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Journal of Food and Nutrition Research, 2018, Vol. 6, No. 8, 497-503
Available online at http://pubs.sciepub.com/jfnr/6/8/2
©Science and Education Publishing
Benefits and Effectiveness of Using Paullinia cupana:
A Review Article
Adele Salomão-Oliveira1,*, Emerson Silva Lima2, Helyde Albuquerque Marinho3, Rosany Piccolotto Carvalho4
1Multi-Institutional Post-Graduate Biotechnology Program, Universidade Federal do Amazonas (UFAM), Manaus, AM, Brazil
2Pharmaceutical Sciences Departement, Universidade Federal do Amazonas (UFAM), Manaus, AM, Brazil
3Department of Research, Society and Health, Instituto Nacional de Pesquisas da Amazônia (INPA), Manaus-AM, Brazil
4Physiological Science Departament, Universidade Federal do Amazonas (UFAM), Manaus, AM, Brazil
*Corresponding author: firstname.lastname@example.org
Received July 07, 2018; Revised August 16, 2018; Accepted August 22, 2018
Abstract Guarana is native to the Amazonian region of Brazil and, widely used in liquid preparations due to its
stimulating effect, along with other therapeutic properties. Its chemical components, methylxanthines and condensed
tannins, exhibiting a marked biological activity, may be found in commercially available powdered guarana brands
at varying levels, possibly due to their provenance and drying processes. However, the chemical standardization of
its extract maintains the same quantified content of active substances on each and every lot of extract produced, thus
asssuring their quality and therapeutic efficacy. Consumption of guarana by the population should be controlled,
since there is controversy as to its dosage and association with allopathic drugs, the interactions of which may result
in increasing the therapeutic effect, reducing efficacy or even bringing about adverse reactions. However, the use of
guarana in adequate concentrations may contribute to achieve therapeutic properties with less toxicity on account of
it being some natural antioxidants source and considered one of the most important new substances directly used as
effective medicinal agents.
Keywords: Paullinia cupana, guaraná, sapindaceae, Amazônia
Cite This Article: Adele Salomão-Oliveira, Emerson Silva Lima, Helyde Albuquerque Marinho, and Rosany
Piccolotto Carvalho, “Benefits and Effectiveness of Using Paullinia cupana: A Review Article.” Journal of Food
and Nutrition Research, vol. 6, no. 8 (2018): 497-503. doi: 10.12691/jfnr-6-8-2.
Paullinia cupana Kunth originates from the Amazon
Basin, belongs to family Sapindaceae and is consumed on
a global scale . Historical data reveal that guaraná was
already known by the Maués, Andirás and Marabitanas
tribes of Amazonia, before the arrival of the Europeans, due
to its stimulating , antidepressant  and diuretic 
Large amounts of methylxanthines, including caffeine,
theophylline and theobromine, in addition to saponins,
polyphenols, and especially condensed tannins, are responsible
for the benefits brought on to the population on account of
being chemical substances bearing bioactive properties .
Therefore, the biologic activities of guarana possess
therapeutic indications, to be investigated in the prevention
treatment of diseases, with promising perspectives for
producing novel phyto drugs.
2. Chemical Characteristics
Guarana seeds (Figure 1), source: Rebelo/INPA-Brazil,
contain a high concentration of bioactive components,
described in 1669, when their daily use by the indigenous
peoples of the Amazon region, was observed.
Figure 1. Guaraná fruit
Among the main chemical constituents of guarana,
methylxanthines, I- Caffeine (1,3,7-trimethylxanthine),
II- Theophylline (1,3-dimethylxanthine) and III- Theobromine
(3,7-dimethylxanthine) (Figure 2 & Figure 3)  and
condensed tannins, are composed of interconnected
monomeric units, the main ones of which being
Journal of Food and Nutrition Research 498
proanthocyanidin: catechin and epicatechin (flavan-3-ol),
due to their antioxidant effect in the protection of
atherosclerotic cardiovascular diseases and the process
of carcinogenesis [6,7,8,9]. Phytochemical composition
includes: xanthine: caffeine (1,3,7-trimethylxanthine) (2 to
7.5%), theobromine (0.02 to 0.03%) and theophylline
(0.25%). In the essential oil, cyclic sesquiterpenes and
cyclic monoterpenes were identified. Minerals were also
identified: calcium (0.1%), phosphorus (0.3%), potassium
(0.3%), magnesium (0.08%), iron (4.3 mg); flavonoids:
catechol and epicatechol; tannins (8.5 to 25%) [2,9-15].
