Relationship of endogenous plasma concentrations of ß-hydroxy ß-methyl butyrate (HMB) with frailty in community dwelling older adults with type-2 diabetes mellitus.

BACKGROUND: Supplementation with ß-hydroxy ß-methyl butyrate (HMB) appears to be effective in preserving muscle in older adults. However, the association between endogenously produced HMB with frailty has not been studied in people with chronic disease. OBJECTIVES: The purpose of this study is to explore whether an association exists between endogenous HMB levels and frailty status in older adults with type-2 diabetes mellitus (T2DM). METHODS: Data were taken from the Toledo Study of Healthy Ageing, a community-dwelling aged (65 years+) cohort. Frailty was assessed at baseline and at 2.99 median years according to the Frailty Phenotype (FP) standardized to our population and the Frailty Trait Scale 12 (FTS12). The associations between HMB levels and frailty were assessed using three nested multivariate logistic regressions and segmented by sex. Glucose, HMB and glucose interaction, age and body composition were used as covariables. RESULTS: 255 participants (mean age 75.3 years, 52.94% men) were included. HMB levels showed an inverse cross-sectional association with frailty, which was modified when the interaction term HMB*glucose was included, remaining significant only for FTS12 [OR (95% CI): 0.436 (0.253, 0.751), p-value 0.003]. The association between HMB endogenous levels and FTS12 appears to be independent of sex, in which the association was maintained after adjusting for the covariates. However, there appears to be threshold points for glucose levels, above which the protective effect of HMB is lost: 145.4 mg/dl adjusted by gender for the whole sample and 149.6 mg/dl and 138.9 mg/dl for men and women, respectively. Endogenous HMB levels were not found to be associated with incident frailty. CONCLUSIONS: Cross-sectional analysis revealed that endogenous HMB levels were inversely associated with frailty as assessed by the FTS12 in older people with T2DM. This association was found to be dependent on circulating fasted glucose levels.

Management of CRSwNP in Latin America: A multidisciplinary consensus from an expert working group.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory condition of the nasal and paranasal tissues, characterized by the presence of bilateral nasal polyps. While etiology and pathogenetic mechanisms are heterogeneous and complex, in most patients, disease is mediated predominantly through type 2 inflammatory processes. Clinical management is challenging, and a multidisciplinary approach is preferred. Principal treatment approaches are the use of local/systemic corticosteroids and sinonasal surgery, although outcomes can be unsatisfactory. Recent availability of biological therapies targeting underlying inflammatory processes can offer effective treatment options in uncontrolled disease. Specialist guidelines greatly assist clinical decision-making, although as these are chiefly written from a global/international perspective, they may not wholly accommodate disease patterns and clinical practice at a regional level. An expert panel of specialists from Latin America was convened to develop regional guidance on the management of CRSwNP through a consensus approach. The present article presents the chief observations and recommendations which can provide guidance for clinicians in the Latin American region.

The Vicious Cycle of Type 2 Diabetes Mellitus and Skeletal Muscle Atrophy: Clinical, Biochemical, and Nutritional Bases.

Today, type 2 diabetes mellitus (T2DM) and skeletal muscle atrophy (SMA) have become increasingly common occurrences. Whether the onset of T2DM increases the risk of SMA or vice versa has long been under investigation. Both conditions are associated with negative changes in skeletal muscle health, which can, in turn, lead to impaired physical function, a lowered quality of life, and an increased risk of mortality. Poor nutrition can exacerbate both T2DM and SMA. T2DM and SMA are linked by a vicious cycle of events that reinforce and worsen each other. Muscle insulin resistance appears to be the pathophysiological link between T2DM and SMA. To explore this association, our review (i) compiles evidence on the clinical association between T2DM and SMA, (ii) reviews mechanisms underlying biochemical changes in the muscles of people with or at risk of T2DM and SMA, and (iii) examines how nutritional therapy and increased physical activity as muscle-targeted treatments benefit this population. Based on the evidence, we conclude that effective treatment of patients with T2DM-SMA depends on the restoration and maintenance of muscle mass. We thus propose that regular intake of key functional nutrients, along with guidance for physical activity, can help maintain euglycemia and improve muscle status in all patients with T2DM and SMA.

Coronary Flow Reserve and Myocardial Resistance Reserve Changes After Transcatheter Aortic Valve Implantation in Aortic Stenosis.

