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Background: Parenteral nutrition (PN) without enteral nutrition (EN) leads to marked atrophy of gut-associated lymphoid tissue (GALT), causing mucosal defense failure in both the gut and the extraintestinal mucosal system. We evaluated the effects of beta-hydroxy-beta-methylbutyrate (HMB) on GALT and gut morphology in PN-fed mice., Methods: Experiment 1: male Institute of Cancer Research mice were assigned to the Chow (n = 12), Control (standard PN: n = 10), or H600 and H2000 (PN containing 600 mg/kg or H2000 mg/kg body weight of Ca-HMB: n = 12 and 10, respectively) groups. After 5 days of dietary manipulation, all mice were killed and the whole small intestine was harvested. GALT lymphocyte cell numbers and phenotypes of Peyer patch (PP), intraepithelial space, and lamina propria lymphocytes were evaluated. Experiment 2: 47 mice (Chow: n = 12; Control: n = 14; H600: n = 11; and H2000: n = 10) were fed for 5 days as in experiment 1. Proliferation and apoptosis of gut immune cells and mucosa, and protein expressions (mammalian target of rapamycin [mTOR], caspase-3, and Bcl2) were evaluated in the small intestine., Results: Compared with the Controls, the Chow and HMB groups showed significantly higher PP cell numbers, prevented gut mucosal atrophy, inhibited apoptosis of gut cells, and increased their proliferation in association with increased mTOR activity and Bcl2 expression., Conclusion: HMB-supplemented PN is a potentially novel method of preserving GALT mass and gut morphology in the absence of EN., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Introduction: Short-term (4 weeks) supplementation with n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has recently been shown to improve protein metabolism in a dose dependent way in normal weight patients with Chronic Obstructive Pulmonary Disease (COPD). Furthermore, EPA/DHA supplementation was able to increase extremity lean soft tissue but not muscle function. No studies are available combining n-3 PUFAs and the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) supplementation in chronic clinical conditions. Whether adding HMB to daily EPA/DHA supplementation for 10 weeks enhances muscle and brain health, daily functional performance, and quality of life of patients with COPD by further improving their protein and amino acid homeostasis remains unknown., Methods: Patients with COPD (GOLD: II-IV, n = 46) received daily for 10 weeks, according to a randomized double-blind placebo-controlled three-group design, EPA/DHA (n = 16), EPA/DHA to which HMB was added (n = 14), or placebo (n = 16). The daily dose of 2.0 g of EPA/DHA or soy + corn oil as the placebo was provided via gel capsules, and 3.0 g of Ca-HMB or maltodextrin as placebo as powders. At pre- and post-intervention, a pulse mixture of multiple amino acids was administered to measure postabsorptive net protein breakdown (netPB as primary endpoint) and whole body production (WBP) and conversion rates of the amino acids. As secondary endpoints, lean soft tissue and fat mass were assessed by dual-energy X-ray absorptiometry, upper and lower muscle function by handgrip and single leg isokinetic dynamometry, brain (cognitive, wellbeing) health by assessments, daily functional performance by measuring 6-min walk distance, 4-m gait speed, and postural balance, and quality of life by questionnaire. Plasma enrichments and concentrations were analyzed by LC-MS/MS, and systemic inflammatory profile and metabolic hormones by Luminex., Results: HMB + EPA/DHA but not EPA/DHA supplementation increased postabsorptive netPB (p = 0.028), and WBPs of glutamine (p = 0.024), taurine (p = 0.039), and tyrosine (p = 0.036). Both EPA/DHA and HMB + EPA/DHA supplementation resulted in increased WBP of phenylalanine (p < 0.05). EPA/DHA but not HMB + EPA/DHA was able to increase WBP of arginine (p = 0.030), citrulline (p = 0.008), valine (p = 0.038), and conversion of citrulline to arginine (p = 0.009). Whole body and extremity fat mass were reduced after HMB + EPA/DHA supplementation only, whereas lean soft tissue was increased after EPA/DHA (p = 0.049) and HMB + EPA/DHA (p = 0.073). No other significant findings were observed. Reductions in several proinflammatory cytokines were observed in the HMB + EPA/DHA group including IL-2, IL-17, IL-6, IL-12P40, and TNF-β (p < 0.05)., Conclusions: Ten weeks of supplementation with 2 g of EPA/DHA daily is sufficient to induce muscle gain in COPD but HMB is needed to induce fat