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Journal of Functional Foods 38 (2017) 308–320

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Journal of Functional Foods


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Yerba mate: An overview of physiological effects in humans


Liza Ghassan Riachi a, Carlos Alberto Bastos De Maria a,b,⇑
a
Nursing and Biosciences Postgraduation Program, Nursing School (PPGENFBIO – UNIRIO), Av. Pasteur 296, CEP 22290-240 Rio de Janeiro, Brazil
b
Collective Health Department, Biomedical Institute, (UNIRIO), Brazil

a r t i c l e i n f o a b s t r a c t

Article history: This review aims to make an outline of the existing clinical studies from the past twenty years concerning
Received 21 June 2017 to maté effects in human health. Physiological effects have been attributed to phenolics, methylxanthines
Received in revised form 11 September and saponins. Antilipemic activity was more consistent than glycaemic control. Maté seems to protect
2017
low-density lipoprotein cholesterol (LDL-c) from oxidation in whole plasma. Results from isolated LDL-
Accepted 13 September 2017
c particles are contradictory. The antioxidant enzymatic complex was positively modulated, indicating
that maté might help in the redox homeostasis maintenance. Most clinical trials did not find a significant
positive effect of maté consumption on glycaemia. However, it seems that maté hypoglycaemic effect is
Keywords:
Ilex paraguariensis
more evident in type-2 diabetes mellitus subjects. Maté had no effect on anti-glycation in vivo. It has
Human shown potential to increase energy expenditure and weight loss. Carcinogenicity is related to consump-
Oxidative stress tion temperature, not maté itself. Long-term randomized double-blind placebo-controlled studies are
Antioxidant enzymes essential to provide more consistent data.
Lipidaemic and glycaemic control Ó 2017 Elsevier Ltd. All rights reserved.
Weight loss

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 308
2. Phytochemicals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309
3. Antioxidant defense . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309
4. Weight loss potential . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
5. Lipid and glycemic profile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314
6. Other physiological activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317
7. Final considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318

1. Introduction of roasted leaves with boiling water. Maté is much appreciated


worldwide for its bittersweet taste and aroma (Márquez et al.,
Yerba mate or maté (Ilex paraguariensis A. St.-Hil.) is a native 2013). The daily consumption can vary between 1 and 6 L per per-
plant from South American countries, such as Brazil, Argentina, son (Bastos, Oliveira, Matsumoto, Carvalho, & Ribeiro, 2007). Maté
Paraguay, and Uruguay. Maté is commonly sold in markets either is known for having stimulant, anticonvulsant and neuroprotective
as dried and green or dried and roasted ground leaves. The first effects on the central nervous system and this is mostly attributed
is used to prepare tereré and chimarrão by adding cold and hot to its high content of caffeine and phenolics (Bastos et al., 2007;
water, respectively, while maté tea is made through the infusion Branco et al., 2013). It is an important source of bioactive com-
pounds, such as phenolic acids, flavonoids, and saponins (Heck &
⇑ Corresponding author at: Collective Health Department, Biomedical Institute, de Mejia, 2007). The presence of these components aroused the
Federal University of Rio de Janeiro State (UNIRIO), Rua Frei Caneca 94, sala A-411, interest of the scientific community on the physiological benefits
CEP 20211-040 Rio de Janeiro, Brazil. of maté consumption. This is primarily related to the high antiox-
E-mail addresses: lizagr00@gmail.com (L.G. Riachi), carreb@uol.com.br idant capacity of the plant. Biological molecules oxidation caused
(C.A.B. De Maria).

http://dx.doi.org/10.1016/j.jff.2017.09.020
1756-4646/Ó 2017 Elsevier Ltd. All rights reserved.
L.G. Riachi, C.A.B. De Maria / Journal of Functional Foods 38 (2017) 308–320 309

by reactive oxygen and nitrogen species (ROS and RNS), would be of caffeine (0.5–2.2 mg mL–1 of caffeine) (Danhelova et al., 2012)
responsible for several chronic pathologies (Lobo et al., 2010; while a serving volume of chimarrão (500 mL) has between
Bracesco, Sanchez, Contreras, Menini, & Gugliucci, 2011). In vitro, 93 mg and 110 mg of caffeine. This value can be greater, consider-
ex vivo and animal model studies have demonstrated beneficial ing that maté ingestion can be up to 6 L per day (Bastos et al.,
effects of maté on lipid, glucose and intrinsic antioxidant metabo- 2007). Maté also has considerable amounts of theobromine which
lism (Bracesco et al., 2011). Furthermore, phenolic components contribute for total methylxanthines ingestion. Although some
and metabolites from maté extract was found to decrease cancer works reported the occurrence of theophylline, its presence is still
cell viability and proliferation in human carcinoma cells (Amigo- controversial (Heck & de Mejia, 2007; Ribeiro et al., 2017).
Benavent, Wang, Mateos, Sarriá, & Bravo, 2017). Maté has a small number of flavonoids that contribute to its
In the past twenty years, clinical trials have been exploiting the overall antioxidant capacity. The most common flavonoids are
possibility to use maté in the prevention or as a complementary quercetin and rutin. Identification of kaempferol is questionable
treatment of some diseases (Boaventura et al., 2015; Gugliucci, since this compound is completely insoluble in water. Maté drinks
1996; Kim, Oh, Kim, Chae, & Chae, 2015; Menini, Heck, Schulze, have also triterpenic saponins formed with oleanolic and ursolic
de Mejia, & Gugliucci, 2007; Petrilli et al., 2016). Given the increas- acids aglycones (Gnoatto, Schenkel, & Bassani, 2005; Heck & de
ing amount of clinical trials concerning maté, this review aims to Mejia, 2007). These compounds are responsible for both foaming
discuss critically the existing research findings on human interven- formation and for the typical bitter taste in maté beverages. More
tion trials and maté consumption. recently, lutein was identified for the first time in tereré
(2.83 lg 100 mL1) and chimarrão extracts (0.43–2.55 lg
100 mL1). This finding suggests maté as a potential source of this
2. Phytochemicals carotenoid (da Silveira et al., 2016).

In general, phytochemicals content is susceptible to environ-


mental conditions (e.g. soil, temperature, light intensity) and to 3. Antioxidant defense
genetic variability (Coelho et al., 2007; Heck, Schmalko, & De
Mejia, 2008). Maté composition can also vary according to the pro- Natural antioxidants are known to retard the oxidative damage
cessing (dried – green maté, or roasted) and brewing conditions caused by the unrestrained production of ROS and RNS. The oxida-
(infusion or use of heated or cold water) used in the preparation tion of cell constituents and other components can lead to struc-
of maté beverages (maté tea, chimarrão and tereré) (Bastos, tural modification and consequently cause loss of their biological
Fornari, Queiroz, & Torres, 2006; da Silveira, Meinhart, Ballus, & activity. This phenomenon is associated with the occurrence of
Godoy, 2014; Isolabella et al., 2010; Meinhart et al., 2010). Since several pathologies, such as cancer, cardiopathy, and diabetes
there was no distinction between all these variables in Table 1, (Bracesco et al., 2011). Maté has shown great antioxidant potential,
the concentration of each compound may vary greatly. In addition, mainly attributed to its phenolics. It has also been proven to be
it was focused on works that used water as a solvent to reproduce more efficient both in the reduction of AGE formation in vitro than
as much as possible the extraction method commonly used and the green tea and in the prevention of protein nitration and cell death
amount of compounds that is theoretically consumed. The single induced by peroxynitrite compared to green tea and red wine
exception was for saponins that required other solvents rather (Bixby, Spieler, Menini, & Gugliucci, 2005; Lunceford & Gugliucci,
than water for extraction and quantification. Table 1 and Fig. 1 2005). The reduction of AGE formation is particularly important
show the most important soluble components of maté aqueous for prevention of oxidative stress and diabetes complications.
extract. Anti-glycation capacity of two major phenolic compounds (caffeic
Maté is a natural source of phenolic compounds that is mainly and chlorogenic acids) and of a sapogenin (oleanolic acid) from
represented by chlorogenic acids (e.g. caffeoylquinic, feru- maté was tested for the first time against AGE generation by
loylquinic and dicaffeoylquinic acids). If a high amount of maté is methylglyoxal using two protein models (histone and bovine
consumed daily the intake of caffeine could be close to that of serum albumin model (BSA)) (Gugliucci, Bastos, Schulze, & Souza,
coffee. A cup of coffee (150 mL) has between 75 mg and 330 mg 2009). Antiglycation effect of phenolics could be attributed to their

Table 1
Bioactive compounds from maté aqueous extract (mg mL–1).

