Beta-hydroxy-beta-methylbutyrate Research Articles

PO-238 Urinary metabolomics study on the anti-depression effect of different exercise modes on CUMS model rats

Objective To study the effects of different exercise modes on CUMS depression model rats by 1H-NMR metabolomics technique, and to explore the mechanism of exercise anti-depression and to find the best exercise mode.
 Methods Forty-eight male SD rats were divided into control group (group C), model group (group M), aerobic exercise group (group A), and resistance exercise group (group R), 12 per group. The group C was routinely reared, chronic mild unpredictable stress + orphaned 8 weeks to establish a depression model of CUMS rats. In the 5th week of modeling, rats in group A and group R were trained in aerobic and resistance exercise for 4 weeks. The changes of body mass were observed during the experiment. The effects of exercise on the behavior of CUMS rats were observed by sucrose preference experiment and open field experiment. The levels of plasma BDNF, CORT and 5-HT were measured to reveal the pathological changes of the model. 1H-NMR metabolomics techniques combined with multivariate statistical analysis methods were used to investigate the regulation of urinary endogenous metabolites and the regulation of metabolic pathways in CUMS depression rats. 
 Results 1) After four weeks of modeling, compared with the group C, the body weight, saccharide water preference rate, the crossing number and the number of erectings in the group M, group A and group R were significantly lower (P<0.05 or P< 0.01), indicating that the modeling was successful; after eight weeks of modeling, compared with the group C, the body weight, saccharide water preference rate, the crossing number and the number of erectings in the group M, was significantly lower (P<0.01). There was no significant difference in the group A and group R. 2)Compared with group C, the levels of BDNF and 5-HT in group M were significantly decreased (P<0.05 or P<0.01), the level of CORT was significantly increased (P<0.01), and the levels of BDNF, 5-HT and CORT in group A were not significantly different, the CORT levels were significantly increased in group R(P <0.01), BDNF and 5-HT levels were not significantly different; compared with group M, BDNF, 5-HT levels in group A were significantly increased (P <0.05) and the level of CORT was significantly decreased (P<0.01), the levels of BDNF and 5-HT in group R were significantly increased (P<0.01), but there was no significant difference in CORT level. Compared with group A, the levels of BDNF and 5-HT in group R were not significant,but CORT levels increased significantly (P<0.05). 3)A total of 14 potential biomarkers in the urine of CUMS depression model rats were found . Compared with group C, the levels of leucine, valine, lactic acid, citric acid, inositol, pyruvic acid, β-hydroxybutyric acid, acetoacetic acid, trimethylamine, pantothenic acid, β-hydroxyisovaleric acid, alanine and succinic acid in the urine of group M were significantly increased, and the level of α-ketoglutaric acid was significantly decreased (P<0.05 or P<0.01). Group A can significantly callback 8 potential biomarkersof leucine, lactic acid, citric acid, pyruvic acid, β-hydroxybutyric acid, alanine, lactic acid and pantothenic acid (P<0.05 or P<0.01) , the group R can significantly callbackt the 6 potential biomarkers of lactic acid, acetoacetic acid, inositol, trimethylamine, β-hydroxy isovaleric acid and alanine. Two types of exercise can regulate urinary metabolites in depressed rats. 4) 1H-NMR metabolic pathway analysis showed that aerobic exercise mainly improves the urine metabolism of depressed rats by regulating TCA cycle, pantothenic acid and COA biosynthesis, and pyruvate metabolism. The resistance exercise mainly improved the urine metabolism characteristics of depressed rats by regulating the synthesis and degradation of ketone bodies, pyruvate metabolism and inositol phosphate metabolism.
 Conclusions Aerobic exercise and resistance exercise all can effectively improve depressive symptoms, adjust the urine biomarkers of depressed rats to varying degrees, which may be related to different metabolic pathways involved in exercise modes.

