Version May 2024
INTRODUCTION — Nonnutritive sweeteners (NNS) are high-intensity sweeteners and are typically noncaloric or very low in calories. Due to recommendations to limit dietary sugar intake, NNS have become widely used.
This topic will review the general use of NNS, including the potential health benefits and adverse effects, as well as contraindications to their use in specific patient populations.
CLASSIFICATION — Some NNS are naturally occurring, plant-derived products, while others are synthetic ("artificial"). The sweetness of NNS is measured in comparison with a sucrose solution of 30 g/L, the minimal detection concentration range for taste buds (table 1).
●Naturally derived NNS – Naturally derived NNS include glycoside and non-glycoside compounds:
•Glycosides include the first generation of polyols (eg, sorbitol, xylitol, and erythritol), stevia glycosides, and luo han guo fruit (monk fruit) extract.
•Non-glycoside, second-generation polyols include maltitol. Non-glycosidic nitrogenous compounds include thaumatin and the flavonoid derivative brazzein.
●Synthetic (artificial) NNS – Synthetic sweeteners include saccharin, cyclamate, alitame, acesulfame potassium, sucralose, aspartame, advantame, and neotame. Although neohesperidin dihydrochalcone is technically a derivative of a natural sweetener (flavonoid), it is chemically modified to the point of synthetic classification.
AVAILABLE SWEETENERS AND USES — NNS are used in a variety of different food products. Depending upon their chemical characteristics, some can be used as tabletop (standalone) sweeteners, while others are used only in industrial (commercial) food and food product preparation. Many commercially prepared products use a combination of different NNS. Most consumers are unaware of the presence of these sweeteners in the processed food and beverages they consume and in the pharmaceutical and personal care products that they use.
●Aspartame – Aspartame is the most commonly used NNS, accounting for 75 percent of sweetener sales. Although the majority of aspartame is used in diet beverages, it is also used in over 6000 other products, including food, pharmaceutical, and personal care items (eg, cosmetics, breath fresheners). It is available in various forms, including liquid, encapsulated, and powder; many are available to the consumer for use as tabletop sweeteners [1].
Aspartame is unstable at high temperatures and cannot be used for baking or cooking; it is often found in gelatin, yogurt, cereals, and frozen "sugar-free" confections. Aspartame is catabolized to phenylalanine among other compounds, making it unsafe for consumption in individuals with phenylketonuria. (See "Overview of phenylketonuria".)
●Neotame – Neotame is similar in structure to aspartame; it is used as a sweetener and as a flavor enhancer, and because of its superior stability, it is widely used in commercially prepared foods and drinks. It has no bitter aftertaste and is often preferred for "diabetic" sugar-free products for this reason. It can be found in soft drinks, beverages that contain lactic acid, sauces, yogurts, chewing gum, and fruit confections; it is also available as a tabletop sweetener. It does not contain phenylalanine, making it safe for individuals with phenylketonuria.
●Sorbitol – Sorbitol and other polyols are typically used in "sugar-free" products, with these sweeteners most frequently found in chewing gum [2]. Other products commonly containing polyols include jams, jellies, baked goods, frozen confections, and candy.
●Stevia glycosides – Stevia glycosides are increasing in popularity globally and can be sold as a dietary supplement in most parts of the world. Stevia can be used as a tabletop sweetener, and since it is relatively stable in heat and over a wide pH range, it is also used commercially in prepared products such as ice cream, yogurt, cakes, sauces, beverages, and pastries [3].
●Advantame – Advantame is acid- and base-stable, tolerant of high temperatures, and used in powdered drinks, yogurt, sauces, chewing gum, and baked and processed foods [4,5]. Although it is a source of phenylalanine, the amount is much less than in aspartame and routine consumption of advantame is considered safe for those with phenylketonuria.
●Acesulfame potassium – Acesulfame potassium (K) is unique in its ability to withstand high cooking temperatures without decomposition, and it is frequently used in prepared entrees, baked goods, and other confections. It is also available in granular form for use as a tabletop sweetener [6]. Potassium comprises 20 percent of the compound by weight.
