Guarana and Its Possible Effects on Health

Abstract

Botanically known as Paullinia cupana (Sapindaceae), guarana is widely grown in Amazon region and naturally in Brazil, Ecuador, Venezuela, Colombia, Peru and the Cooperative Republic of Guyana. It is used in sugar and/or carbonated soft drinks, herbal teas and energy drinks in the form of guarana extract. Guarana has antioxidant, antibacterial, antifungal, antidepressant effects; improves cognitive performance; triggers weight loss and reduces lipid peroxidation. It has important effects on various methods and treatments from cardiovascular to neurological diseases, from memory and liveliness to cancer. It is also known that guarana enhances biological activities and psychological effects on the body. This compilation has been conducted to evaluate the chemical and physical properties of guarana, its metabolites, the mechanism of its effect on psychological activities and health. GUHES 2 (2020) 709067

Full text

Volume 2, April 2020, 709067
GUHES
Journal of Gazi University Health Sciences Institute
journal homepage: https://dergipark.org.tr/tr/pub/guhes
Guarana and Its Possible Effects on Health
Ayfer Beyaz Coşkun1, Nevin Şanlıer2
1 Firat University, Faculty of Health Sciences, Department of Nutrition and Dietetic, Elazig, Turkey
2 Ankara Medipol University, Faculty of Health Sciences, Department of Nutrition and Dietetic, Ankara,
Turkey
Article info:
Received: 25.03.2020
Accepted: 30.04.2020
Keywords:
Guarana,
Paullinia cupana,
caffeine,
health
Abstract
Botanically known as Paullinia cupana (Sapindaceae), guarana is widely grown in Amazon
region and naturally in Brazil, Ecuador, Venezuela, Colombia, Peru and the Cooperative Republic
of Guyana. It is used in sugar and/or carbonated soft drinks, herbal teas and energy drinks in the
form of guarana extract. Guarana has antioxidant, antibacterial, antifungal, antidepressant effects;
improves cognitive performance; triggers weight loss and reduces lipid peroxidation. It has
important effects on various methods and treatments from cardiovascular to neurological
diseases, from memory and liveliness to cancer. It is also known that guarana enhances biological
activities and psychological effects on the body. This compilation has been conducted to evaluate
the chemical and physical properties of guarana, its metabolites, the mechanism of its effect on
psychological activities and health.

