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No Effect of Isolated Anthocyanins from Bilberry Fruit and Black Rice on LDL Cholesterol or other Biomarkers of Cardiovascular Disease in Adults with Elevated Cholesterol: A Randomized, Placebo-Controlled, Cross-Over Trial.
Aboufarrag, H, Hollands, WJ, Percival, J, Philo, M, Savva, GM, Kroon, PA
Molecular nutrition & food research. 2022;66(21):e2101157
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Elevated levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides contribute significantly to the development of atherosclerosis, an underlying pathophysiological cause of cardiovascular disease (CVD). Conversely, elevated levels of circulating high-density lipoprotein cholesterol (HDL-C) provide protection against the development of atherosclerosis and is inversely correlated with the incidence of CVD. The main aim of this study was to determine the effects of two major types of anthocyanins on LDL-C and other cardiometabolic markers for CVD risk in hyperlipidaemic individuals. This study is a randomised, placebo-controlled, double-blind, three arm crossover design. The three treatments were: (i) a bilberry extract delivering 320mg of mostly delphinidin/trihydroxy type anthocyanins, (ii) a black rice extract delivering 320mg of mostly cyanidin/dihydroxy type anthocyanins, and (iii) a placebo control. A total of fifty-five participants were randomly assigned to one of the three treatments. Results show that ingestion of 320mg day of delphinidin or cyanidin type anthocyanins for 28-day did not reduce LDL-C in a study population with elevated cholesterol levels. Additionally, neither did consumption of delphinidin or cyanidin type anthocyanins beneficially alter other biomarkers related to vascular function, glycaemic control or biomarkers of HDL function. Authors conclude that the lack of positive effects in their study may be due to the short duration of the treatments. Thus, future research should conduct studies based on longer time periods (≥12 weeks duration).
Abstract
SCOPE Some dietary interventions with berry fruits, berry fruit extracts, and purified anthocyanins have been reported to beneficially alter lipoprotein profiles in hyperlipidemic participants. The major anthocyanins in human diets are glycosides of cyanidin and delphinidin, and structure can influence both absorption and bioactivity. The aim of this study is to determine the effects of two major types of anthocyanins on low-density lipoprotein cholesterol and other cardiometabolic markers for cardiovascular disease (CVD) risk in hyperlipidemic individuals. METHODS AND RESULTS Fifty-two hyperlipidemic participants complete this randomized, placebo-controlled, double-blind, three arm crossover trial. Participants ingest capsules containing 320 mg of anthocyanins (bilberry trihydroxy-type or black rice dihydroxy-type) or placebo once daily for 28 days. Biomarkers of CVD risk are measured before and after the intervention period. Compared to the placebo, neither anthocyanin treatment significantly (p < 0.05) changes circulating levels of lipoproteins (total-/high-density lipoprotein (HDL)-/low-density lipoprotein (LDL)-cholesterol, triglycerides, Apolipoprotein B (ApoB)), biomarkers of glycemic control (fasting glucose, fructosamine), biomarkers of HDL function (ApoA1, HDL3, paraoxonase-1 (PON1) arylesterase, and lactonase activities), or plasma bile acids. CONCLUSIONS These data do not support the notion that regular consumption of anthocyanins beneficially affects glycemic control or lipoprotein profiles or functions. It is possible the no effect observation is due to the relatively short duration of treatments.
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Nutraceutical approach for the management of cardiovascular risk - a combination containing the probiotic Bifidobacterium longum BB536 and red yeast rice extract: results from a randomized, double-blind, placebo-controlled study.
Ruscica, M, Pavanello, C, Gandini, S, Macchi, C, Botta, M, Dall'Orto, D, Del Puppo, M, Bertolotti, M, Bosisio, R, Mombelli, G, et al
Nutrition journal. 2019;18(1):13
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Probiotics have been shown to reduce total cholesterol (TC) and low-density lipoprotein (LDL-C – often called ‘bad’ cholesterol) in people with moderately raised cholesterol levels. A specific strain of probiotic called Bifidobacterium longum BB536, may decrease TC and LDL-C by reducing the reabsorption of cholesterol from the intestine, and, combined with other natural supplements, may be useful to manage high cholesterol in people at low risk of heart disease. This study was conducted to evaluate the effect of a nutraceutical (Lactoflorene Colesterolo®), containing Bifidobacterium longum BB536 (1bn CFUs) combined with red yeast rice (RYR) extract (10 mg/day monacolin K), niacin (16mg) and coenzyme Q10 (20mg) on levels of cholesterol and fats in the blood. This was a 12-week randomised, parallel, double-blind, placebo-controlled study, in which 33 adults at low risk of heart disease were given either the Bifidobacterium combination, or a placebo. Treatment with the Bifidobacterium combination significantly reduced total cholesterol by 16.7%, LDL-C by 25.7%, non-HDL-C by 24% and apolipoprotein-B by 17%. Triglycerides, HDL-C, apolipoprotein AI, lipoprotein (a) and proprotein convertase subtilisin/kexin type 9 (PCSK9) were unchanged. Markers of cholesterol synthesis and absorption suggested that a reduction in the synthesis of cholesterol had occurred without increased absorption of cholesterol. No adverse effects were reported in the study and the compliance rate was high at 97%. The use of nutraceuticals in the prevention of cardiovascular disease, as well as in other areas related to chronic diseases like cancer, is currently expanding.
