The Effect of a Ketogenic Diet on Liver Health: A Systematic Review and Meta-Analysis.

BackgroundPropolis, a natural resin produced by bees, has been studied for its potential effects on liver enzymes and obesity indices. However, a meta-analysis is necessary to comprehensively understand the impact of propolis on obesity and liver function. ObjectivesThis meta-analysis of randomized controlled trials (RCTs) sought to evaluate the effects of propolis consumption on liver enzymes and obesity indices in adults. MethodsA systematic literature search up to December 2023 was completed in PubMed/Medline, Scopus, and Web of Science, to identify eligible RCTs. Heterogeneity tests of the selected trials were performed using the I2 statistic. Random-effects models were assessed on the basis of the heterogeneity tests, and pooled data were determined as weighted mean differences (WMDs) with a 95% confidence interval (CI). ResultsA pooled analysis of 24 trials showed that propolis consumption led to a significant reduction in alanine aminotransferase (ALT) (WMD: −2.58; 95% CI: −4.64, −0.52; P = 0.01), aspartate aminotransferase (AST) (WMD: −1.84; 95% CI: −3.01, −0.67; P = 0.002), and alkaline phosphatase (ALP) (WMD: −24.90; 95% CI: −42.13, −7.67; P = 0.005) in comparison with the control group. However, there were no significant effects on gamma-glutamyl transferase (GGT), body weight, BMI (in kg/m2), fat mass, body fat percentage, fat-free mass, adiponectin, waist circumference, hip circumference, and waist–hip ratio in comparison with the control group. ConclusionsWe discovered that consuming propolis can lead to a significant decrease in ALT, AST, and ALP levels, without causing significant changes in GGT, anthropometric indices, and adiponectin levels. However, future well-designed RCTs with large numbers of participants and extended durations, focusing on precise propolis dosage and ingredients, are necessary.

We aimed to elucidate the frequency of polymorphic genotypes and alleles of patatin-like phospholipase domain containing 3 rs738409 polymorphism and its possible associations with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis in a cohort from Turkey.We enrolled 200 patients diagnosed with NAFLD and genotyped for rs738409 I148M polymorphism by real-time polymerase chain reaction, particularly by melting curve analysis. SPSS analysis software was used for statistical significance. Continuous variable values were expressed as mean ± standard deviation. Significant statistical level was chosen as p = 0.05.Our results demonstrate in a cohort from Turkey that rs738409 C > G polymorphism (I148M) of patatin-like phospholipase domain containing 3 gene is significantly able to affect individuals to have NAFLD in unadjusted regression model.Consistent with the previous studies in other populations, our study group showed a significantly higher risk of having NAFLD in unadjusted regression model but not in the adjusted model indicating that non-genetic factors such as age and sex may be responsible for the association. However, independent studies need to validate our findings with a larger group of NAFLD patients, as well as in different ethnic cohorts.

BackgroundNonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver ailment worldwide, in which nonpharmacological strategies have a considerable role in the treatment. Probiotic supplementation as well as physical exercise can improve cardiometabolic parameters, but further research is needed to determine the effects of combined treatment versus exercise alone in managing NAFLD-associated biomarkers, primarily liver enzymes, lipid markers, and insulin resistance.ObjectivesThis systematic review and meta-analysis aimed to evaluate the effects of probiotic supplementation, combined with exercise versus exercise alone, on liver enzymes and cardiometabolic markers in patients with NAFLD.MethodsA systematic review and meta-analysis of randomized clinical trials was performed by searching PubMed, Scopus, and Web of Science databases up to April 2024. The search was restricted to articles published in the English language and human studies. Random effects models were used to calculate weighted mean differences (WMD).ResultsPooled estimates (9 studies, 615 patients, intervention durations ranging from 8 to 48 weeks) revealed that probiotics plus exercise decreased aspartate transaminase (AST) [WMD=-5.64 U/L, p = 0.02], gamma-glutamyl transferase (GGT) [WMD=-7.09 U/L, p = 0.004], low-density lipoprotein (LDL) [WMD=-8.98 mg/dL, p = 0.03], total cholesterol (TC) [WMD=-16.97 mg/dL, p = 0.01], and homeostatic model assessment for insulin resistance (HOMA-IR) [WMD=-0.94, p = 0.005] significantly more than exercise only. However, probiotics plus exercise did not significantly change high-density lipoprotein (HDL) [WMD = 0.07 mg/dL, p = 0.9], fasting insulin [WMD=-1.47 µIU/mL, p = 0.4] or fasting blood glucose (FBG) [WMD=-1.57 mg/dL, p = 0.3] compared with exercise only. While not statistically significant, there were clinically relevant reductions in alanine aminotransferase (ALT) [WMD=-6.78 U/L, p = 0.1], triglycerides (TG) [WMD=-21.84 mg/dL, p = 0.1], and body weight (BW) [WMD=-1.45 kg, p = 0.5] for probiotics plus exercise compared with exercise only. The included studies exhibited significant heterogeneity for AST (I2 = 78.99%, p = 0.001), GGT (I2 = 73.87%, p = 0.004), LDL (I2 = 62.78%, p = 0.02), TC (I2 = 72.41%, p = 0.003), HOMA-IR (I2 = 93.86%, p = 0.001), HDL (I2 = 0.00%, p = 0.9), FBG (I2 = 66.30%, p = 0.01), ALT (I2 = 88.08%, p = 0.001), and TG (I2 = 85.46%, p = 0.001). There was no significant heterogeneity among the included studies for BW (I2 = 0.00%, p = 0.9).ConclusionProbiotic supplementation combined with exercise training elicited better results compared to exercise alone on liver enzymes, lipid profile, and insulin resistance in patients with NAFLD.Systematic Review RegistrationPROSPERO registration number CRD42023424290.

