International Journal of Obesity advance online publication 10 November 2015; doi: 10.1038/ijo.2015.177 
 
 P J Rogers1, P S Hogenkamp2, C de Graaf3, S Higgs4, A Lluch5, A R Ness6, C Penfold6, R Perry6, P Putz7, M R Yeomans8 and D J Mela9 
 
 By reducing energy density, low-energy sweeteners (LES) might be expected to reduce energy intake (EI) and body weight (BW). To assess the totality of the evidence testing the null hypothesis that LES exposure (versus sugars or unsweetened alternatives) has no effect on EI or BW, we conducted a systematic review of relevant studies in animals and humans consuming LES with ad libitum access to food energy. In 62 of 90 animal studies exposure to LES did not affect or decreased BW. Of 28 reporting increased BW, 19 compared LES with glucose exposure using a specific ‘learning’ paradigm. Twelve prospective cohort studies in humans reported inconsistent associations between LES use and body mass index (−0.002 kg m − 2 per year, 95% confidence interval (CI) −0.009 to 0.005). Meta-analysis of short-term randomized controlled trials (129 comparisons) showed reduced total EI for LES versus sugar-sweetened food or beverage consumption before an ad libitum meal (−94 kcal, 95% CI −122 to −66), with no difference versus water (−2 kcal, 95% CI −30 to 26). This was consistent with EI results from sustained intervention randomized controlled trials (10 comparisons). Meta-analysis of sustained intervention randomized controlled trials (4 weeks to 40 months) showed that consumption of LES versus sugar led to relatively reduced BW (nine comparisons; −1.35 kg, 95% CI –2.28 to −0.42), and a similar relative reduction in BW versus water (three comparisons; −1.24 kg, 95% CI –2.22 to −0.26). Most animal studies did not mimic LES consumption by humans, and reverse causation may influence the results of prospective cohort studies. The preponderance of evidence from all human randomized controlled trials indicates that LES do not increase EI or BW, whether compared with caloric or non-caloric (for example, water) control conditions. Overall, the balance of evidence indicates that use of LES in place of sugar, in children and adults, leads to reduced EI and BW, and possibly also when compared with water. 
 
 Top of page Introduction Low-energy sweeteners (LES), such as acesulfame-K, aspartame, saccharin, stevia and sucralose are consumed throughout the world.1 The history of their use has been accompanied by debate and disagreements, not least about their potential nutritional impact. The use of LES to replace or partially replace added sugar in foods and beverages might well be expected to reduce energy intake (EI),2, 3, 4 yet over recent years there has been widely reported speculation that consumption of LES might increase the risk of becoming overweight and obese.5, 6, 7 Studies covertly manipulating energy density show higher EI after consumption of a reduced-energy food or beverage, but that the degree of energy ‘compensation’ is variable.8 Crucially, energy compensation is usually lower than the difference in energy content of the comparison foods/beverages, seemingly being lowest of all for liquids.8 This suggests that consuming LES in place of sugar-sweetened products should reduce overall EI, and particularly so for consumption of beverages, the most popular vehicles for LES.1 The question also arises whether the presence of LES in beverages affects appetite and EI relative to plain water.1, 9 Although the imprecise control of short-term energy balance predicts that LES consumption should help reduce EI and therefore reduce risk of overweight and obesity,3, 10 it is possible that, as consumed in everyday life, other effects of LES balance or even outweigh the energy dilution effect. For example, a low calorie or ‘diet’ label may cause the consumer to eat a larger portion of the product or eat more of accompanying foods in the meal, or eat more later.11, 12, 13, 14 More simply, adding sweetness to a product may increase intake owing to increased palatability.15, 16 Or, by ‘uncoupling’ the relationship between sweetness and energy content, the consumption of LES may undermine the usefulness of sweetness as a cue in the control of energy balance.5, 17, 18, 19, 20 The effects of LES consumption on EI and body weight (BW) have been the subject of many studies over the past 30 years; nonetheless there is no clear consensus about this body of evidence. Taken together, a number of narrative reviews1, 2, 3, 4, 21, 22, 23, 24, 25 and systematic reviews of some types of studies26, 27, 28, 29, 30 lead to the consistent but guarded conclusion that substitution of LES for sugar, especially in beverages, can help reduce EI, but that fully convincing evidence for longer-term beneficial effects is lacking. Our principle aim was, therefore, to bring together the totality of evidence to test the primary (null) hypotheses that LES consumption per se or as a replacement for caloric sweeteners in foods or beverages has no effect on EI or BW outcomes in adults or children. We conducted systematic reviews of animal, human observational and human intervention studies providing information on LES consumption and EI and/or BW. We included animal studies particularly because findings from a subset of animal studies appear to suggest that consumption of LES might increase risk of BW gain.19 Within the human intervention studies we furthermore sought to test a secondary (null) hypothesis that the effects of consumption of LES beverages on EI and BW do not differ from the effects of consumption of water. 
 
 Top of page Materials and methods A systematic search of the literature was undertaken to identify studies in humans and animals that assessed the effects of consumption of LES on EI and/or BW and/or body mass index (BMI). LES were defined as ingredients contributing negligible energy to products to achieve a sweetness similar in comparison with caloric sweeteners. Thus LES include intense sweeteners and non-metabolized sugars but exclude most sugar alcohols (see Supplementary Information for full definition and examples). We use ‘sugars’ to refer to caloric sweeteners, usually sucrose. The databases of MEDLINE and EMBASE via OVID interface and Web of Science were searched from their inception to 01 February 2015, using a combination of MeSH terms and key word terms to identify research addressing the relevant combinations of exposures (sweetener types) and outcomes (describing food or EI, anthropometric measures or changes in these). No restrictions were applied regarding language or dates. This search generated 5506 articles, which were processed as summarised in Figure 1. Medline search terms and further details of our methods are provided in the Supplementary Information. Figure 1. Flow of information through the different phases of the systematic review. Full figure and legend (118 K ) 
 
 
 
 Top of page Discussion Table 2 summaries the results of this review. It shows that the weight of the evidence indicates decreased EI and BW with consumption of LES relative to sugar. Furthermore, LES do not appear to increase EI, and in human interventions studies tend to lead to a relatively decreased BW, even compared with consumption of water in the groups tested. These findings are consistently contrary to the concern that has been raised by some authors5, 6, 7 that consumption of LES may increase risk of becoming overweight and obese. The results in favour of a benefit of LES use in BW management come primarily from a substantial number of short-term and sustained intervention studies testing human participants, which can be reasonably said to rank above observational studies and animal studies as sources of evidence for informing health-care decisions, including dietary recommendations. In any case, close examination of the totality of the evidence including that from observational and animal studies does not contradict the conclusion that LES use is helpful, or at least neutral, with respect to BW control. Table 2 - Summary of the results of the review. Full table 
 
