Leucine, isoleucine and valine are essential aminoacids termed branched-chain amino acids (BCAA) due to its aliphatic side-chain. In several pathological and physiological conditions increased BCAA plasma concentrations have been described. Elevated BCAA levels predict insulin resistance development. Moreover, BCAA levels higher than 2mmol/L are neurotoxic by inducing microglial activation in maple syrup urine disease. However, there are no studies about the direct effects of BCAA in circulating cells. We have explored whether BCAA could promote oxidative stress and pro-inflammatory status in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. In cultured PBMCs, 10mmol/L BCAA increased the production of reactive oxygen species (ROS) via both NADPH oxidase and the mitochondria, and activated Akt-mTOR signalling. By using several inhibitors and activators of these molecular pathways we have described that mTOR activation by BCAA is linked to ROS production and mitochondrial dysfunction. BCAA stimulated the activation of the redox-sensitive transcription factor NF-κB, which resulted in the release of pro-inflammatory molecules, such as interleukin-6, tumor necrosis factor-α, intracellular adhesion molecule-1 or CD40L, and the migration of PBMCs. In conclusion, elevated BCAA blood levels can promote the activation of circulating PBMCs, by a mechanism that involving ROS production and NF-κB pathway activation. These data suggest that high concentrations of BCAA could exert deleterious effects on circulating blood cells and therefore contribute to the pro-inflammatory and oxidative status observed in several pathophysiological conditions.

Introduction: Bariatric surgery is an efficient approach to rapidly reduce morbid obesity and associated comorbidities. However, approximately one-fourth of patients experience weight and comorbidity recurrence, and both obesity and bariatric surgery can lead to micronutrient deficiencies. Implementing a structured program of lifestyle modification (PLM) might enhance weight loss and improve micronutrient status. Methodology: A total of 121 severely obese patients underwent Roux-en-Y gastric bypass (RYGB). Among them, 71 adhered to a PLM involving dietary changes (low- and very-low-calorie Mediterranean diets) and physical exercises (aerobic and resistance training) both before and after surgery, while 50 patients followed a conventional protocol. Anthropometric measurements and serological parameter quantifications were conducted throughout the procedures. Results: The obese study population, primarily female (76.9%), with an average age of 47.11 ± 9.68, and a body mass index (BMI) of 44.68 ± 5.08 kg/m², underwent either RYGB with a PLM or a conventional procedure. Before surgery, the PLM group exhibited significant reductions in body weight (6.3%) and phosphoremia compared to the conventional protocol (0.78%). Post-RYGB, the PLM group demonstrated shortened in-hospital stays and further BMI reductions (−16.12 kg/m²) that persisted for up to 2 years. Furthermore, the PLM group experienced increased plasma vitamin D levels (14.79 ng/mL vs. 1.2 ng/mL) for up to 2 years, as well as elevated folic acid (1.52 vs. −0.29 ng/mL) and phosphorus (0.48 vs. 0.06 mg/dL) levels at 1 month and 1 year after intervention, respectively. Notably, these effects were independent of weight loss. Conclusions: Initiating a structured PLM from the early stages of patients’ preparation for RYGB could enhance and extend the benefits of weight loss and positively impact micronutrient (vitamin D, phosphorus, and folic acid) status in obese patients.

Background/Objectives: Primary aldosteronism (PA) is associated with a higher cardiovascular disease (CVD) risk than essential hypertension (EH) and is mainly driven by the excess of aldosterone production. Studies suggest a relationship between aldosterone and parathormone (PTH) homeostasis. Excessive PTH levels seem to also be associated with CVD. The impact of PTH levels on CVD in PA patients has not been totally elucidated. We evaluated the associations of PTH levels and hyperparathyroidism with CVD in patients with PA and EH. Methods: A cross-sectional study of a group of 67 patients was carried out, with 35 patients with PA and a control group of 32 patients with EH. We looked at the presence of CVD and data on the factors associated with its presence were collected and analyzed. A binary logistic regression was performed to assess multivariate relationships. Results: PA patients had higher PTH levels compared to the EH group (64 ± 42 vs. 39 ± 13 pg/mL, p = 0.004). Significative differences in PTH levels were observed according to the grade of hypertension in PA patients. Both hyperparathyroidism and CVD were found at higher rates in patients with PA. Patients with CVD exhibited significantly higher PAC values than patients without it (41.4 ± 18 vs. 21.4 ± 12 ng/dL, p < 0.001). Patients with hyperparathyroidism had higher rates of CVD than patients without it (58 vs. 24%, p = 0.018). Patients with PA and hyperparathyroidism manifested a higher rate of CVD than patients without this combination. A logistic regression showed an independent association of PAC and hyperparathyroidism with the presence of CVD in the total cohort. Conclusions: Hyperparathyroidism is associated with a higher probability of CVD both in PA and EH. The presence of hyperparathyroidism in PA seems to exacerbate the risk of CVD, with higher PTH levels associated with higher grades of hypertension in this cohort.

