Dietary and Health Correlates of Sweetened Beverage Intake: Sources of Variability in the National Health and Nutrition Examination Survey (NHANES).

Recent studies using data from the National Health and Nutrition Examination Survey (NHANES) have used inconsistent approaches to identify and categorize beverages, especially those containing low-calorie sweeteners (LCS), also referred to as low-calorie sweetened beverages (LCSBs). Herein, we investigate the approaches used to identify and categorize LCSBs in recent analyses of NHANES data. We reviewed published studies examining LCS consumption in relation to dietary and health outcomes and extracted the methods used to categorize LCS as reported by the authors of each study. We then examined the extent to which these approaches reliably identified LCSBs using the Internet Archive Wayback Machine to examine beverage ingredients lists across three NHANES cycles (2011-2016). None of the four general strategies used appeared to include all LCSBs while also excluding all beverages that did not contain LCS. In some cases, the type of sweetener in the beverage consumed could not be clearly determined; we found 9, 16, and 18 of such "mixed" beverage identifiers in the periods 2011-2012, 2013-2014, and 2015-2016, respectively. Then, to illustrate how heterogeneity in beverage categorization may impact the outcomes of published analyses, we compared results of a previously published analysis with outcomes when "mixed" beverages were grouped either all as LCSBs or all as sugary beverages. Our results suggest that caution is warranted in design and interpretation of studies using NHANES data to examine dietary and health correlates of sweetened beverage intake.

Consumption of low-calorie sweetened beverages is associated with higher total energy and sugar intake among children, NHANES 2011-2016.

OBJECTIVE: To examine associations between consumption of low-calorie sweetened beverages (LCSBs), sugar, and total energy intake in children in the United States. METHODS: We used 24-hour dietary recalls from 7026 children enrolled in the National Health and Nutrition Examination Survey (NHANES) 2011 to 2016 to assess energy and macronutrient intake among LCSB (≥4 oz LCSB, <4 oz SB), SB (≥4 oz SB, <4 oz LCSB), and LCSB + SB consumers (≥4 oz each) compared with water consumers (≥4 oz water, <4 oz LCSB and SBs). Sample weights and complex survey procedures were used for all analyses. RESULTS: Adjusting for body mass index (BMI) percentile, LCSB, SB, and LCSB + SB consumption was associated with 196, 312, and 450 more total calories and 15, 39, and 46 more grams of added sugar, which amounts to 60, 156, 184 more calories from added sugar, compared with water consumers (P < .05 for all pairwise comparisons). No differences in energy intake were observed between LCSB and SB consumers. [Correction added on 28 May 2019, after first online publication: In the preceding sentence, quantities of added sugar reported are in grams. The corresponding calories have also been specified in this version.] CONCLUSIONS: These findings challenge the utility of LCSB for weight management in children and adolescents.

Associations Between Nonnutritive Sweetener Intake and Metabolic Syndrome in Adults.

OBJECTIVE: Individuals looking to improve their health or weight status often use nonnutritive sweeteners (NNS), yet NNS consumption has been associated with increased risk factors for metabolic syndrome (MetS). Most studies examining NNS only assess total intake using diet soda as a proxy for NNS consumption, without distinguishing potential risks associated with individual sweeteners. The objective of this cross-sectional investigation was to identify whether there were associations between NNS consumption (total or individual) and risk factors for MetS in adults (n = 125) from Southwest Virginia. METHODS: Participants provided three 24-hour dietary recalls and blood pressure, waist circumference, fasting glucose, triglycerides, and high-density lipoprotein cholesterol were assessed. Linear regression models, adjusted for age, sex, caloric intake, dietary quality, and physical activity, examined associations between total and individual types of NNS with MetS and MetS risk factors. RESULTS: Sixty-three participants were classified as NNS consumers and eighteen met the criteria for MetS. While no significant associations between MetS and NNS consumption were found, waist circumference was positively associated with total NNS, saccharin, sucralose, and acesulfame potassium, and both fasting glucose and triglyceride values were positively associated with total NNS and aspartame consumption. CONCLUSION: While these cross-sectional data are consistent with previous work implicating NNS in development of MetS, additional research using randomized controlled trials is needed to clarify whether and how NNS in general or specific NNS might contribute to risk factors for MetS. This trial was registered at clinicaltrials.gov (NCT03364452).

