Risk Assessment of RYR Food Supplements: Perception vs. Reality

Thirty-seven red yeast rice (RYR) food supplements were screened for their mycotoxin and natural statin content. Products included pure RYR capsules and multi-ingredient formulations with standardized amounts of monacolin K (MK), marketed both online and retail in the European Union. In terms of mycotoxins, citrinin (CIT) was found in all the monitored products. As CIT content ranged from 100 to 25100 μg/kg, only four products were compliant with maximum EU levels in force until April 2020, while a single product was compliant with the limit of 100 μg/kg introduced after that date. Four contaminated products were labeled as “citrinin free”. In terms of natural statins, nine products had a lower content vs. label statements (from −30 to −83%), while for 24 a larger MK amount (from 10 to 266%) was noticed. Three products had a negligible MK content and only 19 offered a daily dosage exceeding 10 mg as dictated by the health claim granted by EFSA in the EU. No sample had label values compliant with pharmaceutical Good Manufacturing Practices requirements (95–105% content of active constituent). Variable, but small amounts of simvastatin (0.1–7.5 μg per daily dose) were found in 30 samples. These results suggest that limited efficacy and reported safety issues may stem from an under-regulated and undercontrolled market, weakening both effectiveness and risk assessment evaluations.

152 Effects of nutraceuticals on the control of the lipid-glycaemic structure and on endothelial protection, in patients with low cardiovascular risk profile

Aims Nutraceuticals are dietary supplements that contain a concentrated form of a presumed bioactive substance originally derived from a food. There is a relationship between the consumption of monacolin K from red yeast rice and maintenance of normal blood low density lipoprotein cholesterol (LDL-C) concentrations recognized by the European Agency on Food Safety. The present study evaluates the effects of a therapeutical association of nutraceuticals (a combination of containing fermented red rice, named Monacolin K and Coenzyme Q10) on lipo-glycaemic profile and on the vascular function evaluated as endothelial function and arterial stiffness (using the non-invasive methods of EndoPAT and SphygmoCOR). Methods The present is a single-centre prospective study enrolling 30 patients with low cardiovascular risk profile (SCORE risk, cardiovascular disease risk <10% at 10 years). Patients were consecutive enrolled from March 2019 to February 2020 (recruitment period). The average follow-up was 14 weeks, from intaking monacolin K 10 mg + Coenzyme Q10 10 mg. The scheduled evaluations of the enrolled population were: before the beginning of the therapy and after a period of 14 weeks. Results After 14 weeks of treatment we demonstrated a statistically significant reduction in total cholesterol (P 0.015) and LDL (P 0.003). An important effect on the inflammatory profile was highlighted, resulting in a decrease in Hs-CRP at 12-weeks (P 0.052), associated with a progressive reduction of arterial stiffness (P 0.063) and an improvement in endothelial function (P 0.048). Conclusions Data obtained suggest that formulations with natural nutraceuticals, especially fermented red rice, have a protective cardiovascular effect, not also through reduction of plasma lipids but in endothelial function and arterial stiffness improvement.

Assessment of Citrinin in Spices and Infant Cereals Using Immunoaffinity Column Clean-Up with HPLC-Fluorescence Detection

Historically, the analysis of citrinin has mainly been performed on cereals such as red yeast rice; however, in recent years, more complex and abnormal commodities such as spices and infant foods are becoming more widely assessed. The aim of this study was to develop and validate clean-up methods for spices and cereal-based infant foods using a citrinin immunoaffinity column before HPLC analysis with fluorescence detection. Each method developed was validated with a representative matrix, spiked at various citrinin concentrations, based around European Union (EU) regulations set for ochratoxin A (OTA), with recoveries >80% and % RSD <9% in all cases. The limit of detection (LOD) and the limit of quantification (LOQ) were established at 1 and 3 µg/kg for spices and 0.1 and 0.25 µg/kg for infant cereals, respectively. These methods were then tested across a variety of spices and infant food products to establish efficacy with high recoveries >75% and % RSD <5% across all matrices assessed. Therefore, these methods proved suitable for providing effective clean-up of spices and infant cereals, enabling reliable quantification of citrinin detected. Samples such as nutmeg and infant multigrain porridge had higher levels of citrinin contamination than anticipated, indicating that citrinin could be a concern for public health. This highlighted the need for close monitoring of citrinin contamination in these commodities, which may become regulated in the future.