loss. Whether HMB is solely responsible for the fat mass loss or has a synergistic effect with EPA/DHA remains unclear. The increase in net protein breakdown observed with HMB + EPA/DHA supplementation may indicate a beneficial enhanced protein turnover cycling associated with increased lean soft tissue., Clinical Trial Registry: ClinicalTrials.gov; NCT03796455., Competing Interests: Conflict of interest NEP serves as a speaker for and has received grants from Abbott Nutrition, and SLP is an employee of Abbott Nutrition. The other authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Chronic wounds are characterized by prolonged non-healing, significantly affecting patients' quality of life. Oral formulas may enhance the wound healing process and contribute to cost reduction in care. This review aimed to evaluate the effects of oral nutritional supplementation on chronic wound healing and provide insights into formula characteristics. A comprehensive search across Cinahl, Embase, PubMed, and Web of Science databases yielded nine studies from the past decade involving 741 patients ages 52 to 81.7 across various care settings: hospitals, long-term care facilities, and home care. Primary wound types included pressure injuries (58%), diabetic foot ulcers (40%), and venous ulcers (2%). The intervention duration ranged from 2 to 16 wk, with sample sizes varying from 24 to 270 patients. Notably, four studies reported a reduction in wound area and an increased healing rate with a hypercaloric, hyperproteic formula enriched with zinc and vitamins A, C, and E. However, two studies found no significant differences compared with control groups. Two other studies investigated a combination of arginine, glutamine, and β-hydroxy-β-methylbutyrate; however, they did not yield significant results, and one study favored a hyperproteic formula instead of a hyperproteic formula with arginine. This review provides evidence supporting the potential of oral nutritional supplementation to enhance the healing process of chronic wounds. Based on our findings, a desirable formula should be characterized by a high calorie and protein content and the inclusion of antioxidant micronutrients, including, but not limited to, vitamins A, E, C, and zinc., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Statins, or hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors, are one of the most commonly prescribed medications for lowering cholesterol. Myopathic side-effects ranging from pain and soreness to critical rhabdomyolysis are commonly reported and often lead to discontinuation. The pathophysiological mechanism is, in general, ascribed to a downstream reduction of Coenzyme Q10 synthesis. HMG-CoA is a metabolite of leucine and its corresponding keto acid α-ketoisocaproic acid (KIC) and β-hydroxy-β-methylbutyrate (HMB), however, little is known about the changes in the metabolism of leucine and its metabolites in response to statins., Objective: We aimed to investigate if statin treatment has implications on the upstream metabolism of leucine to KIC and HMB, as well as on other branched chain amino acids (BCAA)., Design: 12 hyperlipidemic older adults under statin treatment were recruited. The study was conducted as a paired prospective study. Included participants discontinued their statin treatment for 4 weeks before they returned for baseline measurements (before). Statin treatment was then reintroduced, and the participants returned for a second study day 7 days after reintroduction (after statin). On study days, participants were injected with stable isotope pulses for measurement of the whole-body production (WBP) of all BCAA (leucine, isoleucine and valine), along with their respective keto acids and HMB., Results: We found a reduced leucine WBP (22 %, p = 0.0033), along with a reduction in valine WBP (13 %, p = 0.0224). All other WBP of BCAA and keto acids were unchanged. There were no changes in the WBP of HMB., Conclusions: Our study shows that statin inhibition of HMG-CoA reductase has an upstream impact on the turnover of leucine and valine. Whether this impairment in WBP of leucine may contribute to the known pathophysiological side effects of statins on muscle remains to be further investigated., Competing Interests: Declaration of competing interest SP is associated with Abbott Nutrition. Apart from this and the funding from the mentioned source, the authors report no other conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (© 2024 International Society for Neurochemistry.)