Distinct Fecal Microbiota and Serum Metabolite Profiles in Male Rat Exposed to Aluminum Oxide and Aluminum Oxide Nanoparticles

The widely application of aluminum oxide nanoparticles (Al2O3 NPs) in industry and personal care products has been raising concerns about their potential adverse consequences. However, the knowledge on their influence on gut microbiota and serum metabolism remains poorly understood. This study employed an integrated approach combining 16S rRNA gene sequencing and untargeted metabolomics profiling to investigate the impact of a 28 days oral exposure to α- and γ-Al2O3 NPs and the equivalent dose of bulk Al2O3 on the toxic response, fecal microbiota composition and serum metabolites of male rats. At the equal dose of 100 mg/kg bw, α-Al2O3 NPs had a greater effect on white blood cell count, percent of monocytes, liver SOD activity and plasma GSH content, than that of γ-Al2O3 NPs and bulk Al2O3. 16S results revealed NPs exposure significantly perturbed the fecal microbiome composition, and the relative abundance of genus such as Desulfovibrio, Steroidobacter and Acidibacter was significantly reduced. A significantly lower alpha diversity and distinct microbial communities, as reflected by beta diversity, were observed in α-Al2O3 NPs treatment, compared to bulk Al2O3 and control. UHPLC-QTOFMS indicated that the circulating serum metabolites (e.g. 3-hydroxyisovaleric acid, dopamine, D-glucuronate) were significantly more abundant with α-Al2O3 NPs, while metabolites (e.g. corticosterone, glycerol, glycerol 3-phosphate) were significantly induced by γ-Al2O3 NPs. Pathway analysis further indicated potential defects in the D-glutamine and D-glutamate metabolism and phenylalanine, tyrosine and tryptophan biosynthesis in α-Al2O3 NPs, while glycerolipid and linoleic acid metabolism were significantly affected by γ-Al2O3 NPs. This study provides novel insights regarding the differential fecal microbiome and serum metabolome affected by nanoparticulate forms versus bulk forms of aluminum oxide in organisms.

Effect of supplementation with a combination ofl‐arginine,l‐glutamine, and hydroxy methyl butyrate on cachexia: A systematic review

Weight loss in the form of cachexia is a comorbid condition which is associated with delayed recovery, especially in cancer and human immunodeficiency virus (HIV)-infected patients. Arginine (Arg), Glutamine (Gln), and the Leucine metabolite, Hydroxy methyl butyrate (HMB) are substrates which have been investigated due to their potential role in ameliorating muscle mass. We conducted a systematic review to appraise available studies assessing the effect of Arg, Gln, and HMB supplementation on improving body weight and muscle mass in those with pathological conditions. A comprehensive search for studies published between January 1990 and November 2017 was performed. The interested primary outcome of this systematic review was weight. Two reviewers independently searched databases and 125 papers were identified from the initial search, overall, we selected five studies that were suitable for our systematic review. The results of the studies shows that this combination can improve fat free mass, weight and immune function in cachexia and morbid weight loss patients. Practical applications Cachexia is one of the main problems in many chronic diseases. Providing a nutritional support is usually the main concern in patients with severe weight loss due to the impaired appetite and gastrointestinal tract irritation. Among nutrition interventions, Protein and amino acid supplementation receive much attention due to the loss of muscle tissue and the negative balance of protein and nitrogen in patients with severe weight loss. Arg, Gln, and HMB (Arg/Gln/HMB) supplementation can improve weight gain and prevent weight loss in chronic diseases.

A synthetic pathway for the production of 2-hydroxyisovaleric acid in Escherichia coli.

Synthetic biology, encompassing the design and construction of novel artificial biological pathways and organisms and the redesign of existing natural biological systems, is rapidly expanding the number of applications for which biological systems can play an integral role. In the context of chemical production, the combination of synthetic biology and metabolic engineering approaches continues to unlock the ability to biologically produce novel and complex molecules from a variety of feedstocks. Here, we utilize a synthetic approach to design and build a pathway to produce 2-hydroxyisovaleric acid in Escherichia coli and demonstrate how pathway design can be supplemented with metabolic engineering approaches to improve pathway performance from various carbon sources. Drawing inspiration from the native pathway for the synthesis of the 5-carbon amino acid L-valine, we exploit the decarboxylative condensation of two molecules of pyruvate, with subsequent reduction and dehydration reactions enabling the synthesis of 2-hydroxyisovaleric acid. Key to our approach was the utilization of an acetolactate synthase which minimized kinetic and regulatory constraints to ensure sufficient flux entering the pathway. Critical host modifications enabling maximum product synthesis from either glycerol or glucose were then examined, with the varying degree of reduction of these carbons sources playing a major role in the required host background. Through these engineering efforts, the designed pathway produced 6.2g/L 2-hydroxyisovaleric acid from glycerol at 58% of maximum theoretical yield and 7.8g/L 2-hydroxyisovaleric acid from glucose at 73% of maximum theoretical yield. These results demonstrate how the combination of synthetic biology and metabolic engineering approaches can facilitate bio-based chemical production.

