Abstract

Introduction

Menopause is associated with an increased frequency of chronic conditions, such as hypertension, cardiovascular disease (CVD), metabolic syndrome, and diabetes mellitus (DM). Traditional cardiovascular risk factors are usually more prevalent after menopause because of loss of estrogenic protection. Menopause has been associated with dyslipidemia, hyperglycemia, and hypertension. The prevalence of hypertension in postmenopausal women is two times higher than in premenopausal women and more than 75% of women older than 60 years have hypertension (¹1. Lima R, Wofford M, Reckelhoff JF. Hypertension in postmenopausal women. Curr Hypertens Rep 2012; 14: 254–260, doi: 10.1007/s11906-012-0260-0.
https://doi.org/10.1007/s11906-012-0260-... ). Moreover, type 2 DM is a disease associated with specific changes in the lipid profile promoting an atherogenic pattern (²2. Fonseca MIH, da Silva IT, Ferreira SRG. Impact of menopause and diabetes on atherogenic lipid profile: is it worth to analyse lipoprotein subfractions to assess cardiovascular risk in women? Diabetol Metab Syndr 2017; 9: 22, doi: 10.1186/s13098-017-0221-5.
https://doi.org/10.1186/s13098-017-0221-... ). These findings contribute to the morbidity of CVD in postmenopausal women.

Yerba mate (Ilex paraguariensis) is a native plant from southern South America, consumed daily by ∼70% of that population in the form of mate, mate tea or tererê. Several classes of phytochemicals are found in its leaf composition: xanthines (such as caffeine and theobromine), saponins (derived from ursolic and oleanolic acids), and phenolic components (such as chlorogenic acid and other classes of polyphenols). Many experimental studies indicate antioxidant, anti-inflammatory, vasodilating, hypocholesterolemic, and hypoglycemic properties related to yerba mate use (³3. Bracesco N, Sanchez AG, Contreras V, Menini T, Gugliucci A. Recent advances on Ilex paraguariensis research: minireview. J Ethnopharmacol 2011; 136: 378–384, doi: 10.1016/j.jep.2010.06.032.
https://doi.org/10.1016/j.jep.2010.06.03... ). In humans, some experimental studies have pointed out a beneficial effect of the consumption of yerba mate on the levels of total cholesterol (CT), triglycerides (TG), and glucose (⁴4. de Morais EC, Stefanuto A, Klein GA, Boaventura BC, de Andrade F, Wazlawik E, et al. Consumption of yerba mate (Ilex paraguariensis) improves serum lipid parameters in healthy dyslipidemic subjects and provides an additional LDL-cholesterol reduction in individuals on statin therapy. J Agric Food Chem 2009; 57: 8316–8324, doi: 10.1021/jf901660g.
https://doi.org/10.1021/jf901660g... –⁶6. Klein GA, Stefanuto A, Boaventura BC, de Morais EC, Cavalcante Lda S, de Andrade F, et al. Mate tea (Ilex paraguariensis) improves glycemic and lipid profiles of type 2 diabetes and pre-diabetes individuals: a pilot study. J Am Coll Nutr 2011; 30: 320–332, doi: 10.1080/07315724.2011.10719975.
https://doi.org/10.1080/07315724.2011.10... ). The aim of this study was to evaluate the association between the consumption of yerba mate and the frequencies of dyslipidemia, DM, and CVDs in postmenopausal women.

Material and Methods

This study was a post hoc analysis of the case-control study (⁷7. da Veiga DTA, Bringhenti R, Bolignon AA, Tatsh E, Moresco RN, Comim FV, et al. The yerba mate intake has a neutral effect on bone: A case-control study in postmenopausal women. Phytother Res 2017; 32: 58–64, doi: 10.1002/ptr.5947.
https://doi.org/10.1002/ptr.5947... ) nested in the Obesity and Bone Fracture Cohort (⁸8. Copes RM, Comim FV, Langer FW, Codevilla AA, Sartori GR, de Oliveira C, et al. Obesity and Fractures in postmenopausal women: a primary-care cross-sectional study at Santa Maria, Brazil. J Clin Densitom 2015; 18: 165–171, doi: 10.1016/j.jocd.2014.09.005.
https://doi.org/10.1016/j.jocd.2014.09.0... ) that aimed to evaluate the association between bone fracture and the intake of the aqueous extract of mate tea consumed as “chimarrão” in postmenopausal women. It was conducted in the municipality of Santa Maria, RS, Brazil. The original cohort recruited 1057 women aged >55 years at primary care facilities. Women at menacme and those with cognitive deficits or communication difficulties were excluded from the survey. All 46 women with confirmed major bone fractures in the original cohort and 49 randomly selected controls without fractures (⁷7. da Veiga DTA, Bringhenti R, Bolignon AA, Tatsh E, Moresco RN, Comim FV, et al. The yerba mate intake has a neutral effect on bone: A case-control study in postmenopausal women. Phytother Res 2017; 32: 58–64, doi: 10.1002/ptr.5947.
https://doi.org/10.1002/ptr.5947... ) were included in this post hoc analysis (n=95).