●Sucralose – Sucralose is heat-stable and can be used for baking and cooking. It is used in desserts, confections, canned fruits, gelatins, yogurts, and some beverages (lactic acid-containing and non-alcoholic). It is also available as a tabletop sweetener. Sucralose is poorly absorbed in the gastrointestinal tract.
●Saccharin – Saccharin is stable at low pH and high temperatures, making it amenable for use in most processed food applications. It is used in fruit juices, processed fruits, gelatins, marmalades, jams, sauces, marinades, desserts, chewing gum, and soft drinks and is available for use as a tabletop sweetener in most countries other than Canada.
●Luo han guo (monk fruit) extract – Luo han guo extract is derived from the fruit of Siraitia grosvenorii, the monk fruit plant. The extract is 250 to 300 times sweeter than sucrose. It is not widely used in commercial products as a sweetener, but it is available as a tabletop sweetener, alone or as a combination product with other NNS.
●Cyclamates – Cyclamates are widely used outside of North America in desserts, canned fruits, gelatins, baked and processed foods, and soft drinks, and they are also available as a tabletop sweetener. Along with saccharin, they are the cheapest and easiest NNS to produce. Cyclamates are not approved for use in the United States. (See 'Regulatory issues' below.)
●Alitame – Alitame is comprised of aspartate and alanine. It is stable, although not fat-soluble, thus limiting its applications in the food processing industry [7]. Alitame, typically used in conjunction with other sweeteners in desserts, is not approved for use in the United States. (See 'Regulatory issues' below.)
●Neohesperidin – Neohesperidin is approved for use as a food additive, but not as a sweetener, in the United States; it is typically used as a stabilizer and thickener. It is soluble in aqueous solution only at high temperatures, and it has a licorice-like aftertaste. Outside of the United States, it is used as a sweetener for ice cream, pastry, milk-based products, soups, beer, vitamin supplement flavoring, and fruit-based confections, and also as a tabletop sweetener [8]. (See 'Regulatory issues' below.)
●Thaumatin – Thaumatin, classified as a flavor enhancer, is proteinaceous, is stable at higher temperatures, and can tolerate an acidic environment. It is soluble in aqueous solution and is commonly used in the pharmaceutical industry. It can also be used in conjunction with other flavor enhancers in soups, sauces, processed vegetables, and egg-based products. It is sweet, but it does have an aftertaste. Due to its cost, it is produced either by recombinant microorganisms or extracted from transgenic (genetically modified) plants [9,10].
●Erythritol – Erythritol, a naturally derived sugar alcohol, is used in large quantities in processed foods due to its relatively low sweetness. It is poorly metabolized and excreted mostly in the urine [11]. It is primarily combined with other sweeteners, such as monk fruit extract and stevia leaf extract, for commercially available nonnutritive sugar substitutes.
REGULATORY ISSUES
●Approval for use in food – In the United States, the US Food and Drug Administration (FDA) classifies six NNS as food additives, including saccharin, aspartame, acesulfame K, sucralose, neotame, advantame, stevia glycosides, and luo han guo fruit (monk fruit) extracts [12]. The sugar alcohols (eg, sorbitol, xylitol) are not considered food additives by the FDA. Additionally, the FDA provides risk assessment recommendations for the consumption of food additives based upon scientific studies or a substantial history of consumption by humans, designating compounds considered safe for consumption as "Generally Regarded as Safe" (GRAS).
In the 1970s, animal studies raised concerns that saccharin caused bladder cancer in rodents, and the FDA removed saccharin's GRAS designation in 1977. However, further evaluation demonstrated no relationship between saccharin consumption and the development of malignancies in humans [13], and the GRAS designation was restored [14]. Although limited observational data suggest a possible weak association between the consumption of NNS with cancer [15], there is no high-quality evidence that any of the available NNS increase the risk of cancer in humans [16-20].
