Guarana as a source of bioactive compounds

Abstract

A high daily intake of fruits and vegetables is an important strategy to promote health. The mechanism explaining the health benefits of plant food materials is attributed, at least in part, to their high content of bioactive phenolics. Guarana (Paullinia cupana) is a typical product from Amazon biota and, mainly as a source of caffeine; its seeds are commonly used as stimulants. However, guarana seeds are also rich in catechin, epicatechin, procyanidin B1, and procyanidin B2. Guarana exhibits potential health benefits in cognitive function and prevention of cardiovascular disease. Furthermore, it is a promising source of antihyperglycemic and antibacterial compounds for prevention and/or management of type 2 diabetes and oral diseases. However, to confirm these benefits in humans, clinical trials are needed to provide evidence to support these anecdotal observations.

Full text

Copyright: © 2019 International Society for Nutraceuticals and Functional Foods.
All rights reserved. 1
Opinion J. Food Bioact. 2019;6:1–5
Journal of
Food Bioactives International Society for
Nutraceuticals and Functional Foods
Guarana as a source of bioactive compounds
Cintia Pereira Silvaa*, Rosana Aparecida Manólio Soares-Freitasa, Geni Rodrigues Sampaioa,
Adriano Costa de Camargoa,b* and Elizabeth Aparecida Ferraz Silva Torresa
aNutrition Department, School of Public Health, University of São Paulo – USP, São Paulo, Brazil
bDepartamento de Ciencias Vegetales, Facultad de Agronomía e Ingeniería Forestal, Ponticia Universidad Católica de Chile, Casilla 306-
22, Santiago, Chile
*Corresponding author: Cintia Pereira Silva and Adriano Costa de Camargo, Nutrition Department, School of Public Health, University
of São Paulo – USP, São Paulo, Brazil. E-mail: cintiasil@usp.br, adrianoesalq@gmail.com
DOI: 10.31665/JFB.2019.6182
Received: June 18, 2019; Revised received & accepted: June 26, 2019
Citation: da Silva, C.P., Soares-Freitas, R.A.M., Sampaio, G.R, de Camargo, A.C, and Torres, E.A.F.S. (2019). Guarana as a source of
bioactive compounds. J. Food Bioact. 6: 1–5.
Abstract
A high daily intake of fruits and vegetables is an important strategy to promote health. The mechanism explain-
ing the health benets of plant food materials is aributed, at least in part, to their high content of bioacve
phenolics. Guarana (Paullinia cupana) is a typical product from Amazon biota and, mainly as a source of caeine;
its seeds are commonly used as smulants. However, guarana seeds are also rich in catechin, epicatechin, procya-
nidin B1, and procyanidin B2. Guarana exhibits potenal health benets in cognive funcon and prevenon of
cardiovascular disease. Furthermore, it is a promising source of anhyperglycemic and anbacterial compounds
for prevenon and/or management of type 2 diabetes and oral diseases. However, to conrm these benets in
humans, clinical trials are needed to provide evidence for these anecdotal observaons.
Keywords: Caeine; Phenolic compounds; Antioxidant properties; Anti-Inammatory potential; Antimicrobial activity.
Non-communicable diseases (NCDs) are the major health chal-
lenges of the 21st century. In 2016, they were responsible for 71%
(41 million) death around the globe. NCDs include cardiovascular
diseases (17.9 million death), cancers (9 million death), chronic
respiratory diseases (3.8 million death), and diabetes (1.6 million
death) (WHO, 2018).
Unhealthy diet is a behavioral risk factor linked to the main
NCDs. However, several studies have shown that a high daily in-
take of vegetables and fruits may be helpful in health promotion.
The mechanisms explaining these health benets are related to the
action of bioactive molecules such as phenolic compounds (Boe-
ing et al., 2012; Abbas et al., 2017; Karasawa and Mohan, 2018),
mainly due to their antioxidant potential.
Guarana (Paullinia cupana) is a typical product from Amazon
biota. As a source of caeine, its seeds are commonly used as a
stimulant. In food processing, guarana seed extract is the base a-
vor used in the manufacture of one of the most popular Brazilian
carbonated drinks. Furthermore, it is also used in the energy drink
industry. Besides that, guarana has been listed in the Brazilian
Pharmacopoeia (Agência Nacional de Vigilância Sanitária, 2017)
and is also introduced in the U.S. Pharmacopeia, under mono-
graphs for guarana seed, its powder and dry extract. The Brazilian
Food Supplement Law recently recognized that guarana presents
bioactive substances, hence supporting its role as a functional food
ingredient (Agência Nacional de Vigilância Sanitária, 2018).
Literature data show that guarana seeds are good sources of cat-
echin, epicatechin, procyanidin B1, procyanidin B2 (Schimpl et
al., 2013; Yonekura et al., 2016). Due to its bioactive compounds,
guarana has attracted considerable interest as an ingredient for the
development of functional foods and food supplements. However,
the health benets of bioactive compounds depend not only on the
intake levels but also on their bioavailability (BAv). The bioavaila-
bility is involved with digestion, absorption, metabolism, distribu-
tion, transporting, excretion, and colonic fermentation. Therefore,
these parameters have to be considered (de Camargo et al., 2018;
Shahidi and Peng, 2018; Shahidi et al., 2019).
In vitro methods to simulate gastrointestinal digestion allow de-
termination of the bioaccessibility (BAcs) of bioactive compounds