Compound Amount* Compound Amount*


Phenolic acids Methylxanthines
5-CQA 51–388a,b,c,d,e Caffeine 187.58–220a,c,e
3- CQA 63.9–175.42b,c Theobromine 88.92c
4- CQA 35.2–136.08b,c
3- FQA 1.85b Flavonoids
4- FQA 0.95b Quercetin-3-rhamnosylglucoside 10.25c
5- FQA 1.56b Quercetin-3-O-glucoside 9.33c
3,4- diCQA 14.3–27.5b,d Kaempferol-3-O-glucoside 11.25c
3,5- diCQA 65.69–158.2b,c,d Rutin 43.40d
4,5- diCQA 37.79–256.8b,c,d
CA 0.66–4.15a,b,d Saponins** 352f

Reference:
a
Bastos et al. (2006).
b
Marques and Farah (2009).
c
Peres et al. (2013).
d
da Silveira et al. (2016).
e
Bastos et al. (2005).
f
Gnoatto et al. (2005).
*
Lower and higher mean values of compounds from different studies with no distinction between maté preparations (maté tea, chimarrão, tereré).
**
Total saponins expressed as ursolic acid. CQA: caffeoyl quinic acid; FQA: feruloyl quinic acid; diCQA: dicafeoyl quinic acid; CA: caffeic acid.
310 L.G. Riachi, C.A.B. De Maria / Journal of Functional Foods 38 (2017) 308–320

Fig. 1. Chemical structure of some maté phytochemicals.

Fig. 2. Inhibition of AGEs formation through maté consumption. *Gugliucci et al. (2009) **Bains and Gugliucci (2017).

capacity to inhibit or reduce the oxidation process. Caffeic acid acids were as potent as aminoguanidine (IC50 = 0.8 mM) display-
(0.5 mmol L–1) was the most effective in inhibiting AGEs genera- ing potent inhibition at concentrations compatible with those
tion (> 95% in BSA and 41% in histone model, P < 0.0001), followed found in the intestinal lumen (Bains & Gugliucci, 2017). The inhibi-
by chlorogenic acid (0.5 mmol L–1) (59% in BSA and 29% in histone tion of AGEs is shown in Fig. 2.
model, P < 0.0001) and oleanolic acid (17% in histone and 24% in Klein et al. (2011) did not find any significant decrease (P 
BSA model, 10 mmol L1). More recently, Bains and Gugliucci 0.05) in serum AGEs value from pre-diabetic individuals (n = 29)
(2017) provided the first evidence for enteral formation of after maté tea consumption (roasted herb, 990 mL/d, 20 mg mL–1),
fructose-derived AGE and its inhibition by maté extract and chloro- dietary intervention or both treatments combined, after 60 days.
genic and caffeic acids, under time, temperature, pH, and concen- Boaventura et al. (2013) also did not find any significant difference
trations compatible with the digestive system lumen. AGEs from in the antioxidant capacity of serum (expressed in ferric ion reduc-
the reaction between free fructose and proteins in the intestinal ing antioxidant power – FRAP) and AGE concentration of pre-
lumen, after being absorbed would activate the AGE receptor diabetic and type-2 diabetic subjects after 60 days of maté tea
inflammatory pathway (Bains & Gugliucci, 2017). Excessive con- (roasted herb) intake (990 mL, 20 mg mL–1). However, they could
sumption of free fructose has been associated with the occurrence find a significant inverse correlation between AGE and GSH con-
of inflammatory disease (DeChristopher, Uribarri, & Tucker, 2015, centrations from type-2 diabetic subjects (R2 = 0.422; P = 0.035),
2016). It was observed in the study a time-dependent formation indicating that some individuals may have a decrease in AGE con-
of AGE fluorescence at a time frame compatible with digestive pro- centration related to the enhancement of blood GSH after maté
cess and in a concentration plausibly found in the intestines. Maté consumption. This statement is merely speculative since AGE con-
tea displayed great inhibition effect, reaching 83% at 50 ll mL–1 centration did not change significantly in the studied group. Highly
concentration (P < 0.001). AGE formation was inhibited by reactive lipid peroxidation products can also undergo additional
aminoguanidine, a standard antiglycation agent, in a dose- oxidation reactions generating carbonyl reactive species, which
dependent manner with an IC50 of 0.9 mM. Caffeic and chlorogenic in turn, can undergo rearrangements, leading to AGEs generation
L.G. Riachi, C.A.B. De Maria / Journal of Functional Foods 38 (2017) 308–320 311

(Ott et al., 2014). Thus, the control of lipid peroxidation is impor- tested. Maté extract had higher in vitro antioxidant activity than
tant in terms of glycation process. Although in vitro studies had chlorogenic or caffeic acids, at the same phenol equivalent concen-
demonstrated antiglycation properties of maté, in vivo cross- tration, indicating a possible synergistic effect of maté constituents.
sectional studies with pre-diabetic and type-2 diabetic subjects It is important to emphasize that it was not clear which kind of
did not corroborate in vitro studies. The small number of clinical maté (green or roasted) was used in these studies (da Silva et al.,
studies makes comparison of in vivo and in vitro data difficult. 2008; Gugliucci, 1996). In our opinion, difference in the maté com-
The great majority of clinical trials was focused on the field of position related to processing condition could impact on its phys-
lipid peroxidation, more specifically regarding the oxidation of iological activity. Matsumoto, Mendonça, Moura de Oliveira, Souza,
LDL-c in plasma, which plays a key role in the onset of atheroscle- and Markowicz Bastos (2009) analysed the effect of maté (roasted)
rosis (Kita et al., 2006; Steinberg & Witztum, 2010). A pioneering on isolated LDL-c from healthy volunteers (n = 5) after acute (1 h)
study demonstrated a strong antioxidant capacity of maté extract and prolonged tea intake (1 week) (500 mL, 0.01 g mL1). LDL-c
against LDL copper/H2O2-induced autoxidation, in a dose- was isolated before and after maté consumption and submitted
dependent manner, in vitro (Gugliucci & Stahl, 1995). Antioxidants to oxidation by copper (CuSO4), lipoxygenase and peroxynitrite
from water extract inhibited the initiation and propagation (until (SIN-1). The formation of diene conjugates and structural modifica-
180 min) processes of isolated LDL-c particles, measured by diene tions on LDL-c apoB after cupper-induced oxidation were evalu-
conjugates and thiobarbituric acid-reactive substances (TBARS). ated. Maté prevented LDL apoB from structural modification after
This inhibition became apparent at concentrations of the extract one week of daily consumption. Although it was observed an
as low as 7.5 lg mL–1. Modification of lysine and other residues increased resistance of isolated LDL-c against copper-induced oxi-
in apolipoprotein B (apoB) by aldehydes formed as end products dation after prolonged tea intake (P < 0.05), there was no signifi-
of unsaturated lipids oxidation was assessed by direct measure- cant difference in diene conjugate formation when SIN-1 or
ment of free amino groups, electrophoretic mobility, and fluores- lipoxygenase were used as oxidants. Protection of maté against
cence. Maté extract was able to suppress the appearance of LDL-c oxidation was attributed to its ability to chelate metal ions,
Schiff-base induced fluorescence, the higher electrophoretic mobil- rather than to scavenge nitrogen free radical species or inhibit
ity and to reduce the modification of free amino groups thought lipoxygenase activity (Matsumoto, Mendonça, et al., 2009).
products of peroxidation (Gugliucci & Stahl, 1995). After showing Consumption of maté extract was also reported to influence the
great antioxidant protection in vitro, questions have been raised expression of antioxidant enzymes. Menini et al. (2007) tested for
about whether the same effects of maté on LDL-c could be repro- the first time the ability of maté to protect high-density lipoprotein
duced in vivo. To test the hypothesis if maté protect LDL-c from cholesterol (HDL-c) from oxidation in vitro and to increase
aqueous environment in a similar way as vitamin C, Gugliucci paraoxonase-1 (PON-1) activity in vivo. PON-1 is an oxidant
(1996) examined the oxidability of LDL in whole plasma from 3 enzyme associated with apolipoprotein A-1 (apoA-1) in HDL-c. It
healthy volunteers before and after 1 h of maté intake (500 mL). is related to HDL-c ability to protect LDL-c from oxidation. Maté
Copper-induced oxidation of LDL-c in whole plasma measured by aqueous extracts (2 mg mL–1–20 mg mL–1) conserved PON-1 activity
TBARS was inhibited after maté consumption. It was also observed and preserved apoA-1 structure from AAPH-induced oxidation of
a reduction in the appearance of Schiff bases in fluorescence anal- HDL-c. PON-1 activity also had a significant increase in all 4 volun-
ysis, in higher electrophoretic mobility and in the fragmentation of teers after maté intake (500 mL) (10% ± 2% vs. 1% ± 2% for control
apoB. LDL-c was also isolated from the same participants before group, P < 0.05) (Menini et al., 2007). Fernandes et al. (2012) anal-
and after maté intake and submitted to copper-induced autoxida- ysed the potential of maté extracts in modulating gene expression
tion, in order to determine whether maté protects isolated LDL-c and activity of paraoxonase-2 (PON-2) in monocytes and
from oxidation by conferring to it an intrinsic antioxidant capacity. monocyte-derived macrophages (MDM), and PON-1 activity in
Oxidation of isolated LDL-c was measured through diene conjugate plasma. Analyses were performed after acute (2 h, n = 20) and
formation. No significant differences were found between both short-term (7 days, n = 15) consumption of chimarrão (green
preparations. It was suggested that maté prevents the oxidation maté, 0.05 g mL–1, 500 mL/acute, 1 L/daily/7 d) and maté tea
of LDL-c from the aqueous environment without increasing the (roasted herb, 0.02 g mL–1, 500 mL/acute, 1 L/daily/7 d). Both green
intrinsic antioxidant capacity of LDL-c particles (Gugliucci, 1996). and roasted herbs significantly increased mRNA expression of
da Silva, Neiva, Shirai, Terao, and Abdalla (2008) reported for the PON-2 in monocytes after acute intake (P < 0.05) and significantly
first time the potential of maté in enhancing resistance of isolated increased mRNA expression of PON-2 in MDM after short-term
LDL-c from participants (n = 12) after 1 h of maté intake (500 mL, maté intake (P < 0.05). Both preparations significantly enhanced
50 mg mL–1) against an AAPH (2,20 -Azobis(2-amidinopropane) PON-2 activity in monocytes after acute maté ingestion (P =
dihydrochloride)/CuCl2 induced-oxidation. They suggested that 0.05), but not after short-term intake. Green maté increased the
antioxidants from maté also might remain adhered to LDL-c parti- arylesterase activity of PON-2, while roasted maté had a greater
cles. Oxidation progress was measured through the formation of effect on the lactonase activity. These differences were reported
cholesteryl-ester hydroperoxide (CE-OOH) and cholesterol oxides to be due to the composition of both maté preparations
by chromatographic techniques. The susceptibility of isolated (Fernandes et al., 2012). We suggest that this could be attributed
LDL-c to lipid peroxidation was significantly reduced (P < 0.05, to the presence of chlorogenic acid lactones in roasted maté. These
52% of inhibition of CE-OOH formation) after incubation (3 h) with lactones could be formed in maté in a similar manner as during the
copper ions. Accumulation of oxysterols in LDL-c particles was also roasting process of coffee (Farah, de Paulis, Trugo, & Martin, 2005).
inhibited after oxidation by copper or AAPH for 6 h (P < 0.05) after Presence of chlorogenic acid lactones, in turn, would stimulate lac-
maté intake. In line with previous study (Gugliucci, 1996), LDL-c in tonase activity in PON-2. The acute and short-term ingestion of
the whole plasma was also less susceptible to oxidation when green and roasted maté also increased PON-1 activity in plasma
compared to control (P < 0.05). Differences regarding the contribu- (Fernandes et al., 2012), confirming previous finding (Menini
tion of maté antioxidants on the resistance of isolated LDL-c parti- et al., 2007). Fernandes et al. (2012) also investigated whether
cles against oxidation, between both studies may be attributed to green or roasted maté and chlorogenic or caffeic acid could modu-
small number of volunteers in Gugliucci (1996) study when com- late the gene expression and activity of PON-2 in vitro, in THP-1
pared with da Silva et al. (2008). In the last study, inhibition of macrophages. Maté extracts and chlorogenic acid increased PON-
plasma lipid peroxidation in vitro with the absence or presence 2 gene expression at concentrations of 1 and 3 mmol/L (P <
of maté extract, caffeic, chlorogenic, ferulic and vanillic acids was 0.05), whereas higher concentrations (5 and 10 mmol/L) only
312 L.G. Riachi, C.A.B. De Maria / Journal of Functional Foods 38 (2017) 308–320

