Sugar Alternatives and Their Effects on Health

Sala Horowitz, PhD

Much attention has been focused on high consumption, in the United States, of sugar-sweetened foods and beverages (an average of 22 teaspoons per day)1 and their deleterious effects on health. This article reviews issues, professional position statements, and research relating to the classification, use, and health effects of alternative natural and artificial sweeteners. purified form of stevia (Stevia rebaudiana), from a plant native to South America. Prior to their approval for use as food additives in 2008 by the FDA, highly refined stevia preparations were allowed to be sold only as dietary supplements because of safety concerns about the effects of whole-leaf or crude stevia extracts.4 (See Table 1.5,6)

Sweeteners Many Guises

Product labeling sometimes makes it difficult to discern whether or not foods and beverages contain sugar (sucrose) or added natural or artificial sweeteners. Sweeteners many aliases include: cane sugar; evaporated cane sugar; brown sugar; raw sugar; crystalline fructose; glucose; high-fructose corn syrup; malt syrup; maltose; molasses; honey; and agave (Agave spp.) nectar. Labels may also list sugar alcohols (also called polyols), which include erythritol, isomalt, lactitol, maltitol, mannitol, sorbitol, and xylitol, as well as artificial low or noncaloric sugar substitutes, such as aspartame, sucralose, and acesulfame potassium (acesulfame K). According to the regulations of the United States Food and Drug Administration (FDA), a product may be labeled sugar-free if it contains < 0.5 sugars per Reference Amounts Customarily Consumed (RACC) and per labeled serving.2

Classification by Glycemic Index

High glycemic-index foods elevate blood glucose and insulin levels, and stimulate lipoprotein lipase and adipose tissue fat storage.7 The glycemic index for sweeteners is calculated as a function of the type and amount of carbohydrates present and the presence of other substances (e.g., soluble fibers) that slow the metabolism of carbohydrates. Tabulated for its effect on blood glucose, glucose receives the reference rating of 100, while the sugar alcohol sucralose (a mixture of sucralose, dextrose, and maltodextrin, commercially available as Splenda; Tate & Lyle, London, UK), for example, is rated as 0. Honey ranks in the midrange with an index of 50.8 (See Table 2.7)

Position Statements on Non-Nutritive Sweeteners

Given the accruing evidence concerning sugars negative effects on healthincluding contributing to obesity, diabetes, heart disease, and possibly cancerthe food industry has been striving to meet the demand for noncaloric substitutes for sugar that do not contribute to these health problems. Because such sweeteners tend to be considerably sweeter than table sugar, they are known as intense sweeteners, and much smaller amounts are typically used. For example, neotame is approximately 700013,000 times sweeter than sugar.9 But debates concerning non-nutritive sweeteners safety and role in health have long marked the use of artificial sweeteners in diet foods and beverages. The position of the AcadDOI: 10.1089/act.2013.19102 MARY ANN LIEBERT, INC. VOL. 19 NO. 1 FEBRUARY 2013

Classification: Artificial or Natural?

Not only is it difficult to identify the presence and types of sweeteners from food labels, there is also the complex issue of whether products derived from naturally occurring substances should be classified as natural or artificial food additives. Artificial sweeteners are subject to regulation by the FDA as food additives, whereas natural products that are generally regarded as safe (GRAS) are not regulated by the FDA. For example, sugar alcoholsGRASare carbohydrates that occur naturally in certain fruits and vegetables but are synthesized from other sources for commercial use.3 This distinction is also ambiguous in the case of rebaudioside A, a highly
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Table 1. FDA-Approved Non-Nutritive Sugar Substitutes

Sample Approval Sweetener brand name Company year Rebaudioside Truvia Cargill, Minneapolis, MN 2008 b The NutraSweet Company, 2002 Neotame Chicago, IL Sucralose Splenda Tate & Lyle, London, UK 1998 Acesulfame K Sunett Nutrinova/Celanese, 1998 Irving, TX Aspartame NutraSweet The NutraSweet Company 1981 Saccharin SweetN Low Cumberland Packing Approved for Corp., Brooklyn, NY use with a warning label in 1958; the label was repealed in 20006 Comments Derived from steviaa extract Derived from aspartame Derived from sugar Approximately 200 times sweeter than sugar Aspartame is metabolized into phenylalanine &, therefore, should not be used by people with phenylketonuria (PKU), a condition in which the amino acid cannot be broken down.5 Although animal studies found a link between saccharin & bladder cancer, overall evidence indicates that saccharin is safe at human levels of consumption

