Obesity and type-2 diabetes mellitus (T2DM) are interrelated metabolic disorders primarily driven by overnutrition and physical inactivity, which oftentimes entails a transition from obesity to T2DM. Compromised musculoskeletal health consistently emerges as a common hallmark in the progression of these metabolic disorders. Skeletal muscle atrophy and dysfunction can further impair whole-body metabolism and reduce physical exercise capacity, thus instigating a vicious cycle that further deteriorates the underlying conditions. However, the myocellular repercussions of these metabolic disturbances remain to be completely clarified. Insulin signaling not only facilitates skeletal muscle glucose uptake but also plays a central role in skeletal muscle anabolism mainly due to suppression of catabolic pathways and facilitating an anabolic response to nutrient feeding. Chronic overnutrition may trigger different myocellular mechanisms proposed to contribute to insulin resistance and aggravate skeletal muscle atrophy and dysfunction. These mechanisms mainly include the inactivation of insulin signaling components through sustained activation of stress-related pathways, mitochondrial dysfunction, a shift to glycolytic skeletal muscle fibers, and hyperglycemia. In the present review, we aim to delve on these mechanisms, providing an overview of the myocellular processes involved in skeletal muscle atrophy and dysfunction under chronic overnutrition, and their contribution to the progression to T2DM.

Extracellular vesicles are membrane-enclosed secreted vesicles involved in cell-to-cell communication processes, identified in virtually all body fluids. Among extracellular vesicles, exosomes have gained increasing attention in recent years as they have unique biological origins and deliver different cargos, such as nucleic acids, proteins, and lipids, which might mediate various health processes. In particular, milk-derived exosomes are proposed as bioactive compounds of breast milk, which have been reported to resist gastric digestion and reach systemic circulation, thus being bioavailable after oral intake. In the present manuscript, we critically discuss the available evidence on the health benefits attributed to milk exosomes, and we provide an outlook for the potential future uses of these compounds. The use of milk exosomes as bioactive ingredients represents a novel avenue to explore in the context of human nutrition, and they might exert important beneficial effects at multiple levels, including but not limited to intestinal health, bone and muscle metabolism, immunity, modulation of the microbiota, growth, and development.

Hypohydration can impair aerobic performance and deteriorate cognitive function during exercise. To minimize hypohydration, athletes are recommended to commence exercise at least euhydrated, ingest fluids containing sodium during long-duration and/or high-intensity exercise to prevent body mass loss over 2% and maintain elevated plasma osmolality, and rapidly restore and retain fluid and electrolyte homeostasis before a second exercise session. To achieve these goals, the compositions of the fluids consumed are key; however, it remains unclear what can be considered an optimal formulation for a hydration beverage in different settings. While carbohydrate–electrolyte solutions such as sports drinks have been extensively explored as a source of carbohydrates to meet fuel demands during intense and long-duration exercise, these formulas might not be ideal in situations where fluid and electrolyte balance is impaired, such as practicing exercise in the heat. Alternately, hypotonic compositions consisting of moderate to high levels of electrolytes (i.e., ≥45 mmol/L), mainly sodium, combined with low amounts of carbohydrates (i.e., <6%) might be useful to accelerate intestinal water absorption, maintain plasma volume and osmolality during exercise, and improve fluid retention during recovery. Future studies should compare hypotonic formulas and sports drinks in different exercise settings, evaluating different levels of sodium and/or other electrolytes, blends of carbohydrates, and novel ingredients for addressing hydration and rehydration before, during, and after exercise.

The use of probiotic microorganisms in clinical practice has increased in recent years and a significant number of pregnant women are regular consumers of these products. However, probiotics might modulate the immune system, and whether or not this modulation is beneficial for perinatal outcomes is unclear. We performed a systematic review and meta-analysis to evaluate the reporting of perinatal outcomes in randomized controlled trials including women supplemented with probiotic microorganisms during pregnancy. We also analyzed the effects that the administration of probiotic microorganisms exerts on perinatal outcomes. In the review, 46 papers were included and 25 were meta-analyzed. Reporting of perinatal outcomes was highly inconsistent across the studies. Only birth weight, cesarean section, and weeks of gestation were reported in more than 50% of the studies. Random effects meta-analysis results showed that the administration of probiotic microorganisms during pregnancy did not have any a positive or negative impact on the perinatal outcomes evaluated. Subgroup analysis results at the strain level were not significantly different from main analysis results. The administration of probiotic microorganisms does not appear to influence perinatal outcomes. Nonetheless, future probiotic studies conducted in pregnant women should report probiotic strains and perinatal outcomes in order to shed light upon probiotics’ effects on pregnancy outcomes.

