Search Results (297)

This pilot, randomized, double-blind, placebo-controlled trial investigated the effects of branched-chain amino acids (BCAAs)—provided in a 2:1:1 ratio of leucine:isoleucine:valine—combined with exercise on fatigue, physical performance, and quality of life in older adults. Twenty participants (63% female; BMI: 35 ± 2 kg/m²; age: 70.5 ± 1.2 years) were randomized to 8 weeks of either exercise + BCAAs (100 mg/kg body weight/d) or exercise + placebo. The program included moderate aerobic and resistance training three times weekly. Physical function was assessed using handgrip strength, chair stands, gait speed, VO₂ max, and a 400 m walk. Psychological health was evaluated using the CES-D, Fatigue Assessment Scale (FAS), Insomnia Severity Index (ISI), and global pain, fatigue, and quality of life using a visual analog scale (VAS). Significant group x time interactions were found for handgrip strength (p = 0.03), chair stands (p < 0.01), and 400 m walk time (p < 0.01). Compared to exercise + placebo, exercise + BCAAs showed greater improvements in strength, mobility, and endurance, along with reductions in fatigue (−45% vs. +92%) and depressive symptoms (−29% vs. +5%). Time effects were also observed for ISI (−30%), FAS (−21%), and VAS quality of life (16%) following exercise + BCAA supplementation. These preliminary results suggest that BCAAs combined with exercise may be an effective way to improve physical performance and reduce fatigue and depressive symptoms in older adults. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra, resulting in motor symptoms such as bradykinesia, tremor, rigidity, and postural instability, as well as a wide variety of non-motor manifestations. Branched-chain amino acids (BCAAs)—leucine, isoleucine, and valine—are essential nutrients involved in neurotransmitter synthesis, energy metabolism, and cellular signaling. Emerging evidence suggests that BCAA metabolism is intricately linked to the pathophysiology of PD. Dysregulation of BCAA levels has been associated with energy metabolism, mitochondrial dysfunction, oxidative stress, neuroinflammation, and altered neurotransmission. Furthermore, the branched-chain ketoacid dehydrogenase kinase (BCKDK), a key regulator of BCAA catabolism, has been implicated in PD through its role in modulating neuronal energetics and redox homeostasis. In this review, we synthesize current molecular, genetic, microbiome, and clinical evidence on BCAA dysregulation in PD to provide an integrative perspective on the BCAA–PD axis and highlight directions for future translational research. We explored the dualistic role of BCAAs as both potential neuroprotective agents and metabolic stressors, and critically examined the therapeutic prospects and limitations of BCAA supplementation and BCKDK targeting. Full article

Background/Objectives: Diabetic kidney disease (DKD) is a major complication of type 2 diabetes mellitus (T2DM), and recent research highlights that amino acid composition—rather than total protein intake alone—may influence DKD risk. This study aimed to evaluate the associations between dietary protein intake, specific amino acid profiles, and the risk of DKD among adults with T2DM. Methods: A total of 378 T2DM patients were enrolled in this cross-sectional study. Dietary intake was assessed via a 24 h recall and a validated semi-quantitative food frequency questionnaire. Nutrient analysis was based on the Taiwanese Food Composition Database. Participants were categorized into three protein intake groups: Group 1 (≤0.8 g/kg), Group 2 (0.9–1.2 g/kg), and Group 3 (≥1.3 g/kg). Cox proportional hazards models were used to evaluate the associations of crude protein, branched-chain amino acids to aromatic amino acids (BCAA/AAA) ratio, and ketogenic amino acid intake with DKD risk. Adjustments were made for age, sex, diabetes duration, and blood pressure. Results: While crude protein intake showed no significant association with DKD risk, higher intake of ketogenic amino acids (e.g., leucine and lysine) was consistently and significantly associated with reduced DKD risk (adjusted HR range = 0.698–0.716, p < 0.01). Our findings highlight the protective potential of ketogenic amino acids such as leucine and lysine, which were significantly associated with lower DKD risk. The BCAA/AAA ratio also showed a downward trend in DKD risk, though not statistically significant. Kaplan–Meier analysis revealed that moderate protein intake (0.9–1.2 g/kg) corresponded to the most favorable DKD-free survival. Conclusions: Our findings suggest that, beyond total protein quantity, the intake of ketogenic amino acids may play a protective role in DKD prevention. Moderate protein consumption combined with higher leucine and lysine intake appears beneficial. These results support incorporating amino acid profiling in dietary strategies for DKD risk reduction. Further longitudinal and interventional studies are recommended to validate these associations. Full article