Figure 2. Guaraná-methylxanthines
Figure 3. Metlhylxanthines
3. Biological Activity
Several studies on the medicinal properties of guarana
seeds have been carried out, especially in the last three
decades, demonstrating the potential of the biological
activities concentrated in guarana with its exceptional
content of methylxanthines and proanthocyanidins .
Thus, the isolated substances have already been analyzed
according to the studies described below (Table 1).
4. Bioactive Compound Contents
In the scientific literature, the data on the concentration
of guarana powder are conflicting, depending on the
region of planting and techniques used for its cultivation
and drying processes. Studies have verified different
levels of caffeine in marketed powdered Guarana brands,
being outside the pharmacopoeia quality specifications.
The caffeine content in the samples presented a great
variability, in the range of 9.52 to 36.71 mg / g of powder.
Due to this variation, the consumers of this product are
liable to ingest uncontrolled doses, which may cause a
health damage . This demonstrates the need to
implement quantitative techniques in the physical-
chemical quality control of plant raw materials, in addition
to the need to qualify suppliers by emphasizing the control
in acquisition, storage and handling .
Under this context, studies will provide better
definitions, showing guarana to bear a higher caffeine
content than that of coffee seeds (7.59 mg caffeine / gram
of guarana powder), verified in the studies , in
threefold higher quantity, with a mean caffeine
concentration of 20.68 mg / g (caffeine / gram of powder),
and this difference can reach up to fourfold .
Technological alternatives are necessary in order to
consume guarana since it tastes bitter and irritates the
gastrointestinal tract. Short-term medicinal effects are
commonly considered to result from caffeine and
associated alkaloids high content as well as considerable
amounts of tannins [4,47]. Thus, future research may
show that various saponins also play an important role in
pharmacology of the drug, particularly with regard to its
long-term influence as a general and prophylactic toner.
Studies have noted that five minutes after consumption,
caffeine can be detected throughout the human body,
reaching its peak action after 30 minutes and lasting from
four to six hours. Excessive consumption of caffeine-rich
foods can cause unpleasant symptoms such as irritability,
headaches, insomnia, diarrhea and tachycardia. Guarana
should not be consumed by individuals, with a history of
heart disease, hypertension, sensitive to caffeine use, and
with gastrointestinal disorders (irritable bowel syndrome,
colitis, diarrhea, gastritis). Eating more than 400mg per
day can lead to so-called "caffeinism" the most common
symptoms of which have shown to be anxiety, restlessness,
irritability, tremors, appetite loss, muscle tension,
insomnia, and heart palpitations. The safe dose of guarana
powder has not been defined as of yet [44,48,49,50].
Conversely, effects can be described as increased
alertness and reduced fatigue associated with improved
performance of activities [3,18,27,44,51].
Studies have shown guarana concentration to be of critical
importance for the cytotoxic activity of the compounds
present in guarana. Low guarana concentrations have been
shown to be harmless, whereas higher ones could be
As to phenols, they are not considered to be toxic in
normal amounts and conditions, except for polymeric
phenols called tannins, which have the ability to complex
and precipitate proteins from aqueous solutions .
When oxidized, tannins turn into quinones, which form
covalent bonds with some functional groups of the
proteins, mainly the cysteine and lysine ε-amino sulfide
More specifically, tannins are high molecular weight
compounds, containing enough phenolic hydroxyl groups,
to allow the formation of stable cross-links with proteins
. They are present in a larger quantity in the foods
normally consumed, in the composition of the dietary
fiber fraction of different foods and may be considered
indigestible or partially digestible [54,56,57,58,59].
Experimental evidence confirms previous observations
that polyphenolic compounds significantly inhibit iron
absorption, but the negative effect of tannin on iron
absorption can be effectively prevented by simultaneous
administration of ascorbic acid [60,61].
499 Journal of Food and Nutrition Research
Table 1. Biological activity verified in the seed of P. cupana
Chemical substance Verified biological activity According to
Therapeutic benefits in gastric disorders on rats pre-treated with guarana (50 and 100
mg / kg powder) showed a significant reduction in the ethanol-induced gastric lesions
severity, similar to that of caffeine (20 and 30 mg / kg powder). This can be accounted
for by the effect of increased blood flow in the gastrointestinal mucosa.
Improvement of cognitive behavior. The effect of chronic treatment on cognitive
behavior was studied in rats submitted to the Morris labyrinthine test, and a beneficial
effect on cognition, weight evolution and survival was observed, showing low toxicity
for lyophilized crude extracts at 30 mg / kg).