Internationally, the Joint Food and Agricultural Organization (FAO)/World Health Organization (WHO) Expert Committee on Food Additives (JEFCA) provides risk assessment and recommendations for acceptable daily intakes (ADIs) of food additives based upon scientific studies. The European Union, however, has a more extensive list of approved NNS than the United States, as well as different ADIs (table 1); cyclamates, alitame, and neohesperidin are approved for use as sweeteners in the European Union, while these compounds are not approved for use in the United States. Of note, the ADI is derived from the total safe lifetime consumption of the sweetener and is set at 1/100th of the maximal level at which no adverse effect is seen in animal studies [16,21].
●Labeling – In the United States, NNS are not required to be listed on food or drink labels unless a threshold amount per serving is reached. Because many of the NNS are vastly sweeter than sucrose and are often used in combination, the amount of a specific sweetener present may be measured in micro- or even nanograms. In addition, since ingredients are listed in order of decreasing amounts, sweeteners are typically among the last ingredients listed. Furthermore, the chemical names of the most common sweetening agents may be unrecognizable to consumers (table 2).
Sweeteners are often combined with bulking agents, inert compounds that increase volume, viscosity, or density, or act as encapsulating or "dusting" agents. In the United States, regulation of labeling these ingredients is determined by individual states rather than by federal agencies.
In the United States, saccharin is the only sweetener for which disclosure of the exact amount present in a food product is required; the maximum allowable quantity is 12 mg/fl ounce [12]. Warning labels, however, are no longer required for saccharin-containing products [22]. Products containing aspartame must display warnings regarding phenylketonuria. (See 'Available sweeteners and uses' above.)
Globally, each country has its own labeling laws, and there are multiple organizations which can influence labeling and disclosure practices. An example is the Codex Alimentarius Commission (CAC), a joint organization between the FAO of the United Nations and the WHO [23].
HEALTH EFFECTS OF NNS CONSUMPTION — A growing body of evidence documents associations between the consumption of products sweetened with NNS and both positive (eg, reduced risk of dental caries) and negative health outcomes (eg, cardiovascular disease [CVD], diabetes, death).
Proposed physiologic mechanisms — The exact mechanisms by which consumption of NNS may adversely affect health is not definitively known. Possible mechanisms for the physiologic effects of NNS consumption include dysbiosis (changes in the gut microbiome) [24-27], energy compensation [28], activation of sweet receptors [29,30], altered taste preferences and reward perception [31-34], incongruent caloric expectations [31], and alterations in gut-brain neuropeptide signaling [26].
There is a lack of a consistent association between consumption of NNS and weight loss; dysbiosis likely plays a major role in the observed "paradoxical" weight and metabolic effects associated with the consumption of NNS. Gut microbiota play an important role in metabolic homeostasis, controlling processes ranging from insulin sensitivity, glucose tolerance, fat storage, appetite, and inflammation [35,36]. Gut bacteria produce short-chain fatty acids in addition to a variety of other metabolites (eg, indoles, phenols, choline derivatives, neurotransmitter precursors), many of which act as signaling molecules for cells within the gut mucosa [37]. A favorable enteric microbial population can positively affect energetics, appetite, adipogenesis, and thermoregulation.
Exposure to NNS may be associated with alterations in the usual proportions of enteric bacteria, with different sweeteners having differential effects [38-42]. Responses to NNS may be mediated by intestinal microbiota and their impact on the gut brain axis. Findings suggest that artificial sweeteners regulate both Escherichia coli and Enterococcus faecalis, and these in turn impact gut hormones and appetitive signals while impacting body weight [43-45]. Additionally, exposure of the gut microbiota to NNS may alter genetic expression of proteins, further impacting the effects of gut microbiota on metabolic homeostasis [46].
