Sweet-tasting steviol glycoside derivatives with antihyperglycaemic and antihypertensive effects

H. Schmandke, Nuthethal

Steviol glycosides are derivatives of the tetracyclic diterpenic carboxylic alcohol steviol present in the leaves of Steva rebaudiana (Compositae) as stevioside, rebaudioside A, B, C, D and E, steviolbioside and dulcoside A. Powderized stevia leaves, refined aqueous extracts from the leaves, enzymatically modified stevia (alpha-glucosyl derivatives) and stevioside are used as non-caloric sweeteners in America and Asia.

The glycosides are obviously not absorbed but metabolized intensively by the cecal microflora forming steviol via steviolbioside. Steviol is partly absorbed. This also applies to subsequently conjugated steviol which is excreted into the intestinal tract by bile.

The no observed effect level (NOEL) for maternal and fetal toxicity of rats is 250 mg steviol/kg BW/day. Extrapolating from rats to humans and allowing a safety factor of 100, the acceptable daily intake (ADI) would be 2.5 mg steviol/kg BW, corresponding to 6.35 mg stevioside/kg BW. This is close to 7.9 mg/kg BW obtained for stevioside in chronic oral toxicity and carcinogenicity tests.

Because of in-vitro mutagenic action, the genotoxic risk of steviol, aglycon and metabolite of stevioside, to humans is not yet known.

Although aqueous extracts of stevia leaves have been traditionally used in South America for the treatment of type 2 diabetes, the corresponding mechanism of action is a subject of present research. An oral dosis of 500 mg stevioside/kg BW produces antihyperglycaemic and insulinotropic effects in insulin-resistent obese Zucker rats. In vitro, stevioside enhances the insulin-stimulated glucose transport in rat skeletal muscles.

8–12 mg stevioside per kg BW, administered intravenously, lower blood pressure in spontaneously hypertensive rats. Intraperitoneal injection of 25 mg stevioside/kg BW also has an antihypertensive effect. In isolated rat aortic rings stevioside caused vasorelaxation by inhibition of calcium release into the blood vessels. This antihypertensive effect has been shown in hypertensive patients who received oral doses of 750 mg stevioside daily and who were checked at monthly intervals over one year.

Keywords: steviol glycoside derivatives / sweetener / metabolism / antihyperglycaemic and antihypertensive effects