Stevia: A Plant for Sweetness?
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Stevia: A Plant for Sweetness?

Antoine Al-Achi, Ph.D.
Associate Professor
Campbell University School of Pharmacy, Buies Creek, NC

Robert Greenwood, Ph.D., R.Ph.
Associate Professor
Campbell University School of Pharmacy, Buies Creek, NC

This herb is used in many parts of the world as a noncaloric sweetener.

Stevia (Asteraceae) is a woody shrub that can reach 80 cm in height when it is fully matured. The Stevia genus comprises at least 110 species1 but there may be as many as 300.2 Its habitat extends from the southwestern United States to the Brazilian highlands.2 Different species of Stevia contain several potential sweetening compounds, with Stevia rebaudiana Bertoni being the sweetest of all.2,3 The use of Stevia rebaudiana as a sweetener can be found in many parts of Central and South America, where this species is indigenous,4 as well as in Japan.3 People in Japan have been using Stevia as a sweetener in products such as seafood, soft drinks, and candies.2 This plant has been used in several areas of the world, such as in Brazil and Paraguay, as a natural control for diabetes.5 Stevia also has been used to help control weight in obese persons.6 In the U.S., Stevia is strictly limited by the FDA for use as a "dietary supplement." It cannot be labeled as a sweetening agent or for any therapeutic indication.7

Chemical Constituents

The complete chemical composition of Stevia species is not yet available. However, a variety of Stevia species have been tested for their chemical compositions. The useful part of this shrub is the leaves.2 Out of 110 species tested for sweetness, only 18 were found to possess this characteristic.2 Eight ent-kaurene glycosides, namely dulcoside A, rebaudiosides A-E, steviolbioside, and stevioside, produce the sweet taste sensation.3 These glycosides are mainly compounds of the diterpene derivative steviol.8 Stevia rebaudiana Bertoni, the sweetest species, contains in its leaves all of the eight ent-kaurene glycosides,3 with stevioside being the major constituent (3%–8% by weight of the dried leaves).4 In addition, Stevia rebaudiana Bertoni contains stigmasterol, beta-sitosterol, and campesterol.9 The same species also contains steviol, a product formed by enzymatic hydroxylation within the plant.10 Other chemicals with no sweet taste are also found in Stevia species and some may even be bitter in taste. Stevisalioside A (from the roots of Stevia salicifolia),11 longipinane derivatives in the roots of Stevia connata,12 epoxylabdane diterpenes and a clerodane derivative in the leaves of Stevia subpubescens,13 flavonoids from the leaves of Stevia nepetifolia,14 Stevia microchaeta, Stevia monardifolia, Stevia origanoides,15 Stevia rebaudiana,1 and Stevia procumbens (aerial parts),16 and sesquiterpene lactones from the aerial parts of Stevia procumbens16 and the leaves of Stevia origanoides,17 are in this group.

Physiological and Pharmacological Actions

Stevia is used in many parts of the world as a non-caloric sweetener.18 Along with sweetness, a bitter taste is also noted in humans.19 As an extract, this herb was found to have similar potency with regard to sweetness as a 10% sucrose solution at either pH 3.0 or 7.0.20 The same study also showed that the herbal extract had similar potency as that of aspartame and a cyclamate/saccharin mixture.20 The potency of Stevia extracts was found to be higher than other herbal sweet extracts such as those of Thladiantha grosvernorii (Cucurbitaceae) or Abrus precatorius (Fabaceae).19 The sweetness of stevioside, the major sweet component in Stevia species, was detected in a concentration as low as 24 mg/ml.19

The effect of administering Stevia on renal function in animals has been examined extensively. The oral administration of a Stevia extract over a 30-day period (2.67 g dry leaves/day) resulted in a significant decrease in arterial pressure in both normal and experimentally induced hypertensive rats as compared to control.21 In hypertensive rats, the glomerular filtration rate increased significantly while that of normal rats remained unchanged with Stevia treatment.21 Renal plasma flow, sodium excretion, and total renal flow all increased following Stevia administration in both normal and hypertensive rats.21 The author of this study concluded that administering Stevia in higher than normal amounts (i.e., higher than that used for sweetening purposes) resulted in vasodilation in both hypertensive and normal rats. When given via intravenous infusion (0.05 mg/min/100 g) to rats, a Stevia rebaudiana extract produced an increase in sodium renal excretion.22 The same infusion produced a significant increase in renal water clearance in water diuresis rats, and increased significantly the reabsorption of water by the collecting duct in antidiuresis animals.22 Steviol, along with its structural analogs isosteviol and glucosilsteviol have been shown to inhibit oxygen uptake and decrease glucose production by rat renal cortical tubules.23 The chronic administration of Stevia rebaudiana extracts in rats for 20 days did not produce any changes in renal function.24 However, when the same extract was administered for 40 and 60 days, hypotension, natriuresis, and diuresis occurred.24 There was also a significant increase in renal plasma flow after 60 days of administering the extract.24 The symptoms seen with chronic administration of the extract over 40 and 60 days are consistent with a systemic and renal vasodilation.24,25 This vasodilating response to the extract of Stevia rebaudiana may be due to the calcium antagonistic effect produced by stevioside, the principal component in this herbal preparation.25 In spontaneously hypertensive rats, stevioside given in an intravenous dose of 50, 100, or 200 mg/kg caused hypo- tension in a dose dependent fashion.26 Stevioside is excreted in urine by renal tubular epithelium,4 and not metabolized by the liver.27

