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.

Supplementation of Bacillus sp. DU-106 reduces hypercholesterolemia and ameliorates gut dysbiosis in high-fat diet rats.

Gut microbiota modulation by a probiotic is a novel therapy for hypercholesterolemia mitigation. This study initially investigated the potential hypocholesterolemic effect of Bacillus sp. DU-106 in hypercholesterolemic rats and explored its potential relation with gut microbiota. Sprague-Dawley rats received a high-fat diet, or a high-fat diet supplemented with 7.5 × 109 and 1.5 × 1010 CFU/kg bw/day Bacillus sp. DU-106 (low-dose and high-dose groups). At the end of 9 weeks, Bacillus sp. DU-106 treatment significantly decreased the body weight, liver index, and total cholesterol. 16S rRNA sequencing showed that Bacillus sp. DU-106 intervention significantly increased bacterial richness and particularly increased the genus abundance of Turicibacter, Acinetobacter, Brevundimonas, and Bacillus and significantly decreased the abundance of Ralstonia. Metabolomic data further indicated that the supplementation of Bacillus sp. DU-106 remarkably changed the gut metabolic profiles of hypercholesterolemic rats and, in particular, elevated the metabolites of indole-3-acetate, methylsuccinic acid, creatine, glutamic acid, threonine, lysine, ascorbic acid, and pyridoxamine. Spearman's correlation analysis showed the close relation between the different genera and metabolites. In conclusion, Bacillus sp. DU-106 supplement ameliorated high-fat diet-induced hypercholesterolemia and showed potential probiotic benefits for the intestine. KEY POINTS: • A novel potential probiotic Bacillus sp. DU-106 ameliorated hypercholesterolemia in rats. • Bacillus sp. DU-106 supplement regulated gut microbiome structure and richness. • Bacillus sp. DU-106 supplement changed metabolic profiles in high-fat diet rats. • Significant correlations were observed between differential genera and metabolites.

Dietary citrus peel essential oil ameliorates hypercholesterolemia and hepatic steatosis by modulating lipid and cholesterol homeostasis.

Citrus peel essential oil (CPEO) contains abundant volatile compounds and exhibits fragrance properties and beneficial pharmacological effects on humans. Herein, we aimed to investigate the effects of CPEO on the prevention of hypercholesterolemia and hepatic steatosis in high-fat diet-fed rats and identify its possible regulatory mechanisms in lipid metabolism by combining lipidomics with gene expression analysis. CPEO at effective supplementation levels of 0.5% and 0.75% significantly ameliorated hypercholesterolemia and hepatic steatosis, including decreased serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), hepatic TC and triglyceride (TG) levels, and hepatic lipid droplet accumulation. Lipidomics analysis revealed that the total levels of fatty acid (FFA), TG and cholesteryl ester (CE) classes in the liver tissue were remarkably decreased after 0.75% CPEO supplementation some of which (3 TGs and 4 CEs) might emerge as potential lipid biomarkers in response to the effects of CPEO. Furthermore, these lipidomics findings were associated with downregulation of lipogenesis-related genes SREBP-1c, ACC and FAS and upregulation of bile acid biosynthesis-related genes LXRα, CYP7A1 and CYP27A1 in the liver. This study indicated that CPEO could effectively prevent hypercholesterolemia and hepatic steatosis, possibly because of its mediation of lipid and cholesterol homeostasis by altering liver lipid metabolites and regulating lipid metabolism-related genes.

White Button Mushroom, Agaricus bisporus (Agaricomycetes), and a Probiotics Mixture Supplementation Correct Dyslipidemia without Influencing the Colon Microbiome Profile in Hypercholesterolemic Rats.

