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Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention.
Li, S, Yin, S, Ding, H, Shao, Y, Zhou, S, Pu, W, Han, L, Wang, T, Yu, H
Cell proliferation. 2023;56(1):e13346
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Multiple risk factors could lead to the development of liver cancer, one of the most common malignant tumours in the world. These risk factors include hepatitis infection, non-alcoholic fatty liver disease and excessive alcohol consumption. Polyphenols are bioactive compounds with antioxidant, anti-inflammatory, anti-mutagenic, anti-viral, hypoglycaemic, anti-hypertensive, antibacterial and anti-proliferative properties. Polyphenols may be effective in reducing the risk of developing liver cancer by altering the metabolism. This review evaluated the effectiveness of polyphenols in protecting the liver and inhibiting hepatocarcinoma development. In addition, the review evaluated several mechanisms by which polyphenols affect glucose and lipid metabolism and mitochondrial metabolism and reduce the effects of oxidative stress, inflammation and toxic metabolites. Further robust studies are required to assess the beneficial effects of polyphenols as a therapeutic agent, as the current knowledge is limited. However, healthcare professionals can use the results of this study to understand the protective effects of polyphenols against liver disease.
Abstract
BACKGROUND Liver cancer is one of the common malignancies. The dysregulation of metabolism is a driver of accelerated tumourigenesis. Metabolic changes are well documented to maintain tumour growth, proliferation and survival. Recently, a variety of polyphenols have been shown to have a crucial role both in liver disease prevention and metabolism regulation. METHODS We conducted a literature search and combined recent data with systematic analysis to comprehensively describe the molecular mechanisms that link polyphenols to metabolic regulation and their contribution in liver protection and liver cancer prevention. RESULTS Targeting metabolic dysregulation in organisms prevents and resists the development of liver cancer, which has important implications for identifying new therapeutic strategies for the management and treatment of cancer. Polyphenols are a class of complex compounds composed of multiple phenolic hydroxyl groups and are the main active ingredients of many natural plants. They mediate a broad spectrum of biological and pharmacological functions containing complex lipid metabolism, glucose metabolism, iron metabolism, intestinal flora imbalance, as well as the direct interaction of their metabolites with key cell-signalling proteins. A large number of studies have found that polyphenols affect the metabolism of organisms by interfering with a variety of intracellular signals, thereby protecting the liver and reducing the risk of liver cancer. CONCLUSION This review systematically illustrates that various polyphenols, including resveratrol, chlorogenic acid, caffeic acid, dihydromyricetin, quercetin, catechins, curcumin, etc., improve metabolic disorders through direct or indirect pathways to protect the liver and fight liver cancer.
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The Effect of Resveratrol on Blood Lipid Profile: A Dose-Response Meta-Analysis of Randomized Controlled Trials.
Cao, X, Liao, W, Xia, H, Wang, S, Sun, G
Nutrients. 2022;14(18)
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It is well known that cardiovascular disease is a leading cause of death. Imbalances in the blood lipid levels, such as elevation of total cholesterol, Triglycerides and LDL cholesterol, may increase the risk of cardiovascular disease. It has been shown that resveratrol, a polyphenol found in grapes, blueberries, mulberries, raspberries, peanuts, and knotweeds, has protective effects against cardiovascular disease. In this meta-analysis, 17 randomised controlled trials were included, with varying durations of 4 to 48 weeks and intervention dosages ranging from 10 to 3000 mg/day. According to the results of this meta-analysis, Resveratrol supplementation significantly reduced total cholesterol, triglycerides, and LDL cholesterol, but not HDL cholesterol. In addition, the reduction in LDL cholesterol was more significant in type 2 diabetic patients when resveratrol was supplemented for 12 weeks or more. A crucial factor in determining the effectiveness of resveratrol supplementation is its dosage. High doses over 500 mg/day were found to have the opposite effect of increasing body mass index and body weight and suppressing the cardioprotective effect. The effects of different dosages and durations of resveratrol supplementation on cardiometabolic health require further robust research. Healthcare professionals may use the results of this study to understand the importance of careful consideration when supplementing resveratrol as a nutraceutical.
