Nonnutritive Sweeteners: Current Use and Health Perspectives
2012; Lippincott Williams & Wilkins; Volume: 126; Issue: 4 Linguagem: Inglês
10.1161/cir.0b013e31825c42ee
ISSN1524-4539
AutoresChristopher D. Gardner, Judith Wylie‐Rosett, Samuel S. Gidding, Lyn M. Steffen, Rachel K. Johnson, Diane Reader, Alice H. Lichtenstein,
Tópico(s)Diet, Metabolism, and Disease
ResumoHomeCirculationVol. 126, No. 4Nonnutritive Sweeteners: Current Use and Health Perspectives Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBNonnutritive Sweeteners: Current Use and Health PerspectivesA Scientific Statement From the American Heart Association and the American Diabetes Association Christopher Gardner, PhD, Chair, Judith Wylie-Rosett, EdD, RD, Co-Chair, Samuel S. Gidding, MD, FAHA, Lyn M. Steffen, PhD, MPH, RD, FAHA, Rachel K. Johnson, PhD, MPH, RD, Diane Reader, RD, CDE and Alice H. Lichtenstein, DSc, FAHA Christopher GardnerChristopher Gardner , Judith Wylie-RosettJudith Wylie-Rosett , Samuel S. GiddingSamuel S. Gidding , Lyn M. SteffenLyn M. Steffen , Rachel K. JohnsonRachel K. Johnson , Diane ReaderDiane Reader and Alice H. LichtensteinAlice H. Lichtenstein and on behalf of the American Heart Association Nutrition Committee of the Council on Nutrition, Physical Activity and Metabolism, Council on Arteriosclerosis, Thrombosis and Vascular Biology, Council on Cardiovascular Disease in the Young, and the American Diabetes Association Originally published9 Jul 2012https://doi.org/10.1161/CIR.0b013e31825c42eeCirculation. 2012;126:509–519Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2012: Previous Version 1 IntroductionA 2009 American Heart Association scientific statement titled "Dietary Sugars Intake and Cardiovascular Health"1 concluded that current intake of added sugars among Americans greatly exceeds discretionary calorie allowances based on the 2005 US Dietary Guidelines.2 For this reason, the American Heart Association Nutrition Committee recommended population-wide reductions in added sugars intake. The present statement from the American Heart Association and the American Diabetes Association addresses the potential role of nonnutritive sweeteners (NNS) in helping Americans to adhere to this recommendation in the context of current usage and health perspectives.By definition, NNS, otherwise referred to as very low-calorie sweeteners, artificial sweeteners, noncaloric sweeteners, and intense sweeteners, have a higher intensity of sweetness per gram than caloric sweeteners such as sucrose, corn syrups, and fruit juice concentrates. As a caloric sweetener replacement, they are added in smaller quantities; hence, they provide no or few calories. In our current food supply, NNS are widely used in thousands of beverages and other food products such as diet soft drinks, yogurts, desserts, and gum. Food manufacturers often use a blend of NNS or use a blend of sugar and NNS to improve the flavor acceptability of NNS. In developing this scientific statement, the writing group reviewed issues pertaining to NNS in the context of data on consumer attitudes, consumption patterns, appetite, hunger and energy intake, body weight, and components of cardiometabolic syndrome. The objective was to review the literature to determine whether there were adequate data to provide guidance for the use of NNS.The focus of the statement is on the 6 NNS that are described in Table 1. Aspartame, acesulfame-K, neotame, saccharin, and sucralose are regulated as food additives by the US Food and Drug Administration and therefore had to be approved as safe before being marketed. Regarding stevia, at this time, the US Food and Drug Administration has not made a determination as to the Generally Recognized As Safe status, but has issued no objection letters for a number of Generally Recognized As Safe notifications for stevia sweeteners (http://www.fda.gov/Food/FoodIngredientsPackaging/GenerallyRecognizedasSafeGRAS/GRASNotificationProgram/default.htm). Because all 6 of these NNS have current US Food and Drug Administration approval, issues related to safety of these compounds are not addressed. In addition, the review of the literature is primarily restricted to human studies in which noncaloric sweeteners are used as a replacement for caloric sweeteners.Table 1. Nonnutritive Sweeteners3–6Sweetener and Chemical StructureCommon Brand NamesADI*/JECFA Toxicology Monograph No. (Year)Year FDA ApprovedRepresentative Amount of Sweetener in 12-oz Soda,† mgNo. of Servings=to ADI for a 150 lb (68 kg) PersonAmount of Sweetener in a Packet (Equivalent to 2 tsp Sugar),‡ mgNo. of Packets=to ADI for 150 lb (68 kg) PersonAcesulfame-K Potassium 6-methyl-2,2-dioxo-oxathiazin-4-olateSweet One15 mg/kg bw 28 (1991)198840 (blended with aspartame)25, 12-oz servings5020Aspartame N-(l-α-Aspartyl)-l- phenylalanine, 1-methyl esterEqual NutraSweet40 mg/kg bw 15 (1980)198118714, 12-oz servings4068Neotame