 A recent systematic review and meta-analysis of the evidence from prospective cohort and sustained intervention studies on LES and BW and composition193 differs from ours in the studies included and excluded for both sources of evidence (see Supplementary Tables S19 and S20 for further details), and in not considering the evidence from short-term intervention studies and animal studies, or the specific comparison with water. The authors, nevertheless, reach similar conclusions to us. They state that ‘substituting LCS (low-calorie sweeteners) options for their regular-calorie versions results in modest BW loss, and may be a useful dietary tool to improve compliance with BW loss or BW maintenance plans’.193 We found that prospective associations between LES consumption and BW change were not consistent across the literature, with beneficial and adverse associations of LES use with BW reported by similar numbers of studies. This could be due to differences in the populations studied and/or the extent to which specific confounding factors were accounted for, chance findings in small studies and publication bias. A major confounder may be the BW control history and strategies used in the different populations. Thus, reverse causation cannot be ruled out. Notably, though, pooled analysis of the three largest studies showed a relative BW reduction for those consuming LES.100 Evidence from a large majority of animal studies favours reduced EI and BW gain or no effect of LES, although increases have been observed as well. A particular series of studies from one research group employing a specific procedure in rats has been widely cited in support of the suggestion that consumption of LES could lead to BW gain.194 The mechanism proposed for this is that LES consumption disrupts learning about the association between sweet taste and energy content. Arguably, however, the complexity of modern human diets is such that sweetness, with or without the inclusion of LES, does not reliably predict energy content foods.195 More likely, what is learned, if anything, is energy content (and its satiating effect) signalled by a configuration of taste, flavour, texture and other cues specific to individual foods. Therefore, whether or not LES are consumed will likely make little difference to the learned control of EI. In any case, without information from further control groups the interpretation of the results of these studies is ambiguous. Their relevance to human consumption of LES therefore remains to be demonstrated, especially in the light of the evidence from sustained human intervention studies of reduced BW with consumption of LES versus sugar, and LES versus water. In general, the animal studies did not mimic the use of LES by humans, either in amounts consumed or pattern of consumption. A variety of human and animal intervention studies provided data on the effects of consumption of LES-sweetened liquids versus water. The results indicate that the exposure to sweetness itself (without energy) is at least neutral in terms of impact on EI and energy balance, and possibly even helpful. This challenges the suggestion that exposure to sweetness itself is detrimental,6, 196, 197 perhaps because exposure to sweetness could help ‘establish and maintain’ a more generalised preference for sweet items.1 Acquired preferences for sweetness levels are relatively food-specific, although this is expressed against the background of a general innate liking for sweetness.198 On the other hand, evidence from studies of ‘sensory-specific satiety’ show that acute exposure to sweetness decreases subsequent desire for the same or other sweet (relative to non-sweet) items.199, 200, 201 Consistent with this, participants in the CHOICE trial receiving LES beverages specifically reduced consumption of dessert items relative to those receiving water.202 One possible interpretation is that access to LES satisfies a pre-existing desire for sweetness, rather than promoting it. A further result is that LES consumed in capsules either had no effect or reduced EI in short-term intervention studies (Figure 3), which argues against stimulation of gut receptors as a route by which LES might contribute toward increased EI and BW. The short-term intervention studies in humans measured the effects of consuming a fixed portion of a LES-sweetened beverage or food on free (ad libitum) consumption of other items presented in the test. In many of the animal studies the manipulated food was also the food that was consumed freely. For the most part the results of these two types of study lead to the equivalent conclusion, namely that there was little effect of the LES versus the equi-caloric control (usually water in the human studies, and unsweetened food in the animal studies) on EI or BW. An exception is increased EI and BW gain in a small number of studies in which saccharin was added to moistened or fat-enriched diets, perhaps owing to saccharin increasing the palatability of these diets. This context differs from the consumption of LES in the human diet, where LES usually replace sugars in foods and beverages.1 Furthermore, as discussed above, there is no substantive evidence that consuming LES-sweetened products increases EI or BW in humans. Our analysis of short-term intervention studies comparing LES with water supports Daniels and Popkin’s27 conclusion that these studies are ‘relatively consistent and found no impact on EI among adults’ (p 505). Their review of a subset of the studies we included found that consumption of water versus LES-sweetened beverages led to essentially no change (1.3% reduction) in EI in adults and a 6.7% reduction in children. Nevertheless, our meta-analysis of three sustained intervention studies with a water comparison finds that LES consumption leads to somewhat reduced BW relative to consumption of water.179, 184, 185 As well as an effect via ‘sensory-specific satiety’ (above), this perhaps suggests an advantage for LES in respect of dietary compliance, in that LES beverages may be preferred to water.179 It would seem appropriate therefore to consider, particularly for consumers already accustomed to sweetened beverages, whether promotion of LES or water as an alternative holds greatest public health effectiveness.203 The answer should come from further appropriately designed intervention studies and perhaps further analyses of already completed trials where participants had free choice of water versus LES beverages.187 Both short-term and sustained intervention studies in humans show LES consumption reduces ad libitum EI. However, possibly for several reasons, short-term studies may underestimate the degree of energy compensation that occurs in response to energy dilution. This is consistent with the finding that BW differences observed in sustained intervention studies are often much smaller that would be the case if no compensation had occurred.182 Nonetheless, sustained studies repeatedly find effects in favour of LES consumption reducing BW relative to sugar consumption, showing that compensation is incomplete. Of course, the same argument and many of the same data are used in making the case that consumption of sugar-sweetened products, and particularly sugar-sweetened-beverages, increase risk of overweight and obesity.182, 204, 205 
 
 Top of page Conclusions We found a considerable weight of evidence in favour of consumption of LES in place of sugar as helpful in reducing relative EI and BW, with no evidence from the many acute and sustained intervention studies in humans that LES increase EI. Importantly, the effects of LES-sweetened beverages on BW also appear neutral relative to water, or even beneficial in some contexts. A selection of animal and observational studies is often cited as the primary basis for strong assertions that LES are a contributing factor toward risk of overeating and obesity.5 In contrast, the present review of a large and systematically identified body of evidence from human intervention studies, with varying designs, settings and populations (including children and adults, males and females, and lean, overweight and obese groups), provide no support for that view. The question then is whether those hypotheses should be rejected or whether, as seems unlikely, the relevant human intervention studies are consistently flawed in a way that leads, in most cases, to exactly the opposite outcome. Commentaries on LES and energy balance frequently suggest that further research is needed, but stop short of proposing any specific new hypothesis to test or new study designs. Although no single study by itself is conclusive, the correspondence of results from the studies reviewed here gives no reason to expect another similar study would yield remarkably different results. Continued selective citation and extrapolation from observational and animal studies on this topic is also likely to be of limited value. Mattes & Popkin1 concluded that replacement of sugar by LES has ‘the potential to aid in BW management, but whether they will be used in this way is uncertain’ (p 10). This seems a reasonable conclusion from the literature, and shifts the issue from whether LES are ‘good’ or ‘bad,’ and re-focuses it on the question of how they are best used in practice to help in the achievement of specific public health goals, such as the reduction of intakes of free sugars and energy. 
 
 Top of page Conflict of interest Peter J Rogers has received grants from Sugar Nutrition, UK in support of research on the effects of sugar on human appetite. Cees de Graaf has received grants from the Dutch Sugar Bureau in support of a study on brain responses to sugars and low energy sweeteners. Suzanne Higgs has received a grant from Canderel in support of research on the effects of low-energy sweeteners on human appetite. Anne Lluch and David J Mela are employees and shareholders of companies that manufacture products containing sugars and low-energy sweeteners. Peter Putz is an employee of ILSI Europe. The remaining authors declare no conflict of interest. 
 
