Positive Effect of Yerba Mate (Ilex paraguariensis) Consumption on Bone Mineral Density in Postmenopausal Women Assessed by Dual Energy X-Ray Absorptiometry-Based 3-Dimensional Modeling
Article information
Abstract
Background
Yerba mate (YM) drinking is associated with higher lumbar spine and femoral neck bone mineral density (BMD) in postmenopausal women. We analyzed its effect on total hip BMD and reported the contribution of the trabecular and cortical components to this effect.
Methods
A control group of 147 non-drinkers was compared to 153 YM drinkers. Left hip BMD was measured using dual energy X-ray absorptiometry (DXA), and three-dimensional (3D)-Shaper software was used to estimate integral volumetric BMD (vBMD), cortical surface BMD (sBMD), and trabecular vBMD through 3D modeling.
Results
No significant difference was found between groups in either age (P=0.746) or body mass index (BMI; P=0.329). The YM group had significantly higher total hip BMD, integral vBMD, cortical sBMD, and trabecular BMD (all P<0.0001). The frequency of DXA-based osteoporosis diagnosis was lower in YM drinkers (3.3% vs. 10.9%; odds ratio [OR], 0.276). The rate of low-impact fractures was significantly reduced in YM drinkers (5.9% vs. 12.9%; OR, 2.197). Linear regression analyses revealed that cortical and trabecular parameters correlated positively with BMI and negatively with age in both groups. The slope of the lines did not differ between groups, but the elevation was uniformly higher in the YM group (P=0.0004 to P<0.0001).
Conclusions
Our study provides novel insights into YM consumption and bone health in postmenopausal women. We confirm its positive association with BMD and demonstrate, for the first time, that both cortical and trabecular compartments contribute to this effect. Our findings also suggest a potential protective role of YM against osteoporosis and fragility fractures.
INTRODUCTION
Osteoporosis is an important health problem with high morbidity and mortality due to fragility fractures.[1] Known risk factors for osteoporosis include age, low body mass index (BMI), low peak bone mass, postmenopausal estrogenic decline, treatment with corticosteroids or anticonvulsants, lifestyle-related factors like low physical activity, low calcium and vitamin D intake, tobacco smoking or excessive coffee or alcohol consumption, and chronic autoimmune, malabsorptive, liver, or kidney diseases.[1–4]
Caffeine, a xanthine compound, has been reported to adversely affect bone mineral density (BMD), particularly under conditions of inadequate calcium intake.[5–9] Yerba mate (YM; Ilex paraguariensis) is a xanthine-containing beverage widely consumed in South America, particularly in Argentina, Uruguay, Paraguay, and Brazil. In Argentina, the average daily caffeine intake among adults is approximately 288 mg, with 50% of this amount derived from YM consumption.[10] Although caffeine consumption has been associated with increased fracture risk in a dose-dependent manner,[11] studies have paradoxically suggested a beneficial association between YM consumption and BMD.[12,13]
Previous research has demonstrated that postmenopausal women who regularly consume YM exhibit significantly higher BMD at the lumbar spine (+9.7%) and femoral neck (+6.2%) compared to non-consumers.[12] Additionally, experimental studies in animal models have shown that YM mitigates bone loss due to calcium deficiency.[13] These effects may be attributable to the high polyphenol content of YM, which has been shown to exert antioxidant and bone-protective effects, similar to those observed with black and green tea (Camellia sinensis).[14–19]
While these findings are promising, no studies to date have examined whether YM consumption is associated with higher total hip BMD, nor have they examined the individual contributions of cortical and trabecular compartments to this potential effect. Given that total hip BMD is a key parameter for assessing fracture risk and monitoring osteoporosis treatment,[20,21] further investigation is warranted.
