RESUMEN
Malnutrition may result in abnormal biochemical and hematological indices. This planned prespecified analysis investigated the effects of a specialized oral nutritional supplement (ONS) on biochemical and hematological indices in community-dwelling older adults at risk of malnutrition. In the Strengthening Health in ELDerly through nutrition (SHIELD) study, 811 older adults aged 65 years and above took part in this randomized, double-blind, placebo-controlled, multi-center study. Participants were randomly allocated to either a complete and balanced specialized ONS (each serving provides 262 kcal, 10.5 g protein, 7.75 µg vitamin D3, and 0.74 g calcium ß-hydroxy-ß-methylbutyrate) and dietary counselling (intervention group) or a placebo and dietary counselling (placebo group). Both groups consumed study products twice a day for 180 days. Data were collected at baseline, day 90, and day 180. Blood analysis results at follow-up visits were analyzed using repeated measures analysis of covariance with adjustments for confounders. Overall, when compared with the placebo group, the intervention group showed significantly greater urea (6.0 mmol/L vs. 5.4 mmol/L, p < 0.001), urea to creatinine ratio (4.39 vs. 4.26, p < 0.001), prealbumin (24.9 mg/dL vs. 24.0 mg/dL, p < 0.001), vitamin B12 (480.0 pmol/L vs. 420.1 pmol/L, p < 0.001), and globulin levels (26.8 g/L vs. 26.5 g/L, p = 0.032). The intervention group also had a significantly higher absolute reticulocyte count (62.0 × 103/µL vs. 58.2 × 103/µL, overall p < 0.001) and mean platelet volume (10.0 fL vs. 9.9 fL, overall p = 0.003). Furthermore, significant improvements were seen in total protein at day 90 (71.7 g/L vs. 71.1 g/L, p = 0.017) and in absolute monocyte count at day 90 (0.50 × 103/µL vs. 0.47 × 103/µL, p = 0.009) in the intervention group. In conclusion, daily consumption of a specialized ONS for six months led to significant improvements in biochemical and hematological indices in community-dwelling older adults at risk of malnutrition.
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Suplementos Dietéticos , Vida Independiente , Desnutrición , Valeratos , Humanos , Anciano , Masculino , Valeratos/administración & dosificación , Femenino , Método Doble Ciego , Desnutrición/sangre , Desnutrición/prevención & control , Anciano de 80 o más Años , Estado Nutricional , Administración Oral , Biomarcadores/sangreRESUMEN
A useful perioperative nutritional therapy for highly invasive esophageal cancer surgical cases needs to be developed. We clarified the usefulness of amino-acid-enriched nutritional therapy using glutamine (Gln)/arginine (Arg)/calcium ß-hydroxy-ß-methylbutyrate (HMB) products on the short-term postoperative outcomes of minimally invasive esophagectomy for esophageal cancer. Altogether, 114 patients (Gln/Arg/HMB group) received perioperative nutritional therapy with Gln/Arg/HMB products, and we retrospectively investigated the change in nutritional parameters including skeletal muscle mass, occurrence of postoperative complications, and short-term postoperative outcomes in this group. The results were compared between the Gln/Arg/HMB and control groups (79 patients not receiving the Gln/Arg/HMB products). The incidence of all postoperative complications, sputum expectoration disorder, and pleural effusion of grade ≥ III was significantly lower in the Gln/Arg/HMB group (62.0% vs. 38.6%, p = 0.001; 44.3% vs. 28.1%, p = 0.020; 27.8% vs. 13.2%, p = 0.011, respectively). The psoas muscle area and postoperative body weight were significantly higher at 1 month and 1 year after surgery in the Gln/Arg/HMB group than in the control group (93.5% vs. 99.9%, p < 0.001; 92.0% vs. 95.4%, p = 0.006). Perioperative amino-acid-enriched nutritional therapy may improve the short-term postoperative outcomes, nutritional status, and skeletal muscle mass of esophageal cancer surgical patients.
