Low-Calorie Sweeteners: Update on Health & Safety
This session was sponsored by ILSI North America and ILSI Europe.
Low-calorie sweeteners (LCS) are ingredients used in formulating foods and beverages to reduce their sugar and caloric contents. Questions have been raised in the popular press and by public health communities regarding their potential benefits and safety. This session focused on common frameworks for addressing such questions. Systematic reviews with meta-analyses, the gold standard for evaluating a body of research regarding diet and health, were discussed. Such reviews have been used in dietary guidance development by the World Health Organization in evaluating evidence on research questions regarding sugars and health. The latest systematic reviews examining the relationship of LCS intake with weight and glycemic response was presented. Additionally, the global frameworks for regulatory and safety evaluations was addressed. Finally, research exploring the science of sweet taste and implications for the use of LCS was discussed.
Low-Calorie Sweeteners and Weight – A Systematic Review of Human and Animal Studies
Peter Rogers, PhD, RNutr (Session Chair)
Bristol University, United Kingdom
Low-Calorie Sweeteners and Glycemic Response
Xavier Pi-Sunyer, MD, MPH
Columbia University Medical Center, USA
Global Safety and Regulatory Processes for the Evaluation of Low-Calorie Sweeteners
Ashley Roberts, PhD
Intertek Regulatory & Scientific Consultancy, Canada
Sweet Taste and Implications with Low-Calorie Sweetener Use
France Bellisle, DSc
Université Paris, France
Low-Calorie Sweeteners and Weight – A Systematic Review of Human and Animal Studies
Peter Rogers, PhD, RNutr
Bristol University
United Kingdom
The major potential benefits for public health of low-calorie sweeteners (LCS) are a reduction in sugar intake and consequent reduction in overweight and obesity. However, the usefulness of LCS for weight management has been challenged on several grounds. First, there is the possibility that food intake increases to compensate for the energy dilution achieved with LCS, second is the suggestion that LCS weaken the relationship between sweet taste and food energy content and thereby disrupt the learned control of appetite, and third is the argument that exposure to sweetness increases desire for sweetness which escalates sweet food intake. There is partial but, importantly, not full energy intake compensation after consumption of LCS versus sugar. Separately, results of animal studies used to support the disruption of dietary learning by LCS hypothesis have been demonstrated to be explained by a procedural artefact. In any case, this hypothesis is irrelevant to the human diet because sweetness and sugar content do not reliably predict energy density, even within and across categories of minimally processed foods. In relation to the ‘sweet tooth’ hypothesis, consumption of LCS versus water has not been found to increase energy intake in the short-term, with other evidence showing a decrease in sweet food intake when a LCS drink is consumed with a meal. The latter is consistent with the phenomenon of ‘sensory-specific satiety.’ There is rather little evidence on the effects of longer-term exposure to sweetness. In one recent study, consumption of a diet low in sweetness for 3 months increased perceived sweetness intensity of sucrose in a pudding and a drink, but it did not affect rated pleasantness of the same test products. Together, these various results largely refute claims about counterproductive effects of LCS and predict that consumption of LCS in place of (some) sugar in the diet should help reduce overall energy intake and body weight. Recent meta-analyses of intervention studies in adults and children, fully support this prediction. The duration of these studies ranged from 1-40 months. Furthermore, if anything, body weight was lower for LCS drinks compared with water, perhaps because, as suggested above, consumption of LCS may help satisfy the desire for sweetness within a meal. Overall, LCS appear to be helpful for weight management. There are nonetheless obviously limits to the extent to which dietary energy content can be reduced (diluted) by replacing sugar with LCS. These include consumers’ current level of free sugars intake and their willingness to consume LCS, and technical constraints on how much sugar can be substituted, especially in foods.
Low-Calorie Sweeteners and Glycemic Response
Xavier Pi-Sunyer, MD, MPH
Columbia University Medical Center
USA
Non-caloric artificial sweeteners (NAS) are widely used globally. Since they came on the market, they have generally been considered metabolically inactive and safe with regard to glucose homeostasis by the FDA and other regulatory agencies. Numerous safety trials with the various products in the market have been done through the years and most have shown little impact on glucose levels during both short-term and longer-term trials. However, there have been a few that have reported small alterations in glucose and insulin levels. Recently, three new important issues have emerged: taste receptors in the gut, the impact of microbiota, and interference with learned ingestive responses. It is evident now that taste receptors, once thought to reside only in the mouth, are also present in the intestinal lumen. NAS can therefore bind to these receptors and can initiate signals that may be relayed to the blood, brain, pancreas, liver, etc and could modify glucose homeostasis. The importance of the gut microbiota in modifying the glucose homeostasis of an organism is unclear and is being explored. Most studies to date have been done in rodents generally utilizing high doses of NAS. With these models, perturbations in the microbiota have been shown and an impact on glucose has been reported. It has been hypothesized that NAS can alter the ability to predict the energy ingested and evoke a learned response that is faulty, leading to metabolic changes in the organism.. The strength of the available evidence base regarding these three potential mechanisms for altering glucose homeostasis will be reviewed and evaluated.
