L-carnitine supplementation for muscle weakness and fatigue in children with neurofibromatosis type 1: A Phase 2a clinical trial.

Reduced muscle tone, muscle weakness, and physical fatigue can impact considerably on quality of life for children with neurofibromatosis type 1 (NF1). Human muscle biopsies and mouse models of NF1 deficiency in muscle show intramyocellular lipid accumulation, and preclinical data have indicated that L-carnitine supplementation can ameliorate this phenotype. The aim of this study is to examine whether daily L-carnitine supplementation is safe and feasible, and will improve muscle strength and reduce fatigue in children with NF1. A 12-week Phase 2a trial was conducted using 1000 mg daily oral levocarnitine tartrate supplementation. Recruited children were between 8 and 12 years old with a clinical diagnosis of NF1, history of muscle weakness and fatigue, and naïve to L-carnitine. Primary outcomes were safety (self-reporting, biochemical testing) and compliance. Secondary outcomes included plasma acylcarnitine profiles, functional measures (muscle strength, long jump, handwriting speed, 6-minute-walk test [6MWT]), and parent-reported questionnaires (PedsQL™, CBCL/6-18). Six children completed the trial with no self-reported adverse events. Biochemical tests for kidney and liver function were normal, and the average compliance was 95%. Plasma acylcarnitine levels were low, but within a range not clinically linked to carnitine deficiency. For strength measures, there was a mean 53% increase in dorsiflexion strength (95% confidence interval [CI] 8.89-60.75; p = 0.02) and mean 66% increase in plantarflexion strength (95% CI 12.99-134.1; p = 0.03). In terms of muscle performance, there was a mean 10% increase in long jump distance (95% CI 2.97-16.03; p = 0.01) and 6MWT distance (95% CI 5.88-75.45; p = 0.03). Comparison with the 1000 Norms Project data showed a significant improvement in Z-score for all of these measures. Parent reports showed no negative impact on quality of life, and the perceived benefits led to the majority of individuals remaining on L-carnitine after the study. Twelve weeks of L-carnitine supplementation is safe and feasible in children with NF1, and a Phase 3 trial should confirm the efficacy of treatment.

Effect of vitamin E and alpha lipoic acid on intestinal development associated with wooden breast myopathy in broilers.

Intestinal development is closely associated with inflammatory wooden breast (WB) myopathy. Vitamin E (VE) and alpha lipoic acid (ALA) with antioxidant and anti-inflammatory effects were used independently and in combination to evaluate their effects on intestinal developmental changes in ileal morphology and expression of genes related with gut nutrient transport, structure, and inflammation in broilers during the first 3 wk posthatch. A total of 160 newly hatched Ross 708 broiler chicks were randomly assigned into a control and 3 dietary treatments with 10 replicates of 4 birds each. Supplementation of VE (160 mg/kg) and ALA (500 mg/kg) independently and in combination were fed during the first 3 wk. At 1, 2, and 3 wk of age, one chick from each pen was harvested. Plasma VE concentration and ileal morphology were determined. Gene expression was measured by real-time quantitative PCR. Broilers in VE and combination of ALA and VE group had higher plasma VE concentration than the control and ALA group at 1, 2, and 3 wk of age (P < 0.01). All dietary treatments increased ileal villus height at 1 wk of age (P < 0.01) and decreased intraepithelial lymphocytes at 3 wk of age compared to the control (P ≤ 0.05). Combination of VE and ALA increased collagen type IV alpha 1 chain expression (P ≤ 0.05) and improved basement membrane structure indicating increased gut basement membrane integrity at 2 and 3 wk of age compared to the control. Expression of lipopolysaccharide-induced tumor necrosis factor-alpha factor associated with inflammation was decreased in all dietary treatments at 3 wk of age compared to the control (P < 0.01). Ileal morphology and gene expression were closely correlated with breast muscle morphology and gene expression. These results suggest that VE and ALA especially when they were combined in the diet had positive effects on mitigating intestinal inflammation and improving nutrient transport beginning at 1 wk of age, which is likely critical in reducing the severity of WB.