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2
Guarana as a source of bioactive compounds da Silva et al.
and evaluate the eect of food processing and to anticipate their
action under systemic conditions. In line with this, recent studies
have suggested the use of gastrointestinal digestion in functional
food design (Cilla et al., 2018; Santana and Macedo, 2018).
Yonekura et al. (2016) have shown BAcs and BAv of phenolic
compounds of guarana seed in their in vivo study. Mendes et al.
(2019) evaluated the eect of macronutrients (milk casein, potato
starch and vegetable oil) on BAcs of guarana catechins in Caco-2
cells. The results demonstrated that the interaction with other food
macronutrients did not aect the permeability values of all tested
compounds.
Guarana consumption may induce changes in lipid metabolism.
Krewer et al. (2011) evaluated the associations of metabolic dis-
orders and anthropometric and biochemical biomarkers of lipid,
glucose and oxidative metabolism and the habitual ingestion of
guarana by an elderly population. The reduction of prevalence of
various metabolic disorders (hypertension, obesity and metabolic
syndrome) was associated with guarana ingestion, thus suggest-
ing a potential protective eect of regular consumption of guarana
ingestion against metabolic disorders.
Oxidation of low-density lipoprotein-cholesterol (LDL-c) is
known as a biomarker related to the development of coronary heart
disease (Amarowicz, 2016). To investigate how guarana consump-
tion protects against metabolic disorders, Portella et al. (2013) car-
ried out an in vivo study to better understand the potential eects of
guarana on LDL-c oxidation. Healthy elderly subjects who habitu-
ally ingested guarana demonstrated lower LDL-c oxidation than
that of the control group (reduction of 27%, p < 0.0014). Further-
more, guarana exhibited a high antioxidant activity in vitro, mainly
at concentrations of 1 and 5 μg/mL, as demonstrated by decreased
values of conjugated dienes (CDs) and thiobarbituric acid reactive
substances (TBARS), tryptophan destruction and high total per-
oxyl radical-trapping potential (TRAP) activity.
Many studies suggest the link between the intake of dietary an-
tioxidants and the reduction/prevention of cardiovascular diseases
(CVD) (Chiu et al., 2018). The impact of these antioxidants stems
from their protection towards LDL-c oxidation, which is recog-
nized by its role in the early atherogenic process (Vauzour et al.,
2010; Billingsley and Carbone, 2018).
Yonekura et al. (2016) assessed the eects of guarana consump-
tion on plasma catechins, erythrocyte antioxidant enzyme activity
(superoxide dismutase, catalase, and glutathione peroxidase) and
biomarkers of oxidative stress (ex vivo LDL-c oxidation, plasma
total antioxidant status and oxygen radical absorbance capacity
(ORAC) values, and lymphocyte single cell gel electrophoresis) in
healthy overweight subjects. These authors showed that daily in-
take of guarana had both acute and cumulative eects on GPx (glu-
tathione peroxidase) and catalase, which are phase II antioxidant
enzymes that reduce peroxides to water molecules. However, the
antioxidant status markers such as reducing ex vivo LDL-c oxida-
tion and hydrogen peroxide-induced DNA damage in lymphocytes
improved only transiently. The authors believe that the daily dose
of guarana was probably not enough to keep the fasting plasma
catechin concentration above a threshold level required to exert
direct antioxidant eects.
The anti-hyperglycemic potential of guarana seed consumption
has been pointed as another important health benet. The aque-
ous extract of guarana seeds was able to inhibit α-glucosidase
and α-amylase activities in vitro (Silva et al., 2018). Studies have
shown that catechins exhibit α-glucosidase and α- amylase inhibi-
tory activities (Cires et al., 2017; Hanhineva et al., 2010; Kim et
al., 2016). Therefore, to conrm this hypothesis, further studies
with guarana are warranted.