Aortic valve stenosis (AS) induces an alteration in hemodynamic conditions that are responsible for coronary microvasculature impairment. Relief of AS by transcatheter aortic valve implantation (TAVI) is expected to improve the coronary artery hemodynamic. We aimed to assess the midterm effects of TAVI in coronary flow reserve (CFR) and myocardial resistance reserve (MRR) by a continuous intracoronary thermodilution technique. At-rest and hyperemic coronary flow was measured by a continuous thermodilution technique in 23 patients with AS and compared with that in 17 matched controls, and repeated 6 ± 3 months after TAVI in 11 of the patients with AS. In patients with AS, absolute coronary flow at rest was significantly greater, and absolute resistance at rest was significantly less, than in controls (p <0.01 for both), causing less CFR and MRR (1.73 ± 0.4 vs 2.85 ± 1.1, p <0.01 and 1.95 ± 0.4 vs 3.22 ± 1.4, p <0.01, respectively). TAVI implantation yielded a significant 35% increase in CFR (p >0.01) and a 39% increase in MRR (p <0.01) driven by absolute coronary flow at rest reduction (p = 0.03). In patients with AS, CFR and MRR determined by continuous thermodilution are significantly impaired. At 6-month follow-up, TAVI improves these indexes and partially relieves the pathophysiologic alterations, leading to a partial restoration of CFR and MRR.

Arginine and Lysine Supplementation Potentiates the Beneficial ß-Hydroxy ß-Methyl Butyrate (HMB) Effects on Skeletal Muscle in a Rat Model of Diabetes.

Skeletal muscle is the key tissue for maintaining protein and glucose homeostasis, having a profound impact on the development of diabetes. Diabetes causes deleterious changes in terms of loss of muscle mass, which will contribute to reduced glucose uptake and therefore progression of the disease. Nutritional approaches in diabetes have been directed to increase muscle glucose uptake, and improving protein turnover has been at least partially an oversight. In muscle, ß-hydroxy ß-methyl butyrate (HMB) promotes net protein synthesis, while arginine and lysine increase glucose uptake, albeit their effects on promoting protein synthesis are limited. This study evaluates if the combination of HMB, lysine, and arginine could prevent the loss of muscle mass and function, reducing the progression of diabetes. Therefore, the combination of these ingredients was tested in vitro and in vivo. In muscle cell cultures, the supplementation enhances glucose uptake and net protein synthesis due to an increase in the amount of GLUT4 transporter and stimulation of the insulin-dependent signaling pathway involving IRS-1 and Akt. In vivo, using a rat model of diabetes, the supplementation increases lean body mass and insulin sensitivity and decreases blood glucose and serum glycosylated hemoglobin. In treated animals, an increase in GLUT4, creatine kinase, and Akt phosphorylation was detected, demonstrating the synergic effects of the three ingredients. Our findings showed that nutritional formulations based on the combination of HMB, lysine, and arginine are effective, not only to control blood glucose levels but also to prevent skeletal muscle atrophy associated with the progression of diabetes.

The Global Otolaryngology-Head and Neck Surgery Workforce.

Importance: A core component of delivering care of head and neck diseases is an adequate workforce. The World Health Organization report, Multi-Country Assessment of National Capacity to Provide Hearing Care, captured primary workforce estimates from 68 member states in 2012, noting that response rates were a limitation and that updated more comprehensive data are needed. Objective: To establish comprehensive workforce metrics for global otolaryngology-head and neck surgery (OHNS) with updated data from more countries/territories. Design, Setting, and Participants: A cross-sectional electronic survey characterizing the OHNS workforce was disseminated from February 10 to June 22, 2022, to professional society leaders, medical licensing boards, public health officials, and practicing OHNS clinicians. Main Outcome: The OHNS workforce per capita, stratified by income and region. Results: Responses were collected from 121 of 195 countries/territories (62%). Survey responses specifically reported on OHNS workforce from 114 countries/territories representing 84% of the world's population. The global OHNS clinician density was 2.19 (range, 0-61.7) OHNS clinicians per 100 000 population. The OHNS clinician density varied by World Bank income group with higher-income countries associated with a higher density of clinicians. Regionally, Europe had the highest clinician density (5.70 clinicians per 100 000 population) whereas Africa (0.18 clinicians per 100 000 population) and Southeast Asia (1.12 clinicians per 100 000 population) had the lowest. The OHNS clinicians deliver most of the surgical management of ear diseases and hearing care, rhinologic and sinus diseases, laryngeal disorders, and upper aerodigestive mucosal cancer globally. Conclusion and Relevance: This cross-sectional survey study provides a comprehensive assessment of the global OHNS workforce. These results can guide focused investment in training and policy development to address disparities in the availability of OHNS clinicians.

