A new case of sodium-dependent multivitamin transporter defect occurring as a life-threatening condition responsive to early vitamin supplementation and literature review.

BACKGROUND: Biallelic pathogenic variants in SLC5A6 resulting in sodium-dependent multivitamin transporter (SMVT) defect have recently been described as a vitamin-responsive inborn error of metabolism mimicking biotinidase deficiency. To our knowledge, only 16 patients have been reported so far with various clinical phenotypes such as neuropathy and other neurologic impairments, gastro-intestinal dysfunction and failure to thrive, osteopenia, immunodeficiency, metabolic acidosis, hypoglycemia, and recently severe cardiac symptoms. METHODS: We describe a case report of a 5-month-old girl presenting two recurrent episodes of metabolic decompensation and massive cardiac failure in the course of an infectious disease. We compare clinical, biological, and genetic findings of this patient to previous literature collected from Pubmed database (keywords: Sodium-dependent multivitamin transporter (SMVT), SMVT defect/disorder/deficiency, SLC5A6 gene/mutation). RESULTS: We highlight the life-threatening presentation of this disease, the stagnation of psychomotor development, the severe and persistent hypogammaglobulinemia, and additionally, the successful clinical response on early vitamin supplementation (biotin 15 mg a day and pantothenic acid 100 mg a day). Metabolic assessment showed a persistent increase of urinary 3-hydroxyisovaleric acid (3-HIA) as previously reported in this disease in literature. CONCLUSION: SMVT deficiency is a vitamin-responsive inborn error of metabolism that can lead to a wide range of symptoms. Increased and isolated excretion of urinary 3-hydroxyisovaleric acid may suggest, in the absence of markedly reduced biotinidase activity, a SMVT deficiency. Prompt supplementation with high doses of biotin and pantothenic acid should be initiated while awaiting results of SLC5A6 sequencing as this condition may be life-threatening.

Supplementation with ß-hydroxy-ß-methylbutyrate after resistance training in post-acute care patients with sarcopenia: A randomized, double-blind placebo-controlled trial.

OBJECTIVES: This study aimed to evaluate the efficacy of adding ß-hydroxy-ß- methylbutyrate (HMB) supplementation to a 12-week exercise-based rehabilitation program in older adults with sarcopenia after discharge from a post-acute geriatric rehabilitation unit. STUDY DESIGN: A randomized, double-blind, placebo-controlled trial with two parallel groups. The intervention group received 3 g/day of Ca-HMB and participated in a 12- week resistance training program (3 sessions/week). The control group received a placebo and followed the same training program. MAIN OUTCOME MEASURES: The primary outcomes were the improvements of handgrip strength and physical performance assessed through the Short Physical Performance Battery (SPPB) and 4-meter gait speed; and handgrip strength. All variables were assessed at baseline, post-intervention, and 1-year follow-up. RESULTS: After completing the 12-week exercise program, the intervention group showed significant improvements in SPPB-Balance (1.3, 95 %CI 0.3 to 2.4) and total SPPB score (2.2, 95 %CI 0.4 to 4.0). Intra-group analysis demonstrated gains in the SPPB-Chair Stand (0.7 points, 95 %CI 0.0 to 1.4) and total SPPB score (2.1 points, 95 %CI 0.3 to 3.9) in the intervention group. Improvements in handgrip strength were observed in women (3.7 kg, 95 %CI: 0.2 to 7.3) at the end of the intervention, and persisted at the 1-year follow-up. CONCLUSIONS: Our findings suggest that the supplementation of 3 g/day of Ca-HMB with resistance exercise may significantly enhance muscle strength and physical performance among older women with sarcopenia after recent hospitalization. Given this study's limitations, the intervention's effectiveness cannot be drawn, and further studies are needed.

Association between endogenous plasma beta-hydroxy-beta-methylbutyrate levels and frailty in community-dwelling older people.

