1,5-Anhydro-D-Mannitol Is a Potentially Low-Energy Carbohydrate: A Dual-Model Approach in Rats and a Randomized, Three-Way Crossover Trial in Humans

Background/Objectives: We hypothesized that orally ingested 1,5-anhydro-D-mannitol (AM) would be absorbed from the gut but poorly metabolized, and it may have low fermentability by gut microbiota based on the breath hydrogen test. Methods: We used a dual-model approach in this study. In animal experiments, AM was administered orally to male Wistar rats. In a randomized, three-way crossover trial (UMIN000054040), 15 healthy young adults consumed a single 5 g dose of AM, mannose, or fructooligosaccharide (FOS). Primary outcome was breath hydrogen concentrations; secondary outcomes included plasma AM, blood glucose concentration, and urinary AM excretion. Results: After ingestion of 5 g AM in humans, the 14 h area under the curve for breath hydrogen excretion was markedly lower after AM than that after FOS ingestion (p < 0.05). Plasma AM peaked at 1 h, whereas blood glucose remained unchanged from baseline. Approximately 30% of ingested AM was excreted unchanged in urine within 24 h. Results of animal experiments were similar to those in humans. Fecal excretion in AM was confirmed to be minimal, accounting for ~1% of the administered dose within 24 h in rats. Conclusions: These findings indicate that AM is potentially a low-energy carbohydrate.