Background/Objectives: Studies have reported an increased risk of type 2 diabetes among people with higher protein intake. Moreover, branched-chain amino acids (BCAA) are reported to be positively associated with insulin resistance (IR). However, it is not understood whether elevated levels of BCAA are causal to IR development, or if higher BCAA are a marker of IR. The objective of this study was to examine the effects of long-term protein and carbohydrate supplementation on plasma BCAA levels, and the relationship between plasma BCAA and IR in postmenopausal women. Methods: Stored samples and data from 84 postmenopausal women who participated in a protein supplementation trial (SPOON) were included. Exclusion criteria consisted of protein intakes less than 0.6 g/kg or greater than 1.0 g/kg, a body mass index (BMI) greater than 32 kg/m² or less than 19 kg/m² diseases, and conditions and medications known to impact musculoskeletal health. Subjects were randomized to a whey protein (PRO: n = 38) or maltodextrin supplement (CHO: n = 46) for 18 months. Plasma BCAA, homeostatic model assessment of insulin resistance (HOMA-IR) and body composition were analyzed at baseline and 18 months. Results: At baseline, there were no significant associations between plasma BCAA and IR. There were also no significant changes in plasma BCAA or IR by study arm. However, there was a significant positive association between plasma BCAA and IR in both groups at 18 months (CHO: r = 0.35, p = 0.02; PRO: r = 0.35, p = 0.03). Conclusions: Findings from this study warrant future research to examine other diet and lifestyle factors that may mediate the relationship between circulating BCAA and IR in postmenopausal women. Full article

Diabetes mellitus (DM) is a complex global pandemic that frequently leads to multiple complications. Diabetic cardiomyopathy (DCM) is the primary cause of heart failure in patients with type 1 and 2 diabetes and is fundamentally characterized by abnormalities in myocardial structure and function. Metabolic disorders occupy a leading role in the pathogenesis of DCM, manifesting as disrupted substrate metabolism, dysregulated signaling pathways, and energy imbalance. Given the limited benefits of conventional therapeutic strategies targeting glucolipid metabolism, increasing research efforts have focused on amino acid metabolism. Amino acids are involved in the synthesis of nitrogen-containing compounds and serve as an energy source under specific conditions. Moreover, emerging studies demonstrate that metabolic disturbances of specific amino acids—such as branched-chain amino acids (BCAAs), glutamine, and arginine—exacerbate mitochondrial dysfunction and oxidative stress, thereby promoting myocardial fibrosis and cardiomyocyte injury. Therefore, this review aims to summarize the general characteristics and regulatory pathways of amino acid metabolism, as well as the specific mechanisms by which metabolic alterations of amino acids contribute to the pathogenesis and progression of diabetic cardiomyopathy, with the hope of advancing more effective translational therapeutic approaches. Full article

Background/Objectives: Weight loss interventions in individuals with overweight or obesity result in reductions in both fat mass and lean body mass (LBM). While fat loss is the primary therapeutic target, preserving LBM may have favorable health implications. This narrative review evaluates the role of amino acid supplementation, including essential amino acids (EAAs) and branched-chain amino acids (BCAAs), in supporting the preservation of LBM during weight loss induced by lifestyle interventions, pharmacotherapy, or bariatric surgery. Methods: This is a narrative review of preclinical and clinical studies examining the effects of amino acid supplementation during calorie restriction on body composition and, when available, functional outcomes. A comprehensive search was conducted in the PubMed, Scopus, and Web of Science databases. Results: Evidence suggests that EAA and peptide-based supplementation may help preserve LBM during periods of reduced energy intake, particularly when protein intake from whole foods is limited. Benefits appear more consistent when supplementation is combined with resistance exercise. BCAA supplementation alone has shown variable effects, especially in sedentary individuals or when total protein intake is already sufficient. Anabolic resistance associated with obesity may attenuate the muscle protein synthesis response to dietary amino acids. Conclusions: Amino acid supplementation may support the maintenance of LBM during weight loss, particularly under conditions of low protein intake or in conjunction with exercise. Further research is needed to determine the clinical significance of LBM changes and identify optimal supplementation strategies. Full article