Source: International Food Information Council Foundation. Stevia Sweeteners: Another Low-Calorie Option. Food Insight, May 2009. Online document at: www.foodinsight.org/ Portals/0/pdf/May-09-Food-Insight.pdf Accessed October 9, 2012. aLatin binomial: Stevia rebaudiana. bNeotame is known by the name of the molecule.

emy of Nutrition and Dietetics is that a consumer can safely consume nutritive and non-nutritive sweeteners as part of an eating plan guided by the current federal nutrition recommendations, individual health goals, and preferences.10 A recent statement issued jointly by the American Heart Association (AHA) and the American Diabetes Association (ADA)11 suggests that non-nutritive sweeteners may have a useful role as an aid for reaching and maintaining healthy weight, which is aimed at reducing risk factors for obesity, heart disease, and other diseases, as well as glucose control for people with diabetes. However, these organizations also issued the caveat that this is the case only when such sweeteners are consumed in moderation; are not used to displace nutritious, lower-calorie foods and beverages; and intake is in the context of a healthy lifestyle. Christopher Gardner, PhD, associate professor of medicine at Stanford University in Palo Alto, California, and his coauthors wrote: Research, to date, is inconclusive whether using non-nutritive sweeteners to displace caloric sweeteners, such as added sugars, can reduce carbohydrate intake. . ., caloric intake or body weight, benefits appetite or lower other risk factors associated with diabetes and heart disease in the long run.11 The AHA recommends no more than 100 calories a day from added sugars for most women, and 150 calories daily for men.11

The FDA has established an acceptable daily intake (ADI) for each non-nutritive sweetener. But artificial sweeteners, just like sugar, may contribute to a pattern of life-long unhealthful eating habits by promoting a craving for sweetened foods and beverages over healthier ones.12 The American Academy of Pediatrics has made no official recommendations regarding the use of noncaloric sweeteners because of the limited number of studies that have been conducted with children.13 A couple of recent randomized studies support substitution of noncaloric beverages for sugary drinks to help weight control in children. One study involved 641 primarily normalweight children ranging in age from 4 years and 10 months to 11 years and 11 months. These participants were randomly assigned to drink 8 oz per day of either a sugar-containing drink or a similar masked sugar-free, artificially sweetened replacement. At the end of the 18-month trial, modest weight reduction occurred in the children who drank the noncaloric beverage.14 In another trial, 224 overweight and obese adolescents who regularly consumed sugar-sweetened beverages were randomly assigned to experimental and control groups. The experimental groups intervention consisted of receiving home delivery of noncaloric beverages for 1 year, with follow-up for an additional year. At the end of the first year, modest but significant differences were observed in body mass index (BMI) between the groupsparticularly among a small subset of obese Hispanic participants. However, this significant difference in BMI was not sustained at 2 years.15

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Non-Nutritive Sweeteners Can Contribute to Obesity and Disease

Notwithstanding the joint AHAADA statement and the research cited above, some experimental and clinical studies provide evidence that drinks and foods containing artificial sweeteners can contribute to obesity and its consequences. An animal model demonstrated that saccharin reduced the ability of sweet tastes to evoke physiologic responses that normally regulate the bodys energy balance. Consequently, the animals had increased food intake, body weight gain, accumulation of body fat, and weaker caloric compensationall of which are associated with obesity, metabolic disorders, and cardiovascular diseasecompared to consumption of foods and fluids containing glucose.16 Similarly, feeding aspartame to diabetes-prone mice for 3 months raised their fasting serum glucose levels.17 Clinical trials have indicated a similar dissociation between sweet taste cues and normal physiologic responses with habitual diet-product consumption. Using functional magnetic resonance imaging (fMRI), a study compared the brains responses to sucrose and sucralose in 12 healthy women. Although the women could not tell the difference between water sweetened with 10% sugar and water sweetened with matched sucralose, the fMRI showed that their brains reward centers were activated to a greater degree by the sugar-sweetened water than by the sucralose-sweetened water.18 In another fMRI study, 24 healthy subjects were randomly assigned to drink small amounts of either saccharin- or sugarsweetened water given in random order following a 12-hour fast. Half of these participants had reported being regular drinkers of sugar-free diet sodas, whereas the other subjects had said that they rarely consumed such drinks. fMRIs of these participants showed that brain regions that were activated when subjects made judgments about the sweeteners pleasurable taste and intensity differed according to the subjects usual consumption patterns of diet drinks. Compared to subjects who did not usually drink diet soda, regular diet-soda drinkers had greater activation in response to both saccharin and sugar in their reward-processing regions of their brains.19 In this study, increased intake of diet soda was strongly associated with diminished activation of a food-motivation and reward-processing area (the caudate head); this link has been correlated with elevated risk of obesity. The researchers concluded that this outcome suggests that nonnutritive sweeteners send confusing feedback to the brain regarding reward processing of sweet tastes, which results in impaired regulation of satiety.19 From the San Antonio Longitudinal Study of Aging (SALSA), data for 474 participants, ages 6574, were assessed for a relationship between consumption of diet soft drinks and long-term change in waist circumference. Participants were assessed at baseline and at 3 times over an average follow-up period of 9.5 years. Overall, the dietdrink users experienced a 70% greater increase in waist circumference, compared to nonconsumers. Frequent users,