Consumption of foods rich in dietary fiber has attracted considerable attention for lowering blood cholesterol and triglycerides through attenuation of gut microbiome. Diets rich in fiber may provide substrates for microbes to digest and proliferate. In response, products of microbial digestion enter systemic circulation and support host energy homeostasis. In the present study, rats with hypercholesterolemia (HC) were supplemented with probiotics (PB) and Agaricus bisporus mushroom to examine the antidyslipidemia effects. Forty adult rats were divided into five treatment groups. The rats in the control group were fed only a chow maintenance diet (CON; n = 8), whereas an atherogenic diet (chow diet supplemented with 1.5% cholesterol and 0.5% cholic acid) was offered to the remaining rats to induce hypercholesterolemia (HC group; n = 32). Rats developed HC following a 24-day continuous supplementation with the atherogenic diet. From day 25 onward, the HC group was further divided into HC-CON, HC-PB (supplemented with PB at 1 mg/rat/day), HC-AB (supplemented with A. bisporus at 5% of diet), and HC-AB.PB (supplemented with both A. bisporus and PB). After 6 weeks of supplementation, rats were killed to collect blood to determine serum lipid profile, oxidative stress, and for metagenomics analysis of colon contents. Results showed that all supplementations corrected HC-induced oxidative stress. Furthermore, A. bisporus supplementation corrected HC-induced dyslipidemia (P ≤ .05). Blautia and Bifidobacterium were the most dominant bacterial genera in HC-AB and HC-PB groups, respectively. Phylum Firmicutes and class Clostridia predominantly occupied the gut microbiome in all groups. However, no significant differences were observed in microbiome diversity and clustering patterns among study groups. In conclusion, supplementation of A. bisporus mushroom and probiotics can lower oxidative stress and dyslipidemia with partial effects on the phylogenetic makeup in the gut microbiome.

Cholesterol-Lowering Action of a Novel Nutraceutical Combination in Uremic Rats: Insights into the Molecular Mechanism in a Hepatoma Cell Line.

Appropriate nutraceutical combinations may represent a valid approach to prevent vascular calcification associated with chronic kidney disease (CKD). In the present study, we tested the effect of a new nutraceutical combination named RenaTris®, containing MK-7, magnesium carbonate, and Sucrosomial® Iron, on vascular calcification in uremic rats. Rats were randomly divided into three groups, i.e. control (high-phosphate diet), uremic (high-phosphate diet containing 0.5% adenine), and supplemented uremic diet (0.5% adenine, MK-7, magnesium carbonate, and Sucrosomial® Iron). After six weeks, sera and vascular calcification were examined. The uremic diet increased creatinine and phosphate levels and induced extensive vascular calcification. The uremic condition also induced a mild hypercholesterolemic condition (+52% of total cholesterol; p < 0.05). The supplemented uremic diet did not reduce creatinine, phosphate levels, or vascular calcification, however, we observed a significant hypocholesterolemic effect (-18.9% in supplemental uremic vs. uremic diet; p < 0.05). Similar to simvastatin, incubation of cultured human hepatoma cells (Huh7) with MK-7 significantly reduced cholesterol biosynthesis (-38%) and induced 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase and low-density lipoprotein receptor (LDLR) at both mRNA and protein levels. The effect of MK-7 on LDLR was counteracted by the co-incubation with squalene. Unlike simvastatin, MK-7 reduced PCSK9 in Huh7. These results indicated that the new nutraceutical combination significantly impacts cholesterol metabolism and its supplementation may help to control mild hypercholesterolemic conditions in CKD patients.

Hypercholesterolemia and cardiovascular disease: What to do before initiating pharmacological therapy.

The availability of efficient lipid-lowering drugs has substantially reduced the incidence and mortality for cardiovascular disease (CVD). Despite that, CVD still represents a major cause of death and disability; efforts are thus required to prevent this disease, since reducing the established CV risk factors may slow or prevent the onset of cardiovascular events. Current guidelines recommend a healthier lifestyle for all CV risk categories, as it may have a beneficial impact on several risk factors; in individuals with a low-to-moderate hypercholesterolemia, which are not eligible for a pharmacological approach and are not far from the cholesterol target recommended for their risk category, functional foods or nutraceuticals may be considered as supplement to reduce their CV risk status. Of note, counseling and lifestyle intervention in people at moderate CV risk represents a major issue for both preventing a further risk increase and reducing the need for drugs. Studies on general populations have clearly indicated that lifestyle interventions translate into a clinical benefit, with reduction of the incidence of myocardial infarction and the risk of developing type 2 diabetes.

