Neurocognitive, behavioural and physiological effects of non-nutritive sweeteners in humans

Abstract

Non-nutritive sweeteners (NNS) constitute a promising tool toward sugar and energy intake reduction. However, NNS effects on appetite and eating behaviour in humans is not yet fully understood. Control of food intake is the result of a complex interaction between homeostatic and hedonic signals, that collectively act to govern eating behaviour. Since oral sweet taste sequentially precedes gastrointestinal chemosensation, it is possible that neurocognitive and reward-related mechanisms contribute to the control of food intake, beyond any physiological and/or post-absorptive signals. The work presented in this thesis takes a multidisciplinary approach using a combination of methodologies to examine the effects of NNS, and in particular stevia, on neurocognitive, behavioural and physiological responses in humans. Initially, I developed a battery of previously described neurocognitive tasks and tested its efficacy to detect differences in food-cue responses in healthy individuals when homeostatic signals are controlled (fasted vs fed state). A visual probe task (VPT) was shown to be sensitive to metabolic state changes and was selected for use in subsequent studies to dissect the effects of sweet taste and calories on food attentional bias (AB). In a next crossover double-blind randomised controlled trial (RCT), I examined the effects of a single exposure to a stevia-sweetened beverage on appetite, food intake and AB to food cues relative to sweet caloric (glucose, sucrose), non-sweet caloric (maltodextrin) and non-sweet non-caloric (water) controls in healthy lean adults. Results showed a significant reduction in total energy intake (meal and beverage) in the stevia-sweetened beverage condition compared to water. Only caloric beverages increased blood glucose levels, stevia and caloric beverages both influenced appetite ratings, but AB to food cues did not differ across conditions. In a following open-label RCT, I examined the effects of daily stevia consumption for 12 weeks on glucose homeostasis, body weight and energy intake in healthy lean adults. My findings suggest that daily stevia consumption does not affect glucose homeostasis, but has a significant effect on energy intake; individuals in the stevia group demonstrated a significant spontaneous reduction in energy intake compared to the control group. In the last piece of work, a double-blind crossover RCT in healthy lean adults, I investigated the neural correlates of acute physiological signals and food-cue elicited responses related to consumption of stevia in comparison with appropriate controls for sweetness and calories (glucose, maltodextrin, water) using functional magnetic resonance imaging (fMRI). Stevia consumption demonstrated a longer-lasting and more robust blood oxygen dependent (BOLD) contrast decrease over time compared to other beverages in the brain. Consumption of stevia and caloric beverages elicited attenuated BOLD response in the visual cortex while performing a food VPT, compared to water. In conclusion, the research presented in this thesis provides considerable evidence that stevia consumption elicits benefits in appetite and food intake and induces a significant attenuation effect in the brain, without affecting physiological responses such as glucose homeostasis. The above findings could be indicative that stevia is beneficial for human consumption, and lays the foundations for this research moving into key clinical areas, such as obesity and type 2 diabetes mellitus.

Date of Award	1 Aug 2021
Original language	English
Awarding Institution	The University of Manchester
Supervisor	John Mclaughlin (Supervisor), Rebecca Elliott (Supervisor) & Shane Mckie (Supervisor)