Effect of sucrose-free brazzein-sweetened ice cream on continuously monitored glycemic response in patients with metabolic dysfunction-associated steatotic liver disease: a randomized controlled double-blind crossover trial.

BACKGROUND & AIMS: Reducing sugar intake is one of the key targets for improving metabolic health in metabolic dysfunction-associated steatotic liver disease (MASLD), and natural sugar substitutes remain insufficiently studied. Brazzein, a natural sweet protein 500-2000 times sweeter than sucrose, may allow replacement of sucrose while preserving sweetness, but clinical data are lacking. We aimed to evaluate postprandial glycemic responses to brazzein-sweetened ice cream, with and without inulin, compared with sucrose-sweetened ice cream in adults with MASLD, using continuous glucose monitoring (CGM). METHODS: In this double-blind, randomized, 3-period crossover trial, 101 adults with MASLD (mean age: 54.6 y; 76% female; 44% with type 2 diabetes) consumed 100 g of ice cream sweetened with sucrose (14 g), brazzein (0.014%), or brazzein plus inulin (0.014% + 4 g) on separate days. Factory-calibrated CGM sensors were used. Principal analytic outcomes were glucose over 150 min and incremental area under the curve (iAUC). Linear mixed-effects models estimated treatment effects with adjustment for baseline glucose, period, sequence, and diabetes status. Complementary analyses evaluated whether between-formulation differences were explained by total carbohydrate content alone. RESULTS: Compared with sucrose-sweetened, both brazzein-containing formulations produced smaller postprandial glucose excursions from 30 to 135 min (treatment × time interaction, P < 0.001). Model-adjusted iAUC was 66.3 mmol/L × min (95% CI: 54.5, 78.0) for sucrose, 31.7 (19.9, 43.6) for brazzein, and 34.3 (22.5, 46.1) for brazzein plus inulin formulations. Relative to sucrose-sweetened, iAUC was 52% lower with brazzein and 48% lower with brazzein plus inulin formulations (both P < 0.001), whereas brazzein and brazzein plus inulin formulations did not differ significantly. Complementary analyses showed that the between-formulation differences were not explained by total carbohydrate content alone. Exploratory analyses showed that formulation-related glucose trajectories differed according to diabetes status (P < 0.001). Within-stratum analyses showed lower iAUC for both brazzein-sweetened products relative to the sucrose control in participants with and without diabetes. No period, sequence, or carryover effects were observed. CONCLUSIONS: In adults with MASLD, the tested sucrose-free brazzein-containing ice cream formulations produced substantially smaller acute CGM-derived postprandial glucose excursions and lower iAUC over 150 min than sucrose-sweetened ice cream. The similar responses observed with brazzein alone and brazzein plus inulin suggest that adding 4 g inulin did not abolish the acute glycemic advantage of the brazzein-containing formulation. Longer-term studies are needed to determine whether repeated substitution of sucrose-containing desserts with brazzein-sweetened alternatives translates into sustained metabolic, hepatic, microbiome, or behavioral benefits. TRIAL REGISTRATION: ClinicalTrials.gov NCT06724913.