Red yeast rice (RYR) is a fermented rice with a long history of use as a food and medicine in East Asia.^[8] RYR is produced by fermenting white rice (Oryza sativa) with an edible fungus, most commonly Monascus purpureus, which results in the production of a variety of bioactive compounds and pigments, the latter of which imparts a reddish-purple color to the rice.^[7] The primary active compound in RYR is thought to be monacolin K, which is structurally identical to the cholesterol-lowering medication lovastatin.^[7] However, the type and amount of monacolins present in RYR can vary depending on the fermentation conditions and the type of yeast used.^[9] The majority of research on RYR has examined its effects on dyslipidemia and general cardiovascular health, with promising results.

In clinical trials, RYR consistently demonstrates the ability to improve lipid profiles in people with dyslipidemia. RYR seems to reduce low-density lipoprotein (LDL) cholesterol, triglyercides, total cholesterol, and apolipoprotein B; it also seems to increase high-density lipoprotein (HDL) cholesterol.^[5][10] Overall, RYR is thought to reduce LDL cholesterol by 15 to 25% within 6 to 8 weeks, and its effect on lipid profiles is comparable to moderate-intensity statin medications (first-line cholesterol-lowering medications).^[11][5] RYR may improve markers of atherosclerosis and protect against major adverse cardiac events; however, most of this research has been conducted in Chinese populations, and its generalizability to other populations is not clearly established.^[3][12][4] RYR may also reduce systemic inflammation, as suggested by reductions in C-reactive protein, although this effect is less thoroughly researched.^[13][14][15]

RYR appears to be well-tolerated by most people, and generally, studies have not found differences in rates of side effects between RYR and placebo.^[9][16] Despite this, several case reports have suggested that, on rare occasions, RYR supplementation at normal dosages (equivalent to 3–10 mg daily of monacolin K) may cause rhabdomyolysis (dangerous muscle breakdown) or hepatitis (liver inflammation).^[17] Rhabdomyolysis is a known risk of treatment with prescription statin medications, including lovastatin, and is estimated to occur in 1 in every 10,000 people.^[18][19] Hepatitis has also very rarely been observed with lovastatin treatment.^[20] Additionally, RYR supplements can contain citrinin which is a potentially harmful compound produced during fermentation. Citrinin can be toxic to the liver and kidneys and care should be taken to choose an RYR supplement that is citrinin-free.^[7]

Importantly, monacolin K is metabolized by cytochrome P450 3A4 (CYP3A4) enzymes. Medications or foods that inhibit CYP3A4 (e.g., verapamil, clarithromycin, ketoconazole, ritonavir, grapefruit) can lead to increased levels of monacolin K in the blood and this combination should be avoided.^[9] Additionally, RYR should not be taken in addition to statin medications. This combination may increase the risk of serious side effects and isn’t likely to provide additional therapeutic benefits.^[17][5]

Lastly, there is a concerning degree of variability in the content of monacolin K in RYR, and most supplements are not transparent about how much of this active compound they contain. For example, a study conducted in the United States found that the amount of monacolin K in 26 tested supplements differed up to 60-fold.^[21] This could lead to inconsistencies in the effectiveness of RYR supplementation.

RYR contains a variety of compounds with biological activity, but monacolins — a class of metabolites produced through fungal fermentation — are considered the main active ingredients. Monacolins, particularly monacolin K, work in the same way as statin medications, which involves the inhibition of a key enzyme involved in cholesterol synthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase.^[4] Therefore, RYR effectively reduces the body's own synthesis of cholesterol. Interestingly, the pigments found in RYR may also contribute to this lipid-lowering effect. Animal research suggests that these pigments may influence lipid metabolism and lead to an increase in the excretion of cholesterol, triglycerides, and bile acids in the feces.^[22]