Health Care Professional Information

Scientific Name
Stevia rebaudiana
Common Name

Kaa he-he, sweet herb of Paraguay, caa-ehe, honey leaf

Clinical Summary

Stevia rebaudiana is an herb native to Brazil and Paraguay. Its raw leaves as well as purified extracts, such as stevioside and its aglycone steviol, have been used as sweeteners and promoted as sugar substitutes for diabetics (2). Stevia extract is said to be 2-300 times sweeter than table sugar (1). The FDA has approved stevia as Generally Recognized as Safe (GRAS) (8).
In vitro and animal studies indicate that stevia has antitumor (5), anti-inflammatory (6), hepato- and reno-protective effects (15).
Stevia was also shown effective in lowering hypertension and hyperglycemia (3) (13). In a placebo-controlled trial in patients with hypertension, stevioside usage improved quality of life when compared to placebo (4). Well designed trials are warranted.

Stevia may have additive effects with other antihypertensive and antidiabetic medications. Gastrointestinal and neurological side effects as well as mutagenic activity have been reported (3) (4) (7).

Purported Uses
  • Sweetener
  • Hypertension
  • Antitumor
  • Inflammation
  • Weight loss
  • Diabetes
Constituents
  • Stevioside (Steviol is an aglycone metabolite)
  • Rebaudioside A
  • Rebaudioside C
  • Dulcoside A
  • Phosphorus, iron, calcium, potassium, sodium, magnesium, zinc
    (2) (14)
Mechanism of Action

The mechanisms underlying the antihypertensive effect of stevioside are still unclear, although it is believed to act as a calcium channel antagonist, similar to the drug verapamil (9). It may also have antitumor properties, as evidenced by its inhibition of the tumor-promoting 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse skin (5). In vitro studies have shown that stevioside suppresses the production of inflammatory mediators (6). Stevia products have been shown to inhibit hepatic gluconeogenesis (10) and increase insulin sensitivity in animal studies (11).

Pharmacokinetics

Stevioside is hydrolyzed to steviol before being absorbed in the intestines.
Steviol is metabolized by the liver microsomes (10).

Warnings

At high doses, steviol was shown to exhibit weak mutagenic activity (7).

Contraindications

Pregnant women should not consume this herb.

Adverse Reactions

Case Report: Four patients in a study experienced abdominal fullness, myalgia, nausea, and asthenia following consumption of 500 mg stevioside powder. Their symptoms disappeared after one week of treatment(4).

Herb-Drug Interactions
  • Verapamil: Stevia may have additive antihypertensive effects (9).
  • Antidiabetics: Stevia may affect blood glucose level, so dosages may have to be adjusted (10).
Dosage (Inside MSKCC Only)
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References
  1. More about stevia, a non-approved sweetener. Harv Womens Health Watch 2005;12(10):6-7.
  2. Geuns, J.M., Stevioside. Phytochemistry 2003;64(5): 913-21.
  3. 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(3):215-20.
  4. Hsieh, M.H., et al., Efficacy and tolerability of oral stevioside in patients with mild essential hypertension: a two-year, randomized, placebo-controlled study. Clin Ther 2003; 25(11): 2797-808.
  5. Yasukawa, K., S. Kitanaka, and S. Seo, Inhibitory effect of stevioside on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin. Biol Pharm Bull 2002; 25(11):1488-90.
  6. Boonkaewwan, C., C. Toskulkao, and M. Vongsakul, Anti-Inflammatory and Immunomodulatory Activities of Stevioside and Its Metabolite Steviol on THP-1 Cells. J Agric Food Chem 2006; 54(3):785-9.
  7. Terai, T. et al., Mutagenicity of steviol and its oxidative derivatives in Salmonella typhimurium TM677. Chem Pharm Bull (Tokyo) 2002; 50(7):1007-10.
  8. Agency Response Letter GRAS Notice No. GRN 000253. CFSAN/Office of Food Additive Safety. December 17, 2008. Accessed July 25, 2011.
  9. Melis, M.S. and A.R. Sainati, Effect of calcium and verapamil on renal function of rats during treatment with stevioside. J Ethnopharmacol 1991;33(3):257-62.
  10. Ferreira, E.B., et al., Comparative effects of Stevia rebaudiana leaves and stevioside on glycaemia and hepatic gluconeogenesis.
  11. Planta Med 2006; 72(8):691-6.
  12. Chang, J.C., et al., Increase of insulin sensitivity by stevioside in fructose-rich chow-fed rats. Horm Metab Res 2005; 37(10):610-6.
  13. Safety Evaluation of Certain Food Additives. WHO Food Additives Series:54, International Programme on Chemical Safety, World Health Organization (Geneva) 2006.
  14. Ulbricht C, Isaac R, Milkin T, et al. An evidence-based systematic review of stevia by the natural standard research collaboration. Cardiovasc Hematol Agents Med Chem. 2010 Apr;8(2):113-27.
  15. Shivanna N1, Naika M, Khanum F, Kaul VK. Antioxidant, anti-diabetic and renal protective properties of Stevia rebaudiana. J Diabetes Complications. 2013 Mar-Apr;27(2):103-13.

Consumer Information

How It Works

Bottom Line: Stevia is an approved substitute for sugar.

Stevia is a sweet herb that is used as a sweetener. The FDA has approved a purified ingredient from Stevia as a food additive. Some studies have shown that stevia helps to lower blood pressure in humans. Other animal and laboratory studies suggest stevia products can suppress inflammation mediators in the body and can help to regulate blood sugar level. However, these effects have not been studied in humans.

Purported Uses
  • Sweetener
    Stevia can be used as a low-calorie sweetener.
  • Hypertension
    Stevia may lower blood pressure.
  • Antitumor properties
    Laboratory studies show that Stevia has antitumor properties but this has not been confirmed in humans.
  • Inflammation
    Laboratory studies suggest that Stevia may reduce inflammation.
  • Diabetes
    Animals studies suggest stevia products can help to regular blood sugar but human data are lacking.
  • Weight loss
    There are no data to support this use.
Patient Warnings

Some studies show that steviol at high dosages may have weak mutagenic activity.

Do Not Take If
  • You are pregnant or nursing.
Side Effects
E-mail your questions and comments to aboutherbs@mskcc.org.