Beta-hydroxy-beta-methylbutyrate Research Articles

β-Hydroxy β-Methyl Butyric Acid (HMB) and Its Potential Doping Relevance: A Pilot Study on Its Urinary Excretion Profile.

β-hydroxy β-methyl butyric acid (HMB), either as the free acid or in the form of its calcium salt, is a component of several dietary supplements marketed to enhance sports performance, due to its role in protein synthesis. In this pilot study, we investigated the urinary excretion profile of HMB, an endogenous metabolite of the essential amino acid leucine. The endogenous reference ranges of HMB, in human urine samples, were monitored by collecting samples from 20 volunteers. Data obtained were compared with those from controlled excretion studies, following the intake of a 3-g oral dose of HMB. Urine samples were analyzed through a targeted procedure employing a conventional GC-MS system operating in SIM mode. Our results show that the excreted urinary concentration of HMB significantly exceeds the range of endogenous concentrations for at least 24 h, making possible to detect its exogenous origin.

Build muscles and protect myelin

Abstract Multiple sclerosis (MS) is a chronic and debilitating autoimmune disease of the central nervous system (CNS) in which a CNS-driven immune response destroys myelin, leading to wide range of symptoms including numbness and tingling, vision problems, mobility impairment, etc. Oligodendrocytes are the myelinating cells in the CNS, which are generated from oligodendroglial progenitor cells (OPCs) via differentiation. However, for multiple reasons, OPCs fail to differentiate to oligodendrocytes in MS and as a result, stimulating the differentiation of OPCs to oligodendrocytes is considered beneficial for MS. The β-hydroxy β-methylbutyrate (HMB) is a widely-used muscle-building supplement in human and recently it has been shown that low-dose HMB is capable of stimulating the differentiation of cultured OPCs to oligodendrocytes for remyelination. Moreover, other causes of autoimmune demyelination are the decrease and/or suppression of Foxp3-expressing anti-autoimmune regulatory T cells (Tregs) and upregulation of autoimmune T-helper 1(Th1) and Th17 cells. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS in which the autoimmune demyelination is nicely visible. It has been reported that in EAE mice, oral HMB upregulates Tregs and decreases Th1 and Th17 responses, leading to remyelination in the CNS. Here, we analyze these newly-described features of HMB, highlighting the putative promyelinating nature of this supplement.

Total Synthesis and Anticancer Evaluation of BZR-cotoxin IV

Anticancer peptides (ACPs) is a potential alternative for future cancer therapy. ACPs specifically inhibit cancer cells through a non-enzymatic membranolysis mechanism. One potential anticancer peptide worthy of investigation is BZR-cotoxin IV. Currently, research on BZR-cotoxin IV is limited to isolation, making it an interesting area for further development. One approach to developing BZR-cotoxin IV is through chemical synthesis techniques. This compound belongs to the group of cyclodepsipeptides that are naturally produced by the fungus Bipolaris zeicola Race 3. The synthesis of BZR cotoxin IV involves 3 steps: (1) Synthesis of the hydroxy acid precursor by conversion of L-valine amino acid to (2R)-hydroxyisovaleric acid, (2) synthesis of the linear depsipeptide using solid-phase peptide synthesis on 2-chlorotrityl chloride resin and (3) cyclization of the linear depsipeptide using solution phase synthesis to produce the BZR cotoxin IV compound with a purity of 11.7 %. BZR-cotoxin IV was characterized using HR-TOF-MS and 1H and 13C-NMR to validate the desired product. Anticancer activity testing was performed using the Resazurin assay on the HeLa cancer cell line, resulting in an IC50 of 187.50 μg/mL (214.014 μM) categorized as moderate. HIGHLIGHTS The chemical synthesis of BZR-cotoxin IV compounds has not been firstly reported. The synthesis of BZR-cotoxin IV was accomplished through a combination of solid-phase and solution-phase peptide synthesis. The objective was to synthesize and evaluate BZR-cotoxin IV for its cancer properties. GRAPHICAL ABSTRACT

A rapid review of nutrition and exercise approaches to managing unintentional weight loss, muscle loss, and malnutrition in cancer.