NNS may affect the brain's responsivity to food cues, resulting in negative consequences for eating behavior. In a 2021 study comparing brain activity, metabolic responses, and eating behaviors among 74 adults after consumption of either sucralose (NNS) or sucrose (nutritive sugar), neural and behavioral outcomes differed based on sex and body mass index (BMI) [47]. When shown food images, individuals with obesity had greater neural responses in reward-related areas of the brain after ingesting sucralose compared with sucrose, and female participants consumed more calories during a buffet meal after sucralose compared with sucrose ingestion.
Specific health outcomes — Consumption of foods and beverages containing NNS has not been found to produce long-term weight loss and may be associated with health risks. Replacing sugar-sweetened products with NNS decreases some health risks, such as the risk of dental caries. However, a growing body of evidence suggests that consumption of NNS, particularly artificially sweetened beverages (ASBs), may increase risks of adverse health outcomes, including type 2 diabetes mellitus, obesity, depression, CVD, and all-cause mortality [48-52].
Guidelines from the World Health Organization recommend against the use of NNS (eg, aspartame, sucralose, stevia, saccharin) for weight loss or the reduction of chronic disease risk [53,54].
Mortality — High consumption of ASBs has been associated with small increased rates of all-cause and cardiovascular mortality [49,51,55]. As an example, a meta-analysis of cohort studies of over 1.5 million participants found an association between consumption of ASBs and all-cause mortality (five additional deaths per 1000 persons for each consumption increase of 250 mL/day) [51]. Similarly, in a meta-analysis of 15 studies (over 1.2 million participants), high ASB consumption was associated with increased risks of all-cause mortality in a linear dose-response fashion (hazard ratio [HR] 1.12; 95% CI 1.04-1.21) [55].
Weight — We do not typically advise patients to use NNS to reduce weight or maintain weight loss. We encourage consumption of water and other nonsweetened beverages [56-59].
Although the use of NNS can result in short-term (three months) weight loss and reductions in BMI, their use does not appear to sustain long-term weight loss [49,60,61].
Many diseases, health conditions, and negative health outcomes are related to overweight and obesity, and overconsumption of high-calorie, sugar-sweetened foods and beverages play a major role in the obesity epidemic [62,63]. For adults who are habituated to sweet taste, particularly among those who are overweight and with obesity, substitution of NNS could conceivably improve health by reducing caloric intake. As an example, in a meta-analysis of 12 randomized trials, higher consumption of NNS reduced sugar intake by approximately 39 g per day [49]. In such individuals, substituting NNS for sugar-sweetened foods could help with a transition to a healthier diet over time. However, since the use of NNS does not appear to sustain long-term weight loss, this should be clearly communicated to patients.
●Impact in general population – Although global marketing promotes NNS products as healthful alternatives to sugar-sweetened foods [64], the preponderance of the evidence does not support their effectiveness for weight reduction or maintenance of weight loss [49,57,60,61,65,66]. As an example, in a 2019 meta-analysis of five randomized trials and 229 adults, consumption of NNS did not result in greater weight loss than consumption of caloric sweeteners or placebo (weight change -1.29 kg, 95% CI -2.8 to 0.21 kg) [57]. Similarly, an earlier meta-analysis of randomized trials found that use of NNS had no significant effect on BMI [60].
Long-term cohort studies document an association between consumption of NNS and incident obesity, including measures of BMI and waist circumference as well as visceral, intramuscular, and subcutaneous adipose tissue accumulation [61,65,66].
●Impact in individuals with overweight or obesity – It is unclear whether a role exists for using NNS for weight management in certain populations, such as individuals with overweight or obesity who consume large amounts of sugar-sweetened beverages or who are participating in a structured weight-loss program. Existing data derive from mostly low-quality, small, randomized trials and show conflicting results; some trials suggest a small weight-loss benefit from substituting NNS for caloric sweeteners or water, whereas other trials demonstrate greater weight loss with water consumption [57,67,68].
Glycemic effects — Limited high-quality data exist on the long-term effects of the NNS consumption on glucose metabolism and the development of diabetes mellitus. Data from cohort studies suggest that NNS consumption may increase the risk of type 2 diabetes. As an example, a 2022 meta-analysis of cohort studies found an association between increased rates of incident type 2 diabetes mellitus and NNS consumption in both beverage (HR 1.23; 95% CI 1.14-1.32) and non-beverage forms (HR 1.34; 95% CI 1.21-1.48) [49].