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Arginina , Neoplasias Esofágicas , Esofagectomía , Glutamina , Atención Perioperativa , Complicaciones Posoperatorias , Valeratos , Humanos , Masculino , Neoplasias Esofágicas/cirugía , Femenino , Arginina/administración & dosificación , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Valeratos/administración & dosificación , Complicaciones Posoperatorias/prevención & control , Glutamina/administración & dosificación , Atención Perioperativa/métodos , Calcio , Terapia Nutricional/métodos , Resultado del Tratamiento , Estado Nutricional , Músculo Esquelético/efectos de los fármacosRESUMEN
Calcium ß-hydroxy-ß-methylbutyrate (CaHMB), a functional calcium salt, is used to maintain and improve muscle health. Here, a new hydrogel material prepared from alginate (ALG) with three M/G ratios (1:1, 2:1, and 1:2) and CaHMB (0-2 mg/mL) was investigated. CaHMB regulates the formation and properties of ALG hydrogels through chelation and hydrogen bonding. When the M/G ratio was 2:1, the anionic groups of CaHMB containing carboxyl and hydroxyl groups formed hydrogen bonds with the polysaccharide chains, hindering the capture of Ca2+ by the G-residue fragments of ALG, which in turn retarded the gelation process. The noncalcium cross-linked polysaccharide chain structure of ALG and the anionic group of CaHMB also affected the water distribution in the hydrogel, especially when M residue content ≥G residue content. Lower M/G ratios and higher CaHMB concentrations could increase the number of "egg box" crosslinking junctions of calcium alginate, and the microstructure was denser in the gel pores, resulting in a stronger gel strength and more free water bound in the gel matrix. This study provides a theoretical and methodological basis for the design of novel hydrogels by studying the crosslinking features of ALG/CaHMB.
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Alginatos , Calcio , Hidrogeles , Alginatos/química , Hidrogeles/química , Calcio/química , Valeratos/química , Iones/química , Enlace de Hidrógeno , Agua/químicaRESUMEN
Chronic wounds are characterized by prolonged non-healing, significantly affecting patients' quality of life. Oral formulas may enhance the wound healing process and contribute to cost reduction in care. This review aimed to evaluate the effects of oral nutritional supplementation on chronic wound healing and provide insights into formula characteristics. A comprehensive search across Cinahl, Embase, PubMed, and Web of Science databases yielded nine studies from the past decade involving 741 patients ages 52 to 81.7 across various care settings: hospitals, long-term care facilities, and home care. Primary wound types included pressure injuries (58%), diabetic foot ulcers (40%), and venous ulcers (2%). The intervention duration ranged from 2 to 16 wk, with sample sizes varying from 24 to 270 patients. Notably, four studies reported a reduction in wound area and an increased healing rate with a hypercaloric, hyperproteic formula enriched with zinc and vitamins A, C, and E. However, two studies found no significant differences compared with control groups. Two other studies investigated a combination of arginine, glutamine, and ß-hydroxy-ß-methylbutyrate; however, they did not yield significant results, and one study favored a hyperproteic formula instead of a hyperproteic formula with arginine. This review provides evidence supporting the potential of oral nutritional supplementation to enhance the healing process of chronic wounds. Based on our findings, a desirable formula should be characterized by a high calorie and protein content and the inclusion of antioxidant micronutrients, including, but not limited to, vitamins A, E, C, and zinc.
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Suplementos Dietéticos , Úlcera por Presión , Cicatrización de Heridas , Humanos , Cicatrización de Heridas/efectos de los fármacos , Enfermedad Crónica , Pie Diabético/terapia , Zinc/administración & dosificación , Úlcera Varicosa/dietoterapia , Úlcera Varicosa/terapia , Anciano , Arginina/administración & dosificación , Arginina/farmacología , Persona de Mediana Edad , Anciano de 80 o más Años , Valeratos/administración & dosificación , Valeratos/farmacología , Vitamina A/administración & dosificación , Glutamina/administración & dosificación , Vitamina E/administración & dosificación , Vitamina E/farmacología , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/farmacología , Femenino , Vitaminas/administración & dosificación , Masculino , Administración OralRESUMEN
3-Hydroxy-3-methylbutyrate (HMB) is a five-carbon branch-chain hydroxy acid currently used as a dietary supplement to treat sarcopenia and exercise training. However, its current production relies on conventional chemical processes which require toxic substances and are generally non-sustainable. While bio-based syntheses of HMB have been developed, they are dependent on biotransformation of its direct precursors which are generally costly. Therefore, in this work, we developed a synthetic de novo HMB biosynthetic pathway that enables HMB production from renewable resources. This novel HMB biosynthesis employs heterologous enzymes from mevalonate pathway and myxobacterial iso-fatty acid pathway for converting acetyl-CoA to HMB-CoA. Subsequently, HMB-CoA is hydrolyzed by a thioesterase to yield HMB. Upon expression of this pathway, our initial Escherichia coli strain produced 660 mg/L of HMB from glucose in 48 hours. Through optimization of coenzyme A removal from HMB-CoA and genetic operon structure, our final strain achieved HMB production titer of 17.7 g/L in glucose minimal media using a bench-top bioreactor. This engineered strain was further demonstrated to produce HMB from other renewable carbon sources such as xylose, glycerol, and acetate. The results from this work provided a flexible and environmentally benign method for producing HMB.
