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Diet plays a pivotal role in shaping the trajectory of chronic diseases. In this regard, the Mediterranean diet has been widely shown to exert beneficial effects on cardiometabolic health. On the contrary, the Western diet, which has also been reported to be an acidogenic dietary pattern, elicits detrimental effects on both metabolic and cardiovascular (CV) health. However, the role of dietary acid load (DAL) as a predictor of cardiometabolic prognosis remains to be elucidated. Thus, this study aims to compare Mediterranean diet adherence (MDA) and DAL focusing on their relationship with metabolic and CV prognosis. A total of 448 individuals aged 55–80 years were grouped depending on their MDA, assessed using food frequency questionnaires, or DAL, evaluated using potential renal load acid (PRAL) and net-endogenous acid production (NEAP). Study participants underwent anthropometric and biochemical measurements. The metabolic syndrome (MetS) prevalence was evaluated according to the National Cholesterol Education Program-Adult Treatment Panel III. Finally, the CV risk was evaluated using three independent algorithms: atherosclerotic cardiovascular disease (ASCVD), European Systematic COronary Risk Evaluation (SCORE), and Cuore risk scores. Mediterranean diet adherence was negatively associated with PRAL and NEAP. Individuals in the higher MDA tertile group had higher HDL cholesterol as well as lower homeostasis model assessment index (HOMA-IR) and fat mass relative to the lowest MDA tertile. However, in the high-MDA tertile group, there was neither a significantly lower MetS prevalence nor CV risk. Instead, both the MetS prevalence and CV risk were higher in individuals in the higher acid PRAL quartile relative to the lower alkaline PRAL quartile. Dietary acid load, especially assessed using PRAL but not MDA, was associated with indices of metabolic and CV prognosis. Thus, DAL assessed by 24-h dietary recalls may represent a better predictor of cardiometabolic health if compared to MDA evaluated using food frequency questionnaires.

Objective This study aimed to evaluate the relationship between physical activity habits, physical performance and cognitive capacity in older adults' population of Italy and Slovenia. Methods Anthropometric characteristics and body composition bioelectrical impedance analysis (BIA) were evaluated in 892 older adults (60-80 y). Aerobic capacity was measured using the 2km walking test and handgrip and flexibility tests were performed. Physical activity habits and cognitive functions were evaluated by the Global-Physical-Activity-Questionnaires (GPAQ) and by Montreal-Cognitive-Assessment (MoCA) questionnaires, respectively. Results GPAQ scores were associated with lower BMI (r=-0.096; p=0.005), lower percentage of fat-mass (r=-0.138; p=0.001), better results in the 2km-walk test (r=-0.175; p=0.001) and a higher percentage of fat-free mass (r=0.138; p=0.001). We also evaluated that, a higher MoCA score correlates with age (r=-0.208; p=0.001), 2km-walk test (r=-0.166; p=0.001), waist-hip ratio (r=-0.200; p=0.001), resting heart-rate (r=-0.087; p=0.025) and heart-rate at the end of 2km-walk test (r=0.189; p=0.001). Conclusions Older adults with a higher level of daily physical activity showed reduction in fat mass and BMI, and higher aerobic fitness; these characteristics have a protection effect on cognitive function.

Energy balance maintenance is crucial to preserve astronaut’s wellness and quality of life during long-duration spaceflight and nutritional intervention can effectively counteract the detrimental effect of microgravity on skeletal muscle mass and metabolism. NutrISS (Nutrition monitoring for the International Space Station) is an Italian Space Agency (ASI) biomedical experiment investigating the changes in body composition during long-term spaceflight. The goal of this proof-of-concept study is to monitor the body composition of astronauts and, if needed, to provide nutritional advice during the mission. It has been executed on the ISS, from July 2019 till January 2020 and sponsored by ESA. The payloads selected for the mission “BEYOND” result from a public-call funded and coordinated by ASI, in the frame of its national mission of promoting and fostering the culture of space across the Country and providing access to the ISS as a laboratory in space to the Italian research community. The utilization support services is ensured by Argotec/Telespazio (UTISS Team). An astronaut underwent to baseline data collections, i.e. body composition, anthropometric evaluation and energy and metabolic assessment carried out by the scientific team. Body composition, estimated through resistance/reactance to a low-intensity current has been assessed with a Bio-Impedance Analyser (BIA) device manufactured by Akern and modified by Kayser Italia. To maintain the participant in near-neutral energy balance, the science team monitored monthly the astronaut body mass during the entire space flight period. Advice on energy intake was given to the astronaut when needed