What Is the Role of Nutritional Supplements in Support of Total Hip Replacement and Total Knee Replacement Surgeries? A Systematic Review.

Nutritional supplements can influence outcomes for individuals undergoing major surgery, particularly in older persons whose functional reserve is limited. Accelerating recovery from total hip replacement (THR) and total knee replacement (TKR) may offer significant benefits. Therefore, we explored the role of nutritional supplements in improving recovery following THR and TKR. A systematic review was conducted to source randomized clinical trials that tested nutritional supplements in cohorts of THR or TKR patients. Our search yielded nine relevant trials. Intake of a carbohydrate-containing fluid is reported to improve insulin-like growth factor levels, reduce hunger, nausea, and length of stay, and attenuate the decrease in whole-body insulin sensitivity and endogenous glucose release. Amino acid supplementation is reported to reduce muscle atrophy and accelerate return of functional mobility. One paper reported a suppressive effect of beta-hydroxy beta-methylbutyrate, l-arginine, and l-glutamine supplementation on muscle strength loss following TKR. There is limited evidence for nutritional supplementation in THR and TKR pathways; however, the low risk profile and potential benefits to adjunctive treatment methods, such as exercise programs, suggest nutritional supplements may have a role. Optimizing nutritional status pre-operatively may help manage the surgical stress response, with a particular benefit for undernourished, frail, or elderly individuals.

Cognitive function is preserved in aged mice following long-term β-hydroxy β-methylbutyrate supplementation

β-hydroxy β-methylbutyrate (HMB) is a nutritional supplement purported to enhance skeletal muscle mass and strength, as well as cognitive function in older adults. The purpose of this study was to determine the potential for long-term HMB supplementation to preserve muscle function and cognition in aged mice, as well as provide evidence of a link between vessel-associated pericyte function and outcomes. Four- (Adult/Ad) and 17 month-old (Aged/Ag) C57BL/6J mice consumed chow containing 600 mg/kg BW/day of either Ca-HMB (Ad, n=16; Ag, n=17) or Ca-Lactate (Ad, n=16; Ag, n=17) for 6 months. HMB did not prevent age-related reductions in muscle mass, strength and coordination (Age main effect, P<0.05). The rate of muscle protein synthesis decreased within the mitochondrial fraction (age main effect, P<0.05), and this decline was not prevented with HMB. Despite no change in muscle mass or function, an age-dependent reduction in active avoidance learning was attenuated with HMB (Age and HMB main effects, P<0.05). Age detrimentally impacted muscle-resident pericyte gene expression with no recovery observed with HMB, whereas no changes in brain-resident pericyte quantity or function were observed with age or HMB. The findings from this study suggest that prolonged HMB supplementation starting in adulthood may preserve cognition with age.

Growth Responses of Preterm Pigs Fed Formulas with Different Protein Levels and Supplemented with Leucine or β-Hydroxyl β-Methylbutyrate

Growth after preterm birth is an important determinant of long-term outcomes. Yet, many preterm infants suffer ex utero growth retardation. We evaluated effects of leucine and the metabolite, β-hydroxy β-methylbutyrate (HMB) on growth of preterm pigs, a previously-validated translational model for preterm infants. After 48 h of parenteral nutrition preterm pigs were fed for 6 to 7 days isocaloric formulas with different levels of protein (50 or 100 g/L) with leucine (10 g/L, 76 mM) or HMB (at 1.1 g/L, 4 mM) added to stimulate protein synthesis or with alanine (6.8 g/L; 76 mM) as the control. Rates of growth of pigs fed the low protein formula with alanine (3.4 ± 0.2% gain per day) or leucine (3.7 ± 0.2) exceeded that of pigs fed the high protein formula (2.8 ± 0.2, p = 0.02 for comparison with both low protein formulas; p = 0.01 compared with low protein + leucine). Supplementing the high protein formula with leucine or HMB did not increase growth relative to alanine (2.72 ± 0.20, 2.74 ± 0.27, and 2.52 ± 0.20, respectively). Small pigs (<700 g birth weight) grew slower during parenteral nutrition and had a more pronounced response to leucine. Females fed the high protein formulas grew faster than males, and particularly for small pigs (p < 0.05). Blood urea nitrogen values were lower for pigs fed the low versus the high protein formulas (p < 0.05). Leucine and HMB improved growth of preterm pigs fed low, but not high protein formulas, even after controlling for birth weight and sex, which independently correlated with growth rates. They offer an option to improve growth without increasing the amino acid load, with its attendant metabolic disadvantages.

