Nutritional and Medicinal Properties
of Stevia Rebaudiana
Fasiha Ahsan*, Shahid Bashir and Faiz-ul-Hassan Shah
University Institute of Diet and Nutritional Sciences, The University of Lahore, Pakistan
Submission: June 25, 2020; Published: July 16, 2020
*Corresponding author: Fasiha Ahsan, PhD Scholar, University Institute of Diet and Nutritional Sciences, The University of Lahore, Pakistan
How to cite this article: Fasiha A, Shahid B, Faiz-ul-Hassan S. Nutritional and Medicinal Properties of Stevia Rebaudiana. Curre Res Diabetes
& Obes J 2020; 13(4): 555867. DOI: 10.19080/CRDOJ.2020.13.555867
Researches on new molecules with the least toxic effects and better potency is on its way and more attention is being given upon medicinal plants for forcing away the above problems. Medicinal plants have been recognized as potential drug candidates. Stevia, a natural sweetener with medicinal properties and also having nutritional, therapeutic and industrial importance is being used all over the world. Stevia rebaudiana leaves are usually referred to as candy, sweet and honey leaves. Diterpene glycosides are responsible for its high sweetening potential of leaves. The phytochemical properties of bioactive chemicals present in stevia leaves are involves in maintaining the physiological functions of human body. Paper also highlights the importance of nutritional aspects of dried stevia leaves, metabolism of stevia, effects of it consumption on human health and clinical studies related to stevia ingestion. Various medicinal properties of stevia leaves discussed in paper like anti-hyperglycemia, anti-oxidative, hypotensive, nephro-protective, hepato protective, antibacterial and antifungal. Basic purpose of this review to understand the medicinal potential of stevia and its acceptance as a significant raw material for human diet.
The emergence of chemical molecules was a blessing at once to combat several diseases, but it paved the way for troublous situations like various adverse effects, the emergence of resistance. Researches on new molecules with the least toxic effects and better potency is on its way and more attention is being given upon traditional plants for forcing away the above problems. Nature has bestowed our world with an enormous wealth of medicinal plants. Medicinal plants have been recognized as potential drug candidates. Stevia, a natural sweetener producing medicinal plant having nutritional, therapeutic and industrial importance is being used all over the world. Stevia rebaudiana is a shrub belongs to Asteraceae family and is indigenous to Paraguay, Brazil. It is being cultivated in some parts of Canada, Asia and Europe. Though there are above 200 species of the genus stevia, only stevia rebaudiana gives the sweetest essence . Leaves of Stevia produce diterpene glycosides (stevioside and rebaudiosides), non-nutritive, non-toxic, high-potency sweeteners and may replace sucrose as well as other artificial sweetners, being 300 times sweeter than sucrose . Stevia rebaudiana leaves are usually referred to as candy, sweet
and honey leaves. This is due to the production of stevoil glycosides sweetening compounds . It is known for its sweetness imparted by its glycosides without causing any dysregulation. Steviol is the common aglycone backbone of the sweet stevia glycosides that have been analyzed by liquid chromatography coupled with UV, MS and ELS detection . The phytochemical studies concluded the existence of tannins, alkaloids, glycosides, saponins, sterols, triterpenes with various potentials [5,6]. Purpose of this review to understand the medicinal potential of stevia and its acceptance as a significant raw material for human diet.
Stevia is a woody shrub and when it fully matured can reach upto 80 cm in height. The stevia genus comprises at least 110 species but there may be as many as 300. Its habitat extends from the southwestern United States to the Brazilian highlands . It is estimated that there are over 250 species of stevia which grows wild around the world. However, sweetening properties have been found in stevia rebaudiana and in some species. Stevia is a cm long leaves. The root system of the plant is extensive, the stem
is woody and weak-pubescent at the bottom. It has white flowers
with a pale purple throat. They are small in size and arranged in
the form of small corymbs . Taxonomic information of stevia
rebaudiana is present in Table 1.