According to previous studies, astaxanthin exerts various biological effects due to its anti-inflammatory and antioxidant capabilities; however, its effects on liver enzymes have not yet been well elucidated. Therefore, we conducted a meta-analysis to assess astaxanthin's effects on liver enzymes. A systematic literature search was conducted using scientific databases including PubMed, Scopus, Web of Science, the Cochrane databases, and Google Scholar up to February 2023 to find relevant randomized controlled trials (RCTs) examining the effects of astaxanthin supplementation on alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP). A random-effects model was used for the estimation of the pooled weighted mean difference (WMD). Overall, we included five trials involving 196 subjects. The duration of the intervention was between 4 and 48 weeks, and the dose was between 6 and 12 mg/day. ALT levels increased in the intervention group compared to the control group following astaxanthin supplementation (WMD: 1.92 U/L, 95% CI: 0.16 to 3.68, P=0.03), whereas supplementation with astaxanthin had a non-significant effect on AST (WMD: 0.72 U/L, 95% CI: -0.85 to 2.29, P=0.36), GGT (WMD: 0.48 U/L, 95% CI: -2.71 to 3.67, P=0.76), and ALP levels (WMD: 2.85 U/L, 95% CI: -7.94 to 13.63, P=0.60) compared to the placebo group. Our data showed that astaxanthin supplementation increases ALT concentrations in adults without affecting the levels of other liver enzymes. Further long-term and well-designed RCTs are necessary to assess and confirm these findings.

Efficacy of sodium-glucose co-transporter 2 inhibitors in treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis

Aim: To correlate liver stiffness with demographical factors and routine liver biochemistry and to assess the predictive value of these as potential markers of fibrosis. Transient elastography was performed in 1268 chronic hepatitis B (CHB) patients. According to a previous validated study for CHB, liver stiffness of >8.1 and >10.3 kPa were used as cut-off values for defining severe fibrosis and cirrhosis respectively. Liver stiffness correlated positively with bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), globulin, alpha-fetoprotein (AFP) and HBV DNA levels and negatively with albumin and platelet levels (P<0.05 for all correlations). From 13 parameters (age, sex, platelet, AST, ALT, GGT, AFP, albumin, globulin, bilirubin, ALP, HBV DNA and hepatitis B e-antigen), four best parameters (AST, platelet, GGT and AFP) were used to derive a liver stiffness model. Using log (index)=1.44+0.1490(GGT)+0.3308 log (AST)-0.5846 log (platelets)+0.1148 log (AFP+1) to predict both severe fibrosis and cirrhosis had area under the receiver operating characteristics curve of 0.85. Routine liver biochemistry correlated well with liver stiffness in Asian CHB patients. A model using simple serum markers can predict liver stiffness, and further studies are required to validate the usefulness of these simple tests as non-invasive markers of fibrosis in CHB.