Is β-hydroxy β-methylbutyrate an effective anabolic agent to improve outcome in older diseased populations?

β-Hydroxy β-methylbutyrate (HMB) has been used for many years in athletes for muscle buildup and strength, and endurance enhancement. In recent years, its interest quickly expanded in older (diseased) populations and during (exercise) rehabilitation and recovery from hospitalization and surgery. We will discuss recent literature about HMB metabolism, its pharmacokinetics compared with the frequently used metabolite leucine, effectiveness of HMB to improve outcome in older diseased adults, and novel approaches for HMB use. HMB supplementation resulted in positive outcomes on muscle mass and functionality, related to its anabolic and anticatabolic properties and prolonged half-life time in blood. Furthermore, it was able to increase the benefits of (exercise) rehabilitation programs to enhance recovery from illness or medical procedures. There is promising evidence that HMB might support bone density, improve cognitive function, and reduce abdominal obesity, which is of importance particularly in the older (diseased) population. The older diseased population might benefit from dietary HMB because of its established positive properties as well as its long lasting (pharmacological) effect. In addition to evaluating its efficacy and application in various clinical conditions, more research is needed into the mechanisms of action, the optimal dosage, and its potential additional beneficial effects on outcome.

Effect Of B-Hydroxy B-Methylbutyrate Supplementation On Sprint Kinetics Across A Collegiate Rugby Season

During a collegiate rugby season, players practice and compete for 1-2 hours on multiple days per week for 3-4 months per year. Practices and matches consist of multiple activities (e.g. sprinting, hitting, etc.) that could result in accumulated damage and affect performance. β-Hydroxy β-Methylbutyrate (HMB) is thought to speed protein synthesis which in turn could maintain performance. PURPOSE: To determine the effect of HMB supplementation on sprint kinetics throughout a rugby season. METHODS: In this cross-over design investigation, 13 collegiate male rugby players were assigned to consume one of two supplementation regimens: 5 g HMB + 5 g creatine per day (HMB) or 5 g creatine + 5 g placebo per day (PLB) for six weeks. During the fall season, players were matched for lean body mass and randomly assigned to HMB (n = 7; 21.1 ± 1.1 y; 88.2 ± 16.5 kg; 176.3 ± 7.9 cm) or PLB (n = 6; 21.5 ± 2.4 y; 88.8 ± 15.4 kg; 179.3 ± 5.2 cm). The supplementation regimen was switched for athletes who returned and completed the spring season (n = 7; 22.5 ± 1.3 y; 96.4 ± 14.7 kg; 179.6 ± 4.5 cm). Prior to and following each supplementation period (i.e., fall or spring), 40-m sprinting kinetics were assessed in all athletes while tethered to a robotic sprinting device. Peak (PK) and mean sprinting power (P), force (F), and velocity were assessed against minimal (1 kg) and heavy (15 kg) resistance. Since only 7 of the original 13 athletes returned and completed the spring season, separate 2 × 2 repeated measures analyses of variance (RMANOVA) with Bonferroni adjustments were used to assess group differences in each variable during the fall, while a 2 × 4 RMANOVA was used to assess the cross-over sub-sample throughout the fall and spring. RESULTS: While no group differences were observed in sprint kinetics during the fall, a significant group × time interaction was observed for PPK at 1kg (F = 4.85, p = 0.020, np2 = 0.55) across the fall and spring seasons, where during the spring, PPK at 1kg decreased for PLBSPRING (-6.9 ± 1.2%, p = 0.020) but not for HMBSPRING (+7.5 ± 10.7%). No other differences were observed. CONCLUSION: Our data suggest a potential benefit from HMB supplementation for maintaining sprinting power in rugby players.

β-Hydroxy β-methylbutyrate (HMB) supplementation during pregnancy and perinatal period in animals studies and possible application in humans

β-Hydroxy β-methylbutyrate (HMB) supplementation during pregnancy and perinatal period in animals studies and possible application in humans

Dietary Supplements for Health, Adaptation, and Recovery in Athletes.