 Top of page References Mattes RD, Popkin BM. Nonnutritive sweetener consumption in humans: effects on appetite and food intake and their putative mechanisms. Am J Clin Nutr 2009; 89 : 1–14. | Article | PubMed | ISI | Drewnowski A. Intense sweeteners and energy density of foods: implications for weight control. Eur J Clin Nutr 1999; 53 : 757–763. | Article | PubMed | CAS | Bellisle F, Drewnowski A. Intense sweeteners, energy intake and the control of body weight. Eur J Clin Nutr 2007; 61 : 691–700. | Article | PubMed | ISI | CAS | Anderson GH, Foreyt J, Sigman-Grant M, Allison D. The use of low-calorie sweeteners by adults: impact on weight management. J Nutr 2012; 142 : 1163S–1169S. | Article | PubMed | Swithers SE. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends Endocrinol Metabol 2013; 24 : 431–441. | Article | Ludwig DS. Artificially sweetened beverages: cause for concern. JAMA 2009; 302 : 2477–2478. | Article | PubMed | Fowler SP, Williams K, Resendez RG, Hunt KJ, Hazuda HP, Stern MP. Fueling the obesity epidemic? Artificially sweetened beverage use and long-term weight gain. Obesity 2008; 16 : 1894–1900. | Article | PubMed | ISI | Almiron-Roig E, Palla L, Guest K, Ricchiuti C, Vint N, Jebb SA et al. Factors that determine energy compensation: a systematic review of preload studies. Nutr Rev 2013; 71 : 458–473. | Article | PubMed | Popkin BM, Armstrong LE, Bray GM, Caballero B, Frei B, Willett WC. A new proposed guidance system for beverage consumption in the United States. Am J Clin Nutr 2006; 83 : 529–542. | PubMed | ISI | CAS | Levitsky DA, Obarzanek E, Mrdjenovic G, Strupp BJ. Imprecise control of energy intake: absence of a reduction in food intake following overfeeding in young adults. Physiol Behav 2005; 84 : 669–675. | Article | PubMed | CAS | Shide DJ, Rolls BJ. Information about the fat content of preloads influences energy intake in healthy women. J Am Diet Assoc 1995; 95 : 993–998. | Article | PubMed | CAS | Miller DL, Castellanos VH, Shide DJ, Peters JC, Rolls BJ. Effect of fat-free potato chips with and without nutrition labels on fat and energy intakes. Am J Clin Nutr 1998; 68 : 282–290. | PubMed | Faulkner GP, Pourshahidi LK, Wallace JMW, Kerr MA, McCaffrey TA, Livingstone MBE. Perceived 'healthiness' of foods can influence consumers' estimations of energy density and appropriate portion size. Int J Obes 2014; 38 : 106–112. | Article | Caputo FA, Mattes RD. Human dietary responses to perceived manipulation of fat content in a midday meal. Int J Obes Relat Metab Disord 1993; 17 : 237–240. | PubMed | CAS | De Graaf C, De Jong LS, Lambers AC. Palatability affects satiation but not satiety. Physiol Behav 1999; 66 : 681–688. | Article | PubMed | ISI | CAS | Yeomans MR. Palatability and the microstructure of feeding in humans: the appetizer effect. Appetite 1996; 27 : 119–133. | Article | PubMed | ISI | CAS | Blundell JE, Hill AJ. Paradoxical effects of an intense sweetener (aspartame) on appetite. Lancet 1986; 327 : 1092–1093. | Article | Blundell JE, Rogers PJ, Hill AJ. Uncoupling sweetness and calories: methodological aspects of laboratory studies on appetite control. Appetite 1988; 11 : 54–61. | Article | PubMed | Swithers SE, Martin AA, Clark KM, Laboy AF, Davidson TL. Body weight gain in rats consuming sweetened liquids. Effects of caffeine and diet composition. Appetite 2010; 55 : 528–533. | Article | PubMed | Tordoff MG. How do non-nutritive sweeteners increase food intake? Appetite 1988; 11 : 5–11. | Article | PubMed | Benton D. Can artificial sweeteners help control body weight and prevent obesity? Nutr Res Rev 2005; 18 : 63–76. | Article | PubMed | Duffy VB, Anderson GH. Position of the American Dietetic Association: use of nutritive and nonnutritive sweeteners. J Am Diet Assoc 1998; 98 : 580–587. | Article | PubMed | ISI | CAS | Foreyt J, Kleinman R, Brown RJ, Lindstrom R. The use of low-calorie sweeteners by children: implications for weight management. J Nutr 2012; 142 : 1155S–1162S. | Article | PubMed | Gardner C. Non-nutritive sweeteners: evidence for benefit vs. risk. Curr Opin Lipidol 2014; 25 : 80–84. | Article | PubMed | Raben A, Richelsen B. Artificial sweeteners: a place in the field of functional foods? Focus on obesity and related metabolic disorders. Curr Opin Clin Nutr Metab Care 2012; 15 : 597–604. | Article | PubMed | Brown RJ, Banate M, Rother KI. Artificial sweeteners: a systematic review of metabolic effects in youth. Int J Pediatr Obes 2010; 5 : 305–312. | Article | PubMed | ISI | Daniels MC, Popkin BM. Impact of water intake on energy intake and weight status: a systematic review. Nutr Rev 2010; 68 : 505–521. | Article | PubMed | de la Hunty A, Gibson S, Ashwell M. A review of the effectiveness of aspartame in helping with weight control. Nutr Bull 2006; 31 : 115–128. | Article | Dennis EA, Flack KD, Davy BM. Beverage consumption and adult weight management: a review. Eating Behav 2009; 10 : 237–246. | Article | ISI | Wiebe N, Padwal R, Field C, Marks S, Jacobs R, Tonelli M. A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes. BMC Med 2011; 9 : 123. | Article | PubMed | Abu-Taweel GM, Zyadah MA, Ajarem JS, Ahmad M. Cognitive and biochemical effects of monosodium glutamate and aspartame, administered individually and in combination in male albino mice. Neurotoxicol Teratol 2014; 42 : 60–67. | Article | PubMed | Anderson RL. Response of male rats to sodium saccharin ingestion: urine composition and mineral balance. Food Cosmet Toxicol 1979; 17 : 195–200. | Article | PubMed | Andrejic B, Mijatovic V, Calasan J, Horvat O, Samojlik I. Influence of saccharin on changes in rat pancreas and liver histol, glycaemia, food intake and weight. J Comp Pathol 2010; 143 : 344. | Article | Bailey CJ, Day C, Knapper JM, Turner SL, Flatt PR. Antihyperglycaemic effect of saccharin in diabetic ob / ob mice. Br J Pharmacol 1997; 120 : 74–78. | Article | PubMed | Beck B, Burlet A, Max JP, Stricker-Krongrad A. Effects of long-term ingestion of aspartame on hypothalamic neuropeptide Y, plasma leptin and body weight gain and composition. Physiol Behav 2002; 75 : 41–47. | Article | PubMed | Bergheim I, Weber S, Vos M, Krämer S, Volynets V, Kaserouni S et al. Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin. J Hepatol 2008; 48 : 983–992. | Article | PubMed | ISI | CAS | Brantom PG, Gaunt IF, Grasso P. Long-term toxicity of sodium cyclamate in mice. Food Cosmet Toxicol 1973; 11 : 735–746. | Article | PubMed | Brathwaite WA, Casterton PL, Nikiforov AI, Rihner MO, Sloter ED, Hlywka JJ. A dietary embryo / fetal developmental toxicity study of arruva, an R,R-monatin salt isomer, in Crl: CD (SD) rats. Food Chem Toxicol 2013; 62 : 68–75. | Article | PubMed | Curry LL, Roberts A. Subchronic toxicity of rebaudioside A. Food Chem Toxicol 2008; 46 : S11–S20. | Article | PubMed | Dalderup LM, Visser W. Effects of sodium cyclamate on the growth of rats compared with other variations in the diet. Nature 1969; 221 : 91–92. | Article | PubMed | ISI | CAS | Dalderup LM, Visser W. Influence of extra sucrose, fats, protein and of cyclamate in the daily food on the life-span of rats. Experientia 1971; 27 : 519–521. | Article | PubMed | Dyrskog SEU, Jeppesen PB, Colombo M, Abudula R, Hermansen K. Preventive effects of a soy-based diet supplemented with stevioside on the development of the metabolic syndrome and type 2 diabetes in Zucker diabetic fatty rats. Metabolism 2005; 54 : 1181–1188. | Article | PubMed | Figlewicz DP, Ioannou G, Bennett Jay J, Kittleson S, Savard C, Roth CL. Effect of moderate intake of sweeteners on metabolic health in the rat. Physiol Behav 2009; 98 : 618–624. | Article | PubMed | Fisher MJ, Sakata T, Tibbels TS, Smith RA, Patil K, Khachab M et al. Effect of sodium saccharin and calcium saccharin on urinary parameters in rats fed Prolab 3200 or AIN-76 diet. Food Chem Toxicol 1989; 27 : 1–9. | Article | PubMed | Friedhoff R, Simon JA, Friedhoff AJ. Sucrose solution vs. no-calorie sweetener vs. water in weight gain. J Am Diet Assoc 1971; 59 : 485–486. | PubMed | Fulop I, Bobes D, Croitoru D, Barbu C. influence of sugars and sweeteners on mouse body weight, stress-induced body weight changes and life expectancy. Farmacia 2014; 62 : 376–389. Geeraert B, Crombe F, Hulsmans M, Benhabiles N, Geuns JM, Holvoet P. Stevioside inhibits atherosclerosis by improving insulin signaling and antioxidant defense in obese insulin-resistant mice. Int J Obes 2009; 34 : 569–577. | Article | Goldsmith LA. Acute and subchronic toxicity of sucralose. Food Chem Toxicol 2000; 38 : 53–69. | Article | Higginbotham JD, Snodin DJ, Eaton KK, Daniel JW. Safety evaluation of thaumatin (talin protein). Food Chem Toxicol 1983; 21 : 815–823. | Article | PubMed | Hlywka J, Brathwaite WA, Rihner MO, Nikiforov AI, Eapen AK. A 90-day oral (dietary) toxicity study of the 2R,4R-isomer of monatin salt in Sprague–Dawley rats. Food Chem Toxicol 2011; 49 : 3249–3257. | Article | PubMed | Ishii H, Koshimizu T, Usami S, Fujimoto T. Toxicity of aspartame and its diketopiperazine for Wistar rats by dietary administration for 104 weeks. Toxicol 1981; 21 : 91–94. | Article | Jeppesen PB, Gregersen S, Rolfsen SED, Jepsen M, Colombo M, Agger A et al. Antihyperglycemic and blood pressure-reducing effects of stevioside in the diabetic Goto-Kakizaki rat. Metabolism 2003; 52 : 372–378. | Article | PubMed | Jürgens H, Haass W, Castaneda TR, Schürmann A, Koebnick C, Dombrowski F et al. Consuming fructose-sweetened beverages increases body adiposity in mice. Obesity Res 2005; 13 : 1146–1156. | Article | Lina BAR, Bos-Kuijpers MHM, Til HP, Bär A. Chronic toxicity and carcinogenicity study of erythritol in rats. Regul Toxicol Pharmacol 1996; 24 : S264–S279. | Article | PubMed | Mitsutomi K, Masaki T, Shimasaki T, Gotoh K, Chiba S, Kakuma T et al. Effects of a nonnutritive sweetener on body adiposity and energy metabolism in mice with diet-induced obesity. Metabolism 2014; 63 : 69–78. | Article | PubMed | Munro IC, Moodie CA, Krewski D, Grice HC. A carcinogenicity study of commercial saccharin in the rat. Toxicol Appl Pharmacol 1975; 32 : 513–526. | Article | PubMed | Nikiforov AI, Eapen AK. A 90-day oral (dietary) toxicity study of rebaudioside A in Sprague-Dawley rats. Int J Toxicol 2008; 27 : 65–80. | Article | PubMed | Nikiforov AI, Rihner MO, Eapen AK, Thomas JA. Metabolism and Toxicity Studies Supporting the Safety of Rebaudioside D. Int J Toxicol 2013; 32 : 261–273. | Article | PubMed | Oser BL, Carson S, Cox GE, Vogin EE, Sternberg SS. Chronic toxicity study of cyclamate: saccharin (10: 1) in rats. Toxicol 1975; 4 : 385–386. | Article | Otabe A, Fujieda T, Masuyama T. Chronic toxicity and carcinogenicity of N-N- [ 3-(3-hydroxy-4-methoxyphenyl) propyl ] -alpha-aspartyl ] -l-phenylalanine 1-methyl ester, monohydrate (advantame) in the rat. Food Chem Toxicol 2011; 49 : S35–S48. | Article | PubMed | Otabe A, Fujieda T, Masuyama T. A two-generation reproductive toxicity study of the high-intensity sweetener advantame in CD rats. Food Chem Toxicol 2011; 49 : S70–S76. | Article | PubMed | Palmnas MS, Cowan TE, Bomhof MR, Su J, Reimer RA, Vogel HJ et al. Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat. PloS One 2014; 9 : e109841. | Article | PubMed | Park J, Cha Y-S. Stevia rebaudiana Bertoni extract supplementation improves lipid and carnitine profiles in C57BL / 6J mice fed a high-fat diet. J Sci Food Agric 2010; 90 : 1099–1105. | Article | PubMed | Polyák E, Gombos K, Hajnal B, Bonyár-Müller K, Szabó S, Gubicskó-Kisbenedek A et al. Effects of artificial sweeteners on body weight, food and drink intake. Acta Physiologica Hungarica 2010; 97 : 401–407. | Article | PubMed | Reis TA, Goulart P, de Oliveira RME, Oliveira Ld, de Abreu PS, Azevedo Ad. Metabolic parameters of wistar rats subjected to diet supplemented with stevia and sugar. Semina: Ciéncias Agrarias (Londrina) 2011; 32 : 1477–1488. Schoenig GP, Goldenthal EI, Geil RG, Frith CH, Richter WR, Carlborg FW. Evaluation of the dose response and in utero exposure to saccharin in the rat. Food Chem Toxicol 1985; 23 : 475–490. | Article | PubMed | Tago K, Naito Y, Nagata T, Morimura T, Furuya M, Seki T et al. A ninety-day feeding, subchronic toxicity study of oligo-N-acetylglucosamine in Fischer 344 rats. Food Chem Toxicol 2007; 45 : 1186–1193. | Article | PubMed | Til HP, Modderman J. Four-week oral toxicity study with erythritol in rats. Regul Toxicol Pharmacol 1996; 24 : S214–S220. | Article | PubMed | Til HP, Kuper CF, Falke HE, Bär A. Subchronic oral toxicity studies with erythritol in mice and rats. Regul Toxicol Pharmacol 1996; 24 : S221–S231. | Article | PubMed | Waalkens-Berendsen DH, Kuilman-Wahls MEM, Bär A. Embryotoxicity and teratogenicity study with neohesperidin dihydrochalcone in rats. Regul Toxicol Pharmacol 2004; 40 : 74–79. | Article | PubMed | Watkins AL, Williams L, Carroll C. Influence of saccharin on growth and tissue lipids in rats fed different fats and carbohydrates. Nutr Rep Int 1980; 21 : 329–339. Xili L, Chengjiany B, Eryi X, Reiming S, Yuengming W, Haodong S et al. Chronic oral toxicity and carcinogenicity study of stevioside in rats. Food Chem Toxicol 1992; 30 : 957–965. | Article | PubMed | Yagi K, Matsuo T. The study on long-term toxicity of D-psicose in rats. J Clin Biochem Nutr 2009; 45 : 271–277. | Article | PubMed | Lina BAR, Dreef-van der Meulen H, Leegwater DC. Subchronic (13-week) oral toxicity of neohesperidin dihydrochalcone in rats. Food Chem Toxicol 1990; 28 : 507–513. | Article | PubMed | Park JS, Yoo SB, Kim JY, Lee SJ, Oh SB, Kim JS et al. Effects of saccharin intake on hippocampal and cortical plasticity in juvenile and adolescent rats. Korean J Physiol Pharmacol 2010; 14 : 113–118. | Article | PubMed | Renwick AG. The intake of intense sweeteners - an update review. Food Addit Contam 2006; 23 : 327–338. | Article | PubMed | EFSA. EFSA Panel on Food Additives and Nutrient Sources added to food. Scientific opinion on the safety of steviol glycosides for the proposed uses as a food additive. EFSA J 2010; 8 : 1–84. D'Anci KE, Kanarek RB, Marks-Kaufman R. Beyond sweet taste: saccharin, sucrose, and polycose differ in their effects upon morphine-induced analgesia. Pharmacol Biochem Behav 1997; 56 : 341–345. | Article | PubMed | D'Anci KE. Tolerance to morphine-induced antinociception is decreased by chronic sucrose or polycose intake. Pharmacol Biochem Behav 1999; 63 : 1–11. | Article | PubMed | de Matos F, Ballard CR, Foletto KC, Batista BAM, Neves AM, Ribeiro MFM et al. Saccharin and aspartame, compared with sucrose, induce greater weight gain in adult Wistar rats, at similar total caloric intake levels. Appetite 2013; 60 : 203–207. | Article | PubMed | Kanarek RB, White ES, Biegen MT, Marks-Kaufman R. Dietary influences on morphine-induced analgesia in rats. Pharmacol Biochem Behav 1991; 38 : 681–684. | Article | PubMed | Kanarek RB, Przypek J, D'Anci KE, Marks-Kaufman R. Dietary modulation of mu and kappa opioid receptor-mediated analgesia. Pharmacol Biochem Behav 1997; 58 : 43–49. | Article | PubMed | Kanarek RB, Mathes WF, Heisler LK, Lima RP, Monfared LS. Prior exposure to palatable solutions enhances the effects of naltrexone on food intake in rats. Pharmacol Biochem Behav 1997; 57 : 377–381. | Article | PubMed | CAS | Kanarek RB, Homoleski B. Modulation of morphine-induced antinociception by palatable solutions in male and female rats. Pharmacol Biochem Behav 2000; 66 : 653–659. | Article | PubMed | Porikos KP, Koopmans HS. The effect of non-nutritive sweeteners on body weight in rats. Appetite 1988; 11 : 12–15. | Article | PubMed | Ramirez I. Stimulation of energy intake and growth by saccharin in rats. J Nutr 1990; 120 : 123–133. | PubMed | Yeomans MR, Clifton PG. Exposure to sweetened solutions enhances the anorectic effect of naloxone but not d-fenfluramine. Physiol Behav 1997; 62 : 255–262. | Article | PubMed | Davidson TL, Martin AA, Clark K, Swithers SE. Intake of high-intensity sweeteners alters the ability of sweet taste to signal caloric consequences: implications for the learned control of energy and body weight regulation. Q J Exp Psychol 2011; 64 : 1430–1441. | Article | Swithers SE, Davidson TL. A role for sweet taste: calorie predictive relations in energy regulation by rats. Behav Neurosci 2008; 122 : 161–173. | Article | PubMed | Swithers SE, Baker CR, Davidson TL. General and persistent effects of high-intensity sweeteners on body weight gain and caloric compensation in rats. Behav Neurosci 2009; 123 : 772–780. | Article | PubMed | Swithers SE, Laboy AF, Clark K, Cooper S, Davidson TL. Experience with the high-intensity sweetener saccharin impairs glucose homeostasis and GLP-1 release in rats. Behav Brain Res 2012; 233 : 1–14. | Article | PubMed | Swithers SE, Sample CH, Davidson TL. Adverse effects of high-intensity sweeteners on energy intake and weight control in male and obesity-prone female rats. Behav Neurosci 2013; 127 : 262–274. | Article | PubMed | Swithers SE, Sample CH, Katz DP. Influence of ovarian and non-ovarian estrogens on weight gain in response to disruption of sweet taste–calorie relations in female rats. Horm Behav 2013; 63 : 40–48. | Article | PubMed | Berkey CS, Rockett HR, Field AE, Gillman MW, Colditz GA. Sugar-added beverages and adolescent weight change. Obes Res 2004; 12 : 778–788. | Article | PubMed | ISI | Chen L, Appel LJ, Loria C, Lin PH, Champagne CM, Elmer PJ et al. Reduction in consumption of sugar-sweetened beverages is associated with weight loss: the PREMIER trial. Am J Clin Nutr 2009; 89 : 1299–1306. | Article | PubMed | ISI | CAS | Duffey KJ, Steffen LM, Van Horn L, Jacobs DR, Popkin BM. Dietary patterns matter: diet beverages and cardiometabolic risks in the longitudinal Coronary Artery Risk Development in Young Adults (CARDIA) Study. Am J Clin Nutr 2012; 95 : 909–915. | Article | PubMed | Laska MN, Murray DM, Lytle LA, Harnack LJ. Longitudinal associations between key dietary behaviors and weight gain over time: transitions through the adolescent years. Obesity 2012; 20 : 118–125. | Article | PubMed | Ludwig DS, Peterson KE, Gortmaker SL. Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis. Lancet 2001; 357 : 505–508. | Article | PubMed | ISI | CAS | Nettleton JA, Lutsey PL, Wang Y, Lima JA, Michos ED, Jacobs DR. Diet soda intake and risk of incident metabolic syndrome and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care 2009; 32 : 688–694. | Article | PubMed | ISI | CAS | Pan A, Malik VS, Hao T, Willett WC, Mozaffarian D, Hu FB. Changes in water and beverage intake and long-term weight changes: results from three prospective cohort studies. Int J Obes 2013; 37 : 1378–1385. | Article | Striegel-Moore RH, Thompson D, Affenito SG, Franko DL, Obarzanek E, Barton BA et al. Correlates of beverage intake in adolescent girls: the National Heart, Lung, and Blood Institute Growth and Health Study. J Pediatr 2006; 148 : 183–187. | Article | PubMed | ISI | Vanselow MS, Pereira MA, Neumark-Sztainer D, Raatz SK. Adolescent beverage habits and changes in weight over time: findings from Project EAT. Am J Clin Nutr 2009; 90 : 1489–1495. | Article | PubMed | ISI | Cecil JE, Palmer CN, Wrieden W, Murrie I, Bolton-Smith C, Watt P et al. Energy intakes of children after preloads: adjustment, not compensation. Am J Clin Nutr 2005; 82 : 302–308. | PubMed | ISI | CAS | Akhavan T, Luhovyy BL, Anderson GH. Effect of drinking compared with eating sugars or whey protein on short-term appetite and food intake. Inter J Obes 2010; 35 : 562–569. | Article | Akhavan T, Anderson GH. Effects of glucose-to-fructose ratios in solutions on subjective satiety, food intake, and satiety hormones in young men. Am J Clin Nutr 2007; 86 : 1354–1363. | PubMed | ISI | CAS | Anderson GH, Saravis S, Schacher R, Zlotkin S, Leiter LA. Aspartame: effect on lunch-time food intake, appetite and hedonic response in children. Appetite 1989; 13 : 93–103. | Article | PubMed | ISI | CAS | Anton SD, Martin CK, Han H, Coulon S, Cefalu WT, Geiselman P et al. Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite 2010; 55 : 37–43. | Article | PubMed | Appleton KM, Blundell JE. Habitual high and low consumers of artificially-sweetened beverages: effects of sweet taste and energy on short-term appetite. Physiol Behav 2007; 92 : 479–486. | Article | PubMed | Bellissimo N, Pencharz PB, Thomas SG, Anderson GH. Effect of television viewing at mealtime on food intake after a glucose preload in boys. Pediatr Res 2007; 61 : 745–749. | Article | PubMed | ISI | Bellissimo N, Thomas SG, Goode RC, Anderson GH. Effect of short-duration physical activity and ventilation threshold on subjective appetite and short-term energy intake in boys. Appetite 2007; 49 : 644–651. | Article | PubMed | Beridot-Therond ME, Arts I, Fantino M, de La Gueronniere V. Short-term effects of the flavour of drinks on ingestive behaviours in man. Appetite 1998; 31 : 67–81. | Article | PubMed | CAS | Birch LL, McPhee L, Sullivan S. Children's food intake following drinks sweetened with sucrose or aspartame: time course effects. Physiol Behav 1989; 45 : 387–395. | Article | PubMed | ISI | CAS | Black RM, Tanaka P, Leiter LA, Anderson GH. Soft drinks with aspartame: effect on subjective hunger, food selection, and food intake of young adult males. Physiol Behav 1991; 49 : 803–810. | Article | PubMed | CAS | Black RM, Leiter LA, Anderson GH. Consuming aspartame with and without taste: differential effects on appetite and food intake of young adult males. Physiol Behav 1993; 53 : 459–466. | Article | PubMed | CAS | Booth DCA, Chase AILE. Temporal bounds of post-ingestive glucose induced satiety in man. Nature 1970; 228 : 1104–1105. | Article | PubMed | CAS | Brala PM, Hagen RL. Effects of sweetness perception and caloric value of a preload on short term intake. Physiol Behav 1983; 30 : 1–9. | Article | PubMed | CAS | Branton A, Akhavan T, Gladanac B, Pollard D, Welch J, Rossiter M et al. Pre-meal video game playing and a glucose preload suppress food intake in normal weight boys. Appetite 2014; 83 : 256–262. | Article | PubMed | ISI | Canty DJ, Chan MM. Effects of consumption of caloric vs noncaloric sweet drinks on indices of hunger and food consumption in normal adults. Am J Clin Nutr 1991; 53 : 1159–1164. | PubMed | CAS | Carvalho P, Sousa M, Barros R, Padrao P, Moreira P, Teixeira V. Impact of morning ingestion of sugary and sweetened beverages on energy and fluid intake throughout day. Ann Nutr Metab 2013; 63 : 1448–1449. DellaValle DM, Roe LS, Rolls BJ. Does the consumption of caloric and non-caloric beverages with a meal affect energy intake? Appetite 2005; 44 : 187–193. | Article | PubMed | ISI | Drewnowski A, Massien C, Louis-Sylvestre J, Fricker J, Chapelot D, Apfelbaum M. The effects of aspartame versus sucrose on motivational ratings, taste preferences, and energy intakes in obese and lean women. Int J Obes Relat Metab Disord 1994; 18 : 570–578. | PubMed | CAS | Drewnowski A, Massien C, Louis-Sylvestre J, Fricker J, Chapelot D, Apfelbaum M. Comparing the effects of aspartame and sucrose on motivational ratings, taste preferences, and energy intakes in humans. Am J Clin Nutr 1994; 59 : 338–345. | PubMed | CAS | Ford HE, Peters V, Martin NM, Sleeth ML, Ghatei MA, Frost GS et al. Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects. Eur J Clin Nutr 2011; 65 : 508–513. | Article | PubMed | Gheller B, Akhavan T, Pollard D, Gladanac B, Constantino M, Luhovyy B et al. A pre-meal glucose drink, but not video game playing, suppresses food intake in overweight and obese boys (1040.8). FASEB J 2014; 28 : 1040–1048. Guss JL, Kissileff HR, Pi-Sunyer FX. Effects of glucose and fructose solutions on food intake and gastric emptying in nonobese women. Am J Physiol Regul Integr Comp Physiol 1994; 36 : R1537. Hetherington MM, Wood C, Lyburn SC. Response to energy dilution in the short term: evidence of nutritional wisdom in young children? Nutr Neurosci 2000; 3 : 321–329. Ho EE, Liszt AF, Pudel V. The effects of energy content and sweet taste on food consumption in restrained and non-restrained eaters. J Am Diet Assoc 1990; 90 : 1223–1228. | PubMed | Holt NS. The effects of sugar-free vs sugar-rich beverages on feelings of fullness and subsequent food intake. Int J Food Sci Nutr 2000; 51 : 59–71. | Article | PubMed | CAS | Kim JY, Kissileff HR. The effect of social setting on response to a preloading manipulation in non-obese women and men. Appetite 1996; 27 : 25–40. | Article | PubMed | King NA, Appleton K, Rogers PJ, Blundell JE. Effects of sweetness and energy in drinks on food intake following exercise. Physiol Behav 1999; 66 : 375–379. | Article | PubMed | CAS | Lavin JH, French SJ, Read NW. The effect of sucrose-and aspartame-sweetened drinks on energy intake, hunger and food choice of female, moderately restrained eaters. Int J Obes Relat Metab Disord 1997; 21 : 37–42. | Article | PubMed | CAS | Maersk M, Belza A, Holst JJ, Fenger-Grøn M, Pedersen SB, Astrup A et al. Satiety scores and satiety hormone response after sucrose-sweetened soft drink compared with isocaloric semi-skimmed milk and with non-caloric soft drink: a controlled trial. Eur J Clin Nutr 2012; 66 : 523–529. | Article | PubMed | ISI | Melanson KJ, Westerterp-Plantenga MS, Campfield AL, Saris WH. Blood glucose and meal patterns in time-blinded males, after aspartame, carbohydrate, and fat consumption, in relation to sweetness perception. Br J Nutr 1999; 82 : 437–446. | PubMed | ISI | CAS | Monsivais P, Perrigue MM, Drewnowski A. Sugars and satiety: does the type of sweetener make a difference? Am J Clin Nutr 2007; 86 : 116–123. | PubMed | CAS | Panahi S, El Khoury D, Luhovyy BL, Goff HD, Anderson GH. Caloric beverages consumed freely at meal-time add calories to an ad libitum meal. Appetite 2013; 65 : 75–82. | Article | PubMed | Patel BP, Bellissimo N, Thomas SG, Hamilton JK, Anderson GH. Television viewing at mealtime reduces caloric compensation in peripubertal, but not postpubertal, girls. Pediatr Res 2011; 70 : 513–517. | Article | PubMed | Ranawana DV, Henry CJK. Are caloric beverages compensated for in the short-term by young adults? An investigation with particular focus on gender differences. Appetite 2010; 55 : 137–146. | Article | PubMed | ISI | Reid M, Hammersley R. Effects of carbohydrate intake on subsequent food intake and mood state. Physiol Behav 1995; 58 : 421–427. | Article | PubMed | Reid M, Hammersley R. The effects of sucrose and maize oil on subsequent food intake and mood. Br J Nutr 1999; 82 : 447–455. | PubMed | CAS | Soenen S, Westerterp-Plantenga MS. No differences in satiety or energy intake after high-fructose corn syrup, sucrose, or milk preloads. Am J Clin Nutr 2007; 86 : 1586–1594. | PubMed | ISI | Tamam S, Bellissimo N, Patel BP, Thomas SG, Anderson GH. Overweight and obese boys reduce food intake in response to a glucose drink but fail to increase intake in response to exercise of short duration. Appl Physiol Nutr Metab 2012; 37 : 520–529. | Article | PubMed | Van Engelen M, Khodabandeh S, Akhavan T, Agarwal J, Gladanac B, Bellissimo N. Effect of sugars in solutions on subjective appetite and short-term food intake in 9-to 14-year-old normal weight boys. Eur J Clin Nutr 2014; 68 : 773–777. | Article | PubMed | Van Wymelbeke V, Beridot-Therond ME, de La Gueronniere V, Fantino M. Influence of repeated consumption of beverages containing sucrose or intense sweeteners on food intake. Eur J Clin Nutr 2004; 58 : 154–161. | Article | PubMed | ISI | CAS | Wilson JF. Lunch eating behavior of preschool children: effects of age, gender, and type of beverage served. Physiol Behav 2000; 70 : 27–33. | Article | PubMed | CAS | Woodend DM, Anderson GH. Effect of sucrose and safflower oil preloads on short term appetite and food intake of young men. Appetite 2001; 37 : 185–195. | Article | PubMed | ISI | CAS | Rodin J. Comparative effects of fructose, aspartame, glucose, and water preloads on calorie and macronutrient intake. Am J Clin Nutr 1990; 51 : 428–435. | PubMed | ISI | CAS | Rogers PJ, Lambert TC, Alikanizadeh LA, Blundell JE. Intense sweeteners and appetite: responses of informed and uninformed subjects consuming food sweetened with aspartame or sugar. Int J Obes 1990; 14 : 105. | PubMed | Rogers PJ, Gadah NS, Kyle LA, Brunstrom JM. Standard preload-test meal study designs may underestimate satiety effects: sugar containing drinks as an example. Proc Nutr Soc 2011; 70 : E401. | Article | Rogers PJ. What is the mechanism for the postingestive anorectic effect of aspartame? Appetite 2013; 71 : 485. | Article | Rogers PJ, Carlyle JA, Hill AJ, Blundell JE. Uncoupling sweet taste and calories: comparison of the effects of glucose and three intense sweeteners on hunger and food intake. Physiol Behav 1988; 43 : 547–552. | Article | PubMed | ISI | CAS | Rogers PJ, Blundell JE. Separating the actions of sweetness and calories: effects of saccharin and carbohydrates on hunger and food intake in human subjects. Physiol Behav 1989; 45 : 1093–1099. | Article | PubMed | CAS | Rogers PJ, Pleming HC, Blundell JE. Aspartame ingested without tasting inhibits hunger and food intake. Physiol Behav 1990; 47 : 1239–1243. | Article | PubMed | Rogers PJ. Why a palatability construct is needed. Appetite 1990; 14 : 