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.[1][2] 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).[3] 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.[4][5] Hepatitis has also very rarely been observed with lovastatin treatment.[6] 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.[1] 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.[3][8]
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.[9] This could lead to inconsistencies in the effectiveness of RYR supplementation.