GUHES 2 (2020) 709067
*Corresponding author: Ayfer Beyaz Coşkun
e-mail address: abeyaz@firat.edu.tr
37
1. Introduction
Guarana is a herbal substance extracted from
Paullinia cupana Kunth (Sapindaceae) which is from
maple family in South America and a rain forest ivy
rooted from Amazon for the products rich in caffeine
(Pennay, Lubman, & Miller, 2011; de Lima Portella
et al., 2013). The main components of guarana seeds
were shown in Table 1 (Hamerski, Somner, &
Tamaio, 2013).
The proportion of caffeine in dry weight of guarana
plant seeds is 2-6%, which corresponds to 2 fold of
the caffeine present in the coffee beans (de Oliveira
Campos et al., 2011; Lima et al., 2005; Haskell,
Kennedy, Wesnes, Milne, & Scholey, 2007; EFSA,
2008; Pennay et al., 2011). Caffeine contents of
leaves, seeds and crusts of the dry weight of guarana
are different. According to a study by Baumann et al.
(1995) examining guarana's purine alkaloid contents,
the caffeine content of guarana was found to be
0.02% in the fruit husk (pericarp) and 1.6% in the
seed husk (testa). The caffeine content of the guarana
tinctures is 9.82-11.02%, which is about 2-3 times
higher than the caffeine in seed (Meurer-Grimes,
Berkov, & Beck, 1998). The caffeine content of
guarana is around 1-2%, while this percentage may
rise up to 3% in coffee beans in some cases; its
percentage in yoco husk is around 3%, in tea leaves
between 2-4% while it may rise to very high levels in
some cases, in cola nuts between 1-3% and yerba
mate leaves around 0.4-2% (EFSA, 2008). In other
words, guarana has 30 times more caffeine than
cacao and 10 times more than yerba tea (Edwards et
al., 2005). With this feature, guarana contains the
highest dose of natural caffeine in the world
(Hamerski et al., 2013). As its absorption in the
gastrointestinal system is slower, it can be considered
that guarana has a longer effect than the caffeine in
coffee beans (Pennay et al., 2011).
The popularity of energy drinks has increased in
adolescents and young adults (de Lima Portella et al.,
2013). Such beverages are used to enhance physical
performance and mental alertness with the addition
of herbal supplements and caffeine, such as guarana,
yerba mate and coke nuts (U.S. Food and Drug
Administration, 2012). It is necessary to consider the
combinations of substances as the ingredients of
energy drinks may give a different reaction in the
same formulation. It is also necessary to understand
how these ingredients effect physiology (Moustakas
et al., 2015). Guarana is sold as a stimulant of energy
drinks and also often as capsules combined with
ginseng (Woods, 2012). The different components
found in energy drinks were presented in Table 2
(Zeidán-Chuliá et al., 2013). In energy drinks, it is
anticipated that low doses of guarana seeds have
short term stimulating effect when combined with
caffeine and glucose but high doses do not have a
long term effect (Moustakas et al., 2015).
2. Biological Activities, Molecular Activities,
Molecular Purposes of Guarana and Relevant
Diseases
It is claimed that guarana reduces the effects of
aging, relieves fatigue, improves vitality, endurance,
strength, concentration and performance in athletes,
reduces rheumatic diseases, tension, migraine,
constipation and diarrhea, facilitates weight loss and
suppresses appetite (Woods, 2012). Guarana is rich
in caffeine and catechins like green tea, and its

GUHES 2 (2020) 709067
*Corresponding author: Ayfer Beyaz Coşkun
e-mail address: abeyaz@firat.edu.tr
38
Table 1. Basic composition of renewable guarana beans (Hamerski et al., 2013)
Determination
Content medium (%)
Starch
30
Protein
15
Tannins
12
Catechutannic acid
5
Caffeine
4
Catechic acid
0.6
Kalium
0.27
Oil
0.16
Calcium
0.08
Magnesium
0.05
Phosphorus
0.01
functional properties related to metabolic disorders
are very similar to green tea (de Lima Portella et al.,
2013; da Costa Krewer et al., 2011). Guarana has
antioxidant, antitumoral, anticarcinogenic,
antimicrobial and antidepressive effects. It is also
suggested that guarana has important biological
effects such as improving cognitive performance and
antidepressive effect (da Costa Krewer et al., 2011).
Guarana is also used as a diuretic and as a pain
reliever for migraine treatment (Hamerski et al.,
2013). Guarana was alos reported to have
hepatoprotective activity and preventive effect on
DNA strand breakage in liver damage caused by
carbon tetrachloride (CCl₄) in rats (Kober et al.,
2016). It is also considered that the high
concentration of caffeine available in guarana
powder contributes to the mating success of lab-
reared male flies (de Aquino, Souza, de Jesus Santos,
& Joachim-Bravo, 2016).
2.1. Effects on Cancer
Guarana extracts have an antioxidant effect on NO
(Hamerski et al., 2013). It is known that it has an
antioxidant effect even at low concentrations (1.2 µg
/ mL). It is stated that it is a natural and powerful
antioxidant beneficial to human health and also
protects the organism from oxidative damage (EFSA,
2010).
The antioxidant properties of the guarana extract are
thought to be caused from the tannins, catechins,
epicatechins, saponins, proanthocyanidols as well as
methylxanthines such as theophylline, theobromine
and caffeine (de Lima Portella et al., 2013; Hamerski
et al., 2013). Guarana also protects the body from
damage stimulated by cadmium (Hamerski et al.,
2013). It was reported that guarana supplementation
reduces oxidative stress at maximum 5 mg/mL
(Bittencourt et al., 2013). There is also a significant
.

