Stevioside metabolism

The metabolism of stevia and stevia extracts has been the subject of much discussion. The available data are inconsistent and it is unclear whether steviol, the aglycone portion of stevioside, is generated in the gut. Steviol produces a mutagen (Phillips, 1987). The generation of steviol has been demonstrated in vitro and in vivo in rats (Phillips, 1987). 

The metabolism of stevioside is discussed in relation with the possible formation of steviol. Different mutagenicity studies as well as studies on carcinogenicity are discussed. Acute and subacute toxicity studies revealed a very low toxicity of Stevia and stevioside. A survey is given of calculated ADI s. Fertility and teratogenicity studies are discussed as well as the effects on the bio-availability of other nutrients in the diet. 

In 1985 it was published [1] that stevioside was completely safe but that metabolically activated steviol was mutagenic in a "Forward Mutation Test". Steviol had to be applied together with the microsomal fraction of liver of animals treated with carcinogenic compounds (polychlorinated biphenyl or phenobarbital plus 5,6-benzoflavone). This publication has led to a confusing discussion between advocates and opponents of the use of Stevia or stevioside. To unravel the problem we must consider the opinion of authoritative international organisations such as OECD (Organisation for Economic Co-Operation and Development) and ICH (International Council of Harmonisation). To accept new substances as food three different mutagenesis tests are accepted and required by the OECD as well as by the ICH. These can be seen in Table 1. 

After metabolic activation of steviol some gene mutation and chromosomal aberration was found in Chinese hamster lung (CHL) fibroblasts [8]. It has to be said that of all animals tested hamsters had the most sensitive response. Moreover, in hamster several metabolites of stevioside were foimd that are not formed in rats or humans. Therefore, the relevance of experiments with hamsters should be questioned. 

Jeppesen PB, Gregersen S, Poulsen CR, Hermansen K (2000) Stevioside acts directly on pancreatic (3 cells to secrete insulin actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K-l—channel activity. Metabolism 49 208-214 Abudula R, Jeppesen PB, Rolfsen SED, Xiao J, Hermansen K (2004) Rebaudioside A potentially stimulates insulin secretion from isolated mouse islets studies on the dose-, glucose-, and calcium-dependency. Metabolism 53 1378-1381... 

Studies on the effect of stevioside on fertility found that it produced no abnormal mating performance or fertUity, and produced no teratogenic effects. Various tests have not shown mutagenic or genotoxic activity however, mutagenic activity of metabolized ste-viol has been reported. ... 

Pezzuto, J.M. Chemistry, metabolism and biological activity of steviol ent-13-hydroxykaur-16-en-19-oic acid), the aglycone of stevioside. Page 371 in A. Rahman and P.W. Le Quesne (eds.). New Trends in Natural Products Chemistry. Studies in Organic Chemistry, Vol. 26. Elsevier Scientific Publishers. Amsterdam (1986). 

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