BACKGROUND: Frailty is a key element in healthy ageing in which muscle performance plays a main role. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation has shown favourable effects in modulating protein synthesis, improving muscle mass and function in interventional studies. Decreased age-related endogenous HMB levels have been shown in previous studies. The aim of the present study is to assess whether there is an association between endogenous plasma HMB levels and frailty. METHODS: Data from 1290 subjects (56.98% women; mean ± standard deviation age 74.6 ± 5.95 years) from the Toledo Study for Healthy Aging were obtained. Participants had their frailty status qualified according to Fried's Frailty Phenotype (FFP) score and the Frailty Trait Scale in its 12-domain version (FTS-12). Plasma HMB levels were analysed by an ultrahigh-performance liquid chromatography tandem mass spectrometry. Differences between groups (frail vs. non-frail) were tested using Mann-Whitney U test, Kruskal-Wallis test and chi-squared test. The association between HMB and frailty was assessed by multivariate linear and logistic regressions when frailty was analysed as continuous and binary, respectively. Models were adjusted by age, gender, comorbidity, body composition and protein intake. RESULTS: HMB levels were lower in those aged ≥75 years than in those aged 65-74 years, with an inverse linear relationship between age and HMB levels (ß = -0.031; P = 0.018), mainly accounted by males (ß = -0.062; P = 0.002). HMB levels were higher in men (0.238 ± 0.065 vs. 0.193 ± 0.051 ng/mL; P ≤ 0.001). HMB levels were significantly lower in frail than in non-frail individuals: 0.204 ± 0.058 versus 0.217 ± 0.063 ng/dL (P = 0.001) according to the FFP and 0.203 ± 0.059 versus 0.219 ± 0.063 ng/mL (P < 0.001) according to FTS-12. These differences showed a dose-dependent profile when we compared them by quintiles of HMB (P for trend: 0.022; 0.012 and 0.0004, respectively, for FFP, FTS-12 binary and FTS-12 continuous). Variables associated with low HMB levels were body mass index, strength, exhaustion and weight loss. Frailty was associated with HMB levels in all the adjusted models, including the fully adjusted ones, no matter the tool used (odds ratio: 0.45 [0.26, 0.77] for FFP and 0.36 [0.20, 0.63] for FTS-12 binary; ß = -4.76 [-7.29, -2.23] for FTS-12 score). This association was also observed when the analyses were done by quintiles, showing such association since Q4 (FFP), Q2 (FTS-12 binary) and Q3 (FTS-12 score). The associations were observed in the whole sample and in each gender. CONCLUSIONS: There is an inverse association between HMB levels and frailty status. These findings support the design of targeted clinical trials to evaluate the effect of HMB supplementation in older frail people with low HMB levels.

Dietary butyrate and valerate glycerides impact diarrhea severity and immune response of weaned piglets under ETEC F4-ETEC F18 coinfection conditions.

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.

Piglets suffer from post-weaning diarrhea associated with Enterotoxigenic Escherichia coli (ETEC) F4 and F18, two prevalent strains on swine farms globally. Short chain fatty acids (SCFAs), such as butyrate and valerate, are natural, organic compounds that could potentially promote intestinal health when used as dietary supplements. During the post-weaning period, piglets are vulnerable to simultaneous infection by ETEC F4 and F18. Therefore, this experiment aimed to develop an experimental disease model for coinfection with ETEC F4 and F18, employing a dose of 0.5 × 109 CFU/1.5 mL of each strain, administered over three consecutive days. In addition, the experiment evaluated treatment diets supplemented with 0.1% butyrate or valerate glycerides compared with the control diet. Results from this experiment revealed that the inoculation dose incited infection and diarrhea in piglets, implying its suitability for use in a disease challenge model. Moreover, the results indicated that the inclusion of butyrate and valerate glycerides to pig's diet reduced the severity of diarrhea. Furthermore, pigs fed SCFA glycerides exhibited lowered levels of inflammatory blood markers. In conclusion, the experimental dose induced diarrhea in piglets, and dietary supplementation of butyrate and valerate glycerides alleviated the severity of diarrhea while augmenting inflammatory status.

Beta-hydroxy-beta-methylbutyrate supplementation and functional outcomes in multitrauma patients: A pilot randomized controlled trial.

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.

Assessing milk response to different combinations of branched-chain volatile fatty acids and valerate in Jersey cows.