Phytosterolemia and γ-glutamyl transferase in adults with parenteral nutrition: Fish versus vegetal lipids: A randomized clinical trial.

OBJECTIVES: Fish oil (FO)-based lipid emulsions (LEs) have been reported to prevent hepatic dysfunction in patients treated with parenteral nutrition (PN). We studied patients with alterations of γ-glutamyl transferase (GGT) associated with the administration of PN containing olive/soybean (O/S)-based LE. The aim of this study was to determine whether the strategy of reducing the lipid dose by 50%, by changing to an FO-based LE, reduced plasma levels of phytosterols (PS) and GGT more effectively and safely, than the strategy of reducing lipid contribution by 50% while maintaining the same LE composition. METHODS: A randomized double-blind clinical trial was carried out in patients with normal initial GGT, who after a minimum of 1 wk of daily PN (0.8 g/kg of O/S-based LE) presented with GGT values twice the upper normal value. At the time of randomization 1:1, lipids were reduced to 0.4 g/kg daily. Group A maintained O/S LE and group B changed to FO LE. The primary endpoints were reduction of plasmatic PS and GGT on day 7 after randomization, performed in the study population per protocol by Student's t test and simple linear regression. Secondary outcomes included alkaline phosphatase (AP), alanine transaminase (ALT), and total bilirubin (BIL), and safety variables. RESULTS: Nineteen patients were included. On day 7 after randomization, GGT and AP values were higher in the O/S group (n = 10; GGT: median [Med], 4.99; interquartile range [IQR], 4.09; AP: Med, 2.59 µkat/L; IQR 1.74) than in the FO group (n = 9; GGT: Med, 2.26 µkat/L; IQR, 1.07; AP: Med, 1.2 µkat/L; IQR 1.44). Although there were no differences in ALT and BIL values, the ALT decrease was larger and more statistically significant in the FO group than in the O/S group (P = 0.009). Total PS (Med, 21.10 µg/mL; IQR, 5.50) in the O/S group was higher than in the FO group (Med, 13.4 µg/mL; IQR, 10.65; P = 0.002). Significant decreases in PS and their fractions were observed, with the exception of campesterol and stigmasterol. CONCLUSION: Plasma accumulation of PS and high values of GGT, AP, and ALT can be prevented with the exclusive administration of FO-based LE.

Diosgenin Supplementation Prevents Lipid Accumulation and Induces Skeletal Muscle-Fiber Hypertrophy in Rats.

Diosgenin (Dio) is a steroid sapogenin found in plants such as Dioscorea species, and is recognized as a phytochemical against various disorders as well as a natural precursor of steroidal drugs. The present study used rats fed high-cholesterol (Chol) diets supplemented with or without 0.5% Dio for 6 wk to investigate the effects of dietary Dio on lipid metabolism. Dio supplementation significantly increased serum high-density lipoprotein Chol concentrations and fecal Chol content, and significantly decreased fecal bile acid content compared rats fed a high-Chol diet alone, showing that dietary Dio may facilitate excretion of Chol rather than bile acids. A reduction in the liver triglyceride content and intra-abdominal visceral fat was observed in Dio-supplemented rats. Interestingly, dietary Dio also significantly increased the skeletal muscle-fiber diameter and area in the thigh muscles of the rats. Mouse myoblast-derived C2C12 cells were used to examine whether Dio directly affected skeletal muscle. Dio promoted fusion of myoblasts into multinucleated cells or myotubes. Furthermore, in myotube C2C12 cells, protein levels of phosphorylated AMP-activated protein kinase (AMPK) increased with Dio treatment in a dose-dependent manner. These results indicate that Dio may not only induce myoblast fusion and enhance skeletal muscle as an energy expenditure organ, but may also activate the catabolic pathway via AMPK in skeletal muscle cells. Thus, these effects of Dio on skeletal muscles may contribute to inhibition of visceral fat accumulation.

