Stevia safety studies

Body Ecology History of use Growing Stevia Recipes and tips Order Stevia
Sources and links BED home page Safety studies Varieties of stevia

Welcome

Safety Studies
Selected examples from the hundreds of studies attesting to the safety of
stevia leaf and its extracts. Contraceptive concerns?: The FDA frequently cites a 32-year-old study about stevia and fertility. Read about the study at issue and what its author has to say.

Stevioside and two generations
of hamsters

     In 1991 a study was done by researchers at the Chulalongkorn University Primate Research Center in Bangkok, Thailand (Yodyingyuad, 1991). The researchers' objective was to study the consequences of daily ingestion of stevioside -- the main active sweetening agent in the stevia plant -- in hamsters and its effects on two subsequent generations.
     This study involved four groups of 20 hamsters (10 males and 10 females) who were one month old. The first group was fed a daily stevioside dosage of 500 mg/kg; the second group received a higher dose at 1,000 mg/kg; and the third group dosage was the highest at 2,500 mg/kg. The fourth group, which served as the control, received no stevioside. (Chinese researchers have estimated that the daily human consumption of stevioside is about 2 mg/kg; Xili, 1992).
The study showed no significant difference in the average growth of the first generation of hamsters in the groups receiving stevioside -- no matter what dosage they were given. Even the third generation of hamsters, at 120 days of age, showed no significant differences in body weight -- no matter which group they were in.
     As to the mating performance, all three generations performed the same, no matter which dose of stevioside they received. Their performance was equal to the controls.
     In summary, no growth or fertility abnormalities were found in hamsters of either sex. Mating was efficient and successful.
     The researchers agreed, "The results of this study are astonishing. Stevioside at a dose as high as 2,500 mg/kg did not do any harm to these animals. We conclude that stevioside at a dose as high as 2.5 grams per kilogram of body weight affects neither the growth nor reproduction in hamsters."

"Assessment of the carcinogenicity of stevioside in rats"
published in: Food and Chemical Toxicology 1997

This study was performed by Dr. K. Toyoda and colleagues, from the Division of Pathology, National Institute of Health Sciences in Tokyo, Japan. For a period of 104 weeks (two years), three groups of lab rats -- 50 males and 50 females -- were tested. One group received stevioside in a concentration that constituted 2.5 percent of its daily diet; the second group received a concentration that constituted 5 percent of its diet. The third group, which served as the control, received no stevoiside.
The rats who received the stevioside weighed less than those in the control group. Considering stevioside has no calories, this makes sense. When the organs and tissues of the rats were examined under a microscope, there was almost no difference between those who were given stevia and those who were not. One interesting difference, however, was that the females who took stevioside had a decreased incidence of breast tumors, while the males displayed a lesser incidence of kidney damage. The researchers state, "It is concluded that stevioside is not carcinogenic in rats under the experimental conditions described."

Quotes and comments

"According to the Herb Research Foundation, numerous scientists, and tens of millions of consumers throughout the world, especially in Japan, the herb is safe and intensely sweet, which could make it a popular noncaloric sweetener."
Rob McCaleb, president, Herb Research Foundation, Boulder, Colo., USA
"...as a scientist with over 15 years researching the safety of stevia and of many other plants used as food or food ingredients, I can assure that our conclusions in these various studies indicate that stevia is safe for human consumption as per intended usage, that is, as a sweetener."
Mauro Alvarez, Ph.D., Brazil
"The petition cites over 120 articles about stevia written before 1958, and over 900 articles published to date. In this well-chronicled history of stevia, no author has ever reported any adverse human health consequences associated with consumption of stevia leaf."
Supplement to GRAS affirmation petition no. 4G0406, submitted by the Thomas J. Lipton Company February 3, 1995
"Stevia leaf is a natural product that has been used for at least 400 years as a food product, principally as a sweetener or other flavoring agent. None of this common usage in foods has indicated any evidence of a safety problem. There are no reports of any government agency in any of the above countries indicating any public health concern whatsoever in connection with the use of stevia in foods."
Gras affirmation petition submitted on behalf of the American Herbal Products Association, April 23, 1992
"...various extract forms of stevia have been extensively studied and tested. These tests include acute, sub-acute, carcinogenic evaluation and mutagenicity studies. These scientific data, while not directly relevant or required for exemption under the common use in food proviso, nevertheless demonstrate cumulatively that there is no safety problem associated with the use of an extract of stevia. It appear to be extraordinarily safe."
Introduction to GRAS affirmation petition submitted by the American Herbal Products Association, April 23, 1992