Table 2. Glycemic Index for Selected Sweeteners

Sweetener Glucose Sucrose Honey Coconut palma sugar Brown riceb syrup Fructose Agavec syrup Xylitol Erythritol Inulin Brazzeind Glycyrrhizine Luo Han Guo (monk fruit)f Miraculin Steviag Acesulfame K Aspartame Neotame Sucralose Type Sugar Processed sugar Natural sugar Natural sugar Modified sugar Sugar Modified sugar Sugar alcohol Sugar alcohol Sugar fiber Natural sweetener Natural sweetener Natural sweetener Natural sweetener Natural sweetener Artificial sweetener Artificial sweetener Artificial sweetener Artificial sweetener Glycemic index 100 65 50 35 25 25 15 12 1 1 0 0 0 0 0 0 0 0 0

Adapted from ref. 7. aDerived from the coconut palm (Cocos nucifera). bDerived from rice (Orzia spp.). cLatin binomial: Agave spp. dA sweet protein derived from oubli berry (Pentadiplandra brazzeana). eDerived from licorice (Glycyrrhiza spp.) fLatin binomial: Siraitia grosvenorii. gLatin binomial: Stevia rebaudiana.

who reported that they consumed 2 or more diet soft drinks per day, had waist circumference increases that were 500% greater than those of nonusers. Helen P. Hazuda, PhD, a clinical epidemiology professor in the School of Medicine at the University of Texas Health Science Center in San Antonio, commented: Data from this and other prospective studies suggest that the promotion of diet sodas and artificial sweeteners may be ill-advised. They may be free of calories but not of consequences.20 When examining data from another longitudinal study the San Antonio Heart Studya research team found an association between artificially sweetened beverages and longterm weight gain in 3682 of the studys surviving participants 78 years later. A significant positive, doseresponse relationship was found between baseline consumption and incidence of overweight and obesity. Consuming > 21 such drinks per week (versus 0 drinks per week) was associated with nearly double the risk of being overweight (BMI > 25) or obese (BMI > 30) among 1250 normal-weight individuals at baseline, and double the risk of obesity among 2571 individuals with baseline BMIs > 25. These findings bring into question whether artificially sweetened drinks might
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unintentionally be fuelingrather than combatingthe obesity epidemic.21 A systematic review of the literature found no strong causal link between artificial sweetener use and weight gain and other metabolic effects in children. However, the researchers concluded that the potential contribution of these common food additives to the global rise in pediatric obesity and diabetes should be considered.22