Anabolic resistance, consisting of a diminished ability of aging muscle to respond to anabolic stimuli such as exercise and protein intake, is a key contributor to age-related declines in muscle mass. However, diseases and lifestyle factors associated with aging, including insulin resistance states, overweight/obesity, persistent inflammation and specifically—as a focus herein—physical inactivity and inadequate dietary protein-intake habits, might interact with chronological impairments in muscle anabolism. In this context, master athletes, as individuals who have engaged in lifelong structured exercise, including regular training and sports participation, offer a valuable model for studying processes of chronological vs. inactivity-related aging. While these lifelong exercisers may present improved body composition parameters and other potential benefits in terms of muscle mass and function, it remains unclear whether exercise practice throughout life can prevent the development of anabolic resistance associated with aging. Albeit limited, evidence has indicated that even in lifelong-trained older individuals there is a blunted post-exercise muscle anabolic response compared to younger athletes. However, there is a paucity of data to systematically understand the differences in postprandial anabolic response to varying protein doses in older vs. young athletes. In lieu of the above, it seems reasonable that master athletes may benefit from increasing protein intake closer to the upper limit of current recommendations (1.6–2.0 g/kg/day). In addition, supplementing their diet with ingredients that have established anabolic potential, including branched chain amino acids (BCAAs) such as leucine, the leucine metabolite β-hydroxy-β-methylbutyrate (HMB), and n3-polyunsaturated fatty acids (n3-PUFA), may potentiate the anabolic response to protein and exercise.

Background: Aging is associated with sustained low-grade inflammation, which has been linked to age-related diseases and mortality. Long-term exercise programs have been shown to be effective to for attenuating this process; however, subsequent detraining might negate some of these benefits. Master athletes, as a model of lifelong consistent exercise practice, have been suggested to present similar inflammatory profiles to untrained young adults. Nonetheless, it is unclear whether maintaining training habits throughout life can completely counteract low-grade inflammation associated with aging. Objectives: We aimed to systematically evaluate comparisons of baseline inflammatory profiles in Master athletes, untrained middle-aged and older adults, and untrained young individuals to elucidate whether lifelong exercise can counteract low-grade inflammation associated with aging. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, and a protocol was prospectively registered in PROSPERO (CRD42024521339). Studies reporting baseline systemic levels of proinflammatory and anti-inflammatory markers in Master athletes and untrained controls were eligible for inclusion. A total of six databases (PubMed [MEDLINE], Embase, Cochrane Central Register of Controlled Trials [CENTRAL], Scopus, SPORTDiscus, and Web of Science [WoS]) were searched in September 2024, and studies were independently screened by two reviewers. Risk of bias was assessed using an adapted version of the Joanna Briggs Institute Critical Appraisal tool for cross-sectional trials, and random-effect meta-analyses of standardized mean differences (SMDs) of inflammatory markers were conducted to evaluate comparisons between Master athletes and age-matched untrained middle-aged and older adults as well as Master athletes and young untrained subjects. Subgroup analyses were performed based on exercise intensity and type, and participants’ sex. Results: A total of 17 studies (n = 649 participants) were included both in qualitative and quantitative synthesis. Lifelong exercise appears to attenuate increases in baseline C-reactive protein, and to elevate anti-inflammatory interleukin (IL)-10 levels compared with untrained middle-aged and older adults (C-reactive protein: SMD − 0.71, 95% confidence interval − 0.97, − 0.45, I ² 0%, p = 0.78; IL-10: SMD 1.44, 95% confidence interval 0.55, 2.32, I ² 87%, p < 0.00001). Statistical significance was maintained in C-reactive protein and IL-10 sub-analyses. No difference in tumor necrosis factor-α levels was observed between Master athletes and untrained middle-aged and older adults (SMD 0.40, 95% confidence interval − 0.15, 0.96, I ² 72%, p = 0.0008). A trend towards decreased IL-6 levels in Master athletes was shown in pooled analyses comparing untrained middle-aged and older adults, and rendered statistically significant in sub-analyses. However, comparisons with young untrained adults indicated that Master athletes still present with elevated levels of tumor necrosis factor-α and IL-6, along with decreased IL-10. Conclusions: Master athletes might exhibit a more anti-inflammatory profile denoted by decreased baseline circulating levels of C-reactive protein and, potentially, IL-6, along with increased IL-10 compared with healthy age-matched untrained peers. However, lifelong exercise might still be insufficient to completely counteract age-related changes in tumor necrosis factor-α, IL-6, and IL-10, as shown in comparisons with untrained young adults.