167–170. | Article | PubMed | Rogers PJ, Keedwell P, Blundell JE. Further analysis of the short-term inhibition of food intake in humans by the dipeptide L-aspartyl-L-phenylalanine methyl ester (aspartame). Physiol Behav 1991; 49 : 739–743. | Article | PubMed | Rogers PJ, Blundell JE. Reanalysis of the effects of phenylalanine, alanine, and aspartame on food intake in human subjects. Physiol Behav 1994; 56 : 247–250. | Article | PubMed | Rogers PJ, Burley VJ, Alikhanizadeh LA, Blundell JE. Postingestive inhibition of food intake by aspartame: importance of interval between aspartame administration and subsequent eating. Physiol Behav 1995; 57 : 489–493. | Article | PubMed | Rolls BJ, Laster LJ, Summerfelt A. Hunger and food intake following consumption of low-calorie foods. Appetite 1989; 13 : 115–127. | Article | PubMed | CAS | Rolls BJ, Kim S, Fedoroff IC. Effects of drinks sweetened with sucrose or aspartame on hunger, thirst and food intake in men. Physiol Behav 1990; 48 : 19–26. | Article | PubMed | CAS | Blundell J, De Graaf C, Hulshof T, Jebb S, Livingstone B, Lluch A et al. Appetite control: methodological aspects of the evaluation of foods. Obesity Rev 2010; 11 : 251–270. | Article | Gibson EL, Carnell S, Wardle J. Learnt satiation in effects of disguised preloads on lunch intake and appetite in preschool children. Appetite 2006; 47 : 280. | Article | Brunstrom JM. Associative learning and the control of human dietary behavior. Appetite 2007; 49 : 268–271. | Article | PubMed | Hogenkamp PS, Stafleu A, Mars M, De Graaf C. Learning about the energy density of liquid and semi-solid foods. Int J Obes 2011; 36 : 1229–1235. | Article | Yeomans MR. Flavour-nutrient learning in humans: an elusive phenomenon? Physiol Behav 2012; 106 : 345–355. | Article | PubMed | Kral TVE, Roe LS, Rolls BJ. Does nutrition information about the energy density of meals affect food intake in normal-weight women? Appetite 2002; 39 : 137–145. | Article | PubMed | CAS | Sclafani A. Sweet taste signaling in the gut. Proc Natl Acad Sci USA 2007; 104 : 14887–14888. | Article | PubMed | Brown RJ, Rother KI. Non-nutritive sweeteners and their role in the gastrointestinal tract. J Clin Endocrinol Metab 2012; 97 : 2597–2605. | Article | PubMed | Renwick AG, Molinary SV. Sweet-taste receptors, low-energy sweeteners, glucose absorption and insulin release. Br J Nutr 2010; 104 : 1415–1420. | Article | PubMed | Sylvetsky A, Rother KI, Brown R. Artificial sweetener use among children: epidemiol, recommendations, metabolic outcomes, and future directions. Pediatr Clin North Am 2011; 58 : 1467–1480. | Article | PubMed | Anderson GH, Catherine NL, Woodend DM, Wolever TM. Inverse association between the effect of carbohydrates on blood glucose and subsequent short-term food intake in young men. Am J Clin Nutr 2002; 76 : 1023–1030. | PubMed | ISI | CAS | Steinert RE, Frey F, Tõpfer A, Drewe J, Beglinger C. Effects of carbohydrate sugars and artificial sweeteners on appetite and the secretion of gastrointestinal satiety peptides. Br J Nutr 2011; 105 : 1320–1328. | Article | PubMed | ISI | Stern SB, Bleicher SJ, Flores A, Gombos G, Recitas D, Shu J. Administration of aspartame in non-insulin-dependent diabetics. J Toxicol Environ Health A 1976; 2 : 429–439. | Article | Knopp RH, Brandt K, Arky RA. Effects of aspartame in young persons during weight reduction. J Toxicol Environ Health 1976; 2 : 417–428. | Article | PubMed | Blackburn GL, Kanders BS, Lavin PT, Keller SD, Whatley J. The effect of aspartame as part of a multidisciplinary weight-control program on short-and long-term control of body weight. Am J Clin Nutr 1997; 65 : 409–418. | PubMed | CAS | Naismith DJ, Rhodes C. Adjustment in energy intake following the covert removal of sugar from the diet. J Hum Nutr Diet 1995; 8 : 167–175. | Article | Njike VY, Faridi Z, Shuval K, Dutta S, Kay CD, West SG et al. Effects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults. Int J Cardiol 2011; 149 : 83–88. | Article | PubMed | Raben A, Vasilaras TH, Müller AC, Astrup A. Sucrose compared with artificial sweeteners: different effects on ad libitum food intake and body weight after 10 wk of supplementation in overweight subjects. Am J Clin Nutr 2002; 76 : 721–729. | PubMed | ISI | CAS | Reid M, Hammersley R, Hill AJ, Skidmore P. Long-term dietary compensation for added sugar: effects of supplementary sucrose drinks over a 4-week period. Br J Nutr 2007; 97 : 193–203. | Article | PubMed | ISI | Reid M, Hammersley R, Duffy M. Effects of sucrose drinks on macronutrient intake, body weight, and mood state in overweight women over 4 weeks. Appetite 2010; 55 : 130–136. | Article | PubMed | Tate DF, Turner-McGrievy G, Lyons E, Stevens J, Erickson K, Polzien K et al. Replacing caloric beverages with water or diet beverages for weight loss in adults: main results of the Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trial. Am J Clin Nutr 2012; 95 : 555–563. | Article | PubMed | CAS | Tordoff MG, Alleva AM. Effect of drinking soda sweetened with aspartame or high-fructose corn syrup on food intake and body weight. Am J Clin Nutr 1990; 51 : 963–969. | PubMed | ISI | CAS | Wolraich ML, Lindgren SD, Stumbo PJ, Stegink LD, Appelbaum MI, Kiritsy MC. Effects of diets high in sucrose or aspartame on the behavior and cognitive performance of children. N Engl J Med 1994; 330 : 301–307. | Article | PubMed | de Ruyter JC, Olthof MR, Seidell JC, Katan MB. A trial of sugar-free or sugar-sweetened beverages and body weight in children. N Engl J Med 2012; 367 : 1397–1406. | Article | PubMed | ISI | Kanders BS, Lavin PT, Kowalchuk MB, Greenberg I, Blackburn GL. An evaluation of the effect of aspartame on weight loss. Appetite 1988; 11 : 73–84. | Article | PubMed | Maersk M, Belza A, Stødkilde-Jørgensen H, Ringgaard S, Chabanova E, Thomsen H et al. Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. Am J Clin Nutr 2012; 95 : 283–289. | Article | PubMed | ISI | CAS | Peters JC, Wyatt HR, Foster GD, Pan Z, Wojtanowski AC, Vander Veur SS et al. The effects of water and non-nutritive sweetened beverages on weight loss during a 12-week weight loss treatment program. Obesity 2014; 22 : 1415–1421. | Article | PubMed | Ebbeling CB, Feldman HA, Osganian SK, Chomitz VR, Ellenbogen SJ, Ludwig DS. Effects of decreasing sugar-sweetened beverage consumption on body weight in adolescents: a randomized, controlled pilot study. Pediatrics 2006; 117 : 673–680. | Article | PubMed | ISI | Ebbeling CB, Feldman HA, Chomitz VR, Antonelli TA, Gortmaker SL, Osganian SK et al. A randomized trial of sugar-sweetened beverages and adolescent body weight. N Engl J Med 2012; 367 : 1407–1416. | Article | PubMed | ISI | CAS | Munsters MJ, Saris WH. The effect of sugar-sweetened beverage intake on energy intake in an ad libitum 6-month low-fat high-carbohydrate diet. Ann Nutr Metab 2010; 57 : 116–123. | Article | PubMed | Stookey JD, Constant F, Gardner CD, Popkin BM. Replacing sweetened caloric beverages with drinking water is associated with lower energy intake. Obesity 2007; 15 : 3013–3022. | Article | PubMed | Williams CL, Strobino BA, Brotanek J. Weight control among obese adolescents: a pilot study. Int J Food Sci Nutr 2007; 58 : 217–230. | Article | PubMed | Levitsky DA. The non-regulation of food intake in humans: hope for reversing the epidemic of obesity. Physiol Behav 2005; 86 : 623–632. | Article | PubMed | CAS | Mattes RD, Pierce CB, Friedman MI. Daily caloric intake of normal-weight adults: response to changes in dietary energy density of a luncheon meal. Am J Clin Nutr 1988; 48 : 214–219. | PubMed | ISI | CAS | Miller P, Perez V. Low-calorie sweeteners and body weight and composition: a meta-analysis of randomized controlled trials and prospective cohorts (391.1). FASEB J 2014; 28 : 391. Swithers SE, Martin AA, Davidson TL. High-intensity sweeteners and energy balance. Physiol Behav 2010; 100 : 55–62. | Article | PubMed | CAS | Viskaal-Van Dongen M, Van Den Berg M, Vink N, Kok FJ, De Graaf C. Taste-Nutrient relations in commonly consumed foods. Appetite 2011; 57 : 567. | Article | Bray GA, Nielsen SJ, Popkin BM. Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr 2004; 79 : 537–543. | PubMed | ISI | CAS | Willett WC, Ludwig DS. Science souring on sugar. BMJ 2013; 346 : e8077. | Article | PubMed | Ventura AK, Mennella JA. Innate and learned preferences for sweet taste during childhood. Curr Opin Clin Nutr Metab Care 2011; 14 : 379–384. | Article | PubMed | Weenen H, Stafleu A, De Graaf C. Dynamic aspects of liking: post-prandial persistence of sensory specific satiety. Food Qual Prefer 2005; 16 : 528–535. | Article | Snoek HM, Huntjens L, van Gemert LJ, De Graaf C, Weenen H. Sensory-specific satiety in obese and normal-weight women. Am J Clin Nutr 2004; 80 : 823–831. | PubMed | CAS | Griffioen-Roose S, Finlayson G, Mars M, Blundell JE, De Graaf C. Measuring food reward and the transfer effect of sensory specific satiety. Appetite 2010; 55 : 648–655. | Article | PubMed | Piernas C, Tate DF, Wang X, Popkin BM. Does diet-beverage intake affect dietary consumption patterns? Results from the Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trial. Am J Clin Nutr 2013; 97 : 604–611. | Article | PubMed | Glasgow RE, Lichtenstein E, Marcus AC. Why don't we see more translation of health promotion research to practice? Rethinking the efficacy-to-effectiveness transition. Am J Public Health 2003; 93 : 1261–1267. | Article | PubMed | ISI | Te Morenga L, Mallard S, Mann J. Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies. BMJ 2013; 346 : e7492. | Article | Malik VS, Schulze MB, Hu FB. Intake of sugar-sweetened beverages and weight gain: a systematic review. Am J Clin Nutr 2006; 84 : 274–288. | PubMed | ISI | CAS | 
 