Anxiolytic, antidepressant and motor stimulant effects. The freeze-dried crude extract
(CB), 30 mg / kg (caffeine 10 mg / kg) following acute and chronic oral administration
in rats, produced an effect similar to that of antidepressant after long-term
Improvement of depression. It has been shown that chronic treatment with semi-
purified extract in rats 8 mg / kg) produced panicolytic and anxiolytic effects, and that
dopaminergic and serotonergic neurotransmission systems are involved in this effect
promoted by the aqueous fraction.
Dental plaque shield. In vitro
evaluation against Streptococcus mutans showed the
effect on the prevention of bacterial plaque prevention. 
Preventive chemo effect on hepatocarcinogenesis and reduced diethylnitrosamine-
induced DNA damage in mice for 14 day with guarana powder (2.0 mg / g diluted in
0.2 mL of filtered water), exhibiting a reduction of 68.6% in the tumor loading area.
Ergogenic and increased reasoning ability. 30 mg / kg was chronically administered,
increasing the physical capacity of mice subjected to stressful situations, such as forced
swimming. The animals had the same average life span, indicating the guarana’s low
Antibacterial and antioxidant activity. An antimicrobial assay proved the ethanol
extract to be active against Gram-negative and Gram-positive bacteria (16 to 64 μg /
mL). Antioxidant assay results demonstrated guarana ethanol extract to considerably
reduced lipid peroxidation with 65.2% cell damage reduction using a guarana extract at
a concentration of 2 μg / mL in vitro.
Pulmonary chemopreventive effect. Studies evaluated the effects of guarana (2.0 mg P.
cupana / g body weight) diluted in 0.2 mL of filtered water and administered in vivo
per oral consumption. The treatment decreased proliferation and increased apoptosis of
tumor cells, thus reducing the tumor loading area, assigning caffeine to play a key role
in controlling the metastasis process and the anticancer effects of catechins (tannins).
Weight loss. Study with healthy overweight adult patients consuming capsules
containing 95 mg of guara
na resulted in delayed gastric emptying, reduced gastric
fullness time, and significant weight loss by 45 days.
Hypolipidic effect. It verified the effect of supplementation on lipid metabolism in rats
supplemented with daily doses of 325 g / kg body weight with lyophilized
hydroalcoholic guarana extract.
Diuretic action. Use to treat edema
associated with congestive heart failure. The
diuretic effect occurs by antagonizing adenosine receptors A1 and A2a. 
Thermogenic effect. Even a low dose of caffeine (100 mg) in humans has the potential
of inducing a thermogenic effect at rest. It is unknown whether this is due to the
increasing fat or carbohydrate oxidation, or both
Anorexigenic and stimulant properties. A randomized, double-blind, placebo-
controlled trial effectively promoted weight loss and fat reduction of overweight men
and women with 240 mg / day of caffeine over the 8-week treatment period.
Psychoactive effects. A double-blind, randomized, placebo-controlled, parallel-group
study on young adults evaluated the acute effects of a vitamin / mineral / guarana
supplement (containing 40 mg of caffeine). The results demonstrated that the
enhancing properties of guarana cognition provide evidence that its addition to a multi-
vitamin-mineral supplement may improve cognitive e performance and reduce mental
fatigue associated with frequent mental effort.
Antidepressant. Guarana extract was evaluated in comparison to caffeine, in the
behavior of rats in forced swimming and in open field tests. At concentrations of (25
and 50 mg / kg, powder) and caffeine (10 and 20 mg / kg, powder) it significantly
reduced the duratio
n of immobility in the forced swimming test, suggesting a similar
effect to that of antidepressant in mice. However, a high dose of guarana (100 mg / kg)
and caffeine (30 mg / kg) significantly increased locomotor activity in the open field
test. Results suggest caffeine to be involved in the antidepressant activity of guarana.
Cardioprotective, thermogenic, hypolipid, and nontoxic. Studies with rats daily
supplemented with 150 mg of caffeine (dose equivalent to that of humans) for 12
months produced no adverse cardiovascular effects, caused significant weight loss in
mice, and induced no vital target organ toxicity or biochemical abnormalities,
suggesting an increase in the basal metabolic rate, by bringing about increased energy
expenditure at the expense of fat
Vasoconstrictor. Migraine, tonic, energetic, and aphrodisiac treatment. The authors
noted that the Sateré-Maués Indians originally used guarana for centuries to obtain
medicinal effects. Meta-
analysis, suggests that caffeine, due to its vasoconstrictive
effect resulting from the blockade of adenosine receptors, may be useful in relieving
headache through the ingestion of 100 mg of caffeine.