Additional studies and citations More quotes and comments

A. Yamada, S. Ohgaki, T. Noda, and M. Shimizu. 1985. Chronic toxicity study of dietary stevia extracts in F344 rats. Journal of the Food Science and Hygiene Society of Japan 26, 169-183. (in English).
1."As a result of this protracted and extensive investigation, it was concluded that no significant dose-related changes were found in the growth, general appearance, hematological and blood biochemical findings, organ weights, and macroscopic or microscopic observations, as a result of feeding male and female F344 rats with S. rebaudiana extracts at levels up to 1% of their feed for about two years. This...study...(involved) nearly 500 test animals that were treated for up to two years..the highest dose level administered to the animals represented some 100 times the estimated daily intake of this sweet material in the human diet. The results obtained are supportive of the safety of S. rebaudiana extracts, stevioside and rebaudioside A when consumed as sucrose substitutes by human populations."
1. Food Ingredient Safety Review: Stevia rebaudiana leaves by A. Douglas Kinghorn, Ph.D.

Acute Toxicity

2. "Crude and purified extracts of Stevia rebaudiana have been subjected to acute toxicity tests in rats and mice, the results of which endorse the use of these materials for human consumption.
In a study performed in the United States, no evidence of acute toxicity was observed when separate 2 g/kg doses of the S. rebaudiana sweet glycoside constituents, stevioside, rebaudiosides A-C, dulcoside A, and steviolbioside were administered to mice...The results of these acute toxicity studies in rodents do not predict any potential risk for human populations by the ingestion of S. rebaudiana extracts and constituents."
2. Ibid. at 1.

3. "Acute toxicity was not demonstrated when separate 2 g/kg doses were administered to mice by oral intubation, indicating that a concentrated extract of stevia is less than 1/10 as toxic (acute) as caffeine."
3.Gras Affirmation Petition, Stevia leaves, presented on behalf of the American Herbal Products Association, April 23, 1992

Subacute Toxicity

4. "It has been concluded by Akashi and Yokoyama (H. Asaki and Y. Yokoyama. 1975. Dried-leaf extracts of stevia. Toxicological tests. Shokuhin Kogyo 18(20), 34-43. In Japanese, partial English translation provided), that laboratory chow containing up to 7.0% w/w stevioside produced no untoward toxic effects, when fed to male and female rats for nearly two months."
4. Ibid. at 1.

5. "A subacute toxicity study was carried out on rats using an aqueous extract of S. rebaudiana containing about 50% w/w stevioside. Two levels of extract were mixed with laboratory chow for feeding studies, allowing each animal to receive either 0.25 g or 0.5 g stevioside in 15 g of feed per day. Animals were fed the experimental diets for 56 days...There were no abnormalities relative to controls reported that were dose-related, except for a significant decrease in serum lactic dehydrogenase levels.
Neither of these two subacute toxicity studies would predict any potential harm on ingestion of S. rebaudiana extracts by humans."
5. Ibid. at 1.

"My government is trying to cause the farms of my country to cease growing marijuana and replace these crops with stevia. This idea is strongly supported by the Drug Enforcement Agency because stevia is an excellent cash crop, grows well in Paraguay...finally and most important, stevia is a completely safe health-promoting herb. This has been well-demonstrated by its extensive use in Paraguay and Japan, where its refined product known as stevioside, enjoys 41% of the sweetener market."
Juan Esteban Aguirre, Paraguayan Ambassador to the United States, in a letter to the U.S. Food and Drug Administration, September 23, 1993
"There are more than 2,000 folders in my office, each with a collection of facts and fables about various medicinal plants. In one of these folders there's an old wrinkled envelope dated 5/19/45. In it are old leaves of Paraguay's..."sweet herb," Stevia rebaudiana. More than 40 years old, one leaf of the Stevia will still sweeten a cup of coffee or tea enough to satisfy my sweet tooth....I predict rough sailing with our FDA for this non-nutritive sweetener. I hope it will make it."
James A. Duke, former chief of Medicinal Plant Research of the USDA; The Business of Herbs, November/December, 1986

