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Main cholesterol-lowering mechanism of action of RYR [28]. RYR = red yeast rice. HMG-CoA = β-hydroxy β-methylglutaryl coenzyme A; HMG-CoAR = β-hydroxy β-methylglutaryl coenzyme A reductase; PP = pyrophosphate.
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![Main components isolated from red yeast rice [17].](publication/370736384/figure/tbl1/AS:11431281158048936@1683998809250/Main-components-isolated-from-red-yeast-rice-17_Q320.jpg)
Reducing low-density lipoprotein cholesterol (LDL-C) levels is a key target for lowering cardiovascular risk and preventing atherosclerotic cardiovascular disease (ASCVD). Red yeast rice (RYR) is a nutraceutical widely used as a lipid-lowering dietary supplement. The main cholesterol-lowering components of RYR are monacolins, particularly monacolin...
Citations
... Red yeast rice is a widely used and clinically tested cholesterol-lowering nutraceutical derived from the fermentation of standard rice by specific mycelia (usually Monascus purpureus Went) with the production of a pigment (making the rice red) and some bioactive compounds, among which monacolins are reversible inhibitors of 3-hydroxy-3-methyl-glutaril Coenzyme A reductase (Figure 2) [107]. The most bioactive compound was monacolin K, which is chemically analogous to lovastatin. ...
Long-term exposure to even slightly elevated plasma cholesterol levels significantly increases the risk of developing cardiovascular disease. The latest evidence recommends an improvement in plasma lipid levels, even in children who are not affected by severe hypercholesterolemia. The risk–benefit profile of pharmacological treatments in pediatric patients with moderate dyslipidemia is uncertain, and several cholesterol-lowering nutraceuticals have been recently tested. In this context, the available randomized clinical trials are small, short-term and mainly tested different types of fibers, plant sterols/stanols, standardized extracts of red yeast rice, polyunsaturated fatty acids, soy derivatives, and some probiotics. In children with dyslipidemia, nutraceuticals can improve lipid profile in the context of an adequate, well-balanced diet combined with regular physical activity. Of course, they should not be considered an alternative to conventional lipid-lowering drugs when necessary.
... The filamentous fungus M. purpureus, known for red yeast rice fermentation [6] and wine starters of brewage industry [7], has been widely used as edible pigments [8], polysaccharides [9] and medicinal agents [10]. Monascus pigments, more precisely, Monascus azaphilone pigments (MonAzPs), are a kind of complex compound mixtures including red (rubropunctamine and monascorubramine), orange (rubropunctatin and monascorubrin) and yellow (monascin and ankaflavin) pigments shared the common skeleton of azaphilone [11]. ...
Background
Taurine, a semi-essential micronutrient, could be utilized as a sulfur source for some bacteria; however, little is known about its effect on the accumulation of fermentation products. Here, it investigated the effect of taurine on co-production of bioethanol and Monascus azaphilone pigments (MonAzPs) for a fungus.
Results
A newly isolated fungus of 98.92% identity with Monascus purpureus co-produced 23.43 g/L bioethanol and 66.12, 78.01 and 62.37 U/mL red, yellow and orange MonAzPs for 3 d in synthetic medium (SM). Taurine enhanced bioethanol titer, ethanol productivity and ethanol yield at the maximum by 1.56, 1.58 and 1.60 times than those of the control in corn stover hydrolysates (CSH), and red, yellow and orange MonAzPs were raised by 1.24, 1.26 and 1.29 times, respectively. Taurine was consumed extremely small quantities for M. purpureus and its promotional effect was not universal for the other two biorefinery fermenting strains. Taurine intensified the gene transcription of glycolysis (glucokinase, phosphoglycerate mutase, enolase and alcohol dehydrogenase) and MonAzPs biosynthesis (serine hydrolases, C-11-ketoreductase, FAD-dependent monooxygenase, 4-O-acyltransferase, deacetylase, NAD(P)H-dependent oxidoredutase, FAD-dependent oxidoredutase, enoyl reductase and fatty acid synthase) through de novo RNA-Seq assays. Furthermore, taurine improved cell membrane permeability through changing cell membrane structure by microscopic imaging assays.
