Increased Intake of Both Caffeine and Non-Caffeine Coffee Components Is Associated with Reduced NAFLD Severity in Subjects with Type 2 Diabetes

Abstract

Coffee may protect against non-alcoholic fatty liver disease (NAFLD), but the roles of the caffeine and non-caffeine components are unclear. Coffee intake by 156 overweight subjects (87% with Type-2-Diabetes, T2D) was assessed via a questionnaire, with 98 subjects (all T2D) also providing a 24 h urine sample for quantification of coffee metabolites by LC–MS/MS. NAFLD was characterized by the fatty liver index (FLI) and by FibroscanÒ assessment of fibrosis. No associations were found between self-reported coffee intake and NAFLD parameters; however, total urine caffeine metabolites, defined as Σcaffeine (caffeine + paraxanthine + theophylline), and adjusted for fat-free body mass, were significantly higher for subjects with no liver fibrosis than for those with fibrosis. Total non-caffeine metabolites, defined as Σncm (trigonelline + caffeic acid + p-coumaric acid), showed a significant negative association with the FLI. Multiple regression analyses for overweight/obese T2D subjects (n = 89) showed that both Σcaffeine and Σncm were negatively associated with the FLI, after adjusting for age, sex, HbA1c, ethanol intake and glomerular filtration rate. The theophylline fraction of Σcaffeine was significantly increased with both fibrosis and the FLI, possibly reflecting elevated CYP2E1 activity—a hallmark of NAFLD worsening. Thus, for overweight/obese T2D patients, higher intake of both caffeine and non-caffeine coffee components is associated with less severe NAFLD. Caffeine metabolites represent novel markers of NAFLD progression.

Preventive effects of caffeine on nicotine plus high-fat diet-induced hepatic steatosis and gain weight: a possible explanation for why obese smokers with high coffee consumption tend to be leaner

“…Obese smokers were more likely to suffer from NAFLD. Caffeine, the main ingredient of coffee, was reported to have a protective effect on NAFLD, with good application prospects (29,30) . Moreover, caffeine was proven to relieve NAFLD induced by HFD (20) , but it is still unknown whether caffeine can alleviate the development of NAFLD caused by HFD plus nicotine.…”

The Influence of Coffee on Reducing Metabolic Dysfunction-Associated Steatotic Liver Disease in Patients With Type 2 Diabetes: A Review

“…Although the BMI and specific weights of the mice are unclear, body weight may also be an essential factor mediating coffee-associated effects on the liver. Later findings by Coelho et al [ 36 ] also show that the effect of coffee on the liver may be related to an individual’s body mass.…”

“…Studying T2D as well, Coelho et al [ 36 ] conducted a survey-based cross-sectional study to investigate the role of coffee components in the MASLD progression of 98 subjects with T2D (Table 1 ). All subjects completed a questionnaire on their consumption of caffeinated beverages and foods and provided a 24-hour urine sample for investigation of coffee metabolites.…”

Diagnostic indicators and lifestyle interventions of metabolic-associated fatty liver disease

“…It has also been suggested that caffeine attenuates liver fat and stiffness in patients with diabetes and NAFLD ( 83 ). Coffee is associated with NAFLD severity in type 2 diabetics ( 84 ). For overweight/obese patients with MASLD and T2D, coffee consumption may have potential benefits ( 85 ).…”