Debates Rage on About the Health Effects of Low-Calorie Sweeteners – Newly Published Study Shows No Effect of Sucralose on Carbohydrate Metabolism

Health Effects of Low-Calorie Sweeteners

Debates Rage on About the Health Effects of Low-Calorie Sweeteners – Newly Published Study Shows No Effect of Sucralose on Carbohydrate Metabolism

  By Kevin C Maki, PhD

A study published recently in the journal Regulatory Toxicology and Pharmacology by Grotz and colleagues investigated the effects of sucralose consumption on glucose homeostasis in healthy men and women.1  Sucralose is one of six high-intensity sweeteners approved by the United States’ Food and Drug Administration (FDA) as food additives.  The approved high-intensity (low-calorie) sweeteners include:  saccharinaspartame, acesulfame potassium (Ace-K), sucralose, neotame, and advantame.2  Sucralose is one of the largest selling of the high-intensity sweeteners on the market, although consumption in the US has declined in recent years along with sales of diet soda, which were more than 20% lower in 2016 than in 2009.

There has been significant controversy about effects of high-intensity sweeteners on health, which seems to have intensified lately.  One of the findings that has generated debate is the relatively recent discovery of gut receptors for sweet taste, which has triggered concern that high-intensity sweeteners might have previously unappreciated effects on metabolism through their interactions with these receptors.1,3  Researchers at Purdue University have also hypothesized that when people consume high-intensity sweeteners, the body produces physiologic responses in anticipation of the arrival of sugar and calories, which could increase appetite and partially or fully offset the reduction in energy consumption of substituting a high-intensity sweetener for calorie-containing sugars.4

The newly published study by Grotz et al.1 was conducted a number of years ago, and the data were submitted to the FDA as part of the food additive petition for sucralose in 1996, but had never appeared in the peer reviewed literature.  Given the recent concerns expressed regarding the potential for high-intensity sweeteners to influence glucose homeostasis through their effects on sweet taste receptors in the gut, the investigators felt it would be useful to publish the results to make them more readily available to the scientific community.

The study was a randomized, double-blind parallel trial in which 48 healthy, normoglycemic males were randomly assigned to receive capsules containing either a cellulose placebo or 333.3 mg of sucralose, three times daily with meals.  The intake of 1000 mg/d in the sucralose group (n = 25) far exceeds the expected consumption from foods and beverages.  For perspective, diet sodas sweetened with sucralose typically contain ≤40 mg per serving.  A packet of Splenda® contains 12 mg of sucralose, which is 300-1000 times as sweet as sucrose.

The subjects underwent assessments of serum chemistry, hematology and glycated hemoglobin (HbA1C) levels, as well as fasting and post-oral-glucose-load (75 g) concentrations of insulin, glucose and C-peptide at baseline (twice), weeks 7 and 12 during the treatment period, and again 4 weeks after the end of the 12-week treatment period.  There were no significant differences between the placebo and sucralose groups for changes from baseline in HbA1C, or in fasting and post-glucose-load levels of glucose, insulin or C-peptide.  No differences were observed in clinical chemistry or hematology values.

Comment.  Given the widespread consumption of high-intensity sweeteners by large segments of the United States’ population, it is important to understand their effects on physiologic processes with implications for human health.  The results from this study in healthy men suggest that even very large intakes have no influence on indicators of glucose homeostasis.  Similar results have been obtained in patients with obesity or type 2 diabetes mellitus.1  Furthermore, reviews of the effects of high-intensity sweeteners, including sucralose, on appetite, gut hormones and gut motility have concluded that there is no evidence for material effects in humans.3,5  It is important for research on the physiological and psychological effects of high-intensity sweeteners to continue.  However, the results of this study and others suggest that sucralose has no adverse effects on glucose homeostasis.  Given evidence that sugar-sweetened products appear to have adverse effects on glucose homeostasis,6 the use of products sweetened with sucralose (and other high-intensity sweeteners) may be an acceptable option for those who would like to limit their intakes of added sugars and calories.7


 Grotz VL, Pi-Sunyer X, Porte, Jr. D, et al. A 12-week randomized clinical trial investigating the potential for sucralose to affect glucose homeostasis. Regul Toxicol Pharmacol. 2017;88:22-33.

  1. S. Department of Health and Human Services. U.S. Food & Drug Administration. High-Intensity Sweeteners. Accessed at on 11 July 2017.
  2. Magnuson BA, Roberts A, Nestmann ER. Critical review of the current literature on the safety of sucralose. Food Chem Toxicol. 2017;106 (Part A):324-355.
  3. Swithers SE, Martin AA, Davidson TL. High-intensity sweeteners and energy balance. Physiol Behav. 2010;100:55-62.
  4. Bryant C, Mclaughlin J. Low calorie sweeteners: evidence remains lacking for effects on human gut function. Physiol Behav. 2016;164 (Pt B):482-485.
  5. Maki KC, Nieman KM, Schild AL, et al. Sugar-sweetened product consumption alters glucose homeostasis compared with dairy product consumption in men and women at risk of type 2 diabetes mellitus. J Nutr. 2015;145:1-8.
  6. 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.
Health Effects of Low-Calorie Sweeteners

MB Clinical Academy Releases its First Two Educational Programs

MB Clinical Academy

MB Clinical Academy Releases its First Two Educational Programs

MB Clinical Academy produces educational materials to help clinicians, clinical research professionals and students more effectively manage the cardiometabolic health of their patients/clients, and to understand the strengths and limitations of the available evidence, including gaps that can be filled with future studies.

We have just completed two new programs, which will be available for purchase and download during the week of July 10, 2017.

Short Course

Diet and Prevention of Type 2 Diabetes Mellitus:  Beyond Weight Loss and Exercise

This short course will review the evidence for dietary factors in the prevention of type 2 diabetes mellitus (T2D).  It contains three modules that will cover:

  • Module 1: Epidemiology and pathophysiology of T2D
  • Module 2: Predictors of T2D risk and effects of interventions on incidence
  • Module 3: Summary of the associations and mechanisms through which diet may affect T2D risk, with an emphasis on insulin sensitivity and glycemic load

Short Course

Interpreting Efficacy Results from Cardiovascular Outcomes Trials

Cardiovascular outcomes trials are integral to evidence-based medicine, and they are the most effective means for demonstrating that an intervention reduces major adverse cardiovascular events.  A sound understanding of the fundamentals of clinical study design and statistical methodology is essential for the interpretation of efficacy results from cardiovascular outcomes trials.  However, most clinicians have not had extensive training on how to interpret measures of association and statistical procedures used to assess the efficacy of interventions intended to reduce cardiovascular event risk.  This course will review of the following concepts and their use in cardiovascular outcomes studies:

  • Measures of cardiovascular event incidence
    1. Relative risk
    2. Hazard ratio
    3. Odds ratio
  • Comparing event rates and treatment effects
    1. Relative risk reduction
    2. Absolute risk reduction
    3. Number needed to treat (or harm)
  • Pitfalls when making comparisons between cardiovascular outcomes trials, including the three most important questions
    1. Who was studied (risk profile)?
    2. What outcomes were assessed?
    3. Over what time period?
  • Additional factors to consider in the interpretation of findings from cardiovascular outcomes trials
    1. Evaluating the roles of chance, bias and confounding
    2. Factors affecting validity and generalizability
    3. Assessing the potential for type I and type II statistical errors

We expect that those who purchase these programs will find them informative and practical.  If you have suggestions for future programs, don’t hesitate to send us an email:


MB Clinical Academy