Nutrition management guideline for very-long chain acyl-CoA dehydrogenase deficiency (VLCAD): An evidence- and consensus-based approach.

The nutrition management guideline for very-long chain acyl-CoA dehydrogenase deficiency (VLCAD) is the fourth in a series of web-based guidelines focusing on the diet treatment for inherited metabolic disorders and follows previous publication of guidelines for maple syrup urine disease (2014), phenylketonuria (2016) and propionic acidemia (2019). The purpose of this guideline is to establish harmonization in the treatment and monitoring of individuals with VLCAD of all ages in order to improve clinical outcomes. Six research questions were identified to support guideline development on: nutrition recommendations for the healthy individual, illness management, supplementation, monitoring, physical activity and management during pregnancy. This report describes the methodology used in its development including review, critical appraisal and abstraction of peer-reviewed studies and unpublished practice literature; expert input through two Delphi surveys and a nominal group process; and external review from metabolic physicians and dietitians. It includes the summary statements of the nutrition management recommendations for each research question, followed by a standardized rating based on the strength of the evidence. Online, open access of the full published guideline allows utilization by health care providers, researchers and collaborators who advise, advocate and care for individuals with VLCAD and their families and can be accessed from the Genetic Metabolic Dietitians International (https://GMDI.org) and Southeast Regional Genetics Network (https://southeastgenetics.org/ngp) websites.

Carnitine insufficiency is associated with fatigue during lenvatinib treatment in patients with hepatocellular carcinoma.

BACKGROUND: Fatigue is a common adverse event during lenvatinib treatment in patients with hepatocellular carcinoma. One mechanism contributing to development of fatigue might involve abnormal adenosine triphosphate synthesis that is caused by carnitine deficiency. To address this possibility, we examined the relationship between carnitine levels and fatigue during lenvatinib treatment. METHODS: This prospective study evaluated 20 patients with hepatocellular carcinoma who underwent lenvatinib treatment. Both blood and urine samples were collected from the patients before starting lenvatinib therapy (day 0), and on days 3, 7, 14, and 28 thereafter. Plasma and urine concentrations of free and acyl carnitine (AC) were assessed at each time point. The changes in daily fatigue were evaluated using the Brief Fatigue Inventory (BFI). RESULTS: Plasma levels of free carnitine (FC) at days 3 and 7 were significantly higher compared with baseline (p = 0.005, p = 0.005, respectively). The urine FC level at day 3 was significantly higher compared with baseline (p = 0.030) and that of day 7 tended to be higher compared with baseline (p = 0.057). The plasma AC concentration at days 14 and 28 was significantly higher compared with that of baseline (p = 0.002, p = 0.005, respectively). The plasma AC-to-FC (AC/FC) ratio on days 14 and 28 was significantly higher compared with baseline (p = 0.001, p = 0.003, respectively). There were significant correlations between the plasma AC/FC ratio and the change in the BFI score at days 14 and 28 (r = 0.461, p = 0.041; r = 0.770, p = 0.002, respectively). CONCLUSIONS: Longitudinal assessments of carnitine and fatigue in patients with hepatocellular carcinoma suggest that lenvatinib affects the carnitine system in patients undergoing lenvatinib therapy and that carnitine insufficiency increases fatigue. The occurrence of carnitine insufficiency may be a common cause of fatigue during the treatment.

Nutritional ketosis improves exercise metabolism in patients with very long-chain acyl-CoA dehydrogenase deficiency.