Artificial sweeteners and metabolic dysregulation: Lessons learned from agriculture and the laboratory.

Escalating rates of obesity and public health messages to reduce excessive sugar intake have fuelled the consumption of artificial sweeteners in a wide range of products from breakfast cereals to snack foods and beverages. Artificial sweeteners impart a sweet taste without the associated energy and have been widely recommended by medical professionals since they are considered safe. However, associations observed in long-term prospective studies raise the concern that regular consumption of artificial sweeteners might actually contribute to development of metabolic derangements that lead to obesity, type 2 diabetes and cardiovascular disease. Obtaining mechanistic data on artificial sweetener use in humans in relation to metabolic dysfunction is difficult due to the long time frames over which dietary factors might exert their effects on health and the large number of confounding variables that need to be considered. Thus, mechanistic data from animal models can be highly useful because they permit greater experimental control. Results from animal studies in both the agricultural sector and the laboratory indicate that artificial sweeteners may not only promote food intake and weight gain but can also induce metabolic alterations in a wide range of animal species. As a result, simple substitution of artificial sweeteners for sugars in humans may not produce the intended consequences. Instead consumption of artificial sweeteners might contribute to increases in risks for obesity or its attendant negative health outcomes. As a result, it is critical that the impacts of artificial sweeteners on health and disease continue to be more thoroughly evaluated in humans.

Not-so-healthy sugar substitutes?

Replacing sugar-sweetened beverages with diet soft drinks containing sugar substitutes that provide few or no calories has been suggested as one strategy for promoting improved public health outcomes. However, current scientific evidence indicates that routine consumption of beverages with non-nutritive sweeteners not only fails to prevent disease, but is associated with increases in risks for the same health outcomes associated with sugar-sweetened beverages, including type 2 diabetes, cardiovascular disease, hypertension and stroke. Results from pre-clinical studies have provided plausible biological mechanisms that could promote these counterintuitive negative health effects of artificial sweeteners. Taken together, scientific studies currently indicate that public health will be improved by reducing intake of all sweeteners, both caloric and non-caloric.

Artificial sweeteners are not the answer to childhood obesity.

While no single factor is responsible for the recent, dramatic increases in overweight and obesity, a scientific consensus has emerged suggesting that consumption of sugar-sweetened products, especially beverages, is casually linked to increases in risk of chronic, debilitating diseases including type 2 diabetes, cardiovascular disease, hypertension and stroke. One approach that might be beneficial would be to replace sugar-sweetened items with products manufactured with artificial sweeteners that provide sweet tastes but with fewer calories. Unfortunately, evidence now indicates that artificial sweeteners are also associated with increased risk of the same chronic diseases linked to sugar consumption. Several biologically plausible mechanisms may explain these counterintuitive negative associations. For example, artificial sweeteners can interfere with basic learning processes that serve to anticipate the normal consequences of consuming sugars, leading to overeating, diminished release of hormones such as GLP-1, and impaired blood glucose regulation. In addition, artificial sweeteners can alter gut microbiota in rodent models and humans, which can also contribute to impaired glucose regulation. Use of artificial sweeteners may also be particularly problematic in children since exposure to hyper-sweetened foods and beverages at young ages may have effects on sweet preferences that persist into adulthood. Taken as a whole, current evidence suggests that a focus on reducing sweetener intake, whether the sweeteners are caloric or non-caloric, remains a better strategy for combating overweight and obesity than use of artificial sweeteners.

Not so Sweet Revenge: Unanticipated Consequences of High-Intensity Sweeteners.