Diterpene glycosides are responsible for its high sweetening
potential of leaves. Steviol glycosides, are extracted and recognized
as stevioside, rebaudioside, steviolbioside and dulcoside. Most
ample glycoside of stevia is stevioside and is found to be 4–13% of
dry weight in the stevia leaves, rbaudioside is 2–5% and dulcoside
0.4–0.7%. Stevioside accounts for 4 up to 13% all glycosides in
stevia. It is bittery or stringent when it is tasted. Comparative
organoleptic analyses showed that pure stevioside is 300 times
sweeter than sucrose at a concentration of 0.4% . Kroyer 
reported that steviosides are stable at various processing and
storage conditions. Rebaudioside is 250–450 times sweeter than
sucrose and it is found in stevia rebaudiana at 2–5% of dry matter.
It is the most stable of glycosides and has no bitter after taste, in
contrast to steviosides. Rebaudioside is metabolised by intestinal
microorganisms to stevioside and finally it is transformed to
glucose and a molecule of steviol. Apart from diterpene glycosides,
sweet leaf also contains diterpenes and triterpenes .
Plants accumulate secondary metabolites called
phytochemicals to defend themselves against microbial infections
or infestations by pests. Phytochemicals are active ingredients
which possess therapeutic properties that are considered as a
medicine or drug . Srivastava et al.  showed the presence
of different phytochemicals in stevia leaves extract with their
respective solvent systems. The phytochemical properties of
bioactive chemicals present in stevia leaves are summarized in
Stevia leaves on a dry weight basis provides an energy
of 2.7 kcal/g and it is considered as low calorie sweetener.
Benefits related to stevia leaf are mostly due to their nutritional
composition because it is a significant source of carbohydrates,
protein and crude fiber that maintains the wellbeing and decrease
the risk of various diseases. Fat content in dried stevia powder
is up to 1.9–4.34 g/100 g whereas, carbohydrates and protein
contents are in range of 52 to 64.06 and 10.0 to 18.0 respectively
[12,13]. The proximate composition of stevia is presented in Table
2. In stevia leaves main source of energy is carbohydrates due to
the presence of poly and fructo-oligosaccharides, which regulates
the metabolism of lipid and reduce the sugar level in blood .
Mineral components also present in dried leaves powder but in
minute quantities but are essential for many metabolic processes
in human body. Minerals plays a vital role in health, reproduction,
growth and involved in the formation of new tissues and cells .
Table 3 represent the mineral contents of dried stevia leaves .
Stevia leaves contain a no calorie, stevioside and rebaudiosides
which are 300 times sweeter than sucrose with more dissolving
power in aqueous solution like water and a positive taste profile
that are significantly metabolized by human body without causing
any harm consequences. Steviol glycosides are absorbed and
excreted through similar pathways in both humans and animals . Metabolization process of rebaudioside in the digestive tract
is start by colon microbes which converted it into the stevioside
that further metabolized into steviol and glucose. Glucose which
is formed in this process directly used by bacteria present in colon
rather to absorbed in blood stream. Benefit of using stevia leaves
is that after processing there is no accumulation of any by product
in human body because all the excess components release through
urine. Furthermore, qualitative and quantitative resemblances
have been identified among the gut microflora of human body and
rats . Another study which was conducted on to the human
gastro-intestinal tract determines that that metabolized form of
stevia is not modified in low and high concentrations as observed
by faeces, study also indicated that much of the steviol glycosides
are absorbed and remaining released by urine through kidneys
with the help of glucuronide bond. Whereas, minute quantities of
glucuronide excreted through fecal mass .
It has been shown that the human body does not absorb
stevioside by the oral route and none of the digestive enzymes of
the gastrointestinal tract can degrade stevioside in its aglycone:
steviol. It is important to notice that bacteria present in human
colon are capable of transforming stevioside to steviol. As
steviosides are not absorbed by the human body because majority
of it after absorption excreted through urine and remaining minute
quantities eliminated through feces, therefore, steviosides are
not a source of caloric energy . Several tests of digestion and
absorption have been performed with stevioside compounds and
the effect of gastric juices and digestive enzymes on them show
their inability to degrade the compounds. The in vitro digestibility
of steviosides by various digestive enzymes has been examined for
many years; studies found that none of the enzymes present in the
digestive tract that digest stevioside, it is only hydrolyzed by colon
bacteria into both steviol and steviol-16, 17 alpha-epoxide. Later,
steviol 16, 17 alpha-epoxide was again converted to steviol, which
was excreted from the body in the urine as steviol glucuronide
. This whole process also describes why stevia rebaudiana
does not provide calories to the human body.