The relationship between NNS consumption and markers of glycemic control is unclear, with data from some randomized trials and observational studies showing an association of NNS intake with increased glucose intolerance, insulin resistance, and release of glucagon-like peptide 1 [27,69-71]. As an example, in a 2022 meta-analysis of randomized trials, NNS intake did not improve glycemic control as measured by levels of hemoglobin A1C, fasting insulin, or fasting glucose. In contrast, some earlier individual studies have reported negative or inconsistent associations between NNS intake and glucose metabolism [17,27,49,57,69-79].
Cardiovascular disease — Multiple prospective cohort studies support an association between consumption of NNS and adverse cardiovascular events [50,51,55]. Consumption of NNS has been associated with cardiometabolic risk factors [80], which in turn can increase the risk of CVD.
●Cardiovascular mortality – Large cohort studies suggest an association between consumption of ASBs and cardiovascular mortality [49,51,55,81]. As an example, a meta-analysis of over 1.5 million participants found an association between consumption of ASBs and cardiovascular mortality (two additional deaths per 1000 persons for each consumption increase of 250 mL/day) [51]. Similarly, in a meta-analysis of four prospective cohorts of over 590,000 participants, high ASB consumption was associated with an increased hazard of cardiovascular mortality (HR 1.19; 95% CI 1.07-1.32) [49].
●Cardiovascular events – Cohort studies in a range of population have found an association between intake of NNS and ASBs with cardiovascular events [11,49,50,81-83]. As an example, in a 2022 meta-analysis of 4 cohort studies of 166,938 participants, consumption of ASBs was associated with an increased rate of cardiovascular events (HR 1.32; 95% CI 1.17-1.50; I2 = 0) [49]. Data from this and other studies suggest a more consistent association between ASB consumption and increased risks of stroke (both ischemic and hemorrhagic) than coronary heart disease events [82,84].
Similarly, in the NutriNet-Santé study, which followed approximately 103,300 participants for over 900,000 person/years, total NNS intake was associated with an increased risk of CVD (HR 1.09; 95% CI 1.01-1.18), with the highest incidence seen among higher consumers [50]. NNS consumption (aspartame in particular) was associated with increased risk of cerebrovascular disease, while acesulfame potassium and sucralose were associated with increased risk of coronary heart disease.
Dental caries — We discourage regular consumption of both sugar- and artificially-sweetened soft drinks for optimal dental health; however, we encourage patients to replace other sugar-sweetened products (eg, chewing gum, candies, and lozenges) with those sweetened with NNS to reduce the risk of dental caries [85-88]. The sugar alcohols found in NNS, such as erythritol and xylitol, are nonnutritive for oral bacteria and disrupt the colonization of cariogenic strains such as Streptococcus mutans [87]. Although carbonated beverages sweetened with NNS rather than sugar reduce dental caries, carbonated beverages themselves are acidic and may weaken tooth enamel.
Other conditions
●Non-alcoholic fatty liver disease – It has been proposed that the consumption of NNS may reduce intrahepatic fat content and thus improve non-alcoholic fatty liver disease (NAFLD) independent of any change in body weight. However, evidence for this is mixed, with some studies demonstrating no association between consumption of ASBs and a reduced incidence of NAFLD [89], and others showing, among individuals who are overweight and with obesity, a reduction in intrahepatic fat with substitution of ASBs for sugar-sweetened beverages [90].
●Effects on alcohol and intoxication – The mixing of alcohol with beverages containing NNS increases blood alcohol levels and quickens inebriation, an effect further aggravated by caffeine [91-93]. Sucrose-sweetened mixers delay gastric emptying in parallel to carbohydrate content, thus decreasing alcohol absorption in comparison with those sweetened with HIS. This relationship holds across sex, age, and BMI.