While no single factor accounts for the significant increases in overweight and obesity that have emerged during the past several decades, evidence now suggests that sugars, in general, and sugar-sweetened beverages, in particular, may be especially problematic. One response to this concern has been an explosion in the availability and use of noncaloric sweeteners as replacements for sugar. While consumers have been led to believe that such substitutes are healthy, long-term epidemiological data in a number of cohorts have documented increased risk for negative outcomes like type 2 diabetes, heart disease, and stroke among users of artificial sweeteners. Experimental data from animals has provided several plausible mechanisms that could explain this counterintuitive relationship. In particular, my research has demonstrated that artificial sweeteners appear to interfere with basic learned, predictive relations between sweet tastes and post-ingestive consequences such as the delivery of energy. By interfering with these relations, artificial sweeteners inhibit anticipatory responses that normally serve to maintain physiological homeostasis, and over the long term, this interference could result in negative health effects like those seen in the human cohort studies. These data suggest that reducing the consumption of all sweeteners is advisable to promote better health.

A view of obesity as a learning and memory disorder.

This articles describes how a cascade of associative relationships involving the sensory properties of foods, the nutritional consequences of their consumption, and perceived internal states may play an important role in the learned control of energy intake and body weight regulation. In addition, we describe ways in which dietary factors in the current environment can promote excess energy intake and body weight gain by degrading these relationships or by interfering with the neural substrates that underlie the ability of animals to use them to predict the nutritive or energetic consequences of intake. We propose that an expanded appreciation of the diversity of orosensory, gastrointestinal, and energy state signals about which animals learn, combined with a greater understanding of predictive relationships in which these cues are embedded, will help generate new information and novel approaches to addressing the current global problems of obesity and metabolic disease.

Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements.

The negative impact of consuming sugar-sweetened beverages on weight and other health outcomes has been increasingly recognized; therefore, many people have turned to high-intensity sweeteners like aspartame, sucralose, and saccharin as a way to reduce the risk of these consequences. However, accumulating evidence suggests that frequent consumers of these sugar substitutes may also be at increased risk of excessive weight gain, metabolic syndrome, type 2 diabetes, and cardiovascular disease. This paper discusses these findings and considers the hypothesis that consuming sweet-tasting but noncaloric or reduced-calorie food and beverages interferes with learned responses that normally contribute to glucose and energy homeostasis. Because of this interference, frequent consumption of high-intensity sweeteners may have the counterintuitive effect of inducing metabolic derangements.

Adverse effects of high-intensity sweeteners on energy intake and weight control in male and obesity-prone female rats.

The use of high-intensity sweeteners has been proposed as a method to combat increasing rates of overweight and obesity in the human population. However, previous work with male rats suggests that consumption of such sweeteners might contribute to, rather than ameliorate, weight gain. The goals of the present experiments were to assess whether intake of high-intensity sweeteners is associated with increased food intake and body weight gain in female rats; to evaluate whether this effect depends on composition of the maintenance diet (i.e., standard chow compared with diets high in energy, fat, and sugar [HE diets]); and to determine whether the phenotype of the rats with regard to propensity to gain weight on HE diets affects the consequences of consuming high-intensity sweeteners. The data demonstrated that female rats fed a low-fat, standard laboratory chow diet did not gain extra weight when fed yogurt dietary supplements sweetened with saccharin compared with those fed glucose-sweetened dietary supplements. However, female rats maintained on a "Westernized" diet high in fat and sugar (HE diet) showed significant increases in energy intake, weight gain, and adiposity when given saccharin-sweetened compared with glucose-sweetened yogurt supplements. These differences were most pronounced in female rats known to be prone to obesity prior to the introduction of the yogurt diets. Both selectively bred Crl:OP[CD] rats and outbred Sprague-Dawley rats fed an HE diet showing high levels of weight gain (diet-induced obese [DIO] rats) had increased weight gain in response to consuming saccharin-sweetened compared with glucose-sweetened supplements. However, in male rats fed an HE diet, saccharin-sweetened supplements produced extra weight gain regardless of obesity phenotype. These results suggest that the most negative consequences of consuming high-intensity sweeteners may occur in those most likely to use them for weight control, females consuming a "Westernized" diet and already prone to excess weight gain.

Influence of ovarian and non-ovarian estrogens on weight gain in response to disruption of sweet taste--calorie relations in female rats.

