ILSI SEA Region Seminar on Uses and Safety of Sweeteners (May 2013) http://www.ilsi.org/sea_region/pages/vieweventdetails.aspx?webid=4d540914-eeb6-40e4-89eb- 0B73BA3D76C1&ListId=478BE3CB-581B-4BA2-A280-8E00CCB26F9C&ItemID=73 Approaches to Evaluating Safety of Natural versus Artificial Sweeteners Is There a Difference? Berna Magnuson, Ph.D. Fellow, Academy of Toxicological Sciences
The short answer-
No differences in the evaluation process for artificial versus natural sweeteners For the following: standards of safety that must be met for approval of use as food additive. Is same potential of toxicity from natural versus artificial compounds. Many natural compounds and plants are not safe! requirement for characterization of material, critical review of toxicology data and approach to set ADI.
Same safety standards for natural and artificial food ingredients FSANZ: From a safety point of view, Food Standards Australia New Zealand (FSANZ) spokesperson Lydia Buchtmannassures that a colouror flavouring (ingredient) with the same molecular make-up would be equally safe whether it was naturally occurring or man-made. US FDA: Food ingredients are subject to the same strict standards regardless of whether they are naturally or artificially derived.
Yes Areas of potential differences in the evaluation process 1. Unlike artificial sweeteners, natural compounds may have a history of use of that can be considered, if appropriate. Must be well documented, in the general population May not be sufficient for use as sweetener in foods 2. Artificial sweeteners are usually standardized, highly purified single compounds. The compositionof natural sweeteners produced by extraction of plant materials is often complex and inconsistent. 3. For natural compounds, variations in growth conditions, harvesting, and processing methods can lead to compositional differences or contaminants. These can affect safety. Case study Steviol glycosides
History of Approval of Steviol Glycosides Pre 1800s Stevia leaves used in South America as sweetener and treatment for diabetes Identification of steviolglycosides from stevia. Investigations into potential uses. Cultivation expands 1940-50s 1960-1980 Initial studies on safety. Stevia extracts used in foods commercially in Japan.
Steviolglycosides Rebaudioside A O glucose O glucose O O glucose glucose O CH 3 CH 2 H H CH 3 Sweetness comes from steviolglycosides, such as rebaudiosidea. Glycosides contain glucose molecules. Number and position of glucose molecules vary with different glycosides. Purified glycosides are 200-300x sweet as sugar
History of Approval of Steviol Glycosides 1985 Scientific Committee on Food concludes use of steviosideas sweetener not toxicologically acceptable due to limited data. Additional studies conducted. JECFA conducts review of steviol 1999 glycosides. No ADI set due to lack of consistent test materials in studies and toxicology concerns. JECFA sets specifications 2004 and temporary ADI for steviolglycosides pending submission of additional safety data.
Safety Concerns with Stevia Extracts JECFA, 1999 Limited data on metabolism of different glycosides. Genotoxicity not adequately addressed. Lack of data on long-term toxicity and carcinogenicity or reproductive and developmental effects. Concerns with historical reports of use of stevia as abortifacientand observations of adverse reproductive effects of stevia extracts in rat studies.
Steviolglycosides: Metabolism glucose O glucose O glucose Steviolglycosides are not absorbed. O CH 3 CH 2 H Steviol OR 2 glucose O O CH 3 H Glucose units removed by bacteria in large intestine. Time varies for different glycosides. All metabolized to steviolbackbone. R 1 O O CH 3 CH 3 CH 2 H H Steviolabsorbed in large intestine, modified by liver, and excreted.
JECFA, 2004 Requests that chemical specifications for extracts be established to allow for comparison of material used in studies to materials used in commercial foods/beverages. Additional studies requested in human subpopulations considered susceptible (individuals with low blood pressure and diabetics).