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Escherichia coli , Ingeniería Metabólica , Escherichia coli/genética , Escherichia coli/metabolismo , Valeratos/metabolismo , Ácido Mevalónico/metabolismoRESUMEN
Adequate diet, physical activity, and dietary supplementation with muscle-targeted food for special medical purposes (FSMP) or dietary supplement (DS) are currently considered fundamental pillars in sarcopenia treatment. The aim of this study is to evaluate the effectiveness of a DS (containing hydroxy-methyl-butyrate, carnosine, and magnesium, for its action on muscle function and protein synthesis and butyrate and lactoferrin for their contribution to the regulation of gut permeability and antioxidant/anti-inflammation activity) on muscle mass (assessed by dual X-ray absorptiometry (DXA)), muscle function (by handgrip test, chair test, short physical performance battery (SPPB) test, and walking speed test), inflammation (tumor necrosis factor-alpha (TNF-a), C-reactive protein (CRP), and visceral adipose tissue (VAT)) and gut axis (by zonulin). A total of 59 participants (age 79.7 ± 4.8 years, body mass index 20.99 ± 2.12 kg/m2) were enrolled and randomly assigned to intervention (n = 30) or placebo (n = 28). The skeletal muscle index (SMI) significantly improved in the supplemented group compared to the placebo one, +1.02 (CI 95%: -0.77; 1.26), p = 0.001; a significant reduction in VAT was observed in the intervention group, -70.91 g (-13.13; -4.70), p = 0.036. Regarding muscle function, all the tests significantly improved (p = 0.001) in the supplemented group compared to the placebo one. CRP, zonulin, and TNF-alpha significantly decreased (p = 0.001) in intervention, compared to placebo, -0.74 mg/dL (CI 95%: -1.30; -0.18), -0.30 ng/mL (CI 95%: -0.37; -0.23), -6.45 pg/mL (CI 95%: -8.71; -4.18), respectively. This DS improves muscle mass and function, and the gut muscle has emerged as a new intervention target for sarcopenia.
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Carnosina , Suplementos Dietéticos , Lactoferrina , Magnesio , Músculo Esquelético , Permeabilidad , Sarcopenia , Humanos , Masculino , Anciano , Femenino , Sarcopenia/tratamiento farmacológico , Sarcopenia/prevención & control , Carnosina/administración & dosificación , Lactoferrina/administración & dosificación , Lactoferrina/farmacología , Magnesio/administración & dosificación , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Permeabilidad/efectos de los fármacos , Anciano de 80 o más Años , Valeratos/administración & dosificación , Valeratos/farmacología , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Butiratos , Método Doble Ciego , Haptoglobinas , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Precursores de ProteínasRESUMEN
We investigated the bioavailability of the calcium salt (HMB-Ca) and the free acid (HMB-FA) forms of ß-hydroxy-ß-methylbutyrate (HMB). Sixteen young individuals received the following treatments on three different occasions in a counterbalanced crossover fashion: (1) HMB-FA in clear capsules; (2) HMB-Ca in gelatine capsules; (3) HMB-Ca dissolved in water. All treatments provided 1 g of HMB. Blood samples were taken before and on multiple time points following ingestion. The following parameters were calculated: peak plasma (Cmax), time to peak (Tmax), slope of HMB appearance in blood, area under the curve (AUC), half-life time (t1/2) and relative bioavailability (HMB-Ca in water set as reference). All treatments led to rapid and large increases in plasma HMB. HMB-Ca in capsules and in water showed similar plasma HMB values across time (p = 0.438). HMB-FA resulted in lower concentrations vs. the other treatments (both p < 0.001). AUC (HMB-Ca in capsules: 50,078 ± 10,507; HMB-Ca in water: 47,871 ± 10,783; HMB-FA: 29,130 ± 12,946 µmol L-1 × 720 min), Cmax (HMB-Ca in capsules: 229.2 ± 65.9; HMB-Ca in water: 249.7 ± 49.7; HMB-FA: 139.1 ± 67.2 µmol L-1) and relative bioavailability (HMB-Ca in capsules: 104.8 ± 14.9%; HMB-FA: 61.5 ± 17.0%) were lower in HMB-FA vs. HMB-Ca (all p < 0.001). HMB-Ca in water resulted in the fastest Tmax (43 ± 22 min) compared to HMB-Ca in capsules (79 ± 40 min) and HMB-FA (78 ± 21 min) (all p < 0.05), while t1/2 was similar between treatments. To conclude, HMB-Ca exhibited superior bioavailability compared to HMB-FA, with HMB-Ca in water showing faster absorption. Elimination kinetics were similar across all forms, suggesting that the pharmaceutical form of HMB affects the absorption rates, but not its distribution or elimination.