Abstract
BACKGROUND Probiotics incorporated into dairy products have been shown to reduce total (TC) and LDL cholesterolemia (LDL-C) in subjects with moderate hypercholesterolemia. More specifically, probiotics with high biliary salt hydrolase activity, e.g. Bifidobacterium longum BB536, may decrease TC and LDL-C by lowering intestinal cholesterol reabsorption and, combined with other nutraceuticals, may be useful to manage hypercholesterolemia in subjects with low cardiovascular (CV) risk. This study was conducted to evaluate the efficacy and safety of a nutraceutical combination containing Bifidobacterium longum BB536, red yeast rice (RYR) extract (10 mg/day monacolin K), niacin, coenzyme Q10 (Lactoflorene Colesterolo®). The end-points were changes of lipid CV risk markers (LDL-C, TC, non-HDL-cholesterol (HDL-C), triglycerides (TG), apolipoprotein B (ApoB), HDL-C, apolipoprotein AI (ApoAI), lipoprotein(a) (Lp(a), proprotein convertase subtilisin/kexin type 9 (PCSK9)), and of markers of cholesterol synthesis/absorption. METHODS A 12-week randomized, parallel, double-blind, placebo-controlled study. Thirty-three subjects (18-70 years) in primary CV prevention and low CV risk (SCORE 0-1% in 24 and 2-4% in 9 subjects; LDL-C: 130-200 mg/dL) were randomly allocated to either nutraceutical (N = 16) or placebo (N = 17). RESULTS Twelve-week treatment with the nutraceutical combination, compared to placebo, significantly reduced TC (- 16.7%), LDL-C (- 25.7%), non-HDL-C (- 24%) (all p < 0.0001), apoB (- 17%, p = 0.003). TG, HDL-C, apoAI, Lp(a), PCSK9 were unchanged. Lathosterol:TC ratio was significantly reduced by the nutraceutical combination, while campesterol:TC ratio and sitosterol:TC ratio did not change, suggesting reduction of synthesis without increased absorption of cholesterol. No adverse effects and a 97% compliance were observed. CONCLUSIONS A 12-week treatment with a nutraceutical combination containing the probiotic Bifidobacterium longum BB536 and RYR extract significantly improved the atherogenic lipid profile and was well tolerated by low CV risk subjects. TRIAL REGISTRATION NCT02689934 .
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Dietary fiber intake and glycemic control: coronary artery calcification in type 1 diabetes (CACTI) study.
Basu, A, Alman, AC, Snell-Bergeon, JK
Nutrition journal. 2019;18(1):23
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The incidence of type 1 diabetes and cardiovascular disease, the major vascular complication of diabetes, have been increasing wordwide. The aim of the study is to identify the associations of dietary fibre with glycaemic control. The study is a cross-sectional longitudinal study which enrolled 1257 individuals in the cross-sectional analysis and a total of 990 participants were included in the longitudinal analysis. The participants had no known history of coronary heart disease. Results indicate an inverse association between total fibre intake and the average blood glucose levels for the last two to three months in both diabetic and nondiabetic participants. Authors conclude that their study provides some evidence on the role dietary fibre intake plays on glycaemic control, which is important in the management of type 1 diabetes in patients at high risk of cardiovascular disease.
