M.P. Engelen

Nutritional depletion in relation to respiratory and peripheral skeletal muscle function in out-patients with COPD

Although increasing attention has been paid to nutritional aspects in chronic obstructive pulmonary disease (COPD), limited information is available regarding the prevalence and consequences of nutritional depletion in a random out-patient COPD population. We studied body composition in relation to respiratory and peripheral skeletal muscle function in 72 COPD patients (mean (SD) forced expiratory volume in one second (FEV1) 53 (15) % predicted), who came to the lung function laboratory for routine lung function measurements. Patients were characterized by the degree of body weight loss and fat-free mass depletion. According to this definition, 14% of the group suffered from both loss of body weight and depletion of fat-free mass, whereas 7% had one of these conditions. We found that tissue depletion was concomitant with lower values for respiratory and peripheral skeletal muscle strength (46.0 (27.2) vs 77.1 (29.8) kg), and a significantly lower transfer coefficient for carbon monoxide (KCO 64.9 (16.2) vs 81.9 (24.5) % pred). Stratification by KCO (< 60% vs > 80%) also revealed significantly lower values for fat-free mass and higher values for intrathoracic gas volumes, total lung capacity (TLC) and residual volume (RV) in the group with a KCO < 60% pred. Analysis of covariance, taking fat-free mass as covariate, indicated an independent contribution of KCO on maximal inspiratory mouth pressure (PImax) but not on peripheral skeletal muscle strength. It is concluded that a substantial number of COPD out-patients suffer from nutritional depletion, preferentially affecting peripheral skeletal muscle function.

Skeletal muscle fibre-type shifting and metabolic profile in patients with chronic obstructive pulmonary disease

The aim of this study was to examine the nature of fibre-type redistribution in relation to fibre metabolic profile in the vastus lateralis in chronic obstructive pulmonary disease (COPD) and COPD subtypes. Fifteen COPD patients (eight with emphysema stratified by high-resolution computed tomography) and 15 healthy control subjects were studied. A combination of myofibrillar adenosine triphosphatase staining and immunohistochemistry was used to identify pure, as well as hybrid fibre types. For oxidative capacity, fibres were stained for cytochrome c oxidase and succinate dehydrogenase activities, and glycogen phosphorylase for glycolytic capacity. The proportion of type‐I fibres in COPD patients was markedly lower (16% versus 42%), especially in emphysema, and the proportion of hybrid fibres was higher (29% versus 16%) compared to controls. The proportion of fibres staining positive for oxidative enzymes was lower in COPD patients, which correlated with the proportion of type‐I fibres. In COPD oxidative capacity was lower within IIA fibres. The authors conclude that fibre-type transitions are involved in the fibre-type redistribution in chronic obstructive pulmonary disease. Low oxidative capacity is closely related to the proportion of type‐I fibres, but an additional reduction of oxidative enzyme activity is present within IIA fibres. Fibre-type abnormalities may be aggravated in emphysema.

Dose-dependent satiating effect of whey relative to casein or soy.

Dietary protein plays a role in body weight regulation, partly because of its effects on appetite. The objective was to compare the effects of high or normal casein-, soy-, or whey-protein breakfasts on appetite, specific hormones, amino acid responses and subsequent energy intake. Twenty-five healthy subjects (mean+/-SEMBMI:23.9+/-0.3 kg/m2; age:22+/-1 years) received standardized breakfasts: custards with either casein-, soy, or whey-protein with either 10/55/35 (normal) or 25/55/20 (high)En% protein/carbohydrate/fat in a randomized, single-blind design. Appetite profile (Visual Analogue Scales) and amino acid concentrations were determined for 4 h whereas plasma glucose, insulin, active Glucagon-like Peptide 1 (GLP-1), and active ghrelin concentrations were determined for 3 h; the sensitive moment for lunch was determined. Subjects returned for a second set of experiments and received the same breakfasts, ad lib lunch was offered 180 min later; energy intake (EI) was assessed. At 10En%, whey decreased hunger more than casein or soy (p <0.05), coinciding with higher leucine, lysine, tryptophan, isoleucine, and threonine responses (p<0.05). At 25En% there were no differences in appetite ratings. Whey triggered the strongest responses in concentrations of active GLP-1 (p<0.05) and insulin (p<0.05) compared with casein and/or soy. There were no differences in EI. In conclusion, differences in appetite ratings between different proteins appeared at a normal concentration; at 10En% whey-protein decreased hunger more than casein- or soy-protein. At 25En% whey-protein triggered stronger responses in hormone concentrations than casein- or soy-protein. The results suggest that a difference in appetite ratings between types of protein appears when certain amino acids are above and below particular threshold values.