A maladaptive shift from fat to carbohydrate (CHO) oxidation during exercise is thought to underlie myopathy and exercise-induced rhabdomyolysis in patients with fatty acid oxidation (FAO) disorders. We hypothesised that ingestion of a ketone ester (KE) drink prior to exercise could serve as an alternative oxidative substrate supply to boost muscular ATP homeostasis. To establish a rational basis for therapeutic use of KE supplementation in FAO, we tested this hypothesis in patients deficient in Very Long-Chain acyl-CoA Dehydrogenase (VLCAD). Five patients (range 17-45 y; 4 M/1F) patients were included in an investigator-initiated, randomised, blinded, placebo-controlled, 2-way cross-over study. Patients drank either a KE + CHO mix or an isocaloric CHO equivalent and performed 35 minutes upright cycling followed by 10 minutes supine cycling inside a Magnetic Resonance scanner at individual maximal FAO work rate (fatmax; approximately 40% VO2 max). The protocol was repeated after a 1-week interval with the alternate drink. Primary outcome measures were quadriceps phosphocreatine (PCr), Pi and pH dynamics during exercise and recovery assayed by in vivo 31 P-MR spectroscopy. Secondary outcomes included plasma and muscle metabolites and respiratory gas exchange recordings. Ingestion of KE rapidly induced mild ketosis and increased muscle BHB content. During exercise at FATMAX, VLCADD-specific plasma acylcarnitine levels, quadriceps glycolytic intermediate levels and in vivo Pi/PCr ratio were all lower in KE + CHO than CHO. These results provide a rational basis for future clinical trials of synthetic ketone ester supplementation therapy in patients with FAO disorders. Trial registration: ClinicalTrials.gov. Protocol ID: NCT03531554; METC2014.492; ABR51222.042.14.

Cardiac tissue citric acid cycle intermediates in exercised very long-chain acyl-CoA dehydrogenase-deficient mice fed triheptanoin or medium-chain triglyceride.

Anaplerotic odd-chain fatty acid supplementation has been suggested as an approach to replenish citric acid cycle intermediate (CACi) pools and facilitate adenosine triphosphate (ATP) production in subjects with long-chain fatty acid oxidation disorders, but the evidence that cellular CACi depletion exists and that repletion occurs following anaplerotic substrate supplementation is limited. We exercised very long-chain acyl-CoA dehydrogenase-deficient (VLCAD-/-) and wild-type (WT) mice to exhaustion and collected cardiac tissue for measurement of CACi by targeted metabolomics. In a second experimental group, VLCAD-/- and WT mice that had been fed chow prepared with either medium-chain triglyceride (MCT) oil or triheptanoin for 4 weeks were exercised for 60 minutes. VLCAD-/- mice exhibited lower succinate in cardiac muscle at exhaustion than WT mice suggesting lower CACi in VLCAD-/- with prolonged exercise. In mice fed either MCT or triheptanoin, succinate and malate were greater in VLCAD-/- mice fed triheptanoin compared to VLCAD-/- animals fed MCT but lower than WT mice fed triheptanoin. Long-chain odd acylcarnitines such as C19 were elevated in VLCAD-/- and WT mice fed triheptanoin suggesting some elongation of the heptanoate, but it is unknown what proportion of heptanoate was oxidized vs elongated. Prolonged exercise was associated with decreased cardiac muscle succinate in VLCAD-/- mice in comparison to WT mice. VLCAD-/- fed triheptanoin had increased succinate compared to VLCAD-/- mice fed MCT but lower than WT mice fed triheptanoin. Cardiac CACi were higher following dietary ingestion of an anaplerotic substrate, triheptanoin, in comparison to MCT.

A systematic review about prophylactic L-carnitine administration in parenteral nutrition of extremely preterm infants.

OBJECTIVE: Preterm infants with total parenteral nutrition are at particular risk of developing carnitine deficiency with impaired tolerance of parenteral lipids. The  objective was to review the scientific literature on potencial benefits of  prophylactic L-carnitine administration in parenteral nutrition of preterm  newborns. METHODS: Selected scientific articles in MEDLINE/PubMed, Scopus, The Cochrane Library, British Library EThOS and TESEO databases were assessed for this  systematic review. The terms used as descriptors were «Total Parenteral  Nutrition¼ and «Carnitine¼. Jadad scale was chosen to evaluate the quality of  them. RESULTS: 18 out of the 93 references retrieved were selected for reviewing after  applying the inclusion and exclusion criteria, 4 of them were discarded for being  considered of low quality. Almost all studies agreed on the analytical variables  measured (free carnitine and acylcarnitine, triglycerides, free fatty acids and  ketone bodies). Other clinical variables such as weight gain, apnea, or lenght of  stay at hospital were also considered. CONCLUSIONS: The present results prove that routine supplementation in the  parenteral nutrition of preterm newborns may help to increase carnitine levels,  but neither a relevant improvement in the lipid profile, or an increase in weight  gain, or a decrease in morbimortality or reduction of hospital stay could be  demonstrated. More studies are needed in preterm infants to know whether  routine supplementation of L-carnitine in neonates requiring total parenteral  nutrition for a long time would provide any clinical benefit.