Some dietary supplements are recommended to athletes based on data that supports improved exercise performance. Other dietary supplements are not ergogenic per se, but may improve health, adaptation to exercise, or recovery from injury, and so could help athletes to train and/or compete more effectively. In this review, we describe several dietary supplements that may improve health, exercise adaptation, or recovery. Creatine monohydrate may improve recovery from and adaptation to intense training, recovery from periods of injury with extreme inactivity, cognitive processing, and reduce severity of or enhance recovery from mild traumatic brain injury (mTBI). Omega 3-fatty acid supplementation may also reduce severity of or enhance recovery from mTBI. Replenishment of vitamin D insufficiency or deficiency will likely improve some aspects of immune, bone, and muscle health. Probiotic supplementation can reduce the incidence, duration, and severity of upper respiratory tract infection, which may indirectly improve training or competitive performance. Preliminary data show that gelatin and/or collagen may improve connective tissue health. Some anti-inflammatory supplements, such as curcumin or tart cherry juice, may reduce inflammation and possibly delayed onset muscle soreness (DOMS). Beta-hydroxy beta-methylbutyrate (HMB) does not consistently increase strength and/or lean mass or reduce markers of muscle damage, but more research on recovery from injury that includes periods of extreme inactivity is needed. Several dietary supplements, including creatine monohydrate, omega 3-fatty acids, vitamin D, probiotics, gelatin, and curcumin/tart cherry juice could help athletes train and/or compete more effectively.

P852 A metabolomics approach to discover biomarkers of chronic intestinal inflammation associated with gut microbiota dysbiosis in ulcerative colitis and Celiac Disease

The effect of gut microbiota dysbiosis on human metabolome and the potential of microbial and endogenous metabolites as biomarkers of chronic intestinal inflammation (CII) are not clear. Forty ulcerative colitis (UC) patients, 43 celiac disease (CD) patients and 42 healthy volunteers (HV) were enrolled. The qRT-PCR was used for fecal microbiota assessment. Serum metabolomic assays were conducted using the GC-MS. UC patients were randomised into A1 and A2 groups and CD patients were randomised into B1 and B2 groups. A1 and B1 groups received oral calcium butyrate plus inulin for 28 days as supplement to oral mesalazine in UC or gluten-free diet (GFD) in CD. A2 and B2 groups received standard treatment or GFD. Butyrate-producing bacteria (BPB) were depleted in UC compared with HV. CD patients had lower Bifidobacterium spp. counts than HV or UC. Taxonomic dysbiosis in both UC and CD was characterised by a higher Bacteroides fragilis/Faecalibacterium prausnitzii ratio compared with HV. Significant changes in gut microbiota in both UC and CD were accompanied by changes in serum microbial metabolites levels. In UC serum lactic acid, 2-hydroxybutyric acid (2-HBA), 3-hydroxyisobutyric acid (3-HIBA), 2-hydroxyisovaleric acid (2-HIVA), 3-hydroxycinnamic acid, succinic acid (SA), benzoic acid (BA) and 4-hydroxyphenylacetic acid (4-HPAA) levels were significantly increased compared with HV. Serum levels of caproic acid, linoleic acid (LA) and eicosadienoic acid (EDA) in UC were significantly lower than in HV. Serum of CD patients showed significant increases in stearic acid (StA), 2-HIVA, SA, fumaric acid and BA compared with HV. De novo lipogenesis index (DNL) (C16:0/C18:2n-6) was significantly elevated in UC compared with both HV and CD. The ELOVL6 elongase activity index (C18:0/C16:0) and the StA/lA ratio (C18:0/C18:2n-6) in UC were significantly increased compared with HV. AA/EDA ratio (C20:4n-6/C20:2n-6) was increased in both UC and CD. Oral butyrate plus inulin significantly enhanced fecal BPB, reduced elevated B. fragilis/F. prausnitzii ratio, lowered serum pro-inflammatory SA and 2-HIVA and restored the initially lowered LA and EDA. 85% of UC patients in A1 (butyrate) group demonstrated significant improvement in rectal bleeding and stool frequency by day 14, compared with 55% in A2 group. The changes in serum metabolome, reflecting metabolic pathways disturbances (glycolysis, TCA cycle, fatty acid metabolism, ketone body metabolism, phenylalanine, tyrosine and tryptophan metabolism, microbial metabolism) are observed in both UC and CD. Some of metabolites and a new metabolomic index (AA/EDA ratio) may be considered as candidate biomarkers of CII. Oral butyrate plus inulin has a prebiotic (butyrogenic) effect, restoring BPB.