This narrative review summarizes the evidence for nutrition, exercise, and multimodal interventions to maintain weight and muscle mass and prevent malnutrition from meta-analysis, systematic reviews, and randomized controlled trials published within the last 5 years, and in comparison to future research priority areas identified by international guidelines. Dietary counseling with oral nutrition support (ONS), escalated to enteral nutrition if weight loss continues, is the gold standard treatment approach to maintaining weight and preventing malnutrition. Recent ONS trials with dietary counseling show promising findings for weight maintenance, extending the literature to include studies in chemoradiotherapy, however, change in body composition is rarely evaluated. Emerging trials have evaluated the impact of isolated nutrients, amino acids, and their derivatives (ie, β-hydroxy β-methylbutyrate) on muscle mass albeit with mixed effects. There is insufficient evidence evaluating the effect of exercise interventions on unintentional weight loss, muscle mass, and malnutrition, however, our knowledge of the impact of multimodal nutrition and exercise interventions is advancing. Prehabilitation interventions may attenuate weight and muscle loss after surgery, particularly for patients having gastrointestinal and colorectal surgery. Multimodal trials that commence during treatment show mixed effects on weight and muscle mass when measured. This review highlights that the evidence for preventing unintentional weight loss and malnutrition from cancer treatment is strong within nutrition. Multimodal interventions are emerging as effective interventions to prevent unintentional weight loss. Promising interventions are demonstrating improvements in muscle mass, however further exploration through studies designed to determine the effect on muscle is required.

Comprehensive stable-isotope tracing of glucose and amino acids identifies metabolic by-products and their sources in CHO cell culture

Mammalian cell culture processes are widely utilized for biotherapeutics production, disease diagnostics, and biosensors, and hence, should be optimized to support robust cell growth and viability. However, toxic by-products accumulate in cultures due to inefficiencies in metabolic activities and nutrient utilization. In this study, we applied comprehensive 13C stable-isotope tracing of amino acids and glucose to two Immunoglobulin G (IgG) producing Chinese Hamster Ovary (CHO) cell lines to identify secreted by-products and trace their origins. CHO cells were cultured in media formulations missing a single amino acid or glucose supplemented with a 13C-tracer of the missing substrate, followed by gas chromatography-mass spectrometry (GC-MS) analysis to track labeled carbon flows and identify by-products. We tracked the sources of all secreted by-products and verified the identity of 45 by-products, majority of which were derived from glucose, leucine, isoleucine, valine, tyrosine, tryptophan, methionine, and phenylalanine. In addition to by-products identified previously, we identified several metabolites including 2-hydroxyisovaleric acid, 2-aminobutyric acid, L-alloisoleucine, ketoisoleucine, 2-hydroxy-3-methylvaleric acid, desmeninol, and 2-aminobutyric acid. When added to CHO cell cultures at different concentrations, certain metabolites inhibited cell growth while others including 2-hydroxy acids, surprisingly, reduced lactate accumulation. In vitro enzymatic analysis indicated that 2-hydroxy acids were metabolized by lactate dehydrogenase suggesting a possible mechanism for lowered lactate accumulation, e.g., competitive substrate inhibition. The 13C-labeling assisted metabolomics pipeline developed and the metabolites identified will serve as a springboard to reduce undesirable by-products accumulation and alleviate inefficient substrate utilization in mammalian cultures used for biomanufacturing and other applications through altered media formulations and pathway engineering strategies.

