Active vitamin D treatment in the prevention of sarcopenia in adults with prediabetes (DPVD ancillary study): a randomised controlled trial.

BACKGROUND: Observational studies show inverse associations between serum 25-hydroxyvitamin D concentrations and sarcopenia incidence; however, it remains unclear whether treatment with vitamin D prevents its development. We aimed to assess whether treatment with active vitamin D (eldecalcitol [0·75 µg per day]) can reduce the development of sarcopenia among adults with prediabetes. METHODS: This randomised, double-blind, placebo-controlled, multicenter trial as an ancillary study was conducted at 32 clinics and hospital sites in Japan. Participants were assigned (1:1) by using a central randomisation method in which a randomisation list was made for each hospital separately using a stratified permuted block procedure. The primary endpoint was sarcopenia incidence during 3 years in the intention-to-treat population defined as weak handgrip strength (<28 kg for men and <18 kg for women) and low appendicular skeletal muscle index (<7·0 kg/m2 for men and <5·7 kg/m2 for women in bioelectrical impedance analysis). Although the usual criterion of hypercalcaemia was 10·4 mg/dL (2·6 mmol/L) or higher, hypercalcaemia that was enough to discontinue the study was defined as 11·0 mg/dL or higher. This study is registered with the UMIN clinical trials registry, UMIN000005394. FINDINGS: A total of 1094 participants (548 in the eldecalcitol group and 546 in the placebo group; 44·2% [484 of 1094] women; mean age 60·8 [SD 9·2] years) were followed up for a median of 2·9 (IQR 2·8-3·0) years. Eldecalcitol treatment as compared with placebo showed statistically significant preventive effect on sarcopenia incidence (25 [4·6%] of 548 participants in the eldecalcitol group and 48 [8·8%] of 546 participants in the placebo group; hazard ratio 0·51; 95% CI 0·31 to 0·83; p=0·0065). The incidence of adverse events did not differ between the two groups. INTERPRETATION: We found that treatment with eldecalcitol has the potential to prevent the onset of sarcopenia among people with prediabetes via increasing skeletal muscle volume and strength, which might lead to a substantial risk reduction of falls. FUNDING: Kitakyushu Medical Association. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

Effect of a 12-Week Multi-Exercise Community Program on Muscle Strength and Lipid Profile in Elderly Women.

This study targeted elderly women over 60 years old (109 persons), divided them into an exercise group and a control group, and implemented a 12-week physical activity program for the exercise group. Body composition, muscle, blood tests, depression, quality of life (QoL), nutritional status, and physical strength were compared and analyzed. The physical activity program was organized through a consultative body of experts, was performed for about 60 min each time in the type and order of exercise appropriate for elderly women, and consisted of a combination of exercise using a band, gymnastics, and stretching. Changes in the muscle index and muscle mass before and after the program were selected as the primary efficacy evaluations. In the exercise group, waist circumference significantly decreased, and the muscle index significantly increased compared to the control group. The number of subjects who showed sarcopenia with a muscle index of 5.4 or less in the exercise group significantly decreased from 22 (38.6%) before program implementation to 13 (22.8%). According to the results of secondary effectiveness evaluation, high-density lipoprotein cholesterol and apolipoprotein (Apo) A were significantly increased in the exercise group compared to the control group, and Apo B, triglyceride, and c-reactive protein showed a significant decrease. Regular physical activity is very important for improving the health and QoL of elderly women, and as a result of applying a customized program, effects such as increased muscle index, improvement of sarcopenia, and improvement of blood lipid status were confirmed. Therefore, it is believed that the physical activity program developed through this study can be applied as a community program for elderly women.

Social-media based Health Education plus Exercise Programme (SHEEP) to improve muscle function among community-dwelling young-old adults with possible sarcopenia in China: A study protocol for intervention development.

