Berna Magnuson, Ph.D. University of Toronto On behalf of Calorie Control Council The Calorie Control Council

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1 Safety and Benefits of Alternative Sweeteners Berna Magnuson, Ph.D. University of Toronto On behalf of Calorie Control Council The Calorie Control Council

2 Low- and Reduced-Calorie Sweeteners Reducing caloric intake by switching from energy-dense sweeteners to lowand reduced-calorie sweeteners is one way that individuals can trim extra calories from their diet without sacrificing taste Low- and reduced-calorie sweeteners are an important tool in weight management

3 Goal today is to answer: What alternative sweeteners are in the market for use? What happens to alternative sweeteners in the body? Are all alternative sweeteners safe? What is the evidence of benefits of use?

4 Alternative Sweeteners Available for Use Advantame Acesulfame K Aspartame Cyclamate Monk Fruit Extract Neotame Saccharin Stevia Sucralose Erythritol Isomalt Lactitol Maltitol Mannitol Polyglycitol Sorbitol Xylitol

5 SAFETY ASSESSMENT Identify Hazard Characterize Dose-Response Assess Exposure Estimate Acceptable Daily Intake (ADI) Estimate Range/Distribution of Human Intakes Characterize Risk What fraction of the population, if any, incurs intakes greater than the ADI? To what extent do intakes exceed the ADI? Food survey for target population

6 Hazard or Toxicity Assessment Studies are required in several species. Include: Absorption, metabolism, distribution and excretion (ADME); Short- and long-term (life-time) toxicity studies; Genetic (mutations); Carcinogenicity (cancer); Reproduction (effects during pregnancy, birth and development); May require additional studies; Human studies: Confirm ADME, Special populations.

7 Acesulfame K About 200 X as sweet as sugar; Commonly blended with aspartame; Rapidly absorbed; Most excreted unchanged in the urine within 24 hours in rats, dogs, and humans; Provides no calories; No accumulation in body;

8 Aspartame Amino Acid Amino Acid Methyl Discovered in 1965; 200X sweeter than sucrose; Approved in over 130 countries; Methylated dipeptide of 2 common amino acids Aspartic acid (aspartate) Phenylalanine

9 Aspartame digestion in intestinal lumen Intestinal Lumen Mucosa Cell Portal Blood Aspartame Aspartame Esterases Methanol Aspartame (10%) Asp/Phe Peptidases Aspartate (40%) + Phenylalanine (50%) Esterases Methanol + Asp/Phe Peptidases Aspartate + Phenylalanine Methanol Aspartate Phenylalanine Aspartame does not enter blood as a whole Components of digestion same as from other foods. Dipeptide Transport System

10 Other dietary sources of aspartame digestion products Food Phenylalanine (mg) Aspartic acid (mg) Methanol (mg) Aspartamesweetened Soft drink (340 ml) Non-fat milk (340 ml) Tomato Juice (340 ml) Orange juice (340 ml)

11 Cyclamate Discovered in 1937; Sweetness potency compared to sucrose is about 35-50; Approved in over 100 countries; Incomplete absorption from the gut most excreted in faeces; Absorbed cyclamate is excreted in the urine.

12 Saccharin (Benzoic sulfimide) Discovered in 1878; 300 times sweeter than sugar; Has metallic aftertaste, which limits use. Often blended with other sweeteners. Not metabolized; Excreted in urine.

13 Extraction and purification Stevia extracts glucose O H CH 3 O glucose H O glucose O O CH 3 CH 2 glucose Purified extracts from the leaves of the South America shrub - Stevia rebaudiana; Sweetness comes from steviol glycosides, such as rebaudioside A; Purified glycosides are x sweet as sugar; Glycosides contain glucose molecules.

14 Steviol glycosides: metabolism glucose O glucose O glucose Steviol glycosides are not absorbed. O Steviol CH 3 CH 2 H glucose O H CH 3 O Glucose units removed by bacteria in large intestine. Time varies for different glycosides. All metabolized to steviol backbone. Steviol absorbed in large intestine, modified by liver, and excreted.

15 Sucralose Cl HO O HO OH 600 X as sweet as sucrose; Structure similar to sucrose, but with 3 OH groups changed to Cl. HO O O Cl OH Cl

16 Sucralose: absorption, digestion, metabolism and elimination About 85% ingested sucralose is not absorbed into the body; Gut microflora unable to hydrolyse sucralose; Unabsorbed sucralose is eliminated in the faeces unchanged; The small amount of sucralose that is absorbed by body: Most unchanged and excreted in urine, Small amount metabolized by liver then excreted in urine.