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Calcio , Valeratos , Agua , Humanos , Disponibilidad Biológica , Preparaciones FarmacéuticasRESUMEN
ß-Hydroxy-ß-methylbutyrate (HMB) is a breakdown product of leucine, which promotes muscle growth. Although some studies indicate that HMB activates AKT and mTOR, others show activation of the downstream effectors, P70S6K and S6, independent of mTOR. Our aim was to study the metabolic effect of HMB around the circadian clock in order to determine more accurately the signaling pathway involved. C2C12 myotubes were treated with HMB and clock, metabolic and myogenic markers were measured around the clock. HMB-treated C2C12 myotubes showed no activation of AKT and mTOR, but did show activation of P70S6K and S6. Activation of P70S6K and S6 was also found when myotubes were treated with HMB combined with metformin, an indirect mTOR inhibitor, or rapamycin, a direct mTOR inhibitor. The activation of the P70S6K and S6 independent of AKT and mTOR, was accompanied by increased activation of phospholipase D2 (PLD). In addition, HMB led to high amplitude and advanced circadian rhythms. In conclusion, HMB induces myogenesis in C2C12 by activating P70S6K and S6 via PLD2, rather than AKT and mTOR, leading to high amplitude advanced rhythms.
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Ritmo Circadiano , Fibras Musculares Esqueléticas , Fosfolipasa D , Valeratos , Valeratos/farmacología , Animales , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Ratones , Fosfolipasa D/metabolismo , Ritmo Circadiano/efectos de los fármacos , Línea Celular , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Desarrollo de Músculos/efectos de los fármacosRESUMEN
BACKGROUND: Hip fractures are prevalent among older people, often leading to reduced mobility, muscle loss, and bone density decline. Malnutrition exacerbates the prognosis post surgery. This study aimed to evaluate the impact of a 12-week regimen of a high-calorie, high-protein oral supplement with ß-hydroxy-ß-methylbutyrate (HC-HP-HMB-ONS) on nutritional status, daily activities, and compliance in malnourished or at-risk older patients with hip fractures receiving standard care. SUBJECTS AND METHODS: A total of 270 subjects ≥75 years of age, residing at home or in nursing homes, malnourished or at risk of malnutrition, and post hip fracture surgery, received HC-HP-HMB-ONS for 12 weeks. Various scales and questionnaires assessed outcomes. RESULTS: During the 12 weeks of follow-up, 82.8% consumed ≥75% of HC-HP-HMB-ONS. By week 12, 62.4% gained or maintained weight (+0.3 kg), 29.2% achieved normal nutritional status (mean MNA score +2.8), and 46.8% improved nutritional status. Biochemical parameters improved significantly. Subjects reported good tolerability (mean score 8.5/10), with 87.1% of healthcare providers concurring. CONCLUSIONS: The administration of HC-HP-HMB-ONS markedly enhanced nutritional status and biochemical parameters in older hip-fracture patients, with high compliance and tolerability. Both patients and healthcare professionals expressed satisfaction with HC-HP-HMB-ONS.
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Suplementos Dietéticos , Fracturas de Cadera , Desnutrición , Estado Nutricional , Valeratos , Humanos , Anciano , Masculino , Femenino , Estudios Prospectivos , Anciano de 80 o más Años , Desnutrición/etiología , Valeratos/administración & dosificación , Dieta Rica en Proteínas , Administración Oral , Ingestión de Energía , Proteínas en la Dieta/administración & dosificación , Resultado del TratamientoRESUMEN
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.