Possible sarcopenia refers to low muscle strength. Prevalence of possible sarcopenia is estimated to be significantly higher in community-dwelling older adults than that of confirmed or severe sarcopenia. However, there are currently far fewer non-pharmacological intervention strategies for possible sarcopenia than for sarcopenia in the community. Meanwhile, one type of non-pharmacological intervention in sarcopenic area, health education, is under-researched, and older people's awareness about sarcopenia is extremely low, necessitating an immediate dissemination tool for prevention. Social media may be a potential, scalable, low-cost tool for this. This study protocol outlines how a social media-based multicomponent intervention will be co-designed with stakeholders to address this evidence gap. Guided by the Medical Research Council's framework, the proposed research covers two phases that employ a co-design approach to develop a theory-based multicomponent intervention to increase sarcopenia prevention in the community. The participants will be recruited from young-old adults (60~69) with possible sarcopenia in the community of Changsha, China. Maximum sample size will be 45 participants in total, with 18~25 participants in the development phase and 15~20 participants in the pre-test phase. During two rounds of focus groups with older adults, a social-media based intervention strategy will be developed from a theory-based conceptual model and an initial intervention plan formulated by the research group. After this, there will be a three-week pre-test phase, followed by a semi-structured interview to further modify the theory-based conceptual model and the social-media based intervention strategy. The focus of the data analysis will be on thematic analysis of qualitative data primarily derived from the group interview and the semi-structured interview with key stakeholders.

Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia.

Mitochondrial dysfunction and low nicotinamide adenine dinucleotide (NAD+) levels are hallmarks of skeletal muscle ageing and sarcopenia1-3, but it is unclear whether these defects result from local changes or can be mediated by systemic or dietary cues. Here we report a functional link between circulating levels of the natural alkaloid trigonelline, which is structurally related to nicotinic acid4, NAD+ levels and muscle health in multiple species. In humans, serum trigonelline levels are reduced with sarcopenia and correlate positively with muscle strength and mitochondrial oxidative phosphorylation in skeletal muscle. Using naturally occurring and isotopically labelled trigonelline, we demonstrate that trigonelline incorporates into the NAD+ pool and increases NAD+ levels in Caenorhabditis elegans, mice and primary myotubes from healthy individuals and individuals with sarcopenia. Mechanistically, trigonelline does not activate GPR109A but is metabolized via the nicotinate phosphoribosyltransferase/Preiss-Handler pathway5,6 across models. In C. elegans, trigonelline improves mitochondrial respiration and biogenesis, reduces age-related muscle wasting and increases lifespan and mobility through an NAD+-dependent mechanism requiring sirtuin. Dietary trigonelline supplementation in male mice enhances muscle strength and prevents fatigue during ageing. Collectively, we identify nutritional supplementation of trigonelline as an NAD+-boosting strategy with therapeutic potential for age-associated muscle decline.

Influences of trans-theoretical model-based diet nursing intervention on sarcopenia and quality of life in maintenance hemodialysis patients.

Introduction: Objective: to explore the influences of a trans-theoretical model-based diet nursing intervention on sarcopenia and quality of life in maintenance hemodialysis patients. Methods: the clinical data of 243 patients with maintenance hemodialysis (MHD) admitted to our hospital from January 2019 to August 2020 were retrospectively analyzed. A 1:1 orientation score matching (PSM) method was adopted, and patients with different intervention methods were matched based on gender, age, education time, dialysis age, body mass index, underlying diseases, annual income, and whether they were malnourished. Finally, 82 cases were included in the control group (routine nursing and dietary guidance) and 80 cases in the intrevention group (dietary nursing intervention based on the trans-theoretical model), respectively. Results: After PSM, 82 cases in the control group and 80 cases in the intrevention group were included in the study. After the intervention, the incidence of sarcopenia, the extracellular water rate (ECF/TBF) value, and the malnutrition rate of the intrevention group were lower than those of the control group (p < 0.05); the scores of self-care, facing difficulties, potassium intake management, salt intake management, fluid restriction management, the levels of serum albumin, prealbumin and transferrin were all higher than those of the control group (p < 0.05); the SF-36 Concise Health Scale score of the intrevention group was higher than that of the control group (p < 0.05). The 1-year survival rate in the intrevention group (95.00 %) was higher than that in the control group (85.37 %) (p < 0.05). Conclusion: a TTM-based diet nursing intervention can help improve the dietary management behavior of MHD patients, prevent malnutrition, reduce the incidence of sarcopenia, and improve their quality of life and survival rate.