β-Hydroxy β-Methylbutyrate (HMB) Supplementation Effects on Body Mass and Performance in Elite Male Rugby Union Players.

McIntosh, ND, Love, TD, Haszard, J, Osborne, H, and Black, KE. β-hydroxy β-methylbutyrate (HMB) supplementation effects on body mass and performance in elite male rugby union players. J Strength Cond Res 32(1): 19-26, 2018-Preseason is characterized by high training volumes with short recovery periods β-hydroxy β-methylbutyrate (HMB) has been postulated to assist with recovery. β-hydroxy β-methylbutyrate has been shown to improve strength and body composition among untrained groups; the benefits of HMB among trained populations are unclear because of the methodologies employed. This randomized control trail determined the effects of 11 weeks HMB supplementation on body mass and performance measures in 27 elite rugby players. β-hydroxy β-methylbutyrate group (n = 13), mean ± SD age 20.3 ± 1.2 years, body mass 99.6 ± 9.1 kg; placebo group (n = 14), age 21.9 ± 2.8 years body mass 99.4 ± 13.9 kg for placebo. During the supplementation period, body mass increased with HMB 0.57 ± 2.60 kg but decreased with placebo 1.39 ± 2.02 kg (p = 0.029). There were no significant differences in any of the 4 strength variables (p > 0.05). However, on the yo-yo intermittent recovery test (YoYo IR-1), the placebo group improved 4.0 ± 2.8 levels but HMB decreased 2.0 ± 3.0 levels (p = 0.003). The results of this study suggest that HMB could be beneficial for gaining or maintaining body mass during periods of increased training load. However, it appears that HMB may be detrimental to intermittent running ability in this group although further research is required before firm conclusions can be made. Only 6 participants on HMB managed to complete both YoYo IR-1 tests because of injury, a larger sample size is required to fully investigate this potentially negative effect. Further, the mechanisms behind this decrement in performance cannot be fully explained and requires further biochemical and psychological investigation.

Effects of Protein, Essential Amino Acids, B-Hydroxy B-Methylbutyrate, Creatine, Dehydroepiandrosterone and Fatty Acid Supplementation on Muscle Mass, Muscle Strength and Physical Performance in Older People Aged 60 Years and Over. A Systematic Review on the Literature.

The objective of this study was to perform a systematic review to investigate the effects protein, essential amino acids (EAA), β-hydroxy β-methylbutyrate (HMB), creatine, dehydroepiandrosterone (DHEA) and fatty acid supplementation on muscle mass, muscle strength and physical performance of elderly subjects. Using the electronic databases MEDLINE and EMBASE we identified RCTs published until February 2016 which assessed the effects of these nutrient supplementation on muscle strength, muscle mass or physical performance. Study selection and data extraction were performed by two independent reviewers. Search strategy allowed us to identify 23 RCTs. Among them, four used proteins as nutritional supplement, seven EAAs, six creatine, four DHEA and finally, two HMB. From our systematic review, it seems that the effects of these supplementations on muscle health are rather limited. Only consistent effects of EAA supplementation on physical performance (3 out of the 4 RCTs using EAA supplementation found significant effect of this supplementation on physical performance) and HMB supplementation on muscle mass (all the 2 identified RCTs using HMB supplementation found significant effect of this supplementation on muscle mass) have been found across studies. No consistent effects were found for the other types of dietary supplementation. Because of the important limitations in study design, inconsistency and lack of directness, the overall quality of the evidence was judged to be low or very low using the GRADE system. This systematic review showed a limited effect of nutritional supplementation on muscle mass, muscle power and physical function. Inconsistent positive effects were observed for some specific supplementations but the results only concerned one aspect of the muscle. Well designed and appropriately powered RCTs are needed to provide evidence for appropriate clinical recommendations.

Biochemical and molecular characterization of 3-Methylcrotonylglycinuria in an Italian asymptomatic girl.