ommends adding a teaspoon of inulin to a food or beverage as a dietary supplement. Dr. Sahelian notes that very high doses can lead to gastrointestinal (GI) distress (e.g., significant intestinal flatus production).28 Sugar Alcohols Sugar alcohols comprise a type of reduced-calorie sweetener that is commonly found in many products, such as certain chewing gums and desserts labeled no sugar added or sugar-free. Although some sugar alcohols occur naturally, commercially, they are either extracted from these sources or synthesized from other sources. (See Sources of Sugar Alcohols.29) Sugar alcoholswhich include sorbitol, mannitol, maltitol, erythritol, and xylitolhave fewer calories than sugar and produce less of an effect on blood-glucose levels than sucrose does. Nonetheless, the American Diabetes Association advises reading labels carefully for people who wish to control glucose levels and weight, because many food products containing sugar alcohols may still contain significant amounts of carbohydrates, fat, and total calories.30 One advantage of sugar alcohols, compared to sugar, is that they are noncariogenic (i.e., they do not contribute to dental cavities, because polyols are poorly fermented by oral flora).31 However, this property of sugar alcohols can produce a laxative effect when consumed in large amounts, because of poor absorption by the body. Isomaltulose is a newer sugar alcohol being developed; it is claimed that this product will not produce GI symptoms.32 Stevia The leaves of the stevia planta small perennial shrub also known as sweet herbhave long been used as a natural sweetener and herbal medicine in the plants native South America. In Brazil, stevia tea and capsules are officially approved for treating diabetes.33 Previously only available as dietary supplements in the United Statesbecause of theoretical concerns about effects on blood-sugar control, renal function, and human cardiovascular and reproductive systemshighly refined preparations of steviol glycosides are now approved for use as sugar-substitute food additives.4 In a 2-year randomized study of patients with mild essential hypertension (87 men, 87 women, ages 2075), those who took capsules containing 500 mg of stevioside powder 3 times daily had significant decreases in systolic and diastolic blood pressure, compared to the placebo group. Quality of life also improved in the stevioside users, and no significant adverse effects were noted.34 A systematic review of stevia studies also found positive results with respect to glucose tolerance and response.35 In one of these studies, stevia preloads significantly reduced postprandial glucose and insulin levels, compared to both sucrose and aspartame preloads.36 In vitro research showed that the phenolic content of stevia-leaf extracts has antioxidant effects,37 activates a receptor involved in mechanisms that improve lipid profile,38 and controls regulation of cells

Natural Sweeteners
Natural sweeteners are derived from plants and other natural products. Agave syrup or nectar, stevia, and honey are widely known ones. Two that are less widely known, but gaining in popularity, are tagatose and Luo Han Guo (monk fruit; Siraitia grosvenorii). Honey As one of the most ancient of sweetening agents, honey may be considered a functional food, because it has beneficial properties in addition to its sweetness. Composed primarily of fructose and glucose, honey also contains small and trace amounts of proteins, vitamins, minerals, trace elements, amino acids, enzymes, and polyphenols.23 These constituents have antioxidant, prebiotic, antimicrobial, and immunomodulating properties.24 In a study, rats who were fed honey, compared to those fed a diet with sucrose, had less weight gain, adiposity, and serum concentrations of triglycerides and leptin.25 Agave Syrup or Nectar Agave nectar or syrup is a sweetener produced primarily from several species of agave, primarily Agave tequilana (blue agave), which is grown in Mexico. For vegans who do not consume animal products, agave is a good alternative to honey. Agave has a low glycemic index, compared to sugar, but consumers should be aware that agaves concentrated natural fructose content (as inulin) may range from 90% to 55%, depending on processing. Highly processed agave syrup is similar to high-fructose corn syrup in content and unhealthy consequences.26 Inulin/FOS Inulin and fructo-oligosaccharides (FOS) occur naturally in many foods of vegetable origin, such as onions, garlic, asparagus, leeks, and Jerusalem artichokes. FOS can be produced from inulin extracted from chicory root (Chicorium intybus). These nondigestible carbohydrates are classified as fructans. They have been found to be effective prebiotics, because inulin fiber reaches the colon largely unabsorbed, where the fiber is fermented. In vitro and in vivo studies have established that adding inulin or FOS to the diet results in an increase in beneficial Bifidobacteria.27 Ray Sahelian, MDa Los Angeles, Californiabased physician, medical writer, and naturalsupplements supplierrec-