Introducción: Objetivo: explorar el impacto de las intervenciones de enfermería dietética basadas en el modelo transteórico sobre la sarcopenia y la calidad de vida en pacientes en hemodiálisis de mantenimiento. Método: se analizaron retrospectivamente los datos clínicos de 243 pacientes con hemodiálisis de mantenimiento (MHD) ingresados en nuestro hospital de enero de 2019 a agosto de 2020. Se utilizó el método de emparejamiento de la puntuación direccional 1: 1 (PSM) para emparejar a los pacientes con diferentes métodos de intervención en función del sexo, la edad, el tiempo de educación, la edad de diálisis, el índice de masa corporal, la enfermedad subyacente, los ingresos anuales y la desnutrición. Finalmente, 82 casos fueron incluidos en el grupo de control (atención rutinaria y orientación dietética) y 80 en el grupo de intervención (intervención dietética basada en el modelo transteórico). Resultados: después del PSM, 82 casos fueron incluidos en el grupo de control y 80 casos en el grupo de observación. Después de la intervención, la incidencia de sarcopenia, los valores de agua extracelular (ecf/tbf) y la tasa de desnutrición del grupo de observación fueron menores que en el grupo de control (p < 0,05); autocuidado, afrontamiento de dificultades, manejo de la ingesta de potasio, manejo de la ingesta de sal, manejo de restricción de líquidos, niveles de albúmina sérica, y tanto la prealbúmina como la transferrina fueron mayores que en el grupo de control (p < 0,05). La puntuación de la escala de salud concisa SF-36 en el grupo de observación fue mayor que la del grupo de control (p < 0,05), y la tasa de supervivencia a un año en el grupo de observación (95,00 %) fue mayor que en el grupo de control (85,37 %) (p < 0,05). Conclusión: las intervenciones de atención dietética basadas en el TTM ayudan a mejorar el comportamiento de manejo dietético de los pacientes con MHD, a prevenir la desnutrición, a reducir la incidencia de sarcopenia y a mejorar la calidad de vida y la supervivencia.

Myoprotective whole foods, muscle health and sarcopenia in older adults.

PURPOSE OF REVIEW: Sarcopenia increases in prevalence at older ages and may be exacerbated by poor diet. Whole foods rich in specific nutrients may be myoprotective and mitigate the risk of sarcopenia. Here we review recent evidence published from observational and intervention studies regarding myoprotective foods and explore their benefit for the prevention and/or treatment of sarcopenia in older adults. RECENT FINDINGS: We found limited new evidence for the role of whole foods in sarcopenia and sarcopenia components (muscle mass, strength, physical performance). There was some evidence for higher consumption of protein-rich foods (milk and dairy) being beneficial for muscle strength in observational and intervention studies. Higher consumption of antioxidant-rich foods (fruit and vegetables) was associated with better physical performance and lower odds of sarcopenia in observational studies. Evidence for other protein- and antioxidant-rich foods were inconsistent or lacking. There remains a clear need for intervention studies designed to identify the role of whole foods for the treatment of sarcopenia. SUMMARY: Although evidence for myoprotective roles of dairy, fruit and vegetables is emerging from observational studies, higher level evidence from intervention studies is needed for these foods to be recommended in diets of older adults to prevent and/or treat sarcopenia.

Novel dietary strategies to manage sarcopenia.

PURPOSE OF REVIEW: Sarcopenia is a wasting disease, mostly age-related in which muscle strength and mass decline, such as physical performance. With aging, both lower dietary protein intake and anabolic resistance lead to sarcopenia. Moreover, aging and sarcopenia display low-grade inflammation, which also worsen muscle condition. In this review, we focused on these two main targets to study dietary strategies. RECENT FINDINGS: The better understanding in mechanisms involved in sarcopenia helps building combined dietary approaches including physical activity that would slow the disease progression. New approaches include better understanding in the choice of quality proteins, their amount and schedule and the association with antioxidative nutrients. SUMMARY: First, anabolic resistance can be countered by increasing significantly protein intake. If increasing amount remains insufficient, the evenly delivery protein schedule provides interesting results on muscle strength. Quality of protein is also to consider for decreasing risk for sarcopenia, because varying sources of proteins appears relevant with increasing plant-based proteins ratio. Although new techniques have been developed, as plant-based proteins display a lower availability, we need to ensure an adapted overall amount of proteins. Finally, specific enrichment with leucine from whey protein remains the dietary combined approach most studied and studies on citrulline provide interesting results. As cofactor at the edge between anabolic and antioxidative properties, vitamin D supplementation is to recommend. Antioxidative dietary strategies include both fibers, vitamins, micronutrients and polyphenols from various sources for positive effects on physical performance. The ω 3 -polyunsaturated fatty acids also display positive modifications on body composition. Gut microbiota modifiers, such as prebiotics, are promising pathways to improve muscle mass and function and body composition in sarcopenic patients. Nutritional interventions could be enhanced by combination with physical activity on sarcopenia. In healthy older adults, promoting change in lifestyle to get near a Mediterranean diet could be one of the best options. In sarcopenia adults in which lifestyle changes appears unprobable, specific enrichement potentialized with physical activity will help in the struggle against sarcopenia. Longitudinal data are lacking, which makes it hard to draw strong conclusions. However, the effects of a physical activity combined with a set of nutrition interventions on sarcopenia seems promising.

