Stevia has been long cultivated as a sweetener. The extracts of the leaves, steviol glycosides, are responsible for its sweet characteristics; the main two steviol glycosides are stevioside and rebaudioside A (reb A). Stevioside is non-caloric and is 250-300 times sweeter than table sugar (sucrose). Stevia has also exhibited blood glucose and insulin lower capabilities1 as well as free radical scavenging, an antioxidant property.2 Therefore, for those trying to control their blood sugar or reduce caloric intake, it offers an excellent alternative to sucrose.
There are many benefits to consuming stevia as an alternative sweetener, although controversy surrounds steviol glycosides and their safety for consumption. A 2007 study by Nunes et al. conducted in Wistar rats concluded stevioside caused DNA damage in multiple organs3. One group of rats (n=5) were fed ad libitum with water containing stevioside (4mg/mL), while the control group drank filtered water for 45 days. In rats fed the stevioside, a significantly greater number of damaged nuclei were noted at weeks 5 and 6, in comparison to that of control animals. In addition, treated rats showed elevated DNA damage in the liver, brain and spleen, leading to the conclusion that stevioside may cause DNA lesions and damage.
In a review by Brusick et al.4, it was reported that several studies have not been able to reproduce the results of Nunes et al.3, due to inconsistences in methodology and questions regarding the levels of stevia consumed. An earlier investigation examined the ingestion of steviol (250-2,000mg/kg body weight) and found no DNA damage in the stomach, colon, liver, kidney or testis.5 The majority of studies reviewed by Brusick et al. concluded stevioside, reb A, and steviol do not induce genotoxicity or mutagenicity. The few in vitro assays that have reported mutagenic properties have not been able to be reproduced in bacteria that possess (like humans) normal reparative DNA processes4.
Genetic abnormalities following the consumption of stevia bioactives have been reported in some but not all research. In hamsters, high doses of steviol (750mg and 1,000mg/kg body weight per day) led to birth defects, declines in survival rate, maternal toxicity and reduced weight gain during gestation6. However, 500mg/kg body weight of steviol resulted in fewer signs of toxicity. Lower doses showed no evidence of toxicity. Dosages that led to toxicity were extremely high and nearly impossible for a human to consume; it would be the equivalent to 60,000mg steviol (at the 1,000mg/kg body weight) for an average 60kg woman.
The possible genotoxic effects of reb A have been assessed using in vitro and in vivo assays7. Concentrations of reb A, ranging from 32.0-5,000ug/mL, were tested in vitro in bacterial strains, rat liver cells, human lymphocyte cells, mouse bone marrow cells and in vivo in a mouse model. The data from all testing indicated reb A was not mutagenic nor genotoxic.
Human research has also been performed. A two-year randomized, double-blinded controlled study investigated the effects of stevioside on blood pressure and tolerability in Chinese men and women (n=168) with mild hypertension8. Subjects consumed 1.5g of stevioside per day (500mg three times a day) or a placebo in powder form for two years. At the conclusion of the study, the stevioside group had significantly lower mean systolic (-10mm Hg) and mean diastolic (-6mm Hg) blood pressure measurements compared to baseline. Over two years, there were no significant changes in the liver enzymes, aspartate aminotransferase (AST) or alanine aminotransferase (ALT), indicators of liver function and damage. Very few cases of adverse effects were noted and were comparable in both groups. Nausea (n=2), abdominal fullness (n=2), headache (n=1), dizziness (n=1), weakness (n=1), and muscle pain (n=1) occurred in the stevioside (n=85) group.
Stevioside and reb A show similar metabolism as reported when eight healthy males received single oral doses of 5mg/kg body weight of reb A and 4.2mg/kg body weight of stevioside9. Both extracts were metabolized to steviol glucuronide and steviol which were excreted in urine and feces, respectively. No safety concerns were noted, based on in-depth hematological and chemical analysis which included the measurement of biomarkers, such as AST, ALT, white blood cells and bilirubin.
The European Food Safety Authority (EFSA) has deemed stevia and its glycosides as safe for consumption up to 4mg/kg body weight per day; for an average 85kg man that would be equivalent to 340mg/day.10 Additionally, the FDA has approved the GRAS (generally recognized as safe) use of stevia in foods.11
The totality of the evidence reviewed by safety authorities, such as EFSA and the FDA, indicates that stevia consumption is safe as a sugar substitute. Clinical research also identifies that stevia has beneficial effects in terms of blood pressure, glucose control and as an antioxidant. Calorie-free sweetness apparently can grow on trees! NS
1Anton SD, Martin CK, Han H, et al. 2010. Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite. 55:37-43.
2 Stoyanova S, Geuns J, Hideg E and Den Ende WV. 2011. The food additives inulin and stevioside counteract oxidative stress. Int J Food Sci Nutr. 62:207-214.
3Nunes AP, Ferreira-Machado SC, Nunes RM, et al. 2007. Analysis of genotoxic potentiality of stevioside by comet assay. Food Chem Toxicol. 45(4):662-666.
4 Brusick DJ. 2008. A critical review of the genetic toxicity of steviol and steviol glycosides. Food Chem Toxicol. 46:S83-S91.
5 Sekihashi K, Saitoh H, Sasaki Y. 2002. Genotoxicity studies of stevia extract and steviol by the comet assay. J Toxicol Sci. 27(S1):1-8.
6Wasuntarawat C, Temcharoen P, Toskulkao C, et al. 1998. Developmental toxicity of steviol, a metabolite of stevioside, in the hamster. Drug Chem Toxicol. 21(2):207-22.
7Williams LD, Burdock GA. 2009. Genotoxicity studies on a high-purity rebaudioside A preparation. Food Chem Toxicol. 47:1831-1836.
8Hsieh MH, Chan P, Sue YM, et al. 2003. Efficacy and tolerability of oral stevioside in patients with mild essential hypertension: A two-year randomized placebo-controlled study. Clin Ther. 25(11):2797-808.
9Wheeler A, Boileau AC, Winkler PC, et al. 2008. Pharacokinetics of rebaudioside A and stevioside after single oral doses in healthy men. Food Chem Toxicol. 46:S54-S60.
10 The European Food Safety Authority. 2010. Scientific Opinion on the safety of steviol glycosides for the proposed uses as a food additive. EFSA J. 8(4):1537.
11United States Food and Drug Administration. 2009. Has Stevia been approved by FDA to be used as a sweetener? Retrieved July 21st 2011 from: www.fda.gov/AboutFDA/Transparency/Basics/ucm194320.htm