Inflammation and oxidative stress are key mechanisms in aging, contributing to neurodegenerative diseases, cardiovascular diseases, type 2 diabetes, obesity, and other conditions. In the aging process, the increase in reactive oxygen species and the decrease in antioxidant pathways damage cellular components, accelerating deterioration. Persistent inflammation and oxidative stress also favor the progression of diseases such as atherosclerosis, where LDL oxidation and infiltration in the arteries generate plaques that can lead to myocardial infarction or stroke. In addition, inflammation and oxidative stress can affect the immune system, as well as the development of chronic inflammatory diseases and nonalcoholic fatty liver disease, and may affect mental health, healthy menopause and muscle recovery. Research from both human studies and laboratory tests indicates that taking 80–320 mg per day of anthocyanin-rich extracts from bilberries and blackcurrants (Anthocyanin-EBB) can moderately enhance cholesterol levels, lower markers of inflammation, boost blood vessel health, increase insulin responsiveness, and reduce indicators linked to cardiovascular and metabolic risks. They also have antioxidant, anti-inflammatory and neuroprotective effects, helping in the prevention and management of chronic diseases. As a result, supplementation with anthocyanin-rich extracts may be a promising strategy to promote healthy aging and reduce the risk of development and progression of conditions related to oxidative stress and chronic inflammation. Nevertheless, due to the limited patient populations and short follow-up periods in most existing studies, long-term clinical trials are necessary to determine the definitive advantages of Anthocyanin-EBB in clinical practice.

Introduction: Obesity heterogeneity by sex and age is crucial for precise risk stratification. Limited phenotyping obscures sex-specific risks and contributes to diagnostic and treatment disparities. Methods: This is a cross-sectional study of 1,014 adults with obesity (68% women; median age 50) from four Madrid Obesity Centers using a digital pathway (OB-DigiThum) including anthropometry, bioimpedance, biomarkers, and comorbidity screening. Fat mass (FM) and skeletal muscle mass (SMM) were normalized to body surface area (FM/BSA; SMM/BSA). Participants were stratified into four predefined sex and age-groups (female <50, female ≥50, male <50, male ≥50). Multidimensional phenotyping was performed using discriminant analysis and hierarchical clustering applied to standardized group-level mean profiles. Results: Women had higher FM/BSA and lower SMM/BSA than men (p < 0.001), highlighting BMI’s limitations. With age, women’s BMI fell despite stable/increasing fat due to muscle loss (sarcopenic risk). Men showed more cardiometabolic disease overall, but post-menopausal women experienced sharp rises in type 2 diabetes, hypertension, and dyslipidemia. Psychological distress was more frequent in women; bulimic behaviors appeared in younger men. Physical inactivity was common; Mediterranean diet adherence was relatively strong, especially in participants aged ≥50 years. The four sex- and age-stratified profiles showed distinct patterns in body composition, metabolic risk, and psychological burden, supporting differential risk stratification across groups. Conclusion: Sex and age strongly shape obesity phenotypes. Post-menopausal women face accelerated metabolic deterioration and sarcopenia. FM/BSA and SMM/BSA enhance risk profiling. Sex- and age-tailored metabolic, physical, and mental health screening should guide personalized management.

Background/Objectives: Obesity care requires nutritional prescriptions that are individualized, nutritionally coherent, understandable, and feasible within high-volume clinical services. We describe the NUTRI-OBEDIGITHUM pathway, which integrates multidimensional digital phenotyping, clinician-supervised exchange-based nutritional prescription, patient-oriented materials, and structured education, and we report preliminary descriptive outcomes from a retrospective real-world cohort. Methods: This descriptive methodological and operational study included a retrospective observational analysis of anonymized routine-care data. NUTRI-OBEDIGITHUM integrates OBEDIGITHUM, a digitally enabled obesity-care pathway, with Dietcamb^®, a software-supported method that translates individualized energy and macronutrient targets into food exchanges, meal distributions, household measures, food lists, and example menus. The source database comprised 3928 unique patients. Among patients with a plausible baseline weight and an observable 6-month window, the eligible outcome was the measurement closest to day 183 within ±60 days, after prespecified plausibility checks. Baseline characteristics were compared descriptively according to outcome availability. Baseline medication exposure was assessed using free-text mentions only. Results: By the data cutoff, the 6-month window had opened for 3215 patients; 929 (28.9%) had an eligible 6-month weight and 2286 (71.1%) did not. In the analyzed cohort, mean age was 53.7 ± 14.0 years, 70.5% were women, and mean body mass index was 35.9 ± 6.3 kg/m². Mean weight changed from 98.5 ± 20.7 kg at baseline to 94.2 ± 20.3 kg at follow-up, corresponding to a descriptive paired change of −4.3 kg (95% CI −4.7 to −3.9); median total body-weight loss was 3.4%. Losses of at least 5%, 10%, and 15% were observed in 39.6%, 17.8%, and 6.4% of patients, respectively. A baseline GLP-1 receptor-agonist mention was present in 151/929 patients (16.3%); medication timing, dose, duration, dispensing, persistence, and adherence were unavailable. Conclusions: NUTRI-OBEDIGITHUM provides an operational framework for converting multidimensional obesity phenotyping into a structured, flexible, clinician-supervised, and patient-oriented nutritional prescription. The observed weight trajectories are descriptive complete-case findings from a selected, uncontrolled cohort and cannot establish the independent effectiveness of the pathway, Dietcamb^®, or pharmacotherapy. Prospective studies should evaluate reach, adoption, fidelity, usability, adherence, nutritional adequacy, safety, NUTRI-specific workload and cost, and metabolic outcomes.