Efficacy of resveratrol supplementation on liver enzymes in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis

Gamma glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) are common liver enzymes. Abnormal serum circulating levels of these enzymes may signal liver or cholestatic damage (1). Circulating GGT is present on the external surfaces of most cells, particularly hepatocytes, and is used as a biological marker of excessive alcohol intake (2). ALT and AST catalyze the transfer of amino groups to generate products in gluconeogenesis and amino acid metabolism (3, 4). Elevated serum levels of these aminotransferases signal acute or chronic liver injury (1). ALP is a hydrolase enzyme that transports metabolites across cell membranes, with elevated serum levels commonly used in clinical practice as a marker of liver or bony disease (1, 5). In addition to their physiological functions, a growing body of evidence indicates that baseline serum levels of these enzymes may be associated with the development of a wide range of disease outcomes. Several reports have indicated that among these enzymes, elevated baseline levels of GGT and ALT are each associated with increased risk of future type-2 diabetes mellitus (T2DM) (6, 7). Indeed, the associations are apparent even within normal ranges of these enzymes. There is, however, considerable uncertainty regarding the association between AST level and risk of T2DM. In a recent review, we synthesized available prospective epidemiological data on the association between AST and incident T2DM (7). The pooled analyses involving 1,912 incident T2DM cases did not show a significant association between AST and risk of future T2DM. In contrast, a recently rigorously conducted prospective study involving 2,182 incident T2DM cases, reported a multivariate adjusted relative risk (RR) of 1.16 (1.02–1.31) for T2DM in a comparison of the highest to the lowest quartile of baseline AST levels (8). The association was continuous and extended well within the normal range of AST levels. This large study adds to the growing body of evidence that like GGT and ALT, elevated AST level may also be associated with increased risk for T2DM. The prospective evidence on the association between AST and T2DM is inconclusive and this may be attributed to several reasons including: lack of adequate power, unmeasured confounding, or even over-adjustment for potential intermediates by previous studies. Given that levels of serum liver enzymes (GGT, ALT, and AST) (i) are strongly environmentally and genetically correlated with one another (9), and (ii) have shared genetic variances (10), the evidence is suggestive of common biological pathways affecting levels of these enzymes. There is therefore a possibility that the association between AST level and risk of T2DM might be mediated through the effects of the other liver enzymes. The potential impact of other liver enzymes on the AST–T2DM association is unclear as it is uncertain whether adjusting for such putative intermediates is appropriate. There are indications that further adjustment for other liver enzymes may be responsible for the substantially attenuated or null associations observed in several studies. To help clarify the evidence, we report an updated review.

This meta-analysis of the randomized controlled trials was performed to assess effects of carnitine supplementation on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. A comprehensive literature search of PubMed, Cochrane's library, Web of Science, Scopus, and Embase was performed up to May 2018. From a total of 2012 articles identified initially, only 17 articles were included in the final meta-analysis to evaluate the effects of carnitine supplementation on serum levels of ALT and AST enzymes. Random effects model meta-analysis showed that carnitine supplementation led to reduction in serum ALT (weighted mean difference [WMD] - 10.25IU/L; 95% CI = - 15.73, - 4.77; p < 0.001) and AST levels (WMD - 7.85IU/L; 95% CI = - 11.85, - 3.86; p < 0.001). The results of subgroup analysis showed that carnitine could reduce serum AST levels at dosages equal to 2000mg/day (p = 0.014) or more than 2000mg/day (p < 0.001). However, carnitine supplementation at dosages of ≤ 1000mg/day (p = 0.035) or equal to 2000mg/day (p = 0.013) resulted in significant reduction in ALT level, while doses more than 2000mg/day did not change ALT significantly. Carnitine exerts its reducing effect on serum ALT and AST levels only when these aminotransferases are raised or when the duration of supplementation lasts at least 3months. Results of the current meta-analysis showed that carnitine supplementation can decrease serum AST and ALT levels significantly, especially when supplementation lasts 3months or more in patients with elevated serum aminotransferase levels.

Effect of novel glucose lowering agents on non-alcoholic fatty liver disease: A systematic review and meta-analysis