Regulation of energy balance in female rats is known to differ along a number of dimensions compared to male rats. Previous work from our lab has demonstrated that in female rats fed dietary supplements containing high-intensity sweeteners that may disrupt a predictive relation between sweet tastes and calories, excess weight gain is demonstrated only when females are also fed a diet high in fat and sugar, and is evidenced primarily in animals already prone to gain excess weight. In contrast, male rats show excess weight gain when fed saccharin-sweetened yogurt supplements when fed both standard chow diets and diets high in fat and sugar, and regardless of their proneness to excess weight gain. The goal of the present experiments was to determine whether ovarian, or other sources of estrogens, contributes to the resistance to excess weight gain in female rats fed standard chow diets along with dietary supplements sweetened with yogurt. Results of the first experiment indicated that when the ovaries were removed surgically in adult female rats, patterns of weight gain were similar in animals fed saccharin-sweetened compared to glucose-sweetened yogurt supplements. In the second experiment, when the ovaries were surgically removed in adult female rats, and local production of estrogens was suppressed with the aromatase inhibitor anastrozole, females fed the saccharin-sweetened yogurt consumed more energy and gained more weight than females fed the glucose-sweetened yogurt. However, when the ovaries were surgically removed prior to the onset of puberty (at 24-25 days of age), females given saccharin-sweetened yogurt along with vehicle gained excess weight. In contrast, weight gain was similar in those given saccharin-sweetened and glucose-sweetened yogurt along with anastrozole. The results suggest that behavioral differences between males and females in response to disruption of sweet→calorie relations may result from differences in patterns of local estrogen production. These differences may be established developmentally during the pubertal period in females.

Saccharin pre-exposure enhances appetitive flavor learning in pre-weanling rats.

In adult rats, data suggest that consumption of sweet tastes that do not deliver anticipated caloric consequences using high-intensity, non-caloric sweeteners, such as saccharin, interferes with learned relations that may contribute to energy balance. The goal of the present study was to assess the development of learning about sweet taste and calories by assessing whether pre-exposure to saccharin solutions reduces cue competition in pre-weanling rats. The results demonstrated that rats pre-exposed to saccharin and then trained with a novel grape flavor paired with a glucose-sweetened solution consumed more of the novel grape flavor presented alone than rats that had been pre-exposed to saccharin and given the grape flavor paired with water alone. No differences in intake of the novel grape flavor were observed in groups given pre-exposure to water or glucose solutions. Thus, by 15 days of age, rats appear to have established an association between sweet tastes and calories, and this association can be weakened by exposure to saccharin.

Experience with the high-intensity sweetener saccharin impairs glucose homeostasis and GLP-1 release in rats.

Previous work from our lab has demonstrated that experience with high-intensity sweeteners in rats leads to increased food intake, body weight gain and adiposity, along with diminished caloric compensation and decreased thermic effect of food. These changes may occur as a result of interfering with learned relations between the sweet taste of food and the caloric or nutritive consequences of consuming those foods. The present experiments determined whether experience with the high-intensity sweetener saccharin versus the caloric sweetener glucose affected blood glucose homeostasis. The results demonstrated that during oral glucose tolerance tests, blood glucose levels were more elevated in animals that had previously consumed the saccharin-sweetened supplements. In contrast, during glucose tolerance tests when a glucose solution was delivered directly into the stomach, no differences in blood glucose levels between the groups were observed. Differences in oral glucose tolerance responses were not accompanied by differences in insulin release; insulin release was similar in animals previously exposed to saccharin and those previously exposed to glucose. However, release of GLP-1 in response to an oral glucose tolerance test, but not to glucose tolerance tests delivered by gavage, was significantly lower in saccharin-exposed animals compared to glucose-exposed animals. Differences in both blood glucose and GLP-1 release in saccharin animals were rapid and transient, and suggest that one mechanism by which exposure to high-intensity sweeteners that interfere with a predictive relation between sweet tastes and calories may impair energy balance is by suppressing GLP-1 release, which could alter glucose homeostasis and reduce satiety.

Fat substitutes promote weight gain in rats consuming high-fat diets.