Although the liver does not metabolize stevioside, this compound does affect liver function. Stevioside, along with steviolbioside, isosteviol, and steviol caused inhibition of oxidative phosphorylation in rat liver mitochondria.28 The same compounds were found to inhibit the enzyme activity of ATPase, NADH-oxidase, succinate-oxidase, succinate dehydrogenase, and L-glutamate dehydrogenase.28 Stevioside inhibited ketogenesis and to a lesser degree the citric acid cycle.29 Steviol, isosteviol and other related glycosides did not affect glutathione
S-transferase activity in mice.30

The chronic administration of stevioside (0.5, 1.0, or 2.5 g/kg/day) in hamsters showed no adverse effects, including histological evidence, on the reproductive systems in both male and female animals.31 This unchanged profile was followed and noted in two generations of hamsters, also continually fed stevioside since birth.31 These findings on the reproductive system in male rats were confirmed in another study.32 The chronic administration (60 days) of Stevia rebaudiana resulted in a decrease in the plasma testosterone level and in the epididymal sperm concentration in male rats.33 The author concluded that this effect was consistent with the belief that administration of Stevia extracts may produce infertility in males.33 It appears at this time that the issue of infertility following the administration of Stevia products remains controversial.

Human Studies

Despite centuries of use, there is still a lack of comprehensive clinical studies on Stevia as a supplement. In normal human volunteers, the effect of administering extracts of Stevia rebaudiana on glucose tolerance tests was investigated. Subjects were given aqueous extracts from 5 grams of leaves every six hours for three days. A glucose tolerance test was performed before and after administration of the extracts. The results showed that treatment with Stevia resulted in an increase in glucose tolerance and a decrease in plasma glucose concentrations.34 Moreover, it was shown recently that both steviol and stevioside can produce a direct effect on beta cells in the pancreas to release insulin.5 The authors concluded that this plant may have a potential use in the management of type 2 diabetes.5

Cariogenic and Mutagenic Effects

Since Stevia products are used as sugar substitutes by many populations, a study was conducted to test whether stevioside and rebaudioside A may have the potential of causing dental caries from prolonged use. Rats were fed a diet containing 0.5% stevioside or 0.5% rebaudioside A for five weeks. Neither compound showed a potential of increasing the risk of developing dental caries.35

Several researchers investigated the risk of mutagenicity. In two studies,18,30 steviol produced a dose-related positive mutagenic effect in some tests. In the same study, stevioside was found to be devoid of this effect. Other reports indicated lack of mutagenicity of both compounds.6,36 Because of these contradictory reports, the FDA is still cautious in introducing this herb as a sugar substitute until its safety is completely established.7

Stevia Products

Some examples of Stevia products available on the market in the U.S. are listed in TABLE 1. Products of Stevia can be purchased directly from various companies or from local pharmacies. Many companies sell Stevia products via the Internet.

Conclusion

Stevia is an herb that is used extensively in various areas of the world (without documentation of long term use and effects) as a noncaloric sugar substitute. Various reports in animals and humans indicate that the safety of this herb is not yet completely determined. The current status of using this herb in the U.S. is as a "dietary supplement." Until further information is available, pharmacists should be advised to conform to the FDA recommendation when counseling patients about this herb. Specifically, mild to moderate use as a supplement should be safe, but increased use for other pharmacological effects may not be warranted. ABLE 1 Some Commercially Available Stevia Products in the U.S.

Some Commercially Available Stevia Products in the U.S.
Product Name Manufacturer Type Suggested "Dose"
Sweetvia At Steviaa  Crystals -
Stevia Extract Life Extension Foundationb Powder Minute quantity
JAJ Stevioside JAJA Group, Inc.c Powder -
Stevia Liquid Extract Baar Products, Inc.d Liquid -
Stevia Dark Liquid Concentrate SteviaNOWe Liquid Concentrate -
Stevia Pure Powder Extract SteviaNOW Powdered Extract -
Stevia Tablets SteviaNOW Tablets (100–400 mg) -
 
a At Stevia LLC, P.O. Box 80253, Valley Forge, PA 19484
b Life Extension Foundation, 995 SW 24th Street, Fort Lauderdale, FL 33315
c JAJA Group, Inc., 8787 Southside Blvd # 4813, Jacksonville, FL 32256
d Baar Products, Inc., P.O. Box 60, Downingtown, PA 19335
e SteviaNOW, P.O. Box 812, Shrub Oak, NY 10588

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