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.

Anticholesterolemic Activity of Three Vegetal Extracts (Artichoke, Caigua, and Fenugreek) and Their Unique Blend

Hepatic-related diseases, in particular hyperlipidemia and hypercholesterolemia, are a thorn on the side of the national health institutes around the globe. Indeed, liver lipid and cholesterol dysregulation could lead to atherosclerotic plaque formation and cardiovascular diseases. Currently, statin administration and monacolin K consumption are the main therapies proposed to counter this alarming connection, but relevant side effects are known. To overcome this issue, safe nutraceutical formulations and/or vegetal extracts, endowed with anticholesterolemic activity, could be instrumental in hypercholesterolemia prevention and treatment. In the present work, the anticholesterolemic efficacy of three vegetal extracts used in traditional medicine (artichoke, caigua, and fenugreek), their unique blend (ACFB), and the monacolin K-containing red yeast extract (RYR), was investigated with an in vitro approach based on hepatic cell line HepG2. The impact on cholesterol of the three extracts, their blend, and RYR were investigated by determining hepatocyte total and free cholesterol and bile acids biosynthesis. According to our results, the anticholesterolemic activity of the vegetal extracts was confirmed, and a novel choleretic activity of caigua extract was evidenced. ACFB showed to be safer than RYR while showing a similar effect on total and free cholesterol and bile acids synthesis compared to it. The anticholesterolemic activity of the blend was obtained with lower vegetal extract concentrations compared with the single vegetal extract, potentially indicating an additive effect between the extracts. In conclusion, the vegetal extracts and their blend, ACFB, are safe and are endowed with anticholesterolemic activity, potentially providing complementary therapies to the statin-based ones for hyperlipidemia and hypercholesterolemia-related complications.

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 Combination of Lactoplantibacillus plantarum Strains CECT7527, CECT7528 and CECT7529 Plus Monacolin K Reduces Blood Cholesterol: Results from a Randomized, Double-Blind, Placebo-Controlled Study

Background: Dietary supplements have been proposed to help manage blood cholesterol, including red yeast rice (RYR) extracts, plant sterols and stanols, beta-glucans, and some probiotics. This study was conducted to evaluate the efficacy of RYR (containing 10 mg of monacolin K) combined with 109 CFU of three Lactoplantibacillus plantarum strains (CECT7527, CECT7528, and CECT7529). Methods: A 12-week randomized, double-blinded, placebo-controlled clinical trial was conducted. In total, 39 adult patients were enrolled, having total cholesterol (TC) ≥200 mg/dL, and being statin-naïve or having recently stopped statin treatment because of intolerance. Active product or placebo were taken once daily, and subjects were evaluated at baseline, 6, and 12 weeks. Results: Study groups were comparable at baseline, except for history of recent hypercholesterolemia treatment (81% in active vs. 22% in placebo). Changes in LDL cholesterol and TC became significant compared to placebo (mean difference between groups and standard error of the mean = 23.6 ± 1.5 mg/dL, p = 0.023 and 31.4 ± 1.9 mg/dL, p = 0.011, respectively) upon adjusting for the baseline imbalance in hypercholesterolemia treatment. No adverse effects were noted during the study. Conclusion: This combination of 10 mg of monacolin K and L. plantarum strains was well tolerated and achieved a statistically significant greater reduction in LDL-C and TC in the intervention group compared to the placebo, once adjusting for recent history of hypercholesterolemia treatment.

Production of Monacolin K in Monascus Pilosus: Comparison between Industrial Strains and Analysis of Its Gene Clusters

Monascus pilosus strains are widely applied to yield a cholesterol synthesis inhibitor monacolin K (MK), also called lovastatin (LOV). However, the mechanism of MK production by M. pilosus strains is still unclear. In this study, we firstly confirmed four Monascus strains, MS-1, YDJ-1, YDJ-2, and K104061, isolated from commercial MK products as M. pilosus and compared their abilities to produce MK in solid-state and liquid-state cultures. Then, we sequenced and analyzed their genomes and MK biosynthetic gene clusters (BGCs). The results revealed that the MK yields of MS-1, YDJ-1, YDJ-2, and K104061 in solid-state cultures at 14 days were 6.13, 2.03, 1.72, and 0.76 mg/g, respectively; the intracellular and extracellular MK contents of MS-1, YDJ-1, YDJ-2, and K104061 in liquid-state cultures at 14 days reached 0.9 and 1.8 mg/g, 0.38 and 0.43 mg/g, 0.30 and 0.42 mg/g, and 0.31 and 0.76 mg/g, respectively. The genome sizes of the four M. pilosus strains were about 26 Mb, containing about 7000–8000 coding genes and one MK gene cluster. The MK BGCs of MS-1, YDJ-2, and K104061 contained 11 genes, and the MK BGC of YDJ-1 contained 9 genes. According to the literature search, there are few comparisons of gene clusters and related genes responsible for the synthesis of LOV and MK. We also compared the LOV BGC in A. terreus with the MK BGCs in different species of Monascus spp., and the results revealed that although LOV and MK were the same substance, the genes responsible for the synthesis of MK were much less than those for LOV synthesis, and the gene functions were quite different. The current results laid a foundation to explore the mechanism of MK produced by Monascus spp. and compare the synthesis of LOV and MK.