Conclusions
Taurine reinforced co-production of bioethanol and MonAzPs by increasing gene transcription level and cell membrane permeability for M. purpureus. This work would offer an innovative, efficient and taurine-based co-production system for mass accumulation of the value-added biofuels and biochemicals from lignocellulosic biomass.
... In particular, a 1% improvement in endothelial function has been estimated to be associated with a 12% reduction in cardiovascular disease events [29]. The anti-inflammatory effect and the positive effect of both red yeast rice [30] and omega-3 PUFAs [31] are well-known but both for higher doses than the one tested in this trial. Consequently, we should argue that the combined effect of both components in a single softgel could have improved their individual efficacy. ...
Introduction
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.
Material and methods
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.
Results
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%.
Conclusions
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.
... RYR has a comparable lipid-lowering activity to statins and lowers the cardiovascular disease risk in patients with statin intolerance or those who do not meet their goals after a single course of treatment with statins or ezetimibe. RYR has been suggested as a treatment option for lowering LDL-C levels and ASCVD risk for people with mild-to-moderate hypercholesterolemia who are ineligible for statin therapy, particularly those who are unable to implement lifestyle modifications, and also for those who are otherwise eligible for statin therapy but unwilling to take a pharmacologic therapy (Cicero et al., 2023). The antihyperlipidemic therapeutic effect of RYR is believed to be due to its principal active constituent monacolins, more specifically monacolin K (2.9 mg from Cholesfytol NG ® supplementation). ...
Background: Hyperlipidemia is associated with a higher rate of cardiovascular, cerebrovascular, and peripheral vascular disease. Conventional drugs such as statins are effective in controlling hyperlipidemia; however, they are associated with various side effects, especially myalgia. Nutraceutical lipid-lowering interventions are becoming increasingly popular, particularly among patients who are intolerant or refractory to statins. Substantial preclinical and clinical evidence suggests that extracts of amla, walnut, and olive, and red yeast rice (RYR) powder possess significant antihyperlipidemic effects.
Aims: This study aimed to evaluate the efficacy, safety, and patient satisfaction of a combined supplementation of standardized dry extracts of amla fruit (500 mg), walnut leaves (50 mg), olive fruit (25 mg), and RYR powder (33.6 mg) (Cholesfytol NG®) in hypercholesterolemic patients.
Methods: This was a real-life setting , retrospective, observational, single-arm, non-randomized study in hypercholesterolemic patients (total cholesterol (TC) ≥ 200 mg/dL or low-density lipoprotein-cholesterol (LDL-C) ≥ 130 mg/dL), enrolled at 57 general practitioner (GP) surgeries in Belgium from March 2020 to January 2022. These patients received a GP-prescribed daily single dosage of two oral tablets of Cholesfytol NG® supplementation for 2 months to overcome their hypercholesterolemia in the absence of a conventional lipid-lowering drug (n = 208) or with a lipid-lowering drug (n = 13). At 2-month follow-up, the lipid profile was re-evaluated, alongside a patient’s questionnaire on treatment general satisfaction and willingness to pursue supplementation.
Results: After supplementation, TC decreased by 15%, LDL-C by 19%, non-high-density lipoprotein-cholesterol (non-HDL-C) by 20% (all p < 0.0001), triglycerides (TG) by 9% ( p = 0.0028) (−18.4%, p = 0.0042, in patients with baseline TG > 180 mg/dL, n = 58), and remnant cholesterol (RC) by 12% ( p = 0.0001). These changes were unaffected by statin intolerance status in patients who received Cholesfytol NG® alongside statin. The supplement was well tolerated by all patients, and no serious adverse events or supplement-emergent effects were reported. Most patients were satisfied with the supplementation and wanted to pursue the nutraceutical.
Conclusion: According to the results of this study, a combined supplementation of amla, walnut, and olive extracts, and RYR powder exerts a significant antihyperlipidemic effect, leading to a decrease in circulatory LDL-C and RC levels in patients with hypercholesterolemia. The supplementation bears excellent safety and tolerability, and is rated as satisfactory and pursuable, even among patients with statin intolerance.
