYR products may have a “citrinin-free” label.  

In the US, regulation of RYR products is a bit complicated (1,2). They are sold as dietary supplements, and anyone can buy these products without prescription. Although sold as dietary supplements, the US Food and Drug Administration (FDA) considers RYR products containing significant amounts of monacolin K to be unapproved drugs which cannot be sold legally in the US. In other words, since lovastatin had already been approved as a drug, monacolin-K-containing RYR supplements are considered unapproved drugs.

The questions then become, “What dosage is considered a significant amount of monacolin K?” and “How do consumers know how much monacolin K is in RYR supplements?” As mentioned above, RYR products do not always contain consistent amounts of monacolin K. Since 1998, the FDA has sent warning letters to manufacturers of RYR products containing high amounts of monacolin K noting that it’s illegal to market those products as supplements in the US. Currently, the FDA is not regulating manufacturers of RYR products. FDA regulations need to be updated to align with the updated research evidence. The European Union has reviewed the safety of monacolins in RYR and has amended its regulations on RYR products. In 2018, the European Food Safety Authority concluded that monacolin K (3-10 mg per day) from RYR supplements could lead to severe adverse effects on the musculoskeletal system and the liver. Currently, this Panel warns not to consume 3 mg or more of monacolin K from RYR supplements.

Cholesterol-lowering effect of RYR products (3-7):  In recent reviews, daily RYR supplementation ranging from 1,200–4,800 mg RYR (~3-10 mg monacolin K) has been tested. These studies investigated effects on metabolic parameters such as blood sugar, blood cholesterol, waist circumference, and blood pressure in people with diabetes, hypercholesterolemia, hypertension, or metabolic syndrome, etc. The duration of RYR intake ranged from 1 month to 5 years. Studies found that RYR products lowered LDL-cholesterol (‘bad’ cholesterol) by 15-31%, total cholesterol by 16-25%, and triglycerides by 5-24%. These studies also reported a slight increase in HDL-cholesterol (‘good’ cholesterol) of  5-10%.   They also noted that RYR is as effective as statins and may cause the same side effects. In one study (8), RYR was tested in patients with familial hypercholesterolemia (an inherited condition that causes very high LDL-cholesterol levels) who had discontinued statins due to muscle pain. This study found that 300 mg RYR (~10 mg of monacolin K) lowered LDL-cholesterol levels in both men and women. These findings suggest that RYR supplement may be a safe alternative for non-statin users, and these conclusions are in opposition to the  2018 EFSA Panel report. In 2022, the International Lipid Expert Panel concluded that RYR products are safe and effective in improving lipid profiles and to some extent in reducing the risk of cardiovascular events. 

RYR may be a treatment to be considered by:

• those not eligible for statin therapy with a lower risk for cardiovascular disease who cannot maintain ideal lipid profile by diet and lifestyle alone

• those who are eligible for statin therapy, but choose not to take a statin

• those with statin intolerance due to its side effects

RYR should not be considered by:

• those already on cholesterol-lowering medications.

• people with liver disease

• people with kidney disease

• people with myopathy (conditions that affect the skeletal muscles)

• women who are pregnant and breastfeeding (due to no available studies)

Overall

You should understand your reasons for selecting a RYR product over a regulated drug prescribed by your doctor. If you have difficulty with the prescribed drug available for cholesterol, RYRs may be tolerable as well as safe and effective in improving lipid profiles and in reducing the risk of cardiovascular events and improving metabolic parameters. Note that it is still possible to have monacolin K-induced side effects. Unfortunately, there is no way at this time for consumers to figure how much monacolin K is in RYR supplements until the FDA updates regulations and labeling to ensure the quality, safety and efficacy of RYR supplements.

If you are considering taking an RYR supplement, talk to your doctor. If you are already taking a RYR product, pay attention to potential side effects.  And as always, please read the product labeling.

References

1. National Center for Complementary and Integrative Health. Red yeast rice: What you need to

   Know. https://www.nccih.nih.gov/health/red-yeast-rice

2. European Food Safety Authority. Scientific opinion on the safety of monacolins in red yeast rice.

   EFSA Journal, 2018, 16(8):5368.

3. Klosiewica-Latoszek, L., Cybulska, B., Stos, K., Tyszki, P. Hypolipaemic nutraceuticals: red yeast

   rice and armopipid, berberine and bergamot. Ann. Agrc.Env. Med. 2021, 28(1):81.

4. Banach, M., Catapano, A.L., Cicero, A.F.G., Escobar, C., Foger, B., Katsiki, N., Latkovskis, G.,

   Rakowski, M., Reiner, Z., Sahebkar, A., Sikand, G., Penson, P.E. Red yeast rice for

   dyslipidaemias and cardiovascular risk reduction: A position paper of the International Lipid

   Panel. Pharma. Res. 2022, 183: 106370.

5. Yuan, R., Yuan, Y., Wang, L., Xin, Q., Shi, W., Miao, Y., Leng, S.X., Chen, K., Cong, W., BPNMI Consortium. Red yeast rice preparations reduce mortality, major cardiovascular adverse effects, and risk factors for metabolic syndrome: A systematic review and meta-analysis. Frontiers in Pharmacol. 2022, 13:744928.

6. Cicero, A.F.G., Fogacci, F., Zambon, A. Red yeast rice for hypercholesterolemia. J Am Col Cardiol. 2021, 77(5):620. 

7. Li, Y., Jiang, L., Xin, J.W., Yang, S., Yang, Q., Wang, L. A meta-analysis of red yeast rice: An effective and relatively safe alternative approach for dyslipidemia. PLoS One 2014, 9(6):e98611.

8. Stafanutti, C., Mazza, F., Mesce, D., Morozzi, C., Giacomo, S.D., Vitale,M., Pergolini, M. Monascus purpureus for statin and ezetimibe intolerant heterozygous familial hypercholesterolaemia patients: A clinical study. Atherosclerosis Supplements 2017, 30:86.

This information is provided for your reference and you use at your own risk; you should rely on your medical professional for medical advice.