The document summarizes research on Truvia rebiana, a zero-calorie sweetener derived from the stevia plant. It details studies showing rebiana is safe for consumption and does not negatively impact blood pressure or blood sugar levels. Regulatory bodies in the US and Europe have approved rebiana as a food additive based on extensive safety testing.

1. Truvia ™ rebiana Zero-calorie sweetness from the stevia leaf Background briefing: history and safety assessment

2. Contents Stevia – unique plant, unique story From Green to White Truvia™ rebiana Overview of research results Expert reviews and approvals Summary of conclusions Implications for consumers Stevia rebaudiana Bertoni

3. Stevia: unique plant, unique story Shrub in the Asteraceae family native to northeastern Paraguay First discovered by indigenous people who used plant’s leaves to sweeten drinks By 1800s, stevia consumption established throughout South America, including Brazil and Argentina Food researchers worldwide have been working with stevia for decades In 1931, French food chemists isolated compounds (steviol glycosides) that give stevia its sweet taste Japan has been using stevia commercially for over three decades Stevia-sweetened food and beverages are now available to consumers on every continent US market opened in 2008 and France in 2009

4. Steviol glycosides – the sweet constituents 2 most predominant stevioside rebaudioside A Stevioside: R=H Rebaudioside A: R= 10+ glycosides in the leaf C H 2 C H 3 H H O O O O H 3 C H O O H O H H O O O O R H O O H O O H O H H O H O O H O O H O H H O

5. From Green to White Steviol Glycosides Stevioside Rebaudioside A Others Rebiana The first fully characterised, high­purity form of rebaudioside A Other components Stevia rebaudiana Bertoni or “ stevia ”

6. Stevia – the vocabulary Stevia General term used to refer to the plant and commercially to food uses of Stevia rebaudiana (botanical name) Stevia extract refers to compounds isolated (extracted) from stevia without regard to purity or identity of the compounds Steviol glycosides Sweet tasting components in leaves of the stevia plant Leaf contains at least 10 unique steviol glycosides including rebaudioside A, stevioside, rebaudioside C Rebaudioside A Best tasting steviol glycoside Also called “reb A” for short Purified from the leaf, it provides a clean, sweet taste Rebiana* Ingredient containing high-purity rebaudioside A Purity assures clean, sweet taste Rebiana is not less than 97% rebaudioside A * Appears on ingredient labels in the US Truvia ™ Brand name of leading sweetener derived from Stevia

7. Attributes of rebiana Plant­derived, high potency, zero­calorie, good tasting sweetener T he best tasting part of the stevia leaf – not less than 97% rebaudioside A 200­300 times sweeter than sucrose Non­caloric, non­glycemic Good solubility Heat and pH stable in food and beverage systems

8. Introduction to Truvia ™ rebiana Truvia™ rebiana is comprised entirely of purified steviol glycosides, containing not less than 97% rebaudioside A Truvia™ rebiana (ingredient) and Truvia™ tabletop sweetener launched in the USA in 2008: Brand has established leadership position in new category of zero-calorie, plant-derived, high intensity sweeteners Cargill, maker of Truvia ™ rebiana, has applied for European regulatory approval European Food Safety Authority recently completed a safety assessment; their Scientific Opinion published on 14 April 2010

9. EFSA Scientific Opinion EFSA confirmed that steviol glycosides are safe for use in foods and beverages “ Steviol glycosides complying with JECFA specifications are not carcinogenic, genotoxic or associated with any reproductive / developmental toxicity” EFSA established an Acceptable Daily Intake (ADI) for their safe consumption Expert panel established same ADI as previously established by JECFA EFSA Scientific Opinion is critical milestone in EU approval process; final EU regulatory approval likely to be in 2011

10. Rebiana safety programme objective Demonstrate the safety of rebiana for consumption by all consumers , in all foods, for all eating occasions in all countries

11. Research on stevia and steviol glycosides Stevia and its components have been evaluated in a range of studies over the past five decades Studies varied widely in purpose, design and quality: Many small studies used a crude extract of stevia, making it impossible to attribute the observed effects to any part of the leaf Others injected steviol glycosides into animals or fed animals very large amounts of steviol (the breakdown product of the steviol glycosides) Minority of these studies raised questions about potential effects on reproductive health and kidney function Some human studies suggested beneficial effects on blood pressure and blood sugar