Intermittent fasting (IF) is a diet strategy with alternate intervals of calorie reduction and normal eating. Despite its beneficial effects on weight loss and cardiometabolic risk factors, the effect of IF on liver function tests (LFTs) remains unclear. This study aimed to investigate the effect of IF on LFTs through a systematic review and meta-analysis of randomized clinical trials. An electronic search was performed using predefined search terms in databases including PubMed, Scopus, and ISI Web of Science until February 2023. The studies were selected according to PRISMA guidelines, and the risk of bias was assessed for the randomized controlled trials. The results of this study are reported as weighted mean differences (WMDs) with 95% CIs. Fourteen RCTs were included in the meta-analysis, with a total sample size of 908. IF significantly reduced alanine aminotransferase (ALT) (WMD: -2.88, 95% CI: -4.72 to -1.04, P-value = .002) and aspartate aminotransferase (AST) levels (WMD: -1.67, 95% CI: -3.12 to -0.22, P-value = .024). The results of the subgroup analysis showed that the impact of IF was significant in both the nonalcoholic fatty liver disease and the healthy groups for ALT. The effects of IF on the serum gamma-glutamyl transpeptidase (GGT) level were significant (WMD: -3.19, 95% CI: -6.00 to -0.39, P-value = .026), but there were no significant changes in the alkaline phosphatase (ALP) level (WMD: 1.06, 95% CI: -0.23 to 2.34, P-value = .106). Furthermore, no substantial heterogeneity between studies was reported. IF can improve ALT, AST, and GGT levels but not ALP enzyme levels and may have a benefit on liver function. PROSPERO registration no. CRD42023396211.

Effects of Propolis Consumption on Glycemic Indices and Liver Enzymes in Adults: A Grading of Recommendations Assessment, Development, and Valuation-assessed Systematic Review and Dose-Response Meta-analysis

Background: Type 2 diabetes mellitus has been linked with abnormal liver function tests. Increased activities of liver enzymes such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), ?-glutamyl transferase (GGT) are markers of liver cell injury. Increased activity of these markers is associated with metabolic syndrome, insulin resistance and type 2 diabetes mellitus. This study was aimed to evaluate the significance of liver enzymes such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), ?-glutamyl transferase (GGT) in type 2 diabetes mellitus patients. Materials & Methods: Total of 108 cases of type 2 diabetes mellitus patients, comprising of 68 males (62.9%) and 40 females (37%) were included in the study. 110 healthy subjects were includes as controls. Age of the subjects ranged between 27 to 75 years. Serum sample was used for the estimation of study parameters such as FBS, PPBS, AST, ALT, ALP, GGT, Total bilirubin, Direct bilirubin, Total proteins and Albumin. Results: In the present study, mean values of AST, ALT, ALP and GGT were statistically significantly increased in type 2 diabetes mellitus patients when compared to controls (P value 0.001). Conclusion: In this study, we found an association between the increased levels of liver enzymes such as AST, ALT, ALP and GGT in type 2 diabetes mellitus patients. Increased levels of ALT and AST are the surrogate markers for associated non alcoholic fatty liver disease in type 2 diabetes mellitus patients. Hence, testing for AST, ALT, ALP, and GGT should be carried out to screen for underlying non alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus patients.

Introduction: Liver disease and diabetes often co-occur and have shared risk factors. We undertook this study to investigate which liver enzyme (alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma-glutamyl transferase (GGT)) would be most strongly associated with incident diabetes in a large, community-based population. Hypothesis: We hypothesized that ALT, AST, and GGT would be independently associated with diabetes and that ALT would be most strongly associated with diabetes due to its liver specificity. Methods: We conducted a prospective analysis of 9,524 participants in the ARIC Study without diagnosed diabetes or a history of high alcohol consumption (&gt;14 [women] and &gt;21 [men] drinks/week). Enzymes were measured from stored plasma samples. We examined the association of sex-specific quartiles of liver enzymes with incident diagnosed diabetes using Cox proportional hazards models adjusted for demographic, lifestyle, and behavioral risk factors. Restricted cubic spline models were fit to model the continuous associations. Results: Median ALT, AST, and GGT were 13, 18, and 22 U/L, respectively. During a median follow-up of 11 years, there were 1,905 self-reported cases of diabetes. All three liver enzymes were significantly associated with diabetes, even after adjustment for all covariates (HRs (95% CIs): ALT, 1.63 (1.44, 1.85); AST, 1.23 (1.09, 1.40); GGT, 1.99 (1.71, 2.30) comparing Q4 versus Q1). The restricted cubic spline models show similar patterns (Figure). After simultaneously adjustment for the other liver enzymes, only ALT and GGT remained significantly associated with diabetes. In analyses further restricted to participants who reported never consuming alcohol only GGT remained significant. Conclusion: In this community-based population, GGT was more strongly associated with diabetes risk than ALT and AST. Although ALT and AST are considered to be more specific markers of liver disease, higher levels of GGT may be a more important risk factor for diabetes.

Comparison of sodium-glucose cotransporter-2 inhibitors and thiazolidinediones for management of non-alcoholic fatty liver disease: A systematic review and meta-analysis