Household use of solid fuel and sarcopenia among middle-aged and older adults: The China Health and Retirement Longitudinal Study.

OBJECTIVE: Few studies have examined the effects of air pollution on the risk of sarcopenia, especially pollution in indoor settings. We explored the cross-sectional and longitudinal associations of household use of solid fuel for cooking and heating, separately and simultaneously, with risk of sarcopenia. METHODS: Cross-sectional and follow-up data from the China Health and Retirement Longitudinal Study were used. Multivariable-adjusted generalized linear models and Cox proportional hazards regression models were performed to estimate the odds ratio and hazard ratio for sarcopenia, respectively. RESULTS: 11,494 (median age: 57.0 years; 47.4 % males) and 7483 (median age: 57.0 years; 46.9 % males) participants were included in the cross-sectional and longitudinal study, respectively. After fully adjusting for covariates, including outdoor concentration of particulate matter (PM2.5), both the use of solid fuels for cooking and use for heating were positively associated with incident sarcopenia in the longitudinal analyses, with hazard ratios (95 % confidence interval) of 1.56 (1.28-1.89) and 1.26 (1.04-1.52), respectively. Moreover, significant multiplicative and/or additive interactions were observed between age, smoking and cooking with solid fuel and risk of sarcopenia (all P for interaction <0.05). Similar results were found in the cross-sectional analyses. CONCLUSIONS: Household use of solid fuel was significantly associated with a higher risk of sarcopenia, while ageing and smoking had synergetic effects with burning solid fuels on the risk of sarcopenia. Our results highlight the importance of taking multi-pronged measures with respect to both air pollution and healthy lifestyle to prevent sarcopenia and promote healthy ageing.

Multidomain interventions for sarcopenia and cognitive flexibility in older adults for promoting healthy aging: a systematic review and meta-analysis of randomized controlled trials.

The global population is undergoing rapid aging, making physical activity a crucial element in preventing mortality and lowering the risk of Alzheimer's disease. Age-related declines in muscle mass and cognitive abilities significantly contribute to frailty and dependency. Thus, this study focuses on a meticulous analysis of the protective effects of multidomain interventions, an emerging resource combating age-related declines. It seeks to underscore their profound impact on cognitive flexibility and sarcopenia, highlighting their pivotal role in mitigating the adverse effects of aging. To identify relevant randomized controlled trials up to November 2023, we reviewed eight online academic databases, following PERSiST guidelines, PRISMA reporting system, and PICOs criteria. Meta-analyses on selected functional outcomes utilized a random-effects model, including the Timed Up and Go Test, Sit to Stand Test, Victoria Stroop Test, and Trail Making Test. Out of 2082 scrutinized articles, 17 were included in the systematic review, and 8 in the meta-analysis. Positive effects (p = 0.05, I2 = 57%; 95% CI - 0.63 to - 0.05) were observed in cognitive flexibility for certain interventions. Similarly, interventions addressing muscle strength demonstrated improvements in the Sit to Stand Test for the exercise group compared to the control group (p = 0.02, I2 = 0%; 95% CI - 0.63 to - 0.05). These findings underscore the importance of incorporating physical activity as a primary component of public health interventions for promoting healthy aging and reducing the burden of age-related diseases. Future interventions may explore more homogeneous approaches and evaluate the impact of thrice multidomain weekly sessions.