OBJECTIVE: The optimal protein intake for elderly individuals who exercise regularly has not yet been clearly defined. The aim of this study was to test the hypothesis that protein intake level is associated with muscle strength in elderly elite athletes. METHODS: We evaluated 50 elite senior athletes (38 men and 12 women) participating in the European Master Games 2011 in an observational cross-sectional study. Participants were divided into two groups-lower (LPI) or higher (HPI) protein intake-according to the median value of their ratio of urinary urea nitrogen to urinary creatinine (i.e., 8.8 g/L), as a marker of protein intake. A dietary interview confirmed differences in protein consumption between the LPI and HPI groups. We also evaluated body composition (bioimpedance), muscle strength, and hematochemical indices. RESULTS: LPI and HPI groups were homogeneous for age (72 [68-74] and 71 [68-74] y, respectively), fat-free mass index (18.4 [17-19.4] and 18.2 [17-19.1] kg/m2), body fat (18.3% [12.3-20.7%] and 16.6% [13.6-21.2%]), and glomerular filtration rate (57.7 [53.8-64.9] and 62.7 [56.1-69.3] mL/min/1.73 m2). The HPI group showed greater leg and trunk muscle strength (N) compared with the LPI group (left leg extension, 339 [238-369] versus 454 [273-561], respectively, P < 0.05; right leg extension, 319 [249-417] versus 432 [334-635], P ≤ 0.05; trunk extension, 435 [370-467] versus 464 [390-568], P ≤ 0.05). CONCLUSIONS: Higher protein intake in elite senior athletes is associated with a greater muscle strength.

BACKGROUND & AIMS: Physical inactivity is associated with lean body mass wasting, oxidative stress and pro-inflammatory changes of cell membrane lipids. Alkalinization may potentially counteract these alterations. We evaluated the effects of potassium bicarbonate supplementation on protein kinetics, glutathione status and pro- and anti-inflammatory polyunsaturated fatty acids (PUFA) in erythrocyte membranes in humans, during experimental bed rest. METHODS: Healthy, young, male volunteers were investigated at the end of two 21-day bed rest periods, one with, and the other without, daily potassium bicarbonate supplementation (90 mmol × d-1), according to a cross-over design. Oxidative stress in erythrocytes was evaluated by determining the ratio between reduced (GSH) and oxidized glutathione (GSSG). Glutathione turnover and phenylalanine kinetics, a marker of whole body protein metabolism, were determined by stable isotope infusions. Erythrocyte membranes PUFA composition was analyzed by gas-chromatography. RESULTS: At the end of the two study periods, urinary pH was 10 ± 3% greater in subjects receiving potassium bicarbonate supplementation (7.23 ± 0.15 vs. 6.68 ± 0.11, p < 0.001). Alkalinization increased total glutathione concentrations by 5 ± 2% (p < 0.05) and decreased its rate of clearance by 38 ± 13% (p < 0.05), without significantly changing GSH-to-GSSG ratio. After alkalinization, net protein balance in the postabsorptive state improved significantly by 17 ± 5% (p < 0.05) as well as the sum of n-3 PUFA and the n-3-to-n-6 PUFA ratio in erythrocyte membranes (p < 0.05). CONCLUSIONS: Alkalinization during long-term inactivity is associated with improved glutathione status, anti-inflammatory lipid pattern in cell membranes and reduction in protein catabolism at whole body level. This study suggests that, in clinical conditions characterized by inactivity, oxidative stress and inflammation, alkalinization could be a useful adjuvant therapeutic strategy.