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Diabetes Mellitus Tipo 2 , Fragilidad , Vida Independiente , Valeratos , Humanos , Masculino , Femenino , Anciano , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Fragilidad/sangre , Valeratos/sangre , Estudios Transversales , Anciano de 80 o más Años , Anciano Frágil/estadística & datos numéricos , Glucemia/análisis , Evaluación Geriátrica/métodosRESUMEN
BACKGROUND: Statins, or hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors, are one of the most commonly prescribed medications for lowering cholesterol. Myopathic side-effects ranging from pain and soreness to critical rhabdomyolysis are commonly reported and often lead to discontinuation. The pathophysiological mechanism is, in general, ascribed to a downstream reduction of Coenzyme Q10 synthesis. HMG-CoA is a metabolite of leucine and its corresponding keto acid α-ketoisocaproic acid (KIC) and ß-hydroxy-ß-methylbutyrate (HMB), however, little is known about the changes in the metabolism of leucine and its metabolites in response to statins. OBJECTIVE: We aimed to investigate if statin treatment has implications on the upstream metabolism of leucine to KIC and HMB, as well as on other branched chain amino acids (BCAA). DESIGN: 12 hyperlipidemic older adults under statin treatment were recruited. The study was conducted as a paired prospective study. Included participants discontinued their statin treatment for 4 weeks before they returned for baseline measurements (before). Statin treatment was then reintroduced, and the participants returned for a second study day 7 days after reintroduction (after statin). On study days, participants were injected with stable isotope pulses for measurement of the whole-body production (WBP) of all BCAA (leucine, isoleucine and valine), along with their respective keto acids and HMB. RESULTS: We found a reduced leucine WBP (22 %, p = 0.0033), along with a reduction in valine WBP (13 %, p = 0.0224). All other WBP of BCAA and keto acids were unchanged. There were no changes in the WBP of HMB. CONCLUSIONS: Our study shows that statin inhibition of HMG-CoA reductase has an upstream impact on the turnover of leucine and valine. Whether this impairment in WBP of leucine may contribute to the known pathophysiological side effects of statins on muscle remains to be further investigated.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Leucina , Valeratos , Leucina/metabolismo , Leucina/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Humanos , Valeratos/farmacología , Masculino , Femenino , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/metabolismo , Cetoácidos/metabolismo , Aminoácidos de Cadena Ramificada/metabolismoRESUMEN
Laying hens, selectively bred for high egg production, often suffer from bone fragility and fractures, impacting their welfare and causing economic losses. Additionally, gut health and muscle quality are crucial for overall health and productivity. This study aimed to evaluate the effects of ß-Hydroxy-ß-methylbutyrate (HMB) supplementation on performance, bone metabolism, intestinal morphology, and muscle quality in laying hens. Forty-eight Bovans Brown hens were divided into a control group and an HMB-supplemented group (0.02% HMB in diet). The study spanned from the 31st to the 60th wk of age. Assessments included bone mechanical testing, serum hormonal analysis, histological analysis of bone and intestine, and muscle quality analysis. The HMB supplementation led to decreased feed intake without affecting body weight or laying rate in laying hens. It caused an increase in both mean daily and total egg weight, indicating improved feed utilization, without influencing the feed intake to egg weight ratio. Enhanced bone formation markers and altered intestinal morphometric parameters were observed, along with improved trabecular bone structure. However, no changes in measured other bone quality indices, including geometric, densitometric, or mechanical properties were observed. Muscle analysis revealed no significant changes in overall meat quality, except for a decrease in cholesterol content and alterations in the fatty acid profile, notably a reduction in total n-3 polyunsaturated and total polyunsaturated fatty acids (PUFA). In conclusion, although not all effects of HMB supplementation were unequivocally beneficial, the positive changes in performance data and trabecular bone microarchitecture support further research into various doses and durations of supplementation. Such studies are necessary to fully understand and optimize the benefits of HMB for enhancing the health and productivity of laying hens.
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Alimentación Animal , Pollos , Dieta , Suplementos Dietéticos , Intestinos , Valeratos , Animales , Pollos/fisiología , Valeratos/administración & dosificación , Valeratos/farmacología , Suplementos Dietéticos/análisis , Femenino , Alimentación Animal/análisis , Dieta/veterinaria , Intestinos/efectos de los fármacos , Intestinos/fisiología , Intestinos/anatomía & histología , Huesos/efectos de los fármacos , Huesos/fisiología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiología , Distribución Aleatoria , Fenómenos Fisiológicos Nutricionales de los Animales/efectos de los fármacosRESUMEN
OBJECTIVES: To investigate the synergist effects of exercise and ß-hydroxy ß-methylbutyrate (HMB) supplementation on disability, cognitive and physical function, and muscle power in institutionalized older people. DESIGN: Cluster-randomized controlled trial. PARTICIPANTS: Seventy-two institutionalized older adults (age = 83 ± 10 years old; 63% women) were randomized in four groups: exercise plus placebo (EX), HMB supplementation, EX plus HMB supplementation (EX + HMB), and control (CT). INTERVENTION: The exercising participants completed a 12-week tailored multicomponent exercise intervention (Vivifrail; 5 days/week of an individualized resistance, cardiovascular, balance and flexibility program), whereas the HMB groups received a drink containing 3 g/day of HMB. MEASUREMENTS: Participants were assessed Pre and Post intervention for disability and cognitive function (validated questionnaires), physical function (short physical performance battery, SPPB), handgrip strength and sit-to-stand relative muscle power. Linear mixed-effect models were used to compare changes among groups. RESULTS: Compared to baseline, both EX and EX + HMB improved cognitive function (+2.9 and +1.9 points; p < 0.001), SPPB score (+2.9 points and +2.4 points; p < 0.001) and relative muscle power (+0.64 and +0.48 W·kg-1; p < 0.001), while CT and HMB remained unchanged (p > 0.05). Significant between-group differences were noted between CT, EX and EX + HMB for cognitive function (p < 0.01), between CT and EX + HMB for physical function (p = 0.043), and between CT, EX and EX + HMB for relative muscle power (p < 0.001). CONCLUSION: The Vivifrail exercise program was effective in improving cognitive and physical function, and muscle power in nursing home residents, while HMB supplementation did not provide additional benefits when combined with exercise. These results emphasize the importance of physical exercise interventions in very old people as an essential basis for improving their overall health and quality of life.
