What we know—and don’t—about non-nutritive sweeteners

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Applied Evidence

What we know—and don’t—about non-nutritive sweeteners

J Fam Pract. 2019 July;68(6):310-315

By

Joy Dugan, MPH, DHSc, PA-C

Jeff W. Chiu, DO

Jay H. Shubrook, DO, FAAFP, FACOFP

Clipper F. Young, PharmD, MPH, CDE, BC-ADM, BCGP

Here’s what’s known about the safety of these sweeteners and their effect on weight, appetite, and the risk for type 2 diabetes.

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PRACTICE RECOMMENDATIONS

› Advise patients who are trying to lose weight that non-nutritive sweeteners (NNSs) are not beneficial for weight loss. A

› Reassure patients that NNSs do not appear to cause, or increase the risk of, developing type 2 diabetes mellitus. A

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

References

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3. Additional information about high-intensity sweeteners permitted for use in food in the United States. US Food and Drug Administration Web site. https://www.fda.gov/food/food-additives-petitions/additional-information-about-high-intensity-sweeteners-permitted-use-food-united-states. Published February 8, 2018. Accessed July 15, 2019.

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9. 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;112:739-758.

10. Ng SW, Slining MM, Popkin BM. Use of caloric and non-caloric sweeteners in US consumer packaged foods, 2005-2009. J Acad Nutr Diet. 2012;112:1828-1834.

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12. Piernas C, Ng SW, Popkin B. Trends in purchases and intake of foods and beverages containing caloric and low-calorie sweeteners over the last decade in the United States. Pediatr Obes. 2013;8:294-306.

13. Sylvetsky AC, Welsh JA, Brown RJ, et al. Low-calorie sweetener consumption is increasing in the United States. Am J Clin Nutr. 2012;96:640-646.

14. Bleich SN, Wolfson JA, Vine S, et al. Diet-beverage consumption and caloric intake among US adults, overall and by body weight. Am J Public Health. 2014;104:e72-e78.

15. Drewnowski A, Rehm CD. Socio-demographic correlates and trends in low-calorie sweetener use among adults in the United States from 1999 to 2008. Eur J Clin Nutr. 2015;69:1035-1041.

16. Peters JC, Wyatt HR, Foster GD, et al. The effects of water and non-nutritive sweetened beverages on weight loss during a 12-week weight loss treatment program. Obesity 2014;22:1415-1421.

17. Peters JC, Wyatt HR, Foster GD, et al. The effects of water and non-nutritive sweetened beverages on weight loss during a 12-week weight loss treatment program. Obesity (Silver Spring). 2014;22:1415-1421.

18. Bellisle F, Drewnowski A. Intense sweeteners, energy intake and the control of body weight. Eur J Clin Nutr. 2007;61:691-700.

19. Malek AM, Hunt KJ, DellaValle DM, et al. Reported consumption of low-calorie sweetener in foods, beverages, and food and beverage additions by US adults: NHANES 2007-2012. Curr Dev Nutr. 2018;2:nzy054.

20. Sylvetsky AC, Figueroa J, Zimmerman T, et al. Consumption of low-calorie sweetened beverages is associated with higher total energy and sugar intake among children, NHANES 2011-2016. Pediatr Obes. 2019;2:e12535.

21. Fowler SPG. Low-calorie sweetener use and energy balance: results from experimental studies in animals, and large-scale prospective studies in humans. Physiol Behav. 2016;164(Pt B):517-523.

22. Azad MB, Abou-Setta AM, Chauhan BF, et al. Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. CMAJ. 2017;189: E929-E939.

23. Ruanpeng D, Thongprayoon C, Cheungpasitporn W, et al. Sugar and artificially-sweetened beverages linked to obesity: a systematic review and meta-analysis. QJM. 2017;110:513-520.

24. Blundell JE, Rogers PJ, Hill AJ. Uncoupling sweetness and calories: methodological aspects of laboratory studies on appetite control. Appetite. 1988;11(Suppl 1):54-61.

25. Bellisle F. Intense sweeteners, appetite for the sweet taste, and relationship to weight management. Curr Obes Rep. 2015;4:106-110.

26. Bryant CE, Wasse LK, Astbury N, et al. Non-nutritive sweeteners: no class effect on the glycaemic or appetite responses to ingested glucose. Eur J Clin Nutr. 2014;68:629-631.