Some cellulolytic bacteria require 1 or more branched-chain volatile fatty acids (BCVFA) for the synthesis of branched-chain AA and branched-chain long-chain fatty acids because they are not able to uptake branched-chain AA or lack 1 or more enzymes to synthesize branched-chain AA de novo. Supplemental BCVFA and valerate were included previously as a feed additive that was later removed from the market; these older studies and more current studies have noted improvements in neutral detergent fiber digestibility and milk efficiency. However, most studies provided a single BCVFA or else isobutyrate (IB), 2-methylbutyrate (MB), isovalerate, and valerate altogether without exploring optimal combinations. Our objective was to determine a combination of isoacids that is optimal for milk production. Sixty (28 primiparous and 32 multiparous) lactating Jersey cows (106 ± 54 days in milk) were blocked and assigned randomly to either a control (CON) treatment without any isoacids, MB [12.3 mmol/kg dry matter (DM)], MB + IB (7.7 and 12.6 mmol/kg DM of MB and IB, respectively), or all 4 isoacids (6.2, 7.3, 4.2, and 5.1 mmol/kg DM of MB, IB, isovalerate, and valerate, respectively). Cattle were fed the CON treatment for a 2-wk period, then were assigned randomly within a block to treatments for 8 wk (n = 15). There was a trend for an interaction of supplement and parity for milk components. There were no differences in components for primiparous cows, whereas MB + IB tended to increase protein concentration by 0.04 and 0.08 percentage units in multiparous cows compared with the CON and MB treatments, respectively. Feeding MB + IB increased fat concentration by 0.23 to 0.31 percentage units compared with all other treatments in multiparous cows. Milk yield and dry matter intake (DMI) did not change with treatment. Treatment interacted with week for milk net energy for lactation/DMI; MB + IB tended to increase milk net energy of lactation/DMI by 0.10 Mcal/kg compared with MB and approached a trend for CON, mainly during the early weeks of the treatment period, whereas differences decreased during the last 2 wk of the treatment period. Cows fed MB had the highest 15:0 anteiso fatty acids in the total milk fatty acid profile, which was greater than that for CON or MB + IB cows, but not cows supplemented with isoacids. Cows fed MB alone had the numerically lowest milk net energy for lactation/DMI. The combination of MB + IB appeared optimal for increasing feed efficiency in our study and was not at the expense of average daily gain. Further research is needed for evaluating how potential changes in supplemental isoacid dosage should vary under differing dietary conditions.

Effects of the use of oral nutrition supplements on clinical outcomes among patients who have undergone surgery for hip fracture: A literature review.

Older adults who have undergone surgery for hip fracture are often malnourished or at risk for malnutrition, and providing oral nutrition supplements is a common intervention used to help meet nutrition needs postoperatively among this population. A literature search was conducted to examine the effects of oral nutrition supplementation on postoperative outcomes among patients ≥55 years old who had undergone surgery for hip fracture. Three randomized controlled trials that met inclusion criteria are examined in this review. Findings suggest that the use of oral nutrition supplements is not associated with decreased hospital length of stay but is associated with improvements in markers of sarcopenia and functional status. Additionally, the literature implies that oral nutrition supplements containing calcium beta-hydroxy-beta-methylbutyrate may have the most benefit for improving postoperative outcomes. This review concludes that oral nutrition supplement use can be incorporated as a part of routine protocols for patients who have had surgery to repair a hip fracture. However, given some inconsistent findings, future research is needed to support the inclusion of oral nutrtition supplement use in clinical practice guidelines for this population. Furthermore, future research should explore how the use of oral nutrition supplements with calcium beta-hydroxy-beta-methylbutyrate compares with the use of oral nutrition supplements without this ingredient.

Effects of Macleaya cordata extract supplementation on digestive parameters of ponies.

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.

The effect of ß-hydroxy ß-methylbutyrate (HMB) with nutritional counselling on anthropometric muscle mass markers, strength, functionality, and quality of life in patients on the waiting list for liver transplantation: A double-blind study.

OBJECTIVE: Patients on the waiting list for liver transplantation (LTx) usually lose muscle mass. Supplementation with ß-hydroxy ß-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.