The role of monacolin in the treatment of dyslipidaemia

Dyslipidaemia is one of the major modifiable risk factors for cardiovascular diseases. According to the current epidemiological data, excessively high serum cholesterol levels are found in 64% of women and 70% of men aged ≥20 years in Poland. Statins are the treatment of choice in patients with high-to-very high cardiovascular risk and high low-density lipoprotein (LDL) cholesterol levels. At the other end of the spectrum, there is a group of patients with low-to-moderate cardiovascular risk and low or moderate LDL cholesterol levels, who should be put on well-planned and appropriately adjusted therapy involving lifestyle modification and, if needed, pharmacotherapy. In such cases, the current guidelines of the European Society of Cardiology make it possible to use monacolin, a nutraceutical which is a natural statin (chemically identical to lovastatin). Monacolin is found in red yeast rice and its action is based on the known mechanism of inhibition of HMG-CoA reductase, a key enzyme in endogenous cholesterol synthesis. Data on the efficacy and safety of monacolin come from many clinical trials showing a significant decrease in triglycerides, total and LDL cholesterol, resulting in a reduced number of cardiovascular events in the absence of significant adverse effects. Monacolin is likely to become an effective pharmaceutical to combat dyslipidaemia in the growing group of (relatively young) patients with low-to-moderate baseline cardiovascular risk and lowto- moderate LDL cholesterol levels, without concomitant indications for statins. This paper summarises the current knowledge on the efficacy, safety and potential indications for the use of monacolin in the treatment of dyslipidaemia.

Dietary Habits and Musculoskeletal Pain in Statin and Red Yeast Rice Users: A Pilot Study

(1) Background: Diet and statins are commonly used to treat high cholesterol (CHOL) levels. (2) Aim: To compare adherence to Mediterranean diet (Med-D), orthorexia nervosa (ON), and musculoskeletal pain in individuals in treatment with statins metabolized by CYP3A4, not metabolized by CYP3A4 or red yeast rice (RYR, containing monacolin K: MON-K). (3) Methods: starting from 80 individuals, after the exclusion of those with other causes of possible pain, 56 individuals were selected and divided into three groups according to the type of statin (CYP3A4, NO-CYP3A4 and MON-K). Adherence to the Med-D was evaluated with the MEDScore and a sub-score was calculated for fruit and vegetables consumption (MEDScore-FV). ON and musculoskeletal pain were assessed with the ORTO-15 and with the Nordic Musculoskeletal questionnaires, respectively. A retrospective analysis of CHOL decrease after treatment was conducted. (4) Results: CHOL levels were lower in CYP3A4 and NO-CYP3A4 after treatment (182.4 ± 6.3 and 177.0 ± 7.8 mg/dL, respectively), compared with MON-K (204.2 ± 7.1 mg/dL, p < 0.05). MON-K and CYP3A4 groups had a high prevalence of reported knee pain (33.3% and 18.8%, respectively) than NO-CYP3A4 group (0%, p < 0.05). A high percentage of individuals in MON-K take supplements and nutraceuticals (87.5%), whereas MEDScore-FV was higher in CYP3A4 (9.4 ± 0.2) compared to NO-CYP3A4 (7.6 ± 0.5, p < 0.05). (5) Conclusions: This study suggests that individuals receiving treatment with statins and RYR should be monitored from the perspective of plant foods’ consumption and nutraceutical use, to prevent musculoskeletal pain.

A Novel Statin Compound from Monacolin J Produced Using CYP102A1-Catalyzed Regioselective C-Hydroxylation

Statins inhibit the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase), which is the rate-limiting enzyme in cholesterol biosynthesis. Statin therapy reduces morbidity and mortality in those who are at high risk of cardiovascular disease. Monacolin J is a statin compound, which is an intermediate in the lovastatin biosynthesis pathway, in the fungus Aspergillus terreus. It is also found in red yeast rice, which is made by culturing rice with the yeast Monascus purpureus. Monacolin J has a hydroxyl substituent at position C’-8 of monacolin L. Here, a new statin derivative from monacolin J was made through the catalysis of CYP102A1 from Bacillus megaterium. A set of CYP102A1 mutants of monacolin J hydroxylation with high catalytic activity was screened. The major hydroxylated product was C-6′a-hydroxymethyl monacolin J, whose structure was confirmed using LC–MS and NMR analysis. The C-6′a-hydroxymethyl monacolin J has never been reported before. It showed a greater ability to inhibit HMG-CoA reductase than the monacolin J substrate itself. Human liver microsomes and human CYP3A4 also showed the ability to catalyze monacolin J in producing the same product of the CYP102A1-catalyzed reaction. This result motivates a new strategy for the development of a lead for the enzymatic and chemical processes to develop statin drug candidates.

Nutraceutical Combinations in Hypercholesterolemia: Evidence from Randomized, Placebo-Controlled Clinical Trials

There is an increasing number of nutraceutical combinations (NCs) on the market for hypercholesterolemia, although clinical trials to verify their safety and efficacy are scarce. We selected fourteen randomized, placebo-controlled clinical trials (RCTs) on different lipid-lowering NCs in hypercholesterolemic subjects. We described each compound′s mechanism of action and efficacy in the mixtures and summarized the clinical trials settings and NCs safety and efficacy results. Almost all NCs resulted efficient against hypercholesterolemia; only one reported no changes. Interestingly, red yeast rice (RYR) was present in eleven mixtures. It is not clear whether the lipid-lowering efficacy of these combinations derives mainly from the RYR component monacolin K “natural statin” single effect. Up to now, few RCTs have verified the efficacy of every single compound vs. NCs to evaluate possible additive or synergistic effects, probably due to the complexity and the high resources request. In conclusion, to manage the arising nutraceutical tide against hypercholesterolemia, it could be helpful to increase the number and robustness of clinical studies to verify the efficacy and safety of the new NCs.