Reytor González, Claudia
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Reytor González, Claudia
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Hot flashes: a potential marker of deterioration of health-related quality of life

2026 , Juan E. Blümel , María S. Vallejo , Peter Chedraui , Eugenio Arteaga , Félix Ayala , Ascanio Bencosme , Calle Miñaca, Andrés , Lucia Costa-Paiva , Maribel Dextre , Karen Díaz , Alejandra Elizalde-Cremonte , Santiago Elizalde-Cremonte , Carlos Escalante , María T. Espinoza , Ircania García , Gustavo Gómez-Tabares , Hugo Gutiérrez-Crespo , Marcela López , Juan Matsumura-Kasana , Paolo Meza , Álvaro Monterrosa-Castro , Mónica Ñañez , Eliana Ojeda , Claudia Rey , Ana Lucia Ribeiro Valadares , Doris Rodríguez-Vidal , Marcio AH. Rodrigues , Javier Saavedra , Carlos Salinas , Lida Sosa , Konstantinos Tserotas , Margot Acuña-San Martín , Marcela S. Aguirre

Objective: Hot flashes are among the most common symptoms of the menopausal transition and have traditionally been considered benign and self-limiting. However, increasing evidence suggests that they may indicate broader neurovascular and inflammatory dysregulation linked to reproductive aging. The possible effect of hot flush severity on health-related quality of life (HRQoL) remains inadequately studied, particularly in Latin American populations. This study aimed to examine the association between hot flash severity and HRQoL in middle-aged women using validated tools and a large, multicenter sample. Method: A cross-sectional study was conducted between June 2024 and January 2025 in 30 healthcare centers across 12 Latin American countries. A total of 3523 women aged 40–60 years were assessed using the Menopause Rating Scale (MRS) to evaluate vasomotor symptoms and the Short Form-36 Health Survey (SF-36) to measure HRQoL. Multivariable logistic regression models were utilized to estimate the association between hot flush severity and low HRQoL, adjusting for sociodemographic, behavioral and clinical covariates. Results: Increasing severity of hot flushes was significantly associated with lower HRQoL scores across all SF-36 domains. In the logistic regression analysis, mild hot flushes (MRS item 1 score = 1) were associated with increased odds of impaired HRQoL (odds ratio [OR] 1.29; 95% confidence interval [CI]: 1.08–1.55), whereas very severe symptoms (MRS item 1 score = 4) demonstrated a substantially stronger association (OR 4.10; 95% CI: 2.93–5.74). Additional factors significantly associated with lower HRQoL included physical inactivity, the presence of comorbidities, obesity, current use of psychotropic medication, age ≥50 years and having two or more children. Conclusion: Hot flush severity is a strong and independent determinant of HRQoL in midlife women. These findings underscore the need for systematic assessment and targeted management of vasomotor symptoms in routine care, supporting the hypothesis that hot flashes may be a clinical marker of systemic aging. © 2026 International Menopause Society.

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Dietary Diversity, Dietary Patterns, and Cardiometabolic Health in University Students: A Cross-Sectional Study

2026 , Diana Fonseca-Pérez , Ludwig Álvarez-Córdova , Cecilia Arteaga-Pazmiño , Víctor Sierra-Nieto , Cagua Ordoñez, Jaen , Evelyn Frias-Toral , Giovanna Muscogiuri , Reytor González, Claudia , Simancas Racines, Daniel