The use of food products designed to mimic the sensory properties of sweet and fat while providing fewer calories has been promoted as a method for reducing food intake and body weight. However, such products may interfere with a learned relationship between the sensory properties of food and the caloric consequences of consuming those foods. In the present experiment, we examined whether use of the fat substitute, olestra, affect energy balance by comparing the effects of consuming high-fat, high-calorie potato chips to the effects of consuming potato chips that sometimes signaled high calories (using high-fat potato chips) and that sometimes signaled lower calories (using nonfat potato chips manufactured with the fat substitute olestra). Food intake, body weight gain and adiposity were greater for rats that consumed both the high-calorie chips and the low-calorie chips with olestra compared to rats that consumed consuming only the high-calorie chips, but only if animals were also consuming a chow diet that was high in fat and calories. However, rats previously exposed to both the high- and low-calorie chips exhibited increased body weight gain, food intake and adiposity when they were subsequently provided with a high fat, high calorie chow diet suggesting that experience with the chips containing olestra affected the ability to predict high calories based on the sensory properties of fat. These results extend the generality of previous findings that interfering with a predictive relationship between sensory properties of foods and calories may contribute to dysregulation of energy balance, overweight and obesity.

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.

Recent results from both human epidemiological and experimental studies with animals suggest that intake of noncaloric sweeteners may promote, rather than protect against, weight gain and other disturbances of energy regulation. However, without a viable mechanism to explain how consumption of noncaloric sweeteners can increase energy intake and body weight, the persuasiveness of such results has been limited. Using a rat model, the present research showed that intake of noncaloric sweeteners reduces the effectiveness of learned associations between sweet tastes and postingestive caloric outcomes (Experiment 1) and that interfering with this association may impair the ability of rats to regulate their intake of sweet, but not nonsweet, high-fat and high-calorie food (Experiment 2). The results support the hypothesis that consuming noncaloric sweeteners may promote excessive intake and body weight gain by weakening a predictive relationship between sweet taste and the caloric consequences of eating.

Body weight gain in rats consuming sweetened liquids. Effects of caffeine and diet composition.

Previous studies show that high-intensity sweeteners can stimulate weight gain in rats. The present studies examined whether caffeine, a stimulant commonly added to beverages consumed by humans, influences intake of saccharin- or glucose-sweetened solutions or body weight gain in rats and whether the nature of the maintenance diet influences the effects of caffeine. In two experiments, rats received glucose or saccharin solution mixed with 0.125 mg/g caffeine or no caffeine. Rats consumed significantly more caffeinated than noncaffeinated solutions when they were maintained on a low-fat chow diet (Experiment 1) and when maintained on a sweet, high-fat, high calorie chow diet (Experiment 2). Consumption of saccharin resulted in higher body weight gain in both experiments. Caffeine reversed this effect in Experiment 1 (low-fat diet) but not Experiment 2 (sweet, high-fat diet). The findings extend what is known about the conditions under which consumption of high intensity sweeteners promote energy dysregulation.

High-intensity sweeteners and energy balance.

Recent epidemiological evidence points to a link between a variety of negative health outcomes (e.g. metabolic syndrome, diabetes and cardiovascular disease) and the consumption of both calorically sweetened beverages and beverages sweetened with high-intensity, non-caloric sweeteners. Research on the possibility that non-nutritive sweeteners promote food intake, body weight gain, and metabolic disorders has been hindered by the lack of a physiologically-relevant model that describes the mechanistic basis for these outcomes. We have suggested that based on Pavlovian conditioning principles, consumption of non-nutritive sweeteners could result in sweet tastes no longer serving as consistent predictors of nutritive postingestive consequences. This dissociation between the sweet taste cues and the caloric consequences could lead to a decrease in the ability of sweet tastes to evoke physiological responses that serve to regulate energy balance. Using a rodent model, we have found that intake of foods or fluids containing non-nutritive sweeteners was accompanied by increased food intake, body weight gain, accumulation of body fat, and weaker caloric compensation, compared to consumption of foods and fluids containing glucose. Our research also provided evidence consistent with the hypothesis that these effects of consuming saccharin may be associated with a decrement in the ability of sweet taste to evoke thermic responses, and perhaps other physiological, cephalic phase, reflexes that are thought to help maintain energy balance.