A 1985 study reported that steviol, a breakdown product from stevioside and rebaudioside (two of the sweet steviol glycosides in the stevia leaf), is a mutagen in the presence of a liver extract of pre-treated rats[33] — but this finding was criticized on procedural grounds that the data were mishandled in such a way that even distilled water would appear mutagenic.[34] Over the following years bioassay, cell culture, and animal studies have shown mixed results in terms of toxicology and adverse effects of stevia constituents, but in general, they have not been found to be harmful. While reports emerged that found steviol and stevioside to be weak mutagens,[35][36] the bulk of studies show an absence of harmful effects.[37][38]
In a 2008 review, 14 of 16 studies cited showed no genotoxic activity for stevioside, 11 of 15 studies showed genotoxic activity for steviol, and no studies showed genotoxicity for Rebaudioside A. Nevertheless, even if a chemical can cause DNA damage in the controlled conditions of a bioassay (e.g., in bacteria, in mammalian cell cultures) it is a fundamentally different question whether it causes cancer in intact organisms (e.g., rodents, humans) or is teratogenic (i.e., causes birth defects). No evidence for stevia constituents causing cancer or birth defects has been found.[37][38]
Other studies have shown stevia improves insulin sensitivity in rats[39] and may even promote additional insulin production,[40] helping to reverse diabetes and metabolic syndrome.[41]
Preliminary human studies show stevia can help reduce hypertension[42] although another study has shown it has no effect on hypertension.[43] Indeed, millions of Japanese have been using stevia for over thirty years with no reported or known harmful effects.[44]
Similarly, stevia leaves have been used for centuries in South America spanning multiple generations in ethnomedical tradition as a treatment of type II diabetes.[45]
In 2006, the World Health Organization (WHO) performed a thorough evaluation of recent experimental studies of stevioside and steviols conducted on animals and humans, and concluded that "stevioside and rebaudioside A are not genotoxic in vitro or in vivo and that the genotoxicity of steviol and some of its oxidative derivatives in vitro is not expressed in vivo."[46]
The report also found no evidence of carcinogenic activity. Furthermore, the report noted that "stevioside has shown some evidence of pharmacological effects in patients with hypertension or with type-2 diabetes"[46] but concluded that further study was required to determine proper dosage.
Whole foods proponents draw a distinction between consuming (and safety testing) only parts, such as stevia extracts and isolated compounds like stevioside, versus the whole herb.[47] However, professionals in pharmacognosy, as well as physicians and science journalists disagree that whole foods are beneficial over extracted components, and may even be harmful.[48][49]