Low-calorie sweeteners (LCS) are widely utilized as sugar substitutes due to their intense sweetness, thermal stability, and applicability in weight management and diabetic-friendly products. However, increasing evidence has raised concerns about their potential long-term effects on metabolic health, glucose regulation, cardiovascular function, carcinogenicity, and gut microbiota composition. This review systematically evaluates the pharmacokinetics, metabolic effects, and associated health outcomes of major LCS. Mechanistically, LCS exert effects via sweet taste receptor-mediated pathways, altering glucose absorption, insulin secretion, and intracellular signaling cascades. Additionally, LCS influence gut microbiota composition, with certain agents promoting dysbiosis and glucose intolerance. While some findings support the metabolic benefits of selected LCS, others underscore potential risks, necessitating cautious interpretation. In conclusion, while LCS offer viable alternatives to sugar, their health effects are context-dependent and may vary across different sweeteners and populations. Long-term, high-quality clinical trials are essential to elucidate their safety and efficacy.

Background: The outcomes for patients with NASH-related HCC after curative resection have not been clarified. This study compared the overall survival (OS), time-to-tumor recurrence (TTR), and recurrence-free survival (RFS) associated with NASH-related HCC and virus-related HCC after resection. Methods: Patients with HCC who underwent curative resection were retrospectively enrolled. Baseline characteristics, including disease etiologies and clinical and tumor features, were reviewed. The primary outcomes were OS, TTR, and RFS. Results: Two hundred and six patients were enrolled (HBV: n = 121, HCV: n = 54, NASH: n = 31). Of those with virus-related HCC, 84.0% achieved viral suppression. In both the overall and propensity-score-matched cohorts, those with NASH-related HCC experienced recurrence significantly earlier than those with virus-related HCC (median TTR: 1108 days vs. non-reached; p = 0.03). Through multivariate analysis, NASH-related HCC (hazard ratio (HR), 2.27; 95% confidence interval (CI), 1.25–4.12) was independently associated with early recurrence. The unadjusted RFS rate of the NASH-related HCC group was lower than the virus-related HCC group. There was no difference in the OS between the two groups. Conclusions: NASH-related HCC was associated with earlier tumor recurrence following curative resection compared to virus-related HCC. Post-surgical surveillance is crucial for detecting early recurrence in patients with NASH-related HCC.

Objectives: Although angiopoietin-like 4 (ANGPTL4) is highly associated with glucose hemostasis and lipid metabolism, the relationships between the serum ANGPTL4 level, glucose status and hepatic steatosis remain unclear. Therefore, this study aimed to quantify the independent effects of glucose intolerance and hepatic steatosis on circulating ANGPTL4 concentrations. Methods: A total of 348 age- and sex-matched participants with normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and newly diagnosed diabetes (NDD) with or without hepatic steatosis were recruited for this cross-sectional study. Serum ANGPTL4 levels were measured, and multivariate linear regression analysis was used to evaluate the relationship between ANGPTL4, glycemic status and hepatic steatosis. Results: Compared with NGT, both IGT and NDD were associated with significantly higher serum ANGPTL4 concentrations, irrespective of hepatic steatosis status. Serum ANGPTL4 did not differ by the presence versus absence of hepatic steatosis. In multiple regression analysis, body mass index, homeostasis model assessment of insulin resistance, NGT vs. IGT, and NGT vs. NDD were independently associated with ANGPTL4 levels after adjustment for cardiovascular risk factors and adiponectin, whereas hepatic steatosis was not. Conclusions: Elevated serum ANGPTL4 concentrations were independently associated with prediabetes and diabetes, irrespective of hepatic steatosis.

Background: Since non-alcoholic fatty liver disease (NAFLD) is highly associated with obesity, cardiovascular disease, and diabetes, biomarkers for the diagnosis of NAFLD have become an important issue. Although cardiotrophin-1 (CT-1) has a protective effect on the liver in NAFLD animal models, the serum levels of CT-1 in human subjects with NAFLD were still unknown. Objective: The present study aimed to investigate the relationship between the circulating concentration of CT-1 and the severity of hepatic steatosis graded by the value of the controlled attenuation parameter (CAP) in humans. Design and Methods: The study was designed as a cross-sectional study, and a total of 182 subjects were enrolled. Hepatic steatosis measurement was carried out with a Firoscan^® device and recorded by CAP. The enrolled study subjects were categorized into CAP < 238 dB/m, 238 ≤ CAP ≤ 259 dB/m, 260 ≤ CAP ≤ 290 dB/m, and CAP > 290 dB/m. Serum CT-1 concentrations were determined by enzyme-linked immunosorbent assay. The association between the serum CT-1 concentration and NAFLD was examined by multivariate linear regression analysis. Results: Body mass index, percentage of body fat, systolic and diastolic blood pressure, alanine aminotransferase (ALT), cholesterol, triglyceride, hemoglobin A1c and homeostatic model assessment for insulin resistance (HOMA-IR) were significantly increased in groups with higher CAP value, whereas high-density lipoprotein cholesterol was significantly decreased. In addition, serum CT-1 concentrations were significantly decreased in subjects with higher CAP values. In multivariate linear regression models, including age, sex, body fat percentage, CAP, high sensitivity- C reactive protein, uric acid, creatinine, ALT, total cholesterol, and HOMA-IR, only age, CAP and uric acid independently associated with CT-1 levels. Moreover, having NAFLD was independently associated with CT-1 after adjustment for sex, obesity and type 2 diabetes. Conclusions: Serum CT-1 concentrations are decreased in subjects with NAFLD and negatively associated with CAP.