Laying hens, selectively bred for high egg production, often suffer from bone fragility and fractures, impacting their welfare and causing economic losses. Additionally, gut health and muscle quality are crucial for overall health and productivity. This study aimed to evaluate the effects of ß-Hydroxy-ß-methylbutyrate (HMB) supplementation on performance, bone metabolism, intestinal morphology, and muscle quality in laying hens. Forty-eight Bovans Brown hens were divided into a control group and an HMB-supplemented group (0.02% HMB in diet). The study spanned from the 31st to the 60th wk of age. Assessments included bone mechanical testing, serum hormonal analysis, histological analysis of bone and intestine, and muscle quality analysis. The HMB supplementation led to decreased feed intake without affecting body weight or laying rate in laying hens. It caused an increase in both mean daily and total egg weight, indicating improved feed utilization, without influencing the feed intake to egg weight ratio. Enhanced bone formation markers and altered intestinal morphometric parameters were observed, along with improved trabecular bone structure. However, no changes in measured other bone quality indices, including geometric, densitometric, or mechanical properties were observed. Muscle analysis revealed no significant changes in overall meat quality, except for a decrease in cholesterol content and alterations in the fatty acid profile, notably a reduction in total n-3 polyunsaturated and total polyunsaturated fatty acids (PUFA). In conclusion, although not all effects of HMB supplementation were unequivocally beneficial, the positive changes in performance data and trabecular bone microarchitecture support further research into various doses and durations of supplementation. Such studies are necessary to fully understand and optimize the benefits of HMB for enhancing the health and productivity of laying hens., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To 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., Design: Cluster-randomized controlled trial., Participants: Seventy-two institutionalized older adults (age = 83 ± 10 years old; 63% women) were randomized in four groups: exercise plus placebo (EX), HMB supplementation, EX plus HMB supplementation (EX + HMB), and control (CT)., Intervention: The exercising participants completed a 12-week tailored multicomponent exercise intervention (Vivifrail; 5 days/week of an individualized resistance, cardiovascular, balance and flexibility program), whereas the HMB groups received a drink containing 3 g/day of HMB., Measurements: Participants were assessed Pre and Post intervention for disability and cognitive function (validated questionnaires), physical function (short physical performance battery, SPPB), handgrip strength and sit-to-stand relative muscle power. Linear mixed-effect models were used to compare changes among groups., Results: Compared to baseline, both EX and EX + HMB improved cognitive function (+2.9 and +1.9 points; p < 0.001), SPPB score (+2.9 points and +2.4 points; p < 0.001) and relative muscle power (+0.64 and +0.48 W·kg -1 ; p < 0.001), while CT and HMB remained unchanged (p > 0.05). Significant between-group differences were noted between CT, EX and EX + HMB for cognitive function (p < 0.01), between CT and EX + HMB for physical function (p = 0.043), and between CT, EX and EX + HMB for relative muscle power (p < 0.001)., Conclusion: The Vivifrail exercise program was effective in improving cognitive and physical function, and muscle power in nursing home residents, while HMB supplementation did not provide additional benefits when combined with exercise. These results emphasize the importance of physical exercise interventions in very old people as an essential basis for improving their overall health and quality of life., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Adequate diet, physical activity, and dietary supplementation with muscle-targeted food for special medical purposes (FSMP) or dietary supplement (DS) are currently considered fundamental pillars in sarcopenia treatment. The aim of this study is to evaluate the effectiveness of a DS (containing hydroxy-methyl-butyrate, carnosine, and magnesium, for its action on muscle function and protein synthesis and butyrate and lactoferrin for their contribution to the regulation of gut permeability and antioxidant/anti-inflammation activity) on muscle mass (assessed by dual X-ray absorptiometry (DXA)), muscle function (by handgrip test, chair test, short physical performance battery (SPPB) test, and walking speed test), inflammation (tumor necrosis factor-alpha (TNF-a), C-reactive protein (CRP), and visceral adipose tissue (VAT)) and gut axis (by zonulin). A total of 59 participants (age 79.7 ± 4.8 years, body mass index 20.99 ± 2.12 kg/m 2 ) were enrolled and randomly assigned to intervention ( n = 30) or placebo ( n = 28). The skeletal muscle index (SMI) significantly improved in the supplemented group compared to the placebo one, +1.02 (CI 95%: -0.77; 1.26), p = 0.001; a significant reduction in VAT was observed in the intervention group, -70.91 g (-13.13; -4.70), p = 0.036. Regarding muscle function, all the tests significantly improved ( p = 0.001) in the supplemented group compared to the placebo one. CRP, zonulin, and TNF-alpha significantly decreased ( p = 0.001) in intervention, compared to placebo, -0.74 mg/dL (CI 95%: -1.30; -0.18), -0.30 ng/mL (CI 95%: -0.37; -0.23), -6.45 pg/mL (CI 95%: -8.71; -4.18), respectively. This DS improves muscle mass and function, and the gut muscle has emerged as a new intervention target for sarcopenia.

β-Hydroxy-β-methylbutyrate (HMB) is a breakdown product of leucine, which promotes muscle growth. Although some studies indicate that HMB activates AKT and mTOR, others show activation of the downstream effectors, P70S6K and S6, independent of mTOR. Our aim was to study the metabolic effect of HMB around the circadian clock in order to determine more accurately the signaling pathway involved. C2C12 myotubes were treated with HMB and clock, metabolic and myogenic markers were measured around the clock. HMB-treated C2C12 myotubes showed no activation of AKT and mTOR, but did show activation of P70S6K and S6. Activation of P70S6K and S6 was also found when myotubes were treated with HMB combined with metformin, an indirect mTOR inhibitor, or rapamycin, a direct mTOR inhibitor. The activation of the P70S6K and S6 independent of AKT and mTOR, was accompanied by increased activation of phospholipase D2 (PLD). In addition, HMB led to high amplitude and advanced circadian rhythms. In conclusion, HMB induces myogenesis in C2C12 by activating P70S6K and S6 via PLD2, rather than AKT and mTOR, leading to high amplitude advanced rhythms.