increased the enzyme activity. Caffeic acid had no effect on PON-2 was found in 50% of the participants, suggesting a potential protec-
gene expression but increased the enzyme activity. Matsumoto, tion against cardiovascular disease in these individuals. In our
Bastos, et al. (2009) demonstrated that consumption of maté tea opinion, this suggestion is quite speculative because it was based
may regulate the plasmatic antioxidant enzyme gene expression. on results of a selected population. LOOH concentration had a pos-
After one week of maté tea intake (roasted herb, 500 mL, 0.01 itive correlation with LDL cholesterol levels for individuals in maté
g mL1), participants (n = 15) experienced a significant (P < tea (r = 0.337, P < 0.005); and MD group (r = 0.241, P < 0.04). LOOH
0.001) increase in gene expression of superoxide dismutase serum level in maté tea group was inversely correlated to HDL-c
(SOD), glutathione peroxidase (GPx), and catalase (CAT). It was concentration (r = 0.309, P = 0.009) and PON-1 activity was found
observed a significant decrease in TBARS level after one hour to be positively associated with HDL cholesterol levels in partici-
(decrease of 17%, p < 0.001) and one week (decrease of 37%, p < pants in the MD group (r = 0.263, P = 0.016) (Boaventura et al.,
0.001) of maté intake. Maté also protected plasma from copper- 2012). Boaventura et al. (2015) evaluated the effect of acute intake
induced peroxidation. The lag time increased 69% after one hour (1 h, 200 mL) of a freeze concentrated maté infusion (CM), in rela-
(p < 0.05) and 91% after one week of maté ingestion (p < 0.05). tion to traditional one (TM, 200 mL, 0.03 g mL–1) on antioxidant
The plasma total antioxidant status increased after one week. and peroxidation parameters of healthy subjects (n = 31). Concen-
Arçari et al. (2011) analysed the effect of maté tea (200 mL, 0.012 tration of phenolics and methylxanthines were from three to seven
g mL1, roasted herb) chronic consumption (60 days) on oxidative times higher in CM. The acute intake of CM significantly (P < 0.05)
stress biomarkers and LDL-c oxidisability in normolipidaemic (n = increased the activity of CAT (28.7%), SOD (21.3%), and GPx (9.6%),
42) and hyperlipidaemic (n = 18) volunteers. Serum total antioxi- and increased the level of GSH (8.8%) and serum antioxidant capac-
dant status and SOD activity from normolipidaemic and hyperlip- ity (FRAP) (7.5%), while TM promoted a significant increase only in
idaemic volunteers significantly increased (P < 0.05), while H2O2- GSH values (8.3%). The serum levels of LOOH did not change after
induced DNA breakage significantly decreased (P < 0.05). They consumption of both maté infusions. It was found a significant pos-
did not find any influence of maté intake on GPx activity. Maté also itive association between GPx activity with GSH (r = 0.36; P = 0.04),
was unable to confer protection to isolated LDL particles against CAT (r = 0.38; P = 0.03), and SOD (r = 0.46; P = 0.01) parameters
copper-induced oxidation in agreement with previous study after CM consumption. In addition, a significant and negative asso-
(Gugliucci, 1996). The reduction of plasma lipid peroxidation prod- ciation was observed between LOOH and FRAP values (r = 0.38;
ucts was only significant (P < 0.05) in the hyperlipidaemic group P = 0.03). In a randomized controlled cross-over study it was
(Arçari et al., 2011). Boaventura et al. (2012) evaluated the long- analysed the effect of roasted maté tea (600 mL, 5 mg mL1) on
term (90 days) effect of maté tea (roasted) intake (990 mL/daily, recovery of muscle strength and blood oxidative stress biomarkers
20 mg mL–1) on antioxidant status of dyslipidaemic individuals in physically active subjects (n = 12) after eccentric exercise (24, 48
(n = 74), with or without qualitative dietary intervention (groups: and 72 h) (Panza et al., 2016). Although not influencing in muscle
maté tea; dietary intervention, DI; and maté tea with dietary inter- strength at all-time points, maté treatment significantly improved
vention, MD). Regardless of dietary intervention, maté consump- (P < 0.05) the rate of strength recovery (8.6%) over 24 h after
tion significantly increased (P < 0.05) serum antioxidant capacity eccentric exercise. The concentration of total phenolic compounds
(FRAP levels). The GSH blood concentration had a significant in plasma was significantly (P < 0.05) higher after maté intake
increase (P < 0.05) in subjects from all groups, with a maximum when compared to control, but it was significantly (P < 0.05)
increase of 21.7% in maté tea group. Only subjects from maté tea decreased at 72 h after exercise in both treatments. GSH blood
group had a significant decrease (P < 0.05) in LDL-c concentration. level was significantly enhanced in maté group and remained sig-
However, there were no significant changes in serum lipid nificantly higher than control after exercise. In agreement with
hydroperoxides (LOOH), protein carbonyl, and PON-1 activity val- previous studies (Boaventura et al., 2012, 2015) no significant
ues. Unlike previous findings (Fernandes et al., 2012; Menini changes were found in serum LOOH level (Panza et al., 2016). A
et al., 2007) it was not observed any significant change in PON-1 summary of the findings on oxidative stress and glycemic and lipid
activity after prolonged maté tea ingestion (Boaventura et al., parameters and the enzymatic antioxidant system is shown in
2012). However, a significant increase (23%) in PON-1 activity Table 2.

