STEVIA dangers, side effects, safety issues - diabetes             Reviewed on April 11, 2014    
Objective of This Article
Some people suffered from diabetes use stevia as a sugar substitute. However, there is a safety concern about overdoses of stevia. Overdoses of
stevia is a danger and lead to serious side effects. This article reviews stevia uses, benefits, side effects..

Stevia Reviews
Stevia is a genus of 240 species of herbs, it is belonged to family Asteraceae. Stevia originally came from the rain forests of Brazil and Paraguay, But,
now we can also find Stevia in South East Asia. Stevia is believed to benefit people suffered from  high blood pressure and help control glucose
levels. Consequently, it has been used as a non-sugar sweetener for food and drinks and as remedy for diabetes [1]

Stevia leave contains various glycosides including stevoside. Stevoside is a natural sweetener. It is a a diterpenic carboxylic alcohol with three
glucose molecules [12] Stevoside is about 100-200 times sweeter than sugar. Some doctors may use it to reduce blood pressure and help patients
suffered from diabetes [2,3]. The sterol fraction of Stevia rebaudiana Bertoni contains, essentially, the following sterols: stigmasterol (45,8%),
beta-sitosterol (39,4%) and campesterol (13,1%). [7]

Stevia accounts for about 40% of the sweetener market in Japan [5] and its ingredients such as rebaudioside A and stevioside are also getting
popular in the US. [A2, A3] Limited side effects of stevia have been reported. [4, 6, 9, 23] However, high doses of stevia may lead to serious side
effects. A study showed that high doses of stevia led to a decrease in weight of testis, seminal vesicle and cauda epididymidis. Consequently, intake
of high dosages of stevia may lead to the side effect of male infertility! In addition, a few studies showed that stevioside (from stevia leaves) is a
vasodilator. [8-14] It has insulinotropic, glucagonostatic, anti-hyperglycemic and blood pressure-lowering effects in type 2 diabetic animal models. [4]

However, researchers from Aarhus University Hospital DK reported no side effect of rebaudioside A (0.025 g/kg BW/day) on blood pressure or weight
development in rats. [4] At the same time, researchers from Toxicology Regulatory Services, Inc. Virginia, found no toxicity side effects of dietary
administration of rebaudioside A in rats in a 90-day study. [A5] Curry LL and his research fellows at Coca-Cola Company, Provident Clinical Research
and Cargill Inc repeatedly reported how safe rebaudioside A in various scientific journals. For instance, reference A2 suggests that high purity
rebaudioside A (rebiana) is safe for human consumption under its intended conditions of use --- as a general purpose sweetener. Purified
rebaudioside A has no side effect on either blood pressure or glucose homeostasis. Reference A1 suggests that administration of high doses of
rebaudioside A reduced the body weight gain and inconsistently reduced the serum bile acids and cholesterol, and claims that all other hepatic
function were within normal limits. Reference 3A reports the consumption of 1000 mg/day of rebaudioside A for 4 weeks produced no clinically
important changes in blood pressure in healthy adults with normal and low-normal blood pressure.

Stevia has been labeled as a dietary supplement in the US, while its rebaudioside A was approved as a food additive in 2008. However, stevia is
considered as a sweetener in most other countries.

Related Names: Sweetleaf, sweet leaf, sugarleaf, stevia rebaudiana
Stevia may have benefits of anti-microbial activities, the scientific evidence is very limited. Amaro-Luis et al isolated
ombuoside from aerial parts of Stevia triflora and prepared derivatives of it- octa-acetylombuoside, ombuine and
retusine. They found these compounds were against a few types of gram positive bacteria. [21]

Rats received a single oral administration of either steviol or stevia mixture; a peak steviol plasma concentration
appeared 15 min after its oral administration. However, after oral administration of stevia mixture, the steviol
concentration in plasma increased steadily over 8 h, [22]

Stevia probably is safe without significant adverse or toxic effects at low doses [4,6,9]. Stevia accounts for about 40% of
the sweetener market in Japan and is widely used in South America. [5] However, I received piles of complaints from
readers on
stevia side effects.