Biomarkers of post-match recovery in semi-professional and professional football (soccer).

High-level football (soccer) players face intense physical demands that result in acute and residual fatigue, impairing their physical performance in subsequent matches. Further, top-class players are frequently exposed to match-congested periods where sufficient recovery times are not achievable. To evaluate training and recovery strategies, the monitoring of players' recovery profiles is crucial. Along with performance and neuro-mechanical impairments, match-induced fatigue causes metabolic disturbances denoted by changes in chemical analytes that can be quantified in different body fluids such as blood, saliva, and urine, thus acting as biomarkers. The monitoring of these molecules might supplement performance, neuromuscular and cognitive measurements to guide coaches and trainers during the recovery period. The present narrative review aims to comprehensively review the scientific literature on biomarkers of post-match recovery in semi-professional and professional football players as well as provide an outlook on the role that metabolomic studies might play in this field of research. Overall, no single gold-standard biomarker of match-induced fatigue exists, and a range of metabolites are available to assess different aspects of post-match recovery. The use of biomarker panels might be suitable to simultaneously monitoring these broad physiological processes, yet further research on fluctuations of different analytes throughout post-match recovery is warranted. Although important efforts have been made to address the high interindividual heterogeneity of available markers, limitations inherent to these markers might compromise the information they provide to guide recovery protocols. Further research on metabolomics might benefit from evaluating the long-term recovery period from a high-level football match to shed light upon new biomarkers of post-match recovery.

Natural Vitamin E Supplementation during Pregnancy in Rats Increases RRR-α-Tocopherol Stereoisomer Proportion and Enhances Fetal Antioxidant Capacity, Compared to Synthetic Vitamin E Administration.

INTRODUCTION: Low dietary intake of vitamin E is a global public health issue. RRR-α-tocopherol (RRR-αT) is the only naturally occurring vitamin E stereoisomer, but the equimolecular mixture of all eight stereoisomers, synthetic vitamin E (S-αT), is commonly consumed. The objective of this study was to evaluate bioavailability and antioxidant activity of RRR-αT versus S-αT, in both mother and fetus, after maternal supplementation during pregnancy. METHODS: Female rats (7 weeks of age) received a modified AIN-93G diet supplemented with 75 IU/kg of RRR-αT (NVE, n = 20) or S-αT (SVE, n = 17). At delivery, the levels of αT, stereoisomer distribution, and antioxidant capacity were analyzed in maternal and fetal plasma. RESULTS: NVE administration significantly increased the proportion of RRR-αT stereoisomer in maternal and fetal plasma. The percentage of RRR-αT increased from 32.76% to 88.33% in maternal plasma, and 35.25% to 97.94% in fetal plasma, in the NVE group compared to SVE. Fetal plasma from the NVE group was found to have higher total antioxidant capacity compared to SVE. Lastly, fetal plasma RRR-αT stereoisomer percentage was positively associated with expression levels of scavenger receptor class B type 1 (SR-B1) in the placenta. CONCLUSIONS: Both natural and synthetic sources of vitamin E showed similar bioavailability. Still, NVE supplementation increased the proportion of RRR-αT and promoted higher antioxidant activity in fetal plasma at birth. Placental SR-B1 might be involved in the stereoselective transfer of RRR-αT stereoisomer across the placenta and may improve αT bioactivity in the fetus.

Compositional Aspects of Beverages Designed to Promote Hydration Before, During, and After Exercise: Concepts Revisited.

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.

Guía de práctica clínica para el tratamiento de la rinosinusitis crónica: versión completa / Clinical practice guideline for the treatment of chronic rhinosinusitis: full version

La rinosinusitis (RS) se define como la inflamación de la nariz y los senos paranasales con dos o más síntomas como bloqueo/obstrucción/congestión o secreción nasal (goteo nasal anterior/posterior) más dolor/presión facial y/o reducción o pérdida del sentido del olfato. Adicional, se tienen en cuenta los hallazgos objetivos como la presencia de pólipos nasales y/o descarga mucopurulenta en meato medio y/o edema u obstrucción de la mucosa en el meato medio en la endoscopia nasal. Se pueden considerar o no, los cambios tomográficos como cambios mucosos en el complejo osteomeatal y la mucosa de los senos paranasales. Se reconoce que los síntomas tienen alta sensibilidad, pero baja especificidad, de ahí la necesidad de hallazgos objetivos.