Dual energy X-ray absorptiometry (DXA) is the gold standard for osteoporosis diagnosis, and recent advances in DXA-based three-dimensional (3D) modeling allow for the separate evaluation of trabecular and cortical compartments, providing additional insights into bone structure and strength.[22–25]
This study aimed to investigate the association between YM consumption and total hip BMD in postmenopausal women using DXA-based assessments. Furthermore, through 3D modeling, we aimed to explore, for the first time, the relative contributions of trabecular and cortical components to the observed differences in total hip BMD between YM drinkers and non-drinkers. By addressing this gap in the literature, our study provides novel insights into the potential bone-protective effects of YM and its clinical implications for osteoporosis prevention.
METHODS
1. Study population
This is a cross-sectional, observational study performed on 300 postmenopausal women from two cities in Argentina, namely Mendoza (32°53′27″S) and Rosario (32º56′48″S). The study was conducted in full accordance with the Declaration of Helsinki. The study was reviewed and approved by the Committee on Research and Education of the Obra Social de Empleados Públicos of Mendoza and Ethics Committee of the School of Medicine, Rosario National University (Argentina). All patients gave written informed consent to participate. To keep their identity confidential, participants were identified by a number assigned to each one (Approval No. 80020220700049UR, Resol CD 4987/2022, December 2022).
YM drinkers (N=153) were defined as women who had consumed at least 1 liter of YM per day for at least 5 years at the time of the study. Non-drinkers who served as the control group (CG; N=147) were matched for age, BMI, and years since menopause. Both groups were asked to report whether they had sustained one or more low-impact bone fractures-also named fragility fracture-defined as a bone fracture resulting from minimal trauma, such as a fall from standing height or less, or even without apparent trauma.
For both groups, exclusion criteria were early menopause (<45 years-old), current or former cigarette smoking, drinking more than 3 cups of coffee or tea per day, drinking more than 50 g of alcohol per week, and being under treatment with drugs with known effects on bone, such as bisphosphonates, denosumab, teriparatide, raloxifene, estrogens, corticosteroids, and anticonvulsants. Women affected by conditions (other than osteoporosis) known to have a significant impact on bone, like malabsorption, chronic hepatic or renal diseases, acquired immunodeficiency syndrome, cancer, severe spine or hip osteoarthrosis, or rheumatoid arthritis, were also excluded.
The baseline characteristics (age, BMI, smoking status, alcohol intake, previous medication, personal and family history of major osteoporotic fractures) were obtained from medical records. Height and weight were measured for each patient without shoes and wearing light clothing. BMI was calculated as weight in kilograms divided by height in meters, squared (kg/m2).
2. DXA and DXA-based 3D modeling
BMD (g/cm2) was measured by DXA (Lunar Prodigy; GE Lunar, Madison, WI, USA) on the left hip. Examinations were performed according to recommendations provided by the manufacturer. Daily measurement of a spine phantom showed stability of the densitometers throughout the study (coefficient of variation [CV], <0.5%). The measurement precision, assessed using 90 duplicated scans obtained from patients during the study period, yielded a CV of 0.86±0.62% for total hip scans. DXA-based osteoporosis diagnosis was defined as a T-score ≤-2.5 in the total hip.
Modeling in 3D was conducted using 3D-Shaper software (version 2.9; Galgo Medical, Barcelona, Spain). Blind central processing by two physicians was performed on the femoral DXA scans. The following parameters were considered: integral volumetric BMD (integral vBMD; mg/cm3), trabecular volumetric BMD (trabecular vBMD; mg/cm3), and cortical surface BMD (sBMD; mg/cm2). Cortical BMD was obtained as the product of cortical volumetric density (mg/cm3) and cortical thickness (cm).
In addition to evaluating total hip BMD and its trabecular and cortical components, we performed a linear regression analysis with age or BMI to assess whether the differences observed between groups could be partially explained by variations in these parameters.