3-Methylcrotonylglycinuria is an organic aciduria resulting from deficiency of 3-methylcrotonyl-CoA carboxylase (3-MCC), a biotin-dependent mitochondrial enzym carboxylating 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA during leucine catabolism. Its deficiency, due to mutations on MCCC1 and MCCC2 genes, leads to accumulation of 3-methylcrotonyl-CoA metabolites in blood and/or urine, primarily 3-hydroxyisovaleryl-carnitine (C5-OH) in plasma and 3-methylcrotonyl-glycine (3-MCG) and 3-hydroxyisovaleric acid (3-HIVA) in the urine. The phenotype of 3-MCC deficiency is highly variable, ranging from severe neurological abnormalities and death in infancy to asymptomatic adults. Here we report the biochemical and molecular characterization of an Italian asymptomatic girl, positive for the newborn screening test. Molecular analysis showed two mutations in the MCCC2 gene, an already described missense mutation, c.691A > T (p.I231F), and a novel splicing mutation, c.1150-1G > A. We characterized the expression profile of the splice mutation by functional studies.

Protein Recommendations for Weight Loss in Elite Athletes: A Focus on Body Composition and Performance.

There exists a large body of scientific evidence to support protein intakes in excess of the recommended dietary allowance (RDA) (0.8gprotein/kg/day) to promote the retention of skeletal muscle and loss of adipose tissue during dietary energy restriction. Diet-induced weight loss with as low as possible ratio of skeletal muscle to fat mass loss is a situation we refer to as high-quality weight loss. We propose that high-quality weight loss is often of importance to elite athletes in order to maintain their muscle (engine) and shed unwanted fat mass, potentially improving athletic performance. Current recommendations for protein intakes during weight loss in athletes are set at 1.6-2.4gprotein/kg/day. However, the severity of the caloric deficit and type and intensity of training performed by the athlete will influence at what end of this range athletes choose to be. Other considerations regarding protein intake that may help elite athletes achieve weight loss goals include the quality of protein consumed, and the timing and distribution of protein intake throughout the day. This review highlights the scientific evidence used to support protein recommendations for high-quality weight loss and preservation of performance in athletes. Additionally, the current knowledge surrounding the use of protein supplements, branched chain amino acids (BCAA), β-hydroxy β-methylbutyrate (HMB), and other dietary supplements with weight loss claims will be discussed.

In ovo feeding of nutrients and its impact on post-hatching water and feed deprivation up to 48hr, energy status and jejunal morphology of chicks using response surface models.

A Box-Behnken design (BBD) in a response surface methodology (RSM) was used to investigate the response of broiler chicks to in ovo feeding (IOF) of beta-hydroxy beta-methylbutyrate (HMB), dextrin and the timing of the first water and feed deprivation. On day 18th of incubation, 1,500 eggs were randomly assigned to 15 experimental runs of BBD, each with 4 replicates, as 3 levels IOF of HMB (0%, 0.5% and 1%) and dextrin (0%, 20% and 40%), and 3 levels of the first water and feed deprivation (6, 27 and 48hr). Day-old chicks from each replicate were then used to assess the effect of IOF and time first water and feed access on chick's responses. The IOF of dextrin leads to respectively 9.7%-15.5% lower hatchability for 20% and 40% inclusion (p<.05), whereas HMB inclusion appeared with no effect on hatchability (p>.05). Administration of dextrin or HMB into the amnion of embryos elevated length, width and surface area of villus, and increased glycogen content of liver and breast (p<.05). In all parameter models, the linear terms showed highest contribution (R2 =0.81-0.97) to explain existing variation in chick's responses. The first water and feed deprivation had largest effect on BW2 and glycogen content of liver and breast. It is concluded that if possible, place chicks before 7hr of hatch to preserve BW loss and have maximum response from IOF. If not possible, use IOF with 40% dextrin+0.5% HMB to preserve gut integrity and energy status up to 48hr. This should give advantage to chicks to recover fast after feeding, but that would have to be confirmed by trials growing birds to slaughter age.

Metabolic phenotyping using kinetic measurements in young and older healthy adults