Rhinosinusitis (RS) is defined as inflammation of the nose and sinuses with two or more symptoms such as blockage/obstruction/congestion or nasal discharge. with two or more symptoms such as nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior runny nose) plus facial pain/pressure and/or reduction or loss of the sense of smell. sense of smell. In addition, objective findings such as the presence of nasal polyps and/or nasal presence of nasal polyps and/or mucopurulent discharge from the middle meatus and/or edema or mucosal obstruction or mucosal obstruction in the middle meatus on nasal endoscopy. Tomographic changes may or may not tomographic changes may or may not be considered as mucosal changes in the osteomeatal complex and mucosal osteomeatal complex and the mucosa of the paranasal sinuses. It is recognized that the symptoms symptoms have high sensitivity but low specificity, hence the need for objective findings. findings.

Guía de práctica clínica para el tratamiento de la rinosinusitis crónica: versión corta para profesionales de la salud. Colombia-2023 / Clinical practice guideline for the management of chronic rhinosinusitis: short version for health care professionals. Colombia-2023

La rinosinusitis (RS) se define como la inflamación de la nariz y los senos paranasales con dos o más síntomas como bloqueo/obstrucción/congestión o secreción nasal (goteo nasal anterior/posterior) más dolor/presión facial y/o reducción o pérdida del sentido del olfato. Adicional, se tienen en cuenta los hallazgos objetivos como la presencia de pólipos nasales y/o descarga mucopurulenta en meato medio y/o edema u obstrucción de la mucosa en el meato medio en la endoscopia nasal.

Rhinosinusitis (RS) is defined as inflammation of the nose and sinuses with two or more symptoms such as blockage/obstruction/congestion or nasal discharge with two or more symptoms such as nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior runny nose) plus facial pain/pressure and/or reduced or lost sense of smell sense of smell. Additionally, objective findings such as the presence of nasal polyps and/or nasal presence of nasal polyps and/or mucopurulent discharge in the middle meatus and/or edema or mucous or mucosal obstruction in the middle meatus on nasal endoscopy.

Intake of slow-digesting carbohydrates is related to changes in the microbiome and its functional pathways in growing rats with obesity induced by diet.

Introduction: The main cause of insulin resistance in childhood is obesity, which contributes to future comorbidities as in adults. Although high-calorie diets and lack of exercise contribute to metabolic disease development, food quality rather than the quantity of macronutrients is more important than food density. The purpose of the present study was to examine the effects of changing the quality of carbohydrates from rapidly to slowly digestible carbohydrates on the composition of the gut microbiota and the profiles of the functional pathways in growing rats with obesity due to a high-fat diet (HFD). Methods: During the course of 4 weeks, rats growing on an HFD-containing carbohydrates with different digestive rates were fed either HFD-containing carbohydrates with a rapid digestion rate (OBE group) or HFD-containing carbohydrates with a slow digestion rate (OBE-ISR group). A non-obese group (NOB) was included as a reference, and rats were fed on a rodent standard diet (AIN93G). An analysis of gut microbiota was conducted using 16S rRNA-based metagenomics; a linear mixed-effects model (LMM) was used to determine changes in abundance between baseline and 4 weeks of treatment, and functional pathways were identified. Gut microbiota composition at bacterial diversity and relative abundance, at phylum and genus levels, and functional profiles were analyzed by integrating the Integrated Microbial Genomes (IMG) database. Results: The groups showed comparable gut microbiota at baseline. At the end of the treatment, animals from the ISR group exhibited differences at the phylum levels by decreasing the diversity of Fisher's index and Firmicutes (newly named as Bacillota), and increasing the Pielou's evenness and Bacteroidetes (newly named as Bacteroidota); at the genus level by increasing Alistipes, Bifidobacterium, Bacteroides, Butyricimonas, Lachnoclostridium, Flavonifractor, Ruminiclostridium 5, and Faecalibaculum and decreasing Muribaculum, Blautia, and Ruminiclostridium 9. Remarkably, relative abundances of genera Tyzzerella and Angelakisella were higher in the OBE group compared to NOB and OBE-ISR groups. In addition, some microbiota carbohydrate metabolism pathways such as glycolysis, glucuronic acid degradation, pentose phosphate pathway, methanogenesis, and fatty acid biosynthesis exhibited increased activity in the OBE-ISR group after the treatment. Higher levels of acetate and propionate were found in the feces of the ISR group compared with the NOB and OBE groups. Conclusion: The results of this study demonstrate that replacing rapidly digestible carbohydrates with slowly digestible carbohydrates within an HFD improve the composition of the gut microbiota. Consequently, metabolic disturbances associated with obesity may be prevented.