About the characteristics of S. rebaudiana beyond its
sweetening potential, several studies have been published where
antimicrobial, antifungal, hepatoprotective, hypoglycaemic
(aqueous extract), antitumor, anti-rotavirus, anti-HIV,
antihypertensive, antiviral and other effects are attributed to it.
Other popular applications of stevia and stevioside (mainly in
Latin America and the East) include stimulation of alertness and as
a supplement against fatigue; it is also attributed an improvement
in the process of digestion and other gastrointestinal functions; in
addition to regulating blood glucose levels, help in the recovery
of liver, pancreas and spleen . Many of these effects are
attributed to the phenolic compounds present in the plant (in
the leaves and, to a lesser extent in the stem), said compounds
are commonly found in both edible and inedible plants. They are
important in the plant for the normal development of growth and
defense against the attack of bacteria, parasites, infections, and
injuries. Also, the presence of these compounds in injured plants
can have an important effect on oxidative stability and microbial
safety. Although phenolic compounds have no known nutritional
function, they can be important for human health because of their
antioxidant potential .
Although the information regarding the reported effects
of stevia rebaudiana is vast. Various studies with different
dosage, duration and results regarding clinical trials conducted
for different durations (Table 4). Clinical studies indicate the
provision of stevia in various forms like powder, aqueous and
stevioside to human and STZ rats. Stevia significantly shown the
hypoglycemic and weight reduction properties.
Diabetes mellitus is a metabolic disorder characterized
by chronic hyperglycemia accompanied by disturbances
in carbohydrate, protein and fat metabolism, due to either
insufficient insulin secretion or insulin insensitivity or both.
Though Stevia rebaudiana is mainly used as a sweetening agent
in foods and beverages, they do not induce a glycaemic response when ingested, rather than it exerts antidiabetic action by the
enhanced secretion of insulin from the beta cells of pancreas
and promoting glucose uptake by enhancing insulin sensitivity
of peripheral tissues. Stevioside also hinders the production of
glucose by preventing the secretion of glucagon secretion [23,24].
The molecular mechanism of action of steviol glycosides as it
modulating pancreatic beta cell function by potentiating TRPM5
(Transient receptor potential cation channel subfamily M member
5), basically a calcium activated cation channel, expressed on
beta cells and peripheral entero-endocrine cells in the gut by
accelerating insulin release in response to glucose stimulation.
Steviol, stevioside, rebaudioside are not the direct agonist of
TRPM5, but the steviol moiety is responsible for interacting
with the protein. Besides, these glycosides can be used as antihyperglycaemic
agents, they are novel leads to the development of
antidiabetic drugs targeting TRPM5. Further, these agents didn’t
produce hypoglycemia, as seen with synthetic agents and hence
will be a great boon for diabetic patients . Steviol glycosides
are able to act as ligands of the insulin receptor (IR or IGF-IR)
activating the P13k/Akt pathway. Upon activation, signal leads to
the Glut 4 translocation from an intracellular pool to the plasma
membrane, allowing glucose entry into cells and thus mimics the
action of insulin. Biscuits incorporated with stevia was found to
inhibit α- glucosidase activity. Aqueous extract of stevia produced
anti-hyperglycemic and restore liver and muscle glycogen levels
in hyperglycemia-induced rabbits by immobilization stress .
Comparison of stevia and pioglitazone, a thiazolidinedione,
both of them having antioxidant properties too can act as ligands
on PPAR-γ (peroxisome proliferator-activated receptor-γ), a
nuclear hormone receptor and induce insulin secretion and
control the level of blood glucose. The mRNA expression of
PPAR-γ can be increased by both stevia and pioglitazone. The
hypoglycemic effect is also aided by its antioxidant nature .