Table 2
Effect of maté on biochemical parameters related to oxidative stress in humans.

Analysed parameters with significant changes (+) (–)


Lipid and glycidic parameters
AGE concentration –Boaventura et al. (2013)–Klein et al. (2011)
Plasma lipid peroxidation –da Silva et al. (2008)–Gugliucci (1996)–Matsumoto, Mendonça, –Petrilli et al. (2016)
et al. (2009)–Matsumoto, Bastos, et al. (2009)
Resistance of isolatedLDL to oxidation –da Silva et al. (2008)–Matsumoto, Mendonça et al. (2009) –Arçari et al. (2011)–Gugliucci (1996)
Serum level of lipid hydroperoxides –Boaventura et al. (2013) –Boaventura et al. (2012)–Boaventura
et al. (2015)–Panza et al. (2016)
Antioxidant enzyme complex
PON-1 activity –Fernandes et al. (2012)–Menini et al. (2007) –Boaventura et al. (2012)
PON–2 activity –Fernandes et al. (2012)
PON–2 gene expression –Fernandes et al. (2012)
SOD activity –Arçari et al. (2011)–Boaventura et al. (2015)
SOD gene expression –Matsumoto, Bastos et al. (2009)
GSH concentration –Boaventura et al. (2012)–Boaventura et al. (2013)–Panza et al. (2016)
GSH activity –Boaventura et al. (2015)
GPx activity –Arçari et al. (2011)
GPx gene expression –Matsumoto, Bastos et al. (2009)
CAT activity –Boaventura et al. (2015)
CAT gene expression –Matsumoto, Bastos et al. (2009)

(+): study that found significant change in the analysed parameters; (–) study that did not find any significant change in the analysed parameter; AGE: advanced glycation end
products; PON-1: paraoxonase-1; PON-2: paraoxonase-2; SOD: superoxide dismutase; GSH: glutathione; GPx: glutathione peroxidase; CAT: catalase.
L.G. Riachi, C.A.B. De Maria / Journal of Functional Foods 38 (2017) 308–320 313

In contrast, Petrilli et al. (2016) did not find any effect of maté fuel source for energy expenditure (30–70%), while CHO predomi-
on plasma lipid peroxidation. In our opinion, this conflicting result nates at heavy exercise intensities (Alkhatib, 2014; Brooks &
is probably because they recruited HIV/AIDS subjects submitted to Mercier, 1994). Although in both conditions FAO was increased
antiretroviral therapy. This treatment can lead to pronounced similarly as a function of power output, higher FAO was found at
alteration in lipid metabolism. The capacity of maté to protect iso- exercise intensities below 70% of the peak of oxygen uptake.
lated LDL-c from oxidation is still controversial. The fact that maté Maté increased energy expenditure derived from FAO by 24% when
aqueous extract does not enhance the intrinsic antioxidant capac- compared to placebo during exercise, without negatively affecting
ity of LDL-c does not mean that maté itself does not have the poten- the maximal performance. These findings indicate maté as a pro-
tial for this. Non-exhaustive water extraction (home extraction) moter of fat metabolism and suggest a glycogen sparing potential
does not extract or extract in small quantities more apolar com- for exercise performance (Alkhatib, 2014).
pounds that could confer this activity. Therefore, ethanolic or When compared to other thermogenic supplements with high
acetanolic extracts could increase the resistance of isolated LDL-c caffeine content (350 mg) (Outlaw et al., 2013), maté supplement
to oxidation. Conflicting results regarding LOOH levels could be displayed similar results (an increase of FAO and energy expendi-
related to health status of recruited volunteers. While Boaventura ture) with a much lower content of the compound (80 mg). Thus,
et al. (2015) recruited healthy volunteers, Boaventura et al. it was suggested that other constituents of maté, rather than caf-
(2013) worked with pre-diabetic and type-2 diabetes mellitus feine itself, could have thermogenic properties (Alkhatib, 2014).
(T2DM) subjects. The effect of maté could be more easily observed Indeed, chlorogenic acid has been shown to inhibit cAMP phospho-
in subjects with altered glucose metabolism, because the produc- diesterase and indirectly increase the fatty acid oxidation
tion of lipid reactive species may already be increased in these (Bruckbauer & Zemel, 2014; Stohs & Badmaev, 2016). Another pos-
individuals. Although the results with PON-1 are controversial, in sible indirect mechanism was through the inhibition of pancreatic
general maté has positively affected the human antioxidant lipase with a consequent reduction of lipid absorption and weight
enzyme complex. Although different studies have shown an anti- loss (Narita, Iwai, Fukunaga, & Nakagiri, 2012; Stohs & Badmaev,
glycation effect of maté in vitro, it was not possible to confirm this 2016). In another study, a treatment with rutin significantly
ability in vivo. Further studies should be conducted to assess reduced adiposity and increased energy expenditure in genetically
whether the effect is reproduced in humans. obese mice and in those with diet-induced obesity (Yuan et al.,
2017). This was attributed to rutin potential in increasing the num-
ber of mitochondria and uncoupling protein 1 (UCP1) activity in
4. Weight loss potential brown adipose tissue (Yuan et al., 2017). In a study with mice,
lutein was also able to stimulate the expression of mitochondrial
The knowledge on maté compounds with thermogenic potential UCP1 of brown adipocytes, in a dose-dependent manner (Serra,
led to research of the plant in the field of weight loss. In the past 20 Bonet, Puigserver, Oliver, & Palou, 1999; Stohs & Badmaev, 2016).
years, only a few clinical studies were conducted to investigate the Activation of UCP1 is involved with uncoupling of the respiratory
potential of maté in enhancing energy expenditure, increasing sati- chain in mitochondria, leading to a rapid fatty acid oxidation with
ety, reducing appetite and body fat composition (Alkhatib, 2014; a low rate of adenosine triphosphate (ATP) production and high
Andersen & Fogh, 2001; Jung & Hur, 2016; Kim, Ko, Storni, Song, ATP utilization and heat energy release. This process is recognized
& Cho, 2012; Kim et al., 2015; Martinet, Hostettmann, & Schutz, as the main event leading to thermogenesis (Stohs & Badmaev,
1999; Oliveira et al., 2016). The thermogenic effect of maté was 2016). Thermogenic effect through uncoupling protein was also
tested in humans for the first time in a double-blind placebo- observed in rodent models after the administration of maté
controlled study using indirect calorimetry for 3 h at rest, after extracts (Arçari et al., 2009; Pang, Choi, & Park, 2008). The intake
the ingestion of 5 capsules of maté (1.5 g of dry extract) or placebo of maté (previously extracted with 15% ethanol) augmented the
(Martinet et al., 1999). Other plant preparations were tested, such expression of both UCP2 and UCP3 in visceral adipose tissue of rats
as Paullinia cupana, Ephedra sinica, Garcinia Cambogia, Camellia thea, that were submitted to a high-fat diet (Pang et al., 2008). These
Cynara scolymus, Iris versicolor, Corylus avellana, Crithmum mariti- proteins are homologs of UCP1 and are also capable of uncoupling
mum, Fucus versiculosus, Phytolacca decandra and Laminara digitate. mitochondrial respiration (Pang et al., 2008). The ingestion of
From all preparations, only maté significantly decreased the respi- roasted maté extract by obese mice also increased mRNA levels
ratory coefficient (P = 0.0043) when compared to placebo, indicat- of PGC-1a and UCP1 in brown adipose tissue. PGC-1a seems to
ing an enhancement in the proportion of fat oxidized. Maté also stimulate mitochondrial biogenesis and respiration in muscle by
showed the advantage of not influencing in blood pressure and inducing the expression of UCPs (Arçari et al., 2009).
heart response (Martinet et al., 1999). A pilot study analysed the Maté has been combined with other plant preparations and
energy expenditure of healthy adults 1 h after intake of maté aque- used as a constituent of commercial formulas to help losing
ous extract (500 mL, 0.01 g mL–1) or placebo (500 mL of water) weight. A plant formulation (YGD capsule) containing maté (112
(Oliveira et al., 2016). Energy expenditure was measured during mg of leave extract), guarana (Paullinia cupana – 95 mg of seeds
30 min through indirect calorimetry. It was observed a significant extract) and damiana (Turnera diffusa var. aphrodisiaca, 36 mg of
(P < 0.05) increase in energy expenditure (125 kcal, 7.7%) when leave extract) was able to slow gastric emptying time over placebo,
compared to control group (Oliveira et al., 2016). Alkhatib (2014) promote weight loss in overweight subjects (n = 48) after 45 days
analysed for the first time the thermogenic effect of maté using dif- of YGD intake (3 capsules daily) in a double-blind study, and
ferent exercise intensities. Subjects ingested two capsules contain- helped to maintain weight (n = 22) after 12 month in an uncon-
ing 500 mg of maté (standardized with 1.5% of caffeine) or placebo trolled maintenance treatment (Andersen & Fogh, 2001). However,
and rested during 1 h before performing incremental exercise. in the study, it was not considered the energy intake and the phys-
Maté ingestion improved fatty acid oxidation (FAO) and reduced ical activity of the participants. In another study, YGD promoted
carbohydrates oxidation (CHO) over a wide range of exercise inten- reduction of food and energy intake after breakfast and lunch,
sities when compared to placebo (P < 0.001). These effects were but the lowest intake was observed when YGD was combined with
particularly predominant in light and moderate exercises intensi- inulin fibre (Harrold et al., 2013). A formulation made with active
ties, which are often prescribed for weight loss, disease prevention ingredients of maté, guarana, and damiana (ZotrimÒ) has shown
and improving endurance performance (Alkhatib, 2014). It is satiety effect in different consumer survey tests, in which partici-
established that in this range of exercise intensity FAO is the main pants self-reported feeling of fullness and weight loss (Ruxton,
314 L.G. Riachi, C.A.B. De Maria / Journal of Functional Foods 38 (2017) 308–320