Dietary supplementation modified attapulgite promote intestinal epithelial barrier and regulate intestinal microbiota composition to prevent diarrhea in weaned piglets.

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.

Advances in muscle health and nutrition: A toolkit for healthcare professionals.

Low muscle mass and malnutrition are prevalent conditions among adults of all ages, with any body weight or body mass index, and with acute or chronic conditions, including COVID-19. This article synthesizes the latest research advancements in muscle health and malnutrition, and their impact on immune function, and clinical outcomes. We provide a toolkit of illustrations and scientific information that healthcare professionals can use for knowledge translation, educating patients about the importance of identifying and treating low muscle mass and malnutrition. We focus on the emerging evidence of mitochondrial dysfunction in the context of aging and disease, as well as the cross-talk between skeletal muscle and the immune system. We address the importance of myosteatosis as a component of muscle composition, and discuss direct, indirect and surrogate assessments of muscle mass including ultrasound, computerized tomography, deuterated creatine dilution, and calf circumference. Assessments of muscle function are also included (handgrip strength, and physical performance tests). Finally, we address nutrition interventions to support anabolism, reduce catabolism, and improve patient outcomes. These include protein and amino acids, branched-chain amino acids, with a focus on leucine; ß-hydroxy-ß-methylbutyrate (HMB), vitamin D; n-3 polyunsaturated fatty acids (n-3 PUFA), polyphenols, and oral nutritional supplements. We concluded with recommendations for clinical practice and a call for action on research focusing on evaluating the impact of body composition assessments on targeted nutrition interventions, and consequently their ability to improve patient outcomes.

Perioperative Oral ß-Hydroxy-ß-Methylbutyrate Supplementation Ameliorates Sarcopenia in Rats Undergoing Major Hepatectomy.

ß-Hydroxy-ß-methylbutyrate (HMB), a metabolite of leucine, is known to increase muscle mass and strength. However, the effect of perioperative HMB supplementation in liver surgery is unclear. Moreover, the impact of HMB on the skeletal muscle fiber type also remains unclear. We investigated the impact of HMB on the body composition and skeletal muscle fiber type in sarcopenic rats undergoing major hepatectomy. Nine-week-old male F344/NSlc rats were maintained in hindlimb suspension (HLS) and were forcedly supplemented with HMB calcium salt (HMB-Ca, 0.58 g/kg×2 times) or distilled water in addition to free feeding. After 2 wk of HLS, the rats underwent 70% hepatectomy and were sacrificed 3 d after surgery. Body composition factors and the proportion of slow-twitch fibers in hindlimb muscles were evaluated. HMB maintained the body composition and hindlimb force and acted against their deterioration in sarcopenic rats, exerting a particular effect on lean mass weight, which was significant. In the histological study, HMB significantly increased the proportion of slow-twitch fibers in the soleus (p=0.044) and plantaris (p=0.001) of sarcopenic rats. HMB ameliorated deterioration of the body composition and increased the proportion of slow-twitch fibers in sarcopenic rats undergoing major hepatectomy.

Evaluation of the recovery after heart surgery following preoperative supplementation with a combination of beta-hydroxy-beta-methylbutyrate, L-arginine, and L-glutamine: a double-blind randomized placebo-controlled clinical trial.

