Mutagenicity stevia

Stevioside and rebaudioside A are diterpene glycosides. The sweetness is tainted with a bitter and undesirable aftertaste. The time—intensity profile is characteristic of naturally occurring sweeteners slow onset but lingering. The aglycone moiety, steviol [471 -80-7] (10), which is the principal metaboHte, has been reported to be mutagenic (79). Wide use of stevia ia Japan for over 20 years did not produce any known deleterious side effects. However, because no food additive petition has been presented to the FDA, stevioside and related materials caimot be used ia the United States. An import alert against stevia was issued by the FDA ia 1991. In 1995, however, the FDA revised this import alert to allow the importation and use of stevia as a diet supplement (80), but not as a sweetener or an ingredient for foods. Several comprehensive reviews of stevia are available (81,82). 

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 regulatory position of stevioside varies in different regions of the world. Japan is the main market for stevioside and consumes 90% of the world s supply of stevia leaves (Richard, 2002). Stevioside is used in Japan in a variety of applications, including soft drinks. In other markets, the use of stevioside, if permitted at all, is limited to supplements. In the United States, the FDA issued an import alert in May 1991 blocking the import of and sale of stevia products, following the results of a preliminary mutagenicity study. In 1995, the FDA revised the import alert to allow the sale of stevia and its extracts as a food supplement, but not as a sweetener. It currently does not have GRAS status and is considered to be an unsafe food additive (Richard, 2002). 

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. 

Figure 32. Stevia diterpene, stevioside, its aglycone, steviol, and a mutagenic derivative, 15-oxo-steviol.

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