GUHES 2 (2020) 709067
*Corresponding author: Ayfer Beyaz Coşkun
e-mail address: abeyaz@firat.edu.tr
39
Table 2. Different components found in energy drinks (Zeidán-Chuliá et al., 2013)
Plant extract
Guarana
Paullinia cupana
*Methylxanthines *Epicatechins
Caffeine *Tannins
Theobromine *Saponins
Theophylline *Catechins
*Proanthocyanidins
*Other compounds
Ginseng
Panax ginseng
*Saponins * Other compounds
Ginsenosides
Yohimbine
Yohimbine
Pausinystalia yohimbe
Snakeroot or sarpagantha
Rauwolfia serpentina
Ginkgo
Ginkgo biloba
*Flavonoids *Terpenes
Quercetin Ginkgolide A
Kaempferol Ginkgolide B
Biflavone Ginkgolide C
Ginkgetin Bilobalide
Bilobetin
Sciadopitysin
Amino acids
Taurine
L-carnitine
B vitamins
Caffeine

GUHES 2 (2020) 709067
*Corresponding author: Ayfer Beyaz Coşkun
e-mail address: abeyaz@firat.edu.tr
40
decrease in oxidative stress types such as protein
carbonylation level, intracellular reactive oxygen
species (ROS) and lipoperoxidation in aging adipose-
derived stem cells (ASCs) of the 5 mg / mL
supplemented plant extract (Machado et al., 2015).
Guarana has been reported to significantly reduce
fatigue after chemotherapy in cancer patients (dos
Santos Martins, Ferreira, & del Giglio, 2017). In a
study conducted on cancer patients with anorectic -
cachectic syndrome causing body weight loss and
appetite reduction of more than 5% of normal
weight, all participants were given guarana extract
twice a day for 4 weeks and the body weight of the
patients remained the same and their appetite
increased (Palma et al., 2016). In another study, it
was found out that Paullinia cupana (PC-18) can be
effective for the treatment of fatigue associated with
chemotherapy in 40 patients who had various solid
tumors and was given 37,5 mg PC-18 twice a day
orally for 3 weeks one week after chemotherapy in
induction phase and either the same dose of PC-18 or
placebo randomly for following three weeks
(damping phase) (del Giglio et al., 2013). Besides the
studies revealing the positive effects of guarana, in
another study, the patient group who were treated
with 50 mg guarana twice a day and received
chemoradiotherapy as they have head and neck
cancer suffered from more intense body weight loss
and used more nasogastric tube (dos Santos Martins
et al., 2017). However, further studies are required to
examine its positive effects.
2.2. Antibacterial and Antifungal Effects
Guarana is a bioactive substance which shows
significant antibacterial effect against gram-positive
and gram-negative bacteria (Basile et al., 2013). It
was found out that alcoholic guarana seed extracts
showed strong antimicrobial activity against the
bacteria such as Pseudomonas fluorescens, P.
aeruginosa, Proteus vulgaris, Escherichia coli,
Bacillus cereus, Proteus mirabilis and Streptococus
mutans and the harmful fungi such as Trichoderma
viride, Aspergillus niger and Penicillium cyclopium
(Hamerski et al., 2013). It is also claimed that sodium
benzoate, flavonoids, vitamins, carbon monoxide and
tannins contained in the guarana have a protective
effect on teeth erosion (Barac et al., 2015). It is used
in tooth paste due to its antimicrobial effects (de
Camargo Smolarek et al., 2015).
This plant has also a strong effect against some
pathogens in the digestive tract. Besides in another
study, it was found out that guarana can
ethnopharmacologically be used against dysentery
and diarrhea (Basile et al., 2005). Owing to its strong
antimicrobial and antioxidant properties, it is
suggested that guarana can be used as a natural
additive in food, cosmetic and pharmaceutical
industries. As a result of another study, it was found
out that guarana seed extract has a significant activity
against growth of th bacteria such as E. coli, B.
cereus and P. fluorescens and fungi such as A. niger,
T. viride and P. cyclopium which are responsible for
the food poisoning (Majhenič, Škerget, & Knez,
2007).
2.3. Effects on Nervous System and Memory
Guarana extracts have antidepressive, anxiolytic and
anti-amnestic effects so it is claimed that guarana
reduces the symptoms of depression, when consumed
moderately (Silvestrini, Marino, & Cosentino, 2013).
It was found out that multivitamin-mineral
supplementation prepared with guarana supplement