Objetivo: Los recién nacidos pretérmino con nutrición parenteral total tienen tanto una reducción de la ingesta de L-carnitina como de las reservas tisulares, lo que podría suponer una peor tolerancia de los lípidos  parenterales. El objetivo fue revisar la literatura científica en busca de los  posibles beneficios clínicos de su administración en la nutrición parenteral.Métodos: Revisión sistemática de los documentos recuperados en las bases de  datos MEDLINE/Pubmed, Scopus, The Cochrane Library, British Library EThOS y  TESEO. Los términos utilizados como descriptores fueron «Total Parenteral  Nutrition¼ y «Carnitine¼. La calidad de los artículos se evaluó mediante la escala de Jadad.Resultados: Tras aplicar los criterios de inclusión y exclusión, se seleccionaron para la revisión 18 artículos de las 93 referencias recuperadas, de  los cuales 4 fueron descartados al no ser considerados de alta calidad. Casi la  totalidad de los estudios coincidían en las variables analíticas medidas (carnitina  libre y acilcarnitina, triglicéridos, ácidos grasos libres y cuerpos cetónicos).  Además, en algunos se tenían en cuenta otras variables clínicas, como la  ganancia ponderal o la apnea.Conclusiones: La suplementación rutinaria en la nutrición parenteral de recién  nacidos pretérmino sí parece mejorar los niveles plasmáticos de carnitina, pero  sin llegar a demostrar una mejoría significativa en el perfil lipídico, ni aumento  de la ganancia ponderal, ni disminución de la morbimortalidad o reducción de la  estancia hospitalaria. Son necesarios más estudios para demostrar si la  suplementación sistemática a recién nacidos pretérmino que requieren nutrición  parenteral total durante más de un mes aportaría beneficios clínicos.

Whey protein hydrolysate supplementation accelerates recovery from exercise-induced muscle damage in females.

A number of different forms of protein and their analogues have been investigated for their efficacy in ameliorating exercise-induced muscle damage (EIMD) and recovery. Preliminary data regarding whey protein hydrolysate (WPH) supplementation are promising. However, its efficacy beyond acute eccentric/resistance exercise bouts or longer term training programmes are limited and all investigations have been conducted in male or mixed-sex groups. This study sought to elucidate whether the benefits of WPH previously reported can be demonstrated in females following repeated-sprint exercise. Twenty physically active females were assigned to consume 2 doses of 70 mL WPH or isoenergetic carbohydrate (CHO) for 4 days post-EIMD. Measures of muscle soreness, limb girth, flexibility, muscle function, and creatine kinase were collected before, immediately after, and 24, 48, and 72 h postexercise. Time effects were observed for all variables (p < 0.05) except limb girth, which is indicative of EIMD. Flexibility improved beyond baseline measures following WPH by 72 h, but had failed to recover in the CHO group (p = 0.011). Reactive strength index was higher throughout recovery in the WPH group compared with CHO (p = 0.016). Reductions in creatine kinase were greater following WPH compared with CHO at 48 h post-EIMD (p = 0.031). The findings suggest that 4-day supplementation of WPH is beneficial for reducing symptoms of EIMD and improving recovery of muscle function in physically active females.

Selected In-Season Nutritional Strategies to Enhance Recovery for Team Sport Athletes: A Practical Overview.

Team sport athletes face a variety of nutritional challenges related to recovery during the competitive season. The purpose of this article is to review nutrition strategies related to muscle regeneration, glycogen restoration, fatigue, physical and immune health, and preparation for subsequent training bouts and competitions. Given the limited opportunities to recover between training bouts and games throughout the competitive season, athletes must be deliberate in their recovery strategy. Foundational components of recovery related to protein, carbohydrates, and fluid have been extensively reviewed and accepted. Micronutrients and supplements that may be efficacious for promoting recovery include vitamin D, omega-3 polyunsaturated fatty acids, creatine, collagen/vitamin C, and antioxidants. Curcumin and bromelain may also provide a recovery benefit during the competitive season but future research is warranted prior to incorporating supplemental dosages into the athlete's diet. Air travel poses nutritional challenges related to nutrient timing and quality. Incorporating strategies to consume efficacious micronutrients and ingredients is necessary to support athlete recovery in season.