A systematic review to assess the impact of amino acids or their derivatives on skeletal muscle wasting in critically ill patients

BackgroundIt is plausible that supplementation with specific amino acids or metabolites could attenuate skeletal muscle wasting during critical illness. The aim of this systematic review was to explore if amino acids or their derivatives impact skeletal muscle wastage in critically ill adults. MethodsFour databases were systematically searched to identify randomised control trials which delivered enteral supplemental amino acids, or their metabolites compared with placebo, standard care or no intervention, to critically ill patients and reported outcomes of skeletal muscle mass, plasma amino acids, nitrogen balance, or muscle strength. Two authors independently completed screening, data extraction, and risk of bias assessment using the Cochrane Risk of Bias 2 Tool. A meta-analysis was planned but heterogeneity in the type of intervention used and outcome assessment precluded this. Therefore, data were synthesised using vote counting. ResultsThirty randomised control trials, comprising 1976 patients were included. The most frequently studied interventional amino acid or metabolite was glutamine (n = 12 trials), a combination (n = 9), arginine (n = 6), β-hydroxy β-methylbutyrate (HMB) (n = 2) or ornithine (n = 1). Six trials (including 284 participants) measured skeletal muscle following supplementation, four of which used HMB alone or in combination as the intervention. Of these, one trial observed an attenuation of muscle wasting with a combination of amino acids, one observed an exacerbation of muscle wasting with HMB, three trials observed no impact on muscle wasting with HMB or a combination of amino acids and one trial reported no information. ConclusionSix trials have investigated the effect of enteral amino acid or amino acid metabolite supplementation on muscle mass in critically ill. Heterogeneity of interventions, outcome assessments and direction of effects limits the certainty regarding the effect of supplemental amino acids, or their metabolites, on skeletal muscle wasting during critical illness.The trial protocol is registered on PROSPERO (CRD42021275989).

Novel Clinical, Immunological, and Metabolic Features Associated with Persistent Post-Acute COVID-19 Syndrome.

The coronavirus disease 2019 (COVID-19) survivors are frequently observed to present persistent symptoms constituting what has been called "post-acute COVID-19 syndrome" (PACS) or "long COVID-19". Some clinical risk factors have been identified to be associated with PACS development; however, specific mechanisms responsible for PACS pathology remain unknown. This study investigates clinical, immunological, and metabolomic risk factors associated with post-acute COVID-19 syndrome (PACS) in 51 patients, assessed 7-19 months after acute infection. Among the participants, 62.7% were male and 37.2% were female, with an average age of 47.8 years. At the follow-up, 37.2% met the criteria for PACS, revealing significant differences in immunological and metabolomic profiles at the time of acute infection. Patients with PACS were characterized by elevated levels of mature low-density granulocytes (LDGs), interleukin-8 (IL-8), pyruvate, pseudouridine, and cystine. Baseline multivariate analysis showed increased pyruvate and decreased alpha tocopherol levels. At follow-up, there was a decrease in absolute B lymphocytes and an increase in non-classical monocytes and 3-hydroxyisovaleric acid levels. These findings suggest that specific immunological and metabolomic markers during acute infection can help identify patients at higher risk of developing persistent PACS.

Determination of calcium β‑hydroxy-β-methylbutyrate content in special medical formula food and sports nutrition food by solid-phase extraction and high performance liquid chromatography

Calcium β‑hydroxy-β-methylbutyrate (CaHMB) can promote muscle growth, prevent muscle atrophy, and enhance immunity, therefore, it is widely used as a nutritional supplement in special medical formula food and sports nutrition food. Many methods for the detection of CaHMB have been reported, but the pretreatment method for these reported literatures directly involves extraction using hydrochloric acid solution, without any purification steps. A method for accurately determining CaHMB in special medical formula food and sports nutrition food was established for the first time using solid-phase extraction (SPE) purification and high-performance liquid chromatography method (HPLC). The samples were extracted and precipitated protein using methanol-water solution, purified using SPE method and analyzed by HPLC on diode array detector (DAD) mode under external standard method. The method obtained excellent calibration linearity (r2>0.9993) and a satisfactory analysis of the targeted compound, which were evaluated with calibration standards over the range of 0.020–2.00 mg/mL. The limit of quantifications (LOQs), which defined as the lowest spiking level, were set at 0.4 g/100 g (special medical formula food) and 1.0 g/100 g (sports nutrition food). The average recoveries were within 92.9–104% for the analytes, and the relative standard deviations (RSDs) were below 3.93%, measured at low, medium, and high concentrations. Moreover, the positive sample analysis results indicated that CaHMB was detected on 10 real special medical formula food and sports nutrition food products, the contents of which were generally consistent with their labeled values, with measured values ranging from 97.1 % to 119 % of the labeled values. These results suggested that the developed highly sensitive and specific method is highly feasible for monitoring of the target analyte in special medical formula food and sports nutrition food.

