UNASSIGNED: Sustained hyperlipidemia contributes to fatty liver and liver cirrhosis. Red yeast rice (RYR) effectively improved the lipid profile; however, the effects of RYR on the risk of incident liver cirrhosis remain to be elucidated. We aimed to evaluate the beneficial effects of RYR use on the risk and outcome of liver cirrhosis.
UNASSIGNED: We identified 156,587 adults who had newly diagnosed hyperlipidemia in 2010-2016 from health insurance data in this retrospective cohort study. Using propensity score matching, we selected 34,367 patients who used RYR and 34,367 patients who used lovastatin. Events of incident liver cirrhosis that occurred in the two cohorts during the follow-up period of 2010-2019 were identified. We calculated adjusted hazard ratios (HRs) and 95% confidence intervals (Cis) for liver cirrhosis risk associated with RYR use in the multiple Cox proportional hazard model.
UNASSIGNED: Compared with patients who used lovastatin, patients who used RYR had a decreased risk of liver cirrhosis (HR 0.60, 95% CI 0.57-0.63), and this association was significant in various subgroups. A biological gradient relationship between the frequency of RYR use and decreased liver cirrhosis was observed (p for trend < 0.0001). Reduced postcirrhosis jaundice (HR 0.56, 95% CI 0.43-0.72), ascites (HR 0.37, 95% CI 0.28-0.50), hepatic coma (HR 0.36, 95% CI 0.26-0.50), and mortality (HR 0.48, 95% CI 0.38-0.61) were also associated with RYR use.
UNASSIGNED: We demonstrated the beneficial effects of RYR use on the risk and outcome of liver cirrhosis; however, the lack of compliance data should be considered. However, our study did not infer causality or claim the superiority of RYR over lovastatin.

Nattokinase (NK) and red yeast rice (RYR) are both indicated for their potential in cardiovascular disease prevention and management, but their combined effects especially in coronary artery disease (CAD) are scarcely examined. This 90-day randomized, double-blind trial aims to investigate the effect of NK and RYR supplementations on cardiometabolic parameters in patients with stable CAD. 178 CAD patients were randomized to four groups: NK + RYR, NK, RYR, and placebo. No adverse effects due to the interventions were reported. In comparisons across groups, NK + RYR showed the maximum effect in reducing triglyceride (-0.39 mmol), total cholesterol (-0.66 mmol/L), diastolic blood pressure (-7.39 mmHg), and increase in high-density lipoprotein cholesterol (0.195 mmol/L) than other groups (all p for multiple groups comparison<0.01). Both NK + RYR and NK groups had significantly better-improved lactate dehydrogenase than the others (-29.1 U/L and - 26.4 U/L). NK + RYR group also showed more potent reductions in thromboxane B2 and increases in antithrombin III compared to placebo (both p < 0.01). These improved markers suggest that combined NK and RYR may preferably alter antithrombin and COX-1 pathways, potentially reducing thrombosis risks in CAD patients. Overall, the combined NK and RYR supplementation is safe and more effective than separately in improving cardiometabolic markers among CAD patients with multiple heart medications use.

Red yeast rice (RYR) is known for its lipid-lowering effects in patients with hypercholesterolemia; however, its comparative efficacy with statins and risk reduction remains uncertain. This retrospective study analyzed data from 337,104 patients with hyperlipidemia in the Chang Gung Research Database cohort, spanning from January 2016 to December 2021. Exclusion criteria were applied to ensure data completeness and compliance, including an age limit of [Formula: see text] years, absence of RYR or statin treatment, and a treatment duration of [Formula: see text] days. Propensity score matching was employed to minimize bias based on baseline factors, with one patient matching with four patients in the comparison group. The study encompassed a total of 5,984 adult hyperlipidemic patients, with 1,197 in the RYR group and 4,787 in the statin group. The patients were also stratified into statin ([Formula: see text]) or combined use ([Formula: see text]) groups for further comparison. Following one year of treatment, both the RYR and statin groups exhibited reductions in total cholesterol and triglyceride levels. Most biochemical parameters showed no significant differences, except for elevated glutamic oxaloacetic transaminase levels in the RYR group ([Formula: see text]) and increased glycohemoglobin levels in the statin group at the three-month mark ([Formula: see text]). In patients with comorbid diabetes, hypertension, kidney, or liver diseases, RYR and statins demonstrated comparable risks for emergency room (ER) visits, stroke, and myocardial infarction (MI). However, the combination of RYR and statins was associated with reduced stroke-related hospitalizations in patients with diabetes, hypertension, and kidney disease, as well as decreased MI-related hospitalizations in patients with hypertension and kidney disease (all [Formula: see text]). In conclusion, both RYR and statins effectively lower blood lipid levels and mitigate related complications. Combining these therapies may lead to fewer ER visits, reduced stroke frequency, and fewer MI hospitalizations in hypertensive and kidney disease patients, and they decreased all-cause mortality in the kidney disease population. Further research on combined therapy is warranted.