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normal apoptosis process.39 Stevia is considered particularly beneficial for persons with diabetes, people who are weightconscious, and children.40 Tagatose Tagatose is a naturally occurring monosaccharide, similar in structure to fructose, found in small amounts in dairy products. Produced from lactose, tagatose was approved in 2003 by the FDA as a general-purpose sweetener. Tagatose is also approved in other countries, including Australia and New Zealand. With a low glycemic index, compared to sugar, tagatose is being studied as a potential antiobesity and antihyperglycemic agent for patients with type 2 diabetes. In a pilot study of 8 adults with type 2 diabetes, patients took 15 g of oral d-tagatose 3 times daily with meals for 1 year. Tagatose evoked very low increases in postprandial blood glucose and insulin levels in these participants, and they had significant improvements in body weight and lipid profiles (raised high-density lipoprotein cholesterol).41 The minimal impact of tagatose on blood glucose and insulin is a result of tagatoses low (15%20%) absorption by the small intestine. The remaining major fraction is fermented by the indigenous microflora into short-chain fatty acids, most of which are absorbed and metabolized by colonocytes. Like other low-digestible carbohydrates, tagatose may have a laxative effect in some individuals.42 Tagatose may also act through hepatic inhibition of glycogenolysis (splitting of glycogen in the liver).43 Tagatose has also shown antioxidant and prebiotic properties.44,45 Persons who have fructose-metabolism disorders and who are deficient in the sucrose-isomaltase enzyme should avoid tagatose as well as the sugar substitutes sorbitol and isomaltulose.46 Monk Fruit Luo Han Guo, also called monk fruit for its historic cultivation by monks in China, refers to the sweet fruit of Siraitia grosvenorii, a member of the Cucurbitaceae family. Native to China, the extract of the small gourdlike fruit has long been used as a sweetener and remedy in Traditional Chinese Medicine.47 A product composed of monk fruit extract combined with erythritol, sugar, and molasses has recently been added to the list of sweeteners that the FDA considers GRAS. The product has recently become available in the United States as NectresseTM (McNeil Nutritionals, LLC, Fort Washington, Pennsylvania). In a meal plan for patients with diabetes, up to 1 teaspoon of Nectresse is considered a free food (i.e., a food containing < 20 calories and equal to < 5 g of carbohydrates per serving).48 Miraculin The small red berry of Richadella dulcifica (cited as Synsepalum dulcificum Daniell by one source),49 an evergreen shrub or tree grown in west Africa, has the unusual property of making many foods taste sweet, hence, the plants common name of

Sources of Sugar Alcohols

The following provides information about where sugar alcohols are derived from: MannitolAsparagus, carrots, olives, pineapples, sweet potatoes, celery, mushrooms, onions, pumpkins, strawberries; extracted from seaweed for use in food manufacturinga,b XylitolMushrooms, some cerealsb; low levels in raspberries and plums; first produced for food use from birch trees; produced commercially from corn and sugar-cane stalksc SorbitolOccurs naturally in apples, apricots, pears, prunes, cherriesd; produced synthetically from glucose derived from cornstarche LactitolManufactured from lactose (milk sugar)f IsomaltFructose portion of sucrose converted into sorbitol and mannitolg ErythritolOccurs naturally in pears, grapes, melons, mushrooms, and fermentation-derived foods, such as wine, cheese and soy sauceh; manufactured from cornstarchi Because they are not completely digested in the small intestine, sugar alcohols can cause diarrhea and other gastrointestinal symptoms in some people.29
www.ynhh.org/about-us/sugar_alcohol.aspx Accessed November 1, 2012; bThe Sugar Association. Sugar Alcohols: Online document at: www.sugar.org/othersweeteners/sugar-alcohols.html Accessed November 1, 2012; cWalters DE. All About Sweeteners: Xylitol. Online document at: www.sweetenerbook.com/xy litol.html Accessed November 1, 2012; dFoodStandards Australia New Zealand. NUTTAB 2010 Online Searchable Database. Foods That Contain Sorbitol. Online document at: www.foodstandards.gov.au/consumerinformation/nuttab2010/ nuttab2010onlinesearchabledatabase/onlineversion.cfm?&action=nutrientFoo ds&category=Proximates&nutrientID=SORB Accessed November 1, 2012; eThe Sugar Association. Sugar Alcohols: What Is Sorbitol? Online document at: www. sugar.org/other-sweeteners/sugar-alcohols.html#sorbitol Accessed November 20, 2012; fSource: European Association of Polyol Producers. Lactitol. Online document at: www.polyols-eu.com/lactitol.php Accessed November 1, 2012; gThe Sugar Association. Sugar Alcohols: What Is Isomalt? Online document at: www.sugar.org/other-sweeteners/sugar-alcohols.html#isomalt Accessed November 20, 2012; hCalorie Control Council. Erythritol. Online document at: www. caloriecontrol.org/sweeteners-and-lite/polyols/erythritol Accessed November 20, 2012; iThe Sugar Association. Sugar Alcohols: What Is Erythritol? Online document at: www.sugar.org/other-sweeteners/sugar-alcohols.html#erythritol Accessed November 20, 2012.
aYale-New Haven Hospital. Eat Any Sugar Alcohol Lately? Online document at:

