Low-Calorie Sweeteners and Glucose Intolerance Craig A. Johnston, Ph.D.

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1 Low-Calorie Sweeteners and Glucose Intolerance Craig A. Johnston, Ph.D. Assistant Professor University of Houston Department of Health and Human Performance

2 OBJECTIVES Describe the evidence regarding the impact of artificial sweeteners on health. Discuss studies of the microbiome. Determine the strength of the evidence.

3 Diabetes Prevalence Prevalence of diabetes has more than doubled in past 30 years. Prevalence will be nearly 600 million by Strategies to prevent and manage diabetes are urgently needed.

4 Lifestyle Management for Diabetes One of the strongest associations in the development of diabetes is excessive weight gain. Reduction in weight has been recommended for both diabetes prevention and management. Diabetes CVD Obesity Other Health Problems Lifestyle Management

5 Interventions for Diabetes Diabetes Prevention Program 58% reduction in incidence of diabetes with lifestyle intervention vs. control* Look AHEAD Partial or complete remission of diabetes Transition from meeting diabetes criteria to a prediabetes or non-diabetic level of glycemia Modest weight losses resulted in partial or complete remission in: 11.5% of patients receiving intervention at 1 year** 7.9% patients at 4 years** *Knowler et al. NEJM, 2002;346: **Gregg et al. JAMA, 2012;308:

6 Lifestyle Management for Diabetes Lifestyle management is limited in maintaining healthy changes long-term. Lifestyle management should focus on the concept of a small changes approach * Small changes in diet and physical activity to reduce weight can help prevent and manage diabetes. *Hill JO. Am J CLin Nutr. 2009;89:

7 Low-Calorie Sweeteners (LCSs) The American Diabetes Association The American Heart Association The Academy of Nutrition and Dietetics LCSs can help: reduce caloric intake aid in maintaining a healthy weight Low calorie sweeteners Safe Inexpensive Small-change strategy

8 Brief History of Sweeteners Low- and no-calorie sweeteners have been in use for many years, with the oldest discovered more than a century ago: 1878: Saccharin 1965: Aspartame 1967: Acesulfame-K 1976: Sucralose 1990: Neotame Stevia and Luo Han Guo Extract approved by the FDA as GRAS

9 Use of Sweeteners is Increasing Sylvetsky et al. Am J Clin Nutr, 2012;96:

10 LCSs Controversy Understanding effective options for the management of type 2 diabetes is important Epidemiological evidence Research with animals LCSs may pose a health threat versus RCTs LCSs can serve an important role in diabetes prevention and management

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12 Headlines come from RODENT STUDIES Causes weight gain Swithers et al. Behav Neurosci. 2013;127: Stimulate glucose absorption Mace et al. J Physiol, 2007;582: Renwick et al. Br J Nutr. 2010;104: Increase insulin release Renwick et al. Br J Nutr. 2010;104: EPIDEMIOLOGICAL STUDIES Increases appetite Malik VS et al. Curr Diab Rep. 2012;12: Causes weight gain Stellman et al. Prev Med. 1986;15:

13 0/pregnant-women-urged-to-avoid-junkfood/ South Australian researchers have found women who overindulge during pregnancy are more likely to deliver kids with unhealthy cravings The researchers have not suggested women cut out junk food altogether during pregnancy, but that women should stick to the guidelines of a normal balance diet... They said while the negative effects of eating junk food during pregnancy can be reversed with a healthy diet, it was likely those children would always struggle with weight Maternal junk-food feeding of rat dams alters food choices and development of the mesolimbic reward pathway in the offspring. Ong, Muhlhausler. FASEB J. 2011;25(7):

14 CORRELATIONAL STUDIES Messerli. N Engl J Med, 2012;367(16): Good. Nature, 1988;332:495

15 NOAEL No Observed Adverse Events Level Expose an organism to a substance Identify the level at which No adverse events occur Over the lifetime of the organism This number is then divided by a safety factor Factor of 10: differences between animals and humans Factor of 10: different sensitivities between humans Acceptable Daily Intake is then derived (dividing by 100)

16 ADI (In the U.S.) Aspartame ADI is 165 packets per day (50 mg/kg bw/d) NOAEL would be 16,500 packets Saccharin ADI is 250 packets per day (15 mg/kg bw/d) NOAEL would be 25,000 packets Sucralose (aka Splenda) ADI is 165 packets per day (5 mg/kg bw/d)

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18 Impact on microbiome Microbiome is in its infancy in terms of study Suez et al. (Nature, 2014) Evidence from a rodent and observational study Human study is done on 7 participants Number reduced to 4 (non-responders) No causative data in this study

19 Overview of recent studies LNCS and Bacteria Interaction Summary Recent Studies in microbiome or bacteria in Culture

20 Do LCS lead to Diabetes? Human studies show that diet beverages do not lead to higher blood glucose level compared to water. Blood glucose level is the most important measure of glucose intolerance (Peters et al, 2014, 2016). The results from the studies on gut microbiome in rodents do not translate to humans ADA/AHA LNCS when used judiciously could promote beneficial effects on metabolic parameters related to weight

21 Final Thoughts We used to use words like Moderation Total diet The issue of demonization Low-fat in the 1980 s Focus on a single micro or macronutrient Focus on a single food