Different patterns of chronic tissue wasting among patients with chronic obstructive pulmonary disease.

BACKGROUND & AIMS Nutritional depletion is frequently present in patients with chronic obstructive pulmonary disease, but it is unknown whether a difference exists between the two subtypes. The aim of this study was to determine whether patterns of tissue depletion were different between emphysema and chronic bronchitis patients and whether these were related to pulmonary function. METHODS In 99 severe COPD patients and 28 healthy volunteers, body weight and composition were assessed by dual-energy X-ray absorptiometry. Patients were stratified into chronic bronchitis (n=50) and emphysema (n=49) by high-resolution computed tomography. RESULTS Lean mass depletion was found in 37% of the emphysema patients and in 12% of the chronic bronchitis patients. The emphysema patients had lower values for body mass index than the other groups (P< 0.01), mainly due to a lower lean mass (P< 0.01) and bone mineral content (P< 0.01). Fat mass was also lower in the emphysema group compared to the chronic bronchitis group (P< 0.001). The chronic bronchitis patients had a higher fat mass (P< 0.05) and a lower bone mineral content (P< 0.01) than the healthy volunteers. CONCLUSIONS Substantial differences in body composition were found not only between chronic obstructive pulmonary disease patients and healthy volunteers, but also between chronic bronchitis and emphysema patients.

Regulation of nitric oxide production in health and disease.

Purpose of reviewThe purpose of this review is to highlight recent publications examining nitric oxide production in health and disease and its association with clinical nutrition and alterations in metabolism. Recent findingsThe role of the cofactor tetrahydrobiopterin in nitric oxide production and its relation with arginine availability is indicated as an important explanation for the arginine paradox. This offers potential for nitric oxide regulation by dietary factors such as arginine or its precursors and vitamin C. Because diets with a high saturated fat content induce high plasma fatty acid levels, endothelial nitric oxide production is often impaired due to a reduction in nitric oxide synthase 3 phosphorylation. Increasing the arginine availability by arginine therapy or arginase inhibition was, therefore, proposed as a potential therapy to treat hypertension. Recent studies in septic patients and transgenic mice models found that inadequate de-novo arginine production from citrulline reduces nitric oxide production. Citrulline supplementation may, therefore, be a novel therapeutic approach in conditions of arginine deficiency. SummaryBoth lack and excess of nitric oxide production in diseases can have various important implications in which dietary factors can play a modulating role. Future research is needed to expand our understanding of the regulation and adequate measurement of nitric oxide production at the organ level and by the different nitric oxide synthase isoforms, also in relation to clinical nutrition.

Dietary protein, metabolism, and body-weight regulation: dose–response effects

Body-weight management requires a multifactorial approach. Recent findings suggest that an elevated protein intake seems to play a key role herein, through (i) increased satiety related to increased diet-induced thermogenesis; (ii) its effect on thermogenesis; (iii) body composition; and (iv) decreased energy-efficiency, all of which are related to protein metabolism. Supported by these mechanisms, relatively larger weight loss and subsequent stronger body-weight maintenance have been observed. Increased insulin sensitivity may appear, but it is unclear whether this is due to weight loss or type of diet. The phenomenon of increased satiety is utilized in reduced energy-intake diets, mainly in the ad libitum condition, whereby sustained satiety is achieved with sustained absolute protein intake in grams, despite lower energy intake. Elevated thermogenesis and glucagon-like peptide-1 (GLP-1) appear to play a role in high-protein induced satiety. Under conditions of weight maintenance, a high-protein diet shows a reduced energy efficiency related to the body composition of the body weight regained, that is, in favor of fat-free mass. Indeed, during body-weight loss, as well as during weight regain, a high-protein diet preserves or increases fat-free mass and reduces fat mass and improves the metabolic profile. In the short-term this may be supported by a positive protein and a negative fat balance, through increased fat oxidation. As protein intake is studied under various states of energy balance, absolute and relative protein intake needs to be discriminated. In absolute grams, a normal protein diet becomes a relatively high-protein diet in negative energy balance and at weight maintenance. Therefore, ‘high protein negative energy balance diets’ aim to keep the grams of proteins ingested at the same level as consumed at energy balance, despite lower energy intakes.

