Safety evaluation of 12-week continuous ingestion of D-allulose in borderline diabetes and type 2 diabetes

Abstract

D-allulose is a rare sugar with an almost zero calorie and is known to suppress postprandial hyperglycemia and fat mass accumulation. Although D-allulose has been reported to be safe in healthy subjects and overweight/obese adults, its safety in borderline diabetes and diabetes patients has not been evaluated. Therefore, we conducted an open trial aimed to investigate the long-term safety of D-allulose in borderline diabetes and type 2 diabetes. Subjects took 5 g of D-allulose with meals three times daily for 12 continuous weeks. The general blood biochemical parameters, hematological parameters, urinary parameters, and anthropometric indicators were measured at 0, 2, 4, 8, and 12 weeks of the consumption periods and 4 weeks after completing consumption. Adverse events were assessed by the principal physician on each examination day. A total of 12 and 6 subjects with borderline and type 2 diabetes, respectively, were analyzed. No serious clinical problems were found in this study, although significant cholesterol variations and the improvements of some indicators of hepatic function were observed. In conclusion, the long-term ingestion of D-allulose is safe in borderline diabetes and type 2 diabetes. D-allulose can potentially suppress postprandial hyperglycemia and fat mass accumulation, and thus might be useful in diabetes.

Safety and efficacy of a 48-week long-term ingestion of D-allulose in subjects with high LDL cholesterol levels

“…Not only biliary enzyme activities but also liver deviance enzyme activities (AST and ALT) and the score of fatty liver improved with D-allulose intake (Table 10, 11). Similar results related to hepatic functions were reported in some previous studies Itoh et al, 2015;Tanaka et al, 2019). CDCA is a strong agonist for the Farnesoid X Receptor (FXR), which is a member of the nuclear receptors superfamily and regulates the metabolism of bile acid, cholesterol, lipoprotein, TG, and glucose.…”

“…Our results, however, demonstrated no significant changes related to renal functions (blood urea nitrogen, creatinine, uric acid, urine specific gravity, urinary microalbumin, and urine pH) by long-term and excessive D-allulose intake in both blood and urinary examinations. Other clinical studies have also reported similar results (Han et al, 2018;Hayashi et al, 2010;Tanaka et al, 2019). Results of other examinations, including physical, blood, and urine examinations, did not show clinical problems.…”

“…These results consequently suggested that there is no evidence that transient variations in cholesterol levels through the long-term intake of D-allulose heightens ASCVD risks. The degree of the cholesterol elevations in this study did not significantly differ from the placebo group and the increases also disappeared with consecutive long-term intakes of D-allulose; therefore, they might be due to a seasonal variation like in a previous open trial (Tanaka et al, 2019). However, there is a possibility that cholesterol variations are related to various metabolism changes.…”

“…D-Allulose is generally recognized as safe (GRAS) by the Food and Drug Administration (FDA) in the USA and as a food category in Japan. However, an open clinical trial of D-allulose consumption for 12 weeks without the placebo group in borderline diabetics and type 2 diabetics demonstrated significant increases in total cholesterol (T-Cho) and lowdensity lipoprotein cholesterol (LDL-C) compared with the first day of consumption (Tanaka et al, 2019). Elevations of T-Cho and LDL-C by food ingredients have also been reported in some clinical trials; for example, n-3 fatty acid (Harris, 1996;Mori et al, 2000), coffee diterpenes cafestol (Urgert et al, 1997), boiled coffee (Aro et al, 1987), and carbohydrate-restricted diets (Foster et al, 2010).…”

“…This mechanism, which activates hepatic SR-B1, is accordingly considered not to be atherogenic due to promoting RCT in spite of decreases in HDL-C levels (Kasai et al, 2012). Some previous studies reported reductions in HDL-C levels within the standard ranges by D-allulose intake (Hayashi et al, 2010;Tanaka et al, 2019), and the mechanism is estimated to enhance HDL-C uptake into the liver through HDL receptors because D-allulose was reported to suppress the decrease in the expression of CLA-1 (cluster of differentiation 36 and Lysosomal integral membrane protein-2 analogous-1: a human homologue of SR-B1) in Hep G2 cells under high glucose level conditions (Iida and Okuma, 2012). In terms of the mechanism, the decrease in HDL-C levels by D-allulose intake was not considered a serious clinical problem.…”