2004; Ruxton, Hinton, & Evans, 2005; Ruxton, Kirkwood, McMillan, individuals who had a slight (0.5 kg) but significant decrease
St John, & Evans, 2007). Problems concerning the studies included (P = 0.02) in body weight after 40 days of maté intake (De Morais
the use of self-reported data that could lead to bias and absence of et al., 2009). Since there was no significant change in energy intake
diet and physical activity control. A supplement known as Melt- during the study, the decrease in body weight might be due to
downÒ is a formulation with maté extract and other ingredients, changes in physical activity practice. In other study, T2DM subjects
such as synephrine, caffeine, phenylethylamine, yohimbine and (n = 29) and pre-diabetes (n = 29) consumed maté tea (roasted
other stimulants of b-adrenergic receptors. Placebo-controlled herb, 990 mL/d, 20 mg mL–1), undertook dietary intervention (DI)
studies have shown positive effects regarding MeltdownÒ adminis- or both (maté tea + DI) for 60 days. T2DM subjects did not show
tration, such as enhancement of respiratory exchange ratio, fat oxi- significant variations in body weight, BMI, abdominal circumfer-
dation, increase in energy expenditure, and increase in ence and blood pressure. However, pre-diabetic subjects in maté
catecholamine secretion and lipolysis markers in blood (Bloomer, tea group had a significant reduction (P < 0.05) in body weight
Canale, et al., 2009; Bloomer, Fisher-Wellman, et al., 2009; (baseline, 73.2 ± 3.1 kg versus 71.6 ± 13.5 kg), BMI (baseline,
Hoffman et al., 2009; Jitomir et al., 2008; Rashti et al., 2009). How- 29.4 ± 4.0 kg/m2 versus 28.7 ± 3.4 kg/m2) and in systolic (baseline,
ever, the supplement had the adverse effect of increasing the heart 137.6 ± 23.6 mmHg versus 130.3 ± 19.7 mmHg) and diastolic
rate and blood pressure. A product containing maté extract, caf- (baseline, 80.5 ± 7.5 mmHg versus 76.1 ± 7.7 mmHg) blood pres-
feine, guarana, green tea, L-carnitine, L-tartrate, pantothenic acid, sure (Klein et al., 2011). Since it is difficult to maintain a daily diet-
chromium picolinate and other substances (Dyma-BurnÒ Xtreme) ary record, the energy consumption is generally assessed through a
also was effective in increasing resting energy expenditure in a 24 h dietary recall or a dietary record of selected days, at baseline
double-blind placebo study (Outlaw et al., 2013). Other product and at different time-points. Thus, discrepancies in results also
available as FitMiss BurnTM combining a mix of ingredients (i.e. could be related to the daily variation of energy intake between
maté extract, green tea, caffeine, guarana seed extract) increased participants.
resting metabolic rate over time in a double-blind placebo study.
Nevertheless, the supplement promoted slight elevations in blood
pressure (Campbell et al., 2016). Analysis of several herb prepara- 5. Lipid and glycemic profile
tions with anti-obesity potential in combination has the limitation
of not identifying which ingredient effectively contributed to the Animal studies have shown a glycemic-control capacity and a
observed effects. Therefore, results obtained with maté in a mix- lipid-lowering effect of maté (Bravo et al., 2014; De Resende
ture of other herb preparations and substances does not necessar- et al., 2015; Pang et al., 2008; Pereira et al., 2012). In a study with
ily reflect maté activity per se. obese rats under high-fat diet administration, the consumption of
The effect of maté on body composition in a double-blind maté extract significantly (P < 0.05) lowered blood and hepatic
placebo-controlled study was assessed for the first time in lipid, glucose and insulin levels (Pang et al., 2008). Pereira et al.
overweight subjects (n = 46) with administration of 1200 mg of (2012) demonstrated that butanolic (n-BuOH) and ethanolic
green maté during 6 weeks under controlled energy intake (EtOAc) maté extracts (200 mg kg–1, P < 0.001) and green (200
(1500 kcal/daily) and physical activity (Kim et al., 2012). Partici- mg mL–1, P < 0.001) and roasted (200 mg mL–1, P < 0.01) maté infu-
pants from maté group had a significant (P < 0.05) reduction in sions improved significantly the oral glucose tolerance curve of
the body fat percentage (0.3%) and body fat mass (0.5 kg), while normal rats with induced hyperglycaemia. Additionally, they
the placebo group had an increase in both measurements (0.6% observed an induced insulin secretion after the acute treatment
and 0.2 kg, respectively). They did not observe any significant with n-BuOH or EtOAc extracts in hyperglycaemic rats. Since
change in weight, body mass index (BMI), lean body mass and n-BuOH and EtOAc extracts and green maté infusion improved
waist circumference. In other study, supplementation with maté the oral glucose tolerance curve but did not influence on glucose-
(3000 mg) in a 12-week period by obese subjects (n =15) also led lowering in diabetic rats, they suggested that the hypoglycemic
to a significant decrease in body fat mass (P = 0.036) and body mechanism involves insulin-secretagogue compounds. Since cate-
fat percentage (P = 0.030) when compared to placebo (n = 15) chin and chlorogenic acid were found in high amount in n-BuOH
(Kim et al., 2015). It was also observed a significant reduction of and green maté extracts, they assumed that these compounds are
the waist-hip ratio (P = 0.004). However, the study lacked in mon- the probable secretagogues (Pereira et al., 2012). It is important
itoring the energy intake and the physical activity of participants. to emphasize that the catechins content found in the study was
More recently (Jung & Hur, 2016), the effect of maté on body higher than is normally found in maté beverages, reaching values
weight and on fat content was investigated in obese women after from three to six times greater than chlorogenic acid. In our opin-
6 weeks of supplementation. Maté group (n = 17) ingested four ion, the hypoglycemic effect above-mentioned also could be attrib-
capsules daily (3000 mg of green maté extract), while control group uted to an incretin-secretagogue compound. Incretins are well
(n = 16) consumed placebo. Volunteers were instructed to reduce known to modulate the amount of insulin secreted after food
their daily caloric intake by 500 kcal per day and maintain their intake (Kim & Egan, 2008). In a previous study, chlorogenic acid
normal amount of physical activity throughout the study. There treatment in rats resulted in beneficial effects on blood glucose
was no difference in energy intake from baseline until the end of response, with modifications in incretin levels (Tunnicliffe, Eller,
the study between both groups. After 6 weeks, it was observed a Reimer, Hittel, & Shearer, 2011). Thus, maté compounds might also
significant reduction in trunk fat (P = 0.03), which comprehends regulate the insulin secretion through this mechanism. Hypotheti-
the fat that is distributed in the abdomen and includes visceral cal mechanisms of insulin secretion through maté consumption are
and subcutaneous fat (1.24 ± 1.72% in the maté group; shown in Fig. 3.
+0.16 ± 1.70% in the control group). However, there was no signif- In a study with db/db mice, chlorogenic acid decreased fasting
icant reduction in weight, BMI and hip circumference between blood glucose in the glucose tolerance test (Ong, Hsu, & Tan,
groups (Jung & Hur, 2016). In a clinical study, normolipidaemic 2012), reinforcing the hypothesis that chlorogenic acid might con-
(n = 15), dyslipidaemic (n = 57) and hypercholesterolemic subjects tribute to the hypoglycemic effect of maté extract found in the
under long-term statin therapy consumed green (50 mg mL–1) or study of Pereira et al. (2012). Moreover, Ong et al. (2012) demon-
roasted maté (20 mg mL–1) infusions (900 mL/d) in a 40-days per- strated for the first time that chlorogenic acid stimulates a glucose
iod. In general, none of the maté infusions were effective in reduc- transport in skeletal muscle through the activation of 5ꞌ adeno-
ing the body weight of participants, except for dyslipidaemic sine monophosphate-activated protein kinase (AMPK). In another
L.G. Riachi, C.A.B. De Maria / Journal of Functional Foods 38 (2017) 308–320 315

