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EVIDENCE- Artificial Sweeteners BASED CARE SHEET What We Know › Artificial sweeteners are non-nutritive sweeteners (NNSs; containing zero to negligible calories) used as substitutes for (table )for the purpose of reducing the caloric and glycemic impact of prepared and beverages. NNSs tend to have a significantly higher intensity of in comparison to sucrose and therefore are able to reproduce the sweetness of sucrose in a fraction of the quantity. Inspite of their intense sweetness, NNSs do not directly impact blood levels, making them useful in the dietary management of diabetes mellitus (DM). The eight NNSs that have been approved by the and Drug Administration (FDA) for use in food production in the United States are acesulfame-potassium (Ace-K),, , luo han guo (i.e., Siraitia grosvenorii Swingle fruit extract [SGFE]), , , steviol glycosides (stevia extracts), and (1,10,11) • Ace-K is about 200 times sweeter than sucrose and is frequently used in combination with other sweeteners. It is sold under the brand names Sunett and Sweet One. Ace-K can be found on food labels as the names acesulfame K, , or Ace-K(1) • Advantame is about 20,000 times sweeter than sucrose(1) • Aspartame is about 200 times sweeter than sucrose. Aspartame is one of the most commonly used NNSs and is sold under brand names Nutrasweet, Equal, and Sugar Twin. is a component of aspartame. Individuals with (PKU) are unable to adequately metabolize phenylalanine; therefore the labels of foods containing aspartame are required to include a statement to inform consumers of phenylalanine content(1) • SGFE, commonly known as luo han guo or monk fruit extract, is about 100–250 times the sweetness of sucrose(1) • Neotame is about 7,000–13,000 times the sweetness of sucrose and is sold under the brand name Newtame(1) • Saccharin is 200–700 times sweeter than sucrose and is sold under the brand names Sweet and Low, Sweet Twin, Sweet’N Low, and Necta Sweet. At one time saccharin-containing foods were required to carry a warning label as a possible . After numerous human studies demonstrated that saccharin is safe for Author human consumption, the National Toxicology Program of the National Institutes of Cherie Marcel, BS Health determined in 2000 that saccharin should be removed from the list of potent Cinahl Information Systems, Glendale, CA . The warning label is no longer required(1) • Steviol glycosides are extracts of stevia (i.e., Stevia rebaudiana Bertoni) leaves and are Reviewer Megan Rabin, MEd 200–400 times sweeter than sucrose. High-purity stviol glycosides are considered safe. Cinahl Information Systems, Glendale, CA However, stevia leaf and crude stevia extracts have not been approved by the FDA for use as sweeteners(1) Editor • Sucralose is about 600 times sweeter than sucrose and is sold under the brand name Diane Pravikoff, RN, PhD, FAAN (1) Cinahl Information Systems, Glendale, CA Splenda › Research findings on artificial sweeteners • Researchers who analyzed data from the Brazilian Longitudinal Study of Adult Health June 23, 2017 (ELSA-Brasil) determined that in normal-weightindividuals, consumption of artificial

Published by Cinahl Information Systems, a division of EBSCO Information Services. Copyright©2017, Cinahl Information Systems. All rights reserved. No part of this may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without permission in writing from the publisher. Cinahl Information Systems accepts no liability for advice or information given herein or errors/omissions in the text. It is merely intended as a general informational overview of the subject for the healthcare professional. Cinahl Information Systems, 1509 Wilson Terrace, Glendale, CA 91206 sweeteners was positively associated with developing diabetes. The same association was not found for overweight and obese individuals, in whom higher artificial sweetener intake was found to be associated with better insulin resistance results(12) • A meta-analysis of randomized controlled trials (RCTs) and prospective cohort studies was conducted to investigate the impact of artificial sweeteners on body weight. While a few observational studies indicated a positive association between artificial sweetener intake and (BMI), the data collected from the RCTs revealed that the substitution of NNSs for regular-calorieversions of the same foods/beverages resulted in modest weight loss(7) • Although many short-term studies have shown little or no detrimental effects associated with the intake of the artificial sweetener aspartame, and it is FDA approved, findings from long-term,population-based studies indicate that there are negative effects associated with aspartame consumption that merit further investigation(2,3,5) –A large study assessing the effects of aspartame intake on rats for the duration of their lifetime found that aspartame intake increased the risk for lymphoma, leukemia, and transitional cell carcinoma of the pelvis, ureter, and bladder.(2) Another study revealed that aspartame consumption raised blood glucose levels in diabetes-prone mice(6) • According to researchers, individuals who consume soft drinks (which primarily use aspartame but can also use saccharin, Ace-K,neotame, or sucralose) daily have a 36% higher risk for metabolic syndrome (MetS; i.e., a condition characterized by hyperglycemia, hypertension, abdominal obesity, and high triglycerides) and a 67% higher risk for diabetes mellitus type 2 (DM2), compared with those who do not regularly consume diet soft drinks.(4,6)Evidence also indicates that overweight and obese adults drink more diet beverages than healthy-weight adults (11% of healthy-weight, 19% of overweight, and 22% of obese adults consume diet beverages)(3) –According to observations made from theFramingham Heart Study Offspring cohort, a long-term community-based study following over 4,300 participants, consumption of artificially sweetened, but not sugar sweetened, soft drinks is positively associated with the risk of both and ischemic .Researchers note that, as an observational study, these results do not prove a causal relationship; further research is necessary to examine the mechanisms potentially responsible for these observed associations(9) –Researchers report that girls who consume caffeinated and artificially sweetened soft drinks have an increased risk of early menarche. Early menarche is associated with DM2, nonalcoholic fatty liver disease (NAFLD), cardiovascular disease (CVD), and hormone-related cancers(8) –Evidence from the San Antonio Longitudinal Study of Aging indicates that increasing diet soda intake is associated with increasing abdominal obesity. Over a follow-up period averaging 2.6years, participants who consumed diet soda had twicethe increase in waist circumference of persons who did not consume diet soda and participants who consumed diet soda daily had 3 times the increase in waist circumference when compared to participants who did not consume diet soda(5)