PURPOSE OF REVIEW: Cachexia is a disease-related multifactorial syndrome characterized by inflammation, massive muscle protein catabolism and carbohydrate and lipid metabolism disorder.Several studies tried to define the impact of either nutrition or physical exercise (single approach strategy) or their combination (multimodal approach strategy) on prevention and/or treatment of muscle wasting in cachectic patients. RECENT FINDINGS: Single approach strategies (i.e. nutrition or physical exercise) have the potential of preventing and improving features of the cachexia syndrome possibly with a differential impact according to the underlying disease. Limited information is available on the beneficial effect of multimodal approach strategies. SUMMARY: Multimodal approaches appear to be more effective than those based on single interventions in physiological condition and in cachectic patients with COPD or chronic kidney disease. Further studies, however, are required in cachexia induced by heart failure, cancer and critical illness.

In chronic diseases, hypoxia and physical inactivity are associated with atherosclerosis progression. In contrast, a lower mortality from coronary artery disease and stroke is observed in healthy humans residing at high altitude in hypoxic environments. Eleven young, male volunteers completed the following 10-day campaigns in a randomized order: hypoxic ambulatory, hypoxic bed rest and normoxic bed rest. Before intervention, subjects were evaluated in normoxic ambulatory condition. Normobaric hypoxia was achieved in a hypoxic facility simulating 4000 m of altitude. Following hypoxia, either in bed rest or ambulatory condition, markers of cardiometabolic risk shifted toward a more atherogenic pattern consisting of: (a) lower levels of total HDL cholesterol and HDL2 sub-fraction and decreased hepatic lipase; (b) activation of systemic inflammation, as determined by C-reactive protein and serum amyloid A; (c) increased plasma homocysteine; (d) decreased delta-5 desaturase index in cell membrane fatty acids, a marker of insulin sensitivity. Bed rest and hypoxia additively decreased total HDL and delta-5 desaturase index. In parallel to the pro-atherogenic effects, hypoxia activated selected anti-atherogenic pathways, consisting of increased circulating TNF-related apoptosis-inducing ligand (TRAIL), a protective factor against atherosclerosis, membrane omega-3 index and erythrocyte glutathione availability. Hypoxia mediated changes in TRAIL concentrations and redox glutathione capacity (i.e., GSH/GSSG ratio) were greater in ambulatory conditions (+34 ± 6% and +87 ± 31%, respectively) than in bed rest (+17 ± 7% and +2 ± 27% respectively). Hypoxia-induced cardiometabolic risk is blunted by moderate level of physical activity as compared to bed rest. TRAIL and glutathione redox capacity may contribute to the positive interaction between physical activity and hypoxia. Highlights: - Hypoxia and bed rest activate metabolic and inflammatory markers of atherogenesis. - Hypoxia and physical activity activate selected anti-atherogenic pathways. - Hypoxia and physical activity positive interaction involves TRAIL and glutathione.

Impulsivity, conceptualized as impulsive personality trait, poor inhibitory control and enhanced reward sensitivity, has been strongly linked to obesity. In particular, a disequilibrium between cognitive control and reward sensitivity has been observed in obese individuals in both behavioural and imaging studies. While this issue has been widely investigated in children and adults, it has received little attention in older adults. Here, obese and non-obese participants aged between 40 and 70 years completed the Barratt Impulsiveness scale (assessing motor, non-planning and attentional impulsiveness), a Go/no-go task with foods and non-foods (assessing inhibitory control) and a reward sensitivity battery with high and low caloric foods (assessing liking, wanting, tastiness and frequency of consumption). We observed that participants with higher BMI reported increased wanting for high calorie foods, but did not show poorer inhibitory control. Interestingly, participants who scored lower on the MMSE reported to consume high calorie more than low calorie foods. Finally, those who presented low scores on non-planning and motor impulsiveness subscales reported higher tastiness ratings for low calorie foods. These results show that increased reward sensitivity but not reduced inhibitory control may characterize higher BMI during aging. Importantly, they also highlight new findings concerning food preferences among older adults.