miracle fruit or miracle berry. Researchers recently identified the mechanism of action for how miraculina protein isolated from the berriessensitizes the tongues sweet sensors to acidic flavors.50 Miraculin is one of the few plant proteins that serves this role instead of plant sugars. FDA approval of miraculins use in food is unlikely in the near future because the novel proteins mechanism of action requires further study and because of the impracticality of producing large quantities of this protein for use.51 Glycyrrhizin The roots and rhizomes of licorice (Glycyrrhiza spp.) have long been used as natural sweeteners and herbal medicines.52 According to James Pendleton, ND, a naturopathic physician with practices in Seattle, Washington, and in New Smyrna Beach, Florida, the extract glycyrrhizin tastes ~ 50 times sweeter than sucrose, with a slower onset and longer duration.53 Because of a potential for causing hypertension and
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hypokalemia (lack of potassium in the blood), the European Commission recommends that the daily dose of glycyrrhizin not exceed 100 mg.54 Other Natural Sweeteners Brazzein is a sweet protein derived from the berry of the oubli (Pentadiplandra brazzeana Baillon), a climbing West African plant long used as a food source in the region. Brazzein was first synthesized as a sugar alternative in 1994 by researchers but is not yet available commercially.55 Other natural sweeteners include maple syrup (which has a sugar content of 60% and contains manganese and zinc),56 coconut palm (Cocos nucifera) sugar (high in potassium),57 and yacon syrup (from the yacon plant, Smallanthus sonchifolius, which is native to Peru and which contains at least 30% FOS).58

5. American Diabetes Association. Size Up Your Sweetener Options. Diabetes Forecast (magazine), July 2009. Online document at: www.forecast.diabetes. org/magazine/foodthought/size-your-sweetener-options Accessed September 21, 2012. 6. National Cancer Institute. Artificial Sweeteners and Cancer. Online document at: www.cancer.gov/cancertopics/factsheet/Risk/artificial-sweeteners Accessed October 8, 2012.

7. Glycemic Research Institute. Glycemic Index Defined. Online document at: www.glycemic.com/GlycemicIndex-LoadDefined.htm Accessed September 20, 2012.

8. Glycemic Index For Sweeteners. Online document at: www.sugar-andsweetenerguide.com/glycemic-index-for-sweeteners.html Accessed September 19, 2012.

9. Calorie Control Council. Neotame. Online document at: www.caloriecontrol.org/sweeteners-and-lite/sugar-substitutes/neotame Accessed October 7, 2012. 10. Fitch C, Keim KS; Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: Use of nutritive and nonnutritive sweeteners. J Acad Nutr Diet 2012;112:739758.

Conclusion
There is some evidence that noncaloric alternatives to sugarsweetened beverages can be beneficial for weight-reduction interventions in children, but other studies suggest that artificial

11. Gardner C, Wylie-Rosett J, Gidding SS, et al. Nonnutritive sweeteners: Current use and health perspectives. A scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care 2012;35:17981808. 12. Harvard Medical School Family Health Guide. Added Sweeteners. Online document at: www.health.harvard.edu/fhg/updates/Added-sweeteners. shtml Accessed September 21 2012.

There is some evidence that noncaloric sweeteners can be beneficial for weight reduction in children.
sweeteners may send confusing messages to the brain regarding energy consumption and satiety. In any case, clinicians should continue to advise patients that a diet in which either sugar-sweetened or sugar-free foods play a major role can result in weight gain, obesity, diabetes, and other health problems. Further rigorous research is needed to clarify the contribution of sweetenerswhether sugar or lowcalorie alternativesto such complex health problems; this research is also needed to inform health strategies. n References
1. Johnson RK, Appel LJ, Brands M, et al. Dietary sugars intake and cardiovascular health: A scientific statement from the American Heart Association. Circulation 2009;120:10111120. 2. U.S. Food and Drug Administration. Food: 9. Appendix A: Definitions of Nutrient Content Claims. October 2009. Online document at: www.fda.gov/Food/ GuidanceComplianceRegulatoryInformation/GuidanceDocuments/FoodLabelingNutrition/FoodLabelingGuide/ucm064911.htm Accessed October 6, 2012.