Cardiometabolic risk is increasingly observed in young adults, particularly during university years, and is not limited to individuals with elevated body mass index. Emerging evidence highlights the presence of normal weight obesity—characterized by excess adiposity and unfavorable body composition despite normal BMI—which may confer early metabolic vulnerability. Dietary diversity is often promoted as a marker of dietary adequacy; however, its relationship with adiposity, body composition, and muscular health remains inconsistent, particularly in Latin American populations. Moreover, few studies have directly contrasted dietary diversity indicators with empirically derived dietary patterns in relation to cardiometabolic and functional outcomes. Objective: To examine the associations between dietary diversity, dietary patterns, and indicators of adiposity, muscular strength, and relative muscle mass in Ecuadorian university students. Methods: A cross-sectional study was conducted among 349 undergraduate students aged 18–26 years enrolled in health sciences programs in Ecuador. Dietary intake was assessed using a validated food frequency questionnaire. Dietary diversity was quantified using the Food and Agriculture Organization’s Individual Dietary Diversity Score, while dietary patterns were identified through principal component analysis followed by k-means clustering. Outcomes included excess body weight, relative muscle mass assessed by bioelectrical impedance analysis, and handgrip strength. Multivariable Poisson and linear regression models were fitted, adjusting for age, sex, academic program, physical activity level, and pre-existing conditions. Results: Despite their young age and low prevalence of diagnosed disease, approximately one-third of the participants exhibited markers of early cardiometabolic risk, including excess body weight and central adiposity. Higher dietary diversity was independently associated with a higher prevalence of excess body weight (adjusted prevalence ratio per one-unit increase in IDDS: 1.17; 95% CI: 1.06–1.30) and with greater relative muscle mass (adjusted β = 0.13; 95% CI: 0.05–0.22), whereas no association was observed with handgrip strength. In contrast, dietary patterns derived from multivariate analysis showed no significant associations with adiposity, muscular strength, or relative muscle mass after adjustment. Conclusions: In this young adult population, dietary diversity captured aspects of overall dietary exposure associated with both increased adiposity and greater lean mass, but not with muscular strength. Empirically derived dietary patterns demonstrated limited discriminatory capacity, likely reflecting dietary homogeneity within the cohort. These findings indicate that dietary diversity alone does not necessarily reflect diet quality and underscore the importance of interpreting diversity metrics alongside indicators of food quality, energy density, and body composition when evaluating early cardiometabolic risk in contemporary food environments.

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The Oral–Gut–Immune–Nutrition Axis in Rheumatoid Arthritis: Molecular Mechanisms and Therapeutic Implications

2026 , Reytor González, Claudia , Náthaly Mercedes Román-Galeano , Lenin Saul Aules-Curicama , Camila Doménica Cevallos-Villacis , Erik González , Dolores Jima Gavilanes , Raquel Horowitz , Simancas Racines, Daniel

Rheumatoid arthritis is a chronic systemic autoimmune disease that arises from complex interactions among genetic susceptibility, environmental factors, and immune dysregulation. Growing evidence indicates that microorganisms residing in the oral cavity and gastrointestinal tract, together with dietary factors, play a central role in shaping inflammatory and autoimmune responses in rheumatoid arthritis, forming an interconnected microbiome–immune–nutrition axis. Alterations in the composition and function of oral and intestinal microbial communities are associated with disruption of mucosal barrier integrity, activation of innate and adaptive immune pathways, increased differentiation of proinflammatory T lymphocyte subsets, and loss of immune tolerance that promotes autoantibody production. In addition, microbially derived metabolites, particularly short-chain fatty acids, provide a mechanistic link between microbial ecology, immune regulation, and bone metabolism. Diet represents a key upstream modulator of this axis. Dietary patterns rich in anti-inflammatory nutrients support microbial diversity and immunoregulatory metabolite production, whereas diets high in processed foods and saturated fats favor proinflammatory microbial profiles. Accumulating clinical evidence suggests that nutritional strategies and microbiome-targeted dietary interventions may reduce systemic inflammation and disease-related comorbidities when used alongside standard pharmacological treatments. Taken together, the microbiome–immune–nutrition axis represents a modifiable and clinically meaningful target in rheumatoid arthritis, emphasizing the need for interdisciplinary research and well-designed clinical trials to translate these insights into personalized approaches for disease management. The aim of this review is to integrate current mechanistic and clinical evidence on the interactions between the microbiome, immune system, and nutrition in rheumatoid arthritis, with a focus on their pathogenic relevance, therapeutic potential, and implications for personalized, diet-based interventions.

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Molecular Bases of Myopathies and Their Impact on Clinical Practice: Advances and Future Perspectives

2026 , Martín Campuzano-Donoso , Reytor González, Claudia , Melannie Toral-Noristz , Yamilia González , Simancas Racines, Daniel

Myopathies represent a highly heterogeneous group of primary muscle disorders, traditionally classified based on clinical presentation and histopathological findings. Recent breakthroughs in molecular genetics, immunology, and pathophysiology have revolutionized the understanding, diagnosis, and management of these conditions. Both inherited and acquired forms of myopathy, including structural, metabolic, inflammatory, endocrine, and mitochondrial subtypes, are now recognized to arise from diverse pathogenic mechanisms such as impaired calcium handling, mitochondrial dysfunction, chronic inflammation, altered metabolism, and defective muscle regeneration. The advent of next-generation sequencing technologies has enabled more precise diagnosis of genetic forms, while the discovery of novel molecular biomarkers and immunological signatures offers promising avenues for disease monitoring and stratification across the broader spectrum. Importantly, molecular and mechanistic insights have redefined clinical classifications, allowing for better prognostic predictions and patient-tailored therapeutic approaches. Innovative treatments, including gene therapy, antisense oligonucleotide therapies, immune-modulating agents, metabolic support strategies, and targeted pharmacological interventions, are progressively translating molecular knowledge into clinical applications. However, technical limitations, biological variability, and ethical considerations continue to pose significant challenges to the implementation of precision medicine in myopathies. In this narrative review, we comprehensively discuss the latest molecular findings, their integration into clinical practice, and the emerging therapeutic strategies based on these discoveries. We also highlight current limitations and propose future research directions aimed at bridging the gap between molecular insights and effective, equitable patient care.