Purpose of review In clinical management of acutely ill adults and children, continuous enteral feeding (CEF), being considered the most tolerable approach, in comparison to other temporal patterns of nutrient administration (i.e. intermittent, cyclic and bolus), is the most frequently applied method. However, uncertainties remain about the most efficient approach to counteract protein catabolism. Recent findings In critically ill adults, protein loss is mainly driven by increased protein breakdown whereas, in pediatric patients, acute illness is mainly characterized by blunted regulation of protein synthesis and stunted growth. Kinetic studies in fed adult volunteers indicate that protein synthesis can be stimulated for a limited period only. However, continuous feeding persistently improves protein balance through a sustained suppression of protein breakdown. This leads to the hypothesis that CEF could be more anticatabolic than intermittent enteral feeding (IEF) in these patients. Differently from adults, experimental models of acute disease in growing animals have consistently indicated that IEF can improve protein anabolism more efficiently than CEF, mainly through protein synthesis stimulation. The scarce number of clinical studies in acutely ill adults or pediatric patients, mostly performed with inadequate methodology, could not define the best approach to maintain protein balance. Summary There is a need for pragmatic studies to directly compare the protein anabolic action of CEF and IEF using accurate methodologies, such as stable isotopes of amino acids, in both adult and pediatric patients with acute illness.

Purpose of review The optimal approach to improve protein metabolism in critical illness is not yet fully defined. Here, we have summarized recent literature dealing with the main catabolic and anabolic factors influencing protein kinetics in acute hypercatabolic patients. Recent findings Protein/amino acid intake levels should be adapted to type and severity of illness, keeping in mind that energy overfeeding is associated with poor outcome. A number of anticatabolic nutraceuticals and drugs have been tested in acute patients. The encouraging results have been obtained with β-hydroxy-β-methylbutyrate, omega-3 fatty acids, oxandrolone, propranolol, and metformin. Their efficacy and lack of side-effects need to be confirmed. Physical therapy, including muscle electro-stimulation, appears a very promising intervention, both effective and safe. Summary Protein catabolism can be minimized in acute patients by adequate nutritional support, early mobilization, and, possibly, pharmacological and nutraceutical interventions. A combination of these strategies should be tested in randomized controlled trials.

Summary Background & aims Arachidonic (AA) and eicosapentaenoic (EPA) polyunsaturated fatty acids can play respectively a pro- and an anti-inflammatory role. We hypothesized that, at the end of 5-week experimental bed rest, baseline AA/EPA in red blood cells (RBC) membranes, considered the result of dietary fat intake over the previous month, could influence lean body mass wasting in twenty-six healthy volunteers (age: 23.5 ± 0.5 years; body mass index: 22.9 ± 0.5 kg/m2). Methods We measured AA and EPA content in RBC membranes at baseline ambulatory conditions and at the end of the study protocol, to verify the PUFA concentrations stability. We assessed changes, between beginning and end of bed, in lean body mass (bioimpedance), insulin resistance (homeostasis model assessment), systemic inflammation (C-reactive protein) and oxidative stress (thiobarbituric acid reactive substances). Volunteers were divided in two groups according to the AA/EPA ratio median value (i.e. AA/EPA = 44): High AA/EPA group (60 ± 3; n = 13) and Low AA/EPA group (37 ± 1; n = 13). Results At baseline, all analyzed anthropometrical and biochemical indices were similar in the two groups. Bed rest induced a major decrease in lean body mass in High AA/EPA group (−5.2 ± 0.5%), when compared to Low AA/EPA group (−3.7 ± 0.5%; p = 0.03; ANOVA). Bed rest mediated-changes of insulin resistance, fat mass, systemic inflammation and oxidative stress, failed to show significant interaction with baseline AA/EPA (ANOVA). In pooled data, baseline AA/EPA ratio and percent lean body mass delta changes showed a significant inverse correlation (n = 26; R = −0.50; p < 0.01). Conclusions Results suggest that baseline AA/EPA, in RBC membranes, can independently predict lean body mass wasting in immobilized subjects during long term disuse.