3. Statistical analysis
To detect a 5% difference in total hip BMD with α=0.05 and power=0.80 with a two-sided t-test, we estimated a sample size of 142 for each group.[26]
D’Agostino and Pearson tests, as well as Shapiro-Wilk tests were used to assess normality to determine whether parametric or non-parametric tests were appropriate. Accordingly, data were compared using either a two-sided Student’s t-test or a two-sided Mann-Whitney test, reporting respectively the results as mean±standard deviation or as median and interquartile range, respectively. Linear regression was used to test the regression correlation (R) between total hip and 3D variables, and the relationship of each densitometric variable with BMI and age. Categorical data were analyzed with Fisher’s exact test. Logistic regression analyses were performed to evaluate the associations between YM consumption and both prevalent fragility fractures and DXA-confirmed osteoporosis, with odds ratios (OR) and 95% confidence intervals (CIs) computed as measures of association. Differences were considered significant if the P-value was less than 0.05. Data were analyzed with GraphPad Prism 8.02 (GraphPad Software, San Diego, CA, USA) and InStat 3.0 for Windows (GraphPad Software).
RESULTS
The main findings are presented in Table 1. No significant differences were observed between groups in terms of age (P=0.746), time since menopause (P=0.681), or BMI (P=0.329). There was no significant difference in total hip variance between groups (P=0.387).
Age, time from menopause, body mass index, fracture history, and total hip bone mineral density for the control group and yerba mate drinkers
Total hip BMD were significantly higher in the YM group (P<0.0001). The frequency of DXA-based osteoporosis diagnosis was significantly different: 3.3% (5/153) in the YM group compared with 10.9% (16/147) in the CG (OR, 0.276; 95% CI, 0.109–0.778; P=0.012). Low-impact fractures (hip, spine, humerus, or wrist) were observed in 19 individuals from the CG (N=147, 12.9%) and 9 individuals among YM group (N=153, 5.9%). The difference was significant (P= 0.046), with an OR of 2.197 and a 95% CI of 1.027 to 4.700 (Table 1).
Moreover, all calculated 3D DXA parameters were significantly higher in the YM group (Table 2).
Three-dimensional dual energy X-ray absorptiometry parameters for the control group and yerba mate drinkers
The results of simple linear regression analysis between total hip BMD and 3D DXA parameters for both groups are shown in Table 3. All calculated R were high, ranging from 0.843 to 0.916.
Linear regression between total hip bone mineral density and 3-dimensional dual energy X-ray absorptiometry parameters for the control group and yerba mate drinkers
Simple linear regression of 3D DXA parameters with BMI and age is shown in Figure 1 and 2, respectively. Age and BMI were correlated with BMD in both YM consumers and controls. Across different age and BMI values, the elevation of the regression lines remained significantly higher in YM consumers compared to controls (Age: cortical sBMD slope P=0.207, elevation P<0.0001; trabecular vBMD slope P= 0.931, elevation P<0.0001; integral vBMD slope P=0.628, elevation P<0.0001; BMI: cortical sBMD slope P=0.117, elevation P=0.0004; trabecular vBMD slope P=0.130, elevation P<0.0001; integral vBMD slope P=0.125, elevation P<0.0001).
Linear regression of 3-dimensional dual energy X-ray absorptiometry parameters versus age. Mean values are shown by the continuous lines and 95% confidence interval by the dashed lines. Red lines correspond to the control group and green lines to yerba mate drinkers. (A) Cortical surface bone mineral density (sBMD) slope P=0.207, elevation P<0.0001. (B) Trabecular volumetric bone mineral density (vBMD) slope P=0.931, elevation P<0.0001. (C) Integral vBMD slope P=0.628, elevation P<0.0001.
Linear regression of 3-dimensional dual energy X-ray absorptiometry parameters versus body mass index (BMI). Mean values are shown by the continuous lines and 95% confidence interval by the dashed lines. Red lines correspond to the control group and green lines to yerba mate drinkers. (A) Cortical surface bone mineral density (sBMD) slope P=0.117, elevation P=0.0004. (B) Trabecular volumetric bone mineral density (vBMD) slope P=0.130, elevation P<0.0001. (C) Integral vBMD slope P=0.125, elevation P<0.0001.