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Cognición , Suplementos Dietéticos , Valeratos , Humanos , Femenino , Masculino , Valeratos/administración & dosificación , Valeratos/farmacología , Cognición/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Fuerza Muscular/efectos de los fármacos , Fuerza de la Mano , Personas con Discapacidad , Terapia por Ejercicio/métodos , Ejercicio Físico/fisiologíaRESUMEN
BACKGROUND: During critical illness skeletal muscle wasting occurs rapidly. Although beta-hydroxy-beta-methylbutyrate (HMB) is a potential treatment to attenuate this process, the plasma appearance and muscle concentration is uncertain. METHODS: This was an exploratory study nested within a blinded, parallel group, randomized clinical trial in which critically ill patients after trauma received enteral HMB (3 g daily) or placebo. Plasma samples were collected at 0, 60, and 180 min after study supplement administration on day 1. Needle biopsies of the vastus lateralis muscle were collected (baseline and day 7 of the HMB treatment intervention period). An external standard curve was used to calculate HMB concentrations in plasma and muscle. RESULTS: Data were available for 16 participants (male n = 12 (75%), median [interquartile range] age 50 [29-58] years) who received placebo and 18 participants (male n = 14 (78%), age 49 [34-55] years) who received HMB. Plasma HMB concentrations were similar at baseline but increased after HMB (T = 60 min: placebo 0.60 [0.44-1.31] µM; intervention 51.65 [22.76-64.72] µM). Paired muscle biopsies were collected from 11 participants (placebo n = 7, HMB n = 4). Muscle HMB concentrations were similar at baseline between groups (2.35 [2.17-2.95]; 2.07 [1.78-2.31] µM). For participants in the intervention group who had the repeat biopsy within 4 h of HMB administration, concentrations were greater (7.2 and 12.3 µM) than those who had the repeat biopsy >4 h after HMB (2.7 and 2.1 µM). CONCLUSION: In this exploratory study, enteral HMB administration increased plasma HMB availability. The small sample size limits interpretation of the muscle HMB findings.
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Enfermedad Crítica , Nutrición Enteral , Músculo Esquelético , Valeratos , Humanos , Masculino , Persona de Mediana Edad , Valeratos/administración & dosificación , Enfermedad Crítica/terapia , Adulto , Nutrición Enteral/métodos , Femenino , Heridas y Lesiones/terapia , Heridas y Lesiones/complicaciones , Atrofia Muscular/etiologíaRESUMEN
5-hydroxyvaleric acid (5-HV) is a versatile C5 intermediate of bio-based high-value chemical synthesis pathways. However, 5-HV production faces a few shortcomings involving the supply of cofactors, especially α-ketoglutaric acid (α-KG). Herein, we established a two-cell biotransformation system by introducing L-glutamate oxidase (GOX) to regenerate α-KG. Additionally, the catalase KatE was adapted to inhibit α-KG degradation by the H2O2 produced during GOX reaction. We searched for the best combination of genes and vectors and optimized the biotransformation conditions to maximize GOX effectiveness. Under the optimized conditions, 5-HV pathway with GOX showed 1.60-fold higher productivity than that of without GOX, showing 11.3â¯g/L titer. Further, the two-cell system with GOX and KatE was expanded to produce poly(5-hydroxyvaleric acid) (P(5HV)), and it reached at 412â¯mg/L of P(5HV) production and 20.5% PHA contents when using the biotransformation supernatant. Thus, the two-cell biotransformation system with GOX can potentially give the practical and economic alternative of 5-HV production using bio-based methods. We also propose direct utilization of 5-HV from bioconversion for P(5HV) production.