A breakfast with alpha-lactalbumin, gelatin, or gelatin + TRP lowers energy intake at lunch compared with a breakfast with casein, soy, whey, or whey-GMP

BACKGROUND & AIMS Dietary protein plays a role in body weight regulation, partly due to its effects on satiety. The objective was to compare the effects of casein-, soy-, whey-, whey without glycomacropeptide (GMP)-, alpha-lactalbumin-, gelatin-, or gelatin with tryptophan (TRP)-protein breakfasts at two concentrations on subsequent satiety and energy intake (EI). METHODS Twenty-four healthy subjects (mean+/-SEM BMI: 24.8+/-0.5 kg/m(2); age: 25+/-2 years) received a breakfast; a custard with casein, soy, whey, whey-GMP, alpha-lactalbumin, gelatin, or gelatin+TRP as protein source with either 10/55/35 (normal) or 25/55/20 (high) En% protein/carbohydrate/fat in a randomized, single-blind design. At the precedingly determined time point for lunch, 180 min, subjects were offered an ad lib lunch. Appetite profile (Visual Analogue Scales, VAS) and EI were determined. RESULTS Both at the level of 10 and 25 En% from protein, EI at lunch was approximately 20% lower after an alpha-lactalbumin or gelatin (+TRP) breakfast (2.5+/-0.2 MJ) compared with after a casein, soy, or whey-GMP breakfast (3.2+/-0.3 MJ, p<0.05). Appetite ratings at 180 min differed 15-25 mm (approximately 40%, p<0.05) between types of protein. Differences in EI were a function of differences in appetite ratings (R(2)=0.4, p<0.001). CONCLUSIONS Different proteins (alpha-lactalbumin, gelatin, gelatin+TRP) that are approximately 40% more satiating than other proteins (casein, soy, whey, whey-GMP) induce a related approximately 20% reduction of subsequent energy intake.

Effects of complete whey-protein breakfasts versus whey without GMP-breakfasts on energy intake and satiety

AIM To compare the effects of whey versus whey without glycomacropeptide (GMP) in a high and a normal amount of protein in a breakfast custard on satiety and energy intake (EI), taking concentrations of amino acids (AA), glucose, insulin, glucagon-like peptide 1 (GLP-1) and ghrelin into account. METHODS Twenty-five healthy subjects (mean+/-S.E.M., BMI: 23.9+/-0.3 kg/m(2); age: 22+/-1 years) received a breakfast containing whey or whey without GMP as protein type with 10/55/35 or 25/55/20 En% protein/carbohydrate/fat in a randomized, single-blind design. Appetite profile (Visual Analogue Scale, VAS), glucose, insulin, GLP-1, ghrelin and AA concentrations were measured, and the adequate moment for ad libitum lunch was determined based on differences in ghrelin concentration. In a second set of experiments subjects received the same breakfasts; ad libitum lunch was offered at the pre-determined moment. RESULTS After a breakfast with 25 En% protein increases in insulin and GLP-1 and decreases in ghrelin concentrations were larger; increases in satiety ratings were lower than after 10 En% (p<0.05); there was a treatment x time interaction effect on glucose and insulin concentrations (p<0.001). After a breakfast with whey without GMP insulin concentrations were increased more than after whey (p<0.05). EI at lunch was lower after whey than after whey without GMP (2877+/-165 kJ versus 3208+/-178 kJ, p<0.05), coinciding with more increased concentrations of serine, threonine, alanine, alpha-aminobutyric acid and isoleucine (p<0.05). CONCLUSION GMP as a whey-fraction reduced energy intake coinciding with increased concentrations of certain amino acids, irrespective of the concentration of whey-protein. Although between different concentrations of whey-protein differences in hormone responses were observed, these were unrelated to satiety ratings or energy intake.