Background/Objectives: Canine intervertebral disc herniation (IVDH) is an important musculoskeletal pathology. Unlike in humans, IVDH mechanisms in dogs are underinvestigated from a system-level integrative omics point of view. The aim of this study was to identify key serum molecular players in canine IVDH. Methods: An integrative multi-omics approach combining high-resolution LC-MS-based untargeted metabolomics and tandem mass tag (TMT)-based proteomics was applied. Additionally, serum zinc concentration was determined by spectrophotometry. Results: Nineteen serum metabolites were differentially abundant in IVDH dogs. Metabolite analysis highlighted dysregulation in lipoic acid and branched-chain amino acid (BCAA) metabolism, with elevated levels of valine, leucine, and isoleucine in IVDH. These findings suggest disrupted energy, nitrogen, and neurotransmitter metabolism, potentially contributing to the IVDH pathophysiology. Additionally, lower serum uridine, possibly influenced by BCAA accumulation, was observed, indicating altered neuroinflammatory responses. ELISA validation confirmed elevated serum levels of zinc-α2-glycoprotein (ZAG), alpha-1-microglobulin/bikunin precursor (AMBP), and vitronectin (VTN) in IVDH, supporting immune modulation and neuroprotective mechanisms. Serum prekallikrein (KLKB1) and Protein C inhibitor (SERPINA5), involved in fibrin cloth formation, were found to be lowered in IVDH patients. Pathway enrichment revealed disturbances in aromatic amino acid biosynthesis, with elevated phenylalanine, tyrosine, and tryptophan influencing neurotransmission and inflammation. In addition, elevated serum Zn concentration emphasized its antioxidant importance in immune response, wound healing, and neuropathic pain signaling. Conclusions: Integration with our prior CSF multi-omics data reinforced the relevance of identified molecules in IVDH-associated neurodegeneration, inflammation, and repair processes. This study offers insight into potential diagnostic biomarkers and therapeutic targets for canine IVDH through serum-based molecular profiling. Full article

Cancer cachexia is a multi-organ and multifactorial syndrome characterized by muscle wasting (with or without adipose tissue loss) and systemic inflammation in patients with advanced malignancies. Gut microbiota dysbiosis, particularly the depletion of short-chain fatty acid (SCFA)-producing bacteria, may contribute to the progression of cancer cachexia. Studies in both murine models and humans consistently associate cachexia with a decline in SCFA-producing gut microbiota commensals and an overgrowth of pro-inflammatory pathobionts. These microbial imbalances may lead to reduced levels of SCFAs and branched-chain amino acids (BCAAs) and alter the normal bile acid profile. BCAAs and the maintenance of a normal bile acid profile are associated with muscle synthesis and decreased breakdown. While SCFAs (acetate, propionate, and butyrate), contribute to intestinal barrier integrity and immune regulation. SCFA depletion may increase gut permeability, allowing bacterial endotoxins, such as lipopolysaccharide (LPS), to enter the bloodstream. This may lead to chronic inflammation, muscle catabolism, and impairment of anabolic pathways. Interventions targeting gut microbiota in preclinical models have mitigated inflammation and muscle loss. While clinical data are limited, it suggests an improvement in immune functions and better tolerance to anticancer therapies. Current evidence is predominantly derived from cross-sectional studies suggesting associations without causality. Thus, future longitudinal studies are needed to identify biomarkers and optimize personalized therapy. Full article

To compare the quality and nutritional differences of crayfish under freshwater and saline-alkali water aquaculture conditions, this study systematically analyzed the biochemical composition, physical properties, and nutritional evaluation of crayfish (Procambarus clarkii) cultivated in saline-alkali water (PC-SW) and freshwater aquaculture (PC-FW), respectively. The results showed that crayfish from PC-SW had higher crude protein, crude fat, water content, and ash content. At the same time, PC-SW had a higher meat yield (16.18 ± 0.74%) than PC-FW (p < 0.05), with no significant changes in the head weight ratio or hepatopancreas weight ratio, indicating superior crayfish quality. The trace element content of PC-SW differed significantly from that of PC-FW (p < 0.05), with the exception of Cu. To some extent, the amino acid and fatty acid compositions were similar. The no essential amino acids content of crayfish cultivated under freshwater and saline-alkali conditions was higher than the essential amino acids content. The total branched-chain amino acids (BCAAs) content was higher than the total aromatic amino acids (AACs) content in both groups; however, the BCAA to AAC ratio was similar, at approximately 2.14. The essential amino acid index results were 69.01 and 68.02, respectively. Finally, betaine and nucleotide concentrations increased and geosmin content was significantly reduced in PC-SW (3.13 ± 0.09 μg/kg) compared to PC-FW (4.32 ± 0.09 μg/kg) (p < 0.05), implying that PC-SW crayfish had a better flavor. Our findings revealed that cultivating crayfish under saline-alkali conditions can significantly improve the nutritional quality and flavor of muscle. Full article