Wooden Breast Myodegeneration of Pectoralis Major Muscle Over the Growth Period in Broilers.

Wooden breast (WB) myopathy of broiler chickens is a myodegenerative disease of an unknown etiology and is macroscopically characterized by a hardened consistency of the pectoralis major muscle. Our aim was to describe the development and morphology of WB over the growth period in broilers. Additionally, the effect of restricted dietary selenium on the occurrence of WB was examined by allocating the birds in 2 dietary groups: restricted and conventional level of selenium. The experiment included 240 male broilers that were euthanized at ages of 10, 18, 24, 35, 38, or 42 days and evaluated for WB based on abnormal hardness of the pectoralis major muscle. The severity and the distribution of the lesion and presence of white striping were recorded. The first WB cases were seen at 18 days; 13/47 birds (28%) were affected and the majority exhibited a mild focal lesion. In subsequent age groups the WB prevalence varied between 48% and 73% and the lesion was usually diffuse and markedly firm. White striping often coexisted with WB. Histological evaluation performed on 111 cases revealed a significant association of myodegeneration and lymphocytic vasculitis with WB. Vasculitis and perivascular cell infiltration were restricted to the veins. Restricted dietary selenium did not affect the occurrence of WB ( P = .44). Our results indicate that WB starts focally and spreads to form a diffuse and more severe lesion.

Primary Carnitine Deficiency and Newborn Screening for Disorders of the Carnitine Cycle.

Carnitine is needed for transfer of long-chain fatty acids across the inner mitochondrial membrane for subsequent ß-oxidation. Carnitine can be synthesized by the body and is also obtained in the diet through consumption of meat and dairy products. Defects in carnitine transport such as those caused by defective activity of the OCTN2 transporter encoded by the SLC22A5 gene result in primary carnitine deficiency, and newborn screening programmes can identify patients at risk for this condition before irreversible damage. Initial biochemical diagnosis can be confirmed through molecular testing, although direct study of carnitine transport in fibroblasts is very useful to confirm or exclude primary carnitine deficiency in individuals with genetic variations of unknown clinical significance or who continue to have low levels of carnitine despite negative molecular analyses. Genetic defects in carnitine biosynthesis do not generally result in low plasma levels of carnitine. However, deletion of the trimethyllysine hydroxylase gene, a key gene in carnitine biosynthesis, has been associated with non-dysmorphic autism. Thus, new roles for carnitine are emerging that are unrelated to classic inborn errors of metabolism.

Round Table Discussion.

The 1st International Carnitine Working Group concluded with a round table discussion addressing several areas of relevance. These included the design of future studies that could increase the amount of evidence-based data about the role of carnitine in the treatment of fatty acid oxidation defects, for which substantial controversy still exists. There was general consensus that future trials on the effect of carnitine in disorders of fatty acid oxidation should be randomized, double-blinded, multicentered and minimally include the following diagnoses: medium-chain acyl coenzyme A (CoA) dehydrogenase deficiency, very long-chain acyl-CoA dehydrogenase deficiency, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and mitochondrial trifunctional protein deficiency. Another area that generated interest was trials of carnitine in cardiomyopathy and, especially, the use of biomarkers to identify patients at greater risk of cardiotoxicity following treatment with anthracyclines. The possibility that carnitine treatment may lead to improvements in autistic behaviors was also discussed, although the evidence is still not sufficient to make any firm conclusions in this regard. Preliminary data on carnitine levels in children and adolescents with primary hypertension, low birth weight and nephrotic syndrome was also presented. Lastly, the panelists stressed that there remains an objective need to harmonize the terminology used to describe carnitine deficiencies (e.g., primary, secondary and systemic deficiency).

