The global rise in overweight and obesity is of major concern due to the associated risk of e.g. type 2 diabetes and cardiovascular diseases. To combat this, reducing the consumption of foods and drinks with added sugar is advocated for, as these products often have low nutri- tional value and mainly provide energy. This has led to an increased use of non- and low- caloric sweeteners (NCS/LCS), allowing a variety of products to maintain palatability without the associated energy and glycemic impact. However, the use of NCS and LCS as a means to prevent overweight and obesity is highly debated, as they have been proposed to potentially lead to weight gain by e.g. increasing appetite and inducing insulin resistance. As a group, NCS and LCS can be defined as sweeteners and sweetness enhancers (S&SEs).
Previous randomized controlled trials (RCTs) have explored the impact of NCS and/or LCS on e.g. appetite and glucose regulation in humans. Overall, no adverse effects of NCS and/or LCS have been observed. The impact of S&SEs on the other side of the energy balance equation, substrate oxidation and energy expenditure, has not been extensively investigated. Conse- quently, the objective of this PhD project was to assess the potential effects of S&SEs on sub- strate oxidation, energy expenditure and appetite – with fat oxidation being the primary out- come.
Paper I systematically reviewed the existing literature assessing the impact of NCS and LCS on substrate oxidation, energy expenditure, and catecholamines compared to caloric sweeten- ers, water, and various doses and types of NCS and LCS. The systematic review found that drinks and meals with NCS or LCS resulted in higher fat and lower carbohydrate oxidation compared to caloric sweeteners under non-isoenergetic conditions; a finding attributed to the extra carbohydrate load in the interventions with caloric sweeteners. The results for en- ergy expenditure were inconsistent. No other conclusions could be made due to insufficient and inconsistent data. The systematic review showed a need for further studies using isoen- ergetic comparators (e.g. water) and of longer duration.
Paper II presented the 1-year European multicenter RCT assessing prolonged effects of S&SEs on health, obesity, and safety: The SWEET WP3 study. The trial was conducted as a part of this PhD project.
Paper III and IV presented the design, conduction and results of an RCT sub-study including participants from SWEET WP3. The objective of the sub-study was to investigate the acute effects of a mixture of acesulfame potassium and cyclamate versus water on postprandial substrate oxidation and energy expenditure, glucose and insulin concentrations, and appetite at baseline, after a 2-month weight loss period, and after a 4–month weight loss maintenance period with either S&SEs or sugar in the diet. The results of the sub-study showed no differ- ences between the 2 groups in fasting or postprandial fat oxidation, carbohydrate oxidation, energy expenditure, glucose, or insulin on or across the 3 test days (p>0.05). However, the S&SEs group rated lower prospective consumption, and desire to eat something sweet across the 3 test days after the test drink with acesulfame potassium and cyclamate compared to the Sugar group consuming water (p<0.05).
Overall, data from the papers included in this thesis find evidence to suggest that NCS have similar effects as water on substrate oxidation and energy expenditure both acutely and in the longer-term. Regarding appetite, Paper IV suggests that acesulfame potassium and cycla- mate may induce sensory-specific satiety both acutely and after regular exposure to S&SEs. This could suggest that NCS may be beneficial in relation to certain aspects of appetite regu- lation. For LCS, less data are in general available, and thus the strength of evidence in this thesis lies with the NCS. However, based on the findings in Paper I, it can be concluded that LCS show higher fat and lower carbohydrate oxidation when compared to caloric sweeteners under non-isoenergetic conditions. Thus, compared to caloric sweeteners, LCS do not seem do exert any effect on substrate oxidation beyond what can be expected based on their en- ergy load and metabolism. However, more research is needed for both NCS and LCS across all outcomes. These studies should incorporate an isoenergetic comparator, a range of S&SEs, modes of administration, and should be conducted over a minimum of 1 year.