The diagnostic potential of urine in paediatric patients undergoing initial treatment for tuberculous meningitis

Tuberculous meningitis (TBM)—the extrapulmonary form of tuberculosis, is the most severe complication associated with tuberculosis, particularly in infants and children. The gold standard for the diagnosis of TBM requires cerebrospinal fluid (CSF) through lumbar puncture—an invasive sample collection method, and currently available CSF assays are often not sufficient for a definitive TBM diagnosis. Urine is metabolite-rich and relatively unexplored in terms of its potential to diagnose neuroinfectious diseases. We used an untargeted proton magnetic resonance (1H-NMR) metabolomics approach to compare the urine from 32 patients with TBM (stratified into stages 1, 2 and 3) against that from 39 controls in a South African paediatric cohort. Significant spectral bins had to satisfy three of our four strict cut-off quantitative statistical criteria. Five significant biological metabolites were identified—1-methylnicotinamide, 3-hydroxyisovaleric acid, 5-aminolevulinic acid, N-acetylglutamine and methanol—which had no correlation with medication metabolites. ROC analysis revealed that methanol lacked diagnostic sensitivity, but the other four metabolites showed good diagnostic potential. Furthermore, we compared mild (stage 1) TBM and severe (stages 2 and 3) TBM, and our multivariate metabolic model could successfully classify severe but not mild TBM. Our results show that urine can potentially be used to diagnose severe TBM.

Dietary Supplementation on Physical Performance and Recovery in Active-Duty Military Personnel: A Systematic Review of Randomized and Quasi-Experimental Controlled Trials.

Warfighters, often called tactical athletes, seek dietary supplementation to enhance training and recovery. Roughly 69% of active-duty US military personnel have reported consuming dietary supplements. The objective of this systematic review was to examine the impact of dietary supplements on muscle-related physical performance and recovery in active-duty military personnel. Randomized controlled trials and quasi-experimental controlled trials of oral dietary supplementation in active-duty military members were examined. A protocol was registered (PROSPERO CRD42023401472), and a systematic search of MEDLINE and CINAHL was undertaken. Inclusion criteria consisted of studies published between 1990-2023 with outcomes of muscle performance and recovery among active-duty military populations. The risk of bias was assessed with the McMaster University Guidelines and Critical Review Form for Quantitative Studies. Sixteen studies were included. Four were conducted on protein or carbohydrate; four on beta-alanine alone, creatine alone, or in combination; two on mixed nutritional supplements; two on probiotics alone or in combination with beta hydroxy-beta methylbutyrate calcium; and four on phytonutrient extracts including oregano, beetroot juice, quercetin, and resveratrol. Ten examined outcomes related to physical performance, and six on outcomes of injury or recovery. Overall, protein, carbohydrate, beta-alanine, creatine, and beetroot juice modestly improved performance, while quercetin did not. Protein, carbohydrates, beta-alanine, probiotics, and oregano reduced markers of inflammation, while resveratrol did not. Nutrition supplementation may have small benefits on muscle performance and recovery in warfighters. However, there are significant limitations in interpretation due to the largely inconsistent evidence of ingredients and comparable outcomes. Thus, there is inadequate practical evidence to suggest how dietary supplementation may affect field performance.