●Neurologic – Consumption of aspartame has been shown to trigger migraine headaches in some individuals. The exact mechanism for this is unknown [94-97]. (See "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults", section on 'Precipitating and exacerbating factors'.)
●Allergenicity – There is a very small possibility of allergic reactions from sweeteners that are proteinaceous (eg, thaumatin) [98], from those that are derived from plants that can elicit hypersensitivity reactions (eg, stevia) [99,100], and from erythritol [101]. (See "Allergic and asthmatic reactions to food additives".)
Special populations
Individuals who are pregnant or breastfeeding — The safety of NNS consumption in pregnancy and lactation are reviewed elsewhere. (See "Maternal nutrition during lactation", section on 'Nonnutritive sweeteners' and "Nutrition in pregnancy: Assessment and counseling", section on 'Use of non-nutritive sweeteners'.)
Children — Few studies evaluate the effects of consumption of NNS in pediatric populations [57,60]. Although NNS could be used to replace high-calorie, sugar-sweetened foods among children and adolescents with overweight or obesity, we do not encourage the use of NNS in children or adolescents [102,103]. This is consistent with recommendations from the American Academy of Pediatrics, which state that NNS should not be a significant part of children's dietary intake, and the American Heart Association, which advises against the prolonged consumption of low-calorie sweetened beverages by children [59,102].
PATIENTS WHO SHOULD AVOID CONSUMPTION OF NNS — In addition to avoidance of certain sweeteners among those with allergic reactions or specific metabolic disorders (eg, avoidance of aspartame in phenylketonuria), consumption of NNS should be minimized or avoided in those with underlying bowel disorders and in patients undergoing bariatric surgery.
●Bowel disorders or symptoms – Patients with bowel disorders should generally avoid the regular use of products sweetened with NNS. Many NNS, particularly the polyols, may cause a disruption in the normal gut microbiota and aggravate symptoms in individuals with various types of bowel disorders, including malabsorption syndromes, inflammatory bowel diseases (Crohn disease, ulcerative colitis), irritable bowel syndrome, celiac disease, gluten sensitivity, small intestinal bacterial overgrowth, and dumping syndromes [104-115]. Evidence suggests that NNS-induced dysbiosis causes intestinal barrier alteration, chronic inflammatory response, and abnormal immunologic activation, which may contribute to the onset of inflammatory bowel disease [116]. In addition, NNS may promote plasmid mediated transfer of antibiotic-resistant genes and increased membrane permeability among intestinal microbiota, which may potentially decrease the efficacy of treatment for bacterial overgrowth in individuals with inflammatory bowel disease [117]. (See "Nutrition and dietary management for adults with inflammatory bowel disease".)
Even among individuals with no known bowel disorders, polyols and other NNS may cause flatulence, bloating, and osmotic diarrhea [112]. In any patient with unexplained bowel symptoms, a careful dietary history should be taken, with attention to the use of any products (particularly candy, chewing gum, nicotine gums and lozenges) that might be sweetened with NNS (table 3). (See "Treatment of irritable bowel syndrome in adults", section on 'Low FODMAP diet'.)
●Bariatrics – In patients planning for bariatric surgery, we generally advise against the use of products sweetened with NNS. Prior to bariatric surgery, some people with severe (class three) obesity may be prescribed a very low-calorie diet to promote preoperative weight loss to reduce the risk of surgical complications. In this capacity, NNS are used to provide sweetness and enhance the flavor of these low energy-density foods [118]. Acclimation to this sweetness can result in upregulation of taste receptors and may dampen satiation signaling due to increased glucagon-like peptide 1 production [119]. These factors may further contribute to postoperative weight-management difficulty.
In the postoperative bariatric patient, we also advise against the use of products sweetened with NNS [120]. Some NNS can increase bowel gas and bloating and cause abdominal discomfort, a concern following any bowel surgery. Within the shortened postoperative bowel, there is little room for non-nutrient-dense foods, let alone excessive gas.