Abstract
(1) Background: The effects of resveratrol on blood lipids are controversial. Whether there is a dose-response of the lipid profile upon resveratrol supplementation is unknown. (2) Methods: This dose-response meta-analysis of randomized controlled trials (RCTs) was performed to explore the effects of resveratrol supplementation on lipid profile. A systematical and comprehensive search of several databases was conducted by 30 June 2022. (3) Results: The results indicated that the intake of resveratrol could significantly decrease the total cholesterol (TC) (mean difference = -10.28; 95%CI: -13.79, -6.76, p < 0.001), triglyceride (TG) (Mean difference = -856; 95%CI: -12.37, -4.75, p < 0.001) and low-density lipoprotein cholesterol (LDL-C) (mean difference = -5.69; 95%CI: -11.07, -0.31, p = 0.038) level, but did not alter the level of high-density lipoprotein cholesterol (HDL-C). In the non-linear dose-response analysis, we observed a significant effect of the supplementation dosage on the level of LDL-C (p-nonlinearity = 0.002). Results from the sub-group analysis showed that the reduction of LDL-C was more significant in the trials with a duration of ≥12 weeks and in subjects with type 2 diabetes mellitus. (4) Conclusion: Findings from this study suggest that resveratrol may be beneficial to reduce TC, TG, and LDL-C levels in the blood. The dosage of the resveratrol intervention is an essential factor that affects the level of LDL-C.
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Polyphenol Intake in Pregnant Women on Gestational Diabetes Risk and Neurodevelopmental Disorders in Offspring: A Systematic Review.
Salinas-Roca, B, Rubió-Piqué, L, Montull-López, A
Nutrients. 2022;14(18)
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In Europe, gestational diabetes affects approximately 10.9% of pregnant women. According to previous research, the cardiometabolic health of the mother and the mother's dietary habits during pregnancy may affect the foetus' neurodevelopment. Taking polyphenol supplements and eating foods rich in polyphenols is beneficial for promoting health across generations. In this systematic review, fourteen studies were included in order to evaluate the effects of polyphenols on gestational diabetes and mental health in the offspring. A higher prevalence of neurodevelopmental diseases in offspring is associated with gestational diabetes. The results of this systematic review revealed that polyphenol intake during pregnancy might have a beneficial effect on improving cardiometabolic health, reducing inflammation, DNA methylation and oxidative stress, thus reducing the risk of developing fetal neurodevelopmental disorders, such as attention deficit hyperactivity disorder, autism spectrum disorder and learning disorders. There is a need for further robust research, as the existing evidence regarding the safety of long-term polyphenol supplementation and its effects on gestational diabetes and fetal neurodevelopment is very limited. In spite of this, healthcare professionals can use the findings of this systematic review to learn more about the positive health benefits of polyphenols in pregnant women.
Abstract
The intake of foods containing polyphenols can have a protective role to avoid comorbidities during pregnancy and, at the same time, promote transgenerational health. This review aims to describe the effect of polyphenol intake through supplements or polyphenol-rich foods during pregnancy on the incidence and evolution of gestational diabetes mellitus (GDM), as well as the link with the neurodevelopment of the fetus. Using PRISMA procedures, a systematic review was conducted by searching in biomedical databases (PubMed, Cinahl and Scopus) from January to June 2022. Full articles were screened (n = 419) and critically appraised. Fourteen studies were selected and were divided into two different thematic blocks considering (i) the effect of polyphenols in GDM and (ii) the effect of GDM to mental disorders in the offspring. A positive relationship was observed between the intake of polyphenols and the prevention and control of cardiometabolic complications during pregnancy, such as GDM, which could be related to thwarted inflammatory and oxidative processes, as well as neuronal factors. GDM is related to a greater risk of suffering from diseases related to neurodevelopment, such as attention deficit hyperactivity disorder, autism spectrum disorder and learning disorder. Further clinical research on the molecule protective mechanism of polyphenols on pregnant women is required to understand the transgenerational impact on fetal neurodevelopment.