Abstract: Fernández-Landa, J, Todorovic, N, Santibañez-Gutierrez, A, Ostojic, SM, Calleja-González, J, Sekulic, D, and Mielgo-Ayuso, J. Effects of HMB on endurance performance in a healthy population: a systematic review and meta-analysis. J Strength Cond Res 38(4): e202-e210, 2024-β-hydroxy-β-methylbutyrate (HMB) has been used extensively as a dietary supplement for athletes and physically active people. However, the ergogenic effect of HMB supplementation on endurance performance is still unclear. Therefore, this systematic review and meta-analysis (SRMA) aimed to assess HMB supplementation on endurance performance and V̇O 2 max . This SRMA followed PRISMA guidelines. Three electronic databases were searched (PubMed/Medline, Web of Science [WOS], and Scopus) from inception until April 3, 2023. In this SRMA, human experimental trials, controlled with a placebo group, assessing the effect of HMB supplementation on endurance performance in a healthy population were included. The quality of the studies was assessed by the Physiotherapy Evidence Database (PEDro) scale. The study protocol was registered in the Prospective Register of Systematic Review (PROSPERO): CRD42022341790. Eleven studies involving 279 participants met the inclusion criteria. The results displayed a significant improvement on endurance performance (pooled standardized mean difference [SMD] = 0.58 [0.28-0.87]) and V̇O 2 max (pooled SMD = 0.58 [0.21-0.95]) after HMB ingestion. Moreover, after the exclusion of the studies not evenly distributed around the base of the funnel plot, the results continued to be significantly positive in endurance performance (pooled SMD = 0.38 [0.22-0.53]) and V̇O 2 max (pooled SMD = 0.25 [0.09-0.42]). In conclusion, HMB (3 g·d -1 ) ingestion during 2-12 weeks significantly improves endurance performance and V̇O 2 max ., (Copyright © 2023 National Strength and Conditioning Association.)

Background: Beta-hydroxy-beta-methylbutyrate (HMB) is a nutrition supplement that may attenuate muscle wasting from critical illness. This trial aimed to determine feasibility of administering a blinded nutrition supplement in the intensive care unit (ICU) and continuing it after ICU discharge., Methods: Single-center, parallel-group, blinded, placebo-controlled, randomized feasibility trial. After traumatic injury necessitating admission to ICU, participants were randomized to receive an enteral study supplement of 3 g of HMB (intervention) or placebo daily for 28 days or until hospital discharge. Primary outcome was feasibility of administering the study supplement, quantified as protocol adherence. Secondary outcomes included change in quadriceps muscle thickness, measured weekly until day 28 or hospital discharge by using ultrasound and analyzed by using a linear mixed model., Results: Fifty randomized participants (intervention, n = 26; placebo, n = 24) showed comparable baseline characteristics. Participants received 862 (84.3%) of the 1022 prescribed supplements during hospitalization with 543 (62.8%) delivered via an enteral feeding tube. The median (IQR) number of study supplements successfully administered per participant was 19.5 (13.0-24.0) in the intervention group and 16.5 (8.5-23.5) in the placebo group. Marked loss of quadriceps muscle thickness occurred in both groups, with the point estimate favoring attenuated muscle loss with the intervention, albeit with wide CIs (mean intervention difference after 28 days, 0.26 cm [95% CI, -0.13 to 0.64])., Conclusion: A blinded, placebo-controlled, randomized clinical trial of daily enteral HMB supplementation for up to 28 days in hospital is feasible. Any effect of HMB supplementation to attenuate muscle wasting after traumatic injury remains uncertain., (© 2023 American Society for Parenteral and Enteral Nutrition.)