DISCUSSION
Our study confirms the association between YM consumption and higher BMD, improved trabecular and cortical parameters assessed through DXA-based 3D modeling, a reduced frequency of DXA-based osteoporosis diagnosis, and lower risk of low-impact fractures. These findings offer new insights into the clinical benefits associated with YM consumption.
We demonstrate, for the first time, an over 8% higher total hip BMD in YM drinkers compared to CG, consistent with previously reported findings on lumbar spine and femoral neck BMD.[12] This result is particularly noteworthy due to the high precision, reproducibility, and strong correlation of total hip BMD with fracture risk, including vertebral fractures.[ 27,28] Moreover, total hip BMD is the preferred parameter for monitoring the efficacy of anti-fracture treatments.[ 29] Additionally, our findings reveal that both trabecular and cortical bone components contribute to the observed differences in total hip BMD between groups.
Both cortical and trabecular components in the two groups showed a positive correlation with BMI and a negative correlation with age.[30] Despite these associations, the elevation of the regression lines remained consistently higher in YM consumers, suggesting that the observed differences in BMD are not solely attributable to BMI- or age-related mechanical effects. Notably, while the difference in elevation between the regression lines remained relatively constant across different ages, it tended to narrow with increasing BMI. These findings suggest that the potential beneficial effect of YM consumption on bone density is preserved across all ages within the sample but may diminish in women with severe obesity.
Obesity has a complex impact on bone health, with both protective and detrimental effects. The mechanical load associated with increased body weight is known to enhance BMD; however, obesity-related inflammation and alterations in adipokine signaling may negatively influence bone quality and increase fracture risk. Previous studies have shown that high BMI is associated with increased cortical thickness but also with compromised trabecular architecture.[ 31] Our findings align with this knowledge, as BMI was positively correlated with both trabecular and cortical bone parameters in our cohort. However, the consistently higher elevation of regression lines in YM consumers suggests that the positive effect of YM on BMD is independent of BMI-related mechanical factors.
Although the present study did not assess obesity-related parameters, it is worth noting that previous research has suggested a potential role of YM polyphenols in modulating energy metabolism, fat oxidation, metabolic rate, and body composition [32–34] through activation of AMPK-dependent and insulin signaling pathways.[35] Future studies should explore whether YM consumption affects adiposity and whether this could contribute to its association with improved BMD.
Fluctuations in sex hormones, particularly the decline in estrogen levels, lead to increased bone resorption and reduced bone formation. Further, vitamin D deficiency, particularly in postmenopausal women, is highly correlated with low BMD and fragility fractures and also with regulation of sex hormones and prolactin.[36,37] However, the interplay between YM, sex hormone fluctuations, and vitamin D pathways remains unexplored, highlighting the need for future studies on this topic.
Several biological pathways could explain the association between YM consumption and improved BMD. One of the most plausible mechanisms is the polyphenol content of YM, which has been extensively studied for its antioxidant properties.[38] Oxidative stress plays a critical role in bone loss, as it promotes osteoclastogenesis (bone resorption) while inhibiting bone formation.[15,16,39] Chlorogenic acid, the main polyphenol in YM, has been demonstrated to promote the proliferation of osteoblast precursors and osteoblastic differentiation of BMSCs via the Shp2/PI3K/Akt/cyclin D1 pathway and by down-regulation of receptor activator of nuclear factor-κB ligand (RANKL). [40,41] Polyphenols in YM have been implicated in upregulating Wnt signaling, which enhances osteoblast differentiation and inhibits osteoclast activity. Additionally, preclinical research suggests that certain bioactive compounds in YM may increase osteoprotegerin levels while decreasing RANKL.[42,43] Future research should aim to confirm these mechanisms through both in vivo and in vitro studies to better understand how YM consumption influences bone remodeling at a cellular level.