27. Canty DJ, Chan MM. Effects of consumption of caloric vs noncaloric sweet drinks on indices of hunger and food consumption in normal adults. Am J Clin Nutr. 1991;53:1159-1164.

28. Meyer-Gerspach AC, Wolnerhanssen B, Beglinger C. Functional roles of low calorie sweeteners on gut function. Physiol Behav. 2016;164(Pt B):479-481.

29. Mattes RD, Popkin BM. Nonnutritive sweetener consumption in humans: effects on appetite and food intake and their putative mechanisms. Am J Clin Nutr. 2009;89:1-14.

30. Bhupathiraju SN, Pan A, Malik VS, et al. Caffeinated and caffeine-free beverages and risk of type 2 diabetes. Am J Clin Nutr. 2013;97:155-166.

31. Schulze MB, Manson JE, Ludwig DS, et al. Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women. JAMA. 2004;292:927-934.

32. de Koning L, Malik VS, Rimm EB, et al. Sugar-sweetened and artificially sweetened beverage consumption and the risk of type 2 diabetes in men. Am J Clin Nutr. 2011;93:1321-1327.

33. Tey SL, Salleh NB, Henry CJ, et al. Effect of non-nutritive (artificial vs natural) sweeteners on 24-hour glucose profile. Eur J Clin Nutr. 2017;71:1129-1132.

34. Bonnet F, Tavenard A, Esvan M, et al. Consumption of a carbonated beverage with high-intensity sweeteners has no effect on insulin sensitivity and secretion in nondiabetic adults. J Nutr. 2018;148:1293-1299.

35. Higgins KA, Considine RV, Mattes RD. Aspartame consumption for 12 weeks does not affect glycemia, appetite, or body weight of healthy, lean adults in a randomized controlled trial. J Nutr. 2018;148:650-657.

36. Romo-Romo A, Aguilar-Salinas CA, Brito-Cordova GX, et al. Effects of the non-nutritive sweeteners on glucose metabolism and appetite regulating hormones: systematic review of observational prospective studies and clinical trials. PloS One. 2016;11:e0161264.

37. Greenwood DC, Threspleton DE, Evans CE, et al. Association between sugar-sweetened and artificially sweetened soft drinks and type 2 diabetes: systematic review and dose-response meta-analysis of prospective studies. Br J Nutr. 2014;112:725-734.

38. Imamura F, O’Conner L, Ye M, et al. Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction. BMJ. 2015;351:h3576.

39. Davis JN, Asigbee FM, Markowitz AK, et al. Consumption of artificial sweetened beverages associated with adiposity and increasing HbA1c in Hispanic youth. Clin Obes. 2018;8:236-243.

40. 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;35:1798-1808.

41. American Diabetes Association. Standards of Medical Care in Diabetes—2019. Diabetes Care. 2019;42(Suppl 1):S1-S183.

42. Dietary Guidelines Advisory Committee. Scientific Report of the 2015 Dietary Guidelines Advisory Committee: advisory report to the Secretary of Health and Human Services and the Secretary of Agriculture. Office of Disease Prevention and Health Promotion Web site. https://health.gov/dietaryguidelines/2015-scientific-report/.Published February 2015. Accessed July 15, 2019.

43. Aune D. Soft drinks, aspartame, and the risk of cancer and cardiovascular disease. Am J Clin Nutr. 2012;96:1249-1251.

44. Artificial sweeteners and cancer. National Cancer Institute Web site. https://www.cancer.gov/about-cancer/causes-prevention/risk/diet/artificial-sweeteners-fact-sheet. Reviewed August 10, 2016. Accessed July 15, 2019.

45. Fung TT, Malik V, Rexrode KM, et al. Sweetened beverage consumption and risk of coronary heart disease in women. Am J Clin Nutr. 2009;89:1037-1042.

46. Lin J, Curhan GC. Associations of sugar and artificially sweetened soda with albuminuria and kidney function decline in women. Clin J Am Soc Nephrol. 2011;6:160-166.

47. Malik VS, Li Y, Pan A, et al. Long-term consumption of sugar-sweetened and artificially sweetened beverages and risk of mortality in US adults. Circulation. 2019;139:2113-2125.

48. Gardener H, Rundek T, Markert M, et al. Diet soft drink consumption is associated with an increased risk of vascular events in the Northern Manhattan Study. J Gen Inten Med. 2012;27:1120-1126.

