The research and evidence base for the safety and efficacy of nonnutritive sweeteners [NNS] spans many decades. This bibliography includes recent publications and is provided by Heartland Food Products Group, the manufacturer of sucralose-based SPLENDA® Sweetener Products. (Within each category the publications are listed in reverse chronological order.)


American Cancer Society: Guidelines on Nutrition and Physical Activity for Cancer Prevention and Physical Activity for Cancer Prevention. Last revised 2016

About NNS: “There is no proof that these sweeteners, at the levels consumed in human diets, cause cancer. Aspartame, saccharin, and sucralose are a few of the non-nutritive sweeteners approved for use by the FDA. Current evidence does not show a link between these compounds and increased cancer risk…”

Academy of Nutrition and Dietetics Position Paper: Interventions for the Treatment of Overweight and Obesity in Adults. J Acad Nutr Diet. 2016; 116(1):129-147.

Summary: The value of reducing sugar-sweetened beverages (SSBs) to reduce weight is discussed briefly. Data from two RCTs demonstrating greater weight loss with the replacement of low calorie sweetened beverages for SSBs are detailed. These RCTs, by Tate et al. (2012) and Peters et al. (2014) are cited and summarized below.

Snacks, Sweetened Beverages, Added Sugars, and Schools – American Academy of Pediatrics Policy Statement from Council on School Health, Committee on Nutrition. Pediatrics. 2015; 135(3):575-583.

About NNS: “Additional improvements in nutrient density of sweet-tasting products could be obtained if nonnutritive sweeteners are used as a tool to replace added sugars and help lower caloric intake. Several nonnutritive sweeteners have been accepted by the US Food and Drug Administration as safe and have shown good safety over time.”

National Cancer Institute, National Institutes of Health. Do Artificial Sweeteners Cause Cancer? Posted 2014

Summary: Researchers have conducted studies on the safety of the many nonnutritive sweeteners, including sucralose and others approved by the FDA for sale in the US. There’s no evidence that they cause cancer in humans.

Nutrition Therapy Recommendations for the Management of Adults with Diabetes - American Diabetes Association (ADA) Position Statement. Evert A, et al. Diabetes Care. 2013; 36:3821-3842.

About NNS: “Use of nonnutritive sweeteners (NNSs) has the potential to reduce overall calorie and carbohydrate intake if substituted for caloric sweeteners without compensation by intake of additional calories from other sources.” Regarding safety the statement refers to the reviews and approvals FDA. Regarding glycemic effect, the statement concludes research supports that NNS do not produce a glycemic effect unless other calorie containing ingredients are in the product.

Nonnutritive Sweeteners: Current Use and Health Perspectives - A Scientific Statement from the American Diabetes Association and the American Heart Association. Gardener C, et al. Diabetes Care. 2012; 35(8):1798-1808; Circulation: 2012; 126:509-519.

Summary: Reducing the intake of added sugars is an important intervention to achieve a healthy weight and nutrient-dense dietary pattern. The use of NNS may result in small decreases in calorie intake and weight loss when used within a structured eating plan and without caloric compensation.

Academy of Nutrition and Dietetics Position Paper: Use of Nutritive and Nonnutritive Sweeteners. J Acad Nutr Diet. 2012; 112(5):739-758.

About NNS: “It is the position of the Academy of Nutrition and Dietetics that consumers can safely enjoy a range of nutritive and nonnutritive sweeteners when consumed within an eating plan that is guided by current federal nutrition recommendations, such as the Dietary Guidelines for Americans and the Dietary Reference Intakes, as well as individual health goals and personal preference.”


Does Low-energy Sweetener Consumption Affect Energy Intake and Body Weight? A Systematic Review, including Meta-analyses of the Evidence from Human and Animal Studies. Rogers PJ, et al. Int J Obesity. 2015; 1–14. (e-pub).

Summary: This systematic review covers a large and lengthy body of evidence including numerous types of animal human studies using varied designs. Studies were conducted with various NNS including several currently available or approved by the U.S. FDA. Conclusions are consistent with other systematic reviews of NNS that demonstrate decreased energy intake and body weight with consumption of NNS used in place of added sugars.

Substitution of SSBs with Other Beverage Alternatives: A Review of Long-term Health Outcomes. Zheng M, et al. J Acad Nutr Diet. 2015; 115(5):767-779.

