D-allulose is a rare sugar with zero energy that can be consumed by obese/overweight individuals. Many studies have suggested that zero-calorie d-allulose has beneficial effects on obesity-related metabolism in mouse models, but only a few studies have been performed on human subjects. Therefore, we performed a preliminary study with 121 Korean subjects (aged 20–40 years, body mass index ≥ 23 kg/m²). A randomized controlled trial involving placebo control (sucralose, 0.012 g × 2 times/day), low d-allulose (d-allulose, 4 g × 2 times/day), and high d-allulose (d-allulose, 7 g × 2 times/day) groups was designed. Parameters for body composition, nutrient intake, computed tomography (CT) scan, and plasma lipid profiles were assessed. Body fat percentage and body fat mass were significantly decreased following d-allulose supplementation. The high d-allulose group revealed a significant decrease in not only body mass index (BMI), but also total abdominal and subcutaneous fat areas measured by CT scans compared to the placebo group. There were no significant differences in nutrient intake, plasma lipid profiles, markers of liver and kidney function, and major inflammation markers among groups. These results provide useful information on the dose-dependent effect of d-allulose for overweight/obese adult humans. Based on these results, the efficacy of d-allulose for body fat reduction needs to be validated using dual energy X-ray absorption.

D-allulose has recently received attention as a sugar substitute. However, there are currently no reports regarding its association with gastrointestinal (GI) tolerance. Thus, we performed a GI tolerance test for D-allulose in order to establish its daily acceptable intake level. When the dose of D-allulose was gradually increased in steps of 0.1 g/kg·Body Weight (BW) to identify the maximum single dose for occasional ingestion, no cases of severe diarrhea or GI symptoms were noted until a dose of 0.4 g/kg·BW was reached. Severe symptoms of diarrhea were noted at a dose of 0.5 g/kg·BW. Similarly, the GI tolerance test did not show any incidences of severe diarrhea or GI symptoms until a dose of 0.5 g/kg·BW was reached. A correlation analysis of the GI tolerance test for D-allulose and sugar revealed significantly higher frequencies of symptoms of diarrhea (p = 0.004), abdominal distention (p = 0.039), and abdominal pain (p = 0.031) after D-allulose intake. Increasing the total daily D-allulose intake gradually to 1.0 g/kg·BW for regular ingestion resulted in incidences of severe nausea, abdominal pain, headache, anorexia, and diarrheal symptoms. Based on these results, we suggest a maximum single dose and maximum total daily intake of D-Allulose of 0.4 g/kg·BW and 0.9 g/kg·BW, respectively.

D-allulose, a C-3 epimer of D-fructose, is a rare monosaccharide used as a food ingredient or a sweetener. In the present study, the in vitro metabolic stability of D-allulose was examined in biorelevant media, that is, simulated gastric fluid (SGF) and fasted state simulated intestinal fluid (FaSSIF) containing digestive enzymes, and in cryopreserved human and rat hepatocytes. The hepatocyte metabolic stabilities of D-allulose were also investigated and compared with those of fructose and erythritol (a sugar-alcohol with no calorific value). D-allulose was highly stable in SGF (97.8% remained after 60 min) and in FaSSIF (101.3% remained after 240 min), indicating it is neither pH-labile nor degraded in the gastrointestinal tract. D-allulose also exhibited high levels of stability in human and rat hepatocytes (94.5–96.8% remained after 240 min), whereas fructose was rapidly metabolized (43.1–52.6% remained), which suggested these two epimers are metabolized in completely different ways in the liver. The effects of D-allulose on glucose and fructose levels were negligible in hepatocytes. Erythritol was stable in human and rat hepatocytes (102.1–102.9% remained after 240 min). Intravenous pharmacokinetic studies in rats showed D-allulose was eliminated with a mean half-life of 72.2 min and a systemic clearance of 15.8 mL/min/kg. Taken together, our results indicate that D-allulose is not metabolized in the liver, and thus, unlikely to contribute to hepatic energy production.

D-allulose, which has 70% of the sweet taste of sucrose but nearly no calories, has been reported to inhibit the absorption of lipids and suppress body weight gain in obese mice. Fats in non-dairy creamer consist of highly saturated fatty acids, which can cause various lipid disorders when consumed over a long period. We investigated whether D-allulose supplementation alleviates the effects of a non-dairy creamer-enriched high-fat diet on lipid metabolism. High-fat diets enriched with non-dairy creamer were administered to C57BL/6J mice with or without D-allulose supplementation for eight weeks by the pair-feeding design. Lipid metabolic markers were compared between the non-dairy creamer control group (NDC) and non-dairy creamer allulose group (NDCA). Body, adipose tissue, and liver weights, and fasting blood glucose levels, were significantly lower in the NDCA group than in the NDC group. Fecal fatty acid and triglyceride levels were significantly higher in the NDCA group than in the NDC group. Supplementing a non-dairy creamer-enriched high-fat diet with D-allulose improved overall lipid metabolism, including the plasma and hepatic lipid profiles, hepatic and adipose tissue morphology, and plasma inflammatory adipokine levels in mice. These results suggest that D-allulose can be used as a functional food component for preventing body fat accumulation from a high-fat diet that includes hydrogenated plant fats.