NMR evaluation of total statin content and HMG-CoA reductase inhibition in red yeast rice (Monascus spp.) food supplements

IntroductionIn the absence of a European standardized postmarketing food supplement surveillance system (nutrivigilance), some member states and companies have developed their own approaches to monitoring potential adverse reactions to secure a high level of product safety. This paper describes the use of a nutrivigilance system in monitoring the incidence of spontaneously reported suspected adverse reactions associated with food supplements containing red yeast rice (RYR).Material and methodsWe report the data from a widely used product marketed under the trademark Armolipid/Armolipid Plus. Postmarketing information was collected in a voluntary nutrivigilance system established by the manufacturing company (Meda Pharma SpA, a Viatris Company, Monza, Italy). From 1st October 2004 to 31st December 2019, this system captured cases of suspected adverse reactions spontaneously reported by consumers, healthcare professionals, health authorities, regardless of causality.ResultsThe total number of case reports received mentioning the RYR food supplement product line was 542, in which 855 adverse events (AEs) were reported. The total reporting rate of AEs was estimated to be 0.037% of 2,287,449 exposed consumers. Of the 542 cases, 21 (0.0009% of exposed consumers) included suspected serious adverse events (SAEs). After careful investigation, 6 cases (0.0003% of consumers exposed) and 6 AEs were assessed by the manufacturer as serious and potentially related to exposure to the above-mentioned RYR-based nutraceutical.ConclusionsThis nutrivigilance-derived data analysis clearly demonstrates a low prevalence of suspected adverse events associated with the red yeast rice product line. Consumer safety of food supplements could be generally improved by raising awareness of the importance of following the indications and warnings detailed in a food supplement’s labeling.

Download Full-text

A quantitative UHPLC-MS/MS method for citrinin and ochratoxin A detection in food, feed and red yeast rice food supplements

World Mycotoxin Journal ◽

10.3920/wmj2015.1971 ◽

2016 ◽

Vol 9 (3) ◽

pp. 343-352 ◽

Cited By ~ 10

Author(s):

J.A.L. Kiebooms ◽

B. Huybrechts ◽

C. Thiry ◽

E.K. Tangni ◽

A. Callebaut

Keyword(s):

Risk Assessment ◽

Ochratoxin A ◽

High Performance ◽

Food Supplements ◽

Red Yeast Rice ◽

Red Yeast ◽

Relative Standard ◽

Future Data ◽

Food And Feed ◽

Feed Samples

Mycotoxins may cause deleterious effects (among others nephrogenic, hepatogenic, carcinogenic, teratogenic, neurogenic) in animals and humans, therefore they have been intensely studied and monitored over the years. For citrinin (CIT), a nephrotoxic mycotoxin, however, this has not yet been the case. According to the latest European Food Safety Authority report, a correct risk assessment of CIT was not possible due to the lack of occurrence data. Besides, traces of CIT or its metabolite, dehydrocitrinone are widely (in up to 90% of samples) present in human urine according to recent Belgian and German scientific reports, which might imply chronic exposure. Only recently, a European maximum limit has been set for CIT in cholesterol reducing food supplements including red yeast fermented rice (RYR). During production of RYR through fungal (among others Monascus purpureus) fermentation of rice other components, like CIT, as well as nephrotoxic ochratoxin A (OTA) may form. Consequently, the present work attempted develop to a robust and routinely applicable ultra-high performance liquid chromatographytandem mass spectrometry (UHPLC-MS/MS) method for the analysis of CIT and OTA in food, feed and in RYR food supplements. The method was successfully validated based on EU/657/2002 and EU/519/2014 in RYR food supplements and wheat flour, achieving respective limits of quantification (LOQ) for CIT of 0.4 μg/kg and 0.1 μg/kg and for OTA of 15 μg/kg and 0.4 μg/kg. The average between-day recoveries varied from 72 to 110% with relative standard deviations ≤16%. Single-day validation in rice, curry and apple matrices showed LOQs ranging from 0.3-1.0 μg/kg. Next, the occurrence of CIT/OTA was surveyed in 138 RYR, food and feed samples, proving the potential of this method for future data acquisition within a risk assessment framework specifically for CIT, while also gaining information about the (co-)occurrence of OTA in edible matrices.