Fig. 3. Hypothetical mechanism of insulin secretion through maté consumption. (A) hypothetical mechanism 1 (Pereira et al., 2012): maté polyphenols stimulates insulin
secretion in pancreas. (B) hypothetical mechanism 2 (suggested by the authors): maté polyphenols stimulate the secretion of incretins in small intestine, which, in turn
stimulates insulin secretion in pancreas.

study, gallic acid has shown to induce the glucose transporter 4 although it was detected a significant and temporary decrease in
(GLUT4) translocation and glucose uptake activity in 3T3-L1 cells HbA1c levels. Although the study from Klein et al. (2011) showed
(Vishnu Prasad, Anjana, Banerji, and Gopalakrishnapillai, 2010). a significant reduction in glucose level of diabetic subjects after
Furthermore, caffeic and cinnamic acids increased glucose uptake maté intake, some results were inconsistent. For instance, subjects
in insulin-resistant mouse hepatocytes (Huang, Shen, & Wu, from maté tea group but not from maté tea + DI group had their
2009). These findings indicate that chlorogenic acid appears to be fasting plasma blood glucose level decreased. The authors attribu-
an important contributor to the hypoglycemic effect of maté in ted the presence of inconsistencies in results to a small number of
rats. individuals and to differences in dietary intake. Boaventura et al.
Although animal studies have found a hypoglycemic effect (2013) analysed the glycemic profile of T2DM (n =11) and pre-
related to maté consumption, evidence in humans is still insuffi- diabetic (n = 11) subjects after 60 days of maté tea intake. T2DM
cient. In an experimental study, normoglycemic subjects (n = 12) subjects had a significant reduction (P < 0.05) in plasma glucose
ingested sumac (1 g or 2 g), Turkish coffee (60 mL) or maté tea (146.39 ± 19.49 mg dL–1 vs. 135.50 ± 16.75 mg dL–1) and HbA1c
(100 or 200 mL) to test the effect on postprandial glycemic after 60 days when compared to baseline, while in pre-diabetic
response to a Lebanese carbohydrate-rich food (mankoucheh) subjects maté intake did not promote a decrease in plasma glucose,
(Kahale, Tranchant, Pakzad, & Farhat, 2015). The glycemic response but significantly lowered the HbA1c concentration after 40 days of
to mankoucheh meal (blood glucose concentration at all times) did treatment. This result agrees partially with Klein et al. (2011) that
not differ with the ingestion of tested items. Aside from a true lack observed a significant reduction in blood glucose in diabetic sub-
of effect of the three constituents tested, the authors attributed the jects, but not in pre-diabetics. It seems that maté hypoglycemic
absence of a statistically significant difference among the glycemic effect is more evident when the concentration of glucose in the
responses to the different meals to some possible factors: the rel- blood is higher. Our research group investigated for the first time
ative low dose used of each constituent, the individual variation, the effect of roasted maté infusion administration (14 days) on
and the fact that mankoucheh is a medium glycemic index (GI) blood glucose of institutionalized patients with traumatic brain
meal, producing a lower overall glycemic response in comparison injury (TBI) (n: maté group = 4, control = 4) (Ribeiro et al., 2017).
with high-GI foods (Kahale et al., 2015). As shown in Table 3, The glycemic control in these subjects is of utmost importance
regardless of the distinctions between each study, the majority of since the stress-induced hyperglycaemia is associated with higher
clinical trials still did not find a significant positive effect of maté mortality after TBI event in non-diabetic patients. Although the
consumption on the blood glucose concentration in non- mean glycemic levels were not significant (P < 0.05) between
institutionalized subjects (Arçari et al., 2011; Jung & Hur, 2016; maté and control group, the first had a lower mean glycaemia.
Kahale et al., 2015; Kim et al., 2012), with the exception of two Throughout the study, the four non-treated patients received a
studies (Boaventura et al., 2013; Klein et al., 2011). In the pilot total lente insulin of 4IU, 32 IU, 2 IU and 34 IU, while two maté-
study from Klein et al. (2011) T2DM subjects (n = 29) and pre- treated patients received 6 IU and 8 IU of lente insulin, due to iso-
diabetes (n = 29) consumed maté tea with or without dietetic coun- lated harmful hyperglycaemia episodes. Two maté-treated patients
selling (maté tea + DI) or only undertook DI for 60 days to test their did not receive insulin therapy because their blood glucose
effect on the glycemic and lipid profile. Only T2DM participants remained stable throughout the study. Despite the limitation of
from maté tea group had their levels of fasting plasma glucose having a small number of volunteers in the study, these prelimi-
and HbA1c significantly decreased (glucose reduction of 25.0 nary results suggest that maté may assist in harmful hypergly-
mg dL–1/17%, when compared with baseline after 60 days, P < caemia management and thus decrease the insulin
0.05; HbA1c level decreased 0.85% after 20 and 60 days, P < administration in TBI patients.
0.05), while no significant change was observed in T2DM subjects The potential of maté to act as a lipid-lowering agent in humans
from maté tea + DI and DI group and pre-diabetics from all groups. is more consistent than as a hypoglycemic agent in terms of num-
In general, the nutritional counselling performed with or without bers of clinical trials and positive results. It is important to empha-
maté tea intake did not promote a significant improvement in size though that despite some studies have found beneficial effects
the glycemic control of T2DM subjects. Additionally, in pre- of maté on lipid profile (Boaventura et al., 2012; De Morais et al.,
diabetic subjects, maté consumption with or without nutrition 2009; Klein et al., 2011; Messina et al., 2015; Yu et al., 2015),
counselling did not promote a reduction in fasting plasma glucose, others did not find significant changes (Arçari et al., 2011; Jung &
316 L.G. Riachi, C.A.B. De Maria / Journal of Functional Foods 38 (2017) 308–320

Table 3
Effect of maté consumption on human lipid and glycaemic profile.

Subjects/Intervention Duration Lipid/glycidic There In which parameter?


parameters analysed were
sgfnt.
changes?
Traumatic brain injury patients ingested maté tea 14 days Glucose No n/a
(roasted herb) 2/day (7 g, 300 mL–1 each) via
nasoenteric feeding tube/orally (n: maté = 4,
control = 4)1
Overweight subjects took maté tablets (3 g/daily, n = 17) 6 weeks TC, glucose No n/a
or placebo (n = 16)2
HIV-infected subjects (n = 92) consumed maté tea, 60 days Lipid profile (not No n/a
placebo-maté, dark chocolate or placebo-chocolate3 specified)
Obese subjects consumed maté capsules (3 g/daily, 12 weeks TC, free fatty acid, No n/a
n = 15) or placebo (n = 15)4 triglycerides, HDL-c,
LDL-c
Subjects with high blood viscosity (n = 142) ingested 6 weeks TC, LDL-c, HDL-c, Yes LDL-c, triglycerides and TC: ; and HDL-c " in maté group
maté tea (16 mg mL–1, 1500 mL/daily, n = 71) or triglycerides (P < 0.05).
placebo tea (n = 71)5
Dyslipidemic subjects consumed different amounts of 12 weeks TC, LDL-c, HDL-c, Yes TC and LDL-c: ; in both groups (P < 0.001)
maté infusion (100 mg mL–1): 500 mL/daily, n = 74 or triglycerides
1 L/daily, n = 476
Normoglycemics (n = 12) ingested a carbohydrate-rich 1 day Glucose No n/a
food (mankoucheh) with sumac, Turkish coffee or maté
tea (100 or 200 mL, 25 mg mL–1) to test the
postprandial glycaemic response7
Pré-diabetic (n = 11) and type-2 diabetic (n = 11) 60 days Glucose, HbA1c Yes Glucose: ; in T2 DM. HbA1c: ; in T2 DM after 60d, and ;in
subjects (T2 DM) ingested maté tea (roasted herb, pré-diabetics after 40d (P < 0.05).
990 mL, 20 mg mL–1, daily)8
Overweigh subjects ingested green maté capsule (3g/d, n 6 weeks TC, triglycerides, HDL- No n/a
= 24) or placebo (n = 22)9 c, glucose
Dyslipidaemics (n = 74) ingested maté tea (roasted herb, 90 days TC, LDL-c, HDL-c non- Yes LDL-c: ; only in maté group (P < 0.05)
990 mL/d, 20 mg mL-1) with or without DI or only HDL-c, triglycerides
undertook DI10
Normolipidaemics (n = 42) and hyperlipidaemics (n = 18) 60 days TC, LDL-c, VLDL-c, No n/a
ingested maté tea (roasted leaves, 0.012 g mL–1)11 HDL-c, triglycerides,
glucose
T2DM subjects (n = 29) and pre-diabetics (n = 29) 60 days TC, LDL-c, HDL-c, non- Yes LDL-c, glycaemia and HbA1c: ; in T2DM from MT group
ingested maté tea (roasted herb, 990 mL/d, HDL, triglycerides, (P < 0.05). LDL-c (P < 0.05), non-HDL (P <0.05),
20 mg mL–1) with (MT + DI) or without DI (MT) or glucose, HbA1c triglycerides (P < 0.01) and HbA1c (P = 0.01): ; in
only undertook DI12 pre-diabetics from MT + DI group. HbA1c (P = 0.01): ;
pre-diabetics from MT group.
Normolipidaemics (n = 15), dyslipidaemics (n = 57) and 40 days TC, LDL-c, HDL-c, non- Yes LDL-c: ; in normolipidaemics (both infusions) (p < 0.01).
hypercholesterolemics under long-term statin HDL, triglycerides, TC, LDL-c, non-HDL, apo B-100 (after 20d) and apo
therapy ingested 990 mL of green (50 mg mL–1) or apoB-100, apoB-100/ B-100/apo A-1 (after 20d) (P < 0.01): ; in dyslipidaemics
roasted maté (20 mg mL–1) infusions daily13 apoA-1 (both infusions). LDL-c: ; and HDL-c " (P < 0.05) in
hypercholesterolemics (roasted herb)