Probiotic strains improve high-fat diet-induced hypercholesterolemia through modulating gut microbiota in ways different from atorvastatin.

Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD). Probiotics are one of the most popular dietary supplements for hypercholesterolemia, but there are questions as to whether there are differences between probiotics and cholesterol-lowering drugs like atorvastatin (ATO) both in effectiveness and in the underlying mechanisms. In this study, the hypocholesterolemia effects of 4 probiotic strains were investigated and compared with ATO, focusing on their impacts on the gut microbiota. A hypercholesterolemia model was established via high-fat diet (HFD) in golden hamsters after which ATO and the 4 probiotics were orally administered individually for 8 weeks. All probiotics were effective, but less than ATO, on body weight, serum parameters (TG, TC, LDL, INS, HbA1c) and expression of inflammatory factors (INF-α, IL-1ß, CRP), with strain JQII-5 being most significant. Besides, these effects were associated with restoration of microbiota dysbiosis induced by HFD. It was worth noting that ATO and probiotics induced different shifts of the gut microbiota in both structure and key phylotypes. Most interestingly, Allobaculum, a HFD-suppressed genus, reported to be involved in alleviating oxidative stress, was enriched by all tested probiotic strains, but not by ATO. Furthermore, Prevotella, also a HFD-suppressed genus, was uniquely reversed by JQII-5. Importantly, most of the alerted genera and reversed genera were found to be correlated with the inflammatory state and serum lipid level. Compared with ATO, the probiotic strains were less effective on body weight, hypercholesterolemia, and inflammation. However, probiotics exert additional favorable effects on the gut microbiota, making them excellent potential complements to cholesterol-lowering drugs like ATO.

Combined Lowering Effects of Rosuvastatin and L. acidophilus on Cholesterol Levels in Rat.

Statins are a class of lipid-lowering drugs commonly used in the prevention of cardiovascular diseases. However, statin therapy presents many limitations, which have led to an increased interest in non-drug therapies, such as probiotics, to improve blood cholesterol levels. Indeed, probiotic strains such as Lactobacillus acidophilus have been found to improve blood lipid profiles, especially in reducing total cholesterol and LDL-C levels. In this study, we established a high-cholesterol rat model and studied the effect of Lactobacillus acidophilus administration alone or in conjunction with rosuvastatin. We were able to show that indeed Lactobacillus exerts a cholesterol-lowering effect. Additionally, we observed that when administered together, rosuvastin and Lactobacillus exert a combined cholesterol-lowering effect. Altogether, our data advocate for the possibility of establishing probiotics as non-drug supplements for the treatment of hypercholesterolemia.

WEIGHT LOSS IN A YOUNG PATIENT WITH TYPE 2 DIABETES: CHALLENGES OF DIABETES MANAGEMENT USING ONLINE PROGRAM OF GOOD NUTRITION (CASE REPORT).

A 31-year-old male with a history of obesity, type 2 diabetes mellitus (T2DM) and hypercholesterolemia came to our clinic for medical weight-loss management. According to his initial anthropometric measurements (weight - 193 kg, height - 181 cm, and body mass index (BMI) - 58 kg/m2) patient had morbid obesity. In order to educate our patient about good nutrition, physical activity and the need of sun exposure we used an online system based on the video lessons, full of humor, pictures, and cartoons. Even one month of watching the short educational movies was sufficient for the patient to form the habits of healthy eating, including restriction of fat and digestible carbohydrates and increase in daily consumption of low-fat dairy products, slow carbohydrates, protein and fiber. Endocrinologist was regularly available for any questions and inquiries that the patient might have had. In addition to the dietary recommendations subcutaneous liraglutide 2.4 mg daily was initiated. After 8 months of treatment the patient has lost 58 kg and reached the body weight of 135 kg; moreover, he had motivation to continue losing weight.

