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B
ottom Line Monographs on Key Foods, Herbs, and Supplements
 

The following is one in an ongoing series of columns entitled Bottom Line Monographs on Key Foods, Herbs, and Supplements by Natural Standard . View all columns in series
Stevia
Natural Standard Bottom Line Monograph, Copyright © 2008 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

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While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.


Related Terms:
Alpha-monoglucosylstevioside, alpha-monoglucosylrebaudioside A, Asteraceae, azucacaa, candyleaf, capim doce, Compositae, dihydroisosteviol (DHISV), dihydropsuedoivalin, dihydrosteviol A, ent-kaurenoic acid, epidihydropseudoivalin, erva doce, glucosilsteviol, isosteviol, ka'a he'e, kaa he-he, kaa jhee, NPI-028, octa-acetylombuoside, ombuine, ombuoside, Paraguayan sweet herb, rebaudioside A (RA), rebaudioside F, retusine, roninowa, ronion, sacharol, SE, Stevia connata, Stevia eupatoria, stevia glycosides, Stevia lita, Stevia pilosa, Stevia rebaudiana (SR), Stevia rebaudiana Bertoni (SrB), Stevia rebaudiana standardized extracts (SSEs), Stevia salicifolia, Stevia subpubescens, Stevia tomentosa, Stevia triflora DC, Stevia viscida, steviol (SV), steviolbioside, stevioside (SVS), stevisalioside A, Stevita, sweet serb, sweetleaf, yerba dulce.
Note: Do not confuse Stevia rebaudiana with Stevia salicifolia, also called ronion or roninowa. Stevia salicifolia contains the bitter glycoside stevisalioside.

Background

Extracts of leaves from Stevia rebaudiana Bertoni have been used for many years in traditional treatment of diabetes in South America. Paraguay's rural and indigenous populations have used Stevia rebaudiana for the control of fertility.
Stevia rebaudiana standardized extracts are used as natural sweeteners or dietary supplements in different countries for their content of stevioside or rebaudioside A. These compounds possess up to 250 times the sweetness intensity of sucrose, and do not have any calories. Stevioside, a natural plant glycoside isolated from the plant Stevia rebaudiana, has been commercialized as a non-caloric sweetener in Japan for more than 20 years.
Stevia and its extracts are not generally recognized as safe (GRAS) nor approved as food additives by the U.S. Food and Drug Administration (FDA). Stevia may be imported only if "explicitly labeled as a dietary supplement or for use as a dietary ingredient in a dietary supplement." Although stevia may be marketed as a dietary supplement or an ingredient of a dietary supplement under the Dietary Supplement Health and Education Act (DSHEA), products that are labeled as using stevia plant parts or extracts as flavoring agents, sweeteners, or for other food additive purposes are deemed as "unsafe" because "available toxicological information on stevia is inadequate to demonstrate its safety," according to the FDA. Regulatory agencies in Canada and Europe also have not approved use of stevia as a food additive.

Evidence

Uses
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Grade*
Hyperglycemia

Stevia has been widely used for diabetes in South America and animal studies have had promising results. Studies report decreases in plasma glucose when stevia was taken in normal volunteers, but there is currently no conclusive evidence of effectiveness when used for diabetes. Additional study is needed in this area to confirm these findings.

B
Hypertension (high blood pressure)

Stevioside is a natural plant glycoside isolated from the plant Stevia rebaudiana, which has demonstrated blood pressure lowering effects. Despite evidence of benefits in some human studies and support from laboratory and animal studies, more research is warranted to compare stevia's effectiveness with the current standard of care and make a firm recommendation. Stevia appears to have no major side effects.

B
* Key to grades: A: Strong scientific evidence for this use; B: Good scientific evidence for this use; C: Unclear scientific evidence for this use; D: Fair scientific evidence against this use (it may not work); F: Strong scientific evidence against this use (it likely does not work).

Tradition/Theory

The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

Alcohol abuse, antibacterial, anti-inflammatory, antimicrobial, antimutagenic, antitumor, antiviral (human rotavirus activity), contraceptive (birth control), digestive aid, immunomodulation, obesity.

USUAL DOSING

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.


Adults (18 years and older):
For hyperglycemia (high blood sugar), 1 gram of stevioside has been taken with meals to lower blood sugar in patients with type 2 diabetes. Water extracts of 5 grams of leaves have also been used at regular six-hour intervals for three days to increase glucose tolerance.
For hypertension (high blood pressure), stevioside (250-500mg) capsules given three times daily decreased systolic and diastolic blood pressure after three months of therapy, and have been studied for up to two years. Despite early evidence that this may be an effective dose, a recent study did not find any benefit of crude stevosides (up to 15mg/kg taken twice daily) for two years.

Children (younger than 18 years):
There is no proven safe or effective dose for stevia, and use in children is not recommended.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies
Avoid in individuals with a known allergy or hypersensitivity to stevia or the daisy family (Asteraceae/Compositae). Other members of the daisy family include ragweed, chrysanthemums, marigolds, and many other herbs.

Side Effects and Warnings
Stevioside may lower blood glucose levels. Caution is advised in patients with diabetes or hypoglycemia (low blood sugar), and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a healthcare provider, and medication adjustments may be necessary.
Myalgia (muscle pain), muscle weakness, dizziness, asthenia (loss of strength), nausea, and abdominal fullness have been reported after taking stevioside. These effects resolved after the first week of treatment. Stevia may also lower systolic and diastolic blood pressure in patients with high blood pressure. Use cautiously in patients with hypotension (low blood pressure) or taking hypotensive drugs since various human and animal studies have shown that stevioside may significantly decrease systolic and diastolic blood pressure.
Higher doses of stevia may affect renal activity and perfusion, sodium excretion, and urinary flow. Avoid using stevia therapeutically in patients with impaired kidney function or other kidney diseases until human safety data is available.