Short-chain fatty acids (SCFAs) are major metabolic products of indigestible polysaccharides in the gut and mediate the function of immune cells to facilitate homeostasis. The immunomodulatory effect of SCFAs has been attributed, at least in part, to the epigenetic modulation of immune cells through the inhibition the nucleus-resident enzyme histone deacetylase (HDAC). Among the downstream effects, SCFAs enhance regulatory T cells (T reg ) over inflammatory T helper (Th) cells, including Th17 cells, which can be pathogenic. Here, we characterize the potential of two common SCFAs-butyrate and pentanoate-in modulating differentiation of T cells in vitro. We show that butyrate but not pentanoate exerts a concentration-dependent effect on T reg and Th17 differentiation. Increasing the concentration of butyrate suppresses the Th17-associated RORγtt and IL-17 and increases the expression of T reg -associated FoxP3. To effectively deliver butyrate, encapsulation of butyrate in a liposomal carrier, termed BLIPs, reduced cytotoxicity while maintaining the immunomodulatory effect on T cells. Consistent with these results, butyrate and BLIPs inhibit HDAC and promote a unique chromatin landscape in T cells under conditions that otherwise promote conversion into a pro-inflammatory phenotype. Motif enrichment analysis revealed that butyrate and BLIP-mediated suppression of Th17-associated chromatin accessibility corresponded with a marked decrease in bZIP family transcription factor binding sites. These results support the utility and further evaluation of BLIPs as an immunomodulatory agent for autoimmune disorders that are characterized by chronic inflammation and pathogenic inflammatory T cells., (© 2022. Controlled Release Society.)

Objective: Patients on the waiting list for liver transplantation (LTx) usually lose muscle mass. Supplementation with β-hydroxy β-methylbutyrate (HMB) may have a promising effect on this clinical condition. This study aimed to evaluate the effects of HMB on muscle mass, strength, functionality, and quality of life in patients on the LTx waiting list., Methods: A double-blind, randomized study was conducted of 3g supplementation of HMB or 3g supplementation of maltodextrin (active control) with nutritional counselling for 12 wk in patients >18 y, evaluated at five points or timepoints. Body composition and anthropometric data (resistance, reactance, phase angle, weight, body mass index, arm circumference [AC], arm muscle area, and adductor pollicis muscle thickness) were collected, and muscle strength was assessed through dynamometry and muscle function by the frailty index (FI). Quality of life was assessed., Results: A total of 47 patients were enrolled (HMB: 23 and active control: 24). There was a significant difference in both groups for AC (P = 0.03), dynamometry (P = 0.02), and FI (P = 0.01). There was an increase in dynamometry between weeks 0 and 12 in both groups (HMB [Δdynamometry: 10.1% ± 16.4%; P < 0.05] and active control [Δdynamometry: 23.0% ± 70.3%; P < 0.05]). The AC increased in both groups between weeks 0 and 4 (HMB [ΔAC: 0.9% ± 2.8%; P < 0.05] and active control [ΔAC: 1.6% ± 3.6%; P < 0.05]) and between weeks 0 and 12 (HMB [ΔAC: 3.2% ± 6.7%; P < 0.05] and active control [ΔAC: 2.1% ± 6.6%; P < 0.05]). The FI decreased in both groups, between weeks 0 and 4 (HMB [ΔFI: -4.2% ± 6.9%; P < 0.05) and active control [ΔFI: -3.2% ± 9.6%; P < 0.05]) and between weeks 0 and 12 (HMB ΔFI: -4.4% ± 11.2%; P < 0.05] and active control [ΔFI: -5.5% ± 11.3%; P < 0.05]). The other variables did not change (P > 0.05)., Conclusions: Nutritional counselling with supplementation with HMB or active control in patients on the LTx waiting list improved AC, dynamometry, and the FI in both groups., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A growing number of in vivo studies demonstrated that β-hydroxy-β-methyl butyrate (HMB) can serve as a lipid-lowering nutrient. Despite this interesting observation, the use of adipocytes as a model for research is yet to be explored. To ascertain the effects of HMB on the lipid metabolism of adipocytes and elucidate the underlying mechanisms, the 3T3-L1 cell line was employed. Firstly, serial doses of HMB were added to 3T3-L1 preadipocytes to evaluate the effects of HMB on cell proliferation. HMB (50 µM) significantly promoted the proliferation of preadipocytes. Next, we investigated whether HMB could attenuate fat accumulation in adipocytes. The results show that HMB treatment (50 µM) reduced the triglyceride (TG) content. Furthermore, HMB was found to inhibit lipid accumulation by suppressing the expression of lipogenic proteins (C/EBPα and PPARγ) and increasing the expression of lipolysis-related proteins (p-AMPK, p-Sirt1, HSL, and UCP3). We also determined the concentrations of several lipid metabolism-related enzymes and fatty acid composition in adipocytes. The HMB-treated cells showed reduced G6PD, LPL, and ATGL concentrations. Moreover, HMB improved the fatty acid composition in adipocytes, manifested by increases in the contents of n6 and n3 PUFAs. The enhancement of the mitochondrial respiratory function of 3T3-L1 adipocytes was confirmed via Seahorse metabolic assay, which showed that HMB treatment elevated basal mitochondrial respiration, ATP production, H + leak, maximal respiration, and non-mitochondrial respiration. In addition, HMB enhanced fat browning of adipocytes, and this effect might be associated with the activation of the PRDM16/PGC-1α/UCP1 pathway. Taken together, HMB-induced changes in the lipid metabolism and mitochondrial function may contribute to preventing fat deposition and improving insulin sensitivity.