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Aminoácido Oxidorreductasas , Biotransformación , Ácidos Cetoglutáricos , Azúcares Ácidos , Ácidos Cetoglutáricos/metabolismo , L-Aminoácido Oxidasa/metabolismo , L-Aminoácido Oxidasa/genética , Peróxido de Hidrógeno/metabolismo , Catalasa/metabolismo , Catalasa/genética , Valeratos/metabolismoRESUMEN
BACKGROUND: Biallelic pathogenic variants in SLC5A6 resulting in sodium-dependent multivitamin transporter (SMVT) defect have recently been described as a vitamin-responsive inborn error of metabolism mimicking biotinidase deficiency. To our knowledge, only 16 patients have been reported so far with various clinical phenotypes such as neuropathy and other neurologic impairments, gastro-intestinal dysfunction and failure to thrive, osteopenia, immunodeficiency, metabolic acidosis, hypoglycemia, and recently severe cardiac symptoms. METHODS: We describe a case report of a 5-month-old girl presenting two recurrent episodes of metabolic decompensation and massive cardiac failure in the course of an infectious disease. We compare clinical, biological, and genetic findings of this patient to previous literature collected from Pubmed database (keywords: Sodium-dependent multivitamin transporter (SMVT), SMVT defect/disorder/deficiency, SLC5A6 gene/mutation). RESULTS: We highlight the life-threatening presentation of this disease, the stagnation of psychomotor development, the severe and persistent hypogammaglobulinemia, and additionally, the successful clinical response on early vitamin supplementation (biotin 15 mg a day and pantothenic acid 100 mg a day). Metabolic assessment showed a persistent increase of urinary 3-hydroxyisovaleric acid (3-HIA) as previously reported in this disease in literature. CONCLUSION: SMVT deficiency is a vitamin-responsive inborn error of metabolism that can lead to a wide range of symptoms. Increased and isolated excretion of urinary 3-hydroxyisovaleric acid may suggest, in the absence of markedly reduced biotinidase activity, a SMVT deficiency. Prompt supplementation with high doses of biotin and pantothenic acid should be initiated while awaiting results of SLC5A6 sequencing as this condition may be life-threatening.
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Biotina , Ácido Pantoténico , Valeratos , Femenino , Humanos , Lactante , Biotina/uso terapéutico , Vitaminas , Suplementos Dietéticos , SodioRESUMEN
Oligodendrocytes are the myelinating cells in the CNS and multiple sclerosis (MS) is a demyelinating disorder that is characterized by progressive loss of myelin. Although oligodendroglial progenitor cells (OPCs) should be differentiated into oligodendrocytes, for multiple reasons, OPCs fail to differentiate into oligodendrocytes in MS. Therefore, increasing the maturation of OPCs to oligodendrocytes may be of therapeutic benefit for MS. The ß-hydroxy ß-methylbutyrate (HMB) is a muscle-building supplement in humans and this study underlines the importance of HMB in stimulating the maturation of OPCs to oligodendrocytes. HMB treatment upregulated the expression of different maturation markers including PLP, MBP, and MOG in cultured OPCs. Double-label immunofluorescence followed by immunoblot analyses confirmed the upregulation of OPC maturation by HMB. While investigating mechanisms, we found that HMB increased the maturation of OPCs isolated from peroxisome proliferator-activated receptor ß-/- (PPARß-/-) mice, but not PPARα-/- mice. Similarly, GW6471 (an antagonist of PPARα), but not GSK0660 (an antagonist of PPARß), inhibited HMB-induced maturation of OPCs. GW9662, a specific inhibitor of PPARγ, also could not inhibit HMB-mediated stimulation of OPC maturation. Furthermore, PPARα agonist GW7647, but neither PPARß agonist GW0742 nor PPARγ agonist GW1929, alone increased the maturation of OPCs. Finally, HMB treatment of OPCs led to the recruitment of PPARα, but neither PPARß nor PPARγ, to the PLP gene promoter. These results suggest that HMB stimulates the maturation of OPCs via PPARα and that HMB may have therapeutic prospects in remyelination.
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Diferenciación Celular , Oligodendroglía , Valeratos , Animales , Valeratos/farmacología , Ratones , Oligodendroglía/efectos de los fármacos , Oligodendroglía/metabolismo , Diferenciación Celular/efectos de los fármacos , Células Precursoras de Oligodendrocitos/efectos de los fármacos , Células Precursoras de Oligodendrocitos/metabolismo , Células Cultivadas , Ratones Endogámicos C57BL , Ratones Noqueados , PPAR-beta/metabolismo , PPAR-beta/agonistasRESUMEN
OBJECTIVES: This study aimed to evaluate the efficacy of adding ß-hydroxy-ß- methylbutyrate (HMB) supplementation to a 12-week exercise-based rehabilitation program in older adults with sarcopenia after discharge from a post-acute geriatric rehabilitation unit. STUDY DESIGN: A randomized, double-blind, placebo-controlled trial with two parallel groups. The intervention group received 3 g/day of Ca-HMB and participated in a 12- week resistance training program (3 sessions/week). The control group received a placebo and followed the same training program. MAIN OUTCOME MEASURES: The primary outcomes were the improvements of handgrip strength and physical performance assessed through the Short Physical Performance Battery (SPPB) and 4-meter gait speed; and handgrip strength. All variables were assessed at baseline, post-intervention, and 1-year follow-up. RESULTS: After completing the 12-week exercise program, the intervention group showed significant improvements in SPPB-Balance (1.3, 95 %CI 0.3 to 2.4) and total SPPB score (2.2, 95 %CI 0.4 to 4.0). Intra-group analysis demonstrated gains in the SPPB-Chair Stand (0.7 points, 95 %CI 0.0 to 1.4) and total SPPB score (2.1 points, 95 %CI 0.3 to 3.9) in the intervention group. Improvements in handgrip strength were observed in women (3.7 kg, 95 %CI: 0.2 to 7.3) at the end of the intervention, and persisted at the 1-year follow-up. CONCLUSIONS: Our findings suggest that the supplementation of 3 g/day of Ca-HMB with resistance exercise may significantly enhance muscle strength and physical performance among older women with sarcopenia after recent hospitalization. Given this study's limitations, the intervention's effectiveness cannot be drawn, and further studies are needed.
