beta-carotene and Non-alcoholic-Fatty-Liver-Disease

Whether supplementation with diet-derived antioxidants is beneficial for nonalcoholic fatty liver disease (NAFLD) is still controversial and we hope to answer this question using population-based genetic data.. A total of 8485 NAFLD cases and 658,849 healthy controls from four independent NAFLD genome-wide association studies were enrolled in this study. Genetic variants closely associated with the diet-derived antioxidants were selected to predict their circulating levels. A bi-directional Mendelian randomization (MR) design was employed to assess their causations.. Genetic correlation analyses suggested inverse associations between diet-derived antioxidants and NAFLD. MR analyses indicated that the odds ratio (OR) of per standard deviation increase in genetically predicted toenail and blood selenium was 1.179 for NAFLD (95% confidence interval [1.083-1.284]). Also, the genetically elevated selenium level was causally associated with increased levels of C-reactive protein, fibrinogen, alkaline phosphatase and glycated hemoglobin. The OR of 1 µg/dL increase in genetically predicted serum lycopene was 1.082 (95%CI [1.051-1.113]). No other causal associations were found for NAFLD. However, we observed protective effects of genetically predicted β-carotene (OR = 0.929[0.911-0.947]) and retinol (OR = 0.483[0.460-0.508]) on type 2 diabetes (T2D), and further they could reduce the serum levels of blood lipids and glucose. Reverse MR analysis suggested genetically predicated NAFLD status would not affect the levels of diet-derived antioxidants.. Overall, we observed the positive associations of genetically predicted selenium and lycopene with NAFLD. However, the genetically predicted β-carotene and retinol levels were inversely associated with the risk of T2D.

Topics: Antioxidants; beta Carotene; Diabetes Mellitus, Type 2; Diet; Genome-Wide Association Study; Humans; Lycopene; Mendelian Randomization Analysis; Non-alcoholic Fatty Liver Disease; Polymorphism, Single Nucleotide; Selenium; Vitamin A

High sodium intake has been linked to the prevalence of non-alcoholic fatty liver disease (NAFLD), but underlying mechanism remains unclear. This study aims to explore the role of chronic inflammation in the association between sodium and NAFLD. We also observed whether β-carotene, which had a strong anti-inflammatory effect, lowers the odds of NAFLD.. We performed mediation analyses to assess the mediating effects of C-reactive protein (CRP) and red cell distribution width (RDW) on the relationship between dietary sodium and NAFLD defined by the hepatic steatosis index (HSI) and the fatty liver index (FLI), respectively.. A total of 6725 participants were included in this study. Compared with the high sodium-low carotene group, participants in the high sodium-high carotene group had 16% and 26% lower odds for HSI and FLI-defined NAFLD, respectively. There were positive indirect effects of dietary sodium intake on the HSI-defined NAFLD (indirect effect: 0.0057, 95% CI: 0.0021-0.0091, P < 0.0001), as well as the FLI defined NAFLD (indirect effect: 0.0081, 95% CI: 0.0024-0.0162, P < 0.0001) when C-reactive protein (CRP) was considered as a mediator. The mediating effects were somewhat attenuated after further adjusting for dietary β-carotene intake. Similar results were found when RDW was considered as a mediator in the HSI-defined NAFLD analysis.. Higher sodium intake increases the odds of NAFLD by upregulating inflammation. Dietary β-carotene may attenuate this association by down regulating inflammation.

Topics: Anti-Inflammatory Agents; beta Carotene; C-Reactive Protein; Carotenoids; Humans; Inflammation; Mediation Analysis; Non-alcoholic Fatty Liver Disease; Sodium; Sodium, Dietary