GUHES 2 (2020) 709067
*Corresponding author: Ayfer Beyaz Coşkun
e-mail address: abeyaz@firat.edu.tr
41
improves decision making performance and ensures a
stable autonomous nervous system regulation in the
first hour (Pomportes, Davranche, Brisswalter, Hays,
& Brisswalter, 2014). In a randomized, prospective
and placebo-controlled study also conducted on 27
healthy individuals (9 of them were given guarana
extract and 15 of them placebo), it was suggested that
guarana extract in recommended quantities (350 mg
x 3/day) has no effect on anxiety, state of mind and
psychological wellness (Silvestrini et al., 2013).
Guarana is considered to promote cognitive
performance, memory and reduces mental fatigue in
healthy young adults (Haskell et al., 2007; Kennedy
et al., 2008). Although guarana is reported to protect
nerves and promote cognitive ability, its possible
mechanism is not fully understood (Ruchel et al.,
2017). In a randomized and controlled study, subjects
were given guarana in 4 different doses and it was
found out that 75 mg of guarana had positive effects
on memory and cognitive functions (Haskell et al.,
2007). As a result of a study in which guarana was
used as a multivitamin, it was observed that there is
an acute beneficial effect on mood and cognitive
performance (Scholey et al., 2013). Moreover, in a
study it was reported that acrolein has a role in
Alzheimer's disease and acrolein-induced toxicity on
neuronal-like cells (SH-SY5Y) was stated to be
inhibited by guarana; therefore, it can be used as a
therapeutic agent for neurodegenerative diseases
(Bittencourt et al., 2014).
According to EFSA, in order to observe guarana’s
effect on vitality and fatigue, it is recommended to
consume guarana; as fruit-seed-root equivalent to
minimum 8 mg caffeine or equivalent to 75 mg
extract (11-13% caffeine), 1-6 g/day pulverized
seeds, as 3% fruit extract equivalent to 1-3 g/day
caffeine or only minimum 50 mg of guarana (EFSA,
2011).
2.4. Relation with Obesity
Guarana seed is increasingly used as a weight loss
product in tablets in powdered and compressed form
(Hamerski et al., 2013). It is considered that guarana
reduces appetite and energy intake and promotes
state of mind (Alkhatib, Seijo, Larumbe, & Naclerio,
2015). Using guarana in natural caffeine sources has
increased significantly in recent years in order to
improve athletic performance and reduce body
weight (Pendleton, Brown, Thomas, & Odle, 2012).
It is extensively consumed by athletes, as it is
believed to be ergogenic and "fat burning" (Hamerski
et al., 2013). Guarana is used in fruit juice drinks,
candy (such as chocolate products), energy drinks, as
well as dietary and herbal supplements and in highly
controversial herbal body weight loss products
(Kennedy, Haskell, Wesnes, & Scholey, 2004).
The metabolic pathways associated with body weight
are related with the role of bioactive components (de
Lima Portella et al., 2013). In a study conducted on
six hundred and thirty-seven elderly individuals (≥60
years), the prevalence of obesity and metabolic
syndrome was found to be lower in guarana-
consuming group than in the group not consuming
guarana. It was found out that the waist
circumference of the male group consuming guarana
was lower than that of the non-consuming group (da
Costa Krewer et al., 2011). In addition, there was no
evidence that weight loss increases when guarana is
consumed alone (Hamerski et al., 2013).