UNASSIGNED: Red yeast rice and omega-3 polyunsaturated fatty acids (PUFAs) are dietary supplements with well-known lipid-lowering, anti-inflammatory, and vascular health improving effects. However, they have rarely been tested in combination. The aim of our study was to test the short-term effect of a combined nutraceutical including red yeast rice and PUFAs on plasma lipids, jigh-sensitive C-reactive protein (hsCRP), and endothelial function in healthy subjects.
UNASSIGNED: We carried out a double-blind, randomized, placebo-controlled clinical trial with parallel groups testing the effect of 8 weeks of supplementation with softgels containing red yeast rice (2.8 mg monacolins) and PUFAs (588 mg of fish oil, standardized in PUFAs: 350 EPA, 45 mg DHA) versus placebo. A full lipid panel, hsCRP, and endothelial reactivity were measured at the baseline and after 8 weeks of treatment.
UNASSIGNED: The tested combined nutraceutical was very well tolerated, and after 8 weeks of supplementation it was associated with a 17.3 ±3.4% reduction of lipid-density lipoprotein-cholesterol (LDL-C), a 12.1 ±2.2% reduction of total cholesterol (TC), a 22.3 ±4.3% reduction of apoB, and a -14.9 ±1.8% reduction of hsCRP, as well as a significant improvement of pulse volume change by 5.0 ±0.9%.
UNASSIGNED: The tested combined dietary supplement containing red yeast rice and PUFAs was very well tolerated and significantly improved LDL-C, TC, apoB, hsCRP and endothelial function in healthy subjects with suboptimal LDL-cholesterolaemia.

Dyslipidemia, a condition implying high cardiovascular risks, has been widely studied on its potential nutrition interventions, including functional foods. This study aims to examine the effect of nattokinase monascus supplements (NMSs) on cardiovascular biomarkers and carotid intima-media thickness (CIMT) in patients with dyslipidemia. A total of 113 eligible subjects were randomly assigned to receive either NMSs or a placebo (55 and 58, respectively). After a 120-day intervention, there were significant mean absolute changes in total cholesterol (TC), low-density cholesterol (LDL-C), non-high-density cholesterol (non-HDL-C), and low-density cholesterol to high-density cholesterol ratio (LDL-C to HDL-C ratio), with values of -0.52 (95% CI: -0.51 to -0.54) mmol/L, -0.43 (95% CI: -0.45 to -0.41) mmol/L, -0.52 (95% CI: -0.52 to -0.52) mmol/L, and -0.29 (95% CI: -0.30 to -0.28) mmol/L, respectively, between the two groups. However, no significant differences were found in triglycerides (TGs), high-density cholesterol (HDL-C), and CIMT. Furthermore, the results for lipids and CIMT remained essentially unchanged after adjusting for various confounding factors using the analysis of covariance model. There were no significant differences in coagulation, liver function, renal function, or other indicators. No intervention-related adverse events, such as mouth ulcers, drooling, and stomach pain, were reported. The study results demonstrate that NMSs can ameliorate lipid levels (TC, LDL-C, non-HDL-C, and the LDL-C to HDL-C ratio) without the occurrence of adverse events. However, it did not significantly affect serum TG, HDL-C, and CIMT.