Background & aims Aging and experimental bed rest are associated with muscle atrophy and resistance to post-prandial stimulation of protein synthesis or anabolic resistance (AR). We have used in young and older adult volunteers, during short-term bed rest, a quick and non-invasive method, based on a single oral bolus of the stable isotope L[ring-2H5]phenylalanine (D5Phe), to determine post-prandial AR, defined as ratio between irreversible hydroxylation and incorporation into body protein of ingested phenylalanine. Methods We compared in older (O, 59 ± 1 y) and young (Y, 23 ± 1 y) healthy male volunteers the effects of two-week bed rest on post-prandial protein kinetics, assessed during absorption of a standard ready-to-use oral nutritional supplement, through stable-labeled isotope amino acid D5Phe, diluted in water, given as single oral load. The metabolic fate of D5Phe is either utilization for protein synthesis or irreversible hydroxylation to L[ring-2H4]tyrosine (D4Tyr). AR was defined as ratio between the areas under the curves of D4Tyr-to-D5Phe plasma concentrations over 6 h meal absorption. To determine the relationships between AR and muscle changes following bed rest, quadriceps muscle volume (QMV) was determined by magnetic resonance imaging (MRI). Results At baseline, in pooled Y and O subjects, values of AR were inversely correlated with QMV (R = −0.75; p < 0.03). Following 2-weeks of inactivity, there were significant bed rest effects on AR (p < 0.01) and QMV (p < 0.03), as well as significant bed rest × group interaction for AR (p < 0.03; +9.2% in Y; +21.9% in O) and QMV (p < 0.05; −5.7% in Y; −%7.3 in O). In pooled subjects, the percentage delta changes in AR and QMV, induced by bed rest, were inversely correlated (R = −0.57; p < 0.05). Conclusion Bed rest-induced AR is much greater in the older than in younger adults. We have developed a new, simple, non-invasive method for the assessment of AR. The results indicate that this metabolic abnormality is a key mechanism for sarcopenia of aging and inactivity.

Coffee consumption is negatively associated with risk of type 2 diabetes and cardiovascular mortality. Coffee roasting can greatly modify the quality-quantitative characteristics of bioactive compounds. We compared the effects of two different roasting intensities of the same naturally low-caffeine Arabica coffee variety (Laurina) on glucose and lipid metabolism as well as oxidative stress.We performed a double-blind, crossover intervention study. Fourteen healthy male volunteers consumed four cups daily of light roasted coffee (LRC) and dark roasted coffee (DRC), each for 1 wk (intervention period 1 and 2 respectively). One wk washout, with total abstinence from coffee and other possible caffeine sources, preceded each intervention. Data were collected at the end of washout and intervention periods.Changes between washout and intervention periods in glucose concentrations at 2 h post-oral glucose tolerance test, were significantly lower after DRC than LRC intake (-0.6 ± 0.3 and 0.4 ± 0.3 mmol/L, P 0.03). Changes in β-cell function, assessed as insulin secretion-sensitivity index-2, were significantly greater after DRC than LRC (34.7 ± 25.0 and -18.8 ± 21.0, P = 0.03). The initial (30 min) post-oral glucose tolerance test area under the curve of glucagon-like peptide-1 was 24± 9% greater (P = 0.03) after DRC than LRC. LRC or DRC did not affect insulin sensitivity. Changes from basal of reduced-to-oxidized glutathione ratio (GSH/GSSG) in erythrocytes were significantly greater after DRC than LRC (+1437 ± 371 and -152 ± 30, P 0.05). The omega-3 index in erythrocyte membranes was 16± 4% greater (P 0.001) after DRC than LRC.DRC consumption improved postload glucose metabolism by increasing incretin and insulin secretions. DRC compared to LRC improved redox balance and increased omega-3 fatty acids. Thus, we suggest greater metabolic benefits related to DRC.

The aim of the study was to assess the relationship between sweet taste genes and dental caries prevalence in a large sample of adults. In addition, the association between sweet liking and sugar intake with dental caries was investigated. Caries was measured by the decayed, missing, filled teeth (DMFT) index in 647 Caucasian subjects (285 males and 362 females, aged 18–65 years), coming from six villages in northeastern Italy. Sweet liking was assessed using a 9-point scale, and the mean of the liking given by each individual to specific sweet food and beverages was used to create a sweet liking score. Simple sugar consumption was estimated by a dietary history interview, considering both added sugars and sugar present naturally in foods. Our study confirmed that polymorphisms in TAS1R2 and GLUT2 genes are related to DMFT index. In particular, GG homozygous individuals for rs3935570 in TAS1R2 gene (p value = 0.0117) and GG homozygous individuals for rs1499821 in GLUT2 gene (p value = 0.0273) showed higher DMFT levels compared to both heterozygous and homozygous for the alternative allele. Furthermore, while the relationship sugar intake–DMFT did not achieve statistical significance (p value = 0.075), a significant association was identified between sweet liking and DMFT (p value = 0.004), independent of other variables. Our study showed that sweet taste genetic factors contribute to caries prevalence and highlighted the role of sweet liking as a predictor of caries risk. Therefore, these results may open new perspectives for individual risk identification and implementation of target preventive strategies, such as identifying high-risk patients before caries development.

