Brain activity and connectivity changes in response to nutritive natural sugars, non-nutritive natural sugar replacements and artificial sweeteners

Nutr Neurosci. 2021 May;24(5):395-405. doi: 10.1080/1028415X.2019.1639306. Epub 2019 Jul 10.


Introduction: The brain plays an important regulatory role in directing energy homeostasis and eating behavior. The increased ingestion of sugars and sweeteners over the last decades makes investigating the effects of these substances on the regulatory function of the brain of particular interest. We investigated whole brain functional response to the ingestion of nutrient shakes sweetened with either the nutritive natural sugars glucose and fructose, the low- nutritive natural sugar replacement allulose or the non-nutritive artificial sweetener sucralose.

Methods: Twenty healthy, normal weight, adult males underwent functional MRI on four separate visits. In a double-blind randomized study setup, participants received shakes sweetened with glucose, fructose, allulose or sucralose. Resting state functional MRI was performed before and after ingestion. Changes in Blood Oxygen Level Dependent (BOLD) signal, functional network connectivity and voxel based connectivity by Eigenvector Centrality Mapping (ECM) were measured.

Results: Glucose and fructose led to significant decreased BOLD signal in the cingulate cortex, insula and the basal ganglia. Glucose led to a significant increase in eigen vector centrality throughout the brain and a significant decrease in eigen vector centrality in the midbrain. Sucralose and allulose had no effect on BOLD signal or network connectivity but sucralose did lead to a significant increase in eigen vector centrality values in the cingulate cortex, central gyri and temporal lobe.

Discussion: Taken together our findings show that even in a shake containing fat and protein, the type of sweetener can affect brain responses and might thus affect reward and satiety responses and feeding behavior. The sweet taste without the corresponding energy content of the non-nutritive sweeteners appeared to have only small effects on the brain. Indicating that the while ingestion of nutritive sugars could have a strong effect on feeding behavior, both in a satiety aspect as well as rewarding aspects, non-nutritive sweeteners appear to not have these effects.

Trial registration: This study is registered at under number NCT02745730.

Keywords: MRI; artificial sweeteners; brain activity; eigen vector centrality; energy ingestion; functional network connectivity; non-nutritive sweeteners; nutritive sweeteners.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Brain / drug effects*
  • Brain / physiology*
  • Brain Mapping
  • Dietary Sugars / administration & dosage*
  • Double-Blind Method
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Sweetening Agents / administration & dosage*
  • Young Adult


  • Dietary Sugars
  • Sweetening Agents

Associated data