UNASSIGNED: There is growing interest in head-to-head comparison between different lipid-lowering nutraceuticals. The aim of our study was to test the lipid-lowering effect of dietary supplementation with low-dose monacolins from red yeast rice (2.8 mg per daily dose) combined with berberine (Armolipid Plus®) or highly standardized artichoke extract versus placebo.
UNASSIGNED: 60 overall healthy adult volunteers with polygenic hypercholesterolemia (baseline low-density lipoprotein cholesterol (LDL-C) = 160.2 ±9.2 mg/dl) were enrolled in a 3-arm, double-blind, non-inferiority, randomized, parallel-group clinical trial. After 4-week diet standardization, enrolled individuals were randomized to be treated for 8 weeks with red yeast rice and highly standardized artichoke extracts (ATC group), Armolipid Plus®, or placebo.
UNASSIGNED: At the enrolment visit, LDL-C values were similar in the compared groups. After 8 weeks, all actively treated subjects experienced significant improvements in baseline total cholesterol (TC), LDL-C and apolipoprotein B (Apo-B) (all p < 0.01) (ATC group: TC = -18.9%, LDL-C = -26.7% (placebo-corrected: -12.4%), Apo-B = -19.6%; Armolipid Plus®: TC = -18.4%, LDL-C = -25.8% (placebo-corrected: -12.1%), Apo-B = -23.2%; placebo: TC = -6.2%, LDL-C = -8%, Apo-B = -8.4%). Participants in the ATC group attained significantly lower body mass index (BMI) values (-2.1%), while individuals treated with Armolipid Plus® showed improvements in baseline high-density lipoprotein cholesterol (HDL-C) (+8.7%) and triglyceride (TG) (+17.5%) levels. Finally, baseline hepatic steatosis index (HSI) values significantly decreased in both actively treated groups (by -2.4% and -2.4% in ATC and in Armolipid Plus®, respectively).
UNASSIGNED: Patients with polygenic hypercholesterolemia experienced a significant improvement in several cardiovascular risk factors in both ATC and Armolipid Plus® groups.

BACKGROUND: Dyslipidemia is a prominent cause of cardiovascular disease as it leads to inflammation and plaque deposition within arteries. Treatment includes lifestyle modifications and lipid-lowering medications. We aimed to assess the therapeutic effects of red yeast rice (RYR) alongside statin therapy.
METHODS: This triple-blind randomized clinical trial involved 92 dyslipidemia patients and was performed in 2019. Standard laboratory tests were used to assess the serum LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), total cholesterol, triglyceride (TG), and high sensitivity C-reactive protein (hs-CRP) levels. Subsequently, patients randomly received one daily RYR or placebo tablet for 1 month beside routine single statin therapy. Subsequently, blood tests were repeated and compared against the baseline. Liver function tests were also requested.
RESULTS: Total cholesterol significantly (P = 0.019) decreased in the treatment group (- 10.2 mg/dL) compared with the placebo group (- 1.3 mg/dL). HDL cholesterol decreased by 2.19 mg/dL in the treatment group but increased by 0.53 mg/dL in the treatment group (P = 0.083). LDL cholesterol declined in both placebo (- 5.09) and treatment (- 0.73) groups (P = 0.187). TG increased by about 7 mg/dL in the treatment group but fell by roughly 1 mg/dL in the placebo group (P = 0.386). Hs-CRP increased by 0.28 mg/dL in the treatment group but decreased by 0.09 mg/dL in the placebo group (P = 0.336).
CONCLUSIONS: We found that adding RYR (Lesstat®) to statin medications significantly decreases total cholesterol. However, no significant effect was seen on other lipid profile components or Hs-CRP. Finally, we showed that RYR is safe to add to statins considering liver function (clinicaltrials.gov: NCT05095480).