Recent studies have identified the incretin pathway, particularly glucagon-like peptide-1 (GLP-1), as a significant contributor to bone metabolism and health. GLP-1 has been shown to influence bone turnover by promoting bone formation and inhibiting bone resorption. Emerging research suggests that YM consumption may enhance GLP-1 activity, thereby potentially impacting bone health and sarcopenia modulating oxidative stress and insulin resistance.[44,45] However, direct evidence linking YM-induced GLP-1 modulation to bone health improvements is currently lacking.
Experimental studies have shown that YM mitigates the effects of low calcium intake on trabecular bone in young female rats.[13] Additionally, a low concentration of YM extract has been demonstrated to enhance the osteoblastic differentiation of mesenchymal cells [46] and reduce the deleterious effects of hydrogen peroxide on MC3T3-E1 osteoblastic cells.[47] While individual components isolated from YM have been found to increase the viability of MC3T3-E1 cells, the YM extract itself has also improved the viability of an osteocytic line (MLO-Y4) and differentiated MC3T3-E1 cells. This suggests the involvement of yet unidentified bioactive compounds within the extract.[48] Further studies are needed to elucidate the relationship between these experimental findings and the increased BMD observed in YM drinkers.
We also observed a lower fracture rate among YM drinkers. In the study by Conforti et al. [12], which assessed lumbar spine and femoral neck BMD, no significant difference in fracture rates was reported. This discrepancy may be explained by the stronger correlation between total hip BMD and fracture risk. Additionally, a case-control study from Brazil involving YM drinkers and non-drinkers found no difference in fracture rates, with both groups showing very high values. However, that study did not report BMD data, and the final analyzed sample consisted of only 95 women. [49] Despite these differences, the present findings suggest that the rate of low-impact fractures may indeed be lower among YM drinkers. Reference values for cortical and trabecular hip bone parameters in adult women and men from Argentina, obtained using DXA-based 3D modeling, have recently been published.[50] Notably, the median integral vBMD observed in YM drinkers (302.0 mg/cm3) aligns closely with the 50th percentile reported for healthy women aged 60 to 69 years (300.2 mg/cm3), whereas the corresponding value for the CG was lower (275.3 mg/cm3).
Several limitations should be acknowledged. First, the cross-sectional design prevents causal inferences, leaving unresolved whether YM consumption enhances BMD. While we controlled for major confounders, residual confounding (e.g., differences in physical activity or micronutrient intake) may persist. This fundamental limitation of observational research could only be resolved through longitudinal cohort studies or randomized controlled trials with standardized YM interventions. Second, our findings are limited to postmenopausal women and may not generalize to other populations. Third, while we used accurate criteria to define consumption and a history of low-impact fractures, self-reported data may be subject to recall bias and could be strengthened in future studies.
Our study provides novel insights into the relationship between YM consumption and bone health in postmenopausal women. Beyond confirming previous findings on the positive association between YM intake and BMD, we demonstrate for the first time that both cortical and trabecular compartments contribute to this effect, as assessed through DXA-based 3D modeling. Furthermore, our results suggest a potential protective role of YM against osteoporosis and fragility fractures. While these findings expand the current understanding of YM’s impact on bone health, further longitudinal and mechanistic studies are needed to establish causality and clarify the underlying biological mechanisms.
Notes
Acknowledgments
Galgo Medical (Spain) for providing temporary free licenses of 3D-Shaper software to carry out this study.
Funding
This study was partially funded by the National Scientific and Technical Research Council from Argentina (PIP 2021–2023 GI 11220200100085CO) to LRB.
Ethics approval and consent to participate
The study protocol was planned and conducted in full accordance with the ethical guidelines of the current version of the World Medical Association Declaration of Helsinki. It was reviewed and approved by the Committee on Research and Education of the Obra Social de Empleados Públicos of Mendoza and Ethics Committee of the School of Medicine, Rosario National University (Argentina) (800 20220700049UR).
Conflicts of interest
No potential conflict of interest relevant to this article was reported.