Lipid-Modifying Effects of Chitosan Supplementation in Humans: A Pooled Analysis with Trial Sequential Analysis.

SCOPE: We performed a pooled analysis with trial sequential analysis (TSA) to evaluate the efficacy and safety of chitosan supplementation on serum lipids in humans. METHODS AND RESULTS: Medline, EMBASE, and CENTRAL databases were queried. Impact was expressed as a weighted mean difference (WMD) and 95% confidence interval (CI). Sensitivity analysis was conducted using the leave-one-out method. Statistical heterogeneity, publication bias, TSA, and subgroup analyses were also assessed. Fourteen trials (21 treatment arms) encompassing 1108 participants were suitable for statistical pooling. Chitosan supplementation significantly improved the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations in all patients. The WMDs were -0.20 mmol L-1 (95% CI, -0.35 to -0.05; p = 0.009) for TC, and -0.20 mol L-1 (95% CI, -0.26 to -0.15; p = 0.0001) for LDL-C, respectively. TSA demonstrated that the cumulative Z-curve crossed the trial sequential monitoring boundary for benefit providing conclusive evidence for the benefit of chitosan. However, no significant changes were seen with high-density lipoprotein cholesterol (HDL-C) and triglycerides. Our findings were robust after sensitivity analyses, and no serious adverse events were reported with chitosan intake. CONCLUSION: Supplementation with chitosan effectively reduces plasma concentrations of TC and LDL-C. Current evidence indicates daily chitosan supplementation as a candidate for therapeutic lipid management strategies.

ß-glucans and cholesterol (Review).

Hypercholesterolemia is one of primary risk factors of cardiovascular disease, together with metabolic syndrome, hypertension and diabetes. Although progress has been made, the search for novel methods of preventing and treating dyslipidemia is ongoing and current therapies for cardiovascular disease induce various side effects. ß­glucans are linear unbranched polysaccharides found in various natural sources, such as mushrooms. Due to their structure they are able to interact with innate immunity receptors, however they also act as dietary fibers in the digestive tract. As there are two forms of ß­glucans, insoluble and soluble forms, they are able to interact with lipids and biliary salts in the bowel and consequently reduce cholesterol levels. Therefore, they may be developed as a suitable therapeutic option to treat patients with dyslipidemia, as they are natural molecules that do not induce any significant side effects. The current review discusses the evidence supporting the effects of ß­glucans on cholesterol levels.

Hypocholesterolemic activity of indigenous probiotic isolate Saccharomyces cerevisiae ARDMC1 in a rat model.

The aim of this study was to investigate probiotic attributes of Saccharomyces cerevisiae ARDMC1 isolated from traditional rice beer starter cake and its hypocholesterolemic effects on Wistar rats fed a high-cholesterol diet. The indigenous isolate ARDMC1 showed potential probiotic characteristics such as tolerance to simulated gastrointestinal stress conditions, autoaggregation properties, and adhesion to intestinal epithelium Caco-2 cell line. In addition, ARDMC1 isolate exhibited in vitro cholesterol assimilation properties in media supplemented with cholesterol. Furthermore, administration of probiotic isolate to rats fed a hypercholesterolemic diet resulted in significant reduction of serum total cholesterol, low-density lipoprotein cholesterol, and triglyceride at the end of 42 days. The present study envisages ARDMC1 as a promising starter culture for the preparation of functional foods with properties to combat cardiovascular diseases.

Epidemiology and management of hyperlipidemia.