Global Safety and Regulatory Processes for the Evaluation of Low-Calorie Sweeteners
Ashley Roberts, PhD
Intertek Regulatory & Scientific Consultancy
Canada
The safety of all food additives such as low/no calorie sweeteners is assessed by extensive reviews undertaken by regulatory authorities and committees such as The Joint FAO/WHO Expert Committee on Food Additives (JECFA), the United States (U.S.) Food and Drug Administration (FDA), the European Food Safety Authority (EFSA) and Food Standards Australia/New Zealand (FSANZ). In the U.S. low/no calorie sweeteners have until recently all gone through the food additive process whereas more recently substances such as steviol glycosides and mogroside from the fruit Lo Han Guo have been considered Generally Recognized as Safe or GRAS. Prior to approval and authorization, a comprehensive database has to be developed and presented in the form of a petition to the Agencies outlined above. The dossier must contain both technical and toxicological components from which a safety assessment is conducted. Safety assurance is based upon toxicological studies (both in vitro and in vivo) and clinical studies where the aim is to define a no-observed-adverse-effect level (NOAEL). The NOAEL is converted to an acceptable daily intake (ADI) by dividing by a safety factor of 100-fold to allow for potential differences between test animals and humans. The ADI determination of itself is then related to the potential daily consumption when incorporated in the foods and beverages and only when the estimated daily intake (EDT) in high consumers is found not to exceed the ADI will approval be established, i.e., the EDI is lower than the ADI.
Sweet Taste and Implications with Low-Calorie Sweetener Use
France Bellisle, DSc
Université Paris
France
The World Health Organisation (WHO) recommends that adults and children reduce their intake of free sugars to less than 10% of the daily energy intake. This recommendation is based on the potential adverse effect of a high intake of sugar on body weight control and metabolic health. If dental health is taken into consideration, then the WHO recommends a further reduction of free sugar intake below 5% of the daily energy intake. Such recommendations are challenging for many individuals and more so in certain parts of the world where the culturally accepted levels of sweetness in the diet are high. Sweetness is a potent psychobiological stimulus in many animal species, including humans of all ages. Human newborns display an innate attraction to sweet substances, manifested by eager acceptance and a stereotyped gusto-facial reflex of relaxation and smile. Such innate responses present a survival advantage in the context of Natural Selection, facilitating the acceptance of energy and nutrient sources by the young organism. Indeed, the appetite for sweetness is high in infants and children. As it does in other species, the human appetite for sweetness spontaneously decreases during growth. Adults vary largely in their preferred intensity of sweetness in a broad range of beverages and foods. Genetic influences and personal experiences with sweetness shape the adult responses. Cultures as well as individuals show large differences in the consumption of sweet tasting products. Sugar brings 4 kcalories per gram and it is easy to see how its pleasant taste could stimulate overeating and weight gain, as suggested by the WHO. Observational studies in many countries, however, show little correlation between the body adiposity status and individual liking or consumption of sweet tasting products. Overweight and obese individuals often display an enhanced appetite for dietary fats (that bring 9 kcalories per gram) rather than sugar. How can a reduction of sugar intake be achieved? Should all sweet tasting substances be limited or can low-calorie sweeteners (LCS) contribute to a decrease in sugar intake (and the associated energy load) while retaining the palatable sweet taste of many favorite foods and drinks? Numerous scientific studies have addressed this issue. Experimental reports confirm that the use of LCS is associated with lower energy and sugar intake in the context of weight loss programs. LCS also facilitate the maintenance of the reduced weight after the end of a diet. Disproving early suggestions that LCS may enhance the natural appetite for sweetness and paradoxically stimulate the consumption of other sweet (sugar-containing) products, experimental trials show that LCS satiate rather than enhance the appetite for sweet tasting products and facilitate the reduction of sugar intake. More research is needed to assess the role of LCS in the management of sweetness appetite over the life span, in the prevention of weight gain, particularly in individuals at risk of overweight and in cultures where the traditional level of sweetness in the diet is high.