Download Full-text

Adverse Events to Food Supplements Containing Red Yeast Rice: Comparative Analysis of FAERS and CAERS Reporting Systems

Drug Safety ◽

10.1007/s40264-018-0661-3 ◽

2018 ◽

Vol 41 (8) ◽

pp. 745-752 ◽

Cited By ~ 11

Author(s):

Emanuel Raschi ◽

Anna Girardi ◽

Elisabetta Poluzzi ◽

Emanuele Forcesi ◽

Francesca Menniti-Ippolito ◽

...

Keyword(s):

Comparative Analysis ◽

Adverse Events ◽

Food Supplements ◽

Red Yeast Rice ◽

Red Yeast ◽

Reporting Systems

Download Full-text

Food supplements with red yeast rice: More regulations are needed

European Journal of Preventive Cardiology ◽

10.1177/2047487317716500 ◽

2017 ◽

Vol 24 (13) ◽

pp. 1429-1430 ◽

Cited By ~ 8

Author(s):

Guy G De Backer

Keyword(s):

Food Supplements ◽

Red Yeast Rice ◽

Red Yeast

Download Full-text

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

Pharmaceuticals ◽

10.3390/ph14100981 ◽

2021 ◽

Vol 14 (10) ◽

pp. 981

Author(s):

Ngoc Tan Cao ◽

Ngoc Anh Nguyen ◽

Chan Mi Park ◽

Gun Su Cha ◽

Ki Deok Park ◽

...

Keyword(s):

Cholesterol Biosynthesis ◽

Liver Microsomes ◽

Red Yeast Rice ◽

High Catalytic Activity ◽

Hmg Coa Reductase ◽

Drug Candidates ◽

New Strategy ◽

Statin Drug ◽

Coa Reductase ◽

Rate Limiting

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.

Download Full-text

Study of the Effects of Monacolin K and Other Constituents of Red Yeast Rice on Obesity, Insulin-Resistance, Hyperlipidemia, and Nonalcoholic Steatohepatitis Using a Mouse Model of Metabolic Syndrome

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/892697 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 18

Author(s):

Makoto Fujimoto ◽

Koichi Tsuneyama ◽

Shao-Yuan Chen ◽

Takeshi Nishida ◽

Jiun-Liang Chen ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Mouse Model ◽

Serum Insulin ◽

Culture Conditions ◽

Red Yeast Rice ◽

Monacolin K ◽

Nonalcoholic Fatty Liver ◽

Red Yeast ◽

Coa Reductase

Purpose. Nonalcoholic fatty liver disease (NAFLD) is a progressive and intractable disease associated with metabolic syndrome. Red yeast rice (RYR) contains monacolin K, a potent inhibitor of HMG-CoA reductase, and its consumption decreases cholesterol and triglyceride levels. We examined the efficacy of RYR constituents using a novel metabolic syndrome-NAFLD mouse model (MSG mice).Methods. Two types of RYR grown under different culture conditions were used. 1P-DU contained only 0.002 g/100 g of monacolin K, whereas 3P-D1 contained 0.131 g/100 g. MSG mice were divided into three groups: control (C) group fed standard food, RYR-C group fed standard food with 1% 1P-DU, and RYR-M group fed standard food with 1% 3P-D1. Mice were examined from 12 to 24 weeks of age.Results. Serum insulin, leptin, and liver damage as well as macrophage aggregation in visceral fat in RYR-C and RYR-M groups were lower than those in C group. The serum adiponectin levels in RYR-C group were significantly higher than those in RYR-M and C groups.Conclusions. RYR was effective against obesity-related inflammation, insulin resistance, and NAFLD in MSG mice irrespective of monacolin K levels. GABA and various peptides produced during fermentation were determined as the active constituents of RYR.

Download Full-text

Citrinin Determination in Food and Food Supplements by LC-MS/MS: Development and Use of Reference Materials in an International Collaborative Study

Toxins ◽

10.3390/toxins13040245 ◽

2021 ◽

Vol 13 (4) ◽

pp. 245

Author(s):

Emmanuel K. Tangni ◽

François Van Hove ◽

Bart Huybrechts ◽

Julien Masquelier ◽

Karine Vandermeiren ◽

...

Keyword(s):

Reference Materials ◽

Ginkgo Biloba ◽

Raw Materials ◽

Collaborative Study ◽

Standard Operating Procedure ◽

Food Supplements ◽

Red Yeast Rice ◽

Proficiency Tests ◽

Red Yeast ◽

Food And Feed

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.

Download Full-text