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*Corresponding author: Ayfer Beyaz Coşkun
e-mail address: abeyaz@firat.edu.tr
42
2.5. Effects on Cardiovascular Diseases and
Hypertension
Lipid peroxidation induced by independent radicals
is involved in the pathogenesis of various diseases.
Using a 2 μg/mL concentration of guarana extract
reduces 62.5% of lipid peroxidation depending on the
dose (Basile et al., 2005). The effect of guarana on
serum oxidation and LDL is probably associated with
some bioactive components (xanthine and catechin)
(de Lima Portella et al., 2013; da Costa Krewer,
2011). However, there is not a certain information on
whether guarana consumption increases low density
lipoprotein (LDL) oxidation resistance (de Lima
Portella et al., 2013).
In the study conducted by da Costa Krewer et al.
(2011), the prevalence of hypertension in individuals
who consumed guarana was lower than those who
did not consume, and cholesterol levels of the female
group consuming guarana were lower than that of the
control group. In another study conducted on 42
healthy adults, it was emphasized that guarana has a
positive effect on LDL oxidation and may have
protective effects, in part, on cardio-metabolic
diseases (de Lima Portella et al., 2013). As a result of
another study, it was found out that the cells with
higher cellular nitric oxide levels exposed to different
concentrations of guarana reduced the level of lipid
peroxidation (Bittencourt et al., 2013).
3. Safe Dose and Toxicology
The results of several studies on long-term intake of
guarana are contradictory (Silvestrini et al., 2013).
The consumption of excessive amounts of energy
drinks and more than 200 mg caffeine per day may
cause health problems (Pennay et al., 2011). The
consumption of caffeine more than 20 mg/kg is
considered as potential toxic amount. Moreover, its
consumption more than 150 mg/kg is regarded as
lethal dose (Pendleton et al., 2012).
Generally, the daily dosage of 20 to 30 mg of
caffeine is recommended (Silvestrini et al., 2013).
The caffeine content of a plant depends on several
conditions such as climate, hydration state and
harvest time (de Carvalho Ferrari, 2011). For this
reason, it is not recommended to consume more than
2 energy drinks per day whether it is alcoholic or not
(Pennay et al., 2011). In the light of this information,
as a result of the calculations made by considering
human dose recommendations and body weight, it is
recommended to consume 150-250 mg extracts of
guarana seeds containing 9-11% of caffeine per day
(Dimpfel, 2013).
Guarana was described as safe by the US Food and
Drug Administration (FDA), although it has side
effects when taken in various quantities (de Lima
Portella et al., 2013). EFSA recommends the use of
125 mg of guarana dry powder extract per day
(EFSA, 2012). However, it is suggested in some
sources that elderly people, which are considered to
be sensitive, should be kept under constant
supervision (Lüde et al., 2016).
4. Conclusion
Guarana is a herb which has been used as a medical
plant for many years. In vivo, in vitro and human
experimens have shown that it can be effective in the
treatment and prevention of many diseases. Although
the positive effects of guarana on health are stated,
safe dosing and interactions of its active ingredient,
caffeine, should be taken into consideration in the

GUHES 2 (2020) 709067
*Corresponding author: Ayfer Beyaz Coşkun
e-mail address: abeyaz@firat.edu.tr
43
treatment of diseases. However, studies show
conflicting results about the safe dose.
Due to the increasing consumption of guarana which
has antioxidant features, it can be used for body
weight loss and it is known to reduce cardiovascular
disease prevalence but there is a need for further
human and animal studies on its functional
properties.
Conflict of interest
The authors declare they have no conflict of interest.
The authors alone are responsible for the content and
writing of this article.
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GUHES 2 (2020) 709067
*Corresponding author: Ayfer Beyaz Coşkun
e-mail address: abeyaz@firat.edu.tr
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