In humans, heart failure (HF) and cancer are among the leading causes of morbidity and mortality. A growing body of evidence highlights a bidirectional relationship between these conditions, underpinned by shared risk factors and overlapping pathophysiological pathways. This review aims to explore the emerging role of the intestinal microbiome as a common mechanistic link between HF and cancer. Specifically, we examine how microbial dysbiosis and its metabolic products—such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids, lipopolysaccharides (LPS), and branched-chain amino acids (BCAAs)—contribute to inflammation, immune dysregulation, oxidative stress, and metabolic dysfunction. These mechanisms promote multiorgan impairment and establish a vicious cycle that fuels both tumorigenesis and cardiac deterioration. HF, cancer, and the gut microbiome are not isolated entities but are deeply interconnected through shared biological mechanisms—including chronic inflammation, microbial dysbiosis, immune and neurohumoral modulation, and metabolic derangement. These findings support the concept of a microbiome-centered axis involving the gut, heart, and tumors, which may underlie many chronic disease processes. Understanding these interactions may provide novel insights into disease pathogenesis and uncover promising therapeutic targets that leverage microbiome modulation to prevent or treat HF, cancer, and other systemic diseases. Full article

Branched-chain amino acids (BCAAs) are essential for protein synthesis and play a crucial role in activating signaling pathways that regulate cell growth and division. Growing evidence reveals their complex role in cancer, particularly in how they support the metabolic reprogramming of tumor cells. BCAAs contribute to an environment that promotes tumor growth and survival by affecting energy balance and key cellular signaling networks. This review highlights recent advances in understanding how BCAAs influence cancer metabolism, emphasizing their dual function as both essential nutrients and sources of metabolic fuel. It also explores how BCAAs interact with other metabolic pathways, revealing potential targets for therapy. By uncovering these cancer-specific dependencies on BCAAs, this work points to promising strategies for disrupting tumor progression and developing new treatment approaches. Full article

Background: Muscle loss during sarcopenia and atrophy is also commonly associated with age-related insulin resistance. Interestingly, branched-chain amino acids (BCAA) which are known for stimulating muscle protein synthesis are commonly elevated during insulin resistance and sarcopenic obesity. Objectives: This study investigated the effects of the interplay between atrophy and insulin resistance on insulin sensitivity, mitochondrial metabolism, and BCAA catabolic capacity in a myotube model of skeletal muscle insulin resistance. Methods: C2C12 myotubes were treated with dexamethasone to induce atrophy. Insulin resistance was induced via hyperinsulinemia. Gene and expression were measured using qRT-PCR and Western blot, while mitochondrial and lipid content were assessed using fluorescent staining. Cell metabolism was analyzed via Seahorse metabolic assays. Results: Both dexamethasone-induced atrophy and insulin resistance independently reduced insulin-stimulated pAkt levels, as well as mitochondrial function and content. However, neither treatment affected gene or protein expression associated with mitochondrial biogenesis or content. Although dexamethasone independently reduced insulin sensitivity in otherwise previously insulin-sensitive cells, dexamethasone had no significant effect on extracellular BCAA content. Conclusions: Our findings indicate the metabolic interplay between atrophy and insulin resistance and demonstrate that both can reduce mitochondrial function, though only limited effects were observed on indicators of BCAA catabolism and utilization. This emphasizes the need for future studies to investigate the mechanisms that underlie atrophy and other metabolic disorders to develop new interventions. Full article

Cancer-associated sarcopenia is closely linked to the prognosis of cancer patients, making its management a critical aspect of cancer treatment. Branched-chain amino acids (BCAAs) are known to promote skeletal muscle growth in healthy individuals; however, their efficacy in cancer patients remains controversial. In this study, we investigated the effects of BCAAs on cancer-associated sarcopenia to identify the underlying mechanisms that may suppress their effectiveness. In both a mouse cachexia model and an in vitro cachexia model, BCAAs did not significantly reduce oxidative stress, improve oxidative phosphorylation, suppress cytokine production, or enhance muscle mass and maturation, as observed in non-cancer-bearing models. Furthermore, treatment with 5-fluorouracil exacerbated sarcopenia in the mouse cachexia model, independent of tumor weight reduction, and this deterioration was not ameliorated by a BCAA-supplemented diet. The ineffectiveness of BCAAs was attributed to impaired BCAA catabolism, characterized by the decreased expression of branched-chain α-ketoacid dehydrogenase (BCKD) and increased levels of its inactive phosphorylated form, which were driven by elevated expression of BCKD kinase. These metabolic alterations were induced by high-mobility group box-1 (HMGB1). Notably, caprylic acid reversed these impairments in BCAA metabolism, thereby restoring BCAA efficacy. Our findings suggest that enhancing BCAA metabolism may improve their therapeutic potential in the treatment of cancer-associated sarcopenia. Full article