Historical Perspective on Clinical Trials of Carnitine in Children and Adults.

The metabolic roles of carnitine have been greatly clarified over the past 50 years, and it is now well established that carnitine is a key player in mitochondrial generation of energy and metabolism of acetyl coenzyme A. A therapeutic role for carnitine in treatment of nutritional deficiencies in infants and children was first demonstrated in 1958, and since that time it has been used to treat a number of inborn errors of metabolism. Carnitine was approved by the US Food and Drug Administration in 1985 for treatment of 'primary carnitine deficiency', and later in 1992 for treatment of 'secondary carnitine deficiency', a definition that included the majority of relevant metabolic disorders associated with low or abnormal plasma carnitine levels. Today, carnitine treatment of inborn errors of metabolism is a safe and integral part of many treatment protocols, and a growing interest in carnitine has resulted in greater recognition of many causes of carnitine depletion. Notwithstanding, there is still a lack of data from randomized clinical trials, even on the use of carnitine in inborn errors of metabolism, although ethical issues may be a contributing factor in this regard.

De novo fatty acid biosynthesis and elongation in very long-chain acyl-CoA dehydrogenase-deficient mice supplemented with odd or even medium-chain fatty acids.

An even medium-chain triglyceride (MCT)-based diet is the mainstay of treatment in very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD). Previous studies with magnetic resonance spectroscopy have shown an impact of MCT on the average fatty acid chain length in abdominal fat. We therefore assume that medium-chain fatty acids (MCFAs) are elongated and accumulate in tissue as long-chain fatty acids. In this study, we explored the hepatic effects of long-term supplementation with MCT or triheptanoin, an odd-chain C7-based triglyceride, in wild-type and VLCAD-deficient (VLCAD(-/-) ) mice after 1 year of supplementation as compared with a control diet. The de novo biosynthesis and elongation of fatty acids, and peroxisomal ß-oxidation, were quantified by RT-PCR. This was followed by a comprehensive analysis of hepatic and cardiac fatty acid profiles by GC-MS. Long-term application of even and odd MCFAs strongly induced de novo biosynthesis and elongation of fatty acids in both wild-type and VLCAD(-/-) mice, leading to an alteration of the hepatic fatty acid profiles. We detected de novo-synthesized and elongated fatty acids, such as heptadecenoic acid (C17:1n9), eicosanoic acid (C20:1n9), erucic acid (C22:1n9), and mead acid (C20:3n9), that were otherwise completely absent in mice under control conditions. In parallel, the content of monounsaturated fatty acids was massively increased. Furthermore, we observed strong upregulation of peroxisomal ß-oxidation in VLCAD(-/-) mice, especially when they were fed an MCT diet. Our data raise the question of whether long-term MCFA supplementation represents the most efficient treatment in the long term. Studies on the hepatic toxicity of triheptanoin are still ongoing.

Very long-chain acyl-coenzyme A dehydrogenase deficiency in Chinese patients: eight case reports, including one case of prenatal diagnosis.

OBJECTIVE: Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) is a rare mitochondrial fatty acid ß-oxidation disorder. We aimed to explore the clinical, biochemical, and genetic findings, treatments and outcomes in eight Chinese VLCADD patients. METHODS: Eight patients from six unrelated Chinese families with symptomatic VLCADD were diagnosed in the past 4 years. The clinical features and ACADVL gene mutations were analyzed. RESULTS: One patient underwent newborn screening and has been treated timely, she hardly had any symptoms. The remaining seven patients were found because of edema, diarrhea, coma, liver damage and psychomotor retardation. Seven patients had fatty liver. Five had myopathy. All patients had elevated blood tetradecanoylcarnitine. Nine heterozygous mutations of the ACADVL gene were found. Three (c.1102C > T, c.1795G > A and IVS10, +6T > A) were novel. Seven patients completely recovered after treatment. One patient died before diagnosis due to cardiomyopathy. His mother underwent amniocentesis for prenatal diagnosis. The fetus had the same gene mutation of the proband and markedly elevated tetradecanoylcarnitine in amniotic fluid. The boy has been treated after birth and he is healthy now. CONCLUSIONS: Dietary treatment usually leads to good outcomes to VLCADD patients. Amniocytes ACADVL mutations and amniotic fluid tetradecanoylcarnitine analysis are useful for the prenatal diagnosis.