Summary: This systematic review culled studies from six literature databases to identify prospective cohort studies (PCS) and randomized controlled trials (RCTs) in children and adults with four month or longer duration. Six PCS and 4 RCTs were included. Results showed that replacing SSBs with low-calorie beverage alternatives demonstrates a favorable effect on long term body weight.

Intense Sweeteners, Appetite for the Sweet Taste, and Relationship to Weight Management. Bellisle F. Curr Obes Rep.: 2015; 4:106–110.

Summary: This paper, which analyzed research about how human NNS consumption may change the appetite for and intake of sweet tasting products, draws three main conclusions: 1) no consistent relationship exists to demonstrates a heightened appetite for sweet foods, 2) some research shows use of NNS is associated with consumption of less sweets, 3) intervention studies in children and adults show use of NNS can reduce intake of caloric sweeteners and support weight loss efforts.

Low-calorie Sweeteners and Body Weight and Composition: A Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies. Miller PE, et al. Am J Clin Nutr. 2014; 100:765–77.

Summary: This meta-analysis analyzed results from randomized control trials (RCTs) and prospective cohort studies on NNS and body weight, fat mass, BMI, and waist circumference. It showed that in RCTs NNS reduced body weight compared to placebo and modestly, but “significantly” reduced BMI, fat mass, and waist circumference. This meta-analysis was accompanied by the editorial, What Do You Say When Your Patients Ask Whether Low-calorie Sweeteners Help with Weight Management? Hill JO. Am J Clin Nutr.: 2014; 100: 739-740. Miller: Hill:





Low Calorie Beverage Consumption Is Associated with Energy and Nutrient Intakes and Diet Quality in British Adults. Gibson SA, et al. Nutrients. 2016; 8, 9:1-15 (e-pub).

Summary: This analysis of adults in the UK National Diet and Nutrition Survey (NDNS) observed associations between consumption of sugar-sweetened beverages (SSB), low-calorie sweetened beverages (LCB), non-consumers of soft drinks (NC) and consumers of both beverages (BB) with energy intake and diet quality. Results showed LCB and NC groups consumed less energy and sugars than consumers of SSB or BB. NC and LCB consumers had higher quality diets compared to SSB and BB consumers. They did not compensate for the sugar or energy deficit with more sugary foods.

The Effects of Water and Non-nutritive Sweetened Beverages on Weight Loss During a 12-week Weight Loss Treatment Program. Peters JC, et al. Obesity. 2014; 22(6):1415-21.

Summary: The study group in this 12 week weight control RCT trial was instructed to drink 24 fl.oz/day diet beverages (any type) and the control group was instructed to drink 24 fl.oz/day of water and no diet beverages. Results showed the diet beverage group lost significantly more weight, average of 13 pounds, or 44 percent more than control group (average 9 pounds). 64% of study group lost >5% of body weight, compared with 43% of control group. Diet beverage group experienced significantly less hunger. (Peters et al. 2016, below, summarizes the 9 month maintenance phase of this RCT.) Peters, 2014:

The Effects of Water and Non-nutritive Sweetened Beverages on Weight Loss and Weight Maintenance: A Randomized Clinical Trial. Peters JC, et al. Obesity. 2016; 24(2):297-304.

Summary: After completing the 9 month maintenance phase of this 1 year behavioral treatment program, the diet beverage group showed statistically significant greater weight loss (6.21 ± 7.65 kg) than subjects in the water treatment group (2.45 ± 5.59 kg). Peters, 2016:

Sugar- and Artificially Sweetened Beverages and Intrahepatic Fat: A Randomized Controlled Trial. Campos V, et al. Obesity. 2015; 23:2335-2339.

Summary: Over a 12 week study period this RCT compared the impact of Artificially Sweetened Beverages (ASB) with Sugar-Sweetened Beverages (SSB) on intrahepatic fat among overweight adults who usually consumed two or more 22- fl.oz. SSB daily. Results showed participants consuming ASB had significantly decreased total energy, carbohydrate, and sugar intakes. Subjects continuing to consume SSB showed no differences in intake. Dietary changes in the ASB group were accompanied by a significant decrease in intrahepatic fat.

Nonnutritive Sweeteners are not Supernormal Stimuli. Antenucci RG, et al. Int J Obes. 2015; 39(2):254-9.

