| Summary: | This systematic review aimed to reveal the differential brain processing of sugars and sweeteners in humans. Functional magnetic resonance imaging studies published up to 2019 were retrieved from two databases and were included into the review if they evaluated the effects of both sugars and sweeteners on the subjects’ brain responses, during tasting and right after ingestion. Twenty studies fulfilled the inclusion criteria. The number of participants per study ranged from 5 to 42, with a total number of study participants at 396. Seven studies recruited both males and females, 7 were all-female and 6 were all-male. There was no consistent pattern showing that sugar or sweeteners elicited larger brain responses. Commonly involved brain regions were insula/operculum, cingulate and striatum, brainstem, hypothalamus and the ventral tegmental area. Future studies, therefore, should recruit a larger sample size, adopt a standardized fasting duration (preferably 12 h overnight, which is the most common practice and brain responses are larger in the state of hunger), and reported results with familywise-error rate (FWE)-corrected statistics. Every study should report the differential brain activation between sugar and non-nutritive sweetener conditions regardless of the complexity of their experiment design. These measures would enable a meta-analysis, pooling data across studies in a meaningful manner.
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