BackgroundThe aging process is often associated with the presence of sarcopenia. Although changes in the plasma concentration of several amino acids have been observed in older adults, it remains unclear whether these changes are related to disturbances in whole body production and/or interconversions. MethodsWe studied 10 healthy young (~22.7y) and 17 older adults (~64.8y) by administering a mixture of stable amino acid tracers in a pulse and in a primed constant infusion. We calculated whole body production (WBP) and metabolite to metabolite interconversions. In addition, we measured body composition, muscle function, and provided questionnaires to assess daily dietary intake, physical activity, mood (anxiety, depression) and markers of cognitive function. Plasma enrichments and metabolite concentrations were measured by GC- and LC-MS/MS and statistics were performed by student t-test. ResultsOlder adults had a 11% higher body mass index (p=0.04) and 27% reduced peak leg extension force (p=0.02) than the younger group, but comparable values for muscle mass, mood and cognitive function. Although small differences in several plasma amino acid concentrations were observed, we found older adults had about 40% higher values of WBP for glutamine (221±27 vs. 305±21μmol/kgffm/h, p=0.03) and tau-methylhistidine (0.15±0.01 vs. 0.21±0.02μmol/kgffm/h, p=0.04), 26% lower WBP value for arginine (59±4 vs. 44±4μmol/kgffm/h, p=0.02) and a reduction in WBP (50%; 1.23±0.15 vs. 0.69±0.06μmol/kgffm/h, p=0.001) and concentration (25%; 3.5±0.3μmol/l vs. 2.6±0.2μmol/l, p=0.01) for β-Hydroxy β-Methylbutyrate. No differences were observed in protein catabolism. Clearance of arginine was decreased (27%, p=0.03) and clearance of glutamine (58%, p=0.01), leucine (67%, p=0.001) and KIC (76%, p=0.004) were increased in older adults. ConclusionsSpecific differences exist between young and older adults in amino acid metabolism.

Effects of maternal treatment with β-hydroxy-β-metylbutyrate and 2-oxoglutaric acid on femur development in offspring of minks of the standard dark brown type.

The aim of the study was to evaluate the effect of the diet, mother type and sex of the offspring on the mechanical and geometric parameters of long bones as well as bone tissue density in minks. Primiparous and multiparous dams were supplemented with β-hydroxy β-methylbutyrate (a metabolite of leucine, at the daily dosage of 0.02g/kg of body weight) and/or 2-oxoglutaric acid (a precursor of glutamine, at the daily dosage of 0.4g/kg of body weight) during gestation. The diet did not influence bone tissue density and the length of the humerus. An increase in the length of the femur was noted in male offspring delivered by multiparous dams. The diet resulted in an increase in the weight of the humerus in males from multiparous dams and a decrease in offspring from primiparous dams. Heavier femora were noted in male offspring delivered by both types of dams. The maximum elastic strength of the humerus was higher in the offspring delivered by multiparous than primiparous dams, irrespective of the offspring sex. The diet resulted in reduction in the ultimate strength of the femur in the male offspring delivered by primiparous dams. Only females born by multiparous dams, irrespective of the diet, showed a significant increase in the cross-sectional area of the humerus, while a significant decline was noted in males delivered by multiparous dams and in all the offspring delivered by primiparous dams. An increase in the cross-sectional area of the femur was noted in the offspring delivered by multiparous dams, while reduction was observed in the offspring delivered by primiparous dams. These results have shown for the first time that the presence of β-hydroxy-β-methylbutyrate or 2-oxoglutaric acid in the diet of pregnant primiparous or multiparous dams unambiguously affects the geometry and mechanical properties of offspring's long bones.

NMR-based metabolomic approach to study urine samples of chronic inflammatory rheumatic disease patients.

The nuclear magnetic resonance (NMR)-based metabolomic approach was used as analytical methodology to study the urine samples of chronic inflammatory rheumatic disease (CIRD) patients. The urine samples of CIRD patients were compared to the ones of both healthy subjects and patients with multiple sclerosis (MS), another immuno-mediated disease. Urine samples collected from 39 CIRD patients, 25 healthy subjects, and 26 MS patients were analyzed using 1H NMR spectroscopy, and the NMR spectra were examined using partial least squares-discriminant analysis (PLS-DA). PLS-DA models were validated by a double cross-validation procedure and randomization tests. Clear discriminations between CIRD patients and healthy controls (average diagnostic accuracy 83.5 ± 1.9%) as well as between CIRD patients and MS patients (diagnostic accuracy 81.1 ± 1.9%) were obtained. Leucine, alanine, 3-hydroxyisobutyric acid, hippuric acid, citric acid, 3-hydroxyisovaleric acid, and creatinine contributed to the discrimination; all of them being in a lower concentration in CIRD patients as compared to controls or to MS patients. The application of NMR metabolomics to study these still poorly understood diseases can be useful to better clarify the pathologic mechanisms; moreover, as a holistic approach, it allowed the detection of, by means of anomalous metabolic traits, the presence of other pathologies or pharmaceutical treatments not directly connected to CIRDs, giving comprehensive information on the general health state of individuals. Graphical abstract NMR-based metabolomic approach as a tool to study urine samples in CIRD patients with respect to MS patients and healthy controls.