Reduction in the level of inflammatory cytokine IL-6, which
potentiate the elevation of insulin resistance and therefore helpful
in type 2 diabetes . Stevia could control the neuronal synaptic
plasticity in conditions of metabolic disorders induced by the
high consumption of dietary fructose by influencing NOX-(NADPH
oxidase level) specific targets and thus have a neuroprotective
Oxidative damage to biological materials is inflicted
on biomolecules such as proteins, nucleic acid, lipids, and
carbohydrates. Oxidative stress happens when there occurs a
disproportion among the secretion of reactive oxygen species
(ROS) and the capability of human body to voluntarily detoxify
the free radicals to repair the subsequent impairment. In vitro, the
antioxidant activity of stevia extract was confirmed by diphenyl-
1-picrylhydrazyl-hydrate (DPPH) radical scavenging assay, FRAP
(ferric ion reducing activity) assay, and phosphomolybdenum
assay [30,31]. Both methanolic and aqueous extract of dried stevia
leaves is enriched with polyphenols like hesperidin, ellagic acid,
chlorogenic acid, eugenol, coumarin, vanillin and flavonoids and
hence can be used as a significant source of antioxidant in food and
beverages and a promising candidate for diseases like diabetes,
cancer, neural disorders, arthritis and aging which is caused by
the production of ROS. The potentiality of stevia antioxidants is
able to supersede the synthetic antioxidants like BHA (Butylated
hydroxyanisole) and BHT (Butylated hydroxytoluene), which
recently limited in its use due to their carcinogenic potential .
Hydrogen peroxide, an abiotic stress elicitor resulted in an
increased steviol glycoside production such as rebaudioside and
stevioside and non-enzymatic antioxidants that play a defensive
role against an oxidative stress induced by hydrogen peroxide
. The antioxidant activity of phenolic compounds is due to the
radical scavenging by donationg hydrogen. Other radical quenching
mechanisms include electron donation and singlet oxygen
quenching. The antioxidant effects of flavonoids are ascribed to
their power to neutralize the free radicals, chelate metal catalyst,
activate antioxidant enzymes, reduce alpha-tocopherol radicals
and prevent the actions of oxidases. A significant decrease in the
cellular oxidation biomarkers like protein carbonyl content (PCC),
antioxidant enzymes (SOD and CAT) was seen in the presence of
stevia glycosides in CCl4 induced oxidative stress in a fish model
(Cyprinus carpio) .
Aqueous extract of stevia rebaudiana exerts a hypolipidemic
effect by decreasing cholesterol and fatty acid synthesis, attenuating total cholesterol, triglycerides, and LDL levels and
elevating HDL cholesterol . Stevia leaves help in regulating
the blood pressure by relaxing arteries and prevent the buildup of
calcium on artery walls, that promotes vasodilation and reduces
total peripheral resistance and volume of extracellular fluid as
result of elevated natriuresis and diuresis. Both hypolipidemic
and hypotensive effect exerts a cardio-protective action .
Stevioside has shown a marked effect against various cancers
like skin cancer, ovarian cancer and breast cancer as demonstrated
in various cell line studies. The mechanisms for antitumor effects
as it mediated the apoptosis induced by reactive oxygen species
by scavenge free radicals, increased the expression of apoptotic
proteins like Bax, Bc1-2, caspase 9 and reducing the cell viability by
inhibiting DNA synthesis and inducing cell apoptosis. Iso-steviol, a
breakdown product of stevioside, manifested an inhibitory activity
against the enzymes DNA polymerase and DNA topoisomerase
II and inactivates P13K/AKT signaling pathway by inhibiting
phosphorylation of P13 and AKT. From the methanolic extract of
Stevia one compound was isolated and further confirmed by NMR
to be centaureidin, which has an antimitotic effect to be used for
tumor therapy [31,34].
