Valutazione della sicurezza di una pianta : un case report

Steviol glycosides are high intensity sweeteners, extracted from Stevia rebaudiana. They are 250-300 times sweeter than sucrose and have been used for several years in a number of countries as sweeteners for a range of food products. Steviol glycosides are approved for use in a number of countries. In particular, Japan has used Stevia as its main non-sucrose sweetener source for more than 30 years. Other countries which allow the use of steviol glycosides include China, Russia, Korea, Brazil, Paraguay, Argentina, Indonesia and Israel. Steviol glycosides do not have Generally Recognised As Safe (GRAS) status in the United States of America (US) and are therefore not currently permitted to be added to foods in the US; although they are sold as a dietary supplement. The European Union (EU) considers steviol glycosides to be a food additive and has not approved them for use in food. Stevia rebaudiana is approved for use as an active and/or excipient ingredient in Listed medicines in Australia. There have been no known adverse effects for stevioside reported to the Therapeutic Goods Administration to date in this country. Steviol glycosides5 are a mixture of high intensity sweeteners which are readily extracted from the leaves of the plant Stevia rebaudiana. The steviol glycosides in highest concentration in extracts, namely stevioside and rebaudioside A, are two of around ten other steviol glycosides present. The Joint (FAO/WHO) Expert Committee on Food Additives (JECFA) first assessed the toxicity of stevioside at its 51st meeting (WHO, 1999). Owing to an incomplete toxicological database JECFA was unable to recommend an ADI. JECFA reconsidered stevioside at its 63rd meeting (WHO, 2005) and noted that most of the data requested at the 51st meeting was available. JECFA therefore decided to allocate a temporary ADI, of 2 mg/kg body weight/day, expressed as steviol, pending submission of further data on the pharmacological effects of steviol glycosides in humans. Stevioside has very low acute toxicity and there is no evidence of carcinogenicity, developmental, reproductive or genotoxicity effects. Several studies in animals and humans indicate that steviol glycosides have antihypertensive and antiglycaemic effects. While the exact mechanism of action has not been fully elucidated, the absence of urinary metabolites apart from conjugated steviol suggests that unconjugated steviol is pharmacologically active in humans. Steviol glycosides are well tolerated and unlikely to have adverse effects on blood pressure, blood glucose or other parameters in normal, hypotensive or diabetic subjects at doses up to 11 mg/kg bw/day. The adequacy of the existing database and a new study in humans provides a basis for revising the uncertainty factors that were used by JECFA to derive the temporary ADI for steviol glycosides in 2005 (2 mg/kg bw/day steviol). In particular, the evidence surrounding the pharmacological effects of steviol glycosides on blood pressure and blood glucose has been strengthened so that the additional 2-fold safety factor for uncertainty related to effects in normotensive or diabetic individuals is no longer required. Therefore a full ADI of 4 mg/kg bw/day, derived by applying a 100-fold safety factor to the NOEL of 970 mg/kg bw/day (equivalent to 383 mg/kg bw/day steviol) in a 2-year rat study, has been established by Australia and new Zealand Food Agency.