INTRODUCTION — Non-nutritive 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 non-nutritive sweeteners (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 — Non-nutritive sweeteners (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].
REGULATORY ISSUES
●Approval for use in food – In the United States, the US Food and Drug Administration (FDA) classifies six non-nutritive sweeteners (NNS) as food additives, including saccharin, aspartame, acesulfame K, sucralose, neotame, advantame, stevia glycosides, and luo han guo fruit (monk fruit) extracts [11]. 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 [12], and the GRAS designation was restored [13]. Although limited observational data suggest a possible weak association between the consumption of NNS with cancer [14], there is no high-quality evidence that any of the available NNS increase the risk of cancer in humans [15-19].
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 [15,20].
●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 [11]. Warning labels, however, are no longer required for saccharin-containing products [21]. 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 [22].
HEALTH EFFECTS OF NNS CONSUMPTION — The consumption of products sweetened with non-nutritive sweeteners (NNS) may have health effects, including favorable effects (eg, reduced risk of dental caries) and possibly negative effects (eg, weight, glycemia, bowel function). 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.
Proposed physiologic mechanisms — Possible mechanisms for the physiologic effects of the consumption of NNS include dysbiosis (changes in the gut microbiome) [23-26], energy compensation [27], activation of sweet receptors [28,29], altered taste preferences and reward perception [30-33], incongruent caloric expectations [30], and alterations in gut neuropeptide signaling [25].
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 [34,35]. 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 [36]. 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 [37-41]. 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 [42-44]. Additionally, exposure of the gut microbiota to NNS may alter genetic expression of proteins, further impacting the effects of gut microbiota on metabolic homeostasis [45].
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) [46]. 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 — Many diseases, health conditions, and negative health outcomes are related to overweight and obesity, with overconsumption of high-calorie, sugar-sweetened foods and beverages a major contributor to the obesity epidemic [47,48]. It is unclear, however, that replacement of dietary sugar with products sweetened with NNS can reverse the health consequences of sugar overconsumption [49-51]. Although there are some conditions, such as dental caries, in which the replacement of NNS for sugar-sweetened products is clearly of benefit, the evidence for other health outcomes such as weight loss, prevention of diabetes, and effects on cardiovascular disease (CVD) is less clear.
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 [52].
●Dental caries – Replacing sugar-sweetened products (eg, carbonated beverages, chewing gum, candies, and lozenges) with those sweetened with NNS reduces the risk of dental caries [53-56]. In particular, the sugar alcohols such as erythritol and xylitol are non-nutritive for oral bacteria and disrupt the colonization of cariogenic strains such as Streptococcus mutans [55]. Although products containing polyols are cariostatic, carbonated beverages themselves are acidic and may weaken tooth enamel; regular consumption of artificially sweetened soft drinks should be discouraged for this reason.
●Weight – In response to the obesity epidemic, global marketing of NNS products as healthful alternatives to sugar-sweetened foods has increased [57]. However, evidence supporting the use of NNS for weight reduction or maintenance of weight loss is mixed, with some studies demonstrating weight loss, some no weight change, and others an association between the consumption of NNS with weight gain.
The consumption of products sweetened with NNS may be ineffective for weight management. As examples:
•In a 2019 meta-analysis including 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) [50].
•In the San Antonio Heart Study in which over 5000 adults were followed for eight years, consumption of artificially sweetened beverages (ASBs) was associated with an increased BMI [58]. Including individuals of all weights (normal, overweight, and obese), consumption of >21 ASBs per week was associated with an increase in BMI of 0.47 kg/m2 (95% CI 0.26-0.66 kg/m2) compared with no consumption of ASBs. Furthermore, in a nine-year follow-up of over 700 individuals from the same cohort, increasing consumption of ASBs was associated with ascending abdominal obesity as measured by waist circumference [59].
However, there may be a role for the use of NNS for weight management in certain populations, such as patients who are overweight or with obesity, patients who consume large amounts of sugar-sweetened beverages, and those participating in a structured weight-loss program. As examples:
•In a subgroup analysis of the meta-analysis cited above, when only patients who were overweight or with obesity (BMI ≥25 kg/m2) were included, consumption of NNS resulted in greater weight loss compared with consumption of caloric sweeteners or placebo (-1.99 kg, 95% CI -2.84 to -1.14 kg) [50].
It is not clear if the consumption of water versus diet beverages (beverages sweetened with NNS) results in greater weight loss among individuals who are overweight and with obesity. As examples:
•In a randomized trial including over 300 people who were overweight or with obesity participating in a weight-loss program, patients consuming ≥24 ounces of NNS beverage per day lost more weight at one year than those consuming water in the same quantity (-5.01 kg, 95% CI -6.59 kg to -3.43 kg) [60].
•In a 2018 randomized trial including over 70 women with a BMI 27 to 40 kg/m2 participating in a weight-loss and weight loss maintenance program, replacement of water for diet beverages (five times per week) resulted in greater weight loss at 12 months than continuing usual diet beverage consumption (-1.7 versus -0.1 kg) [61].