BACKGROUND: The preoperative period is a good time to improve nutrition status, compensate for nutrient deficiencies, and optimize immune function in patients' underlying surgery. In some medical conditions, supplementation with a combination of L-glutamine (Gln), ß-hydroxy-ß-methylbutyrate (HMB), and L-arginine (Arg) had promising effects on improving recovery. The present study aimed to evaluate the effect of supplementation with Gln/Arg/HMB in patients undergoing heart surgery. METHODS: This randomized clinical trial was conducted on 70 patients undergoing cardiac surgery. Participants were requested to consume 2 sachets of a combination of 7 g L-arginine, 7 g L-glutamine, and 1.5 g daily HMB or placebo 30 days before operation. At the baseline and end of the study, left ventricular ejection fraction and the serum levels of troponin, creatine phosphokinase (CPK), CPK-MB, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin were measured. Also, the Sequential Organ Failure Assessment (SOFA) score, time of stay in hospital and intensive care unit (ICU), and postoperative complications were recorded after surgery. RESULTS: In total, 60 preoperative patients (30 in each group) with a mean age of 53.13 ± 14.35 years completed the study (attrition rate = 85.7%). Subjects in the Gln/Arg/HMB group had lower serum levels of CPK-MB (median [IQR] = 49 [39.75] vs. 83 [64.55]; P = 0.011), troponin (median [IQR] = 2.13 [1.89] vs. 4.34 [1.99]; P < 0.001), bilirubin (median [IQR] = 0.50 [0.20] vs. 0.40 [0.22]; P < 0.001), and SOFA score (median [IQR] = 2 [2] vs. 5 [2]; P < 0.001) at end of the study compared to the placebo. Also, the time of stay in the hospital (median [IQR] = 5 [1] vs. 6 [3]; P < 0.001) and ICU (median [IQR] = 2.50 [1.00] vs. 3.50 [1.50]; P = 0.002) was lower in the Gln/Arg/HMB group. CONCLUSION: The present study showed that perioperative supplementation with a combination of Gln, Arg, and HMB enhances the recovery, reduces myocardial injury, and decreases the time of hospital and ICU stay in cardiac surgery patients. These results need to be confirmed in a larger trial. TRIAL REGISTRATION: IRCT.ir IRCT20120913010826N31. Registered on 13 October 2020.

An umbrella review of systematic reviews of ß-hydroxy-ß-methyl butyrate supplementation in ageing and clinical practice.

The compound ß-hydroxy-ß-methyl butyrate (HMB) is proposed to increase or mitigate the loss of skeletal muscle and improve muscle function. We undertook a review of systematic reviews of HMB supplementation to promote gains or mitigate muscle loss in ageing and clinical populations. Following PRISMA guidelines, we searched for systematic reviews reporting the effect of HMB in our target populations. Dual-energy X-ray absorptiometry (DXA) measured lean soft-tissue mass (LSTM) was accepted as a proxy for muscle. We identified 15 systematic reviews that met our inclusion criteria, which were independently evaluated. The methodological quality of the reviews was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and standardized effectiveness statements were generated. Five of 15 studies found some evidence that HMB augmented LSTM; the remaining 10 studies reported some evidence favouring no difference (6/10 studies) or insufficient evidence to determine an effect (4/10 studies). Of the 12 studies that evaluated strength, 4/12 found some evidence, 5/12 found some evidence of no effect with one article finding some evidence in favour of patients in peri-hospitalized and no evidence for those that are community-dwelling, 4/12 had insufficient evidence to determine an effect, and 1/12 had insufficient evidence. No]study reported a positive effect of HMB on physical function; however, 2/10 studies found some evidence favouring no effect, and 7/10 studies reported insufficient evidence to determine an effect. The effectiveness of HMB supplementation in augmenting LSTM was heterogeneous, with most reviews finding no effect or inconclusive evidence to determine an effect. Most reviews concluded that HMB supplementation did not affect strength outcome measures or studies were inconclusive. The current evidence is insufficient to assess the impact of HMB supplementation on functional outcome measures. Our analysis shows minor, inconsistent support for HMB as part of an oral nutritional supplement or as a stand-alone supplement (or combined with other amino acids) to increase or promote retention of LSTM, improve strength, and no evidence that it improves physical function in older persons or clinical populations.

Substituting ryegrass-based pasture with graded levels of forage rape in the diet of lambs decreases methane emissions and increases propionate, succinate, and primary alcohols in the rumen.