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Nutrition and longevity – diet in centenarians

2026 , Evelyn Frias-Toral , Reytor González, Claudia , Giuseppe Annunziata , Ludovica Verde , Emilia Jimenez-Flores , Keya Sen , Martina Galasso , Giovanna Muscogiuri , Simancas Racines, Daniel , Maria Dalamaga , Luigi Barrea

Background: Nutrition plays a central role in the biological mechanisms that shape aging, health span, and longevity. Micronutrients—including vitamins, trace elements, and polyphenols—support genomic stability, mitochondrial integrity, and antioxidant defense, while dietary patterns rich in plant-based foods modulate inflammation, metabolic regulation, and epigenetic processes. Centenarian populations consuming Mediterranean, Okinawan, Nordic, and Nicoyan diets offer a natural model for understanding how nutrient-rich, minimally processed foods, moderate caloric intake, and balanced lifestyles interact with molecular pathways to extend functional life. Main Body: This review synthesizes current evidence on how micronutrients influence DNA repair, oxidative stress reduction, and mitochondrial protection, particularly through the actions of vitamins C and E, niacin-dependent PARP activity, folate-mediated methylation, and metal cofactors involved in antioxidant enzymes. Plant-based diets rich in fiber and polyphenols enhance microbial diversity and promote beneficial taxa such as Akkermansia and Bifidobacterium, supporting gut barrier integrity and immune balance. Caloric restriction and intermittent fasting activate nutrient-sensing pathways, including AMPK and sirtuins, reduce mTOR activity, and stimulate autophagy, collectively improving cellular resilience. Findings from centenarian regions highlight the convergence of lifestyle, nutrition, and cultural practices that reduce systemic inflammation, maintain metabolic flexibility, and support healthy aging trajectories. Conclusions: Diet emerges as a decisive modifiable determinant of lifespan and health span. The convergence of molecular nutrition, microbiome composition, and traditional dietary habits underlies the exceptional longevity observed in centenarian populations. Future research should integrate nutrigenomics, metabolomics, and microbiome profiling to clarify causal mechanisms and guide precision nutrition strategies for aging societies. © The Author(s) 2026.

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Single vs. Dual Agonist Pharmacotherapy for Managing Insufficient Weight Loss and Weight Regain Following Metabolic and Bariatric Surgery: A Comparative Review

2026 , Reytor González, Claudia , Martín Campuzano-Donoso , Gerardo Sarno , Martha Montalvan , Raquel Horowitz , Gianluca Rossetti , Vincenzo Pilone , Luigi Barrea , Giovanna Muscogiuri , Luigi Schiavo , Simancas Racines, Daniel

Weight management after metabolic and bariatric surgery remains a persistent clinical challenge, particularly when patients experience insufficient weight loss or progressive weight regain following the postoperative nadir. In recent years, pharmacological therapies targeting gut-derived hormones have reshaped the therapeutic approach, offering nonsurgical strategies that directly influence appetite regulation, satiety, and energy balance. Single agonists acting on the glucagon-like peptide one receptor have demonstrated meaningful reductions in body weight among postoperative patients, while dual agonists that target both the glucagon-like peptide one receptor and the glucose-dependent insulinotropic polypeptide receptor have shown even greater weight reduction in early studies, suggesting enhanced therapeutic potential. These benefits, however, must be interpreted within the unique anatomical, nutritional, and behavioral context of individuals who have undergone metabolic and bariatric procedures, as they are inherently at higher risk for micronutrient deficiencies, gastrointestinal intolerance, and maladaptive eating patterns. Successful treatment requires a balanced integration of pharmacotherapy, individualized nutritional guidance, psychological support, and a patient-centered model of long-term care. Although emerging evidence is promising, dedicated clinical trials are still needed to directly compare the efficacy, safety, and sustainability of single versus dual agonist therapies in postoperative populations. Furthermore, culturally sensitive dietary strategies and shared decision-making processes are essential to enhance adherence, optimize long-term outcomes, and ensure equitable access to treatment. Ultimately, these therapies represent a significant advance in addressing postoperative weight challenges, but their full potential will rely on comprehensive, multidisciplinary frameworks that support both biological and behavioral aspects of chronic weight management.