What We Can Do › Become knowledgeable about the physiologic effects of consuming NNSs so you can accurately assess your patients’ personal characteristics and health education needs; share this information with your colleagues › Assess your patients’ health and diet history for intake of NNSs and assess risk factors for obesity, DM2, and CAD. As appropriate, provide your patients with evidence-based information regarding the impact of NNS intake on these conditions › Educate your patients on the benefits of eating a balanced diet that includes unsaturated , lean , complex , and a wide variety of fresh fruits and vegetables Coding Matrix References are rated using the following codes, listed in order of strength:

M Published meta-analysis RV Published review of the literature PP Policies, procedures, protocols SR Published systematic or integrative literature review RU Published research utilization report X Practice exemplars, stories, opinions RCT Published research (randomized controlled trial) QI Published quality improvement report GI General or background information/texts/reports R Published research (not randomized controlled trial) L Legislation U Unpublished research, reviews, poster presentations or C Case histories, case studies PGR Published government report other such materials G Published guidelines PFR Published funded report CP Conference proceedings, abstracts, presentation

References 1. Additional information about high-intensity sweeteners permitted for use in food in the United States. (2015, May 26). U. S. Food and Drug Administration. Retrieved May 23, 2017, from https://www.fda.gov/food/ingredientspackaginglabeling/foodadditivesingredients/ucm397725.htm (GI) 2. Aune, D. (2012). Soft drinks, aspartame, and the risk of cancer and cardiovascular disease. American Journal of Clinical , 96(6), 1249-1251. doi:10.3945/ ajcn.112.051417 (R) 3. Bleich, S. N., Wolfson, J. A., Vine, S., & Wang, Y. C. (2014). Diet-beverage consumption and caloric intake among US adults, overall and by body weight. American Journal of , 104(3), e72-e78. doi:10.2105/AJPH.2013.301556 (R) 4. The diet soda-weight debate. (2012). Environmental Nutrition, 35(7), 7. (GI) 5. Fowler, S. P., Williams, K., & Hazuda, H. P. (2015). Diet soda intake is associated with long-term increases in waist circumference in a biethnic cohort of older adults: The San Antonio Longitudinal Study of Aging. Journal of the American Society, 63(4), 708-715. doi:10.1111/jgs.13376 (R) 6. Franz, M. (2010). Diet soft drinks: How safe are they? Diabetes Self-Management, 27(2), 8, 11-13. (GI) 7. Miller, P. E., & Perez, V. (2014). Low-calorie sweeteners and body weight and composition: A meta-analysis of randomized controlled trials and prospective cohort studies. American Journal of , 100(3), 765-777. doi:10.3945/ajcn.113.082826 (M) 8. Mueller, N. T., Jacobs, D. R., MacLehose, R. F., Demerath, E. W., Kelly, S. P., Dreyfus, J. G., & Pereira, M. A. (2015). Consumption of caffeinated and artificially sweetened soft drinks is associated with risk of early menarche. American Journal of Clinical Nutrition, 102(3), 648-654. doi:10.3945/ajcn.114.100958 (R) 9. Pase, M. P., Himali, J. J., Beiser, A. S., Aparicio, H. J., Satizabal, C. L., Vasan, R. S., ... Jacques, P. F. (2017). Sugar- and artificially sweetened beverages and the risks of incident stroke and dementia – A prospective cohort study. Stroke, 48(5), 1139-1146. doi:10.1161/STROKEA.H.A.116.016027 (R) 10. Qurrat-ul-Ain, & Khan, S. A. (2015). Artificial sweeteners: Safe or unsafe? Journal of the Pakistan Medical Association, 65(2), 225-227. Retrieved from http://jpma.org.pk/ full_article_text.php?article_id=7178 (RV) 11. Schlenker, E. D. (2015). Carbohydrates. In E. D. Schlenker & J. Gillbert (Eds.), Williams’ essentials of nutrition and diet (11th ed., p. 54). St. Louis, MO: Elsevier. (GI) 12. Yarmolinsky, J., Duncan, B. B., Chambless, L. E., Bensenor, I. M., Barreto, S. M., Goulart, A. C., ... Schmidt, M. I. (2016). Artificially sweetened beverage consumption is positively associated with newly diagnosed diabetes in normal-weight not in overweight or obese Brazilian adults. Journal of Nutrition, 146(2), 290-297. doi:10.3945/ jn.115.220194 (R)