High amounts of grains in the equine diet led to high starch intake, causing gut alterations. Aimed at reducing harmful effects, Macleaya cordata extract (MCE) is a phytogenic additive that stands out for its antibiotic and anti-inflammatory effects proven in different species. However, there is no useful information for horses. The objective of this study was to evaluate the effects of different levels of the inclusion of commercial MCE on body weight (BW), body condition score (BCS), total apparent digestibility (AD) of nutrients, faecal pH and fermentative products, on ponies fed a high-starch diet. Eight healthy gelding Mini Horse ponies were used. The study design was contemporary double Latin-square 4 × 4 in the experimental unit, with the animal inside each experimental period ( n  = 8 experimental units per group). The experiment was conducted over four 20-d periods. Basal diet attended 1.75% BW dry matter daily and starch intake was 2.2 g/kg BW/meal. The experimental groups were as follows: control - without food additive; S1-1 mg/kg BW MCE; S1.5-1.5 mg/kg BW MCE and S2-2 mg/kg BW MCE. The data were analysed by PROC MIXED of SAS ( p  < 0.05). Tendency was considered when 0.05 < p  < 0.1. Our results showed higher ether extract (EE) AD for S2 group (63.75%) when compared with the control (54.55%) ( p  = 0.0377). Lactate was lower ( p  = 0.0391) in S1 (3.27 mmol/l) and S2 (3.24 mmol/l) groups, although pH was not different between groups. Iso-valerate was greater in S1 group (2.29 mmol/l; p  = 0.0289), and a tendency of higher butyrate values was found for S1 and S2 groups ( p  = 0.0980). We concluded that MCE supplementation probably positively influences equine resident microbiota, improving EE AD and increasing iso-valerate concentration. It can also minimise harmful high-starch impact. We recommend further studies using MCE in horses for a better understanding of its local activity and possible benefits.

Attapulgite is a kind of natural clay mineral. Its unique pore structure makes it an ideal adsorption material and carrier material. However, the beneficial effect of modified attapulgites (SLK) in livestock is still unknown. The study was aimed to investigate the beneficial effect of modified attapulgites on diarrhea. 135 piglets were randomly divided into 5 groups and fed with control diet, traditional antibiotic substitute (TAS) supplementation diet, 0.5 mg/kg SLK supplementation diet, 1 mg/kg SLK supplementation diet, and 1.5 mg/kg SLK supplementation diet. This experiment lased two weeks. According to our result, 1.5 mg/kg SLK supplementation diet significantly decreased diarrhea score and diarrhea frequency, and effectively increased survival rate (P < 0.05). Dietary supplementation with 1.5 mg/kg SLK significantly increased high density lipoprotein cholesterol (HDLC), and choline esterase (CHE) concentration in serum (P < 0.05). AS compared with TAS group, 1.5 mg/kg SLK supplementation diet significantly decreased villus height and increased goblet number in jejunum, and increased villus height and decreased goblet number in ileum (P < 0.05). 1.5 mg/kg SLK supplementation diet also significantly changed cecal microbial community composition, including increased Limosilactobacillus abundance (P < 0.05). 1.5 mg/kg SLK supplementation diet significantly increased colonic microbial community composition, including decreased Escherichia-shigella abundance and increased Limosilactobacillus abundance (P < 0.05). Moreover, 1.5 mg/kg SLK supplementation diet significantly increased valerate, propionate, butyrate, and total short chain fatty acid contents in colon (P < 0.05). Valerate, propionate, butyrate, and total short chain fatty acid significantly associated with Lactobacillus. Fourerenilla and Fourerenilla.unclassfied significantly associated with acetate contents in colon (P < 0.05). In conclusion, dietary supplementation with modified apptapulgites significantly regulate intestinal microbial community composition and alleviate intestinal epithelial barrier to prevent diarrhea in piglets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Enterotoxigenic Escherichia coli (ETEC) causes post-weaning diarrhea in piglets, significantly impacting animal welfare and production efficiency. The two primary ETEC pathotypes associated with post-weaning diarrhea are ETEC F4 and ETEC F18. During the post-weaning period, piglets may be exposed to both ETEC F4 and ETEC F18. However, the effects of coinfection by both strains have not been studied. Short chain fatty acid feed additives, such as butyrate and valerate, are being investigated for their potential to improve animal performance and disease resistance. Therefore, this pilot experiment aimed to test the effects of butyrate glycerides or valerate glycerides on growth performance, diarrhea incidence, and immune responses of piglets under ETEC F4-ETEC F18 coinfection conditions. Twenty piglets were individually housed and assigned to one of the three dietary treatments immediately at weaning (21 to 24 d of age). The dietary treatments included control (basal diet