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Entrenamiento de Fuerza , Sarcopenia , Valeratos , Humanos , Femenino , Anciano , Sarcopenia/terapia , Fuerza de la Mano , Atención Subaguda , Fuerza Muscular/fisiología , Método Doble Ciego , Suplementos Dietéticos , Músculo Esquelético/fisiologíaRESUMEN
BACKGROUND: Alterations in the production of short-chain fatty acids (SCFAs) may reflect disturbances in the gut microbiota and have been linked to metabolic dysfunction-associated steatotic liver disease (MASLD). We assessed plasma SCFAs in patients with MASLD and healthy controls. METHODS: Fasting venous blood samples were collected and eight SCFAs were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). Relative between-group differences in circulating SCFA concentrations were estimated by linear regression, and the relation between SCFA concentrations, MASLD, and fibrosis severity was investigated using logistic regression. RESULTS: The study includes 100 patients with MASLD (51% with mild/no fibrosis and 49% with significant fibrosis) and 50 healthy controls. Compared with healthy controls, MASLD patients had higher plasma concentrations of propionate (21.8%, 95% CI 3.33 to 43.6, p = 0.02), formate (21.9%, 95% CI 6.99 to 38.9, p = 0.003), valerate (35.7%, 95% CI 4.53 to 76.2, p = 0.02), and α-methylbutyrate (16.2%, 95% CI 3.66 to 30.3, p = 0.01) but lower plasma acetate concentrations (- 30.0%, 95% CI - 40.4 to - 17.9, p < 0.001). Among patients with MASLD, significant fibrosis was positively associated with propionate (p = 0.02), butyrate (p = 0.03), valerate (p = 0.03), and α-methylbutyrate (p = 0.02). Six of eight SCFAs were significantly increased in F4 fibrosis. CONCLUSIONS: In the present study, SCFAs were associated with MASLD and fibrosis severity, but further research is needed to elucidate the potential mechanisms underlying our observations and to assess the possible benefit of therapies modulating gut microbiota.
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Butiratos , Hígado Graso , Enfermedades Metabólicas , Humanos , Propionatos , Espectrometría de Masas en Tándem , Ácidos Grasos Volátiles , Valeratos , FibrosisRESUMEN
Short-chain fatty acids (SCFAs) are produced by the intestinal microbiota during the fermentation of dietary fibers as secondary metabolites. Several recent studies reported that SCFAs modulate the development and function of immune-related cells. However, the molecular mechanisms by which SCFAs regulate mast cells (MCs) remain unclear. In the current study, we analyzed the function and gene expression of mouse MCs in the presence of SCFAs in vitro and in vivo. We found that the oral administration of valerate or butyrate ameliorated passive systemic anaphylaxis and passive cutaneous anaphylaxis in mice. The majority of SCFAs, particularly propionate, butyrate, valerate, and isovalerate, suppressed the IgE-mediated degranulation of bone marrow-derived MCs, which were eliminated by the Gi protein inhibitor pertussis toxin and by the knockdown of Gpr109a. A treatment with the HDAC inhibitor trichostatin A also suppressed IgE-mediated MC activation and reduced the surface expression level of FcεRI on MCs. Acetylsalicylic acid and indomethacin attenuated the suppressive effects of SCFAs on degranulation. The degranulation degree was significantly reduced by PGE2 but not by PGD2. Furthermore, SCFAs enhanced PGE2 release from stimulated MCs. The SCFA-mediated amelioration of anaphylaxis was exacerbated by COX inhibitors and an EP3 antagonist, but not by an EP4 antagonist. The administration of niacin, a ligand of GPR109A, alleviated the symptoms of passive cutaneous anaphylaxis, which was inhibited by cyclooxygenase inhibitors and the EP3 antagonist. We conclude that SCFAs suppress IgE-mediated activation of MCs in vivo and in vitro involving GPR109A, PGE2, and epigenetic regulation.