Gut microbiome is involved in the etiology of obesity and obe-
sity-related complications such as non-alcoholic fatty liver disease
(NAFLD), insulin resistance and type 2 diabetes mellitus (T2DM).
The main species of the colonic microbiota are the genera Bac-
teroides, Bidobacterium, Ruminococcus, Eubacterium and Lac-
tobacillus (Canfora et al., 2019). Silveira et al. (2018) evaluated
the eects of guarana seed powder (GSP) on gut microbial com-
position in Wistar rats after 21 days of treatment. GSP altered gut
microbiota in a negative way, loss in diversity, decreased Bacte-
roidetes and increased Cyanobacteria abundance, probably due
to other metabolites than caeine. The modulation of gut micro-
biota by polyphenols is not fully understood. Human intervention
studies provide the best models for studying the eect of phenolic
compounds on modulation of gut microbiota. However, human in-
tervention studies hold inevitable practical and ethical limitations
(Ozdal et al.,2016).
Several phenolic compounds (e.g. catechins and proanthocyani-
dins) have been recognized as potential antimicrobial agents with
bacteriostatic or bactericidal actions (de Camargo et al., 2017;
Ozdal et al., 2016). Majhenič et al. (2007) tested guarana seed
extracts against three food-borne fungi: Aspergillus niger, Tri-
choderma viride and Penicillium cyclopium, and three pathogenic
bacteria: Escherichia coli, Pseudomonas uorescens and Bacillus
cereus. The results suggested that seed extracts of guarana possess
strong antimicrobial action. Besides that, in vitro assessment of the
antibacterial potential of the guarana extracts against Streptococ-
cus mutans showed that these could be used in the prevention of
bacterial dental plaque (Yamaguti-Sasaki et al.,2007).
Numerous plant extracts such as guarana have shown the ability
to prevent carcinogenesis by reducing tumor size or relieve cancer-
related symptoms. Fukumasu et al. (2008) evaluated the eects of
guarana in an experimental metastasis model. Cultured B16/F10
melanoma cells (5 × 105 cells/animal) were injected into the tail
vein of mice on the 7th day of guarana treatment (2.0 mg·g–1 body
weight, per gavage) and the animals were treated with guarana
daily up to 14 days until euthanasia (total treatment time: 21 days).
Guarana treatment decreased proliferation and increased apoptosis
of tumor cells, consequently reducing the tumor burden area.
Hertz et al. (2015) evaluated the eects of guarana on breast
cancer cell response to 7 chemotherapeutic agents currently used
in the treatment of breast cancer. MCF-7 breast cancer cells were
cultured under controlled conditions and exposed to 1, 5 and 10
μg.mL–1 guarana concentrations, with and without chemothera-
peutics (gemcitabine, vinorelbine, methotrexate, 5-uorouracil,
paclitaxel, doxorubicin and cyclophosphamide). The main results
demonstrated the antiproliferative eect of guarana at concentra-
tions of 5 and 10 μg.mL–1 and a signicant eect on chemothera-
peutic drug action.
Cadoná et al. (2017) investigated the in vitro antitumor eect
of guarana by inhibiting the AKT/mTOR/S6K and MAPKs path-
ways. Colorectal and breast cancer cell lineages, HT-29 and MCF-
7 cells, respectively, were exposed to dierent guarana concentra-
tions (0.1, 1, 10, and 100 μg. mL–1) as well as its main bioactive
molecule, caeine, at proportional concentrations to those found
in the extract. The results showed that guarana could serve as an
important agent in antitumor pharmacologic therapies by inhibit-
ing mTOR and MAPKs pathways. However, the most published
studies are in vitro so it is necessary to explore novel ways to ex-
trapolate the overwhelming benecial evidence seen in pre-clinical
studies to humans Table 1.
Increasing evidence suggests that ingested food polyphenols
can have benecial eects in neuronal protection by acting against
oxidative stress and inammatory injury (Ashafaq et al., 2012; de
Camargo et al., 2019; John and Shahidi, 2019; Wang et al., 2018;
Zhang and Tsao, 2016; Zhang et al., 2018). Moreover, polyphenols