Peter Rogers, PhD, RNutr
Bristol University
United Kingdom
Peter Rogers is a Professor of Biological Psychology at the University of Bristol, UK. He trained in biological sciences and experimental psychology at the University of Sussex UK (1972-1976). He completed his PhD and postdoctoral work at the University of Leeds UK, moving to the Institute of Food Research, Reading UK in 1990. Dr. Rogers moved to the University of Bristol UK in 1999, where he teaches biological psychology and does research on nutrition and behavior: which includes work on human appetite and weight control, food choice, dietary effects on mood and cognitive function, and the psychopharmacology of caffeine. He is a Chartered Psychologist, a Fellow of the British Psychological Society, and a Registered Nutritionist.
Xavier Pi-Sunyer, MD, MPH
Columbia University Medical Center
USA
Xavier Pi-Sunyer is co-Director of the New York Obesity Research Center and Professor of Medicine at the College of Physicians and Surgeons of Columbia University. He is also Professor in the Institute of Human Nutrition at Columbia. Dr. Pi-Sunyer is a Senior Attending Physician at the New York-Presbyterian Hospital and a Core Laboratory Director of the Nutrition/Obesity Research Center and of the Diabetes Research Center both sponsored by the NIH. He was previously Director of Endocrinology, Diabetes and Nutrition and Senior Attending Physician at the St. Luke’s-Roosevelt Hospital in New York, as well as a Professor of Applied Physiology at Columbia’s Teachers College, Director of the Theodore B. Van Itallie Center for Nutrition and Weight Management, Director of the Joslin Center for Diabetes at St. Luke’s, and Visiting Physician at the Rockefeller University Hospital. He holds a B.A. from Oberlin College, an M.D. from Columbia University College of Physicians and Surgeons and an M.P.H. from Harvard University. He trained in Internal Medicine at St. Luke’s Hospital in New York and St. Bartholomew’s Hospital and Medical School in London, England. He did fellowships in Endocrinology at the Boston City Hospital Harvard Service and St. Luke’s Hospital/Columbia in New York.
His research interests are in the hormonal control of carbohydrate metabolism, diabetes mellitus, obesity and regulation of food intake. He has over 450 publications in these areas and six books. Dr. Pi-Sunyer is a past president of the American Diabetes Association, of the American Society for Clinical Nutrition, and of the North American Association for the Study of Obesity. He served as a Counsellor of the Society of Experimental Biology and Medicine. He has been honored as a Fellow of the Fogarty International Center of the National Institutes of Health. Dr. Pi-Sunyer chaired the NHLBI Task Force for the Prevention and Treatment of Obesity in 1995-8 and was a member of NHLBI Clinical Guidelines for Obesity Treatment and Prevention from 2008 to 2010. He has served on numerous NIH study sections and review groups such as on the Advisory Committee to the FDA Director. He has been a member of a number of task forces of the Institute of Medicine. He served as a member of the New York State Health Research Council. Dr. Pi-Sunyer was also an Associate Editor and then Editor-in-Chief of the Journal Obesity and Associate Editor of the International Journal of Obesity.
Ashley Roberts, PhD
Intertek Regulatory & Scientific Consultancy
Canada
Dr. Roberts is an accomplished Regulatory Toxicologist with extensive knowledge in international regulatory affairs. He has considerable experience in designing, conducting and reporting pre‐clinical and clinical research studies. While in the food industry he was largely responsible for developing scientific strategies, for establishing safety and gaining regulatory approvals for new food ingredients throughout the world. During his time in industry and academia, he has published a number of papers in peer‐ reviewed journals primarily in the area related to safety, mechanisms of toxicity and pre‐clinical/clinical pharmacokinetics. Prior to working for Intertek, Dr. Roberts worked in the area of scientific and regulatory affairs for a multi‐national food company for more than 10 years. Prior to this he worked in two leading European contract research organizations conducting drug metabolism and pharmacokinetics studies and phase I clinical trials. Dr. Roberts is available to advise and assist our international clients with issues that are scientific, regulatory and toxicological in nature. In addition, he is able to assist those clients wishing to design and develop scientific research programmes and for those developing regulatory strategies for food additives, foods that are Generally Recognized as Safe (GRAS), and novel foods.
France Bellisle, DSc
Université Paris
France
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