Oat beta glucan versus iso dietary fiber or placebo in MASLD: A multicenter, randomized, placebo-controlled dietary study

Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease globally. Nutritional intake and Tthe gut-liver axis areis considered a key drivers in MASLD. Enriching diet of MASLD patients with fiber has been discussed a way to alter intestinal microbiota and thereby also disease. Oat beta glucan (ß-Glucan) has shown potential in reducing blood cholesterol and protecting against steatohepatitis in preclinical models via its interaction with the gut microbiome. We aimed to compare the beneficial effect of nutritional monitoring and an enrichment of diet with different fibers e.g., soluble dietary supplementation with (oat branß-Glucan) and insoluble fiber (spelt bran) compared with iso dietary fiber or to placebo (low in fiber) in patients with MASLD. Methods A diet for liver health (ADLH) was an investigator-initiated, randomisedrandomized, double-blind, placebo-controlled, multi-center dietary study conducted at the University Hospital RWTH Aachen, Department of Medicine III in Germany and Medical University of Vienna, University Hospital for Internal Medicine III, in Austria. Eligible participants were adults (aged 18-80 years) with steatotic liver disease (CAP >280dB) and without fibrosis or evidence of increased alcohol intake. After a three-week run-in-washout phase and an 1st assessment of dietary intake with a 3-day weighing protocol, participants were randomly allocated (1:1:1) through block randomization to receive oat bran( ß-Glucan (4.5g, total dietary fiber: 11.7g) daily, spelt bran (=iso dietary fiber, total dietary fiber (11.7g) daily, or matched placebo (flakes mix, 2.1 g total dietary fiber) for 12 weeks. Randomization was done in blocks of 3. The primary endpoint was a decrease in CAP value and ALT-concentration in blood samples from baseline to end of treatment. Exploratory endpoints included fecal microbiota composition and function analyzed using shotgun metagenomics and serum bile acid profiling as well as markers of intestinal barrier function in serum. Trial registration: NCT03897218. Findings Between April, 2019, and October 2021, 48 patients with a history of MASLD and no significant alcohol consumption or other liver disease and fibrosis, were screened and randomly assigned to either oat bran ß-Glucan, spelt bran iso dietary fiber or placebo. Interestingly, during the run-in when dietary intake was assessed by a 3d-weighing protocol pre-washout phase, participants demonstrated a significantly decreased in BMI, and ALT, AST and ?-GT levels being , which was associated with a significant increase in microbiota alpha diversity. The Ssustainability of these effects was most pronounced in patients receiving spelt bran or placebo, while patients in the oat bran group, However, these improvements were not sustained during the dietary intervention phase . Oat ß-beta glucan did not improve steatosis or ALT levels thus failed to meet the primary endpoints. Relative reductions in AST at 12 weeks were significantly higher in participants in the iso dietary fiber compared to the oat-ß-glucan group. While some correlations were observed between specific bacterial taxa, the overall microbiamicrobiota composition and l functions remained stable after the initial shift during the run-in phase, indicating that the and dietary groups, the overall impact of the dietary interventions did not cause any further changes. on microbiota composition and function was minimal. Serum bile acid levels remained unchanged across all groups . Conclusions Assessment of nutritional intake (3-day weighing dietary protocol) improved BMI, and markers of MASLD being related to changes in microbiota alpha diversity. Moreover, repeated assessment of nutritional intake in combination with the consumption of insoluble fiber or a placebo helped to maintain these improvements during the study and, in part throughout, the follow-up. dDuring the pre-washout phase significantly improved steatosis and ALT levels. However, dietary supplementation with oat ß-glucan did not improve hepatic steatosis or serum ALT levels in individuals with MASLD any further. None of the treatments had a significant impact on the gut microbiome or serum bile acids. This study underscores the need for dietary counseling as a key component in the clinical management of MASLD and emphasizes the importance of rigorous controls in dietary studies related to this condition.