Gas exchange responses to continuous incremental cycle ergometry exercise in primary pulmonary hypertension in humans.

Abstract In patients suffering from primary pulmonary hypertension (PPH), a raised pulmonary vascular resistance may limit the ability to increase pulmonary blood flow as work rate increases. We hypothesised that oxygen uptake (V˙O2) may not rise appropriately with increasing work rate during incremental cardiopulmonary exercise tests. Nine PPH patients and nine normal subjects performed symptom-limited maximal continuous incremental cycle ergometry exercise. Mean peak V˙O2 [1.00 (SD 0.22) compared to 2.58 (SD 0.64) l · min−1] and mean V˙O2 at lactic acidosis threshold [LAT, 0.73 (SD 0.17) compared to 1.46 (SD 0.21 · l) ml · min−1] were much lower in patients than in normal subjects (both P < 0.01, two-way ANOVA with Tukey test). The mean rate of change of V˙O2 with increasing work rate above the LAT [5.9 (SD 2.1) compared to 9.4 (SD 1.3) ml · min−1 · W−1, P < 0.01)] was also much lower in patients than in normal subjects [apparent δ efficiency 60.3 (SD 38.8)% in patients compared to 31.0 (SD 4.9)% in normal subjects]. The patients displayed lower mean values of end-tidal partial pressure of carbon dioxide than the normal subjects at peak exercise [29.7 (SD 6.8) compared to 42.4 (SD 5.8) mmHg, P < 0.01] and mean oxyhaemoglobin saturation [89.1 (SD 4.1) compared to 93.6 (SD 1.8)%, P < 0.05]. Mean ventilatory equivalents for CO2 [49.3 (SD 11.4) compared to 35.0 (SD 7.3), P < 0.05] and O2 [44.2 (SD 10.7) compared to 29.9 (SD 5.1), P < 0.05] were greater in patients than normal subjects. The sub-normal slopes for the V˙O2-work-rate relationship above the LAT indicated severe impairment of the circulatory response to exercise in patients with PPH. The ventilatory abnormalities in PPH suggested that the lung had become an inefficient gas exchange organ because of impaired perfusion of the ventilated lung.

Metabolic and molecular responses to leucine‐enriched branched chain amino acid supplementation in the skeletal muscle of alcoholic cirrhosis

Skeletal muscle loss (sarcopenia) is a major clinical complication in alcoholic cirrhosis with no effective therapy. Skeletal muscle autophagic proteolysis and myostatin expression (inhibitor of protein synthesis) are increased in cirrhosis and believed to contribute to anabolic resistance. A prospective study was performed to determine the mechanisms of sarcopenia in alcoholic cirrhosis and potential reversal by leucine. In six well‐compensated, stable, alcoholic patients with cirrhosis and eight controls, serial vastus lateralis muscle biopsies were obtained before and 7 hours after a single oral branched chain amino acid mixture enriched with leucine (BCAA/LEU). Primed‐constant infusion of l‐[ring‐2H5]‐phenylalanine was used to quantify whole‐body protein breakdown and muscle protein fractional synthesis rate using liquid chromatography/mass spectrometry. Muscle expression of myostatin, mammalian target of rapamycin (mTOR) targets, autophagy markers, protein ubiquitination, and the intracellular amino acid deficiency sensor general control of nutrition 2 were quantified by immunoblots and the leucine exchanger (SLC7A5) and glutamine transporter (SLC38A2), by real‐time polymerase chain reaction. Following oral administration, plasma BCAA concentrations showed a similar increase in patients with cirrhosis and controls. Skeletal muscle fractional synthesis rate was 9.63 ± 0.36%/hour in controls and 9.05 ± 0.68%/hour in patients with cirrhosis (P = 0.54). