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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 Moderate Weight Loss on a Non-Invasive Biomarker of Liver Fibrosis: A Randomised Controlled Trial.
Koutoukidis, DA, Jebb, SA, Aveyard, P, Astbury, NM
Obesity facts. 2020;13(2):144-151
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Non-alcoholic fatty liver disease covers a range of conditions from excess fat in the liver through inflammation and fibrosis, to advanced fibrosis, and cirrhosis. The Enhanced Liver Fibrosis (ELF) score is emerging as a promising blood biomarker for fibrosis. The aim of this study was to examine whether a community weight loss programme reduces ELF score over 12 months compared with a weight-loss intervention which is less effective. This study is a secondary analysis of a published randomised controlled trial. Participants (n=73) were equally randomised to a community weight loss programme (WeightWatchers) or usual care. Results indicate that there was no evidence of an effect of a community weight loss programme on changes in the ELF score and no association between weight loss and the ELF score in people who had, on average, an ELF score compatible with moderate fibrosis. Authors conclude that using the ELF test to assess weight loss treatment efficacy in improving liver fibrosis may be of limited value, thus biopsy remains the gold-standard assessment for liver fibrosis.
Abstract
BACKGROUND Referral to weight loss programmes is the only effective treatment for non-alcoholic fatty liver disease (NAFLD). Clinicians should advise weight loss and screen for liver fibrosis using the Enhanced Liver Fibrosis (ELF) score. AIM: To examine if the ELF score changes with weight loss. DESIGN AND SETTING Randomised controlled trial (ISRCTN85485463) in UK primary care during 2007-2008. METHOD Adults with a BMI of 27-35 kg/m2 and ≥1 risk factor for obesity-related disease were randomised to attend a community weight loss programme (n = 45) or receive usual weight loss advice from a practice nurse (n = 28). Weight and the ELF score were measured at baseline and 1 year. Analysis of covariance examined mean changes in the ELF score between groups and its relationship with weight loss. RESULTS Mean (SD) BMI was 31.10 kg/m2 (2.55) with evidence of moderate levels of liver fibrosis at baseline (mean ELF score: 8.93 [0.99]). There was no evidence that the community weight loss programme reduced the ELF score compared with usual care (difference +0.13 points, 95% CI: -0.25 to 0.52) despite greater weight loss (difference: -2.66 kg, 95% CI: -5.02 to -0.30). Mean weight loss in the whole cohort was 7.8% (5.9). There was no evidence of an association between weight change and change in ELF; the coefficient for a 5% weight loss was -0.15 (95% CI: -0.30 to 0.0002). CONCLUSION We found no evidence that the ELF score changed meaningfully following moderate weight loss. Clinicians should not use the ELF score to measure improvements in NAFLD fibrosis following weight loss programmes.
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Protective effect of probiotics in patients with non-alcoholic fatty liver disease.
Cai, GS, Su, H, Zhang, J
Medicine. 2020;99(32):e21464
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Non-alcoholic fatty liver disease (NAFLD) is common in people with obesity and is characterised by high amounts of fat stored in the liver. Diet and exercise are the standard treatments, however recent studies have indicated that the gut microbiota may have an important role. This randomised control trial of 140 patients with NAFLD, aimed to assess the effect of probiotics when added to standard therapy for 3 months. The results showed that although gut microbiota, some aspects of liver function, blood lipids and blood sugars were all improved in individuals on standard therapy, there were additional improvements in those on standard therapy plus probiotics. It was concluded that although standard therapy alone is adequate to improve NAFLD, probiotics plus standard therapy was superior to standard therapy alone and effective in treatment of NAFLD. This study could be used by health professionals to justify the addition of probiotics to standard therapy to further improve NAFLD outcomes.
Abstract
To investigate the effects of probiotics on liver function, glucose and lipids metabolism, and hepatic fatty deposition in patients with non-alcoholic fatty liver disease (NAFLD).Totally 140 NAFLD cases diagnosed in our hospital from March 2017 to March 2019 were randomly divided into the observation group and control group, 70 cases in each. The control group received the diet and exercise therapy, while the observation group received oral probiotics based on the control group, and the intervention in 2 groups lasted for 3 months. The indexes of liver function, glucose and lipids metabolism, NAFLD activity score (NAS), and conditions of fecal flora in 2 groups were compared before and after the treatment.Before the treatment, there were no significant differences on alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamine transferase (GGT), total bilirubin (TBIL), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), insulin resistance index (HOMA-IR), NAFLD activity score (NAS), and conditions of fecal flora in 2 groups (P > .05). After the treatment, ALT, AST, GGT, TC, TG, HOMA-IR, NAS, and conditions of fecal flora in the observation group were better than those in the control group, and the observation group was better after treatment than before. All these above differences were statistically significant (P < .05).Probiotics can improve some liver functions, glucose and lipids metabolism, hepatic fatty deposition in patients with NAFLD, which will enhance the therapeutic effects of NAFLD.
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Vitamin D supplementation improves SIRT1, Irisin, and glucose indices in overweight or obese type 2 diabetic patients: a double-blind randomized placebo-controlled clinical trial.