Sgfnt: significant; DI: dietary intervention; TC: total cholesterol; LDL-c: low-density lipoprotein cholesterol; HDL-c: High-density lipoprotein cholesterol; HbA1c:
haemoglobin A1c; ApoB-100: Apolipoprotein B-100; apoA-1: Apolipoprotein A-1.
Ref.: Reference.
1
Ribeiro et al. (2017).
2
Jung and Hur (2016).
3
Petrilli et al. (2016).
4
Kim et al. (2015).
5
Yu et al. (2015).
6
Messina et al. (2015).
7
Kahale et al. (2015).
8
Boaventura et al. (2013).
9
Kim et al. (2012).
10
Boaventura et al. (2012).
11
Arçari et al. (2011).
12
Klein et al. (2011).
13
De Morais et al. (2009).

Hur, 2016; Kim et al., 2012, 2015; Petrilli et al., 2016). In the study ± 169.7 lEq L–1; control: 575.3 ± 220.1 lEq L–1). Kim et al. (2012)
of Jung and Hur (2016) blood cholesterol levels decreased in maté did not find significant differences (P < 0.05) in the levels of choles-
group (n = 17) in relation to control group (n = 16), but values did terol, triacylglycerol and HDL-c between participants who con-
not differ significantly (P < 0.05) after 6 weeks (maté group: 11.65 sumed maté capsules (n = 24) and placebo (n = 22), but the mean
± 31.78 mg dL–1, control group: 12.63 ± 27.24 mg dL–1). Petrilli cholesterol level in maté group was lower than in placebo (172.3
et al. (2016) did not find a significant increase in HDL-c level after mg dL–1 vs. 183.2 mg dL–1; P = 0.09). Arçari et al. (2011) did not
maté intake when compared with baseline. Kim et al. (2015) observe a significant (P < 0.05) lipid profile improvement of hyper-
observed a decrease in free fatty acid after maté capsules intake lipidaemic (n = 18) and normolipidaemic (n = 42) subjects after
(n = 15), although the difference from placebo group (n = 15) maté tea intake for 60 days. De Morais et al. (2009) was the first
was not significant (P < 0.05) after 12 weeks (maté group: 443.5 clinical trial to demonstrate a cholesterol- and lipoprotein-
L.G. Riachi, C.A.B. De Maria / Journal of Functional Foods 38 (2017) 308–320 317

lowering property of maté infusion in humans. In the study, the (11 mg dL–1), non-HDL-c (21.5 mg dL–1) and triglycerides
consumption of green or roasted maté tea by normolipidaemic (53 mg dL–1) levels. In this case, it was suggested that the decrease
(n = 15) and dyslipidaemic subjects (n = 57) significantly improved in LDL-c and non-HDL-c levels was due to a reduction in total fat
serum lipid parameters after 40 days of treatment. The results from intake (23%), particularly saturated fatty acid (36%) and cholesterol
both green and roasted maté consumption were undistinguished (28%), and the concomitant enhancement of fibre consumption
because both infusions had a similar hypocholesterolemic effect. (35%). The results were conflicting since maté had not effect in
In normolipidaemic participants the level of LDL-c and LDL-c/ the lipid profile of diabetic subjects from maté tea + DI group and
HDL-c ratio had a significant reduction (P < 0.05) after 20 days on pre-diabetic subjects from maté tea group (Klein et al., 2011).
(LDL-c: 8.7% or 9.9 mg dL–1; LDL-c/HDL-c ratio: 16%) and 40 days Boaventura et al. (2012) also analysed the effect of maté tea with
(LDL-c: 7.3% or 8.3 mg dL–1; LDL-c/HDL-c ratio: 10%), when com- or without dietary intervention (maté tea, maté tea + DI or DI) on
pared with baseline. In dyslipidaemic subjects, intake of maté for the lipid profile of dyslipidaemic subjects (n = 74) for 90 days.
20 and 40 days reduced levels of total cholesterol by 3.5 and The single significant improvement found was in participants from
4.6% (8.1 and 10.7 mg dL–1, P < 0.01), LDL-c by 8.1 and 8.6% (12.9 maté tea group, which had a significant reduction in LDL-c level,
and 13.7 mg dL–1, P < 0.001), non-HDL by 5.4 and 6.5% (10.1 and when compared with baseline level (160.2 ± 5.7 mg dL–1 vs.
12 mg dL–1, P < 0.05), and LDL-c/HDL-c ratio by 12.1 and 11.2% 150.1 ± 4.8 dL–1, P < 0.05). These results also were conflicting since
(P < 0.01), respectively when compared with baseline. After 20 lipid parameters in dyslipidaemic subjects from maté tea + DI and
days HDL-c increased by 4.4% (2.1 mg dL–1) (P < 0.01), apoB-100 DI group did not change. In another study, Messina et al. (2015)
reduced by 6% (P < 0.05) and apoB/apoA-1 ratio lowered by 6.4% analysed the lipid-lowering potential of different amounts of
(P < 0.05). In normolipidaemic individuals, the HDL-c level had a maté infusion in dyslipidaemic subjects for 12 weeks (group 1 con-
similar increase but was it was not statistically significant, proba- sumed 500 mL/daily, n = 74 and group 2 consumed 1L/daily, n =
bly because of the small number of participants. The mechanism 47; 100 mg mL–1). Both amounts of maté infusion were effective
by which maté may increase HDL-C level is not clear. Since it in decreasing LDL-c (group 1: 151.35 ± 21.39 mg dL–1 vs. 133.52
was not found a significant increase in apoA-1 level after maté ± 27.61 mg dL–1, P < 0.001; group 2: 148.16 ± 19.77 mg dL–1 vs.
ingestion, it was suggested that HDL-c synthesis may not play a 129.98 ± 23.73 mg dL–1, P < 0.001) and total cholesterol levels
role in the observed HDL-c enhancement (De Morais et al., 2009). (group 1: 231.28 ± 27.29 mg dL–1 vs. 209.70 ± 31.08 mg dL–1,
In our opinion, maté may inhibit the removal of HDL apoA-1 sub- P < 0.001; group 2: 223.08 ± 24.01 mg dL–1 vs. 201.26 ± 26.33
factor by inhibiting hepatocyte HDL catabolism receptor. Previous mg dL–1, P < 0.001). Maté consumption also showed to be beneficial
study suggested that niacin, by inhibiting the hepatocyte surface in lipid profile of subjects with high blood viscosity (Yu et al.,
expression of b-chain adenosine triphosphate synthase (a recently 2015). Blood lipid levels play a role in erythrocyte aggregation both
reported HDL-apo A-I holoparticle receptor), inhibits the removal by altering membrane phospholipids and by influencing plasma
of HDL-apo A-I (Kamanna & Kashyap, 2008). The inhibition of the factors that regulate blood cell-blood cell interactions. Maté intake
HDL apoA-1 subfraction catabolism would increase circulant levels significantly increased HDL-c (P < 0.00) and reduced LDL-c, triglyc-
of the lipoprotein favoring cholesterol reverse transport (De Maria erides and total cholesterol levels (P < 0.00) of subjects with high
& Moreira, 2011). In addition, roasted maté tea intake provided a blood viscosity (n = 71) after 6 weeks. In fact, blood lipid profile
further LDL-c reduction in subjects undergoing statin therapy (n of maté tea drinkers was significantly improved to levels exhibited
= 30) (simvastatin – 10 mg/daily; atorvastatin – 20 mg/daily; or by control patients unaffected by irregularities in microcirculation
lovastatin – 40 mg/daily). Their LDL-c level reduced by 10.0% or blood viscosity.
(13.5mg dL–1), from 135.4 ± 15.1 to 121.9 ± 13.0 mg dL–1
(P < 0.01) after 20 days and by 13.1% (17.7 mg dL–1) after 40 days
(P < 0.05). The synergistic effect of maté with statin was explained 6. Other physiological activities
based on a dual cholesterol inhibition, that is, blocking intestinal
absorption by maté and decreasing endogenous biosynthesis by For a long time, case-control studies have been associating maté
statins and maté phenolics (De Morais et al., 2009). Indeed, caffeic consumption with the occurrence of cancer (Deneo-Pellegrini
acid lowered plasma triglyceride and cholesterol concentrations et al., 2013; Szymańska et al., 2010; Vassallo et al., 1985). They
and efficiently inhibited liver cholesterol biosynthesis in mice have suggested a strong association between maté drinking and
under diet-induced hyperlipidaemia (Liao, Ou, Wu, & Wang, cancer of the upper gastrointestinal tract. However, residual con-
2013). Khan, Baboota, Ali, Narang, and Narang (2016), used chloro- founding by alcohol drinking and tobacco smoking could not be
genic acid in a nanostructured lipid carrier (NLC) aiming to develop excluded entirely (IARC., 1991). The association could be due to
an optimized oral NCL atorvastatin formulation and observed a the composition of the beverage, the temperature at which it is
highly significant (P < 0.01) reduction in cholesterol and triglyc- consumed or both, as the analysed studies were conducted in pop-
eride value when compared with ATORVAÒ tablets in a pharmaco- ulations that consume hot maté (IARC, 1991). Additionally, no
dynamic study with rats. Saponins from maté inhibited the passive studies were available on a population that consumes cold maté.
diffusion of cholic acid through dialysis membranes (Ferreira, Therefore, IARC from World Health Organization (WHO) concluded
Vázquez, Güntner, & Moyna, 1997). This was attributed to the for- that maté is not classifiable as to its carcinogenicity to humans, but
mation of large macromolecular mixed micelles between cholic hot maté drinking is probably carcinogenic to humans (IARC,
acid and maté saponins, which could increase sterols excretion 1991). Recently, a working group convened by IARC evaluated
(Ferreira et al., 1997). the carcinogenicity of drinking coffee, mate, and very hot bever-
In the study of Klein et al. (2011) maté consumption also pro- ages (Loomis et al., 2016). It was suggested that drinking very
moted beneficial effects on lipid profile of T2DM and pre-diabetic hot beverages (above 65 °C), including very hot maté, is one prob-
subjects after maté tea consumption and/or dietary intervention able cause of oesophageal cancer and classified this behaviour as
(maté tea, maté tea + DI, or DI). In general, nutritional counselling probably carcinogenic to humans. On the other hand, cold maté
performed with or without maté tea intake did not promote a sig- did not have carcinogenic effects in experiments on animals or in
nificant improvement in the lipid parameters of T2DM subjects. In epidemiological studies, thus drinking maté at temperatures that
pre-diabetics when maté was combined with dietary counselling, are not very hot was not classifiable as to its carcinogenicity to
the hypolipidaemic effect was greater. After 60 days of treatment, humans. Consequently, temperature, and not maté itself, appears
there were a reduction in total lipids (19 mg dL–1), LDL-c to be responsible for the carcinogenic effect (Loomis et al., 2016).
318 L.G. Riachi, C.A.B. De Maria / Journal of Functional Foods 38 (2017) 308–320