Abstract
BACKGROUND Dietary fiber has been recommended for glucose control, and typically low intakes are observed in the general population. The role of fiber in glycemic control in reported literature is inconsistent and few reports are available in populations with type 1 diabetes (T1D). METHODS Using data from the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study [n = 1257; T1D: n = 568; non-diabetic controls: n = 689] collected between March 2000 and April 2002, we examined cross-sectional (baseline) and longitudinal (six-year follow-up in 2006-2008) associations of dietary fiber and HbA1c. Participants completed a validated food frequency questionnaire, and a physical examination and fasting biochemical analyses (12 h fast) at baseline visit and at the year 6 visit. We used a linear regression model stratified by diabetes status, and adjusted for age, sex and total calories, and diabetes duration in the T1D group. We also examined correlations of dietary fiber with HbA1c. RESULTS Baseline dietary fiber intake and serum HbA1c in the T1D group were 16 g [median (IQ): 11-22 g) and 7.9 ± 1.3% mean (SD), respectively, and in the non-diabetic controls were 15 g [median (IQ): 11-21 g) and 5.4 ± 0.4%, respectively. Pearson partial correlation coefficients revealed a significant but weak inverse association of total dietary fiber with HbA1c when adjusted for age, sex, diabetes status and total calories (r = - 0.07, p = 0.01). In the adjusted linear regression model at baseline, total dietary fiber revealed a significant inverse association with HbA1c in the T1D group [β ± SE = - 0.32 ± 0.15, p = 0.034], as well as in the non-diabetic controls [- 0.10 ± 0.04, p = 0.009]. However, these results were attenuated after adjustment for dietary carbohydrates, fats and proteins, or for cholesterol and triglycerides. No such significance was observed at the year 6 follow-up, and with the HbA1c changes over 6 years. CONCLUSION Thus, at observed levels of intake, total dietary fiber reveals modest inverse associations with poor glycemic control. Future studies must further investigate the role of overall dietary quality adjusting for fiber-rich foods in T1D management.
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Systemic and vascular inflammation in an in-vitro model of central obesity.
Ahluwalia, A, Misto, A, Vozzi, F, Magliaro, C, Mattei, G, Marescotti, MC, Avogaro, A, Iori, E
PloS one. 2018;13(2):e0192824
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Overweight and obesity are major risk factors for a number of chronic diseases, including diabetes, cardiovascular disease and cancer. Obese individuals often have excess fat around the middle, known as central adiposity, a condition known to contribute to an increase in blood levels of compounds such as glycerol and triglycerides. This study builds on a series of studies in which it has been demonstrated that circulation of these compounds reduces glucose uptake and increases lactate availability in all cells. The aim of the study was to challenge the system in-vitro with increasing levels of adiposity to determine the impact this had on compounds in the blood and the extent to which this reflects obesity-related vascular and systemic stress observed in humans. The focus of the study was primarily on lipid-related molecules and pro-inflammatory markers. Visceral adipose tissue was obtained from 9 donors undergoing liver resection for metastatic/benign liver lesions without any underlying chronic liver disease or diabetic complications and body mass index ranging from 20-25. The study outlines that an increase of adiposity in-vitro determines a pro-inflammatory state and results in endothelial stress.
Abstract
Metabolic disorders due to over-nutrition are a major global health problem, often associated with obesity and related morbidities. Obesity is peculiar to humans, as it is associated with lifestyle and diet, and so difficult to reproduce in animal models. Here we describe a model of human central adiposity based on a 3-tissue system consisting of a series of interconnected fluidic modules. Given the causal link between obesity and systemic inflammation, we focused primarily on pro-inflammatory markers, examining the similarities and differences between the 3-tissue model and evidence from human studies in the literature. When challenged with high levels of adiposity, the in-vitro system manifests cardiovascular stress through expression of E-selectin and von Willebrand factor as well as systemic inflammation (expressing IL-6 and MCP-1) as observed in humans. Interestingly, most of the responses are dependent on the synergic interaction between adiposity and the presence of multiple tissue types. The set-up has the potential to reduce animal experiments in obesity research and may help unravel specific cellular mechanisms which underlie tissue response to nutritional overload.
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A Randomized Study of the Effects of Additional Fruit and Nuts Consumption on Hepatic Fat Content, Cardiovascular Risk Factors and Basal Metabolic Rate.
Agebratt, C, Ström, E, Romu, T, Dahlqvist-Leinhard, O, Borga, M, Leandersson, P, Nystrom, FH
PloS one. 2016;11(1):e0147149
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Fruits and vegetables intake has been advocated to improve blood lipids profile and reduce risk of cardiovascular disease, diabetes and cancer. However, a low fat diet rich in fruits and vegetables has showed no effect on cardiovascular disease and cancer in a large randomized American trial. This might be due to the high sugar content in fruits, particularly fructose. The aim of this study was to compare the effects of adding either fruits or nuts to the diet of 30 healthy non-obese individuals on liver fat, metabolic rate and cardiovascular risk markers. Authors concluded that the trial only showed small effects on cardiovascular risk factors. Nevertheless, there was a significant change in lipoprotein (fats that transport fats in the blood) levels between the two groups, which tends to give an advantage to the consumption of nuts over fruits. They deduced that increased intake of fruits doesn’t negatively impact cardiovascular disease risk factors in healthy non-obese individuals. However, further research needs to evaluate the effects on obese and insulin-resistant participants.