Pregnancy and Breastfeeding
Stevia is not recommended in pregnant or breastfeeding women due to a lack of available scientific evidence.

INTERACTIONS

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs
Stevia may lower blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia (low blood sugar), and in those taking drugs that affect blood sugar. Serum glucose levels may need to be monitored by a healthcare provider, and medication adjustments may be necessary.
Based on clinical observations in humans, stevioside may decrease systolic and diastolic blood pressure. Caution is advised in patients taking blood pressure lowering medications.
Although not well researched, stevia may also interact with monoketocholate (a substance that may affect glucose and lipid levels), diuretics (medications that increase urine flow), or hypocalcemic agents. Caution is advised.
Steviol is a vasodilator (medication that causes the blood vessels to dilate or expand). Caution is advised when taking stevia with other vasodilators. Consult with a qualified healthcare professional, including a pharmacist, before combining therapies.
Verapamil is a calcium antagonist and may exhibit additive effects with stevioside. In an animal study, verapamil tended to increase the renal (kidney) and systemic effects of stevioside. Caution is advised.

Interactions with Herbs and Dietary Supplements
Although not well researched, stevia may also interact with monoketocholate, diuretics (herbs and supplements that increase urine flow), or hypocalcemic agents. Caution is advised.
Stevia may lower blood sugar levels. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.
Stevioside may decrease systolic and diastolic blood pressure. Caution is advised in patients taking blood pressure lowering herbs and supplements.
Steviol is a vasodilator. Caution is advised when taking stevia with other herbs and supplements that are vasodilators. Consult with a qualified healthcare professional, including a pharmacist, before combining therapies.

AUTHOR/UPDATE INFORMATION

This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

REFERENCES

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.


  1. Abudula R, Jeppesen PB, Rolfsen SE, et al. Rebaudioside A potently stimulates insulin secretion from isolated mouse islets: studies on the dose-, glucose-, and calcium-dependency. Metabolism 2004;53(10):1378-1381. View Abstract
  2. Boonkaewwan C, Toskulkao C, Vongsakul M. Anti-Inflammatory and Immunomodulatory Activities of Stevioside and Its Metabolite Steviol on THP-1 Cells. J Agric.Food Chem 2-8-2006;54(3):785-789. View Abstract
  3. Chan P, Tomlinson B, Chen YJ, 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):215-220. View Abstract
  4. Chen TH, Chen SC, Chan P, et al. Mechanism of the hypoglycemic effect of stevioside, a glycoside of Stevia rebaudiana. Planta Med 2005;71(2):108-113. View Abstract
  5. Ferri LA, Alves-Do-Prado W, Yamada SS, et al. Investigation of the antihypertensive effect of oral crude stevioside in patients with mild essential hypertension. Phytother Res. 2006 Sep;20(9):732-6. View Abstract
  6. Gregersen S, Jeppesen PB, Holst JJ, Hermansen K. Antihyperglycemic effects of stevioside in type 2 diabetic subjects. Metabolism 2004;53(1):73-76. View Abstract
  7. Hsieh MH, Chan P, Sue YM, 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):2797-2808. View Abstract
  8. Koyama E, Kitazawa K, Ohori Y, et al. In vitro metabolism of the glycosidic sweeteners, stevia mixture and enzymatically modified stevia in human intestinal microflora. Food Chem.Toxicol. 2003;41(3):359-374. View Abstract
  9. Lailerd N, Saengsirisuwan V, Sloniger JA, et al. J. Effects of stevioside on glucose transport activity in insulin-sensitive and insulin-resistant rat skeletal muscle. Metabolism 2004;53(1):101-107. View Abstract
  10. Liu JC, Kao PK, Chan P, et al. Mechanism of the antihypertensive effect of stevioside in anesthetized dogs. Pharmacology 2003;67(1):14-20. View Abstract
  11. Mizushina Y, Akihisa T, Ukiya M, et al. Structural analysis of isosteviol and related compounds as DNA polymerase and DNA topoisomerase inhibitors. Life Sci 9-9-2005;77(17):2127-2140. View Abstract
  12. Raskovic A, Gavrilovic M, Jakovljevic V, Sabo J. Glucose concentration in the blood of intact and alloxan-treated mice after pretreatment with commercial preparations of Stevia rebaudiana (Bertoni). Eur J Drug Metab Pharmacokinet. 2004;29(2):87-90. View Abstract
  13. Raskovic A, Jakovljevic V, Mikov M, Gavrilovic M. Joint effect of commercial preparations of Stevia rebaudiana Bertoni and sodium monoketocholate on glycemia in mice. Eur J Drug Metab Pharmacokinet. 2004;29(2):83-86. View Abstract
  14. Wong KL, Chan P, Yang HY, et al. Isosteviol acts on potassium channels to relax isolated aortic strips of Wistar rat. Life Sci 3-26-2004;74(19):2379-2387. View Abstract
  15. Wong KL, Yang HY, Chan P, et al. Isosteviol as a potassium channel opener to lower intracellular calcium concentrations in cultured aortic smooth muscle cells. Planta Med 2004;70(2):108-112. View Abstract


Natural Standard Monograph (www.naturalstandard.com)
Copyright © 2008 Natural Standard Inc. Commercial distribution or reproduction prohibited.

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.
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Natural Standard was founded by clinicians and researchers to provide high quality, evidence-based information about complementary and alternative therapies. This international multidisciplinary collaboration now includes contributors from more than 100 eminent academic institutions. ...more
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