Herbal dietary supplements (HDS) used for dyslipidemia represent a category of concern in Italy for suspected adverse reactions (ARs). However, we cannot estimate their safety, as we do not know their commercial profile. Sales data of HDS, and particularly, those used for dyslipidemia, were monitored for 2 years in two pharmacies of Rome. Meanwhile, spontaneous reports of suspected ARs potentially related to dyslipidemia supplements were collected by the Italian Phytovigilance System. The 50% of the total dietary supplements are herbal-derived; the 9% of HDS are recommended for dyslipidemia. From our data, 113 different brands have claims for improving lipids profile and 91% of them are multiingredient preparations. Fifteen spontaneous reports of suspected ARs concerned HDS used, for dyslipidemia. The most frequent ARs were joint, abdominal, and muscles pain; vomiting; erythema and hematological disorders; nausea; and rhabdomyolysis. Our findings point out the limited compliance of commercial dyslipidemia-HDS and scientific research about their intrinsic safety. A wide range of ingredients could not support the risk/benefit profile of the supplement. The variable compositions of HDS do not assure the safety, as they do not support the reproducibility of their pharmacological activities. This study could contribute to optimize consumer guidance about what they purchase and consume.

The development of incurred reference materials containing citrinin (CIT) and their successful application in a method validation study (MVS) in order to harmonize CIT determination in food and food supplements are demonstrated. CIT-contaminated materials made of red yeast rice (RYR), wheat flour, and Ginkgo biloba leaves (GBL), as well as food supplements made of red yeast rice (FS-RYR) and Ginkgo biloba leaves (FS-GBL), were manufactured in-house via fungal cultivation on collected raw materials. The homogeneity and stability from randomly selected containers were verified according to the ISO 13528. CIT was found to be homogenously distributed and stable in all contaminated materials, with no significant degradation during the timescale of the MVS when storage was performed up to +4 °C. Next, an MVS was organized with eighteen international laboratories using the provided standard operating procedure and 12 test materials, including three RYRs (blank, <50 µg/kg, <2000 µg/kg), two wheat flours (blank, <50 µg/kg), two GBL powders (blank, <50 µg/kg), three FS-RYRs (blank, <50 µg/kg, <2000 µg/kg), and two FS-GBLs (blank, <50 µg/kg). The results of seven CIT-incurred materials showed acceptable within-laboratory precision (RSDr) varying from 6.4% to 14.6% and between-laboratory precision (RSDR) varying from 10.2% to 37.3%. Evidenced by HorRat values < 2.0, the results of the collaborative trial demonstrated that the applied analytical method could be standardized. Furthermore, the appropriateness of producing CIT reference materials is an important step towards food and feed quality control systems and the organization of proficiency tests.

Phytosterols and red yeast rice are largely studied cholesterol-lowering nutraceuticals, respectively inhibiting the bowel absorption and liver synthesis of cholesterol. Our aim was to test the effect of combined nutraceutical-containing phytosterols and red yeast rice vs. a placebo on the lipid profile. We performed a parallel arms, double-blind, placebo-controlled clinical trial, randomizing 88 moderately hypercholesterolemic subjects to treatment with a combined nutraceutical containing phytosterols (800 mg) and red yeast rice, standardized to contain 5 mg of monacolins from Monascus purpureus, with added niacin (27 mg) and policosanols (10 mg) (LEVELIP DUO®), or placebo. The mean LDL-Cholesterol (LDL-C) change at Week 8 was -32.5 ± 30.2 mg/dL (-19.8%) in the combined nutraceutical group and 2.5 ± 19.4 mg/dL (2.3%) in the placebo group. The estimated between-group difference of -39.2 mg/dL (95% CI: -48.6; -29.8) indicates a statistically significant difference between treatments in favor of the combined nutraceutical (p < 0.0001). Total Cholesterol (TC), non-HDL cholesterol (non-HDL-C), Apolipoprotein B, TC/HDL-C and LDL-C/HDL-C improved in a similar way in the combined nutraceutical group only. No significant changes in other clinical and laboratory parameters were observed. In conclusion, the tested combined nutraceutical was well tolerated, while significantly reducing the plasma levels of LDL-C, TC, non-HDL-C, ApoB, TC/HDL-C and LDL-C/HDL-C ratios in mildly hypercholesterolemic patients. Trial registration (ClinicalTrials.gov): NCT03739242.