August 2001; Volume 3; 62-63
By Adriane Fugh-Berman, MD, and Anthony R. Scialli, MD
Stevia (stevia rebaudiana bertoni) is a small shrub native to high altitude regions of Brazil and Paraguay. The leaves are sweet, due to the presence of stevioside and other glycosides (mainly rebaudiosides A and C). Dried stevia leaves contain 6-8% stevioside, which has little caloric value and is 300 times sweeter than sucrose at 0.4%.1 The sweet taste of stevia is stable to heat and yeast fermentation. Stevioside does not increase the risk of dental caries.
Stevia extracts and stevioside have been used as food additives in Japan for more than 20 years. Stevia and its extracts are not approved as food additives in the United States but are available in North America as dietary supplements. Two or three leaves are used to sweeten a beverage, or 2 tablespoons can be substituted for 1 cup of sugar. The limited popularity of stevia may be partly due to its somewhat bitter and metallic aftertaste.
A randomized, double-blind, placebo-controlled study in 106 Chinese hypertensive men and women (100 completed) tested stevioside (250 mg tid) for one year.2 Subjects, who were not receiving other antihypertensive medications, were assessed monthly. After three months, both systolic and diastolic blood pressure in the treated group decreased significantly, an effect that persisted throughout the year. No changes were seen in lipid levels and no significant adverse effects were observed.
In spontaneously hypertensive rats, intravenous stevioside (50, 100, and 200 mg/kg) had a dose-related hypotensive effect on both systolic and diastolic blood pressure; the highest dose had an effect that lasted longer than an hour.3
Effects on Glucose
Although claims have been made that stevia reduces glucose levels in humans, the only evidence that supports this effect is a small clinical trial reported as a letter to the Brazilian Journal of Medical and Biological Research in 1986. Sixteen healthy adults underwent a glucose tolerance test (GTT) before and after receiving 13 doses of an aqueous extract of stevia; each dose was made from 5 g of dry leaves and doses were apparently administered six hours apart.4 Six controls received arabinose (250 mg) over the same schedule (arabinose was used as a control because large amounts of arabinose are found in stevia). Mean plasma glucose levels after stevia ingestion were reported to be significantly lower at 30, 60, 90, 120, 150, and 180 minutes compared to baseline GTT. Controls experienced no change from baseline.
However, the Chan study found that stevioside caused no changes in glucose levels in 100 subjects who were treated for a year.2 And in animals, feeding studies found no changes in glucose levels in rats consuming 0.5-1.0 g stevia extract or stevioside as 7% of the diet for 56 days; intravenous stevioside transiently lowers glucose levels in alloxan-treated diabetic rabbits.1
In rats, the LD50 of intraperitoneally administered stevia extract (containing 50% stevioside) is 3.4 g/kg; the oral LD50 of stevioside in rats is reportedly 8.2 g/kg.1 High doses of orally administered stevioside (2.0 g/kg) are acutely toxic in mice. Up to 7% stevioside fed to rats for three months produced no remarkable toxic effects. Another study found that up to 3% dietary stevioside caused no changes in mating, fertility problems, or teratogenic effects in male or female rats.1
In hamsters, stevioside in doses up to 2.5 g/kg body weight (BW)/d did not affect growth or reproduction.5
A daily dose of a stevia decoction purportedly has been used as an oral contraceptive by Paraguayan Matto Grosso Indian tribes,6 but this claim is controversial.1 Stevia may reduce fertility in both sexes. A water decoction of stevia reduced fertility in adult female rats (calculated as a percentage of rats that became pregnant) by 57-90%; fertility still was reduced by half two months after ingestion of the decoction ceased.6 This 1968 report was limited by a lack of details on important aspects of the study. For example, a very high concentration of stevia was used and no information was given on the clinical status (including feed intake and weight changes) in treated animals. Generalized toxicity or poor feed intake could have profoundly decreased fertility. A subsequent study in mice was said to have produced similar effects, but we have not been able to review the original manuscript of this study.7
In contrast, several Japanese studies cited in an extensive review found no effects on fertility.1 In one of these studies, three doses of stevioside were given to groups of 10 female rats for 21 days prior to mating (after which stevioside-free rations were given). Pregnancy rates were 80% in controls, 60% in rats fed 0.28% stevioside, 80% in those receiving 1.4%, and 70% in those fed 7.0% stevioside. In another study, up to 3% dietary stevioside did not affect mating performance or fertility, nor were teratogenic effects noted.1
Twenty male Wistar rats were given an aqueous extract of stevia (66.7 g dried leaves/100 ml bid) for 60 days. There was a significant decrease in concentration of spermatozoa in the cauda epididymis and the weights of cauda epididymis, seminal vesicles, and testes decreased.8 There was a significant decrease in plasma testosterone levels but not in luteinizing hormone levels. Stevia did not cause any significant change in food consumption, body weight, or blood glucose levels.
Stevioside and another component in stevia, rebaudioside A, are degraded to the more toxic steviol by rat cecal flora; it is unclear whether this property is shared by humans.1 In pregnant hamsters, steviol in doses up to 0.25 g/kgBW/d had no observable effect. Very high doses of steviol (750 and 1,000 mg/kgBW/d) were highly toxic to both dams and fetuses.9 This dose caused maternal death and weight loss, with a reduction in number of live fetuses and mean fetal weight as would be expected in the face of this degree of maternal toxicity. An intermediate but still large dose of 500 mg/kgBW/d produced a more modest decrease in maternal weight gain and small decrease in mean fetal weight, also an expected association. No effects were observed at 250 mg/kgBW/d.
Stevia, an herbal sweetener sold as a dietary supplement, has been used as a food additive in Japan for more than 20 years. Although small amounts of stevia in foods and beverages are not harmful, potential reproductive effects of long-term use of large quantities have been identified in experimental rodent studies. These worrisome reproductive effects have prevented stevia from being adopted more widely as an artificial sweetener.
1. Kinghorn AD, Soejarto DD. Current status of stevioside as a sweetening agent for human use. Econ Med Plant Res 1985;1:2-44.
2. Chan P, et al. A double-blind placebo-controlled study of the effectiveness and tolerability of oral stevioside in human hypertension. Br J Clin Pharmacol 2000;50: 215-220.
3. Chan P, et al. The effect of stevioside on blood pressure and plasma catecholamines in spontaneously hypertensive rats. Life Sci 1998;63;1679-1684.
4. Curi R, et al. Effect of Stevia rebaudiana on glucose tolerance in normal adult humans. Braz J Med Biol Res 1986;19:771-774.
5. Yodyingyuad V, Bunyawong S. Effect of stevioside on growth and reproduction. Hum Reprod 1991;6: 158-165.
6. Planas GM, Kuc J. Contraceptive properties of Stevia rebaudiana. Science 1968;162:1007.
7. Portella Nunes BA, Pereira NA. Efeito de Caá-heê (Stevia rebaudiana) Bertoni sobre a fertilidade de animais experimentais. Rev Bras Farm 1988;69:46-50.
8. Melis MS. Effects of chronic administration of Stevia rebaudiana on fertility in rats. J Ethnopharmacol 1999;167:157-161.
9. Wasuntarawat C, et al. Developmental toxicity of steviol, a metabolite of stevioside, in the hamster. Drug Chem Toxicol 1998;21:207-222.
August 2001; Volume 3; 62-63
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.