Feeding 100% forage rape to sheep consistently lowers methane emissions per unit of intake (CH4/DMI) compared to those fed 100% ryegrass pasture. However, forage rape is usually supplemented with other feeds, which might impact the mitigation potential provided by forage rape. The objective of this study was to determine the effect of substituting ryegrass with graded levels of forage rape in the diet of lambs on methane emissions and rumen fermentation characteristics. Seventy wether lambs (n = 14/treatment) were fed a ryegrass-based pasture substituted with 0%, 25%, 50%, 75%, and 100% of forage rape (Brassica napus; FR0, FR25, FR50, FR75, and FR100, respectively) on a dry matter basis. Methane emissions and dry matter intake were measured for 48 h in respiration chambers and a rumen fluid sample was collected. CH4/DMI decreased (P < 0.01) with increasing forage rape inclusion in the diet so that sheep fed FR100 and FR75 emitted 34% and 11% less, respectively, than those fed FR0. CH4/DMI differences for lambs fed FR25 and FR50 were much smaller (<6%) relative to FR0. The pH of rumen fluid decreased (P < 0.01) at higher levels of forage rape inclusion in the diet (FR75 and FR100) compared to low levels of inclusion (FR0, F25, and F50). The proportion of ruminal acetate was least in FR100 (30%) followed by FR75 (10%), FR50 (8%), and FR25 (4%) compared with FR0 (P < 0.001). The proportion of propionate plus succinate was greater for FR100 (+40%), FR75 (+28%), and FR50 (+29%) compared with FR0, with FR25 intermediate (P < 0.001). The methanol concentration, and ethanol and propanol proportions in rumen fluid were greater for FR100 compared with any other treatment (P < 0.001). In conclusion, CH4/DMI decreased at high levels of forage rape inclusion in the diet and especially feeding FR100 was associated with a pronounced shift in rumen fermentation profile, with a significant presence of succinate, ethanol, propanol, methanol, valerate, and caproate.

The methane yield (g methane/kg dry matter intake) was 34% lower in sheep fed 100% forage rape and 11% lower in sheep fed 75% forage rape compared to sheep fed 100% ryegrass-based pasture. Sheep fed 25% and 50% forage rape as part of their diet had similar methane yields to sheep fed 100% ryegrass pasture. Sheep fed 100% forage rape had a ruminal fermentation profile with a smaller proportion of acetate and greater proportions of fermentation products like propionate, succinate, and valerate. Acetate formation is associated with hydrogen gas formation, which in turn is converted to methane in the rumen. Propionate, succinate, and valerate are alternatives to acetate plus hydrogen production and so fermentation shifts to them result in less methane formation.

ß-hydroxy-ß-methylbutyrate-enriched nutritional supplements for obese adults during weight loss: study protocol of a randomised, double-blind, placebo-controlled clinical trial.

INTRODUCTION: Obesity is a public health challenge worldwide. To maintain a healthy weight, dieting and lifestyle changes are the first-line interventions; however, these interventions are of poor compliance and may cause body composition changes, mainly skeletal muscle wasting (sarcopenia). Dietary supplements for improving body composition while inducing weight loss are therefore needed. ß-hydroxy-ß-methylbutyrate (HMB) has been proven to be effective for improving muscle mass and muscle strength in athletes, older adults and patients with cancer. We aim to evaluate the effectiveness and safety of HMB-enriched nutritional supplements for improving muscle mass and muscle function in obese adults during calorie restriction. METHOD AND ANALYSIS: A total of 72 Chinese adults with obesity will be randomised to receive HMB-enriched nutritional supplements (65 g/day) or a placebo for 12 weeks. Participants in both groups will also receive calorie restrictions based on the individualised nutrition guidance of dietitians. Participants and investigators will be blinded to the allocations. The primary outcome will be the mean change in whole-body skeletal muscle mass (measured by bioelectrical impedance analysis). The secondary outcomes will include the mean change of appendicular skeletal muscle mass, body fat mass, basal metabolic rate, phase angle, muscle function and serum biomarkers. The enrolment will commence in December 2021 and will proceed until March 2022. ETHICS AND DISSEMINATION: This protocol has been approved by the Biomedical Ethics Committee of West China Hospital (2021-771). All potential subjects will be required to sign a written informed consent. The results of this study will be reported in peer-reviewed academic journals and conferences. TRIAL REGISTRATION NUMBER: NCT04953936.

Randomized Clinical Trial: Effects of ß-Hydroxy-ß-Methylbutyrate (HMB)-Enriched vs. HMB-Free Oral Nutritional Supplementation in Malnourished Cirrhotic Patients.

ß-Hydroxy-ß-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.

Short Chain Fatty Acids and Bacterial Taxa Associated with Reduced Salmonella enterica serovar I 4,[5],12:i:- Shedding in Swine Fed a Diet Supplemented with Resistant Potato Starch.

