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Context Rare sugars are monosaccharides and disaccharides (found in small quantities in nature) that have slight differences in their chemical structure compared with traditional sugars. Little is known about their unique physiological and cardiometabolic effects in humans. Objective The objective of this study was to conduct a systematic review and synthesis of controlled intervention studies of rare sugars in humans, using PRISMA guidelines. Data Sources MEDLINE and EMBASE were searched through October 1, 2020. Studies included both post-prandial (acute) and longer-term (≥1 week duration) human feeding studies that examined the effect of rare sugars (including allulose, arabinose, tagatose, trehalose, and isomaltulose) on cardiometabolic and physiological risk factors. Data extraction In all, 50 studies in humans focusing on the 5 selected rare sugars were found. A narrative synthesis of the selected literature was conducted, without formal quality assessment or quantitative synthesis. Data synthesis The narrative summary included the food source of each rare sugar, its effect in humans, and the possible mechanism of effect. Overall, these rare sugars were found to offer both short- and long-term benefits for glycemic control and weight loss, with effects differing between healthy individuals, overweight/obese individuals, and those with type 2 diabetes. Most studies were of small size and there was a lack of large randomized controlled trials that could confirm the beneficial effects of these rare sugars. Conclusion Rare sugars could offer an opportunity for commercialization as an alternative sweetener, especially for those who are at high cardiometabolic risk. Systematic Review Registration OSF registration no. 10.17605/OSF.IO/FW43D.

Rare sugars and their health effects in humans: a systematic review and narrative synthesis of the evidence from human trials