Summary: Study participants were exposed to a series of taste tests with various caloric and nonnutritive sweeteners. Participants rated perceived sweetness. Results showed participants perceived the sweetness of NNS at lower concentrations than the caloric sweeteners and indicated caloric sweeteners all had higher sweetness ratings than NNS. Researchers concluded that results don’t support the claim that NNS produce a negative effect by over-stimulating peoples’ sweet taste receptors to produce supernormal stimuli. (abstract)

Low/No Calorie Sweetened Beverage Consumption in National Weight Control Registry (NWCR). Catenacci VA, et al. Obesity. 2014; 22(10):2244-2251.

Summary: This study surveyed consumption of beverages with NNS in NWCR members with sustained weight loss for > 7 years. Results showed 53% regularly consumed NNS beverages, 10% regularly consumed sugar-sweetened beverages (SSB). 78% of NNS consumers reported they helped control calorie intake. Choice of beverage was “very important” for weight loss (42%), weight maintenance (40%).

Consumption of LCS among U.S. Adults is Associated with Higher Healthy Eating Index (HEI 2005) Scores and More Physical Activity. Drewnowski A, et al. Nutrients. 2014; 6:4389-4403.

Summary: This study analyzed NHANES data from 22,000 participants between 1999-2008 who consumed beverages, foods and tabletop sweeteners with NNS. The USDA’s Healthy Eating Index was used to measure diet quality. Results showed people who use NNS have a higher HEI than non-consumers largely explained by lower calorie intake from solid fats, added sugars and alcohol. NNS users were found to practice other healthy lifestyle behaviors, such as physical activity, and less tobacco and alcohol use.

Non-Nutritive Sweeteners: No Class Effect on the Glycaemic or Appetite Responses to Ingested Glucose. Bryant CE, et al. Eur J Clin Nutr. 2014; 68:629-631.

Summary: This study examined the individual effect of acesulfame-K (AceK), aspartame and saccharin responses on glycemia and appetite in humans when consumed in combination with glucose in commonly used amounts. Results showed no additional effect of aspartame or saccharin on glucose response any time during the 60 minute post-ingestion period. No NNS individually had an effect on perceptions of hunger or fullness. (abstract)

Artificial Sweeteners Have No Effect on Gastric Emptying, Glucagon-like Peptide-1, or Glycemia after Oral Glucose in Healthy Humans. Wu T, et al. Diabetes Care.2013; 36:e202-e203.

Summary: This study fed four different drinks to healthy men: 1) water, 2) water with sucralose, 3) water with acesulfame-K (AceK), and 4) water with both sucralose and AceK. 10 minutes after consumption, a 75 gram oral glucose load was administered. Results showed neither sucralose alone, or when combined with AceK, had any acute effect on gastric emptying, GLP-1, or glycemic responses.

Replacing Caloric Beverages with Water or Diet Beverages for Weight Loss in Adults: Main Result of the Choose Healthy Options Consciously Everyday (CHOICE) Randomized Control Trial. Tate D, et al. Am J Clin Nutr. 2012; 95:555-563.) Does Diet-Beverage Intake Affect Dietary Consumption Patterns? Results from the Choose Healthy Options Consciously Everyday (CHOICE) Randomized Clinical Trial. Piernas C, et al. Am J Clin Nutr. 2013; 97:604-611.

Summaries: CHOICE was a 6-month RCT with 3 groups: 1) diet beverage, 2) water or 3) control. Eligible subjects had to consume > 280 kcal/day sweetened beverages and commit to making a dietary change. Diet beverage and water groups substituted >2 servings/day of sweetened beverage with a diet beverage or water, respectively. Results: At 6 months diet beverage drinkers were more likely to achieve a 5% weight loss than water drinkers. A secondary analysis Piernas, et al., showed both study groups reduced total energy, carbohydrate, and added sugars. Diet beverage group participants reduced dessert consumption more than water drinkers. Tate: Piernas:

The literature cited here is consistent with the extensive evidence base on NNS which concludes that NNS can be used safely and efficaciously as part of a healthy eating pattern. Using NNS, including sucralose, the sweetening ingredient in SPLENDA® Sweetener Products, can assist people with managing their weight and/or various aspects of metabolic health by reducing calories, total carbohydrate and added sugars.

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