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Endometriosis as a Systemic and Complex Disease: Toward Phenotype-Based Classification and Personalized Therapy

2026 , Simancas Racines, Daniel , Emilia Jiménez-Flores , Martha Montalvan , Raquel Horowitz , Valeria Araujo , Reytor González, Claudia

Endometriosis is traditionally conceptualized as a pelvic lesion–centered disease; however, mounting evidence indicates it is a chronic, systemic, and multifactorial inflammatory disorder. This review examines the molecular dialog between ectopic endometrial tissue, the immune system, and peripheral organs, highlighting mechanisms that underlie disease chronicity, symptom variability, and therapeutic resistance. Ectopic endometrium exhibits distinct transcriptomic and epigenetic signatures, disrupted hormonal signaling, and a pro-inflammatory microenvironment characterized by inflammatory mediators, prostaglandins, and matrix metalloproteinases. Immune-endometrial crosstalk fosters immune evasion through altered cytokine profiles, extracellular vesicles, immune checkpoint molecules, and immunomodulatory microRNAs, enabling lesion persistence. Beyond the pelvis, systemic low-grade inflammation, circulating cytokines, and microRNAs reflect a molecular spillover that contributes to chronic pain, fatigue, hypothalamic–pituitary–adrenal axis dysregulation, and emerging gut–endometrium interactions. Furthermore, circulating biomarkers—including microRNAs, lncRNAs, extracellular vesicles, and proteomic signatures—offer potential for early diagnosis, patient stratification, and monitoring of therapeutic responses. Conventional hormonal therapies demonstrate limited efficacy, whereas novel molecular targets and delivery systems, including angiogenesis inhibitors, immune modulators, epigenetic regulators, and nanotherapeutics, show promise for precision intervention. A systems medicine framework, integrating multi-omics analyses and network-based approaches, supports reconceptualizing endometriosis as a systemic inflammatory condition with gynecologic manifestations. This perspective emphasizes the need for interdisciplinary collaboration to advance diagnostics, therapeutics, and individualized patient care, ultimately moving beyond a lesion-centered paradigm toward a molecularly informed, holistic understanding of endometriosis.

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Natural Products Targeting Key Molecular Hallmarks in Gastric Cancer: Focus on Apoptosis, Inflammation, and Chemoresistance

2026 , Simancas Racines, Daniel , Cagua Ordoñez, Jaen , Angamarca Iguago, Jaime , Parise Vasco, Juan Marcos , Reytor González, Claudia

Natural products have emerged as promising multi-target agents for addressing the complex biology of gastric cancer, a malignancy characterized by marked molecular heterogeneity, late clinical presentation, and frequent resistance to systemic therapies. This narrative synthesis integrates primarily preclinical evidence, with emerging clinical data, on how naturally derived compounds modulate three central molecular processes that drive gastric tumor progression and therapeutic failure: evasion of programmed cell death, persistent tumor-promoting inflammation, and chemoresistance. Compounds such as curcumin, resveratrol, berberine, ginsenosides, quercetin, and epigallocatechin gallate restore apoptotic competence by shifting the balance between pro-survival and pro-death proteins, destabilizing mitochondrial membranes, promoting cytochrome c release, and activating caspase-dependent pathways. These agents also exert potent anti-inflammatory effects by inhibiting nuclear factor kappa B and signal transducer and activator of transcription signaling, suppressing pro-inflammatory cytokine production, reducing cyclooxygenase activity, and modulating the tumor microenvironment through changes in immune cell behavior. In parallel, multiple natural compounds function as chemo-sensitizers by inhibiting drug efflux transporters, reversing epithelial–mesenchymal transition, attenuating cancer stem cell-associated traits, and suppressing pro-survival signaling pathways that sustain resistance. Collectively, these mechanistic actions highlight the capacity of natural products to simultaneously target interconnected hallmarks of gastric cancer biology. Ongoing advances in formulation strategies may help overcome pharmacokinetic limitations; however, rigorous biomarker-guided studies and well-designed clinical trials remain essential to define the translational relevance of these compounds.