12. Rebiana safety programme Cargill and The Coca Cola Company collaborated to develop the ingredient rebiana – high purity rebaudioside A With guidance from global food safety experts and leading external scientists, Cargill’s research programme set out to: Systematically evaluate a fully characterised , high ­ purity form of rebaudioside A Ensure stevioside safety data are relevant to rebaudioside A Resolve questions raised by regulatory authorities, with further clinical studies where appropriate

13. Research results overview Programme Area Findings / Implications Metabolism studies Metabolism of rebaudioside A is similar to that of stevioside Extensive toxicology data on stevioside can be applied to rebiana General toxicology No signs of toxicity associated with daily consumption of the equivalent of 2,000 250ml servings of a rebiana-sweetened beverage (for a 68kg person) No treatment-related effects on any organ, including kidneys and male reproductive organs Multigenerational/ reproductive toxicology No treatment effects on reproductive health or developmental outcomes

14. Clinical programme Address JECFA request for additional data pertaining to potential pharmacological effects of steviol glycosides in humans Blood pressure lowering effects Effects on blood glucose in people with diabetes Provide definitive data to further support the safety of rebiana Hemodynamic effects of rebaudioside A in healthy adults with normal and low-normal blood pressure (Blood pressure study) Chronic consumption of rebaudioside A in men and women with type 2 diabetes mellitus (Diabetes study) Comparative pharmacokinetics of rebaudioside A and stevioside in humans

15. Blood pressure study: Changes from baseline to treatment for resting, seated blood pressure *ANCOVA; initial model included terms for baseline value, treatment, site, and treatment by site interaction. Values for pre- to post-treatment change in DBP were ranked prior to analysis. SBP – systolic blood pressure; DBP – diastolic blood pressure; MAP – mean arterial pressure Maki et al. (2008) Food and Chem Toxicol 46:S40-S46 Resting, Seated Measurements Rebaudioside A (n=50) Placebo (n=50) p-value* Mean ±SEM Baseline SBP (mm Hg) 110.0 ± 1.2 110.7 ± 1.3 0.683 SBP Δ -1.3 ± 0.7 -0.4 ± 0.8 0.237 Baseline DBP (mm Hg) 70.3 ± 0.9 71.2 ± 0.9 0.529 DBP Δ -1.3 ± 0.5 -0.7 ± 0.5 0.154 Baseline MAP (mm Hg) 83.6 ± 0.9 84.3 ± 1.0 0.554 MAP Δ -1.3 ± 0.6 -0.6 ± 0.6 0.192

16. Diabetes study: Glycosylated hemoglobin at baseline to weeks 4, 8, 12, 16 *P-values for the change from baseline are for the analysis of covariance with baseline value as the covariate. All values were ranked prior to analysis. Maki et al. (2008) Food and Chem Toxicol. 46:S47-S63 Glycosylated hemoglobin Rebaudioside A (n=60) Placebo (n=62) p-value* Mean ±SEM Baseline (%) 6.71 ± 0.11 6.70 ± 0.10 0.964 Week 4 Δ (%) 0.02 ± 0.03 0.02 ± 0.903 0.982 Week 8 Δ 0.11 ± 0.05 0.04 ± 0.04 0.574 Week 12 Δ 0.11 ± 0.05 0.07 ± 0.05 0.248 Week 16 Δ 0.11 ± 0.06 0.09 ± 0.05 0.355

17. Diabetes study: Results of secondary outcomes No effect of rebaudioside A on the following outcomes: Fasting glucose, insulin, C-peptide Body weight Total-C, LDL-C, HDL-C, Non-HDL-C, triglycerides Maki et al. (2008) Food and Chem Toxicol. 46:S47-S63 Rebaudioside A (n=60) Placebo (n=62) p-value Mean ± SEM Baseline SBP (mm Hg) 121.6 ± 1.4 126.0 ± 1.6 0.051 Δ (mm Hg) -0.2 ± 1.0 -0.9 ± 1.1 0.775 Baseline DBP 72.5 ± 1.0 71.3 ± 1.1 0.429 Δ 0.2 ± 0.8 -1.1 ± 0.7 0.132

