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.

D-allulose is a non-caloric natural sugar with health benefits. A few clinical trials with continuous D-allulose intake have been reported; one indicated significant increase in low-density lipoprotein cholesterol (LDL-C) levels, though the study was not a randomized controlled trial. D-allulose is predicted to be widely used in the near future by various people; therefore, the influence of D-allulose on those who have high risk for LDL-C elevation needs to be determined. Here, the effects of D-allulose on LDL-C levels in patients with hypercholesterolemia under statin therapy were investigated in a randomized controlled trial. Twenty subjects were randomly assigned to two groups: 15 g D-allulose/day or 15 g erythritol/day (placebo); each subject consumed a daily test substance for 48 weeks. Clinical examinations were performed every eight weeks, from initial consumption until week 52. No significant increase in LDL-C was observed, although significant decrease was observed in high-density lipoprotein cholesterol (HDL-C) in the D-allulose group. HDL-C values stayed within the standard ranges during the consumption period, and the mechanism was reported to be anti-atherosclerotic. In terms of risk assessment, D-allulose did not affect all risk factors that were measured for atherosclerotic cardiovascular disease. Taken together, these results suggested that long-term D-allulose consumption did not affect LDL-C values and atherosclerotic cardiovascular disease risk in patients with hypercholesterolemia under statin therapy.