Dietary strategies to recover from exercise-induced muscle damage.

Exhaustive or unaccustomed intense exercise can cause exercise-induced muscle damage (EIMD) and its undesirable consequences may decrease the ability to exercise and to adhere to a training programme. This review briefly summarises the muscle damage process, focusing predominantly on oxidative stress and inflammation as contributing factors, and describes how nutrition may be positively used to recover from EIMD. The combined intake of carbohydrates and proteins and the use of antioxidants and/or anti-inflammatory nutrients within physiological ranges are interventions that may assist the recovery process. Although the works studying food instead of nutritional supplements are very scarce, their results seem to indicate that food might be a favourable option as a recovery strategy. To date, the only tested foods were milk, cherries, blueberries and pomegranate with promising results. Other potential solutions are foods rich in protein, carbohydrates, antioxidants and/or anti-inflammatory nutrients.

Nutritional targets to enhance exercise performance in chronic obstructive pulmonary disease.

PURPOSE OF REVIEW: This review presents current knowledge regarding the rationale and efficacy of nutrition as an ergogenic aid to enhance the effects of exercise and training in chronic obstructive pulmonary disease (COPD). RECENT FINDINGS: Altered body composition and skeletal muscle dysfunction in COPD suggest that exercise capacity can be targeted via several metabolic routes. Muscle metabolic alterations in COPD include a reduced oxidative metabolism and enhanced susceptibility for oxidative stress. Muscle wasting may be associated with deficiencies of vitamin D and low branched-chain amino acid levels. Exercise training is of established benefit in COPD but clear-cut clinical trial evidence to support the performance enhancing effect of nutritional intervention is lacking. One randomized controlled trial suggested that augmentation of training with polyunsaturated fatty acids may improve exercise capacity. Conflicting results are reported on dietary creatine supplementation in patients with COPD receiving pulmonary rehabilitation and results from acute intervention studies do not directly imply long-term effects of glutamate or glutamine supplementation as an ergogenic aid in COPD. Recent data indicate that not only muscle but also visceral fat may be an important additional target for combined nutrition and exercise intervention in COPD to improve physical performance and decrease cardiometabolic risk. SUMMARY: There is a clear need for adequately powered and controlled intervention and maintenance trials to establish the role of nutritional supplementation in the enhancement of exercise performance and training and the wider management of the systemic features of the disease.

Effect of volume of milk consumed on the attenuation of exercise-induced muscle damage.

Exercise-induced muscle damage (EIMD) leads to decrements in muscle performance, increases in intramuscular proteins and delayed-onset of muscle soreness (DOMS). Previous research demonstrated that one litre of milk-based protein-carbohydrate (CHO) consumed immediately following muscle damaging exercise can limit changes in markers of EIMD possibly due to attenuating protein degradation and/or increasing protein synthesis. If the attenuation of EIMD is derived from changes in protein metabolism then it can be hypothesised that consuming a smaller volume of CHO and protein will elicit similar effects. Three independent matched groups of 8 males consumed 500 mL of milk, 1,000 mL of milk or a placebo immediately following muscle damaging exercise. Passive and active DOMS, isokinetic muscle performance, creatine kinase (CK), myoglobin and interleukin-6 were assessed immediately before and 24, 48 and 72 h after EIMD. After 72 h 1,000 mL of milk had a likely benefit for limiting decrements in peak torque compared to the placebo. After 48 h, 1,000 mL of milk had a very likely benefit of limiting increases in CK in comparison to the placebo. There were no differences between consuming 500 or 1,000 mL of milk for changes in peak torque and CK. In conclusion, decrements in isokinetic muscle performance and increases in CK can be limited with the consumption of 500 mL of milk.

Physiological and nutritional aspects of post-exercise recovery: specific recommendations for female athletes.