A survey of nurses' knowledge, attitudes, and practice of sarcopenia: A cross-sectional study.

AIM: This paper aims to assess the current knowledge, attitudes, and behaviors of nursing staff regarding sarcopenia and explore associating factors that influence them. BACKGROUND: Sarcopenia has an insidious onset and is easily overlooked. However, it is has become very common in older people, seriously jeopardizing the quality of life in patients. The present situation of nurses in China is inadequate, even though they are the primary professionals tasked with screening for sarcopenia, the ability to recognize and effectively manage the disease, and the critical role they play in preventing and controlling sarcopenia in patients. DESIGN: We conducted a cross-sectional design of nurses. METHODS: Facilitated sampling was used in seven hospitals in Jiangsu Province, China. A total of 409 hospital nursing staff participated in the survey from December 2022 to March 2023. The main survey instruments were the nursing staff about the knowledge of sarcopenia, beliefs, a behavior questionnaire, and a self-designed general information questionnaire. Descriptive of general data, t-test, and ANOVA for influencing factors of three dimensions, whereas multiple linear regression analyses were performed using SPSS23.0 software. RESULTS: Questionnaires were distributed to 460 nurses, and of the 426 (92.6%) questionnaires returned, 409 (96.0%) were valid. The total mean score of nurses' knowledge, beliefs, and behavior about sarcopenia was 125.42 (SD 18.97), the mean score of knowledge latitude was 29.09 (SD 7.80), the mean score of attitude dimension was 57.53 (SD 7.63), and the mean score of behavior latitude was 38.80 (SD 10.71). Multiple linear regression analysis revealed that the nurse's position, Knowledge of sarcopenia, whether or not they were specialist nurses and years of experience in the workplace were the most significant factors correlated with the level of knowledge, belief, and practice (P < 0.05). CONCLUSIONS: In China, nurses have little knowledge about sarcopenia, but their attitude towards sarcopenia care is positive. However, there is potential for improvement in nursing behavior toward sarcopenia management. RELEVANCE TO CLINICAL PRACTICE: Managers are advised to develop targeted training programs for nurses. Further, it improves their screening and diagnosing abilities, allowing them to prevent and control sarcopenia more effectively.

Ashwagandha Ethanol Extract Attenuates Sarcopenia-Related Muscle Atrophy in Aged Mice.

The investigation focused on the impact of Withania somnifera (ashwagandha) extract (WSE) on age-related mechanisms affecting skeletal muscle sarcopenia-related muscle atrophy in aged mice. Beyond evaluating muscular aspects, the study explored chronic low-grade inflammation, muscle regeneration, and mitochondrial biogenesis. WSE administration, in comparison to the control group, demonstrated no significant differences in body weight, diet, or water intake, affirming its safety profile. Notably, WSE exhibited a propensity to reduce epidermal and abdominal fat while significantly increasing muscle mass at a dosage of 200 mg/kg. The muscle-to-fat ratio, adjusted for body weight, increased across all treatment groups. WSE administration led to a reduction in the pro-inflammatory cytokines TNF-α and IL-1ß, mitigating inflammation-associated muscle atrophy. In a 12-month-old mouse model equivalent to a 50-year-old human, WSE effectively preserved muscle strength, stabilized grip strength, and increased muscle tissue weight. Positive effects were observed in running performance and endurance. Mechanistically, WSE balanced muscle protein synthesis/degradation, promoted fiber differentiation, and enhanced mitochondrial biogenesis through the IGF-1/Akt/mTOR pathway. This study provides compelling evidence for the anti-sarcopenic effects of WSE, positioning it as a promising candidate for preventing sarcopenia pending further clinical validation.

Nutrition and Exercise Interventions on Skeletal Muscle Physiology, Injury and Recovery: From Mechanisms to Therapy.

Interventional strategies involving nutrition and physical exercise have been widely proposed to positively modulate skeletal muscle function, in both physiological and pathological states, such as obesity, T2DM, inflammatory diseases, cardiovascular diseases, aging, and sarcopenia [...].