N-[N-(3,3-dimethylbutyl)-l-α-aspartyl]-l-phenylalanine 1-methyl esterNeotame2 mg/kg bw 52 (2004)2002Not in carbonated beverages…No consumer product…Saccharin 1,1-Dioxo-1,2-benzothiazol-3-oneSweet'N Low5 mg/kg bw 32 (1993)Before 19588 (blended with aspartame)42, 12-oz servings408.5Sucralose 1,6-Dichloro-1,6-dideoxy-β-d-fructofuranosyl-4-chloro-4-deoxy-α-d-galactopyranosideSplenda15 mg/kg bw 28 (1991)19996815, 12-oz servings1130Plant-Based Sweeteners§ Stevia (as stevia glucosides)Truvia PureVia Sweet Leaf4 mg/kg bw60 (2009)20081716, 12-oz servings930ADI indicates acceptable daily intake; JECFA, Joint Expert Commission on Food Additives of the World Health Organization and the Food and Agriculture Organization (http://www.codexalimentarius.net/web/jecfa.jsp); FDA, US Food and Drug Administration; tsp, teaspoon.*ADI is a measure of the amount of a specific substance in food or drinking water that can be ingested over a lifetime without an appreciable health risk. Measurement is usually expressed in milligrams of sweetener per kilogram of body weight (mg/kg bw). The amount is usually set at 1/100 of the maximum level at which no adverse effect was observed in animal experiments.†The amount of sweetener if the product is exclusively sweetened with 1 sweetener. Very frequently >1 sweetener is used in soda or other products. Usually this information is proprietary and is not available to the public; the exception is saccharin. The amount of saccharin must be listed in the ingredient list. The maximum amount is 12 mg/fluid ounce.‡One packet has the sweetness of 2 teaspoons of sugar. One packet of sweetener has 6000.9 Of the 6 available NNS, sucralose (found in 2500 products), acesulfame-K (found in 1103 products), and aspartame (found in 974 products) were the most popular.9 NNS are most commonly used in carbonated beverages.3 Estimates of consumption patterns are typically made by reporting amounts of beverage and food items containing NNS, rather than amounts of specific NNS consumed.Nationwide Food Consumption Survey, National Health and Nutrition Examination Survey, and US Department of Agriculture Economic Research Service DataMattes and Popkin3 examined the trends in consumption of foods and beverages with NNS among Americans aged ≥2 years by use of the US Department of Agriculture Nationwide Food Consumption Survey for 1965, 1977 to 1978, and 1989 to 1991 and the National Health and Nutrition Examination Survey (NHANES) for 1999 to 2000, 2001 to 2002, and 2003 to 2004. Consumption of NNS in both beverages and foods increased over time. The survey data indicate that, on any given day, 15% of the US population consumed NNS in 2003 to 2004 in comparison with 3% in 1965. The proportion of the population choosing beverages with NNS remained relatively stable between 1989 and 2004 (10.1% and 10.8%, respectively), whereas the proportion consuming NNS in foods increased from 3.2% to 5.8% during that time period.3 Notably, the increase in NNS products was not accompanied by a corresponding decrease in reported consumption of products sweetened with added sugars, which indirectly suggests that NNS are not being used to displace products sweetened with added sugars. This same pattern of parallel increases in both NNS products and products with added sugars has been reported elsewhere10,11 and is evident from per capita food availability data, as compiled by US Department of Agriculture Economic Research Service for regular versus diet soft drinks, with intake increasing primarily from 1980 to 1990 and then leveling off between 1990 and 2003 (Figure 1).Download figureDownload PowerPointFigure 1. Carbonated soft drinks, gallons per year per capita. US availability as determined by US Department of Agriculture Economic Research Service. http://www.ers.usda.gov/Data/FoodConsumption.One of the authors (L.M.S.) examined the prevalence of consuming NNS foods and beverages in children and adults with the use of data from NHANES 2007–2008. Dietary intake in NHANES was assessed by a 24-hour recall in-person interview, which presents a "snapshot" of foods and beverages consumed by NHANES participants on a given day. The most frequently reported and consumed NNS product was NNS beverages in comparison with intake of NNS foods or packets of artificial sweeteners among male and female children and adults in NHANES 2007–2008 (Figure 2; L.M. Steffen, unpublished data, 2011). After further examination of NNS beverage intake by age group, the prevalence of consumption of these beverages increased across age groups, especially among females (Figure 3; L.M. Steffen, unpublished data, 2011). In general, more adults were NNS beverage consumers than children or adolescents.Download figureDownload PowerPointFigure 2. Prevalence (%, SE) of nonnutritive sweetened beverage and food intake in the US population as determined by one 24-hour recall (National Health and Nutrition Examination Survey 