Both stevioside and extracts of stevia show nephroprotective
action due to the coinciding activities like suppression of
oxidative stress, inflammation, and apoptosis. Renal hypertrophy,
glomerular hyper-filtration are two known complications in
the initial stages of diabetes mellitus as characterized by then
increased cortical volume (80%) and its subcomponents PCT
(Proximal Convoluted Tubule), DCT (Distal Convoluted Tubule),
glomeruli, interstitial tissue rather than medullary volume. The
molecular mechanism of these two complications includes the
production of Transforming growth factor β (TGF-β) by mesangial
components and overproduction of free radicals following
hyperglycemia. Expression of inducible nitric oxide synthase NOS
in response to cytokines . Stevia and its glycosides attenuate
not only diabetes related kidney injury but also cisplatin-induced
nephrotoxicity. Cisplatin is a chemotherapeutic agent which
exerts its action by activating cell cycle arrest, apoptosis and
DNA repair. The mechanism of nephron-protective action by
attenuation of oxidative and nitro-sative stress, anti-inflammatory
activity by decreasing p65 and TNF-α expression, anti-apoptotic
effect by suppressing the release of caspase-activating proteins
and restoring cell cycle by reduced p21 expression and increased
cyclin D1 expression by suppressing ERK1/2 activation, associated
with apoptosis and cell cycle arrest .
The antioxidant potential of stevia can be utilized to alleviate
hepatic injury like cirrhosis, hepatic carcinoma which is induced
by the oxidative stress. The hepato-protective ability of stevia is
confirmed against CCl4 induced and lipopolysaccharide-induced
injury in rat and chicken embryo model. The mechanism of CCl4
induced liver injury is its metabolic activation by CYP450 and forms
tri-chloro-methyl free radical CCl3. These free radicals stimulate
lipid peroxidation, protein covalent binding. Glutathione
depletion, and disturbance of calcium and iron ions ultimately
leading to cell death. Lipopolysaccharide is an endotoxin, a potent
inflammagen and the glycolipid component of the cell membrane
of gram-negative bacteria. It exerts liver injury by releasing
inflammatory cytokines like TNF-α (Tumor Necrosis Factor –α),
IL-1β, IL-6 (Interleukins) & ROS . The molecular mechanism
of hepato-protective action of stevia is induction of Nrf2 pathway
which is an endogenous pathway to reduce the level of reactive
metabolites. Immunomodulatory action- by inhibiting NF-κβ that
leads to the downregulation of pro-inflammatory cascade and
thereby prevents necrosis, cholestasis, and preservation of liver
parenchyma structure and function .
Plants have provided a source of inspiration for novel
drug compounds to many scientists. Scientists used different
solvent extracts (methanol, ethanol, ethylacetate, acetone,
petroleumether, chroloform) to investigate the antimicrobial
activity of stevia leaves. Stevia is thought to inhibit the growth
of certain bacteria and other infectious organisms. In some
antimicrobial activity screening studies, these extracts exhibited
susceptibility enough to inhibit the growth of certain pathogenic
bacteria such as Escherichia coli, Bacillus subtilis, Salmonella typhi,
Enterococcus faecalis, Proteus mirabilis, Pseudomonas aeruginosa,
Staphylococcus aureus, Vibrio cholerae, Aeromonas hydrophila
. Antifungal activity was observed against Aspergillusniger,
Penicillium chrysogenum, Alternariasolani. Fusariumoxysporum
showed maximum zone of inhibition by methanolic plant extracts
of stevia rebaudiana in the study of Arya et al. . Therefore,
plant extracts and phytochemicals with known antimicrobial
properties can be of great significance in therapeutic treatments.
The presence of phytochemicals in leaves might have contributed
to the antibacterial activity .
Stevia rebaudiana has become an important plant that needs
to be commercialized without no time because of its medicinal
and therapeutic applications. Constituents of honey leaves can be
used directly or in raw form by human body and provide various
physiological benefits. Dried stevia leaves powder is also a good
source of major and minor nutrients and it is also well known
as an efficient medication for curing chronic diseases. Future
researches also needed to determine its further positive potentials
against diseases and to evaluate its accurate daily intake which
is suitable for human consumption without causing any negative
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