Journal of Food and Nutrition Research 500
Chemical substance Verified biological activity According to
Theophylline (1,3-dimethylxanthine) The authors, in reviewing the literature, mention the bronchial protective, early aging,
anti-inflammatory, and vasodilator effects. 
Condensed tannins (proanthocyanin-dins:
catechin and epicatechin)
Antioxidant effects. It was shown that even in low concentrations (1.2 μg / ml) in vitro,
it also inhibited the lipid peroxidation process in rats and mice c
(intraperitoneal and oral, 0.3 and 3.0 mg / ml), probably due to its tannin content. And
at high doses of 1000-2000 mg / kg, it induced no significant changes in the
parameters for toxicological screening.
The authors report on the antidiarrheal effect conferred to tannins since they bear
astringent properties useful for the cases of diarrheal states. 
Antioxidant,anti-inflammatory, protection against cardiovascular diseases, and
increased activity of glutathione peroxidase and catalase on delaying early aging.
Clinical trials with healthy overweight adult volunteers have shown the catechins
present in guarana to be an important bioactive component. The consumption of 3 g of
guarana powder suspended in 300 ml of water in the morning before breakfast was
evaluated by means of oxidative stress markers, with the presence of catechins (30.0 g
± 0.1 / 100 g guarana) blood circulation.
Preventive chemo effect on hepatocarcinogenesis. Some tannins are known to have
protective effects against DNA damage. Findings show a reduction of 54% in the
image length of the exposed animals (p < 0.05).
Efficacy of tannic acid on inhibiting the growth of intestinal bacteria due its strong iron
binding ability, affecting the growth of some intestinal bacteria that require iron for
their growth. The study was carried out in vitro at a concentration of up to 500 μg / mL
and could have an impact on human health.
Anti-inflammatory. Preservation of cartilage and chondrocytes in vitro and in vivo.
Action of the extract verified with consumption of 2.0 mg / 2 times per day in humans
and of a dose of 20 mg / kg of weight in rats, administered intraperitoneally
Vasodilator. These flavonoids measured a significant arterial dilatation response in
humans supplemented with 1.5 mg / kg body weight of epicatechin and epicatechin
over a period of 3 to 4 weeks.
However, no effect of tannins on calcium absorption
was observed in rats . For the authors, the explanation
of the results may be due to the fact that tannins
preferentially bind to the iron leaving the calcium free.
With respect to calcium homeostasis, data compiled
in a review indicate that caffeine is not detrimental to
bone metabolism of individuals whose calcium intake is
adequate to their daily metabolic needs .
Thus, moderate consumption of guarana (maximum
4.6mg/kg body weight/day) in healthy adults of
reproductive age is not associated with adverse effects
[64,65,66]. Therefore, it is important to carefully instruct
the use of guarana to the population with prescription and
5. Drug Interactions
The use of caffeine in the form of drugs, as for instance,
in anti-flu drugs, and of a lot it in the composition of a
variety of dietary supplements, is mainly used because of
its high content [12,70,71].
Guarana potentiates the action of analgesics, antidepressant
activity, and, consumed with anticoagulants can lead to
inhibition of platelet aggregation, thus increasing the risk
of bleeding .
Drug interactions are pharmacological responses, in
which the effects of one or more medicinal products
are altered by their concomitant administration. These
interactions are both observed with synthesized chemicals
(allopathic drugs), and those present in plants being used
in home preparations and herbal medicines .
However, interactions with guarana may result in its
therapeutic effect potentiation, efficacy reduction or the
appearance of adverse reactions [72,73,74].
6. Use of Guarana in Allopathy
As a medicinal plant guarana holds an essential content
of caffeine makes part of the pharmacopoeia of Brazil, 
and several European countries, Mexico and the United
States. "Guarana” is used in migraines as a sedative and
tranquilizer, has shown to be an excellent in the
convalescence of serious diseases; inestimable cardiovascular,
exerting a generalized tonic action in the senile evolution.
