Safety of Stevia


by Jan M. C. Geuns 

Stevioside and Stevia are used in Brazil, China and South-Korea. In Japan it is used since the restriction of artificial sweeteners in 1970. In the USA it was banned in 1990, but allowed as a dietary supplement since 1995. In Europe several tons of Stevia leaves have been imported and consumed since 1986. However, since 1997 it is considered as a Novel Food and banned in 2001 due to lack of sufficient scientific information on safety issues.

In acute toxicity studies with rats, mice and hamsters a LD50 between 8 –15 g/kg BW was found. In chronic toxicity studies Xili et al. (1992) suggested an ADI of 7.9 mg/kg BW. This has to be considered as a minimum ADI as no concentrations higher than 793 mg/kg BW were tested. Fom the literature an ADI of over 20 mg/kg BW may be estimated (Geuns, 2002). By substituting for all added sugar in food (in Belgium about 135 g sugar per person per day) 450 mg stevioside would be required, and this is still below the ADI of 7.9 mg/kg BW (513 mg stevioside required for a person of 65 kg). Moreover, there is no risk of overuse because food is not tasty anymore when it is to sweet.Stevioside added to the feed of animals did not influence growth curves, proving that stevioside did not interfere with the uptake of essential elements (Geuns et al., 2003b). In chronic studies stevioside did not enhance tumor formation. On the contrary, use of stevioside significantly reduced the incidence of adenomas of the mammary gland in the female F344 rats (Toyoda et al., 1997). 

Stevioside, rebaudioside A and steviol had no harmful effects on developing chicken embryos (Geuns et al., 2003c).Stevioside is not taken up by the intestines and is not metabolised by the enzymes of the digestive tract. However, in the caecum and colon of respectively rodents and man stevioside is degraded into steviol by the bacteria present. Weak mutagenic activity has been found of steviol in Salmonella typhimurium TM 677 but not in various other Salmonella strains or in E. coli. Terai et al. (2002) found a weak mutagenic effect of steviol and 15-oxo-steviol (1/3000 of the activity of 3,4-benzopyrene and 1/24500 of that of furylfuramide). 

Although free steviol is found in the blood of rodents after feeding stevioside, no steviol was detected in the blood of chickens and pigs (Geuns et al., 2003 a,b). The steviol in the blood of rodents might be the result of coprophagy, hence the uptake of steviol due to reingestion of the faeces. Anyway, the low amounts of steviol taken up do not induce cancer as in chronic experiments with rats fed stevioside during 2 years, no increase in tumor formation was found. Moreover, in Paraguay, Brazil, Japan and the USA no enhancement of cancers is observed since the introduction of stevioside. In uptake studies it was shown that stevioside and rebaudioside A are not taken up by the intestines, whereas steviol was easily taken up (Koyama et al., 2003, Geuns et al., 2003a). Steviol fed to hamsters had no harmful effects up to 250 mg/kg BW (Wasuntarawat et al., 1998). The free steviol concentration in the plasma could be estimated to be around 102 µg/ml or around 320 µM. In pigs and human volunteers these steviol concentrations were never detected in the plasma after administration of 68 mg stevioside/kg BW (pigs) or 11 mg/kg BW (humans), proving that stevioside used as a sweetener is absolutely safe (Geuns, 2003). 

After the administration of high doses of stevioside (250 mg thrice a day) blood pressure of hypertensive patients was lowered starting 3 months ofter the onset of the experiments (Chan et al., 2000). This effect is explained by an inhibition of Ca2+-influx from extra-cellular fluid (Liu et al., 2003). No effects were found on blood biochemical parameters nor on glucose level. 
It can be concluded that stevioside is absolutely safe for diabetics, phenylketonuria patients and slimming people. It is not suited for regulating blood glucose levels. High amounts (3x250 mg/day) will decrease blood pressure without negative side-effects.

 

Acknowledgements

The author acknowledges the "Onderzoeksraad KULeuven" for grant OT/00/15, the FWO for grant G.0111.01. 

 

Literature cited.

Geuns, J.M.C., 2002. Safety evaluation of Stevia and stevioside. In: Atta-ur-Rahman (Ed.), Studies in Natural Products Chemistry, Vol. 27: Bioactive Natural Products (Part H), Elsevier, Amsterdam, pp.299-319.

 

Geuns, J.M.C., 2003. Molecules of interest: Stevioside. Phytochemistry

 

Geuns, J.M.C., Augustijns, P., Mols, R., Buyse, J.G., Driessen, B., 2003a. Metabolism of stevioside in pigs and intestinal absorption characteristics of Stevioside, Rebaudioside A and Steviol. Food Chem. Toxicol. 41, 1599-1607.

 

Geuns, J.M.C., Malheiros, R.D., Moraes, V.M.B., Decuypere, E.M.-P., Compernolle, F., Buyse, J.G., 2003b. Metabolism of stevioside by chickens. J. Agric. Food Chem. 51, 1095-1101. 

 

Geuns, J.M.C., Bruggeman, V., and Buyse, J.G., 2003 c. Effect of stevioside and steviol on the developing broiler embryos. J. Agric. Food Chem. 51, 5162-5167.

 

Koyama, E., Sakai, N., Ohori, Y, Kitazawa, K, Izawa, O., Kakegawa, K., Fujino, A., Ui, M., 2003. Absorption and metabolism of the glycosidic sweeteners, Stevia related compounds in human and rat. Food Chem. Toxicol. 41, 875-883.

 

Terai, T., Ren, H., Mori, G., Yamaguchi, Y., Hayashi, T., 2002. Mutagenicity of steviol and its oxidative derivatives in Salmonella typhimurium TM677. Chem. Pharm. Bull. 50, 1007-1010. 

 

Totté, N., Charon,L., Rohmer, M., Compernolle, F., Baboeuf, I., Geuns, J.M.C., 2000. Biosynthesis of the diterpenoid steviol, an ent-kaurene derivative from Stevia rebaudiana , via the methylerythritol phosphate pathway. Tetrahedron Letters 41, 6407-6410.

 

Toyoda, K., Matsui, H., Shoda, T., Uneyama, C., Takada, K., Takahashi, M., 1997. Assessment of the Carcinogenicity of Stevioside in F344 Rats. Food Chem. Toxicol. 35, 597-603.

 

Wasuntarawat, C., Emcharoen, P., Toskulkao, C., Mungkornkarn, P., Suttajit, M., Glinsukon, T., 1998. Developmental Toxicity of Steviol, a Metabolite of Stevioside, in the Hamster. Drug Chem. Toxicol. 21, 207-222.

 

Xili, L., Chengjiany, B., Eryi, X., Reiming, S., Yuengming, W., Haodong S., Zhiyian, H., 1992. Chronic oral Toxicity and Carcinogenicity Study of Stevioside in Rats. Food Chem. Toxicol. 30, 957-965.