49. Fitch C, Keim KS. Position of the Academy of Nutrition and Dietetics: use of nutritive and nonnutritive sweeteners. J Acad Nutr Diet. 2012;112:739-758.

50. US Food and Drug Administration. Additional information about high-intensity sweeteners permitted for use in food in the United States. https://www.fda.gov/food/ingredientspackaginglabeling/foodadditivesingredients/ucm397725.htm#Aspartame. Accessed May 26, 2019.

51. Sylvetsky AC, Gardner AL, Bauman V, et al. Nonnutritive sweeteners in breast milk. J Toxicol Environ Health. 2015;78:1029-1032.

52. Rajani C, Jia W. Disruptions in gut microbial-host co-metabolism and the development of metabolic disorders. Clin Sci (Lond). 2018;132:791-811.

53. Kho ZY, Lal SK. The human gut microbiome—a potential controller of wellness and disease. Front Microbiol. 2018;9:1835.

54. Nettleton JE, Reimer RA, Shearer J. Reshaping the gut microbiota: impact of low calorie sweeteners and the link to insulin resistance. Physiol Behav. 2016;164(Pt B):488-493.

55. Turnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457:480-484.

56. Cotillard A, Kennedy SP, Kong LC, et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500:585-588.

57. Le Chatelier E, Nielsen T, Qin J, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500:541-546.

58. Abou-Donia MB, El-Masry EM, Abdel-Rahman AA, et al. Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome P-450 in male rats. J Toxicol Environ Health A. 2008;71:1415-1429.

59. Anderson RL. Effect of saccharin ingestion on stool composition in relation to caecal enlargement and increased stool hydration. Food Chem Toxicol. 1983;21:255-257.

60. Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514:181-186.

An estimated 93.3 million Americans (roughly 40% of the US population) were obese in 2015-2016, and most of them had at least 1 chronic disease.¹ As a result, patient education focused on lifestyle modification, including healthy nutrition and physical activity, has become an integral part of our everyday practice.

At the same time, the most recent dietary guidelines recommend that added sugar make up < 10% of daily calories.² In the United States, low-calorie food and beverages containing non-nutritive sweeteners (NNSs; TABLE^3-8) have become a popular means of keeping the sweetness in our diet without the health ramifications associated with sugar. These NNSs (aka, artificial sweeteners, high-intensity sweeteners, and non-caloric sweeteners) are ubiquitous in soft drinks, processed grains (including breads, cereals, and granola bars), and dairy products (including yogurts, flavored milk, and ice cream). As examples, NNSs are present in 42% of flavored waters, 33% of yogurts, and all diet beverages.^9,10 They can even be found in medications, multivitamins, toothpaste, and mouthwash.

Business is booming

Global NNS consumption has been growing more than 5% per year, meaning that by 2020, NNSs are expected to be a $2.2 billion industry.¹¹ One study using data from the National Health and Nutrition Examination Survey (NHANES) found that the use of NNSs in the United States increased from 21.1% in 2003 to 24.9% in 2009-2010 among adults and increased from 7.8% to 18.9% over the same time period among children.¹²

The main increase in the consumption of NNSs across all age groups has been via the consumption of beverages. Approximately 11% of healthy weight, 19% of overweight, and 22% of obese adults consume diet beverages.^13,14 Consumption of diet beverages or NNSs increases with age¹² and is especially common among women with higher levels of education and income.¹⁵

However, concerns remain about the safety of these agents and their effect on weight, appetite, and the body’s glycemic response. This article reviews the available research and current recommendations regarding the use of NNSs.

WHAT EFFECT DO NNSs HAVE ON WEIGHT?

The data on NNSs and weight are inconsistent. One randomized controlled trial(RCT) compared weight loss over the course of 1 year (12-week weight loss phase; 9-month weight maintenance phase) when 303 participants consumed either water or drinks sweetened with NNSs.¹⁶ Weight loss was significantly greater in the NNS drink group when compared with the water group.¹⁶

Observational studies have revealed similar findings.^17,18 Data from NHANES revealed that US adults (n = 14,098) during 2 nonconsecutive 24-hour dietary recall periods demonstrated lower total energy (calorie) intake if they consumed NNSs vs no NNSs.¹⁹ Another study using 2011-2016 NHANES data on adolescents (n = 7026) found no difference in energy intake between those who consumed beverages containing NNSs vs those who consumed beverages containing sugar.²⁰

Continue to: Other lines of investigation...