Early recruitable coronary collaterals preserve miocardial viability in late presentation infarctions.

BACKGROUND: Previous studies showed conflicting results regarding the contribution of coronary collateral circulation (CCC) to myocardial perfusion and function in the setting of myocardial infarction (MI). In the primary angioplasty era, the role of CCC in these studies may have been influenced by the effect of early reperfusion. The true impact of CCC could be clarified by studying its effect on nonreperfused patients. The aim of our study was to evaluate the effect of CCC on myocardial viability of late presentation MI. METHODS AND RESULTS: Between 2008 and 2019, we included 167 patients with a late presentation MI who had a complete angiographic occlusion in a major coronary artery in which myocardial viability of the culprit territory was assessed. Patients were divided according to the presence of angiographic early recruited CCC (ERCC) (Rentrop 2-3) or poor CCC (PCC) (Rentrop 0-1). A lower left ventricular ejection function (LVEF) at discharge (54.2 ± 9 vs. 47.9 ± 12; <0.01) and a more severe left ventricular wall motion abnormalities in the culprit territory were observed in PCC patients. The presence of ERCC was the main independent predictor of myocardial viability in late presentation MI (hazard ratio, 4.24; 95% confidence interval, 1.68-10.6; P < 0.001). At follow-up, wall motion score increased significantly (2.05 ± 0.16; P = 0.02) in patients with ERCC but not in PCC patients (0.07 ± 0.16; P = 0.4), and LVEF improvement was significantly higher in ERCC than in PCC patients (9.7 ± 2.6 vs. 3.8 ± 4.2; P = 0.02). CONCLUSION: The presence of ERCC was the main independent predictor of myocardial viability in late presentation MI.

Calcifediol During Pregnancy Improves Maternal and Fetal Availability of Vitamin D Compared to Vitamin D3 in Rats and Modifies Fetal Metabolism.

The fetus depends on the transplacental transfer of vitamin D. Calcifediol (25-OH-D3) is the vitamin D metabolite that crosses the placenta. Previously, oral 25-OH-D3 improved serum 25-OH-D3 compared to vitamin D3 in non-pregnant subjects, although no studies are available in pregnant women. We evaluated the availability of oral 25-OH-D3 compared to vitamin D3 during pregnancy, as well as, their levels in the fetus and effect on metabolism-related proteins. Twenty female rats per group were fed with 25 µg/kg of diet of vitamin D3 (1,000 UI vitamin D/kg diet) or with 25 µg/kg diet of 25-OH-D3. We analyzed 25-OH-D3 levels in maternal and fetal plasma; protein levels of vitamin D receptor (VDR), fatty acid translocase (FAT), and scavenger-receptor class B type-1 (SR-B1) in both maternal liver and placenta; and protein levels of VDR and Glutamate decarboxylase (GAD67) in fetal brain. 25-OH-D3 doubled the concentration of 25-OH-D3 in both maternal and fetal plasma compared to vitamin D3. In addition, maternal liver VDR, FAT, and SR-BI increased significantly in the 25-OH-D3 group, but no changes were found in the placenta. Interestingly, 25-OH-D3 decreased GAD67 expression in the fetal brain and it also tended to decrease VDR (P = 0.086). In conclusion, 25-OH-D3 provided better vitamin D availability for both mother and fetus when administered during pregnancy compared to vitamin D3. No adverse effects on pregnancy outcomes were observed. The effects of 25-OH-D3 on the expression of VDR and GAD67 in fetal brain require further investigation.

Quality More Than Quantity: The Use of Carbohydrates in High-Fat Diets to Tackle Obesity in Growing Rats.