It regulates the cardiac energy, combats and prevents the
passive congestions so peculiar and frequent in the aged
“organs" . Thus, treating the therapeutic value of this
Sapindácea reveals that daily consumption has a
neurostimulating effect . Guarana is one of the most
important and advantageous medicines of modern therapy,
on account of properties. Its therapeutic value, evidenced
in studies and trials, is increasing and, represents an important
role of worldwide repercussion, in medicine . The
compendia and pharmacological catalogs clearly describe
numerous and vast uses of guarana in the various formulas.
It can be observed that the therapeutic knowledge of
guarana is ancient, and it was observed that in the Upper
Amazon, the general use of chewing small fragments of
guarana paste, can prevent one from feeling thirsty,
hungry, and even physically and mentally fatigued, and
able to work longer hours. And that the use of the guaraná
paste this way leaves a bitter taste in the mouth, which can
be sweetened by the ingestion of water .
A specified study has found guarana to act as a
physiological functions stimulant and an excellent
intestinal regulator . Aiming at the development of its
culture and use, they report its action as an aphrodisiac to
be the most important one [4,47].
Due to being a source of bioactive substances with
multifaceted activity, guarana is used in therapeutics to
501 Journal of Food and Nutrition Research
treat human diseases as well as to rise its effectiveness in
acting as stimulants [20,32,81].
The interest in its consumption is due to its high content
of caffeine and tannins , with antioxidant action in the
promotion, prevention and recovery of health, in addition
to other biological properties . Thus, caffeine appears
to have an effect on the control of the metastasis process
 and the catechins associated with other derivative tannins
present in guarana, such as epicatechin, ent-epicatechin
and procyanidins B1, B2, B3, B4, A2 and C1 , have
been contributing to the control of in vivo melanoma
growth by reducing cell proliferation and increasing cell
death through apoptosis, in addition to antiaging activity,
and verified in this Amazonian fruit .
The studies on the antibacterial activity of guarana could
justify some ethnopharmacological uses, such as against diarrhea
and dysentery, since they demonstrate the strong activity of
this plant against some pathogens of the digestive tract .
According to studies, the alcoholic extracts presented
a higher antimicrobial activity against all the tested
microorganisms than that of the aqueous extract in vitro,
when found in three fungi transmitted by foods:
Aspergillus niger, Trichoderma viride and Penicillium
cyclopium and in three bacteria harmful to health:
Escherichia coli, Pseudomonas fluorescens and Bacillus
cereus . However, the authors observed that in the
aqueous extract, they presented higher amounts of caffeine
and catechins, conferring greater antioxidant activity.
Due to the ongoing emergence of antibiotic-resistant
strains, there is a continuing demand for new antibiotics.
In many developing countries, about 80% of available
medicines come from medicinal plants, and in developed
countries plants are the raw material for processes that
synthesize pure chemical derivatives .
Among the therapeutic effects of guarana, it it comes to
cotribute in a beneficial and effective way when included
in the development of new drugs in intermediate and final
pharmaceutical forms, since it minimized side effects ,
when administered correctly, and is more more cost
effective since it can be obtained from natural sources and
does not need to be industrialized [86,87,88].
Complexes containing caffeine and catechins (and their
dimers) may be responsible for antiplatelet aggregating activity
in guarana seeds and may offer health benefits by lowering
the risk of thrombosis and cardiovascular disease .
For decades, the phenolic compounds of guarana have been
of interest for studies, due to their phytochemicals bearing
beneficial effects on human health, able to stabilize free
radicals, increasing antioxidant activity, among other biological
and pharmacological effects. Therefore, recent studies
have verified that guarana catechins are bioavailable and
contribute to reduce the oxidative stress of clinically
healthy individuals by the direct antioxidant action of the
absorbed photochemistry and the positive regulation of
enzymes, thus reinforcing the published research on the
benefits to human health with the use of guarana .
The therapeutic properties of guarana are attributable to
more than one potentially bioactive component. These
include the relatively high levels of saponins, tannins, and
caffeine contained in guarana extracts. The perspective of
association with single or multiple vitamins and minerals
deserves to be investigated in order to make part of new
drugs. Thus, the relationship between the concentration of
guarana bioactive compounds and their antioxidant
capacity is associated with the therapy of diseases and
beneficial effects for health. The study of the presence and
concentration of these compounds in guaraná should be
expanded, in order to allow a better evaluation of their
effects, allowing a broader understanding that aims to
contribute in several aspects regarding their use, such as:
chemical composition, quality control, kind of extraction,
therapeutic value, posology, pharmacological potential
and association with allopathic drugs.
The authors are grateful to the Federal University of
Conflict of Interest
The authors declare no conflict of interest.
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