Clinical Trial Registration: clinicaltrials.gov ; identifier number: NCT06002893
... Standard pharmacological therapy with lipid-lowering medications is regarded as the first-line therapy in circumstances when physical exercise and a regulated diet are insufficient. The main limitation of conventional therapy is related to the side effects the patients experience, consequently leading to the discontinuation of the treatment [10,11] . The American Heart Association has stressed the use of implemented preventive measures as the primary strategy for promoting cardiovascular health, even though several challenges must be overcome [12] . ...
Background: During the last decades, the role of lipid-lowering nutraceuticals in cardiovascular disease prevention is gathering attention.
... Monacolin K is structurally identical to lovastatin; both are rapidly converted in vivo from their lactone to an identical hydroxy acid form, the latter being responsible for inhibiting 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase, the key enzyme involved in the biosynthesis of cholesterol [12]. In RYR, monacolin K is present as a lactone and as a hydroxy acid, the ratio depending on the pH [12]. ...
... Monacolin K is structurally identical to lovastatin; both are rapidly converted in vivo from their lactone to an identical hydroxy acid form, the latter being responsible for inhibiting 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase, the key enzyme involved in the biosynthesis of cholesterol [12]. In RYR, monacolin K is present as a lactone and as a hydroxy acid, the ratio depending on the pH [12]. Lovastatin, conversely, is administered in the lactone form and must be converted to the active hydroxy acid form [12]. ...
... In RYR, monacolin K is present as a lactone and as a hydroxy acid, the ratio depending on the pH [12]. Lovastatin, conversely, is administered in the lactone form and must be converted to the active hydroxy acid form [12]. ...
Purpose of Review:
Elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) are a major risk factor for athero-sclerotic cardiovascular disease (ASCVD), and lowering LDL-C reduces the risk of cardiovascular adverse events. Among natural approaches known for their lipid-lowering properties, red yeast rice (RYR) has a cholesterol-lowering effect due to the presence of bioactive components (monacolins) that act by inhibiting the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. In August 2018, the European Food Safety Authority (EFSA) concluded in its assessment of the use of RYR (further amended in June 2022) that monacolins from RYR raise significant safety concerns when used as a food supplement at a dose of 10 mg/day. In particular, individual cases of serious adverse effects of monacolins from RYR have been reported at intakes as low as 3 mg/day. The EFSA Panel pointed out several uncertainties regarding the available data.
Recent Findings:
We conducted an in-depth and updated analysis of the serious adverse events, with a focus on rhabdo-myolysis and acute hepatitis, associated with the consumption of RYR. An analysis of the Food and Drug Administration reporting systems revealed a very small number of cases of rhabdomyolysis or severe acute hepatitis associated with RYR use. In addition, only a few case reports of these serious adverse events associated with RYR use have been published.
Summary:
Based on data from adverse event reporting systems and available case reports, the occurrence of rhabdomyolysis or severe acute hepatitis that could be associated with the use of RYR appears to be extremely rare compared to the occurrence with statins, which is rare to common.
... However, the tested combined nutraceutical has been shown to improve a relatively large number of cardiometabolic risk factors, in agreement with what is expected for a well-designed combined nutraceutical [20]. Considering the recent European Commission concerns about the use of red yeast rice products containing high dosages of monacolin K [21,22], the current development of new combined nutraceuticals is needed to balance the strong reduction in the daily dose of monacolins required by the new EU rules. ...
Introduction
The scientific community and consumers are increasingly interested in the potential cholesterol-lowering effect of various nutraceuticals and their combinations. The aim of our study was to test the short-term effect of a new lipid-lowering nutraceutical formulation in mildly hypercholesterolemic patients.
Material and methods
We consecutively enrolled 80 mildly hypercholesterolemic patients with low-density lipoprotein-cholesterol (LDL-C) between 130 and 190 mg/dl with a low-estimated cardiovascular disease risk. After a 8 week-stabilization diet, the enrolled subjects were randomized to take 1 pill/evening of Zeta Colest (including: 400 mg of Berberis aristata dry extract with 340 mg of berberine, 98 mg of red yeast rice extract with 2.9 mg of total monacolins, 87.5 mg of milk thistle dry extract with 70 mg of silymarin, 50 mg of guggul dry extract with 1.3 mg of guggulsterones) or placebo for 8 weeks. Patients were followed up for metabolic and haemodynamic parameters.