13. American Academy of Pediatrics. Healthy Living: Sweeteners and Sugar Substitutes. Online document at: www.healthychildren.org/English/healthyliving/nutrition/pages/Sweeteners-and-Sugar-Substitutes.aspx Accessed September 21, 2012.

14. de Ruyter JC, Olthof MR, Seidell JC, Katan MB. A trial of sugar-free or sugar-sweetened beverages and body weight in children. N Engl J Med 2012; 367:13971406. 15. Ebbeling CB, Feldman HA, Chomitz VR, et al. A randomized trial of sugar-free or sugar sweetened beverages and adolescent body weight. N Engl J Med 2012;367:14071416.

16. Swithers SE, Martin AA, Davidson TL. High-intensity sweeteners and energy balance. Physiol Behav 2010;100:5562.

17. Fowler SP, Halade GV, Fernandes G. Aspartame Consumption is Associated with Elevated Fasting Glucose in Diabetes-Prone Mice. Abstract 2011; abstract No. 788-P. Online document at: http://professional.diabetes.org/Ab stracts_Display.aspx?=1&CID=87338 Accessed September 22, 2012. 18. Frank GK, Oberndorfer TA, Simmons AN, et al. Sucrose activates human taste pathways differently from artificial sweetener. NeuroImage 2008;39:15591569. 19. Green E, Murphy C. Altered processing of sweet taste in the brain of diet soda drinkers. Physiol Behav 2012;107:560567.

20. University of Texas Health Science Center, San Antonio. Related Studies Point to the Illusion of the Artificial. News Release; June 27, 2011. Online document at: www.uthscsa.edu/hscnews/singleformat2.asp?newID=3861 Accessed September 22, 2012. 21. Fowler SP, Williams K, Resendez RG, et al. Fueling the obesity epidemic? Artificially sweetened beverage use and long-term weight gain. Obesity (Silver Spring) 2008;16:18941900. 22. Brown RJ, de Banate MA, Rother KI. Artificial sweeteners: A systematic review of metabolic effects in youth. Int J Pediatr Obes 2010;5:305312.

3. Utah State University Cooperative Extension. Food and Nutrition: Sugar Substitutes: Artificial Sweeteners and Sugar Alcohols. Online document at: http://extension.usu.edu/files/publications/publication/FN_General_201201pr.pdf Accessed October 4, 2012. 4. Zeratsky K. [Answer to Question] Stevia: Can It Help With Weight Control? Online document at: www.mayoclinic.com/health/stevia/AN01733 Accessed September 7, 2012.

23. Bogdanov S, Jurendic T, Sieber R, Gallmann P. Honey for nutrition and health: A review. J Am Coll Nutr 2008;27:677689.

24. Bogdanov S. Nutritional and functional properties of honey [in Russian]. Vopr Pitan 2010;79:413. 25. Nemoseck TM, Carmody EG, Furchner-Evanson A, et al. Honey promotes lower weight gain, adiposity, and triglycerides than sucrose in rats. Nutr Res 2011;31:5560.

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26. Zelman KM. The Truth About Agave: Is This Natural Sweetener Healthier than Table Sugar? Online document at: www.webmd.com/diet/ features/the-truth-about-agave Accessed September 6, 2012.

43. Espinosa I, Fogelfeld L. Tagatose: From a sweetener to a new diabetic medication? Expert Opin Investig Drugs 2010;19:285294.

27. Rossi M, Corradini C, Amaretti A, et al. Fermentation of fructooligosaccharides and inulin by bifidobacteria: A comparative study of pure and fecal cultures. Appl Environ Microbiol 2005;71:61506158.

44. Lu Y, Levin GV, Donner TW. Tagatose, a new antidiabetic and obesity control drug. Diabetes Obes Metab 2008;10:109134.

28. Sahelian R. Inulin Fiber Supplement Health Benefit. Online document at: www.raysahelian.com/inulin.html Accessed October 3, 2012.

45. Grant LD, Bell LN. Physical and chemical stability of tagatose powder. J Food Sci 2012;77:C308C313.

29. Appleton N, Jacobs GN. Killer Colas: The Hard Truth About Soft Drinks. New York: Square One Publishers, 2011. 30. American Diabetes Association. Sugar Alcohols: Reduced Calorie Sweeteners. Online document at: www.diabetes.org/food-and-fitness/food/whatcan-i-eat/sugar-alcohols.html Accessed November 1, 2012.

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