Simultaneous detection of monacolins and citrinin of angkak produced by Monascus purpureus strains using Liquid Chromatography-Mass Spectrometry (LC-MS/MS)

Angkak or red mold rice is produced from the fermentation of white rice using Monascus purpureus, which results in the red color of the fermented rice. Angkak has been used as a natural coloring agent for food, spices, and medicine. The active compound in angkak that contributes to lower blood cholesterol is known as monacolin (monacolin K). However, the presence of citrinin, the byproduct of angkak fermentation, needs to be considered as it can cause hepato-nephrotoxic mycotoxin. The contents of pigments, monacolins, and citrinin as secondary metabolites depends on the Monascus strain and fermentation conditions. This study aims to analyze simultaneously monacolins and citrinin in angkak produced by M. purpureus strains using Liquid Chromatography-Mass Spectrometry (LCMS/MS). The angkak was prepared by fermentation using M. purpureus FNCC 6008 and M. purpureus JK2. A total of 107 M. purpureus spores/mL was inoculated into the rice. The fermentation was carried out at room temperature (25-30oC) for 14 days. The detection using LC-MS/MS showed that the monacolin K in angkak from both strains was below LOQ (< limit of quantification). The analysis of citrinin content in angkak showed that JK2 strain produced lower citrinin (1.10±0.021µg/g) compared to FNCC 6008 (3.01±0.072 µg/g). The other monacolins found in angkak from both strains were including dehydromonacolin K, monacolin J (qualitative), and mevastatin. Based on t-test, the amount of both mevastatin and citrinin in angkak produced by two different strains were significantly different. In contrast, the amount of dehydromonacolin K in both angkak was comparable. The simultaneous detection result of LC-MS/MS could determine the choice of Monascus strains quickly. JK2 strain was considered as safe, thus it could be chosen to be applied to food products.

The effect of high monacolin K red yeast rice supplement on performance, egg quality, egg yolk cholesterol, plasma lipids and enzyme profile of laying hens

Context Reducing egg cholesterol has been a major goal of many researchers over four decades. Monacolin K, a 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor, identical to the active ingredient in the prescription statin drug lovastatin, could be a promising feed supplement for layers. Aims To determine the effects of high monacolin K red yeast rice (RYR) supplement on feed intake, egg production, egg cholesterol content, plasma lipid and enzyme metabolites in laying hens. Methods Hyline brown layers were fed RYR supplement at 0, 0.2, 0.4, 0.8 and 1.6% of the diet for 6 weeks. Total and daily feed intake, egg production, egg weights and feed conversion ratio between the RYR treated groups and the control were compiled. Egg cholesterol and egg quality at the 3rd and 6th week of the feeding trial were analysed. Plasma lipids and enzymes were sampled towards the end of the trial. Key results Egg cholesterol were significantly lower (P &lt; 0.05) in the 0.8 and 1.6% RYR supplemented group. Supplementation with 0.8% RYR resulted in 11.16% reduction in egg cholesterol at the 3rd week with no further improvements with longer feeding. There were no significant differences (P &gt; 0.05) in total and daily feed intake, egg production, egg weights and feed conversion ratio (FCR) between the RYR treated and control group. Total plasma cholesterol and triglycerides were significantly lower (P &lt; 0.05) in the 0.8 and 1.6% RYR supplemented group when compared with the control group. RYR supplementation exert no significant differences (P &gt; 0.05) in plasma enzyme levels. Conclusions The present study suggests that RYR supplementation of 0.8% resulted in egg cholesterol reduction by 11.16% with no adverse effects on laying hens. Implications The feeding trial showed that RYR supplement can be used as a feed additive in layer diets to lower egg cholesterol, plasma cholesterol and triglycerides with no adverse effects on layer egg production and plasma enzymes over the feeding period.