Childhood obesity prevention is important to avoid obesity and its comorbidities into adulthood. Although the energy density of food has been considered a main obesogenic factor, a focus on food quality rather that the quantity of the different macronutrients is needed. Therefore, this study investigates the effects of changing the quality of carbohydrates from rapidly to slowly digestible carbohydrates on metabolic abnormalities and its impact on obesity in growing rats fed a high-fat diet (HFD). Growing rats were fed on HFD containing carbohydrates with different digestion rates: a HFD containing rapid-digesting carbohydrates (OBE group) or slow-digesting carbohydrates (ISR group), for 4 weeks and the effect on the metabolism and signaling pathways were analyzed in different tissues. Animals from OBE group presented an overweight/obese phenotype with a higher body weight gain and greater accumulation of fat in adipose tissue and liver. This state was associated with an increase of HOMA index, serum diacylglycerols and triacylglycerides, insulin, leptin, and pro-inflammatory cytokines. In contrast, the change of carbohydrate profile in the diet to one based on slow digestible prevented the obesity-related adverse effects. In adipose tissue, GLUT4 was increased and UCPs and PPARγ were decreased in ISR group respect to OBE group. In liver, GLUT2, FAS, and SRBP1 were lower in ISR group than OBE group. In muscle, an increase of glycogen, GLUT4, AMPK, and Akt were observed in comparison to OBE group. In conclusion, this study demonstrates that the replacement of rapidly digestible carbohydrates for slowly digestible carbohydrates within a high-fat diet promoted a protective effect against the development of obesity and its associated comorbidities.

Beneficial Effects of Bovine Milk Exosomes in Metabolic Interorgan Cross-Talk.

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.

Effects of ß-Hydroxy ß-Methylbutyrate Supplementation on Working Memory and Hippocampal Long-Term Potentiation in Rodents.

ß-hydroxy ß-methylbutyrate (HMB), a metabolite of the essential amino acid leucine, has been shown to preserve muscle mass and strength during aging. The signaling mechanism by which HMB elicits its favorable effects on protein metabolism in skeletal muscle is also preserved in the brain. However, there are only a few studies, all at relatively high doses, addressing the effect of HMB supplementation on cognition. This study evaluated the effects of different doses of HMB on the potentiation of hippocampal synapses following the experimental induction of long-term potentiation (LTP) in the hippocampus of behaving rats, as well as on working memory test (delayed matching-to-position, DMTP) in mice. HMB doses in rats were 225 (low), 450 (medium), and 900 (high) mg/kg body weight/day and were double in mice. Rats who received medium or high HMB doses improved LTP, suggesting that HMB administration enhances mechanisms related to neuronal plasticity. In the DMTP test, mice that received any of the tested doses of HMB performed better than the control group in the overall test with particularities depending on the dose and the task phase.

Dietary Complex and Slow Digestive Carbohydrates Promote Bone Mass and Improve Bone Microarchitecture during Catch-Up Growth in Rats.

Catch-up growth is a process that promotes weight and height gains to recover normal growth patterns after a transient period of growth inhibition. Accelerated infant growth is associated with reduced bone mass and quality characterized by poor bone mineral density (BMD), content (BMC), and impaired microarchitecture. The present study evaluated the effects of a diet containing slow (SDC) or rapid (RDC) digestible carbohydrates on bone quality parameters during the catch-up growth period in a model of diet-induced stunted rats. The food restriction period negatively impacted BMD, BMC, and microarchitecture of appendicular and axial bones. The SDC diet was shown to improve BMD and BMC of appendicular and axial bones after a four-week refeeding period in comparison with the RDC diet. In the same line, the micro-CT analysis revealed that the trabecular microarchitecture of tibiae and vertebrae was positively impacted by the dietary intervention with SDC compared to RDC. Furthermore, features of the cortical microstructure of vertebra bones were also improved in the SDC group animals. Similarly, animals allocated to the SDC diet displayed modest improvements in growth plate thickness, surface, and volume compared to the RDC group. Diets containing the described SDC blend might contribute to an adequate bone formation during catch-up growth thus increasing peak bone mass, which could be linked to reduced fracture risk later in life in individuals undergoing transient undernutrition during early life.

Curcumin Enhances Fed-State Muscle Microvascular Perfusion but Not Leg Glucose Uptake in Older Adults.