Results
After 8 week-supplementation with the tested combined nutraceuticals, we observed a significant reduction in total cholesterol (–16.7 ±1.5%), LDL-C (–18.1 ±1.9%), non-high-density lipoprotein cholesterol (–19.2 ±2.1%), apoB (–20.7 ±2.3%) and high-sensitivity C-reactive protein (–3.0 ±0.6%), versus both baseline (p < 0.05) and the control group (p < 0.05). No other metabolic or liver parameters significantly changed during the observation period. Endothelial reactivity also mildly but significantly improved by 2.96 ±0.23% with the tested product.
Conclusions
In the short term, the tested combined nutraceutical improved lipid metabolism, systemic inflammation and vascular function in mildly hypercholesterolemic overweight subjects.
The red yeast rice has been used in therapy for hypercholesterolemia, however data on the phytochemical constitution and other biological properties of this product are scarce in the scientific literature. This objective work evaluates the antioxidant capacity and phytochemical constitution of a commercial phytotherapic and extracts obtained from red yeast rice. The results demonstrated that both the commercial phytotherapic (EMFC), and aqueous (EA), hydroalcoholic (EHA) and ethanolic (EE) exctract presented antioxidant effects, and showed a direct relationship with the phenolic content. Among the extracts evaluated, EE has a higher amount of flavonols/flavones, while extract EA has a higher content of flavonones. The different methods used in the preparation of phytotherapics promote variations in the phytochemical constitution, which may compromise the efficacy and safety of such products. Given this, it is essential that phytotherapic and nutraceuticals are subjected to phytochemical constituents quantification processes in order to guarantee the therapeutic benefits of these natural products on cardiovascular diseases and those associated with oxidative stress.
The objective of this work is to better understand the use of plants and herbal products for medicinal purposes in Portuguese households, namely which plants are most used and which health conditions are most targeted. It also seeks to evaluate the attitudes and habits related to this use, its role in their health management, the sources of information used and the frequency of consultation with professionals specialized in the area. A descriptive cross-sectional study was conducted using an online questionnaire. A total of 210 responses were obtained. 78% of the respondents were female. 71.9% of the respondents had a university degree. 41.4% reported having salary above € 1000 and 27.1% above € 2000. The mean age in the sample was 50.8 years. More than 50% of the respondents reported using medicinal plants in the flu and cough, to aid digestion and to aid sleep. The plants with more respondents were eucalyptus and peppermint (in respiratory conditions), lemon balm (in digestive and nervous conditions), chamomile (in respiratory, digestive and skin conditions), linden (in respiratory and nervous conditions), rosemary (for digestive, circulatory and nervous diseases) and arnica (for joint and skin diseases). The most common form of use was infusion (87.6%), followed by essential oils (51.0%), tablets or similar forms (48.1%) and external forms (46.7%). The most frequent places of acquisition of medicinal plants were the stores of natural products (71.4%). 31.4% of the respondents put medicinal plants as the first option in their health management, and 30.5% said they used them together with conventional medicines. The main sources of information for decisions on this topic mentioned by the sample were family knowledge (54.8%), consultations with naturopaths and similar (41.9%), counseling with friends (37.1%), specialized means in natural health (35.2%) and generalist means (34.3%). 23.8% of the respondents said they make consultations with phytotherapy professionals or naturopaths, while 23.3% said they do it only in severe cases. This study found a substantial use of medicinal plants in Portugal, especially for the mildest health conditions and with the safest plants. The evaluation of the answers in the face of scientific knowledge about the properties of plants points to a mostly correct use. However, the issues of adverse reactions, contraindications and drug interactions were not addressed in this study. We recognize that a reasonably detailed web questionnaire is answered mainly by the people with the most interest in the subject, and therefore the sample obtained may not be representative of the general Portuguese population. Bearing in mind that fact, this study will still provide useful information the most used plants and target conditions, as well as on the usage patterns of the people who use them the most.