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Buckwheat and Cardiometabolic Health: A Systematic Review and Meta-Analysis.
Llanaj, E, Ahanchi, NS, Dizdari, H, Taneri, PE, Niehot, CD, Wehrli, F, Khatami, F, Raeisi-Dehkordi, H, Kastrati, L, Bano, A, et al
Journal of personalized medicine. 2022;12(12)
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Buckwheat is a gluten-free, pseudo-grain rich in bioactive compounds that are cardiometabolic health protective. Bioactive cardioprotective compounds include proteins, fibre, and polyphenols such as rutin and quercetin-3-glucoside. This systematic review and meta-analysis investigated the supplementation and consumption of buckwheat and its effects on cardiovascular risk markers. Sixteen studies were included in the systematic review, and ten were included in the meta-analysis. This systematic review and meta-analysis showed a modest, non-significant improvement in total cholesterol and glucose levels. Further robust studies are required to investigate the beneficial effects of bioactive compounds found in buckwheat due to the high heterogeneity of the included studies and the poor quality of the included studies. However, healthcare professionals can use the results of this research to understand the potential of buckwheat in improving or maintaining cardiometabolic health.
Abstract
Buckwheat (BW) is suggested to have beneficial effects, but evidence on how it affects cardiometabolic health (CMH) is not yet established. We aimed to assess the effects of BW and/or its related bioactive compounds on cardiovascular disease (CVD) risk markers in adults. Five databases were searched for eligible studies. Observational prospective studies, nonrandomized or randomized trials were considered if they assessed BW, rutin or quercetin-3-glucoside intake and CVD risk markers. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting. We selected 16 human studies based on 831 subjects with mild metabolic disturbances, such as hypercholesterolemia, diabetes and/or overweight. Eight studies, investigating primarily grain components, were included in the meta-analyses (n = 464). High study heterogeneity was present across most of our analyses. Weighted mean difference (WMD) for subjects receiving BW supplementation, compared to controls, were - 0.14 mmol/L (95% CI: -0.30; 0.02) for total cholesterol (TC), -0.03 mmol/L (95% CI: -0.22; 0.16) for LDL cholesterol, -0.14 kg (95% CI: -1.50; 1.22) for body weight, -0.04 mmol/L (95% CI: - 0.09;0.02) for HDL cholesterol, -0.02 mmol/L (95% CI: -0.15; 0.11) for triglycerides and -0.18 mmol/L (95% CI: -0.36; 0.003) for glucose. Most of the studies (66.7%) had concerns of risk of bias. Studies investigating other CVD markers were scarce and with inconsistent findings, where available. Evidence on how BW affects CMH is limited. However, the available literature indicates that BW supplementation in mild dyslipidaemia and type 2 diabetes may provide some benefit in lowering TC and glucose, albeit non-significant. Our work highlights the need for more rigorous trials, with better methodological rigor to clarify remaining uncertainties on potential effects of BW on CMH and its utility in clinical nutrition practice.
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Effects of the Treatment with Flavonoids on Metabolic Syndrome Components in Humans: A Systematic Review Focusing on Mechanisms of Action.