[1] Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Foods, Drugs, and Cosmetics, 2d ed. New York: John Wiley & Sons, 1996, 478–
80.[2] Curi R, Alvarez M, Bazotte RB, et al. Effect of Stevia rebaudiana on glucose tolerance in normal adult humans. Braz J Med Biol Res 1986;19:771–4. [3]
White JR Jr, Kramer J, Campbell RK, Bernstein R. Oral use of a topical preparation containing an extract of Stevia rebaudiana and the chrysanthemum flower in
the management of hyperglycemia. Diabetes Care 1994;17:940.[4] Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Foods, Drugs, and
Cosmetics, 2d ed. New York: John Wiley & Sons, 1996, 478–80. [5] Blumenthal M. FDA rejects AHPA stevia petition. Whole Foods 1994:Apr;61–4. [6] Geuns
JM. Stevioside. Phytochemistry. 2003 Nov;64(5):913-21. [7] D'Agostino M, De Simone F, Pizza C, Aquino R. Sterols in Stevia rebaudiana Bertoni. Boll Soc Ital
Biol Sper. 1984 Dec 30;60(12):2237-40.[8] Melis MS Stevioside effect on renal function of normal and hypertensive rats. J Ethnopharmacol. 1992 Jun;36(3):213-
7.[9] 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 Sep;50(3):215-20.[10] Chan P et al, The effect of stevioside on blood pressure and plasma catecholamines in spontaneously hypertensive rats. Life Sci.
1998;63(19):1679-84. [11] Lee CN et al Inhibitory effect of stevioside on calcium influx to produce antihypertension. Planta Med. 2001 Dec;67(9):796-9].[12] Hsu
YH et al, Antihypertensive effect of stevioside in different strains of hypertensive rats. Zhonghua Yi Xue Za Zhi (Taipei). 2002 Jan;65(1):1-6. [13]Liu JC et al
Mechanism of the antihypertensive effect of stevioside in anesthetized dogs. Pharmacology. 2003 Jan;67(1):14-20.[14] Hsieh MH et al Efficacy and tolerability
of oral stevioside in patients with mild essential hypertension: a two-year, randomized, placebo-controlled study. Clin Ther. 2003 Nov;25(11):2797-808.[15] Curi R
et al, Effect of Stevia rebaudiana on glucose tolerance in normal adult humans. Braz J Med Biol Res. 1986;19(6):771-4.[16] Jeppesen PB et al, Stevioside acts
directly on pancreatic beta cells to secrete insulin: actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel
activity. Metabolism. 2000 Feb;49(2):208-14.[17] Jeppesen PB et al, Stevioside induces antihyperglycaemic, insulinotropic and glucagonostatic effects in vivo:
studies in the diabetic Goto-Kakizaki (GK) rats. Phytomedicine. 2002 Jan;9(1):9-14. 18] Gregersen S, Jeppesen PB, Holst JJ, Hermansen K. Antihyperglycemic
effects of stevioside in type 2 diabetic subjects. Metabolism. 2004 Jan;53(1):73-6.[19] Chen TH et al Mechanism of the hypoglycemic effect of stevioside, a
glycoside of Stevia rebaudiana. Planta Med. 2005 Feb;71(2):108-13.[20] Yasukawa K  et al Inhibitory effect of stevioside on tumor promotion by 12-O-
tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin. Pharm Bull. 2002 Nov;25(11):1488-90.[21] Amaro-Luis et al Isolation, identification
and antimicrobial activity of ombuoside from Stevia triflora. Ann Pharm Fr. 1997;55(6):262-8[22] Koyama E et al. Absorption and metabolism of glycosidic
sweeteners of stevia mixture and their aglycone, steviol, in rats and humans. Food Chem Toxicol. 2003 Jun;41(6):875-83.
[23] Sekihashi K et al Genotoxicity studies of stevia extract and steviol by the comet assay, J Toxicol Sci. 2002 Dec;27 Suppl 1:1-8.[24] Melis MS. Effects of
chronic administration of Stevia rebaudiana on fertility in rats. J Ethnopharmacol. 1999 Nov 1;67(2):157-61.
Potential Health Benefits of Stevia Extract Supplements

Physiological and pharmacological experiments have suggested that stevioside from the leaves of Stevia rebaudiana
acts as a typical systemic vasodilator.

