Given the detrimental consequences of dyslipidemia and in light of certain limitations to statin use, this randomized clinical trial (RCT) sought to assess the effects of red yeast rice (RYR) in patients with dyslipidemia already on statin therapy. We found that RYR, alongside statin therapy, can significantly decrease total cholesterol levels without adversely affecting liver enzymes levels (AST, ALT).
Several meta-analyses have confirmed the strong relationship between LDL levels and the risk of cardiovascular disease (CVD) . One meta-analysis by the Cholesterol Treatment Trialists’ (CTT) Collaboration worked on data from 14 RCTs and about 90,000 subjects. The study suggested that as the serum level of LDL-C falls, the risk of CVD decreases accordingly . Another CTT meta-analysis on more than 170,000 patients revealed that each time the LDL concentration drops by one mmol/L, the risk of ischemic stroke, coronary artery disease, and revascularization drops by over one-fifth . Because of the benefits of LDL-C reduction, lipid-lowering agents – especially statins – are highly popular.
Recently, RYR has gained popularity as an alternative LDL-lowering agent with few adverse effects . Several meta-analyses have confirmed the effect of RYR on the reduction of LDL-C. One recent study worked on 20 RCTs and 6663 individuals; it showed that after 2 months to 2 years of therapy, RYR decreased the serum LDL-C level by 1.02 mmol/l (~ 39.4 mg/dl) (with 95% confidence) in comparison with the placebo, indicating considerable efficacy similar to that of low-intensity or low-dose statins (pravastatin 40 mg, simvastatin 10 mg, lovastatin 20 mg). The researchers also confirmed a slight increase in HDL-C and an insignificant decrease in TG . Another study showed that patients receiving RYR experienced significant decrements in serum LDL-C (23.0%) and total cholesterol (15.5%) levels relative to a control group following a sixteen-week treatment period (P < 0.001) . The lipid-lowering effect of RYR is believed to be due to the presence of monacolin K, which possesses the same structure as lovastatin . It is thought that RYR limits the rate of hepatic cholesterol production by inhibiting the 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase enzyme .
One consideration in the use of novel lipid-lowering agents is hepatotoxicity. A meta-analysis of seven trials [16, 24,25,26,27,28,29] assessed serum AST levels before and after intervention with RYR. The researchers showed that although the serum AST level were considerably higher in those who received RYR relative to controls, they remained within the normal range (0–40 U/L) [Total WMD = 1.55 (95% CI: 0.26, 2.84) U/L, I2 = 0%, P = 0.02, 7 trials (8 comparisons), n = 443]. Our study found that after 1 month of treatment, the serum AST level was only slightly higher in the intervention group than the placebo group (P = 0.074) and remained within the normal range. In the mentioned trials [16, 24,25,26,27,28,29], the serum ALT levels was significantly higher in the intervention group compared with the placebo group but again remained within the normal range (0–40 U/L) [Total WMD = 1.47 (95% CI: 0.42, 2.51) U/L, I2 = 0%, P = 0.006, 7 trials (8 comparisons), n = 443]. At the end of our study, the ALT level was also negligibly higher in the intervention group relative to the placebo group (P = 0.714) and remained within the normal range.
Another important aspect related to RYR is that it may improve endothelial function. In one study, 50 coronary heart disease patients randomly received either RYR (1200 mg daily, containing 11.4 mg of monacolin K) or a placebo, and the serum hs-CRP concentration was monitored. After 6 weeks, those receiving RYR experienced reductions in hs-CRP (P < 0.001) . However, in our study, changes in hs-CRP levels after 4 weeks of intervention were not significant compared with the placebo (P = 0.78).
Although some recent studies only worked on the effect of RYR in isolation on LDL-C, our study investigated the effect of RYR when accompanied by another statin (atorvastatin or rosuvastatin) on both total cholesterol and LDL-C levels. Due to our limited sample size, further large-scale studies seem warranted. Another limitation was the significant differences in baseline total cholesterol and LDL levels between the study groups. Although the study was randomized, this may be due to the small sample size. We also measured the effect of RYR with only a one-month follow-up; future studies should consider an extended period of follow-up.
Although in this randomized trial, we showed that use of RYR is sfae with statin, this need further larger trials to show the effect of RYS on lipid profile.