Cardiovascular disease (CVD) is the leading cause of death among adults in the United States, and people with hyperlipidemia are at roughly twice the risk of developing CVD as compared to those with normal total cholesterol levels.1 Patients with familial hypercholesterolemia (FH) have an even greater risk of developing CVD at an earlier age; therefore, early detection and treatment are imperative to reduce cardiovascular events and premature death. Statins are the mainstay treatment for hyperlipidemia; however, the limitations of statins include treatment resistance, intolerance due to adverse events, and a lack of adherence which contribute to poor outcomes. As such, many patients require adjunct therapies to properly control hyperlipidemia including niacin, bile acid sequestrants, fibric acids, and ezetimibe. FH can be even more challenging to treat, often requiring the use of lomitapide, mipomersen, proprotein convertase subtilisin/kexin type 9 inhibitors, or low-density lipoprotein cholesterol apheresis, in addition to high dose conjunction with statins or other agents.2 The approach to determining the appropriate treatment options has also undergone important changes. Guidelines for the management of patients with hyperlipidemia vary in their recommendations, with the American College of Cardiology/American Heart Association recommending that treatment decisions be based on the intensity of response associated with various statins, while multiple other guidelines (eg, National Lipid Association (NLA) and the American Association of Clinical Endocrinologists and American College of Endocrinology) still support attaining prespecified lipid values to reduce cardiovascular risk.3-5 This article will review the epidemiology of hyperlipidemia and FH, risk factors associated with the development of disease, as well as the efficacy and safety of statins and adjunct treatment options.

Shiitake Culinary-Medicinal Mushroom, Lentinus edodes (Agaricomycetes): A Species with Antioxidant, Immunomodulatory, and Hepatoprotective Activities in Hypercholesterolemic Rats.

Lentinus edodes is a culinary-medicinal mushroom that has an established history of use in Asian therapies. The mushroom offers well-documented beneficial health effects such as antihypercholesterolemic, antitumor, and antibacterial activities. In this study, dried powder of L. edodes fruiting bodies was used to evaluate immunomodulatory, hepatoprotective, and antioxidant effects in hypercholesterolemic rats. Albino rats (n = 24) were divided into 3 groups: the control (CON) group, the hypercholesterolemia-only group (HCG), and the L. edodes group (LEG). Hypercholesterolemia was induced in rats in the HCG and LEG by feeding cholesterol and cholic acid in a chow maintenance diet (CMD) for 24 days. The CON group was fed the CMD throughout the experiment. The HCG continued on the high-cholesterol diet without any L. edodes supplement. The LEG was fed the high-cholesterol diet supplemented with L. edodes for an additional 42 days. Various biological health biomarkers, such as total antioxidant capacity, total oxidant status, arylesterase, paraoxonase activity, and liver enzymes in serum were studied to evaluate antioxidant and hepatoprotective responses. Cell-mediated immunity was evaluated in each group through a delayed type of hypersensitivity reaction. The total oxidant status decreased significantly (P ≤ 0.05) after administration of L. edodes in the diet. The cell-mediated immune response significantly increased (P ≤ 0.05) in the LEG. The significant decrease in liver enzymes supports the hepatoprotective effect of L. edodes. In conclusion, the results show the immunomodulatory, hepatoprotective, and antioxidant activities of L. edodes supplementation in hypercholesterolemic rats.

A dietary cholesterol challenge study to assess Chlorella supplementation in maintaining healthy lipid levels in adults: a double-blinded, randomized, placebo-controlled study.