CELL CULTURE Researchers found that stevioside (from Stevia rebaudiana leaves) mediated vasorelexation effect
through Ca(2+) influx inhibition. [11]

RATS Melis MS. demonstrated that stevioside (from Stevia rebaudiana leaves) provoked hypotension (blood pressure
lowering effect), diuresis and natriuresis in both the normal and hypertensive rats.  Normal rats presented an increase
in renal plasma flow (RPF) and glomerular filtration rate (GFR) constant following stevioside administration. The last
effect is in part due to vasodilation of both the afferent and efferent arterioles. [8]

Chan P et al demonstrated the blood pressure lowering effect of stevioside (from Stevia rebaudiana leaves) on both
systolic and diastolic blood pressure of rats. It is in a dose-proportional fashion. They found no significant changes in
serum dopamine, norepinephrine and epinephrine levels 60 min after intravenous injection of stevioside 100 mg/kg in
anesthetized rats. [10]

Drinking of 0.1% stevioside (from Stevia rebaudiana) solution in mature spontaneously hypertensive rats could have
antihypertensive (blood pressure lowering) effect and also prevented hypertension (high blood pressure) in immature
spontaneously hypertensive rats. [12]
Stevioside (from Stevia rebaudiana leaves) caused vasorelaxation via an inhibition of Ca(2+) influx into the blood
vessel in a study of normal rats. [11]

DOG Stevioside (from the leaves of Stevia rebaudiana) also showed significant hypotensive effects in renal
hypertensive dogs, in a dose-dependent manner and its hypotensive (blood pressure lowering effect) mechanism may
be probably due to inhibition of the Ca(2+) influx. [13]

HUMAN Chan P et al demonstrated the antihypertensive (blood pressure lowering) effect of stevioside (from Stevia
rebaudiana leaves) in a 3-month, multi-center, randomized, double-blinded, placebo-controlled study. [9]

A 2-year study of 168 patients suffered from hypertension (aged 20-75) demonstrated that oral stevioside (from
Stevia rebaudiana Bertoni) decreased systolic and diastolic blood pressure without significant adverse effects [14]
Stevia extracts may benefit people at risk of diabetes, as they may help to control blood glucose levels. However, users
must be careful, if they are also on anti-diabetic medications. In 1986, Curi R et al, Universidade de Maringa, Brasil,
demonstrated that aqueous extracts of Stevia rebaudiana leaves could increase glucose tolerance in a study of 16
healthy human subjects. [15]

About 14 years later, Jeppesen PB and co-workers at Aarhus University Hospital, Denmark demonstrated that stevioside
and steviol (from stevia) stimulated insulin secretion via a direct action on beta cells. The results suggested that the
stevia may be beneficial to people suffered from type 2 diabetes mellitus. [16] In 2002, Jeppesen PB et al reported that
stevioside (from stevia) had antihyperglycaemic, insulinotropic, and glucagonostatic activities from a study of type 2
diabetic rat. [17] In 2004, Jeppesen PB et al finally studied the anti-hyperglycaemic properties of stevioside (from stevia)
in human subjects. They recruited 12 patients suffered from Type 2 diabetes and successfully demonstrated that
stevioside reduces postprandial blood glucose levels in the patients. [18]

On the other hand, Chen TH and co-workers found that stevioside (from stevia) was able to regulate blood glucose
levels by enhancing not only insulin secretion, but also insulin utilization in insulin-deficient rats; the latter was due to
decreased phosphoenol pyruvate carboxykinase gene expression in rat liver by stevioside's action of slowing down
gluconeogenesis. [19]

Stevia may benefit people at risk of certain cancers, but the evidence is very limited. Yasukawa K and his co-workers
isolated four steviol (ent-kaurene-type diterpenoid) glycosides, stevioside, rebaudiosides A and C, and dulcoside A)
from Stevia rebaudiana BERTONI and they found a strong inhibitory effect of these steviols on
12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. [20]