Potential nutritional strategies to prevent and reverse sarcopenia in aging process: Role of fish oil-derived ω-3 polyunsaturated fatty acids, wheat oligopeptide and their combined intervention.

INTRODUCTION: Nutritional support is potentially considered an essential step to prevent muscle loss and enhance physical function in older adults. OBJECTIVES: This study aimed to assess the role of potential nutritional strategies, i.e., fish oil-derived ω-3 polyunsaturated fatty acids (PUFAs), wheat oligopeptide and their combined intervention, in preventing and reversing sarcopenia in aging process. METHODS: One hundred 25-month-old Sprague-Dawley rats were randomly divided into 10 groups, and 10 newly purchased 6-month-old rats were included in young control group (n = 10). Fish oil (200, 400 or 800 mg/kg body weight), wheat oligopeptide (100, 200 or 400 mg/kg body weight), fish oil + wheat oligopeptide (800 + 100, 400 + 200 or 200 + 400 mg/kg body weight) or the equal volume of solvent were administered daily by gavage for 10 weeks. The effects of these interventions on natural aging rats were evaluated. RESULTS: All intervention groups had a significant increase in muscle mass and grip strength and reduction in perirenal fat weight when compared to the aged control group (P < 0.05). The results of biochemical parameters, magnetic resonance imaging, proteomics and western blot suggested that the combination of wheat oligopeptide and fish oil-derived ω-3 PUFA, especially group WFM 2 (400 + 200 mg/kg body weight fish oil + wheat oligopeptide), was found to be more effective against aging-associated muscle loss than single intervention. Additionally, the interventions ameliorated fatty infiltration, muscle atrophy, and congestion in the intercellular matrix, and inflammatory cell infiltration in muscle tissue. The interventions also improved oxidative stress, anabolism, hormone levels, and inflammatory levels of skeletal muscle. CONCLUSIONS: The combination of fish oil-derived ω-3 PUFA and wheat oligopeptide was found to be a promising nutritional support to prevent and reverse sarcopenia. The potential mechanism involved the promotion of protein synthesis and muscle regeneration, as well as the enhancement of muscle strength.

Optimal serum 25-hydroxyvitamin D level to prevent sarcopenia in patients with heart failure: Insights from a dose-response relationship.

BACKGROUND AND AIMS: Low serum 25-hydroxyvitamin D (25 [OH]D) levels have been associated with sarcopenia, frailty, and risk of cardiovascular disease, whereas high levels negatively impact clinical outcomes. We determined optimal serum 25(OH)D concentrations to minimise the probability of sarcopenia in patients with heart failure (HF) by examining the dose-dependent relationship between serum 25(OH)D levels and sarcopenia. METHODS AND RESULTS: We enrolled 461 consecutive patients with HF (mean age, 72 ± 15 years; 39% female) who underwent dual-energy X-ray absorptiometry. Serum 25(OH)D levels were measured using a chemiluminescence immunoassay. Sarcopenia was diagnosed according to the 2019 Asian Working Group for Sarcopenia criteria. Overall, 49% of enrolled patients were diagnosed with sarcopenia. Adjusted logistic regression with restricted cubic spline function revealed that the odds ratio (OR) of sarcopenia increased in patients with HF presenting serum 25(OH)D levels <14.6 ng/ml or > 31.4 ng/ml, reaching the lowest OR at ∼20 ng/ml. Multivariate logistic regression revealed that a serum 25(OH)D level below 14.6 ng/mL was independently associated with the presence of sarcopenia (adjusted OR: 2.16, 95% confidence interval [CI]: 1.24-3.78). Incorporating serum 25(OH)D levels <14.6 ng/ml, but not <20.0 ng/ml, in the baseline model improved continuous net reclassification (0.334, 95% CI: 0.122-0.546) in patients with HF. CONCLUSION: A U-shaped relationship exists between serum 25(OH)D levels and sarcopenia probability in patients with HF. Maintaining serum 25(OH)D levels between 14.6 and 31.4 ng/ml may help prevent sarcopenia in patients with HF.

Potential of prehabilitation in hepatocellular carcinoma: a narrative review of available evidence.

BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths. Patients with HCC are often significantly affected by sarcopenia and cancer cachexia. Prehabilitation, a multimodal pre-operative exercise and nutritional intervention, has been implemented with varying degrees of success in enhancing outcomes among other gastrointestinal (GI) malignancies. However, remarkably little is described how prehabilitation may be beneficial in improving outcomes among those with HCC. Thus, a narrative review is warranted to examine previously developed prehabilitation models and determine how interventions affected sarcopenia as a prognosticator in HCC and other GI malignancies. This article seeks to offer guidance on how prehabilitation may be implemented for those with HCC based on available data published on other GI malignancies and serve as a call for additional research specific to the value of prehabilitation in HCC. METHODS: Independent key-term searches were conducted by all authors of various databases (PubMed, ScienceDirect, Google Scholar) for relevant articles examining role, safety, and efficacy of prehabilitation in HCC and/or other GI malignancies. Relevant articles pertaining to sarcopenia, Enhanced Recovery After Surgery (ERAS) guidelines, and prehabilitation models were collected and analyzed. Review authors held multiple meetings to ensure coherence of narrative review process and final product. KEY CONTENT AND FINDINGS: Patients with HCC often suffer from sarcopenia and/or cachexia, which are known to be associated with poorer outcomes. The benefits of a prehab program in patients with HCC are not well described in current literature, but in referencing the benefits of prehab programs in other GI malignancies and ERAS protocols on patients undergoing liver resection and liver transplant, there is potential for a similar multimodal program to yield similar benefits and healthcare cost-savings. However, further investigation is needed as HCC has multiple etiologies and affects a wide variety of people. CONCLUSIONS: A multimodal prehabilitation program emphasizing regular aerobic and resistance exercise, nutritional optimization, lifestyle modifications, mental health and wellness practices, with a nurse and rehabilitation physician's oversight may improve outcomes in patients undergoing treatment for HCC. However further investigation into specific exercise models, optimal nutrition regimens and benefit/cost analysis of a multimodal prehabilitation program within this complex patient population is needed.

Synergistic effects of MFG-E8 and whey protein on mitigating d-galactose-induced sarcopenia through PI3K/AKT/PGC-1α and MAPK/ERK signaling pathways.

Milk fat globule epidermal growth factor 8 (MFG-E8) and whey protein have emerged as promising bionutrient supplements for enhancing skeletal muscle mass and function. In the present study, aging-related sarcopenia rat model was employed to elucidate the effects of the combined administration of MFG-E8 and whey protein on the catabolism and anabolism of gastrocnemius protein. Combined intervention led to notable enhancements in the antioxidative stress status and mitochondrial biogenesis capacity of gastrocnemius muscle fibers in the aging rats, concomitant with a significant inhibition of lipid accumulation. Moreover, the synergistic effect of MFG-E8 and whey protein was found to exert modulatory effects on key signaling pathways, including PI3K/Akt/PGC-1α pathway and MAPK/ERK signaling pathways in the gastrocnemius muscle of the aging rats. Specifically, this combined intervention was observed to promote mitochondrial biogenesis and regulate the expression of protein anabolism and catabolism-related regulators, thereby facilitating the alleviation of mitochondrial oxidative stress and enhancing biogenesis in gastrocnemius tissues. The findings of our study provide compelling evidence for the potential of MFG-E8 as a promising dietary supplement with antisarcopenic properties to ameliorate muscle protein metabolism disorders and mitigate mitochondrial-mediated myoblast apoptosis induced by oxidative stress.

Walking exercise through smartphone application plus branched-chain amino acid supplementation benefits skeletal muscle mass and strength in liver cirrhosis: A prospective control trial.