Approval for this study was obtained from the Ethics Committee of the Universidade Federal de Santa Maria (CAAE 04320312.2.0000.5346) and from the Secretaria de Saúde da Prefeitura de Santa Maria (Ofício 492/2012/SMS/NEPeS) and followed the Declaration of Helsinki principles. All participants who agreed to participate in the study signed the informed consent term.

A standardized questionnaire including risk factors for CVD and self-reported CVD was applied at baseline (⁸8. Copes RM, Comim FV, Langer FW, Codevilla AA, Sartori GR, de Oliveira C, et al. Obesity and Fractures in postmenopausal women: a primary-care cross-sectional study at Santa Maria, Brazil. J Clin Densitom 2015; 18: 165–171, doi: 10.1016/j.jocd.2014.09.005.
https://doi.org/10.1016/j.jocd.2014.09.0... –9. Hooven FH, Adachi JD, Adami S, Boonen S, Compston J, Cooper C, et al. The global longitudinal study of osteoporosis in women (GLOW): rationale and study design. Osteoporos Int 2009; 20: 1107–1116, doi: 10.1007/s00198-009-0958-2.
https://doi.org/10.1007/s00198-009-0958-... ¹⁰10. Baecke JA, Burema J, Frijters JE. A short questionnaire for the measurement of habitual physical activity in epidemiological studies. Am J Clin Nutr 1982; 36: 936–942, doi: 10.1093/ajcn/36.5.936.
https://doi.org/10.1093/ajcn/36.5.936... ). Yerba mate intake was evaluated by a food frequency questionnaire. The intake of the aqueous extract of yerba mate consumed as “chimarrão” (mate) was quantified per day. More information regarding data collection is shown in the Supplementary Material.

Serum albumin, CT, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), TG, glucose, and creatinine were measured using the standard methods on Cobas MIRA¯ (Roche Diagnostic, Switzerland) automated analyzer. The serum levels of nitrite/nitrate (NO), ferric reducing ability of plasma (FRAP), and advanced oxidation protein products (AOPP) also were measured using Cobas MIRA¯.

Statistical analysis was performed using the IBM SPSS program (version 19.0 for Windows, Brazil). Data are reported as prevalence rates (percentages) or means (standard deviations). The cutoff considered for mate consumption was 1 L/day, a criterion adapted and modified from Conforti et al. (¹¹11. Conforti AS, Gallo ME, Saravi FD. Yerba Mate (Ilex paraguariensis) consumption is associated with higher bone mineral density in postmenopausal women. Bone 2012; 50: 9–13, doi: 10.1016/j.bone.2011.08.029.
https://doi.org/10.1016/j.bone.2011.08.0... ). The chi-square and Student's t-tests were used to determine possible differences between the two groups. Differences were considered significant when the two-tailed P-value was less than 0.05. The power of this study for the evaluation of the association between mate intake and the frequency of coronary disease was 0.991.

Results

The characteristics of the original cohort and the case-control study are described in detail elsewhere (⁷7. da Veiga DTA, Bringhenti R, Bolignon AA, Tatsh E, Moresco RN, Comim FV, et al. The yerba mate intake has a neutral effect on bone: A case-control study in postmenopausal women. Phytother Res 2017; 32: 58–64, doi: 10.1002/ptr.5947.
https://doi.org/10.1002/ptr.5947... ,⁸8. Copes RM, Comim FV, Langer FW, Codevilla AA, Sartori GR, de Oliveira C, et al. Obesity and Fractures in postmenopausal women: a primary-care cross-sectional study at Santa Maria, Brazil. J Clin Densitom 2015; 18: 165–171, doi: 10.1016/j.jocd.2014.09.005.
https://doi.org/10.1016/j.jocd.2014.09.0... ). Table 1 shows the clinical characteristics of the participants with a daily consumption of mate. There was no difference between groups regarding age, body mass index, waist circumference, physical activity, tobacco use, and years of schooling. The women who drank at least 1 L/day of mate had significantly fewer diagnoses of dyslipidemia, hypertension, and coronary disease (Table 1).