We investigated the ability of pentoxifylline, a drug with hemorheological actions known to block tumor necrosis factor-alpha (TNF-alpha) release, to modulate whole-body protein kinetics in undialyzed patients with chronic uremia.Leucine rate of appearance (Ra) from proteolysis and leucine oxidation, a marker of net protein loss, were determined by infusing l-[1-13C]leucine and using the reciprocal pool model for calculations.Intravenous infusion of pentoxifylline in the postabsorptive state (1 mg/kg within 3 hours) decreased the intracellular leucine Ra from proteolysis by -16% +/- 4% versus -3% +/- 2% of saline (P = 0.02) and leucine oxidation by -16% +/- 4% versus +4% +/- 2% of saline (P = 0.003). Combined infusions of pentoxifylline and a balanced amino acid mixture (0.2 mg/kg/min) decreased whole-body proteolysis by -53% +/- 7% versus -26% +/- 6% of amino acid infusion alone (P = 0.02). Circulating levels of TNF-alpha and TNF-alpha soluble receptors (sTNF-Rs) were elevated (P0.001) in patients compared with healthy controls. Pentoxifylline infusion did not significantly affect TNF-alpha levels, but decreased sTNF-Rs both in the postabsorptive state and during hyperaminoacidemia.Pentoxifylline acutely decreased whole-body proteolysis in chronically uremic patients. Potential explanations for these pharmacological effects may include downregulation of the TNF-alpha system or other mechanisms related to the rheological action of the drug (eg, increased amino acid or insulin delivery to target cells).

Background & aims: The lysosomal cathepsin system contributes to degrading cellular skeletal muscle proteins in many catabolic diseases. We have assessed the relationships between cathepsin B mRNA levels and the enzyme activity for this protease in the skeletal muscle of acutely ill patients with severe trauma (n=7) and in patients with a variety of chronic disease states (hemodialysis, n=3; nervous anorexia, n=1; type 2 diabetes, n=2; prolonged immobilization, n=1). Methods: Muscle biopsies were taken from the vastus lateralis muscle in patients and controls to assess tissue levels of cathepsin B mRNA by competitive–quantitative polymerase chain reaction, cathepsin B proteolytic activity and myofibrillar protein content as alkali-soluble protein to DNA ratio (ASP/DNA). In the trauma patients, muscle protein loss was assessed by the arteriovenous balance technique as rate of phenylalanine release from leg muscle. Results: The acute trauma patients exhibited a significant net phenylalanine release from leg muscle (33±4 nmol phenylalanine/min/100 ml leg volume) despite a continuous nutritional support. The muscle ASP/DNA ratio was lower (P

Purpose of review The increased age observed in most countries, with the associated higher rates of chronic illnesses and cancer, and a diffuse sedentary lifestyle, will increase the number of patients with clinically relevant anabolic resistance, sarcopenia and its complications. The need for solutions to this major health issue is, therefore, pressing. Recent findings The metabolic derangements and other consequences associated with sarcopenia can be slowed or even prevented by specific nutritional interventions. New evidence is available about the efficacy of omega-3 fatty acid dietary supplementation to improve protein metabolism and counteract anabolic resistance through indirect effects. Studies show that the anabolic stimuli from substrates (e.g. amino acids or proteins), hormones (e.g. insulin) and/or physical activity in skeletal muscle can be enhanced by long-term fish oil administration. Summary The review of data from recent studies on this topic suggests that dietary omega-3 fatty acid supplementation, in association with an anabolic stimulus, could potentially provide a safe, simple and low-cost intervention to counteract anabolic resistance and sarcopenia. This intervention may contribute to prevent cachexia and disabilities. Supplementation should be given in the earlier stages of sarcopenia (e.g. precachexia). Further research should, however, be performed to better understand the mechanisms involved and the best dosage and timing of administration.