2007–2008) among individuals. Sample sizes: for females and males aged ≤18 years, n=1781 and n=1911, respectively; and for females and males aged ≥19 years, n=2820 and n=2742, respectively.Download figureDownload PowerPointFigure 3. Prevalence (%, SE) of nonnutritive sweetened beverage intake among US children and adults as determined by one 24-hour recall (National Health and Nutrition Examination Survey 2007–2008) according to age group. The sample size of participation by age group for females was ages 1 to 3 (n=575), 4 to 8 (n=435), 9 to 13 (n=418), 14 to 18 (n=353), 19 to 30 (n=513), 31 to 50 (n=950), 51 to 70 (n=873), and >70 (n=484). The sample size of participation by age group for males was ages 1 to 3 (n=617), 4 to 8 (n=502), 9 to 13 (n=412), 14 to 18 (n=380), 19 to 30 (n=518), 31 to 50 (n=889), 51 to 70 (n=869), and >70 (n=466).Other Perspectives on NNS UsersDietary intake assessed by FFQ, as is common in observational cohort studies, provides an estimate of those who "ever" versus "never" use NNS-containing beverage or food items included in the questionnaire; this is a different perspective than that derived from 24-hour recall data as above. The prevalence of saccharin intake in 1980 (the only NNS available at that time) was assessed in a subset of the Nurses' Health Study (NHS) characterized as being free from major illnesses and other lifestyle factors that might modify weight gain. Intake was assessed by use of a 61-item FFQ completed by 31 940 women. The report indicated that the prevalence of saccharin users was 56%.12 In the Health Professionals Follow-up Study (HPFS), artificially sweetened beverage intake was assessed in 1986 and every 4 years after that during 20 years of follow-up with use of a 131-item FFQ.13 By use of a cumulative average over this time period, 54% of the men reported consuming artificially sweetened beverages at least 2 times per month. The San Antonio Heart Study enrolled a randomly selected sample from non-Hispanic white and Mexican American neighborhoods. Among 3682 participants who were examined first between 1979 and 1988 and then again 7 to 8 years later, 48% reported some consumption of NNS in beverages that included diet soft drinks, coffee, or tea. Consumption of NNS in food items was not assessed.14Appetite, Hunger, and Energy IntakeFor NNS-sweetened items to successfully contribute to reductions in calories from added sugars or other sources, they must also avoid causing compensatory energy intake immediately or later in the day. If choosing a diet soft drink over a regular calorie soft drink leads to a decrease of ≈100 kcal per 8-oz serving, but later in the day causes an alteration in appetite or hunger that results in an additional 50, 100, or 200 kcal of intake, the initial "calorie saving" effect would be altered or reversed. Or, if choosing a diet soft drink enables an individual to simultaneously justify eating a 150-calorie snack, the calorie savings from the NNS would also be negated.Mattes and Popkin3 critically examined the evidence for effects of NNS on compensatory appetite and food intake. The 8 potential mechanisms they reviewed are listed and briefly described in Table 2. The review concluded that the available evidence either refuted or was insufficient to refute or support each of these potential mechanisms or hypotheses for NNS increasing appetite, hunger, or energy intake.3Table 2. Potential Mechanisms of Effects of NNS on Compensatory Appetite and Food IntakePotential MechanismsDescriptionCephalic phase stimulationRefers to a phase of early gastric secretions when food is in the mouth but has not yet reached the stomach; NNS might affect hunger and appetite at this phase.Nutritive and osmotic effectsRefers to the possibility that the lower energy density and lower osmotic load of NNS versus caloric sweeteners could alter the rate of gastric emptying or other factors of digestion and absorption that might affect sensations of satiety.Gut peptide responseRefers to the effect dietary macronutrients have on gut peptides that signal satiety; if NNS were to diminish the release of these peptides relative to caloric sweeteners, it could theoretically result in lower satiety and increased energy intake.PalatabilityNNS are typically added to increase palatability, and palatability is assumed to stimulate hunger and/or reduce satiation/satiety, thus increasing intake.Informed use leading to overcompensationExpected energy savings attributed to the substitution of an NNS-containing product could lead to subsequent indulgence rationalized by the previous energy savings and then overcompensation.Loss of signal fidelitySensory properties signal information about the metabolic response required by consumption of the product. If the sensory cue of sweetness leads to inaccurate or inconsistent predictive power, energy regulation may be disrupted and could lead to positive energy balance