2. How to evaluate clinical and scientific studies on non-caloric sweeteners Bernadene Magnuson, PhD, FATS University of Toronto, Canada
3. Introduction Hundreds of studies and reports have been published on non-caloric sweeteners. Yet, is still controversial topic! Regulatory agencies approve safety-
4. Introduction Yet, many websites and articles claim that sweeteners are associated with a wide variety of potential adverse effects and should be avoided.
5. Introduction How can we determine what to believe? How can we explain the different opinions? What advice to give patients, family, friends?
6. Outline Overview of approaches to evaluation of studies Preclinical studies, clinical studies, reviews Examples Sweeteners and weight loss/gain? Aspartame and cancer? Conclusions
7. Critical points to consider What type of study and how conducted? Will discuss in detail in next slides Was the study/report published in peer-reviewed literature? Recent conference presentation on soft drinks and obesity widely publicized but never published reports on websites and media not reviewed by scientists What are the credentials of the author(s)?
9. Methods for assessing reliability of scientific reports Toxicology studies ToxRtool (Schneider et al., 2009, Toxicology Letters) Clinical studies Institute for Clinical Systems Improvement( ICSI) 2003 American Dietetic Association – Evidence Analysis
10. Assessing preclinical studies If using cells or cell material (enyzmes), consider: Are simplified, isolated systems Effect of digestion and absorption? I.e. Aspartame is completely digested to amino acids and methanol, which is rapidly metabolized to CO2; Direct addition of aspartame to cells? – never occurs in human Concentration – how compares to amount from diet? Response of cells – is effect within the normal range? What is the control treatment?
11. Assessing preclinical studies If using animals, consider: Dose given orally? added to diet? Number of doses? Diet defined composition? nutritionally adequate? stability and consistency? Animals background historical incidence of disease health of animals Methods Appropriate protocols?
12. Interpretation of results Evidence of dose response? If at high dose only, due to inflammation or metabolic overload? Is dose relevant to human exposures? Increase over historical controls? Is tumor type relevant to humans? i.e. forestomach tumors Is mechanism relevant to humans? i.e. formaldehyde and nasal tumors in rats ToxRTool - to assess the reliability of toxicological data. Schneider et al., 2009, available online
19. Primary Study Considerations Were inclusion/exclusion criteria clearly stated? Adhered to? Any question of bias introduced in the study ? Does report show statistically significant but clinically insignificant effect? Or lack power? Too small sample size? Are the results generalizable to other populations? Any traits of a poorly-designed study? Examples: treatment and control groups different at baseline, low compliance with the intervention, important outcomes not measured, inappropriate statistics for study design. (www.icsi.com)
20. Secondary Report Considerations Was search for primary studies comprehensive and current? Were clear criteria given for inclusion/exclusion of studies? Was quality of the articles assessed and reported? If a meta-analysis was done, was homogeneity assessed? If no meta-analysis was done, did the authors state why not? Was there at least a narrative synthesis of primary studies? Are studies in review generalizable to target population? Are conclusions valid (i.e., based on primary evidence)? (www.icsi.com)
22. Body weight changes in rats fed non-caloric sweeteners Aspartame-either have no difference or reduced body weight (and reduced food intake) compared to controls. Saccharin –increased weight gain (Switherset al., 2009); due to increased food intake. Effect on appetite or section of gastrointestinal peptides No effect of sweetener (aspartame, acesulfame K or sucralose) on appetite or section of gastrointestinal peptides that regulate appetite in rats or humans (Steinertet al., 2011) ; in contrast to studies with isolated cells in culture. Preclinical studies
23. Critical review of Clinical Studies American Dietetic Association, January 2009 Does aspartame affect appetite or food intake? Evidence Analysis method used to evaluate each study, based on ICSI guidelines. 19 studies in adults ; 14 randomized controlled; 4 nonrandomized; 1 short term. Conclusion: “There is good evidence that aspartame does not affect appetite or food intake in adults.” Grade 1 = good evidence to support conclusion.
24. Epidemiological studies Examine relationship between reported use of sweeteners and weight gain. Need to control for confounding variables. Example - Fowler et al. (2008) - Reported use of sweeteners associate with obesity. Number of methodological concerns – main issue is that data collection taken over 2 phases (1979-1982) and (1984-1988). Aspartame was not approved for food until (1981) and beverages in 1983! Thus inferences made against Aspartame are invalid!
25. Do non-caloric sweeteners promote weight loss? Or gain? Conclusion: Well-conducted clinical studies have shown that weight loss and weight maintenance is more successful with use of non-caloric sweeteners.
26. Does aspartame cause cancer? Preclinical studies Cells and bacteria studies have shown aspartame does NOT cause mutations 16 chronic animal studies: multiple species 14 found no evidence of carcinogenic or promoting effects of aspartame Only studies reporting positive results by Soffrittiet al. Detailed review of protocol and data of Soffrittiby numerous experts: EFSA; FDA; Health Canada; US National Toxicology Program; International expert panel (Crit Rev Toxicology, 2007) All conclude that: Are serious flaws in methodology and interpretation in Soffrittistudy “there is no credible evidence that aspartame is carcinogenic” “no need to revise previously established ADI”
28. Does aspartame cause cancer? Most preclinical studies aspartame does NOT cause cancer. few positive studies - serious flaws. Epidemiological studies if measured consumption – all find no association Conclusion: Aspartame does not cause cancer.
29. EFSA review of Aspartame At the request of the European Commission, EFSA has reviewed the safety of aspartame 4 times since first approved. Most recent – Feb 2011. Each time concluded - no need to conduct further studies, or to alter Acceptable Daily Intake (ADI). May 2011 – announced will review again in 2012 as part of the systematic re-evaluation of all authorized food additives in the European Union.
30. Conclusions Critical review of primary studies is required to identify weaknesses or limitations. Several published guidelines for conducting reviews are available. The overall weight of evidence from well-conducted studies supports the use of approved non-caloric sweeteners.
34. Clinical study - Appetite Anton et al., 2010. tested effect of preloads containing stevia, aspartame, or sucrose on food intake, satiety, and postprandial glucose and insulin levels. Design: 19 healthy lean and 12 obese individuals Preload, given before lunch and dinner; food intake measured. Hunger and satiety levels reported before and after meals, and every hour. Results: Despite caloric difference in preloads , did not compensate by eating more at meals Self- reported hunger and satiety levels did not differ.
42. Secondary review of literature American Dietetic Association, January 2009 Does aspartame affect appetite or food intake? Evidence Analysis method used to evaluate each study Only 2 studies in children ; 1 randomized controlled; 1 nonrandomized. Conclusion: “Limited evidence indicates that aspartame consumption does not affect appetite or food intake in children. Grade III = limited evidence to support conclusion
Hinweis der Redaktion
cohort prospective study two groups (cohorts) of subjects are identified, one of which is exposed to a clinical intervention, an environmental condition, or health risk factor, and the other group is not. The major disadvantage of the cohort study, compared to the randomized study, is that the groups may not be equivalent on other factors such as diet or smoking history. case-control study a group of patients who already have a disease or other outcome (the cases) is compared to another group of controls who do not. Thus, such studies are conducted retrospectively, not prospectively.
cohort prospective study two groups (cohorts) of subjects are identified, one of which is exposed to a clinical intervention, an environmental condition, or health risk factor, and the other group is not. The major disadvantage of the cohort study, compared to the randomized study, is that the groups may not be equivalent on other factors such as diet or smoking history. case-control study a group of patients who already have a disease or other outcome (the cases) is compared to another group of controls who do not. Thus, such studies are conducted retrospectively, not prospectively.
