Low-calorie sweetener use and energy balance: Results from experimental studies in animals, and large-scale prospective studies in humans

Abstract

For more than a decade, pioneering animal studies conducted by investigators at Purdue University have provided evidence to support a central thesis: that the uncoupling of sweet taste and caloric intake by low-calorie sweeteners (LCS) can disrupt an animal's ability to predict the metabolic consequences of sweet taste, and thereby impair the animal's ability to respond appropriately to sweet-tasting foods. These investigators’ work has been replicated and extended internationally. There now exists a body of evidence, from a number of investigators, that animals chronically exposed to any of a range of LCSs – including saccharin, sucralose, acesulfame potassium, aspartame, or the combination of erythritol + aspartame – have exhibited one or more of the following conditions: increased food consumption, lower post-prandial thermogenesis, increased weight gain, greater percent body fat, decreased GLP-1 release during glucose tolerance testing, and significantly greater fasting glucose, glucose area under the curve during glucose tolerance testing, and hyperinsulinemia, compared with animals exposed to plain water or – in many cases – even to calorically-sweetened foods or liquids. Adverse impacts of LCS have appeared diminished in animals on dietary restriction, but were pronounced among males, animals genetically predisposed to obesity, and animals with diet-induced obesity. Impacts have been especially striking in animals on high-energy diets: diets high in fats and sugars, and diets which resemble a highly-processed ‘Western’ diet, including trans-fatty acids and monosodium glutamate. These studies have offered both support for, and biologically plausible mechanisms to explain, the results from a series of large-scale, long-term prospective observational studies conducted in humans, in which longitudinal increases in weight, abdominal adiposity, and incidence of overweight and obesity have been observed among study participants who reported using diet sodas and other LCS-sweetened beverages daily or more often at baseline. Furthermore, frequent use of diet beverages has been associated prospectively with increased long-term risk and/or hazard of a number of cardiometabolic conditions usually considered to be among the sequelae of obesity: hypertension, metabolic syndrome, diabetes, depression, kidney dysfunction, heart attack, stroke, and even cardiovascular and total mortality. Reverse causality does not appear to explain fully the increased risk observed across all of these studies, the majority of which have included key potential confounders as covariates. These have included body mass index or waist circumference at baseline; total caloric intake and specific macronutrient intake; physical activity; smoking; demographic and other relevant risk factors; and/or family history of disease. Whether non-LCS ingredients in diet beverages might have independently increased the weight gain and/or cardiometabolic risk observed among frequent consumers of LCS-sweetened beverages deserves further exploration. In the me...

Is There an Optimal Diet for Weight Management and Metabolic Health?

“…However, their role in helping people to manage their weight effectively is controversial and has been widely debated. Indeed, there is evidence that artificially sweetened beverages (ASBs) are associated with weight gain in the same way as sugar (78).…”

Sugar and Type 2 diabetes

“…2014), artificially sweetened drinks are also associated with weight gain (Brown et al 2010). Only an association, but experimental animals only gain weight when both drinking water and foods are sweetened, either with sugar or artificial sweeteners (Fowler 2016). Human epidemiology can be explained by essentially the same story: both SSBs and artificially-sweetened 'diet' versions cause tolerance to unnatural sweetness which promotes weight gain, but mainly by promoting consumption of very sweet energy-dense foods, rather than from sugar in the drinks themselves (Lean & Te Morenga 2016;Faculty of Public Health 2013).…”

The effect of moderate consumption of non-nutritive sweeteners on glucose tolerance and body composition in rats

“…Although presumed to be metabolically inert, NNS consumption has been associated with weight gain and altered glucose tolerance in some human and animal studies (Fowler 2016), suggesting that NNS D r a f t may, in fact, have metabolic effects. Possible mechanisms for the metabolic activity of NNS include altered ability to compensate for calories expected by sweet taste (Swithers et al 2009;Davidson et al 2011), alterations in the gut microbiota processing of nutrients (Palmnas et al 2014;Abou-Donia et al 2008;Suez et al 2014) and/or inhibition of intestinal alkaline phosphatase (Gul et al 2017).…”

“…Although presumed to be metabolically inert, NNS consumption has been associated with weight gain and altered glucose tolerance in some human and animal studies (Fowler 2016), suggesting that NNS may, in fact, have metabolic effects, including an altered ability to compensate for calories expected by the sweet taste. Aspartame, a methyl ester of aspartic acid and phenylalanine, and sucralose, a chlorinated derivative of sucrose, are widely used sweeteners in beverages and foods; their use has been linked to obesity, metabolic syndrome, and diabetes (Fowler 2016). The purpose of this study was to examine the effects of low-dose aspartame or sucralose treatment on weight gain, body composition, and glucose tolerance in rats where NNS delivery method and diet are consistent.…”