Objective Increments in red blood cell count (RBC), hemoglobin (Hb) and hematocrit (Ht) levels are reportedly associated with higher insulin resistance (IR). Obesity may cause IR, but underlying factors remain incompletely defined, and interactions between obesity, hematological parameters and IR are incompletely understood. We therefore determined whether: 1) BMI and obesity per se are independently associated with higher RBC, hemoglobin and hematocrit; 2) hematological parameters independently predict insulin resistance in obese individuals. Design and Methods We investigated the associations between BMI, hematological parameters and insulin resistance as reflected by homeostasis model assessment (HOMA) in a general population cohort from the North-East Italy MoMa epidemiological study (M/F = 865/971, age = 49±1). Results In all subjects, age-, sex- and smoking-adjusted hematological parameters were positively associated with BMI in linear regression (P

Carnitine is a conditionally essential metabolite that plays a critical role in cell physiology by participating in transesterification reactions and preventing organic acid accumulation. A number of disease states are characterized by carnitine depletion that may lead to metabolic and clinical disturbances. In maintenance hemodialysis, carnitine is lost through dialytic membranes, leading in selected patients to carnitine depletion with a relative increase of the esterified forms. Carnitine supplementation after or during dialysis counteracts such alterations and may be associated with some clinical benefits. Recent meta-analyses of the literature indicate that carnitine supplementation in hemodialysis patients may improve the hematological status (allowing a reduction of the requirement for erythropoietin), the exercise tolerance, the plasma lipid profile, and the intradialytic symptoms. In addition, carnitine supplementation may improve cardiac functions, protein metabolism, and insulin resistance. Carnitine supplementation has been recently approved by the US Food and Drug Administration not only for the treatment, but also for the prevention of carnitine depletion in dialysis patients. Furthermore, clinical guidelines developed by both American and European nephrological societies suggest that a trial with carnitine supplementation could be recommended in selected dialysis patients who do not adequately respond to standard therapy for certain conditions, such as severe and persistent muscle cramps or hypotension during dialysis, lack of energy affecting quality of life, skeletal muscle weakness or myopathy, cardiomyopathy, and anemia of uremia unresponsive to or requiring large doses of erythropoietin.

To investigate the relationship between decline in renal function and alterations of protein metabolism we determined the rate of whole-body protein turnover in a group of 15 postabsorptive chronically uremic patients (9 males and 6 females) with different levels of serum creatinine concentrations (average 5.7 ± 0.4 (SE) mg·dl–1; range 3.3–9.1). Patients’ age and body mass index were 53 ± 4 years (range 26–73) and 24.7 ± 0.6 kg/m2 (range 20.3–28.7), respectively. Nutritional status (plasma albumin 3.6 ± 0.4 g·dl–1) and acid-base equilibrium (arterial pH 7.38 ± 0.01) were fairly controlled by therapy. Whole-body leucine rate of appearance (Ra), an index of whole-body protein turnover, was assessed using a stable isotope technique. L-[1-13C]leucine was continuously infused and plasma [1-13C]α-ketoisocaproic acid enrichment was determined in steady-state conditions as a marker of the intracellular leucine enrichment. The average leucine Ra was 2.03 ± 0.13 µmol·kg–1·min–1 (range 1.29–3.19). Using simple linear regression analysis, the coefficient of correlation between the individual values of serum creatinine concentration and leucine Ra was 0.59 (n = 15; p = 0.02). Leucine Ra did not significantly correlate with blood pH or plasma albumin. In conclusion, we found a positive linear relationship between the values of plasma creatinine concentration and the rate of whole-body protein degradation. This correlation suggests that the progression of renal insufficiency is associated with accelerated rates of turnover of body proteins.