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Silva et al. Guarana as a source of bioactive compounds
have been reported to promote cognitive functions (Filosa et al.,
2018). A double-blind, randomised, placebo-controlled, parallel
groups study assessed the acute eects of either a vitamin/min-
eral/guarana supplement or placebo drink in 129 healthy young
adults (18–24 years). Participants completed a 10 min version of
the Cognitive Demand Battery. Thirty minutes following their
drink participants made six consecutive completions of the battery
(i.e. 60 min). The vitamin/mineral/guarana combination resulted
in improved task performance, in comparison to placebo and the
increase in mental fatigue associated with extended task perfor-
mance was also attenuated by the supplement (Kennedy et al.,
2008). Scholey et al. (2013) also conrmed the acute benets of
multivitamins with guarana on mood and cognitive performance.
It is, however, not fully understood which bioactive compound
of guarana improves the mental health. Probably the eect of guar-
ana is due to its caeine content (Scholey et al., 2013). Adeno-
sine seems to inhibit the release of many neurotransmitters in the
central nervous system such as serotonin, noradrenaline and dopa-
mine. Therefore, adenosine receptor antagonists, such as caeine,
promote the release of these various neurotransmitters (Mclellan
et al., 2016; Kolahdouzan and Hamadeh, 2017). However, animal
studies suggest that the powerful neuroprotective eects are due
phenolic compounds content (chlorogenic acid, epigallocatechin
gallate, curcumin, tannins). Their mode of action range from pro-
tection against oxidative stress to interaction with signaling path-
ways involved in maintaining energy homeostasis (Kennedy et al.,
2008; Gomez-Pinilla and Nguyen, 2012).
Globally, depression is rising in an alarming manner, in almost
every community of the world. The pathophysiology of depression
is very complex, but the literature has shown the involvement of
brain-derived neurotrophic factor (BDNF) as a crucial biomarker
of this neural disorder. Some studies with phenolic compounds
from blueberry and grape have shown that phenolic compounds
are able to modulate important marker in brain tissue and could be
an important factor to prevent brain diseases (Williams et al; 2008;
Gomez-Pinilla and Nguyen, 2012; Dani et al., 2017). Therefore,
further studies with guarana should investigate its role in modula-
tion of BDNF.
In summary, this contribution shows that the potential health
benets of guarana go beyond the action of caeine. Prevention of
Table 1. Studies in vitro or in vivo about health eects of guarana
Health eects In vitro/in vivo Dose References
Eects on metabolic comorbidies
(obesity, hypertension, type 2
diabetes, and metabolic syndrome)
In vivo: elderly humans Twice or more mes a week Krewer et al. (2011)
Oxidave stress and metabolic
disorders (eects on the
oxidaon of LDL-c)
In vivo: blood samples
of elderly humans; In
vitro: isolated LDL-c
In vivo: at least 5 mes per week In
vitro: 0.05, 0.1,0.5,1, and 5 µg·mL−1;
Portella et al. (2013)
Oxidave stress In vivo: overweight
humans; Ex vivo: oxidaon
of LDL-c and total plasma
anoxidant capacity
In vivo: 3 g of the powder diluted
in 300 ml of water before intake,
daily for 15 days before breakfast
Yonekura et al. (2016)
Anhyperglycemic In vitro: inhibion of acvity
of carbohydrate-hydrolyzing
enzymes (α-amilase
and α-glucosidase)
Guarana extracts aer in vitro
digeson α-amilase: 0.315,
0.525 and 0.875 mg·mL−1);
α-glucosidase: 0.4 and 0.8 mg·mL−1
Silva et al. (2018)
Gut microbial composion and redox
and inammatory parameters
In vivo: Wistar rats Guarana seed powder the major
compounds are caeine (34.19
± 1.26 mg·g−1), theobromine
(0.14 ± 0.01 mg·g−1), (+)- catechin
(3.76 ± 0.12 mg·g−1), and
(−)-epicatechin (4.05 ± 0.16 mg·g−1)
Silveira et al. (2018)
Anmicrobial acvity In vitro: anbacterial potenal
of the guarana extracts against
Streptococcus mutans
The aqueous extract (AqE) from
the 5% (w/v) guarana seeds;
crude (EBPC) extracts and semi-
puried (EPA and EPB) fracons
Yamagu-Sasaki
et al. (2007)
Cognive performance
and mental fague
In vivo: healthy young adults vitamin/mineral/guarana
combinaon
Kennedy et al. (2008)
Mood, cognive performance
and funconal brain acvaon
In vivo: healthy young adults vitamin/mineral/guarana
combinaon
Scholey et al. (2013)
Anproliferave eect In vitro: breast cancer
cells MCF-7
Guarana extracts 1, 5
and 10 µg·mL−1
Hertz et al. ( 2015)
Ancancer eect In vivo: female C57Bl/6 mice 2.0 mg·g−1 body weight Fukumasu et al. (2008)
Antumor eect In vitro: Colorectal and
breast cancer cell lineages
HT-29 and MCF-7 cells
0.1, 1, 10, and 100 µg·mL−1 Cadoná et al. (2017)

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4
Guarana as a source of bioactive compounds da Silva et al.
cardiovascular diseases and benets on cognitive performance re-
lated to phenolics from guarana have been reported. Besides that,
due to their inhibitory eect towards α-glucosidase and α-amylase,
its promising action as a new antihyperglycemic agent for preven-
tion and/or management of type 2 diabetes has been highlighted.
Finally, as antibacterial ingredient, phenolic bioactives from guar-
ana may counteract oral diseases (plaque and periodontal diseas-
es). However, to conrm the benets of guarana in humans, these
evidences must be further addressed in clinical trials.
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