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Physical activity as an alternative or adjunct to menopausal hormone therapy for symptom management in women with primary ovarian insufficiency

2026 , Félix Ayala , Juan E. Blümel , María S. Vallejo , Peter Chedraui , Hugo Gutiérrez-Crespo , Marcela López , Juan Matzumura-Kasana , Paolo Meza , Álvaro Monterrosa-Castro , Mónica Ñañez , Eliana Ojeda , Claudia Rey , Ana Lucia Ribeiro Valadares , Doris Rodríguez-Vidal , Marcio A.H. Rodrigues , Javier Saavedra , Carlos Salinas , Lida Sosa , Konstantinos Tserotas , Margot Acuña-San Martín , Marcela S. Aguirre , Eugenio Arteaga , Ascanio Bencosme , Calle Miñaca, Andrés , Lucia Costa-Paiva , Maribel Dextre , Karen Díaz , Alejandra Elizalde-Cremonte , Santiago Elizalde-Cremonte , Carlos Escalante , María T. Espinoza , Ircania García , Gustavo Gómez-Tabares

Background: Physical activity alleviates menopausal symptoms in women whose menopause occurs after the age of 45; however, its effect in primary ovarian insufficiency, which occurs before the age of 40, remains unknown. Objective: To examine the association between physical activity, menopausal symptoms, and the use of menopausal hormone therapy in women with primary ovarian insufficiency. Methods: We analysed data from 4708 participants from two studies conducted in 12 Latin American countries. After applying eligibility criteria, 564 women with primary ovarian insufficiency (351 idiopathic and 213 surgical) were included. Menopausal symptoms were assessed using a validated scale, and severe symptoms were defined according to established cut-offs. Physical activity was classified according to international recommendations for moderate-intensity activity. Logistic regression models were adjusted for sociodemographic, clinical, and lifestyle variables. Results: The prevalence of severe menopausal symptoms was 39.2%, with no significant difference between idiopathic and surgical primary ovarian insufficiency. Women with severe symptoms were less likely to meet recommended levels of physical activity or to be current users of menopausal hormone therapy. In adjusted models, regular physical activity (OR 0.65; 95% CI 0.45–0.94) and current use of menopausal hormone therapy (OR 0.27; 0.17–0.42) were associated with a lower likelihood of severe symptoms, whereas obesity and use of psychotropic medication were associated with a higher likelihood. Conclusions: Women with primary ovarian insufficiency who engage in regular physical activity or currently use menopausal hormone therapy report less severe menopausal symptoms. Regular exercise may be an important non-hormonal option for women who cannot or prefer not to use hormone therapy. © 2026 Elsevier B.V.

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Obesity, Bariatric Surgery, and Cancer Risk: Nutritional Perspectives and Long-Term Clinical Implications

2026 , Reytor González, Claudia , Gerardo Sarno , Martha Montalvan , Ludovica Verde , Giuseppe Annunziata , Luigi Barrea , Giovanna Muscogiuri , Simancas Racines, Daniel

Obesity is recognized as a causal risk factor for the development of multiple cancers, with risk magnitude varying by tumor site, sex, life stage, and adipose tissue distribution. This narrative review synthesizes recent epidemiological evidence linking excess body fatness with cancer incidence and mortality and integrates the biological mechanisms that explain this association. Chronic low-grade inflammation, insulin resistance with compensatory hyperinsulinemia, dysregulation of adipose-derived hormones and sex steroids, impairment of anti-tumor immune responses, alterations in the gut microbiota, and remodeling of the tumor microenvironment collectively create conditions that favor tumor initiation and progression. Bariatric surgery is the most effective clinical intervention for achieving substantial and sustained weight loss in individuals with severe obesity, and growing evidence indicates that it is associated with a reduction in overall cancer risk and cancer-related mortality, particularly for malignancies strongly linked to obesity. However, the extent of this benefit differs by surgical technique and remains less consistent for colorectal cancer. Beyond metabolic improvements, bariatric surgery produces long-term changes in nutritional physiology that may also influence oncologic outcomes. Persistent deficiencies of micronutrients such as iron, folate, vitamin B12, vitamin D, and calcium can affect DNA synthesis, methylation, oxidative balance, and cellular repair. Altered protein and energy intake may contribute to loss of lean mass and reduced metabolic resilience, while changes in alcohol absorption and metabolism can increase systemic exposure to ethanol and its carcinogenic metabolites. In addition, bariatric surgery induces sustained remodeling of the gut microbiome and bile acid metabolism, which may further modulate tumorigenic signaling. Overall, the oncological impact of bariatric surgery reflects a balance between metabolic improvement and long-term nutritional management, underscoring the need for structured follow-up and targeted nutritional strategies to optimize cancer risk reduction.

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