The metabolic response to trauma and sepsis involves an increased loss of body proteins. Specific sites of changes of protein and amino acid metabolism have been identified. In skeletal muscle, the rate of proteolysis is accelerated greatly. The rate of protein synthesis also may be increased but not enough to match the increase in degradation. Intramuscular glutamine concentration is decreased because of increased efflux and possibly decreased de novo synthesis. In the liver, the rate of synthesis of selected proteins (i.e., albumin, transferrin, prealbumin, retinol-binding protein, and fibronectin) is decreased, whereas acute phase protein synthesis is accelerated. Tissues characterized by rapidly replicating cells, such as enterocytes, immune cells, granulation tissue, and keratinocytes, exhibit early alterations in the case of decreased protein synthesis capacity. In these tissues, glutamine use is accelerated. Increased stress hormone (cortisol and glucagon) and cytokine secretion, as well as intracellular glutamine depletion, are potential mediators of altered protein metabolism in trauma and sepsis. However, the relative importance of these factors has not been clarified. Therapy of acute protein catabolism may include the use of biosynthetic human growth hormone, possibly in combination with insulin-like growth factor-1, and the administration of metabolites at pharmacologic doses. We recently studied the effects of carnitine and alanyl-glutamine administration in severely traumatized patients. We found that both carnitine and the glutamine dipeptide restrained whole-body nitrogen loss without affecting selected indices of protein metabolism in the skeletal muscle.

summary Background & aims: Sarcopenic obesity may be defined by a high fat to fat-free mass (FM/FFM) ratio. Skeletal muscle may be negatively influenced by the pro-inflammatory milieu associated with visceral fat, while the loading effect induced by a heavier body mass index (BMI) may enhance muscle anabolism. Recently, a new anthropometric measure based on waist circumference (A Body Shape Index, ABSI) was developed. In this study we have assessed the predictive power of ABSI on the FFM index (FFMI), a surrogate marker of lean mass. Methods: Standard anthropometric parameters and ABSI as well as body composition data (fat and fatfree mass determined by bioelectrical impedance analysis) were assessed in 111 female and 89 male overweight/obese subjects, with no clinically significant co-morbidities. Groups with higher- or lowerABSI were identified according to median values of this index. Results: In women and men, ABSI did not correlate with BMI, while multiple linear regression indicated that BMI ( b-coefficients: 0.62 and 0.77, respectively) and ABSI (b-coefficients: � 0.26 and � 0.22, respectively) independently predicted FFMI (multiple R: 0.72 and 0.83, respectively, P < 0.001). Men and women with lower-ABSI exhibited significantly greater FFMI than the higher-ABSI groups for comparable values of BMI. In men, ABSI was correlated positively with C-reactive protein (CRP) (R ¼ 0.30; P < 0.05) and negatively with the reciprocal of insulin (R ¼ 0.28; P < 0.05), an index of insulin sensitivity. FM/FFM ratio significantly (P < 0.01) correlated with CRP (R ¼ 0.31) in women only. Conclusions: ABSI, a recently introduced marker of abdominal adiposity, may contribute to define the risk of sarcopenia in overweight/obese individuals. 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.

Malnutrition and protein wasting are common features of chronically uremic patients, whether on conservative or dialysis treatment. Optimization of protein-energy intake is difficult because of anorexia, catabolic factors (acidosis, insulin resistance, cytokines, etc.) and intercurrent infections. The use of growth hormone may improve the efficiency of dietary protein utilization. Evidence suggests a small but appreciable effect of very low protein diets on progression of renal insufficiency.

We have investigated the effects of 24 h human recombinant growth hormone (hGH) administration on leg muscle glutamine exchange and protein kinetics in severely traumatized patients. Muscle amino acid exchange and protein balance were evaluated using the leg arteriovenous balance technique, whereas changes in skeletal muscle free amino acid concentrations were evaluated in biopsy specimens. hGH infusion decreased phenylalanine release from protein degradation by 56 +/- 14%, and the rate of branched chain amino acid catabolism by 51 +/- 10%. Glutamine release from leg muscle was suppressed by 58 +/- 12%. This latter effect was completely accounted for by a hGH-mediated suppression of glutamine synthesis in skeletal muscle. In conclusion, growth hormone administration in trauma patients may restrain protein and amino acid catabolism in skeletal muscle. However, the growth hormone-mediated suppression of glutamine production we have observed in this study could decrease the systemic availability of this amino acid. During growth hormone treatment, this potential side-effect could be prevented by an exogenous glutamine administration.