There was no significant difference in the levels of albumin, serum lipids, markers of oxidative stress, and creatinine between the women with mate intake equal to or greater than 1 L/day and women with a lesser intake. The fasting serum levels of glucose were lower in the women with a higher consumption of mate (Table 2).

Discussion

In this post hoc analysis, postmenopausal women who consumed more than 1 L/day of mate reported fewer diagnoses of dyslipidemia, hypertension, and coronary disease. Although some metabolic findings have been reported in previous studies (⁴4. de Morais EC, Stefanuto A, Klein GA, Boaventura BC, de Andrade F, Wazlawik E, et al. Consumption of yerba mate (Ilex paraguariensis) improves serum lipid parameters in healthy dyslipidemic subjects and provides an additional LDL-cholesterol reduction in individuals on statin therapy. J Agric Food Chem 2009; 57: 8316–8324, doi: 10.1021/jf901660g.
https://doi.org/10.1021/jf901660g... –⁶6. Klein GA, Stefanuto A, Boaventura BC, de Morais EC, Cavalcante Lda S, de Andrade F, et al. Mate tea (Ilex paraguariensis) improves glycemic and lipid profiles of type 2 diabetes and pre-diabetes individuals: a pilot study. J Am Coll Nutr 2011; 30: 320–332, doi: 10.1080/07315724.2011.10719975.
https://doi.org/10.1080/07315724.2011.10... ,¹²12. Gugliucci A. Antioxidant effects of Ilex paraguariensis: induction of decreased oxidability of human LDL in vivo. Biochem Biophys Res Commun 1996; 224: 338–344, doi: 10.1006/bbrc.1996.1030.
https://doi.org/10.1006/bbrc.1996.1030... ), to the best of our knowledge, this is the first study to report the beneficial effect of yerba mate consumption on the incidence of chronic diseases in postmenopausal women.

The acute effect of mate tea on blood pressure was first described by de Morais et al. They evaluated the impact of an intake of 1 L/day of mate tea within 40 days in adult subjects and found a reduction of 2.3% in systolic blood pressure in the experimental group (⁴4. de Morais EC, Stefanuto A, Klein GA, Boaventura BC, de Andrade F, Wazlawik E, et al. Consumption of yerba mate (Ilex paraguariensis) improves serum lipid parameters in healthy dyslipidemic subjects and provides an additional LDL-cholesterol reduction in individuals on statin therapy. J Agric Food Chem 2009; 57: 8316–8324, doi: 10.1021/jf901660g.
https://doi.org/10.1021/jf901660g... ). Although we did not find an effect on the blood pressure measured at the time of blood sample collection, the women in our study presented significantly fewer diagnoses of hypertension and coronary disease. However, the exact mechanism by which yerba mate consumption has favorable effects on the cardiovascular system is not known. Schinella et al. (¹³13. Schinella G, Fantinelli JC, Mosca SM. Cardioprotective effects of Ilex paraguariensis extract: evidence for a nitric oxide-dependent mechanism. Clin Nutr 2005; 24: 360–366, doi: 10.1016/j.clnu.2004.11.013.
https://doi.org/10.1016/j.clnu.2004.11.0... ) described the protective effect of the aqueous extract of mate on myocardial dysfunction induced by ischemia and reperfusion in an experimental animal model. In their study, the cardioprotective effect appears to be linked to an NO-dependent mechanism (¹³13. Schinella G, Fantinelli JC, Mosca SM. Cardioprotective effects of Ilex paraguariensis extract: evidence for a nitric oxide-dependent mechanism. Clin Nutr 2005; 24: 360–366, doi: 10.1016/j.clnu.2004.11.013.
https://doi.org/10.1016/j.clnu.2004.11.0... ). Other studies conducted on rats fed a high-fat diet found that mate aqueous extract showed beneficial effects on the vascular endothelium (¹⁴14. Gao H, Liu Z, Qu X, Zhao Y. Effects of Yerba Mate tea (Ilex paraguariensis) on vascular endothelial function and liver lipoprotein receptor gene expression in hyperlipidemic rats. Fitoterapia 2013; 84: 264–272, doi: 10.1016/j.fitote.2012.12.024.
https://doi.org/10.1016/j.fitote.2012.12... ,¹⁵15. Paganini Stein FL, Schmidt B, Furlong EB, Souza-Soares LA, Soares MC, Vaz MR, et al. Vascular responses to extractable fractions of Ilex paraguariensis in rats fed standard and high-cholesterol diets. Biol Res Nurs 2005; 7: 146–156, doi: 10.1177/1099800405280521.
https://doi.org/10.1177/1099800405280521... ).

