The study confirms the findings from studies in the general population that the use of NNS is high in overweight and obese adults [18,19,20,21]. Half of the subjects used more than 3.3 units of NNS per day, which corresponds to 330 ml beverages with NNS. An intake of 2 – 4 l was not uncommon.
The main finding was the associations between NNS and an unhealthy lifestyle. In literature, less is known about these clinically relevant outcomes than about the weight. In this study, NNS was associated with a less healthy diet, reduced physical activity, low well-being and fatigue, which indicate an unhealthy lifestyle. The results indicate that the intake of NNS-containing beverages was approximately 100 ml higher in subjects with diabetes than in those without, and the same difference was seen between those with strong physical activity less than 1 hour/week compared to those with more than 2 h, and in subjects with low mood. The clinical significance of these effects are uncertain, but is indicative of an unhealthy lifestyle associated with the use of NNS.
A high intake of NNS was associated with increased intake of fat, proteins, carbohydrates including sugar, and salt; and reduced intake of some vitamins. The high intake of energy is harmful to obese subjects. The association with the intake of sugar could support the hypothesis that NNS encourage sugar craving and dependence by an altered metabolism and processing of sweet taste in the brain [22, 23]. Most of the unfavorable associations were related to the use of NNS in carbonated beverages, probably because the highest intake of NNS was from carbonated beverages. The stongest correlations were between intake of NNS containing beverages and salt. It is likely that these users combine the beverages with intake of salted food and snacks, which has also been shown by others [18]. Most of the associations between intake of NNS and energy and nutrients were weak (rho <0.2) and NNS explain only a minor part of the variation. The negative associations between intake of NNS and c-peptid, HbA1c and perhaps also Hb might have been confounded by diabetes. To adjust the analyses for all comorbidity including diabetes, in addition to age, gender and BMI was judged as inappropriate. The users of NNS in non-carbonated beverages, tea, and coffee seem to have a more conscious and correct use of NNS with a slightly reduced intake of total energy, carbohydrates, and sugar. They also reduced the intake of β-Carotene and vitamin C, indicating that they reduced all kinds of food including the healthy fruits and vegetables. Opposed to the findings in this study, population-based studies in the UK, US and Canada suggest a higher dietary quality in NNS consumers than in nonconsumers [19, 20]. The way NNS are used and the physiological and psychological effect of NNS might differ between subjects randomly selected from the population and subjects referred for treatment of morbid obesity at a spesialised hospital unit. Although NNS have been accused of a diabetogenic effect, the associations between NNS and diabetes and c-peptide in this study are probably explained by the higher use of NNS by subjects with diabetes [24, 25].
Reduced physical and mental health was also associated with NNS. The users of NNS had a feeling of poor well-being and more fatigue, and were less physically active. These aspects have not been focused on in literature as far as we know. Caffeine- and NNS-containing beverages might have been used to counteract fatigue and as an excuse for less physical activity. Diarrhea associated with NNS for use in coffee and tea might have been an adverse event related to some of the NNS.
The association between the use of NNS and BMI is not clear [8, 26]. The lack of associations between the use of NNS and BMI in this study was likely because all subjects were morbidly obese, but could indicate a lack of weight-reducing effect of NNS. In population-based observational studies, the use of NNS is higher in overweight and obese subjects than in healthy-weight subjects [18,19,20]. The findings could indicate that NNS induce weight gain, but it more likely reflects the use of NNS for weight reduction by overweight and obese subjects.
Numerous studies from agriculture, in the laboratory and in humans indicate a counterintuitive effect of NNS with increased food intake and body weight, accumulation of fat, weaker caloric compensation, metabolic syndrome and cardiovascular diseases [27,28,29]. Animal studies have shown weight gain and metabolic dysregulation after intake of NNS [29, 30]. NNS are not inert substances, and physiological effects on metabolism and energy balance have been proposed to explain an unexpected weight-inducing effect in long-term follow-up studies in children and adults [7, 31,32,33]. NNS affect the glucose metabolism and have been associated with type 2 diabetes [24, 34,35,36]. Concerns have also been raised about effects on appetite, eating behaviour, satiation, satiety, craving, reward, addiction, cognitive functions, neurophysiology, and brain function [22, 23, 37,38,39,40].
More recently, the effect of NNS on the gut microbiome has achieved considerable attention. The disturbed gut-brain interaction caused by the NNS-induced dysbiosis might in part explain the effects associated with obesity such as weight gain, metabolic changes including glucose intolerance, neurophysiological and psychological changes [41,42,43].
Except for a slightly favourable effect in the subgroup of subjects using NNS-containing non-carbonated beverages, the overall findings were discouraging. It was anticipated that subjects who were referred for obesity and therefore motivated for weight-reducing interventions, had a conscious relation to the use of NNS as a way to reduce energy intake. Most of them had bariatric surgery later on.
Despite numerous concerns and an extensive literature, the correct use of NNS is unknown [25]. The actual knowledge has been summarized by the U.S. Department of Health and Human Services and U.S. Department of Agriculture in “Dietary Guidelines for Americans 2015-2020”: “…. replacing added sugar with high-intensity sweeteners may reduce calorie intake in the short-term, yet questions remain about their effectiveness as a long-term weight management strategy”, and “Based on available scientific evidence, these high-intensity sweeteners have been determined to be safe for the general population” [44]. Shankar et al. gave an intelligent advice “…for optimal health it is recommended that only minimal amounts of both sugar and NNS be consumed” [45].
Strengths and limitations
The focus on an unselected group of consecutive subjects with morbid obesity from a general hospital and their health and lifestyle, and not on overweight and obesity in general and body weight only, was a strength. This study from a general hospital is likely to be representative of unselected consecutive subjects referred to a specialized unit for morbid obesity. The validity of the results for all subjects with overweight and obesity is unknown. The lack of information about the use of NNS in other products than beverages and the different types of NNS was a limitation. The FFQ only asked for the use of NNS-containing carbonated beverages, non-carbonated beverages and units of NNS in tea and coffee and not the specific products. Information about NNS in packets added to other beverages or food was not asked for. The limited sample size reduces the ability to control for confounders. No correction was performed for the numerous correlations, which increased the risk of type I errors.