Abstract
BACKGROUND Fruit has since long been advocated as a healthy source of many nutrients, however, the high content of sugars in fruit might be a concern. OBJECTIVES To study effects of an increased fruit intake compared with similar amount of extra calories from nuts in humans. METHODS Thirty healthy non-obese participants were randomized to either supplement the diet with fruits or nuts, each at +7 kcal/kg bodyweight/day for two months. Major endpoints were change of hepatic fat content (HFC, by magnetic resonance imaging, MRI), basal metabolic rate (BMR, with indirect calorimetry) and cardiovascular risk markers. RESULTS Weight gain was numerically similar in both groups although only statistically significant in the group randomized to nuts (fruit: from 22.15 ± 1.61 kg/m(2) to 22.30 ± 1.7 kg/m(2), p = 0.24 nuts: from 22.54 ± 2.26 kg/m(2) to 22.73 ± 2.28 kg/m(2), p = 0.045). On the other hand BMR increased in the nut group only (p = 0.028). Only the nut group reported a net increase of calories (from 2519 ± 721 kcal/day to 2763 ± 595 kcal/day, p = 0.035) according to 3-day food registrations. Despite an almost three-fold reported increased fructose-intake in the fruit group (from 9.1 ± 6.0 gram/day to 25.6 ± 9.6 gram/day, p<0.0001, nuts: from 12.4 ± 5.7 gram/day to 6.5 ± 5.3 gram/day, p = 0.007) there was no change of HFC. The numerical increase in fasting insulin was statistically significant only in the fruit group (from 7.73±3.1 mIE/L to 8.81±2.9 mIE/L, p = 0.018, nuts: from 7.29±2.9 mIE/L to 8.62±3.0 mIE/L, p = 0.14). Levels of vitamin C increased in both groups while α-tocopherol/cholesterol-ratio increased only in the fruit group. CONCLUSIONS Although BMR increased in the nut-group only this was not linked with differences in weight gain between groups which potentially could be explained by the lack of reported net caloric increase in the fruit group. In healthy non-obese individuals an increased fruit intake seems safe from cardiovascular risk perspective, including measurement of HFC by MRI. TRIAL REGISTRATION ClinicalTrials.gov NCT02227511.
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An antiinflammatory dietary mix modulates inflammation and oxidative and metabolic stress in overweight men: a nutrigenomics approach.
Bakker, GC, van Erk, MJ, Pellis, L, Wopereis, S, Rubingh, CM, Cnubben, NH, Kooistra, T, van Ommen, B, Hendriks, HF
The American journal of clinical nutrition. 2010;91(4):1044-59
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Increasing numbers of the population are overweight or obese, which increases the risk of metabolic diseases such as diabetes and heart disease. Overweight/obese individuals have increased low grade inflammation, which is thought to be an underlying process in disease development. This double blinded randomised controlled trial (RCT) aimed to investigate if dietary supplements could reduce inflammation and oxidative stress. Dietary supplements contained six nutrients (fish oil, green tea extract, resveratrol, vitamin E, vitamin C, and tomato extract) that had evidence of anti-inflammatory properties. Supplements were taken by thirty-six overweight male subjects for five weeks, following a crossover study design. Blood, urine and fat tissue samples were taken as markers of inflammation, oxidative stress and nutrigenomics. Although the main inflammatory marker was unchanged, the study did show a decrease in other inflammatory and oxidative markers, and increase in antiinflammatory markers. The highly sensitive nutrigenomnic measures were able to detect an overall metabolic change. The authors suggested that greater changes might be seen with a longer intervention period. The study showed that supplementation with antiinflammatory food extracts had a beneficial effect on inflammatory and metabolic processes in overweight individuals.
Abstract
BACKGROUND Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. OBJECTIVE It was hypothesized that specific dietary components are able to reduce low-grade inflammation as well as metabolic and oxidative stress. DESIGN Dietary products [resveratrol, green tea extract, alpha-tocopherol, vitamin C, n-3 (omega-3) polyunsaturated fatty acids, and tomato extract] selected for their evidence-based antiinflammatory properties were combined and given as supplements to 36 healthy overweight men with mildly elevated plasma C-reactive protein concentrations in a double-blind, placebo-controlled, crossover study with treatment periods of 5 wk. Inflammatory and oxidative stress defense markers were quantified in plasma and urine. Furthermore, 120 plasma proteins, 274 plasma metabolites (lipids, free fatty acids, and polar compounds), and the transcriptomes of peripheral blood mononuclear cells and adipose tissue were quantified. RESULTS Plasma adiponectin concentrations increased by 7%, whereas C-reactive protein (principal inflammation marker) was unchanged. However, a multitude of subtle changes were detected by an integrated analysis of the "omics" data, which indicated modulated inflammation of adipose tissue, improved endothelial function, affected oxidative stress, and increased liver fatty acid oxidation. CONCLUSION An intervention with selected dietary products affected inflammatory processes, oxidative stress, and metabolism in humans, as shown by large-scale profiling of genes, proteins, and metabolites in plasma, urine, and adipose tissue. This trial was registered at clinical trials.gov as NCT00655798.