formulation), control supplemented with 0.1% butyrate glycerides or 0.1% valerate glycerides. After a 7-d adaptation, all pigs were inoculated with ETEC F4 and ETEC F18 (0.5 × 109 CFU/1.5 mL dose for each strain) on three consecutive days. Pigs and feeders were weighed throughout the trial to measure growth performance. Fecal cultures were monitored for hemolytic coliforms, and blood samples were collected for whole blood and serum analysis. Pigs fed valerate glycerides tended (P = 0.095) to have higher final body weight compared with control. The overall severity of diarrhea was significantly (P < 0.05) lower in both treatment groups than control. Pigs fed valerate glycerides tended (P = 0.061) to have lower neutrophils and had significantly (P < 0.05) lower serum TNF-α on day 4 post-inoculation. This pilot experiment established an appropriate experimental dose for an ETEC F4-ETEC F18 coinfection disease model in weaned piglets. Results also suggest that butyrate glycerides and valerate glycerides alleviated diarrhea and regulated immune responses in piglets coinfected with ETEC F4 and ETEC F18., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The rumen simulation technique (RUSITEC) was used to investigate the effect of ergot alkaloids (EA) and a mycotoxin deactivating product (Biomin AA; MDP) on nutrient digestion, ruminal fermentation parameters, total gas, methane, and microbial nitrogen production. Ruminal fermentation vessels received a feedlot finishing diet of 90:10 concentrate:barley silage (DM basis). Using a randomized complete block design, treatments were assigned (n = 4 vessels/treatment) within two RUSITEC apparatuses in a 2 × 2 factorial arrangement. Treatments included: (1) control (CON) diet (no EA and no MDP); (2) CON diet + 1 g/d MDP; (3) CON diet + 20 mg/kg EA; and (4) CON diet + 20 mg/kg EA + 1 g/d MDP. The study was conducted over 14 d with 7 d of adaptation and 7 d of sample collection. Data were analyzed in SAS using PROC MIXED including fixed effects of EA, MDP, and the EA×MDP interaction. Random effects included RUSITEC apparatus and cow rumen inoculum (n = 4). Ergot alkaloids decreased dry matter (DMD) (P = 0.01; 87.9 vs. 87.2%) and organic matter disappearance (OMD) (P = 0.02; 88.8 vs. 88.4%). Inclusion of MDP increased OMD (P = 0.01; 88.3 vs. 88.9%). Neutral detergent fiber disappearance (NDFD) was improved with MDP; however, an EA×MDP interaction was observed with MDP increasing (P < 0.001) NDFD more with EA diet compared to CON. Acetate proportion decreased (P = 0.01) and isovalerate increased (P = 0.03) with EA. Consequently, acetate:propionate was reduced (P = 0.03) with EA. Inclusion of MDP increased total volatile fatty acid (VFA) production (P < 0.001), and proportions of acetate (P = 0.03) and propionate (P = 0.03), and decreased valerate (P < 0.001), isovalerate (P = 0.04), and caproate (P = 0.002). Treatments did not affect (P ≥ 0.17) ammonia, total gas, or methane production (mg/d or mg/g of organic matter fermented). The inclusion of MDP reduced (P < 0.001) microbial nitrogen (MN) production in the effluent and increased (P = 0.01) feed particle-bound MN. Consequently, total MN decreased (P = 0.001) with MDP. In all treatments, the dominant microbial phyla were Firmicutes, Bacteroidota, and Proteobacteria, and the major microbial genus was Prevotella. Inclusion of MDP further increased the abundance of Bacteroidota (P = 0.04) as it increased both Prevotella (P = 0.04) and Prevotellaceae&#95;UCG-003 (P = 0.001). In conclusion, EA reduced OMD and acetate production due to impaired rumen function, these responses were successfully reversed by the addition of MDP., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

β-Hydroxy-β-methylbutyrate (HMB) supplementation increases muscle and strength mass in some muscle-wasting disorders. Malnutrition and sarcopenia are often present in liver cirrhosis. We aimed to investigate the effects of oral HMB supplementation on changes in body composition and liver status in patients with cirrhosis and malnutrition. In a randomized, controlled, double-blind trial, 43 individuals were randomized to receive twice a day and for 12 weeks an oral nutritional supplement (ONS) enriched with 1.5 g of calcium HMB per bottle or another supplement with similar composition devoid of HMB. Inclusion criteria were liver cirrhosis with at least one previous decompensation and clinical malnutrition. Liver function, plasma biochemistry analyses, and physical condition assessment were carried out at baseline, then after six and 12 weeks of supplementation. A total of 34 patients completed the clinical trial. An improvement in liver function and an increase in fat mass index were observed in both groups. None of the two ONS changed the fat-free mass. However, we observed an upward trend in handgrip strength and a downward trend in minimal hepatic encephalopathy in the HMB group. At the end of the trial and regardless of the supplement administered, fat mass content increased with no change in fat-free mass, while liver function scores and nutritional analytic markers also improved.