 Top of page Acknowledgements This work was conducted by an expert group of the European branch of the International Life Science Institute (ILSI Europe). The expert group received funding from the ILSI Europe Eating Behaviour and Energy Balance Task Force. Industry members of this task force are listed on the ILSI Europe website at www.ilsi.eu. For further information about ILSI Europe, please e-mail: info@ilsieurope.be or call +32 2 771 00 14. The opinions expressed herein and the conclusions of this publication are those of the authors and do not necessarily represent the views of ILSI Europe, nor those of its member companies and the authors affiliations. Part of the research leading to this review received funding from the European Union Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 607310 (PJR). The contributions of Andy R Ness, Christopher Penfold and Rachel Perry were supported by the National Institute for Health Research Bristol Nutrition Biomedical Research Unit based at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The authors would like to thank Dr Sanne Griffioen-Roose (then at Wageningen University) for her contribution at an early stage of this review, and ILSI Europe staff for their invaluable support in keeping this project on track and in the preparation of the manuscript. 
 
 Supplementary Information accompanies this paper on International Journal of Obesity website 

 Coca-Cola, Pepsi Once Again Fund Study Claiming Diet Soda Is Better For You Than Water 
 
 Back in 2014, the soft drink industry funded a study that, coincidentally, concluded that diet soda is better for weight loss than water . These same companies are at it again, not only providing the backing for another study extolling the virtues of diet drinks, but also — according to new reports — directly paying money to the researchers involved. 
 