Therapeutic interventions aimed at enhancing blood flow may combat the postprandial vascular and metabolic dysfunction that manifests with chronological ageing. We compared the effects of acute curcumin (1000 mg) coupled with an oral nutritional supplement (ONS, 7.5 g protein, 24 g carbohydrate and 6 g fat) versus a placebo and ONS (control) on cerebral and leg macrovascular blood flow, leg muscle microvascular blood flow, brachial artery endothelial function, and leg insulin and glucose responses in healthy older adults (n = 12, 50% male, 73 ± 1 year). Curcumin enhanced m. tibialis anterior microvascular blood volume (MBV) at 180 and 240 min following the ONS (baseline: 1.0 vs. 180 min: 1.08 ± 0.02, p = 0.01 vs. 240 min: 1.08 ± 0.03, p = 0.01), and MBV was significantly higher compared with the control at both time points (p < 0.05). MBV increased from baseline in the m. vastus lateralis at 240 min after the ONS in both groups (p < 0.05), and there were no significant differences between groups. Following the ONS, leg blood flow and leg vascular conductance increased, and leg vascular resistance decreased similarly in both conditions (p < 0.05). Brachial artery flow-mediated dilation and middle cerebral artery blood flow were unchanged in both conditions (p > 0.05). Similarly, the curcumin and control groups demonstrated comparable increases in glucose uptake and insulin in response to the ONS. Thus, acute curcumin supplementation enhanced ONS-induced increases in m. tibialis anterior MBV without potentiating m. vastus lateralis MBV, muscle glucose uptake, or systemic endothelial or macrovascular function in healthy older adults.

Differences in muscle energy metabolism and metabolic flexibility between sarcopenic and nonsarcopenic older adults.

BACKGROUND: Metabolic flexibility is the ability of skeletal muscle to adapt fuel utilization to the demand for fuel sources [carbohydrates (CHO) and fats (FAT)]. The purpose of this study was to explore muscle energy metabolism and metabolic flexibility under various conditions in sarcopenic (S) versus nonsarcopenic (NS) older adults. METHODS: Twenty-two older adults aged 65 years or older were categorized as NS [n = 11; mean ± standard deviation (SD); age = 73.5 ± 6.0 years (males, n = 5; females, n = 6)] or S [n = 11; 81.2 ± 10.5 years (males, n = 6; females, n = 5) based on handgrip strength, body composition and physical performance. Indirect calorimetry was recorded before and after consumption of a high-CHO meal and during aerobic and anaerobic exercise. Respiratory quotient (RQ), CHO and FAT oxidation were assessed. Venous blood samples were collected for glucose and insulin concentrations. RESULTS: At rest, compared with NS, S exhibited a 5-8% higher RQ at 0 (0.72 vs. 0.76) and 120 (0.77 vs. 0.82), 150 (0.76 vs. 0.80), and 180 min (0.74 vs. 0.80) (P = 0.002-0.025); 59-195% higher CHO oxidation at 0, 120, and 180 min (0.0004-0.002 vs. 0.001-0.002 g·min-1 ·kg-1) (P = 0.010-0.047); and 20-31% lower FAT oxidation at 0, 15, and 90-180 min (0.0009-0.0022 vs. 0.0011-0.002 g·min-1 ·kg-1 ) (P = 0.004-0.038). Glucose levels were significantly elevated in S versus NS at 0, 60 and 75 min (144.64-202.78 vs. 107.70-134.20 mg·dL-1 ) but not insulin. During aerobic exercise, RQ was 5% greater (0.90 vs. 0.86) (P = 0.039), and FAT oxidation was 35% lower at 6-8 min (0.003 vs. 0.005 g·min-1 ·kg-1 ) (P = 0.033) in S versus NS. During anaerobic exercise, CHO oxidation was 31% greater in NS versus S at 60-80% time to exhaustion (0.011 vs. 0.007 g·min-1 ·kg-1 ) (P = 0.015). Per cent contribution to energy expenditure was greater in S for CHO but lower for FAT at 0 (CHO: 22% vs. 10%; FAT: 78% vs. 91%) and 120-180 min (CHO: 35-42% vs. 17-25%; FAT: 58-65% vs. 75%-84%) (P = 0.003-0.046) at rest and 6-8 min during aerobic exercise (CHO: 70% vs. 57%; FAT: 30% vs. 45%) (P = 0.046). CONCLUSIONS: The data show differences in skeletal muscle energy metabolism and substrate utilization between S and NS at rest, transitioning from fasted to fed state, and during exercise. Compared with NS, S displayed a diminished ability to adapt fuel utilization in response to feeding and exercise, reflecting metabolic inflexibility. Impaired metabolic flexibility could be a mechanism underlying the losses of strength and physical function accompanying sarcopenia.