"(The FDA action on stevia is) a restraint of trade to benefit the artificial sweetener industry."
Jon Kyl (R), AZ in a 1993 letter to former FDA Commissioner David Kessler about the 1991 stevia "import alert."
"Stevia has a political problem."
Rob McCaleb, president Herb Research Foundation
"I had one guy from the FDA tell me 'if we wanted to make carrots (be) against the law, we could do it.'"
Kerry Nielson, former director of operations at Sunrider International, discussing the 1985 FDA seizure of his company's stevia.
"Even if they have reviewed these studies, the only possible way to report that the results showed detrimental effects is by taking information out of context. If this is the case, one concludes that these FDA scientists are incompetent and irresponsible, or if not, they must belong to some sort of conspiracy group to carry on a sinister agenda against this plant with the objective to keep it away from American consumers by attributing to it safety issues that do not exist." Mauro Alvarez, Ph.D., responding in a 1998 letter to the fact that the FDA cited stevia studies he conducted as evidence that stevia is unsafe.

In 1968 Professor Joseph Kuc, then a member of Purdue University's department of biochemistry, performed a study on rats to see if stevia had any contraceptive effect. Undertaken with a faculty member at the University of the Republic in Montevideo, the study was prompted by a rumor that Indian women in South America used the herb for contraceptive purposes. It should be noted that researchers have been unable to duplicate the conclusions of this study.

While the results of the Kuc study might appear at first glance to bear out such rumors, closer examination raises doubts about the methods that were used, and how they apply to the typical way in which stevia is consumed. In fact, Kuc himself, although still standing by his findings of marked, relatively long-term reductions in the numbers of offspring born to female rats administered his stevia solution, acknowledges that those results aren't necessarily applicable to human consumption.

The Kuc study involved a very high concentration -- ten milliliters of a dosage administered in about 20 minutes -- of a concoction derived by drying to a powder and boiling not just the leaves, but material from the stevia plant that would not ordinarily be consumed. This liquid replaced the animals' drinking water, and was given at such a rate as to equate with a person drinking 2.5 quarts of liquid in less than half an hour.

The study also only utilized one dosage level. Typically, a biological effect (such as what Kuc reported) would be demonstrated by using a variety of doses to establish what is known as a dose-response relationship.

Kuc acknowledges that the study "absolutely needs to be redone" (just as all research, in his view, needs to be "checked and rechecked" to determine whether it "stands the test of time"). He further concedes that this finding, in itself does not constitute an important reason for keeping stevia off the U.S. market.

Kuc also notes something else: that effects in rats aren't necessarily experienced by people -- as illustrated by the apparent lack of any correlation between the results of his rat research and birth rates among regular stevia consumers. As pointed out in the Lipton petition to the FDA, "...if this reproductive effect in rats is real and can be extrapolated to humans, then one might suspect that there would be very few children in some regions of Paraguay."

Scraping the bottom of the research barrel

A second study dealing with stevia's supposed contraceptive effect was performed on female mice and published in a Brazilian pharmacological journal in 1988. It was later informally translated by an FDA employee familiar with Portuguese. The only problem is that, outside of the FDA, no one in the scientific community gives it credence.

The research at issue, according to one authority who analyzed it (Professor Mauro Alvarez of Brazil's State University of Maringa Foundation) "caused surprise with regard to the lack of information about the quantities that were administered and the preparation of the infusions, because mice, due to their low body weight, cannot receive high volumes intragastrically without suffering major stress." What's more, the study involved a small number of test animals and was "highly susceptible to external influences," he observed.

The same study was characterized by Mark Blumenthal, editor of Herbalgram -- a newsletter published jointly by the American Botanical Council and Herb Research Foundation -- as "the kind of research which FDA would never accept if a petitioner was using it (as a basis for) his or her arguments." In his opinion, "The FDA would laugh them out of the room."

What's perhaps most interesting about the FDA's citation of these two studies, however, is that what it regards as a possibly harmful effect is just as apt to be viewed as a beneficial one. As the authors of the Lipton petition put it, "One would think that this effect would make stevia extract the perfect contraceptive agent -- easy to consume... and effective long-term -- and would be intensely pursued by pharmaceutical companies, the World Health Organization, etc. Obviously this has not happened (or if it has, then there was no effect), which casts further doubt on the validity of the data."