Example of Purification Process for High Purity SteviolGlycosides Stevia Leaves Water or ethanol extraction Separation and filtration Ion Exchange Decolorization Deionization Crystallization of glycosides Drying Packaging
History of Approval of Steviol Glycosides JECFA extends temporary ADI due to 2007 continued safety concerns. 2008 JECFA establishes permanent ADI for high purity steviol glycosides of 0-4 mg/kg. 2010- present JECFA continues to evaluate safety of newly identified natural steviol glycosides.
Natural not same as Approved For many years, the authorities still had safety concerns despite this being naturally sourced ONLY extracts that are purified to >95% steviol glycosides are approved for use in foods and beverages by JECFA and many jurisdictions. Natural stevia extracts that are not adequately purified to meet specifications are NOT approved by JECFA or many countries as safety has not been adequately established.
Natural Safe Many people have a FALSE perception that anything natural is safe and healthy. This misunderstanding has caused many illnesses and deaths. Many naturally occurring compounds are carcinogens or toxic. Aristolochicacids, mushroom poisons, and hundreds more. Focusing on natural as a safety criterion is not scientifically valid.
Natural Safe Isolation and concentration of compounds from plants may change toxicity. Example: Isolated green tea catechins associated with liver toxicity and currently not considered safe for use as food ingredient. The dose makes the poison, regardless of whether natural or artificial. Thus it is amountof the compound consumed, not the source, that is critical for safety.
When Natural is no longer Natural? The source of Natural sweeteners may not be from a natural food. For example, the sweetener, xylitol is now commercially produced through fermentation of wood pulp or other waste cellulose. Thus, the safety evaluation of sweeteners is based on the properties of the final compound, not the source or method of production.
What about sweetener that does not occur naturally, but is digested to naturally occurring compounds? Amino Acid Methyl group Amino Acid Artificial sweetener, Aspartame Produced through fermentation. 200 X sweet as sucrose Methylated dipeptide of 2 common amino acids found in proteins Aspartic acid (aspartate) Phenylalanine Digested to naturally-occurring compounds
Intestine cell Aspartame does not enter body as a Aspartame Methanol + AA-AA Aspartate + Phenylalanine whole X X Blood vessel wall Portal Blood Methanol Aspartate Phenylalanine VERY IMPORTANT Only breakdown products of aspartame can enter blood! Aspartame does not enter body as a whole molecule. Only amino acids and free methanol enters portal blood which goes directly to liver. Results in same amino acids and methanol as with digestion of proteins, fruits and vegetables.
Amino Acids and Methanol In Foods Food Phenylalanine (mg) Aspartic acid (mg) Methanol (mg) Aspartamesweetened Soda (340 ml) Non-fat milk (340 ml) Tomato Juice (340 ml) Orange juice (340 ml) 90 72 18 606 953-58 346 107 24 180 23
Portal Blood Methanol Aspartate Phenylalanine Fate of digestion products from aspartame is the same as the digestion products from foods -Portal blood flows directly to the liver. Methanol -Amino acids are used in synthesis of new proteins that are needed by body. Proteins -Methanol is metabolized in the liver to endogenous products. Liver
The Safety Assessment of Artificial AND Natural Sweeteners Requires: Consistent composition and purity. Same test material used in toxicology studies as in commercial applications. Understanding of metabolism and fate of metabolites. Demonstration of No Observed Adverse Effects in chronic toxicity and carcinogenicity studies. Consideration of potential susceptible subgroups, such as pregnant women and children. Demonstration that exposures to sweeteners are predicted to be below the established ADI, for all subgroups.
References and Resources Abdel-Rahmanet al. 2011. The Safety and Regulation of Natural Products Used as Foods and Food Ingredients. Toxicological Sci. 123(2), 333 348. FSANZ position on natural versus man-made http://www.bodyandsoul.com.au/food+diet/nutri tion/your+diet+de+coded.13631 US FDA position on natural versus artificial http://www.fda.gov/food/ingredientspackagingla beling/foodadditivesingredients/ucm094211.htm
Thank you! Questions? b.magnuson@utoronto.ca