Salmonella enterica serovar I 4,[5],12:i:- is a foodborne pathogen of concern because many isolates are multidrug-resistant (resistant to ≥3 antimicrobial classes) and metal tolerant. In this study, three in-feed additives were individually tested for their ability to reduce Salmonella I 4,[5],12:i:- shedding in swine: resistant potato starch (RPS), high amylose corn starch, and a fatty acid blend, compared with a standard control diet over 21 days. Only RPS-fed pigs exhibited a reduction in Salmonella fecal shedding, different bacterial community compositions, and different cecal short chain fatty acid (SCFA) profiles relative to control animals. Within the RPS treatment group, pigs shedding the least Salmonella tended to have greater cecal concentrations of butyrate, valerate, caproate, and succinate. Additionally, among RPS-fed pigs, several bacterial taxa (Prevotella_7, Olsenella, and Bifidobacterium, and others) exhibited negative relationships between their abundances of and the amount of Salmonella in the feces of their hosts. Many of these same taxa also had significant positive associations with cecal concentrations of butyrate, valerate, caproate, even though they are not known to produce these SCFAs. Together, these data suggest the RPS-associated reduction in Salmonella shedding may be dependent on the establishment of bacterial cross feeding interactions that result in the production of certain SCFAs. However, directly feeding a fatty acid mix did not replicate the effect. RPS supplementation could be an effective means to reduce multidrug-resistant (MDR) S. enterica serovar I 4,[5],12:i:- in swine, provided appropriate bacterial communities are present in the gut. IMPORTANCE Prebiotics, such as resistant potato starch (RPS), are types of food that help to support beneficial bacteria and their activities in the intestines. Salmonella enterica serovar I 4,[5],12:i:- is a foodborne pathogen that commonly resides in the intestines of pigs without disease, but can make humans sick if unintentionally consumed. Here we show that in Salmonella inoculated pigs, feeding them a diet containing RPS altered the colonization and activity of certain beneficial bacteria in a way that reduced the amount of Salmonella in their feces. Additionally, within those fed RPS, swine with higher abundance of these types of beneficial bacteria had less Salmonella I 4,[5],12:i:- in their feces. This work illustrates likely synergy between the prebiotic RPS and the presence of certain gut microorganisms to reduce the amount of Salmonella in the feces of pigs and therefore reduce the risk that humans will become ill with MDR Salmonella serovar I 4,[5],12:i:-.

Estrogen valerate pretreatment with the antagonist protocol does not increase oocyte retrieval in patients with low ovarian response: a randomized controlled trial.