18. Publication of the science supporting safety EFSA Scientific Opinion (14 April 2010) “ Steviol glycosides complying with JECFA specifications are not carcinogenic, genotoxic or associated with any reproductive / developmental toxicity” “ The Panel considers that there is no need to further test the potential of carcinogenicity of steviol glycosides in other species (e.g. mouse)” 12 papers evaluating the safety of rebiana have been published electronically in the peer-reviewed journal Food and Chemical Toxicology. The published studies clearly establish the safety of rebiana for use as a sweetener in food and beverages. Ref: Food and Chemical Toxicology, Vol 46:7 S1-S92 (2008)

19. Expert reviews - 2008 Food and Chemical Toxicology Published safety studies Joint FAO/WHO Expert Committee on Food Additives (JECFA) Comprehensively examined the safety data and set a permanent ADI GRAS (Generally Recognised As Safe) Independent Expert Panel Critically reviewed Truvia ™ rebiana database of studies Determined its safety for general purpose use as a sweetener Food and Drug Administration (FDA) Issued no-objection letter Rebiana affirmed as Generally Recognised as Safe (GRAS) Toxicology Forum Panel multi-stakeholder symposium Reviewed safety of rebaudioside A

20. Expert reviews - 2009/10 French Food Safety Agency AFSSA Assessed safety of rebaudioside A Temporary legal approval of ≥97% rebaudioside A for up to a maximum of 2 years, for use in certain food and beverages in France, published on 6 September 2009 First market in EU to approve European Food Safety Authority (EFSA) Reviewed safety of steviol glycosides, including rebaudioside A Expert panel’s Scientific Opinion officially published on 14 April 2010

21. Acceptable Daily Intake (ADI) Definition of ADI Estimate of the amount of a food additive that can be consumed daily over an entire lifetime without appreciable health risk ADI for steviol glycosides is 4 mg/kg bw/day on a steviol basis Established by JECFA and EFSA Translated for rebiana is 12 mg/kg bw/day Approximately equivalent to 23 teaspoons of Truvia™ tabletop sweetener every day over the course of a lifetime EFSA said ADI could be exceeded at max. proposed usage level Projected uses were based on provisional industry estimates and may need to be adjusted before final EU regulation

22. Summary of conclusions Truvia™ rebiana is safe for use in food and beverages High purity rebaudioside A (rebiana) is fully differentiated from crude stevia Truvia™ rebiana is reproducibly purified to specifications that exceed regulatory requirements Clinical studies indicate lack of pharmacological action of steviol glycosides No effect on blood pressure in individuals with normal and low-normal blood pressure No effect on glucose homeostasis Successive independent expert assessments have validated the weight of safety evidence EFSA is the latest and most relevant to European regulatory approval

23. Implications for consumers Truvia™ sweetener provides a zero-calorie sweetening choice for consumers Truvia™ sweetener is already in use in France following French regulatory approval of rebaudioside A Once approved for EU-wide use, it will be available as a tabletop sweetener and as an ingredient in foods and beverages As research and safety assessments show, it can safely be used by all consumers, whether watching weight or managing diabetes

24. Key references Food and Chemical Toxicology 46 (2008) S1-S92 Peer-reviewed published papers; available on request from Cargill EFSA Journal 2010;8(4):1537 http//www.efsa.europa.eu/en/scdocs/scdoc/1537 Joint FAO/WHO Expert Committee on Food Additives. 69 th Meeting, 2008. JECFA/69/SC, 4 July 2008. Steviol glycosides ADI Food and Drug Administration (FDA), 2008. http://www.fda.gov/Food/FoodIngredientsPackaging/GenerallyRecognizedasSafeGRAS/GRASListings/ucm154989.htm Journal officiel de la République Fran çaise, 6 September 2009, éd. no. 206 http://textes.droit.org/JORF/2009/09/06/0206 - item 6

25. For further information or to request Food and Chemical Toxicology reprints contact: Amy Boileau, Ph.D, R.D. Manager, Regulatory & Scientific Affairs Food Ingredients & Systems, Cargill [email_address] Truvia™ sweetener Zero-calorie sweetness from the stevia leaf