17 So are these sweeteners safe? What about the concerns that I read about?

18 Do low-calorie sweeteners cause cancer? Answer = No! Many allegations, but many studies have been conducted. Before alternative sweeteners can be approved for use, studies must show: Do not cause mutations or DNA damage When fed every day for animal life time, do NOT cause cancer at doses that humans will be exposed to. Must also consider whether mechanism is relevant in humans (such as for saccharin) Recently, when Soffritti et al. reported aspartame caused cancer in rats and mice, in contrast to all previous studies on aspartame. Resulted in: Extensive review of protocol and data by numerous experts: (European Food Safety Authority; FDA; Health Canada; US Toxicology Program; International expert panel) All concluded that: Serious flaws in methodology & interpretation in Soffritti studies There is no credible evidence that aspartame is carcinogenic (EFSA, 2013; Magnuson et al., Crit Rev Tox, 2007)

19 Overwhelming majority of epidemiological studies find no association between low-calorie sweeteners & cancer Author Type of study (N) Assessment of Consumption Conclusions Olney (1996) Number of brain tumors cases from 9 US locations Not measured Higher after aspartame approval Gurney (1997) 56 brain tumor cases 94 controls Dietary recall - Personal interview No association Hardell (2001) 30 brain tumor cases 45 controls Recall of low-calorie soft drinks. No association Bunin (2005) 315 child brain tumor cases, 315 controls Food frequency by mothers of children No association Lim (2006) Prospective 473,984 subjects, 5 yr. Hematopoietic and brain cancers Food frequency questionnaires No associations Gallus (2007) Case control; various cancers (8976 cases, 7028 controls) Food frequency questionnaires No association Bosetti (2009) Case control; various cancers (1010 cases, 2107 controls) Food frequency questionnaires No association Schernh ammer (2012) Prospective: 22 yr. Nurses Health Cohort (77,218 F); Health Professionals Follow-Up Cohort (47,810 M). Hematopoietic cancers Food frequency questionnaires every 4 years No association with combined cohorts. Some weak positive when separate

20 Are low-calorie sweeteners safe for pregnant women? Children? Answer = Yes! This question MUST be answered before sweetener is approved for use in foods and beverages!

21 Do low-calorie sweeteners increase appetite? body weight? Answer No! Hypothesis based on observational studies showing positive correlations between low-calorie sweeteners and body weight. Cause or result? Association does not establish CAUSE!

22 Studies conclude low-calorie sweeteners do not cause weight gain Meta-analysis: 16 studies assessing effect of aspartame on weight loss, found using foods and drinks sweetened with aspartame instead of sucrose results in a significant reduction in both energy intakes and body weight (de la Hunty et al., 2006). No evidence that low-calorie sweeteners are cause of higher body weights in adults (Anderson et al., 2012). Short-term randomized controlled trials find low-calorie sweetener use is BMI neutral or weight-reducing in overweight/obese adolescents. Long-term data are lacking (Foreyt et al., 2012).

23 What Experts Are Saying About Weight Control and Low-Calorie Sweeteners Consumers find it difficult to know who to believe. In the final analysis, all health experts agree that weight loss is best achieved by a combination of reducing caloric intake, lowering energy density of the diet, and increasing physical activity. By all accounts, lowcalorie sweeteners do help. Suggesting that lowcalorie sweeteners actually cause people to gain weight is an irresponsible direct application of rat models to dietary counseling and to public health. -Dr. Adam Drewnowski University of Washington, Professor of Epidemiology

24 AHA & ADA Statement on Low-Calorie Sweeteners On July 9, 2012, the American Heart Association and the American Diabetes Association released a joint statement on low-calorie sweeteners, concluding: The evidence reviewed suggests that when used judiciously, non-nutritive sweeteners could facilitate reductions in added sugars intake, thereby resulting in decreased total energy and weight loss/weight control, and promoting beneficial effects on related metabolic parameters.

25 Academy of Nutrition and Dietetics on Low-Calorie Sweeteners In 2012, the Academy of Nutrition and Dietetics released their position statement on low-calorie sweeteners concluding: 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.

26 Conclusions on Safety Low-calorie sweeteners are quickly used or excreted from the body. Extensive testing, with animal lifetime studies is required to confirm safety. Many human epidemiological studies have shown no association with adverse effects. All approved low-calorie sweeteners are safe.

27 Conclusions on Benefits Well-conducted clinical studies have shown that weight loss and weight maintenance is more successful with use of low-calorie sweeteners.

28 Thank you! For More Information CalorieControl.org Acesulfamek.org Aspartame.org Cyclamate.org Fructose.org Polyol.org Saccharin.org Steviabenefits.org Sucralose.org The Calorie Control Council

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