Objectives: To evaluate the efficacy of resistance training (RT) combined with beta-hydroxy-beta-methylbutyric acid (HMB) in the treatment of elderly patients with sarcopenia after hip replacement., Methods: From January 1, 2018 to December 31, 2018, 200 elderly patients (68 men, mean age 76.3 years and 137 women, mean age 79.1 years) who experienced femoral neck fracture with sarcopenia after hip arthroplasty were assigned to four groups: RT + HMB group, RT group, HMB group, and negative control group. Baseline data, body composition, grip strength, Barthel index (BI), Harris hip score (HHS), and visual analog scale score (VAS) were compared among the four groups before and 3 months after surgery., Results: A total of 177 participants completed the trial, including 43 in the HMB + RT group, 44 in the HMB group, 45 in the RT group, and 45 in the negative control group. At the 3-month follow-up, the body composition and grip strength of the HMB + RT group and RT group were significantly improved compared with those before operation. The HMB group had no significant change, while the measures in the negative control group significantly decreased. Postoperative BI and HSS did not reach pre-injury levels in any of the four groups, but postoperative VAS score was significantly improved. However, there was no significant difference in BI, HSS, or VAS among the four groups., Conclusion: RT, with or without HMB supplementation, can effectively improve body composition and grip strength in elderly patients with sarcopenia after hip replacement at short-term follow-up. Simultaneously, use of exclusive HMB supplementation alone may also help to prevent decreases in muscle mass and grip strength in these patients., (© 2022 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Purpose of Review: Skeletal muscle wasting is a serious consequence of critical illness, which may impact on long term physical and functional disability. To date, no intervention has been proven to reduce skeletal muscle wasting. Leucine and it's metabolite β-hydroxy-β-methylbutyrate (HMB) have been proposed as interventions. This review details the mechanism of action of both leucine and HMB, discusses the most recent research for both leucine and HMB and lastly discusses considerations for future research., Recent Findings: Only one study of leucine in critical illness has recently been published. This was a feasibility study where the physiological and muscle related outcomes were not reported to be feasible. Three studies on HMB have been reported recently with no effect seen on either muscle mass or strength. The main limitation in our understanding of the potential use of leucine or HMB on skeletal muscle wasting is the lack of mechanistic studies available in this population., Summary: Mechanistic studies should be a priority before embarking on further randomized controlled trials related to this topic., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Short-chain fatty acids (SCFAs) are a group of microbial metabolites of undigested dietary fiber, protein and unabsorbed amino acids in the colon, well-known for their gut health promoting benefits. A relatively high intestinal level of valerate was found in the healthy human subjects. However, the intestinal protection effects and the underlying mechanism of valerate are waiting to be verified and elucidated., Methods and Results: In the present study, valerate, a SCFAs mainly converted from proteins or amino acids, was demonstrated to promote intestinal barrier function at its physiological concentrations of 0-4 mM in the Caco-2 cell monolayer model of intestinal barrier using transepithelial electrical resistance (TEER) assay and paracellular permeability assay. Valerate achieved the maximum increase in the TEER at 2 mM and reduced the paracellular permeability. Its intestinal barrier function promoting activity is similar to that of butyrate, with a broader range of effective concentrations than the later. Through western blot analysis, this activity is linked to the valerate-induced AMPK activation and tight junctions (TJs) assembly, but not to the reinforced expression of TJs related proteins., Conclusions: It provides direct experimental evidence supporting valerate's function in intestinal health, implying the once under-valued function of valerate and its amino acid precursors. The valerate's role in regulating intestine homeostasis and its possible synergetic effects with other SCFAs warranted to be further investigated., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)