In our study, the women with a higher consumption of mate had fewer diagnoses of dyslipidemia, despite the fact that no significant differences were observed in the evaluation of the serum levels of CT, LDL-C, HDL-C, and TG. These results might suggest that mate intake could have a long-term effect or an indirect mechanism. Different studies have reported different effects on the serum lipid levels (⁴4. de Morais EC, Stefanuto A, Klein GA, Boaventura BC, de Andrade F, Wazlawik E, et al. Consumption of yerba mate (Ilex paraguariensis) improves serum lipid parameters in healthy dyslipidemic subjects and provides an additional LDL-cholesterol reduction in individuals on statin therapy. J Agric Food Chem 2009; 57: 8316–8324, doi: 10.1021/jf901660g.
https://doi.org/10.1021/jf901660g... ,⁵5. Messina D, Soto C, Mendez A, Corte C, Kemnitz M, Avena V, et al. [Lipid-lowering effect of mate tea intake in dyslipidemic subjects]. Nutr Hosp 2015; 31: 2131–2139.,¹⁶16. Boaventura BDP PF, Klein GA, Stefanuto A, de Morais EC, de Andrade D, Wazlawik E, et al. Antioxidant potential of mate tea (Ilex paraguariensis) in type 2 diabetic mellitus and pre-diabetic individuals. J Funct Foods 2013; 5: 1057–1064, doi: 10.1016/j.jff.2013.03.001.
https://doi.org/10.1016/j.jff.2013.03.00... ). In a study conducted on adult subjects, the intake of 990 mL/day of mate for 40 days decreased the serum levels of CT and LDL-C and increased the serum levels of HDL-C in subjects with dyslipidemia. Conversely, only the serum levels of LDL-C decreased in normolipemic individuals (⁴4. de Morais EC, Stefanuto A, Klein GA, Boaventura BC, de Andrade F, Wazlawik E, et al. Consumption of yerba mate (Ilex paraguariensis) improves serum lipid parameters in healthy dyslipidemic subjects and provides an additional LDL-cholesterol reduction in individuals on statin therapy. J Agric Food Chem 2009; 57: 8316–8324, doi: 10.1021/jf901660g.
https://doi.org/10.1021/jf901660g... ). These findings suggest that yerba mate consumption might have a different effect on lipid levels depending on the previous metabolic status of the subject. Another study also conducted in middle-aged subjects described a decrease in the serum levels of TC and LDL-C but no changes in the serum levels of TG (⁵5. Messina D, Soto C, Mendez A, Corte C, Kemnitz M, Avena V, et al. [Lipid-lowering effect of mate tea intake in dyslipidemic subjects]. Nutr Hosp 2015; 31: 2131–2139.).

In the present study, a significant difference was observed in serum glucose levels between the higher-consumption mate group and the controls. The reduction in serum glucose levels and improvement in insulin resistance have been described in previous studies (⁶6. Klein GA, Stefanuto A, Boaventura BC, de Morais EC, Cavalcante Lda S, de Andrade F, et al. Mate tea (Ilex paraguariensis) improves glycemic and lipid profiles of type 2 diabetes and pre-diabetes individuals: a pilot study. J Am Coll Nutr 2011; 30: 320–332, doi: 10.1080/07315724.2011.10719975.
https://doi.org/10.1080/07315724.2011.10... ,¹⁶16. Boaventura BDP PF, Klein GA, Stefanuto A, de Morais EC, de Andrade D, Wazlawik E, et al. Antioxidant potential of mate tea (Ilex paraguariensis) in type 2 diabetic mellitus and pre-diabetic individuals. J Funct Foods 2013; 5: 1057–1064, doi: 10.1016/j.jff.2013.03.001.
https://doi.org/10.1016/j.jff.2013.03.00... ). In a clinical trial, Boaventura et al. (¹⁶16. Boaventura BDP PF, Klein GA, Stefanuto A, de Morais EC, de Andrade D, Wazlawik E, et al. Antioxidant potential of mate tea (Ilex paraguariensis) in type 2 diabetic mellitus and pre-diabetic individuals. J Funct Foods 2013; 5: 1057–1064, doi: 10.1016/j.jff.2013.03.001.
https://doi.org/10.1016/j.jff.2013.03.00... ) evaluated the consumption of 1 L of mate per day for 60 days on glycemia, advanced glycation end-products (HbA1c), and oxidative stress in subjects with DM and pre-DM. They observed reductions in the levels of glucose, HbA1c, and lipid peroxidation, suggesting that yerba mate intake could have a long-term beneficial effect on DM.