INTRODUCTION AND OBJECTIVES: Whether a combination of exercise and branched-chain amino acid (BCAA) supplementation was more beneficial than those given alone in sarcopenia related to liver cirrhosis (LC) is unknown. Widely used smartphone applications provide continuous and easily expandable management of chronic liver disease (CLD). This study is to investigate the effects of unsupervised walking exercise using WeChat combined with BCAA supplementation on skeletal muscle mass and strength in LC. MATERIALS AND METHODS: The 127 LC patients of Child-Pugh A/B were assigned to group A (BCAA supplements, n=42), group B (walking exercise, n=43) and group C (walking exercise plus BCAA supplements, n=42). Laboratory data, average daily steps, serum BCAA, skeletal muscle mass index (SMI) and grip strength were analyzed pre- and 3 months after interventions. RESULTS: Of the 124 patients who completed interventions, albumin and daily steps were significantly increased in all groups (p=0.0001). Post-intervention BCAA were significantly elevated in group A (A vs B, p=0.001) and C (C vs B, p=0.012;). While post-intervention daily steps in group B (B vs A, p=0.0001) and C (C vs A, p=0.0001) were higher. Grip strength (C vs A, p=0.020; C vs B, p=0.036) and SMI (C vs A, p=0.035; C vs B, p=0.012) were increased in group C. Prevalence of sarcopenia was significantly decreased in group C (p=0.015). CONCLUSIONS: A combination of unsupervised walking exercise using smartphone applications and BCAA supplementation might be an effective and safe treatment for cirrhosis patients with Child-Pugh A/B to improve skeletal muscle mass and strength or to prevent progress of sarcopenia.

Nutrition Interventions on Muscle-Related Components of Sarcopenia in Females: A Systematic Review of Randomized Controlled Trials.

Sarcopenia is a skeletal muscle disease categorized by low muscle strength, muscle quantity or quality, and physical performance. Sarcopenia etiology is multifaceted, and while resistance training is widely agreed upon for prevention and treatment, disease progression is also highly related to poor diet. The incidence of sarcopenia appears sex-specific and may be increased in females, which is problematic because dietary quality is often altered later in life, particularly after menopause. Identifying effective nutrition or supplementation interventions could be an important strategy to delay sarcopenia and related comorbidities in this vulnerable population. This systematic review examined randomized controlled trials (RCTs) of nutrition strategies on muscle-related components of sarcopenia in middle-aged and older females. A protocol was registered (PROSPERO CRD42022382943) and a systematic search of MEDLINE and CINAHL was undertaken. RCTs from 2013 to 2023 that assessed nutrition-only interventions on muscle mass, muscle strength, and physical function in female participants were included. Fourteen RCTs were included based on selection criteria. Study designs and interventions were heterogeneous in supplementation type and amount, age, and duration. Six RCTs reported beneficial effects of protein, Vitamin D, Vitamin D and Magnesium (Mg), and fish oil on muscle protein synthesis, muscle strength, and/or muscle function. Eight studies that examined various protein interventions, VitD alone, Mg alone, and dairy derivatives did not demonstrate any effect. Exercise appeared to modulate results in several studies. Nutrition interventions alone are likely to have a limited but positive effect on muscle-related components of sarcopenia in females. Current evidence suggests that a combination of dietary intervention and exercise is likely to be key to preventing and treating sarcopenia in middle aged and older females and there is a need for well-designed nutrition based studies in this population.

Butyrate supplementation reduces sarcopenia by repairing neuromuscular junction in patients with chronic obstructive pulmonary disease.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is associated with an intestinal leak and neuromuscular junction (NMJ) degradation, which contributes to physical compromise and accelerated age-related muscle loss, called sarcopenia. However, the relevant interventions partly remain ineffective. We investigated the effects of exogenous butyrate on sarcopenia and physical capacity with relevance to intestinal permeability and NMJ integrity in COPD patients. METHODS: COPD patients were randomized into placebo (n = 67) and butyrate (n = 64) groups in a double-blind manner. The patients in the butyrate group received one 300 mg capsule a day for 12 weeks. We measured circulating markers of intestinal leak (zonulin), systemic bacterial load (LBP), and NMJ loss (CAF22), along with handgrip strength (HGS), and short physical performance battery (SPPB) at baseline and 12 weeks. RESULTS: Butyrate supplementation improved HGS and gait speed in COPD patients. Among SPPB indices, butyrate improved the ability to maintain postural balance and walking and prevented a decline in the ability to rise from a chair. Butyrate also reduced the plasma levels of zonulin, LBP, and CAF22 levels in COPD patients (all p < 0.05). Regression analysis revealed significant associations of plasma zonulin and CAF22 with HGS, gait speed, and cumulative SPPB scores in butyrate group. These changes were associated with reduced markers of inflammation and muscle damage. CONCLUSION: Butyrate may provide a therapeutic approach to sarcopenia and physical dependency in COPD by repairing intestinal leak and NMJ loss.