Recently, evidence of a protective effect of maté drinking on the variations in processing and preparation methods, environmental
risk of breast cancer was found (Ronco, Stefani, Mendoza, variables, and experimental design, including interpersonal
Deneo-Pellegrini, et al., 2016; Ronco, Stefani, Mendoza, Vazquez, variations. In addition to the above-mentioned limitations, other
et al., 2016). In a case-control study high consumption of maté factors, such as small sample size and lack of longitudinal clinical
was inversely associated with breast cancer risk (odds ratio = trials may have masked the effect of maté on human parameters
0.40, 95% confidence interval: 0.26–0.57, P < 0.001) (Ronco, analysed in the studies. These factors might be responsible for con-
Stefani, Mendoza, Deneo-Pellegrini, et al., 2016). Another study troversial results regarding PON-1 activity, LDL-c oxidation and
suggested a favourable combination regarding breast cancer risk glycemic and lipid controls in humans. Maté showed an antioxida-
when high maté intake is associated with high consumption of tive activity on LDL-c in whole plasma, but results from the iso-
tea and even a stronger positive effect when it is combined with lated LDL-c particles are inconclusive. Further, future studies
a high antioxidant diet (Ronco, Stefani, Mendoza, Vazquez, et al., should address the influence of maté on oxidized LDL-c particles
2016). and LDL-c size. Although different studies had shown an anti-
Case-control and cross-sectional studies have been showing a glycation effect of maté in vitro, it was not possible to confirm this
beneficial effect of maté intake in relation to different issues. A ability in vivo. In most studies maté was not able to control effi-
cross-sectional study associated maté consumption with higher ciently the glycaemia. Favourable results only were found in
bone mineral density in postmenopausal women, suggesting a pro- T2DM subjects. The influence of maté on stimulation of incretin
tective effect of chronic maté consumption on bone mass (Conforti, secretion and/or insulin liberation is an interesting topic for future
Gallo, & Saraví, 2012). Maté drinking showed a positive correlation research. Despite the limitations, it was observed a positive effect
with density of both lumbar spine (P < 0.0001) and femoral neck of maté on human antioxidant enzymatic complex. There is a unan-
(P = 0.0028) (Conforti et al., 2012). A case-control study found an imous tendency of maté in helping to restore human redox balance
inverse association between maté drinking and Parkinson’s disease on the short-term. It would be interesting to analyse if this effect is
(odds ratio 0.64, 95% confidence interval: 0.54–0.76, P = 0.00001), sustained for a long period of time (eg. 5 years). Maté supplemen-
suggesting a possible protective effect of maté on the expression, tation showed a positive effect on energy expenditure and in the
development, and progression of the disease (Gatto, Melcon, reduction of body fat in humans, with additional advantage of all
Parisi, Bartoloni, & Gonzalez, 2015). Regarding the safety of maté treatments being well tolerated. Although maté has been pointed
consumption during pregnancy, a preliminary case-control study out as a potential thermogenic, the supplement still should be used
did not find harmful effect of maté drinking on intrauterine growth with caution until more clinical controlled studies prove its
or duration of pregnancy (Santos, Matijasevich, & Valle, 2005). It efficacy and safety. Considering to the carcinogenicity of maté bev-
was suggested that the amount of maté regularly consumed during erages, temperature, and not maté itself, appears to be responsible
pregnancy in South Brazil is probably safe for the foetus. for the carcinogenic effect.
Clinical studies reported other effects of maté, different from Despite the existing studies, the amount of controlled clinical
what was previously investigated, demonstrating new possible trials is still scarce. Therefore, assessment of long-term random-
applications. In a double-blind placebo-controlled study, maté sig- ized double-blind placebo-controlled studies with more consistent
nificantly (P < 0.05) improved parameters of blood viscosity and sampling will provide a better understanding of the effects of maté
microcirculation of subjects with high blood viscosity. Maté played on human health. Furthermore, compounds from different maté
a role in the regulation of various indexes of hemorheology, nail- extracts should be properly identified and quantified to better
fold microcirculation, and the platelet aggregating factors 6-keto- understand their contribution to the expected physiological
PGF1a and TXB2, showing a potential in reducing the incidence effects. If positive and consistent results are confirmed over time,
of risk factors attributed to cardiovascular disease (Yu et al., maté could be recognized as a functional food.
2015). Petrilli et al. (2016) analysed the effect of maté tea intake
(3g) on HIV-infected subjects for 60 days but they did not find
any change in oxidative or inflammatory parameters (high- Acknowledgements
sensitivity C-reactive protein, fibrinogen, white blood cell profile
and lipid peroxidation). A pioneering study done by our group This work was supported by Coordenação de Aperfeiçoamento
(Ribeiro et al., 2017) analysed the effect of short-term (14 days) de Pessoal de Nível Superior (Capes) and Conselho Nacional de
consumption of roasted maté on blood total creatine phosphoki- Desenvolvimento Científico e Tecnológico (CNPq).
nase (CPK) level in institutionalized patients with traumatic brain
injury (TBI) (n: maté group = 4, control = 4). Elevated levels of total References
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