D ‐Allulose as a Low‐Calorie Sweetener: A 30‐Day Randomized, Double‐Blind Study on Gastrointestinal Tolerance and Systemic Safety to Support Its Application in Healthy Diets
Lijuan Qi, Junyu Ning, Jiangli Han, Nan Zhang, Wenjing Zhang, Fangfang Wang, Dan Li, Zinan Li, Yanmin Nie, Haiming Jing, Shan GaoABSTRACT
Long‐term safety, tolerance, and population‐specific effects of innovatively fermented D ‐allulose are lacking in the Chinese population. This study aimed to address these gaps and support its application as a novel food ingredient in China. A 30‐day randomized, double‐blind, parallel‐group design with pre‐post comparison trial was conducted, enrolling 50 healthy Chinese adults (high‐dose group: 36 g/day, 0.6 g/kg body weight, n = 26; low‐dose group: 24 g/day, 0.4 g/kg body weight, n = 24). Gastrointestinal tolerance was monitored via daily questionnaires; systemic safety was evaluated using hematological tests, serum biochemical tests, urinalysis, fecal analysis, and body composition measurements. The incidence of gastrointestinal symptoms was 48.0%, which were mild, transient, and most frequent on Days 1–3, with no significant intergroup differences. All statistically significant changes in safety indicators remained within normal clinical reference ranges. Compared with baseline, the 30‐day intervention resulted in reduced red blood cell count, hematocrit, and platelet count, as well as elevated mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration in both groups. For serum biochemical parameters, levels of alkaline phosphatase, gamma‐glutamyl transferase, uric acid, total cholesterol, and high‐density lipoprotein cholesterol decreased in both groups, while fasting blood glucose was reduced only in high‐dose group. Notably, high‐dose D ‐allulose intervention decreased bone mineral density T‐scores in participants aged 35 years and older. All statistically significant alterations in the measured indicators remained within normal clinical ranges and were clinically insignificant. This study provides critical safety data to support the planned approval of D ‐allulose as a novel food ingredient in China in 2025. Its modulation of hematological and serum biochemical parameters suggests effects on hematopoiesis and glycolipid metabolism. Given the limitations of the 30‐day intervention duration, relatively modest sample size, and restriction to healthy normal‐BMI adults, a provisional safe intake limit of 0.4 g/kg body weight per day is proposed for Chinese adult population, requiring validation in longer‐term and larger‐scale studies.