BACKGROUND: Previous animal studies suggested that Chlorella, a unicellular green alga, has a preventive role in maintaining serum cholesterol levels against excess dietary cholesterol intake. This study aimed to conduct a pioneering investigation to clarify this issue in healthy subjects by adopting a dietary cholesterol challenge, which has not been used previously in similar studies of Chlorella in hypercholesterolemia. METHODS: In this double blind, randomized, placebo-controlled study, 34 participants ingested 510 mg of dietary cholesterol from three eggs concomitantly with a usual dose of Chlorella (5 g/d) or a matched placebo for 4 weeks. RESULTS: The dietary cholesterol challenge induced consistently higher concentrations of serum total cholesterol (TC, P < 0.001), LDL-C (P = 0.004), and HDL-C (P = 0.010) compared with baseline values, suggesting that the challenge was reliable. Thus, we observed a preventive action of Chlorella in maintaining serum TC versus placebo levels (3.5 % versus 9.8 %, respectively; P = 0.037) and LDL-C versus placebo levels (1.7 % versus 14.3 %, respectively; P = 0.012) against excessive dietary cholesterol intake and in augmenting HDL-C versus placebo levels (8.3 % versus 3.8 %, respectively). Furthermore, serum α-carotene showed the best separation between the placebo and Chlorella groups (R(2)X and R(2)Y > 0.5; Q(2) > 0.4). CONCLUSION: The results suggest that a fully replicated dietary cholesterol challenge may be useful in assessing the effectiveness of dietary supplements in maintaining the serum lipid profiles of adults whose habitual diets are high in cholesterol. TRIAL REGISTRATION: WHO International Clinical Trials Registry Platform ( KCT0000258 ).

Middle-Term Dietary Supplementation with Red Yeast Rice Plus Coenzyme Q10 Improves Lipid Pattern, Endothelial Reactivity and Arterial Stiffness in Moderately Hypercholesterolemic Subjects.

AIM: The aim of our study was to investigate whether treatment with red yeast rice added with Coenzyme Q10 is associated with changes in endothelial function and arterial stiffness. METHODS: This double blind, placebo-controlled, randomized clinical trial was carried out on 40 non-smoker moderately hypercholesterolemic subjects (ClinicalTrial.gov ID NCT02492464). After 4 weeks of diet and physical activity, patients were allocated to treatment with placebo or with an active product containing 10 mg monacolins and 30 mg Coenzyme Q10, to be assumed for 6 months. Endothelial reactivity and arterial stiffness have been measured through the validated Vicorder® device. RESULTS: During monacolin treatment, patients experienced a more favorable percentage change in low density lipoprotein (LDL)-cholesterol (after monacolin treatment: -26.3%; after placebo treatment: +3.4%, p < 0.05). Endothelial reactivity (pulse volume displacement after monacolin treatment: +6.0%; after placebo treatment: -0.3%, p < 0.05), and arterial stiffness (pulse wave velocity (PWV) after monacolin treatment: -4.7%; after placebo: +1.1%, p < 0.05) also significantly improved only after monacolin treatment. CONCLUSION: The long-term assumption of the tested dietary supplement is associated with an improvement in LDL-cholesterolemia, endothelial reactivity and PWV in moderately hypercholesterolemic subjects.

Overview of Flaxseed Patent Applications for the Reduction of Cholesterol Levels.

BACKGROUND: Flaxseed is becoming an increasingly widely used food ingredient. The rising interest of the food industry in this nutraceutical is primarily because of functional nutrients, such as alpha-linolenic acid and lignans, which have health benefits due to their lipid-lowering properties. OBJECTIVE: The objective of this study was to provide an overview of the patenting of flaxseed products with cholesterol-lowering effects. METHOD: Patent applications filed by country of origin were retrieved from the Derwent Innovations Index®database. RESULTS: A total of 307 patent documents were identified, of which 184 claim the use of flaxseed or parts of the flax plant in the product formulation, for their lipid-lowering effect when consumed by humans. A few of the patent applications contain claims for new products based on flaxseed in isolation, including the preparation of foods designed to inhibit the production of cholesterol. Most of the claims were for flaxseed in the form of oil and in association with other lipid-lowering compounds, mainly for the food industry, in the form of dietary supplements or baked products designed to raise their high-density lipoprotein content, and for treating heart problems. China and the United States are the leading countries of flax-related applications. CONCLUSION: These results may have important implications for the production of functional food products that meet specific societal demands.