Gender-based differences in the physiological response to exercise have been studied extensively for the last four decades, and yet the study of post-exercise, gender-specific recovery has only been developing in more recent years. This review of the literature aims to present the current state of knowledge in this field, focusing on some of the most pertinent aspects of physiological recovery in female athletes and how metabolic, thermoregulatory, or inflammation and repair processes may differ from those observed in male athletes. Scientific investigations on the effect of gender on substrate utilization during exercise have yielded conflicting results. Factors contributing to the lack of agreement between studies include differences in subject dietary or training status, exercise intensity or duration, as well as the variations in ovarian hormone concentrations between different menstrual cycle phases in female subjects, as all are known to affect substrate metabolism during sub-maximal exercise. If greater fatty acid mobilization occurs in females during prolonged exercise compared with males, the inverse is observed during the recovery phase. This could explain why, despite mobilizing lipids to a greater extent than males during exercise, females lose less fat mass than their male counterparts over the course of a physical training programme. Where nutritional strategies are concerned, no difference appears between males and females in their capacity to replenish glycogen stores; optimal timing for carbohydrate intake does not differ between genders, and athletes must consume carbohydrates as soon as possible after exercise in order to maximize glycogen store repletion. While lipid intake should be limited in the immediate post-exercise period in order to favour carbohydrate and protein intake, in the scope of the athlete's general diet, lipid intake should be maintained at an adequate level (30%). This is particularly important for females specializing in long-duration events. With protein balance, it has been shown that a negative nitrogen balance is more often observed in female athletes than in male athletes. It is therefore especially important to ensure that this remains the case during periods of caloric restriction, especially when working with female athletes showing a tendency to limit their caloric intake on a daily basis. In the post-exercise period, females display lower thermolytic capacities than males. Therefore, the use of cooling recovery methods following exercise, such as cold water immersion or the use of a cooling vest, appear particularly beneficial for female athletes. In addition, a greater decrease in arterial blood pressure is observed after exercise in females than in males. Given that the return to homeostasis after a brief intense exercise appears linked to maintaining good venous return, it is conceivable that female athletes would find a greater advantage to active recovery modes than males. This article reviews some of the major gender differences in the metabolic, inflammatory and thermoregulatory response to exercise and its subsequent recovery. Particular attention is given to the identification of which recovery strategies may be the most pertinent to the design of training programmes for athletic females, in order to optimize the physiological adaptations sought for improving performance and maintaining health.

Effect of 5-day vitamin E supplementation on muscle injury after downhill running in rats.

Antioxidant supplementation has been suggested to prevent exercise-induced muscle injury, but the findings are inconsistent. The objective of this study was to investigate the potential protective role of vitamin E treatment against eccentric exercise-induced muscle injury by examining morphological and functional alterations in rat soleus muscle after downhill running as well as muscle injury markers in the blood. Sixty adult male Wistar rats were randomly assigned to vitamin E-treated or placebo-treated groups studied at rest, immediately post-exercise or 48 h post-exercise (n = 10 per group). Vitamin E was administered by daily intraperitoneal injections of 100 mg/kg body mass of DL: -α-tocopheryl acetate for five consecutive days prior to exercise, resulting in the doubling of its plasma concentration. Downhill running resulted in significant (P < 0.05) changes in all injury markers for the placebo-treated rats at 0 and 48 h post-exercise. However, significantly smaller soleus muscle single-twitch tension (P (t)) and unfused (40 Hz) tetanic force, and greater plasma creatine kinase (CK) and lactate dehydrogenase (LD) activities compared with the control were found only immediately post-exercise for the vitamin E-treated rats (P < 0.05). Maximal tetanic force (P (o)) did not decline significantly compared to sedentary controls at neither time points measured. The vitamin E-treated rats had significantly (P < 0.05) higher soleus muscle P (t) immediately post-exercise than the placebo-treated rats as well as lower plasma CK and LD activity 48 h post-exercise. However, there was no difference in P (o) decline between groups at either time points measured. Vitamin E-treated rats had less pronounced morphological alterations in muscle in the immediate and 48-h post-exercise period. In conclusion, the effect of short-term vitamin E supplementation against eccentric exercise-induced muscle injury did not appear to be physiologically significant, because vitamin E failed to prevent the decline in the functional measure of P (o) compared to the placebo conditions.