Inhibition of BCAT1-mediated cytosolic leucine metabolism regulates Th17 responses via the mTORC1-HIF1α pathway

Branched-chain amino acids (BCAAs), particularly leucine, are indispensable AAs for immune regulation through metabolic rewiring. However, the molecular mechanism underlying this phenomenon remains unclear. Our investigation revealed that T-cell receptor (TCR)-activated human CD4+ T cells increase the expression of BCAT1, a cytosolic enzyme responsible for BCAA catabolism, and SLC7A5, a major BCAA transporter. This upregulation facilitates increased leucine influx and catabolism, which are particularly crucial for Th17 responses. Activated CD4+ T cells induce an alternative pathway of cytosolic leucine catabolism, generating a pivotal metabolite, β-hydroxy β-methylbutyric acid (HMB), by acting on BCAT1 and 4-hydroxyphenylpyruvate dioxygenase (HPD)/HPD-like protein (HPDL). Inhibition of BCAT1-mediated cytosolic leucine metabolism, either with BCAT1 inhibitor 2 (Bi2) or through BCAT1, HPD, or HPDL silencing using shRNA, attenuates IL-17 production, whereas HMB supplementation abrogates this effect. Mechanistically, HMB contributes to the regulation of the mTORC1-HIF1α pathway, a major signaling pathway for IL-17 production, by increasing the mRNA expression of HIF1α. This finding was corroborated by the observation that treatment with L-β-homoleucine (LβhL), a leucine analog and competitive inhibitor of BCAT1, decreased IL-17 production by TCR-activated CD4+ T cells. In an in vivo experimental autoimmune encephalomyelitis (EAE) model, blockade of BCAT1-mediated leucine catabolism, either through a BCAT1 inhibitor or LβhL treatment, mitigated EAE severity by decreasing HIF1α expression and IL-17 production in spinal cord mononuclear cells. Our findings elucidate the role of BCAT1-mediated cytoplasmic leucine catabolism in modulating IL-17 production via HMB-mediated regulation of mTORC1-HIF1α, providing insights into its relevance to inflammatory conditions.

Construction and characterization of alginate/calcium β-hydroxy-β-methylbutyrate hydrogels: Effect of M/G ratios and calcium ion concentration

Calcium β-hydroxy-β-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.

Determination of calcium β-hydroxy-β-methyl butyrate content in milk and dairy products by solid-phase extraction and high performance liquid chromatography

In this paper, an analytical method based on solid-phase extraction (SPE) purification and high-performance liquid chromatography method (HPLC) was developed for the first time to determine the content of calcium β-hydroxy-β-methyl butyrate (CaHMB) in milk and dairy products. The quantitative detection was performed by HPLC with diode array detector (DAD) under external standard method. The limit of quantification (LOQ), calculated as 10 times the standard deviation, was 0.10 g/100 g. The average recoveries were in the range of 92.40–103.00 %, with relative standard deviations (RSDs) of 1.25–3.77 %, measured at three concentration levels. The real sample analysis results showed that CaHMB was detected in infant formula, formulated milk powder, and milkshake samples, the contents of which were in the range of 0.60–8.66 g/100 g, respectively. The developed method features good purification effect, good separation specificity, good repeatability, accuracy and reliability, and can meet the content determination of CaHMB in milk and dairy products.

Bacterial Growth Modulatory Effects of Two Branched-Chain Hydroxy Acids and Their Production Level by Gut Microbiota.

Branched-chain hydroxy acids (BCHAs), produced by lactic acid bacteria, have recently been suggested as bioactive compounds contributing to the systemic metabolism and modulation of the gut microbiome. However, the relationship between BCHAs and gut microbiome remains unclear. In this study, we investigated the effects of BCHAs on the growth of seven different families in the gut microbiota. Based on in vitro screening, both 2-hydroxyisovaleric acid (HIVA) and 2-hydroxyisocaproic acid (HICA) stimulated the growth of Lactobacillaceae and Bifidobacteriaceae, with HIVA showing a significant growth promotion. Additionally, we observed not only the growth promotion of probiotic Lactobacillaceae strains but also growth inhibition of pathogenic B. fragilis in a dosedependent manner. The production of HIVA and HICA varied depending on the family of the gut microbiota and was relatively high in case of Lactobacillaceae and Lachnosporaceae. Furthermore, HIVA and HICA production by each strain positively correlated with their growth variation. These results demonstrated gut microbiota-derived BCHAs as active metabolites that have bacterial growth modulatory effects. We suggest that BCHAs can be utilized as active metabolites, potentially contributing to the treatment of diseases associated with gut dysbiosis.