Background: During aging, protein nutrition has a bidirectional role in regulating healthy lifespan by modulating body metabolism and neurological function. However, the current “low-high” hypothesis on the dynamics of protein requirements is mainly based on male animal models, and its applicability to female physiology (e.g., estrogen fluctuations) is unclear. The present study aims to fill the gap in the study of protein demand dynamics in female naturally aging mice and to investigate the effects of different protein levels on the health status of female C57BL/6J mice at different stages of aging. Methods: In this study, four dietary interventions (high protein, HP; low protein, LP; model test, MT; and control, C) were evaluated by constructing a C57BL/6J female mouse model at three ages, 9 M (9 months), 16 M (16 months), and 20 M (20 months), which are approximately equivalent to 34, 65, and 78 years of age in humans, respectively, to determine the effects on naturally aging mice. The effects of the interventions were quantitatively described by behavioral, neuropathological, oxidative, and inflammatory indices and NMR metabolomics using Principal Component Analysis to construct a comprehensive quantitative scoring method. Results: The comprehensive quantitative scores Fsum was highest in the HP group, lowest in the LP group, and in between in the MT group. The HP intervention showed the most significant improvement in the aged group (20 M) mice, with a 35.2% reduction in avoidance latency (p < 0.01) and a 32.9% increase in pyramidal cell density in the hippocampal CA1 region (p < 0.05), while the LP intervention led to a cognitive decline in the mice, with an avoidance latency that was prolonged by 15.2% (p < 0.05). Metabolomics analysis revealed that mouse samples of all ages showed age-dependent metabolic re-adaptation: the 9 M group may reflect gut microbial metabolism rather than direct host TCA cycle activity, suggesting an indirect association with energy metabolism; an enhanced degradation of branched-chain amino acids (BCAAs) was seen in the middle-aged group (16 M); and amino acid biosynthesis was predominant in the old group (20 M). Conclusions: Female mice have sustained neuromotor benefits to high-protein diets at different aging stages, and the dynamics of their protein requirements differ significantly from those of males. The study reveals the critical role of gender factors in protein nutritional strategies and provides an experimental basis for precise protein supplementation in older women. Full article

Background: Higher circulating branched-chain amino acids (BCAAs) are linked to cardiometabolic and neurological diseases. While diet is the primary BCAA source, its impact on circulating levels remains unclear. This study examined the association between dietary intake and circulating BCAA concentrations in a large population-based sample. Methods: Data from 2159 participants (58.2% women, mean age 53.4 ± 8.6 years) were analyzed. Dietary intake was assessed using a questionnaire covering 91 individual food items, 9 nutrient categories, and 3 dietary patterns. BCAA concentrations were measured via LC-MS. All analyses were stratified by gender. Results: Circulating BCAA levels were higher in men than in women. BCAA levels were negatively associated with vegetables (standardized β = −0.029, p = 0.088; −0.051, p = 0.003; −0.038, p = 0.043 for leucine, isoleucine, and valine, respectively), dairy (−0.037, p = 0.029; −0.063, p < 0.001; −0.041, p = 0.028), and fruit (−0.031, p = 0.084; −0.039, p = 0.030; −0.041, p = 0.034), and a positive trend was observed for meat and meat-derived products, but the associations did not reach statistical significance. Vegetal protein, total carbohydrates, and monosaccharides showed a significant negative association with circulating BCAAs levels. Participants who complied with “dairy ≥ 3/day”, “meat ≤ 5/week”, or “at least three guidelines” had lower circulating BCAA levels. Conclusions: Circulating BCAA levels were negatively associated with dairy, vegetables, fruits, plant protein, carbohydrates, non-digestible fiber, calcium, and iron. While circulating BCAA levels were linked to meat consumption and adherence to dietary guidelines, the association was not linear. Differences were observed between men and women, which may be attributed to variations in dietary intake and preferences. Full article