Gouveia, HJCB, Urquiza-Martínez, MV, Manhães-de-Castro, R, Costa-de-Santana, BJR, Villarreal, JP, Mercado-Camargo, R, Torner, L, de Souza Aquino, J, Toscano, AE, Guzmán-Quevedo, O
International journal of molecular sciences. 2022;23(15)
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Metabolic syndrome is a condition characterised by at least three of the five risk factors, such as abdominal obesity, elevated fasting glucose, blood pressure and triglycerides and reduced high-density lipoprotein cholesterol (HDL-c). There is a strong link between metabolic syndrome and the development of cardiovascular disease and Type 2 diabetes. Research suggests that increasing consumption of flavonoid-rich foods can be beneficial in reducing cardiovascular morbidity and mortality. Flavonoids are bioactive compounds that possess antioxidative, anti-inflammatory, anti-cancerous, anti-mutagenic, and enzymatic properties. This systematic review of 29 randomised controlled trials evaluated the beneficial effects of long-term flavonoid supplementation in reducing the risk factors of metabolic syndrome. This review included a variety of flavonoid supplements, such as anthocyanin, hesperidin, quercetin, epigallocatechin gallate (egcg), genistein, theaflavin, catechin, and eriocitrin. Additionally, this research investigated the mechanisms behind the beneficial effects of flavonoid supplementation. Results showed that flavonoid supplementation for at least three weeks improved metabolic parameters and inflammatory markers, with hesperidin showing the greatest improvements in metabolic parameters. Healthcare professionals can use these findings to understand the potential benefits of long-term flavonoid supplementation in improving metabolic parameters. However, more robust studies are needed to determine the therapeutic dosages of different flavonoids.
Abstract
Diets high in bioactive compounds, such as polyphenols, have been used to mitigate metabolic syndrome (MetS). Polyphenols are a large group of naturally occurring bioactive compounds, classified into two main classes: non-flavonoids and flavonoids. Flavonoids are distributed in foods, such as fruits, vegetables, tea, red wine, and cocoa. Studies have already demonstrated the benefits of flavonoids on the cardiovascular and nervous systems, as well as cancer cells. The present review summarizes the results of clinical studies that evaluated the effects of flavonoids on the components of the MetS and associated complications when offered as supplements over the long term. The results show that flavonoids can significantly modulate several metabolic parameters, such as lipid profile, blood pressure, and blood glucose. Only theaflavin and catechin were unable to affect metabolic parameters. Moreover, only body weight and body mass index were unaltered. Thus, the evidence presented in this systematic review offers bases in support of a flavonoid supplementation, held for at least 3 weeks, as a strategy to improve several metabolic parameters and, consequently, reduce the risk of diseases associated with MetS. This fact becomes stronger due to the rare side effects reported with flavonoids.
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A Review of Dietary (Phyto)Nutrients for Glutathione Support.
Minich, DM, Brown, BI
Nutrients. 2019;11(9)
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Glutathione is made up of 3 amino acids (cysteine, glutamic acid and glycine) and plays important roles in the body, including oxidative stress reduction, supporting the immune system and contributing to detoxification processes. Evidence suggests that it is an important marker and target for treatment in many chronic, age-related diseases. This review article explores the evidence of nutritional strategies to improve glutathione status. The authors examine the evidence for supplementation of the precursors of glutathione as well as with various forms of supplemental glutathione itself, and the impacts on glutathione status and clinical impacts. Crucially, the review article provides information on dietary sources of precursors of glutathione and glutathione itself, which will provide Nutrition Practitioners with compelling information for use in clinic. Lean protein, brassica vegetables, polyphenol-rich fruits and vegetables, green tea, herbs and spices and omega-3 rich foods are all discussed in detail.
Abstract
Glutathione is a tripeptide that plays a pivotal role in critical physiological processes resulting in effects relevant to diverse disease pathophysiology such as maintenance of redox balance, reduction of oxidative stress, enhancement of metabolic detoxification, and regulation of immune system function. The diverse roles of glutathione in physiology are relevant to a considerable body of evidence suggesting that glutathione status may be an important biomarker and treatment target in various chronic, age-related diseases. Yet, proper personalized balance in the individual is key as well as a better understanding of antioxidants and redox balance. Optimizing glutathione levels has been proposed as a strategy for health promotion and disease prevention, although clear, causal relationships between glutathione status and disease risk or treatment remain to be clarified. Nonetheless, human clinical research suggests that nutritional interventions, including amino acids, vitamins, minerals, phytochemicals, and foods can have important effects on circulating glutathione which may translate to clinical benefit. Importantly, genetic variation is a modifier of glutathione status and influences response to nutritional factors that impact glutathione levels. This narrative review explores clinical evidence for nutritional strategies that could be used to improve glutathione status.