 The latest research to be criticized over this apparent conflict of interest comes from the International Journal of Obesity, which recently published a review [PDF] of existing scientific research on the link between “low-energy sweetener consumption” and “energy intake and body weight.” 
 
 The study does disclose that it was funded, in part, by the International Life Sciences Institute — Europe, a group whose board of directors features not just a bunch of heavily credentialed academics, but also executives from Coca-Cola, Nestlé, PepsiCo, Mars, and Unilever. In fact, while there are some 19 people on the ILSI Europe board, three out of five of its officers are representing the food industry. 
 
 Additionally, one of the researchers himself is an employee of ILSI Europe, while the study’s lead author previously received research funding from a group called “Sugar Nutrition, UK,” an industry lobbying group formerly known as the British Sugar Bureau. Others on the team have previously been paid for research by the Dutch Sugar Bureau, UK sweetener brand Canderel, or are — as disclosed at the end of the study — “employees and shareholders of companies that manufacture products containing sugars and low-energy sweeteners.” 
 
 According to the Times on Sunday [reg. required], the researchers didn’t just get their funding for this study from ILSI Europe, the group also directly paid some of the academics involved around $1,090 each. 
 
 Which may not be a concern if the review hadn’t come to such a pro-industry conclusion — that the effect of diet drinks on body weight “appear neutral relative to water, or even beneficial in some contexts.” 
 
 As The Independent notes, of the 5,500 studies included in this review, it appears as if the researchers are only using the results of three to reach that conclusion. And of those three, only one — the 2014 paper, funded by the American Beverage Association, mentioned at the start of this story — actually showed any weight loss benefit compared to water. 
 
 The University of Bristol, where the study’s lead author teaches, stands by the research, pointing out that it has been peer-reviewed, “which means the data and conclusions have been scrutinised by other scientists.” The school also contends that the study received additional funding from the National Health Service and the European Union. 
 
 This news comes on the heels of Coca-Cola’s attempt to start a “political campaign” by providing more than $1 million to the University of Colorado Foundation “for the purposes of funding” a group called the Global Energy Balance Network, which stressed the importance of diet and exercise and downplayed the role of sugary foods in the obesity epidemic. 
 
 When Coke’s involvement in the GEBN became known, the beverage biggie claimed it took a hands-off approach to the group. However, subsequently revealed emails showed that Coca-Cola was heavily involved in shaping the group’s message, likening it to “a political campaign, we will develop, deploy and evolve a powerful and multi-faceted strategy to counter radical organizations and their proponents.” 
 
 On Nov. 30, weeks after the university gave back $1.1 million to Coca-Cola, GEBN disbanded, posting a notice to the website that Coca-Cola had registered on the group’s behalf. 
 
 Then came the news that Coca-Cola had paid $550,000 directly to the man who would eventually head GEBN, and even offered to help his son find a job. 
 
 Did you enjoy this? We’re a non-profit! You can get more stories like this in our twice weekly ad-free newsletter! Click here to sign up.
– You'll never believe who paid for a study that found drinking diet soda could be better than water for losing weight. Well, OK, you'll probably guess. The Independent reports the study—published in the International Journal of Obesity in November—was partly funded by ILSI Europe, an "industry-backed research consortium" that counts Coca-Cola and PepsiCo as members. Not only that, but the group directly paid some of the researchers. Consumerist has even more: One of the researchers is an ILSI Europe employee; the study's lead author once got funding from a lobbying group called Sugar Nutrition, UK—formerly the British Sugar Bureau; and other members of the study's team are "employees and shareholders of companies that manufacture products containing sugars and low-energy sweeteners.” "Overall, the balance of evidence indicates that use of low-energy sweeteners in place of sugar, in children and adults, leads to reduced energy intake and body weight, and possibly also when compared with water," the study states. The Independent reports the study was based on results from three out of 5,500 related papers. Two of the papers found no difference between water and diet soda for weight loss. The sole paper claiming you're actually more likely to lose weight drinking diet soda over water was funded by the American Beverage Association. It flies in the face of numerous other studies, and one expert calls it "laughable, unscientific nonsense." "If you want good science, you cannot allow corporate sponsorship of research," he says. (It's not the first time Coca-Cola has been involved in a controversy like this.)