STUDY QUESTION: Does luteal phase estrogen valerate pretreatment improve oocyte yield and clinical outcomes in patients with low ovarian response during ovarian stimulation with the antagonist protocol? SUMMARY ANSWER: Pretreatment with oral estrogen valerate from Day 7 after ovulation to Day 2 of the next menstrual cycle did not increase oocyte yield in patients with a low ovarian response compared to no pretreatment. WHAT IS KNOWN ALREADY: Previous studies showed that patients with a normal ovarian response can obtain better clinical outcomes after pretreatment with estrogen in the antagonist protocol. For patients with advanced age and low ovarian response, it remains unclear if estrogen valerate pretreatment with the antagonist protocol yields more oocytes and improves pregnancy outcomes. STUDY DESIGN, SIZE, DURATION: This non-blinded randomized controlled trial (RCT) was conducted between November 2017 and March 2021. Participants were 552 women with low response who requested IVF treatment. The primary endpoint was comparison of the total number of retrieved oocytes between the two groups. The secondary endpoints were the total number of retrieved metaphase II (MII) oocytes, duration and total dosage of recombinant FSH (rFSH), good-quality embryo rate and clinical pregnancy rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at a reproductive center. The RCT enrolled 552 infertile women with a low ovarian response (according to the Bologna criteria) who were undergoing IVF. In the study group, on Day 7 after ovulation patients were administered oral estrogen valerate (2 mg twice a day) until Day 2 of their next menstruation. Ovary stimulation was performed using rFSH, and a GnRH antagonist (0.25 mg/day) was started when a dominant follicle had a mean diameter ≥13 mm. MAIN RESULTS AND THE ROLE OF CHANCE: No significant difference was observed in the number (mean [SD]) of oocytes retrieved from the estrogen valerate pretreatment and control group (3.2 [2.8] versus 3.4 [2.6], respectively). The treatment difference was -0.18 (95% CI -0.67, 0.32, P = 0.49). No significant differences were observed in the number of MII oocytes (2.9 [2.5] versus 3.1 [2.4], mean difference -0.23, 95% CI (-0.69, 0.23), P = 0.16) and good-quality embryos (1.0 [1.3] versus 1.20 [1.6], mean difference -0.23, 95% CI (-0.50, 0.04), P = 0.19) between the two groups. The duration of rFSH treatment was significantly longer in the estrogen valerate pretreatment group than in the control group (10.3 [2.2] versus 8.6 [2.1] days, mean difference 1.7, 95% CI (1.3, 2.2), P = 0.00), and the total rFSH dosage was significantly higher in the estrogen valerate pretreatment group than in the control group (3081 [680] versus 2548 [649] IU, mean difference 553.7, 95% CI (405.8, 661.6), P = 0.00). The clinical pregnancy rate in the pretreatment group (19.3% [23/119]) was not significantly different from that in the control group (28.7% [43/150]). The mean difference was -0.09, 95% CI (-0.20, 0.01), P = 0.08. LIMITATIONS, REASONS FOR CAUTION: The major limitation was the high dropout rate of patients. Some patients did not return to the hospital for treatment because of predicted low success rates and for economic reasons. In addition, it is possible that the fixed dose of 300 IU rFSH was not sufficient to see differences in oocyte yield between the groups. WIDER IMPLICATIONS OF THE FINDINGS: Estrogen valerate pretreatment with an antagonist protocol did not increase oocyte yield in patients with low ovarian response. Similar to the number of retrieved oocytes, there was no significant difference in clinical pregnancy rate between estrogen pretreatment group and control group. More research is needed on whether patients with low ovarian response need pretreatment and which pretreatment is more appropriate. STUDY FUNDING/COMPETING INTEREST(S): This study was supported in part by a research grant from the Investigator-Initiated Studies Program of MSD (China) Holding Co., Ltd. and Organon (Shanghai) Pharmaceutical Technology Co., Ltd. (Grant number: IIS 56284). The authors declare that they have no competing interests regarding authorship or publication of this study. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03300518. TRIAL REGISTRATION DATE: 28 September 2017. DATE OF FIRST PATIENT'S ENROLMENT: 15 November 2017.

Gut microbiota production of trimethyl-5-aminovaleric acid reduces fatty acid oxidation and accelerates cardiac hypertrophy.

Numerous studies found intestinal microbiota alterations which are thought to affect the development of various diseases through the production of gut-derived metabolites. However, the specific metabolites and their pathophysiological contribution to cardiac hypertrophy or heart failure progression still remain unclear. N,N,N-trimethyl-5-aminovaleric acid (TMAVA), derived from trimethyllysine through the gut microbiota, was elevated with gradually increased risk of cardiac mortality and transplantation in a prospective heart failure cohort (n = 1647). TMAVA treatment aggravated cardiac hypertrophy and dysfunction in high-fat diet-fed mice. Decreased fatty acid oxidation (FAO) is a hallmark of metabolic reprogramming in the diseased heart and contributes to impaired myocardial energetics and contractile dysfunction. Proteomics uncovered that TMAVA disturbed cardiac energy metabolism, leading to inhibition of FAO and myocardial lipid accumulation. TMAVA treatment altered mitochondrial ultrastructure, respiration and FAO and inhibited carnitine metabolism. Mice with γ-butyrobetaine hydroxylase (BBOX) deficiency displayed a similar cardiac hypertrophy phenotype, indicating that TMAVA functions through BBOX. Finally, exogenous carnitine supplementation reversed TMAVA induced cardiac hypertrophy. These data suggest that the gut microbiota-derived TMAVA is a key determinant for the development of cardiac hypertrophy through inhibition of carnitine synthesis and subsequent FAO.