β-Carotene has been reported to alleviate hepatic steatosis (SS), inflammation, and fibrosis in vivo and vitro studies. However, the clinical relevance of serum β-carotene and β-carotene-to-retinol (SC/SR) ratio with histological severity in nonalcoholic fatty liver disease (NAFLD) patients is unknown. This case-control study enrolled 24 control subjects and 62 NAFLD patients. Liver biopsies were collected and histological characteristics were assessed. Information with regard to demographic, anthropometric and dietary intake was assessed by face-to-face interviews with questionnaire. Serum β-carotene and retinol concentrations were determined by the HPLC method. Serum β-carotene and SC/SR levels in NAFLD patients were significantly lower than these in controls (0.23 ± 0.01 vs. 0.35 ± 0.04 μmol/L, 0.38 ± 0.03 vs. 0.84 ± 0.10). Compared with individuals without SS, both β-carotene and SC/SR levels were significantly decreased in those with moderate SS (0.34 ± 0.03 vs. 0.21 ± 0.02 μmol/L, 0.76 ± 0.09 vs. 0.37 ± 0.05). Subjects with mild inflammation had a significantly lower β-carotene and SC/SR levels than those without inflammation (0.23 ± 0.01 vs. 0.33 ± 0.04 μmol/L, 0.77 ± 0.09 vs. 0.38 ± 0.03). Serum SC/SR was significantly lower in patients with mild fibrosis than those without fibrosis (0.45 [0.27-0.83] vs. 0.34 [0.26-0.51]). According to the NAFLD Activity Scoring score, both β-carotene and SC/SR gradually decreased with disease progression from normal liver, simple SS to steatohepatitis borderline (ptrend ≤ 0.001). These results show that NAFLD patients have lower circulating β-carotene concentration and SC/SR ratio, which are associated with the histological severity of NAFLD.

Topics: Adult; beta Carotene; Case-Control Studies; Female; Humans; Inflammation; Liver; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Vitamin A

Many recent studies have shown that antioxidant vitamins and/or carotenoids may reduce liver disease, but this association has not been well established with thorough longitudinal cohort studies. The objective of this study was to longitudinally investigate whether serum carotenoids at baseline are associated with the risk of developing elevated serum alanine aminotransferase (ALT) among Japanese subjects. We conducted a follow-up study of 1073 males and females aged between 30 and 79 years at baseline from the Mikkabi prospective cohort study. Those who participated in the baseline study and completed follow-up surveys were examined longitudinally. Exclusions included excessive alcohol consumption (≥60 g alcohol/d), hepatitis B and C and having a history of medication use for liver disease. A cohort of 213 males and 574 females free of elevated serum ALT (>30 IU/ml) at baseline was studied. Over a mean follow-up period of 7·4 (sd 3·1) years, thirty-one males and forty-nine females developed new elevated serum ALT. After adjustments for confounders, the hazard ratios for elevated serum ALT in the highest tertiles of basal serum β-carotene, β-cryptoxanthin and total provitamin A carotenoids against the lowest tertiles were 0·43 (95 % CI 0·22, 0·81), 0·51 (CI 0·27, 0·94) and 0·52 (CI 0·28, 0·97), respectively. For α-carotene and lycopene, borderline reduced risks were also observed; however, these were not significant. Our results further support the hypothesis that antioxidant carotenoids, especially provitamin A carotenoids, might help prevent earlier pathogenesis of non-alcoholic liver disease in Japanese subjects.

Topics: Adult; Aged; Alanine Transaminase; Antioxidants; beta Carotene; Beta-Cryptoxanthin; Carotenoids; Cohort Studies; Female; Humans; Japan; Liver Diseases; Longitudinal Studies; Lycopene; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Prospective Studies; Risk Factors; Vitamin A

This study aimed to investigate the possible therapeutic effects and active components of Lycium barbarum polysaccharides (LBP) on a high fat diet-induced NASH rat model. We induced NASH in a rat model by voluntary oral feeding with a high-fat diet ad libitum for 8 weeks. After 8 weeks, 1 mg/kg LBP was orally administered for another 4 weeks with a high-fat diet. When compared with NASH rats treated for 12 weeks, therapeutic LBP treatment for 4 weeks during 12 weeks of NASH induction showed ameliorative effects on: (1) increased body and wet liver weights; (2) insulin resistance and glucose metabolic dysfunction; (3) elevated level of serum aminotransferases; (4) fat accumulation in the liver and increased serum free fatty acid (FFA) level; (5) hepatic fibrosis; (6) hepatic oxidative stress; (7) hepatic inflammatory response; and (8) hepatic apoptosis. These improvements were partially through the modulation of transcription factor NF-κB, MAPK pathways and the autophagic process. In a palmitate acid-induced rat hepatocyte steatosis cell-based model, we also demonstrated that l-arabinose and β-carotene partially accounted for the beneficial effects of LBP on the hepatocytes. In conclusion, LBP possesses a variety of hepato-protective properties which make it a potent supplementary therapeutic agent against NASH in future clinical trials.

Topics: Animals; Anti-Obesity Agents; Apoptosis; Arabinose; Autophagy; beta Carotene; Cell Survival; Cells, Cultured; Diet, High-Fat; Drugs, Chinese Herbal; Female; Hepatocytes; Insulin Resistance; Lipid Metabolism; Liver; MAP Kinase Signaling System; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress; Rats, Sprague-Dawley