Safarpour, P, Daneshi-Maskooni, M, Vafa, M, Nourbakhsh, M, Janani, L, Maddah, M, Amiri, FS, Mohammadi, F, Sadeghi, H
BMC family practice. 2020;21(1):26
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Type 2 diabetes (T2D) is often preceded by a condition known as insulin resistance (IR). Recent studies have shown that low levels of vitamin D in the body are related to an increased incidence of IR and individuals with T2D have lower levels of vitamin D than healthy individuals. Vitamin D may have the ability to increase enzymes in the body that breakdown sugar and decrease IR. This 12-month double blind randomised control trial on 90 obese type 2 diabetics, aimed to assess the effects of vitamin D on these enzymes and blood sugar levels. The results showed that individuals on vitamin D had significantly increased enzymes which are involved in sugar breakdown and this translated into improved blood sugar levels, however this did not translate into improved markers for IR. It was concluded that compared to placebo, vitamin D supplementation improved blood sugar levels possibly due to the increase in enzymes involved in sugar breakdown. Healthcare professionals could use this study to recommend vitamin D supplementation to obese type 2 diabetics to improve their blood sugar levels.
Abstract
BACKGROUND Vitamin D (VD) may increase sirtuin 1 (SIRT1) and subsequently PPAR-γ coactivator 1α (PGC-1α) and irisin levels and these improvements may reduce insulin resistance (IR). The aim was to assess the effects of vitamin D supplementation on SIRT1, irisin, and IR in overweight/obese type 2 diabetes (T2D) patients. METHODS Ninety T2D males and females were recruited as a clinical trial study (mean of age and body mass index (BMI) of intervention and placebo groups were 50.05 ± 10.17 and 50.36 ± 10.2 yrs. and 31.37 ± 3.4 and 30.43 ± 3.2 kg/m2, respectively). The inclusion criteria were T2D, VD deficient, BMI > 25 kg/m2, and serum HbA1c < 8.5%. The exclusion criteria were using vitamin and mineral supplements, having any acute disease, recent modifying dose or type of drugs. The supplementation was 50,000 IU/week VD or placebo for 8 weeks. The demographic characteristics, anthropometrics, dietary intakes and physical activity status, sun exposure status, fasting blood sugar (FBS) and insulin, glycosylated hemoglobin (HbA1c), irisin, SIRT1, 25-hydroxy D3 (25(OH)VD), homeostasis model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) were determined. The significant P-value was ≤0.05. RESULTS The increase of serum VD, SIRT1, and irisin in the intervention group was significant (p < 0.001). HbA1c was decreased significantly by 1%. The changes in the other glucose indices (FBS, insulin, and IR) were non-significant. CONCLUSIONS VD supplementation may improve T2D by decreasing HbA1c and increasing SIRT1 and irisin in VD deficient T2D patients. Further trials are suggested. TRIAL REGISTRATION Iranian Registry of Clinical Trials, IRCT201604202365N11. Registered 21/08/2016, http://en.irct.ir/trial/2019.
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Silymarin in the prevention and treatment of liver diseases and primary liver cancer.
Féher, J, Lengyel, G
Current pharmaceutical biotechnology. 2012;13(1):210-7
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Non-alcoholic fatty liver disease (NAFLD) is a recognised health problem with no convincing interventions to date. This randomised trial aimed to examine the efficacy of silymarin plus vitamin E in the treatment of NAFLD. 36 patients were randomized to either group Ι or group ΙΙ. Group Ι was treated with 2 tablets of silymarin plus vitamin E per day, hypocaloric diet and exercise. Group ΙΙ was treated only with a hypocaloric diet. Study duration was 3 months for both groups. Diagnosis of NAFLD was confirmed for all participants by liver biopsy. Patients in group Ι showed significant decrease in anthropometric measurements. Both groups experienced reductions in markers of NAFLD, however in group I, these reductions were independent of weight loss, whereas in group II, those who failed to lose 5% of body weight didn’t show a change in biochemical markers. Authors conclude that intervention with silymarin plus vitamin E, alone or along with other treatments, can help NAFLD patients who fail to lose weight with diet.
Abstract
In chronic liver diseases caused by oxidative stress (alcoholic and non-alcoholic fatty liver diseases, drug- and chemical-induced hepatic toxicity), the antioxidant medicines such as silymarin can have beneficial effect. Liver cirrhosis, non-alcoholic fatty liver and steatohepatitis are risk factors for hepatocellular carcinoma (HCC). Insulin resistance and oxidative stress are the major pathogenetic mechanisms leading the hepatic cell injury in these patients. The silymarin exerts membrane-stabilizing and antioxidant activity, it promotes hepatocyte regeneration; furthermore it reduces the inflammatory reaction, and inhibits the fibrogenesis in the liver. These results have been established by experimental and clinical trials. According to open studies the long-term administration of silymarin significantly increased survival time of patients with alcohol induced liver cirrhosis. Based on the results of studies using methods of molecular biology, silymarin can significantly reduce tumor cell proliferation, angiogenesis as well as insulin resistance. Furthermore, it exerts an anti-atherosclerotic effect, and suppresses tumor necrosis factor-alpha-induced protein production and mRNA expression due to adhesion molecules. The chemopreventive effect of silymarin on HCC has been established in several studies using in vitro and in vivo methods; it can exert a beneficial effect on the balance of cell survival and apoptosis by interfering cytokines. In addition to this, anti-inflammatory activity and inhibitory effect of silymarin on the development of metastases have also been detected. In some neoplastic diseases silymarin can be administered as adjuvant therapy as well.