In the postmenopausal period and consequent estrogen reduction, there is an imbalance in oxidative stress, with decreased antioxidant defenses and increased oxidation, mainly lipid peroxidation (¹⁷17. Cakir T, Goktas B, Mutlu MF, Mutlu I, Bilgihan A, Erdem M, et al. Advanced oxidation protein products and malondialdehyde - the new biological markers of oxidative stress - are elevated in postmenopausal women. Ginekol Pol 2016; 87: 321–325, doi: 10.5603/GP.2016.0001.
https://doi.org/10.5603/GP.2016.0001... ). In our study, the markers of oxidative stress were not modified by the consumption of mate, which was partly different from the findings of the study by Boaventura et al. (¹⁶16. Boaventura BDP PF, Klein GA, Stefanuto A, de Morais EC, de Andrade D, Wazlawik E, et al. Antioxidant potential of mate tea (Ilex paraguariensis) in type 2 diabetic mellitus and pre-diabetic individuals. J Funct Foods 2013; 5: 1057–1064, doi: 10.1016/j.jff.2013.03.001.
https://doi.org/10.1016/j.jff.2013.03.00... ). Although they found no change in serum levels of FRAP, there was an increase in the erythrocyte levels of reduced glutathione after 60 days of treatment with 1 L of mate per day.

Several factors may explain the negative findings of our study regarding oxidative stress. First, the markers in our study were measured from samples of blood instead of liver. Sometimes, serum markers may not reflect what is occurring in other tissues. Second, many variables other than yerba mate intake in non-experimental conditions, such as the systemic inflammation present in CVDs, could influence the markers of oxidative stress. Finally, the preparation and consumption manner of yerba mate may also have affected the results (¹⁸18. Meinhart AD, Bizzotto CS, Ballus CA, Poloni Rybka AC, Sobrinho MR, Cerro-Quintana RS, et al. Methylxanthines and phenolics content extracted during the consumption of mate (Ilex paraguariensis, St. Hil) beverages. J Agric Food Chem 2010; 58: 2188–2193, doi: 10.1021/jf903781w.
https://doi.org/10.1021/jf903781w... ,¹⁹19. Blum-Silva CC VC, Schenkel EP, Coelho GC, Reginatto FH. The influence of leaf age on methilxanthines, total phenolic content, and free radical scavenging capacity of Ilex paraguariensis extracts. Rev Bras Farmacogn 2015; 25: 1–6, doi: 10.1016/j.bjp.2015.01.002.
https://doi.org/10.1016/j.bjp.2015.01.00... ).

The main strength of our study is its pragmatic nature with a sample representative of the Brazilian primary care users, which makes the generalization of the findings more intuitive. However, it also has some weaknesses. The study is a post hoc analysis; therefore, the results must be confirmed with other studies. The small sample size could have contributed to the negative results in blood pressure, blood lipid levels, and oxidative stress. Blood pressure was only measured once at the time of blood sample collection. We also did not have information on the patients' treatment, which may have affected blood pressure and biochemistry measurements. Moreover, the diagnoses were self-reported. Nonetheless, there is no reason to believe that the recall bias was different between mate drinkers and non-mate drinkers.

In conclusion, we described a potential beneficial effect of yerba mate use on the cardiovascular system, as indicated by fewer diagnoses of dyslipidemia, hypertension, and coronary disease in postmenopausal women.

Supplementary Material

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Acknowledgments

This study was supported by grants from the Universidade Federal de Santa Maria (edital FIPE/CCS 2013) and the Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq, #472211/2013-7 and #307057/2013-5).

References

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