from overconsumption triggered by this signaling.Activation of reward systemsRefers to the possibility that the enhanced palatability conferred by NNS could play a role in reward-motivated feeding, thus added caloric intake when a nonfood reward could be provided.Training the palate/learning to like the familiarRefers to the possibility that repeated exposure to NNS may perpetuate a preference for sweet items in the diet, including items sweetened with caloric sweeteners.A review by Mattes and Popkin3 concluded that the available evidence either refuted or was insufficient to refute or support each of these potential mechanisms or hypotheses for NNS increasing appetite, hunger, or energy intake.NNS indicates nonnutritive sweeteners.The complexity in attributing the extent to which NNS consumption is compensated for by intake of other foods is fraught with methodological challenges both in controlled feeding experiments and free-living trials. According to International Food Information Council Foundation research, <10% of Americans can accurately estimate the number of calories they should consume in a day. Consumer education on daily energy requirements is needed, and that products containing NNS may assist in weight control when used in place of full-calorie products, if not compensated for otherwise. Controlled feeding experiments might or might not show an impact of NNS on future caloric intake, but, by definition, these are not real-world situations. Conversely, in the real world, so many factors impact food choice that attributing caloric intake after NNS consumption uniquely to that consumption may also not be true and may be confounded particularly by reverse causality; that is, the previous NNS choice might be deliberate in anticipation of a known future exposure to higher caloric meal.Energy Intake CompensationVarious studies that have examined energy intake as a primary or secondary outcome have used designs that contrast beverages and foods made with caloric sweeteners versus NNS. In a meta-analysis of weight loss studies that tested the effectiveness of aspartame in reducing energy intake, data from 12 studies were pooled to address energy intake compensation.15 The weighted average of energy intake compensation in the ≈24 hours that followed aspartame intake was 32% (ie, 68% of the original energy deficit was uncompensated and was maintained through the subsequent period of intake). Of the 4 studies from the meta-analysis that used beverages alone, the compensation was just 15% for the subsequent 24 hours; that is, the data suggest there is less compensation in beverages than foods, resulting in a more effective net reduction in calories when replacing sweetened beverages with NNS beverages.15 The implication here is that anything <100% compensation results in a net reduction in 24-hour energy intake.One of the studies included in the meta-analysis involved 24 men and women who consumed 4 different beverages, each for 4 weeks, in a crossover design. Subsequent food intake was monitored. The beverages included a full caloric beverage (sucrose) versus an NNS beverage (aspartame), provided with either an orange or raspberry flavor. Data were collected at baseline and after 4 weeks of habituation.16 The investigators observed a significant lack of energy intake compensation over the course of the day among study participants when they were consuming the full caloric beverages relative to the NNS beverages. In another study, 21 overweight adults were assigned to consume 28% of their energy intake as sucrose, mostly as beverages. After 10 weeks, there was a significant increase in their energy intake, body weight, fat mass, and blood pressure.17 These effects were not observed in a similar group of 20 overweight adults who consumed NNS in place of the sucrose, but otherwise had a similar dietary intake composition in comparison with the other group.17 In a controlled feeding experiment that involved a preload snack containing sucrose (493 kcal), aspartame (290 kcal), or stevia (290 kcal), the energy intake of subsequent meals was similar; the energy intake for the combined preload snack and later meals combined was lower for the aspartame and stevia phases versus the sucrose phase (P=0.01).18 All of these studies, therefore, observed a net reduction in energy intake for NNS use relative to the comparison condition with sucrose.Not all such studies have observed a net reduction in overall energy intake when NNS were used instead of caloric sweeteners. A 4-week trial, providing either diet soft drinks (sweetened with aspartame) or regular calorie soft drinks resulted in similar total energy intake in healthy-weight adults of both sexes,19 and in overweight women, as well.20 Similarly, the results of a 25-week study conducted in adolescents suggested that normal-weight youth compensated for the energy reduction when consuming diet