In addition, dumping syndrome is common following bariatric surgery. Consumption of NNS may predispose to dumping syndrome and diarrhea, possibly through alterations in the gut microbiota [121,122]. (See "Bariatric operations: Late complications with subacute presentations", section on 'Dumping syndrome'.)
OTHER CONSIDERATIONS — The widespread use of NNS has implications beyond the direct effects on human health, including environmental contamination and impact on domestic animals.
●Environmental contamination – NNS are recognized as emerging environmental contaminants with high stability and persistence in water supplies. In a review, 24 NNS were identified in global ground, surface, ocean, and drinking water samples, suggesting that they represent a bioaccumulation hazard and an increasing threat to aquatic food webs [123]. Monitoring of these environmental risks as well as the search for methods of biodegradation is ongoing [124].
●Toxicity to canines – Xylitol (and to a lesser extent the other polyols) are highly toxic to canines [125]. Xylitol is potent stimulator of insulin release and the resultant hypoglycemia can be severe. In addition, metabolites of xylitol can accumulate, causing hepatocyte necrosis and liver failure, with vomiting, diarrhea, anorexia, lethargy, ataxia, seizures, icterus, coagulopathy, coma, and even death [126].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Obesity in adults" and "Society guideline links: Obesity in children" and "Society guideline links: Healthy diet in adults" and "Society guideline links: Healthy diet in children and adolescents" and "Society guideline links: Irritable bowel syndrome".)
SUMMARY AND RECOMMENDATIONS
●Overview and common uses of NNS – Nonnutritive sweeteners (NNS) are high-intensity sweeteners and are typically noncaloric or very low in calories. Some NNS are naturally occurring, plant-derived products, while others are synthetic ("artificial") (table 1). Due to recommendations to limit dietary sugar intake, NNS have become widely used. Depending upon their chemical characteristics, some can be used as tabletop (standalone) sweeteners, while others are used only in industrial (commercial) food preparation (table 2). Most consumers are unaware of the presence of NNS in the processed food and beverages they consume and in the pharmaceutical and personal care products that they use. (See 'Introduction' above and 'Available sweeteners and uses' above.)
●Labeling and regulatory requirements – In the United States, NNS are not required to be listed on food or drink labels unless a threshold amount per serving is reached; saccharin is the only sweetener for which disclosure of the exact amount present in a food product is required. (See 'Regulatory issues' above.)
●Health effects related to NNS consumption – We do not encourage the use of NNS for weight loss or other chronic disease management. The consumption of products containing NNS may have health effects, including favorable effects (eg, dental caries) and negative effects (eg, weight, glycemia, bowel function). Consumption of NNS, particularly artificially sweetened beverages, may increase risks of adverse health outcomes, including type 2 diabetes mellitus, obesity, cardiovascular disease, and all-cause mortality. (See 'Specific health outcomes' above.)
The exact mechanisms by which consumption of NNS may adversely affect health is not definitively known but likely includes dysbiosis (changes in the gut microbiome), alterations in sweet preferences, and impacts on gut-brain signaling. Many diseases, health conditions, and negative health outcomes are related to overweight and obesity. It is unclear, however, that replacement of dietary sugar with products sweetened with NNS can reverse the health consequences of sugar overconsumption. (See 'Health effects of NNS consumption' above.)
●Role for NNS – For adults who are habituated to sweet taste, particularly among those who are overweight and with obesity, the use of NNS beverages may be a reasonable strategy to reduce the use of sugar-sweetened drinks. However, consumption of water and other non-sweetened beverages should be encouraged over diet drinks. (See 'Specific health outcomes' above.)
●Individuals who should minimize or avoid consumption of NNS – In addition to avoidance of certain sweeteners among those with allergic reactions or specific metabolic disorders (eg, avoidance of aspartame in phenylketonuria), consumption of NNS should be minimized or avoided in those with underlying bowel disorders and in patients undergoing bariatric surgery. (See 'Patients who should avoid consumption of NNS' above.)
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