The majority of the data on the effects of NNS on weight come from studies evaluating the consumption of diet beverages; it is possible that consumption of diet beverages affects weight in a different way than consumption of NNS in other dietary vehicles. In addition, in observational studies, consumption of NNS tends to be associated with unfavorable weight effects (eg, weight gain or no change in weight), while randomized trials involving NNS are more likely to show weight loss [62].
In addition, the majority of information on the effects of consumption of NNS is based upon adult studies, with limited information available in the pediatric population. Although the consumption of NNS in children is not encouraged, there may be role for the use of these products as a replacement for high-calorie, sugar-sweetened foods among children and adolescents who are overweight and with obesity [63,64]. However, the Institute of Medicine [65] and the American Academy of Pediatrics [63] have stated that NNS should not be a significant part of children's dietary intake, and the American Heart Association advises against the prolonged consumption of low-calorie sweetened beverages by children [52].
●Glycemic effects – There are limited high-quality data on the long term effects of the consumption of NNS on glucose metabolism. In some observational studies and randomized trials, consumption of NNS (in the form of ASBs) is associated with adverse glycemic effects, including glucose intolerance, increased insulin resistance, increase in glucagon-like peptide 1 (GLP-1) release, and development of type 2 diabetes mellitus [26,66-69]. However, in other studies, there is no evidence of any effect on glucose metabolism [16,50,70-73], or a conclusion cannot be drawn due to low-quality evidence [74-76].
●Cardiovascular disease – Consumption of NNS has been associated with cardiometabolic risk factors [77], which in turn can increase the risk of CVD. However, evidence for the effects of NNS consumption on cardiovascular outcomes is mixed. As examples:
•In the NutriNet-Santé cohort study, which followed approximately 103,300 patients for over 900,000 person/years, total NNS intake was associated with an increased risk of CVD (hazard ratio [HR] 1.09, 95% CI 1.01-1.18), with the highest incidence seen among higher consumers [78]. 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.
•In the Framingham Heart Study Offspring cohort, almost 3000 individuals over age 45 years and almost 1500 individuals over age 60 years underwent regular dietary assessments and were followed 10 years for incident stroke and dementia respectively [79]. Consumption of ≥1 artificially sweetened soft drink per day was associated with an increased incidence of ischemic stroke after adjustment for cardiovascular risk factors (2.58, 95% CI 1.21-5.57). There was no association with dementia.
•In the Women's Health Initiative, a retrospective cohort study including almost 60,000 post-menopausal women with no CVD at baseline, participants were followed for an average of 8.7 years [80]. Compared with infrequent consumption of diet drinks (zero to three per month), consumption of ≥2 diet drinks per day was associated with a higher risk of major cardiovascular events, CVD mortality, and overall mortality after adjustment for CVD risk factors (HR 1.3, 95% CI 1.1-1.5; HR 1.5, 95% CI 1.03-2.3; and HR 1.3, 95% CI 1.04-1.5, respectively). Among this cohort, at 11.9 years, the association between high consumption of ASBs and cardiovascular events (eg, ischemic stroke, coronary heart disease, and all-cause mortality) persisted [81].
•In the Health Professionals Follow-Up Study, a prospective cohort study including approximately 43,000 men followed for 22 years, consumption of ASBs was not associated with an increased incidence of coronary heart disease or adverse changes in serum lipids [82].
●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 [83], and others showing, among individuals who are overweight and with obesity, a reduction in intrahepatic fat with substitution of ASBs for sugar-sweetened beverages [84].
●Pregnancy and lactation – 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'.)
●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 [85-87]. Sucrose-sweetened mixers delay gastric emptying in parallel to carbohydrate content, thus decreasing alcohol absorption in comparison to 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 [88-91]. (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) [92], from those that are derived from plants that can elicit hypersensitivity reactions (eg, stevia) [93,94], and from erythritol [95]. (See "Allergic and asthmatic reactions to food additives".)
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 non-nutritive sweeteners (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 [96-107]. Evidence suggests that NNS-induced dysbiosis causes intestinal barrier alteration, chronic inflammatory response, and abnormal immunological activation, which may contribute to the onset of inflammatory bowel disease [108]. 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 [109]. (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 [104]. 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 [110]. Acclimation to this sweetness can result in upregulation of taste receptors and may dampen satiation signaling due to increased glucagon-like peptide 1 (GLP-1) production [111]. 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 [112]. 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 [113,114]. (See "Late complications of bariatric surgical operations", section on 'Dumping syndrome'.)
OTHER CONSIDERATIONS — The widespread use of non-nutritive sweeteners (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 [115]. Monitoring of these environmental risks as well as the search for methods of biodegradation is ongoing [116].
●Toxicity to canines – Xylitol (and to a lesser extent the other polyols) are highly toxic to canines [117]. 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 [118].
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 – Non-nutritive 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 – The consumption of products containing NNS may have health effects, including favorable effects (eg, dental caries) and possibly negative effects (eg, weight, glycemia, bowel function). 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.)