beverages. However, as evidence of the complexity of this issue, the same study reported that the use of NNS beverages did result in a net energy deficit in those adolescents in the highest body mass index (BMI) tertiles (a conclusion that should be tempered by awareness that the intervention group was counseled to replace sugar-sweetened beverages with diet beverages and/or water, making it difficult to differentiate the effects of NNS versus water).21Overall, the limited human studies literature in this area of NNS research suggests that compensation is an important factor to consider when assessing impact on energy intake over periods of ≥24 hours. Further studies are warranted to address some of the complexities inherent in this issue, including the potential impact of being informed versus naïve about the presence or absence of NNS in items being consumed. It is worth noting that, in preschool children, when energy intake is reduced by substitution of nutrient-dense, lower-calorie food choices instead of NNS (eg, fruits and vegetables), some energy intake compensation occurs, but net energy intake remains lower over several days.22,23Appetite, or Preference, for Sweet TasteExamination of the potential effects of NNS on appetite requires consideration of genetic and environmental factors that may regulate preference for intensity of sweet taste.24–26 One focus of such research concerns the metabolic/hormonal responses to both caloric sweeteners and NNS to determine whether these can be linked to mechanisms that promote future weight gain or other adverse physiological consequences. Sweet taste is mediated largely by a single receptor composed of the 2 subunits TAS1R2 and TAS1R3. Understanding how the polymorphism of this receptor gene affects preferences is important to understanding usage of NNS. Recent data in mice suggest that additional mechanisms may exist, but these have not been confirmed in humans.27 Newer animal research also suggests the possibility that sweet-taste receptors exist in the gut, triggering complex metabolic/hormonal responses to NNS. The impact of these receptors and their metabolic consequences on obesity and diabetes mellitus in humans is just beginning to be studied.28 Although ingestion of foods containing NNS may trigger a wide array of responses related to food absorption that may impact future food consumption,29 adverse effects related to these gut receptors have yet to be identified.30,31A preference for higher intensity of sweetness exists in humans in infancy, declines in adolescence in comparison with infancy, and then plateaus or slowly declines in young adulthood, and may or may not decline further in old age.32,33 There is significant interindividual variation in sweet- and bitter-taste preference, and this preference may be genetically determined.34–37 These genetic differences may impact preferences for both caloric sweeteners and NNS, which may also have a bitter-taste component. Although animal research suggests that sweet-taste preference can be conditioned through repeated exposure,38 preference for sweet taste in humans is more complex and involves many central receptor mechanisms, including but not limited to dopamine signaling.39 Critical factors such as food culture and social expectations may also have an impact.3 The presence of caloric sweeteners may also enhance taste acceptance.40Cardiovascular and Metabolic Health OutcomesThe potential effects of NNS on body weight, cardiometabolic variables, and diabetes mellitus/glycemic response were examined. The evidence considered was limited to prospective studies and controlled trials conducted in humans. For the controlled trials, primary emphasis was given to study designs that involved replacing caloric sweeteners with NNS. Prospective cohort studies were also considered, but cross-sectional data were not considered. Although NNS intake may precede and lead to changes in weight or metabolic variables, the opposite is also plausible (ie, individuals who become overweight/obese may seek out NNS items after becoming overweight/obese or being informed they have type 2 diabetes mellitus). Therefore, it is not possible to distinguish the temporal relationship between these by using cross-sectional studies, and, as will be discussed, it can be difficult to distinguish this relationship even in some prospective studies.Body WeightThe vast majority of data available related to NNS consumption and body weight has focused on creating an energy deficit by substituting NNS for sugars in the beverage component of the diet, with only a few intervention studies also targeting foods. Findings in both controlled intervention trials and prospective observational studies have been inconsistent.Controlled intervention trials have reported that use of products with NNS results in weight loss or has negligible effects on
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