297 Effects of plasma zinc concentration on longissimus thoracis metabolic status of beef steers

Abstract The objective of this study was to examine the role of Zn status on muscle glucose and other metabolites. Angus steers [n = 144; body weight (BW) = 525 ± 30 kg] with varying plasma Zn concentration and implant status served as the initial pool for this secondary experiment. Steers were assigned to one of two implant (IMP) treatments: no implant (NO) or Component TE-200 (TE-200; Elanco, Greenfield, IN) on d 0. Zinc was supplemented as ZnSO4 at 0 mg Zn/kg dry matter (DM; analyzed 54 mg Zn/kg DM), 30 mg Zn/kg DM, or 100 mg Zn/kg DM, starting 60 d before implant day. Steers were fed via GrowSafe bunks (GrowSafe Systems Ltd., Airdie, AB, Canada), and steer was experimental unit. Steers were fed in two blocks with a 14-d stagger for sample logistics. Blood and muscle biopsies of the longissimus thoracis were collected on d 40 after implant, a minimum of 2 h post-feed delivery. Plasma Zn was quantified via ICP-OES and 144 samples were stratified into quantiles by plasma Zn concentration. Samples (n = 12 low and 12 high from NO and TE-200 groups) were identified and designated as low plasma Zn (LOW, 1.1 mg Zn/L average) and high plasma Zn (HI, 1.6 mg Zn/L average) treatments (TRT). Muscle samples from these 48 steers were homogenized and derivatized for subsequent analysis via gas chromatography-mass spectrometry (GCMS) for non-targeted metabolomic analysis. Data were analyzed as a complete randomized design using the MIXED procedure of SAS 9.4 (SAS Inst. Inc., Cary, NC) with fixed effects of TRT, IMP, BLOCK, and TRT×IMP. A TRT×IMP effect was observed for muscle glycine (P = 0.02) where LOW/IMP was similar to HI/NO but had greater glycine concentrations than LOW/NO and HI/IMP. There was a tendency for a TRT×IMP (P = 0.07) effect where LOW/IMP and HI/NO tended to have greater concentrations of hydroxyisovaleric acid. Given the role of glycine in protein synthesis and hydroxyisovaleric acid in leucine metabolism these data suggest differential protein responses to implants in cattle of lesser vs. greater plasma Zn concentrations. Hydroxybutyric acid, a ketone body which can be utilized for energy, tended to be greater in muscle of steers receiving an IMP (P = 0.09). Contrary to our hypothesis that greater plasma Zn would support differential muscle glucose metabolism, no effects of plasma Zn TRT or IMP were noted for glucose, lactate, and other detected metabolites. Both LOW and HI plasma Zn concentrations were still considered adequate, and future research should explore the impact of distinctly deficient and adequate plasma Zn concentration on glucose metabolism pathways in muscle.

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

BackgroundSupplementation with β-hydroxy β-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. ObjectivesThe 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). MethodsData 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. Results255 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. ConclusionsCross-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.

1H-NMR-Based Plasma Metabolomic Profiling of Crossbred Beef Cattle with Divergent RFI Phenotype

