Health and safetyA 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 rats pretreated with a PCB blend[44] — but this finding was criticized on procedural grounds that the data were mishandled in such a way that even distilled water would appear mutagenic.[45] Over the following years, bioassay, cell culture, and animal studies have shown mixed results in terms of toxicology and adverse effects of stevia constituents. While reports emerged that found steviol and stevioside to be weak mutagens,[46][47] the bulk of studies show an absence of harmful effects.[48][49] In a 2008 review, 14 of 16 studies cited showed no genotoxic activity for stevioside, 11 of 15 studies showed no genotoxic activity for steviol, and no studies showed genotoxicity for rebaudioside A. No evidence for stevia constituents causing cancer or birth defects has been found.[48][49]
In relation to diabetes, studies have shown stevia to have a revitalizing effect on β-cells of pancreas,[10] improve insulin sensitivity in rats,[50] and possibly even to promote additional insulin production,[51] helping to reverse diabetes and metabolic syndrome.[52] Stevia consumed before meals significantly reduced postprandial insulin levels compared to both aspartame and sucrose.[53] A 2011 review study concluded that stevia sweeteners would likely benefit diabetic patients.[54]
Preliminary human studies suggest stevia can help reduce hypertension,[55] although another study has shown it to have no effect on hypertension.[56] Indeed, millions of Japanese have been using stevia for over thirty years with no reported or known harmful effects.[57] Similarly, stevia leaves have been used for centuries in South America, spanning multiple generations in ethnomedical tradition as a treatment for diabetes mellitus type 2.[58]
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 "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."[59] The report also found no evidence of carcinogenic activity. Furthermore, the report noted "stevioside has shown some evidence of pharmacological effects in patients with hypertension or with diabetes mellitus type 2",[59] but concluded further study was required to determine proper dosage. The WHO's Joint Experts Committee on Food Additives has approved, based on long-term studies, an acceptable daily intake of steviol glycoside of up to 4 milligrams per kilogram of body weight.[60]
Beginning in 2009 in the United States, the U.S. FDA considers "Rebiana (rebaudioside A) to be Generally Recognized As Safe (GRAS)".[61] With respect to the measure of toxicity, which can be described as the median lethal dose or LD50, a report submitted to the FDA documents "the observed LD50 values were 5.2 g/kg bw for male hamsters and 6.1 g/kg bw for female hamsters."[61] The report includes a detailed list of international studies, references, and chemical analysis.[61]
Two 2010 review studies found no health concerns with stevia or its sweetening extracts.[54][62] In addition, a 2009 review study found that stevioside and related compounds have anti-hyperglycemic, anti-hypertensive, anti-inflammatory, anti-tumor, anti-diarrheal, diuretic, and immunomodulatory actions.[63]
The European Food Safety Authority evaluated the safety of steviol glycosides, extracted from the leaves of the Stevia rebaudiana Bertoni plant, as sweetener and expressed its opinion on 10 March 2010. The Authority established an Acceptable Daily Intake (ADI) for steviol glycosides, expressed as steviol equivalents, of 4 mg/kg bodyweight/day. On 11 November 2011, the European Commission allowed the usage of steviol glycosides as a food additive, establishing maximum content levels for different types of foods and beverages.[64]
[edit] Political controversyIn 1991, after receiving an anonymous industry complaint, the United States Food and Drug Administration (FDA) labeled stevia as an "unsafe food additive" and restricted its import.[34][65][66] The FDA's stated reason was "toxicological information on stevia is inadequate to demonstrate its safety."[67] This ruling was controversial, as stevia proponents pointed out that this designation violated the FDA's own guidelines under which natural substances used prior to 1958, with no reported adverse effects, should be generally recognized as safe (GRAS) as long as the substance was being used in the same way and format as prior to 1958.
Stevia, the plant, is ineligible as a natural substance for patent protection. A process for extracting its "active ingredient" could, all other legal requirements being met, be patented. As a consequence, since the import ban in 1991, marketers and consumers of stevia have shared a belief that the FDA acted in response to industry pressure.[34] Arizona congressman Jon Kyl, for example, called the FDA action against stevia "a restraint of trade to benefit the artificial sweetener industry."[68] To protect the complainant, the FDA deleted names in the original complaint in its responses to requests filed under the Freedom of Information Act.[34]
Stevia remained banned until after the 1994 Dietary Supplement Health and Education Act forced the FDA in 1995 to revise its stance to permit stevia to be used as a dietary supplement, although not as a food additive – a position that stevia proponents regard as contradictory because it simultaneously labels stevia as safe and unsafe, depending on how it is sold.[1]
Unresolved questions remain about whether metabolic processes can produce a mutagen from stevia in animals.[citation needed] Early studies prompted the European Commission in 1999 to ban stevia's use in food in the European Union pending further research.[69] More recent data compiled in the safety evaluation released by the World Health Organization in 2006[59] suggest that these policies may be obsolete. Since 2008, the Russian Federation has allowed stevioside as a food additive "in the minimal dosage required".[27]
In December 2008, the FDA gave a "no objection" approval for GRAS status to Truvia (developed by Cargill and The Coca-Cola Company) and PureVia (developed by PepsiCo and the Whole Earth Sweetener Company, a subsidiary of Merisant), both of which use rebaudioside A derived from the Stevia plant.[70]