This study focused on exploring the metabolomic profiles of crossbred beef cattle with varying levels of residual feed intake (RFI), a measure of feed efficiency in beef cattle. Sixty-seven crossbred growing beef steers (BW = 277 ± 29.7 kg) were subjected to a high-forage total mixed ration for 64 days to determine their RFI phenotypes. At the end of the 64d feeding trial, beef steers were divided into two groups based on their RFI values: low (or negative)-RFI beef steers (n = 28; RFI = −1.08 ± 0.88 kg/d) and high (or positive)-RFI beef steers (n = 39; RFI = 1.21 ± 0.92 kg/d). Blood samples were collected, and plasma samples were analyzed using Nuclear Magnetic Resonance spectroscopy, resulting in the identification of 50 metabolites. The study found a distinct metabolomic signature associated with RFI status. Eight metabolites, including amino acids (tyrosine, glycine, valine, leucine, and methionine) and other compounds (dimethyl sulfone, 3-hydroxy isovaleric acid, citric acid, creatine, and L-carnitine), showed differential abundance between low- and high-RFI groups. Specifically, tyrosine, glycine, and dimethyl sulfone exhibited significant specificity and sensitivity, which produced a discriminatory model with an area under the receiver operating characteristic (ROC) curve of 0.7, making them potential markers for RFI. A logistic regression model incorporating these biomarkers effectively distinguished between high- and low-RFI steers, with a threshold cutoff point of 0.48, highlighting a distinctive metabolite profile associated with efficient nutrient utilization in low-RFI cattle. The logistic regression model, incorporating these biomarkers, holds promise for accurately categorizing RFI values, providing insights into the metabolic basis of feed efficiency in beef cattle.

Abstract 59: Sugar-Sweetened Beverages, Gut Microbiota, Circulating Metabolites, and Risks of Cardiometabolic Diseases: The Hispanic Community Health Study / Study of Latinos (HCHS/SOL)

Introduction: Sugar-sweetened beverages (SSBs) remain the top contributor to added sugar intake and contribute to significant cardiometabolic disease burdens. However, associations of SSB intake with gut microbiota and blood metabolites, a potential pathway linking SSB intake to cardiometabolic risks, are unclear. Hypothesis: Higher SSB intake alters gut microbial composition and blood metabolites which contribute to higher cardiometabolic risks. Methods: We assessed associations of SSB intake with gut microbiome (metagenomics, n=2970) and 653 serum metabolites (untargeted metabolomics, n=6115) among US Hispanic/Latino adults. We examined cross-sectional associations of gut microbiota with cardiometabolic traits and metabolites, and prospective associations of metabolites with risks of cardiovascular disease (i.e., myocardial infarction, stroke, and heart failure) and diabetes over median follow-ups of 7.6 and 10.5 years, respectively. Results: Higher SSB intake (median=0.9 servings/d) was related to the enrichment of 2 microbial species and depletion of 7 species with multivariable adjustment ( Fig. 1 ). A gut microbiota score, calculated based on the 9 SSB-related species, was related to poorer glycemic, triglyceride, and renal traits ( Fig. 1 ). Among 64 metabolites related to both SSB intake and gut microbiota score ( Fig. 1 ), 7 metabolites (e.g., 5-aminovaleric acid betaine) were associated with cardiovascular disease risk, and 30 metabolites were associated with diabetes risk, including those in the branch-chained amino acid metabolism (e.g., 2-hydroxyisovaleric acid), tryptophan metabolism (indole-3-propionic acid), and ursodeoxycholic acid, which were reported to closely relate to gut microbiota. Conclusion: Among US Hispanics/Latinos, higher SSB intake was associated with unfavorable gut microbiota and circulating metabolites for cardiometabolic risks, suggesting a potential role of gut microbiota and related metabolites in the link of SSB intake with cardiometabolic diseases.

Effects of multicomponent training and HMB supplementation on disability, cognitive and physical function in institutionalized older adults aged over 70 years: a cluster-randomized controlled trial

ObjectivesTo investigate the synergist effects of exercise and β-hydroxy β-methylbutyrate (HMB) supplementation on disability, cognitive and physical function, and muscle power in institutionalized older people. DesignCluster-randomized controlled trial. ParticipantsSeventy-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). InterventionThe 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. MeasurementsParticipants 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. ResultsCompared 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). ConclusionThe 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.

Muscle-building supplement β-hydroxy β-methylbutyrate stimulates the maturation of oligodendroglial progenitor cells to oligodendrocytes.

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 β-hydroxy β-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 β-/- (PPARβ-/-) mice, but not PPARα-/- mice. Similarly, GW6471 (an antagonist of PPARα), but not GSK0660 (an antagonist of PPARβ), 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 PPARβ 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 PPARβ 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.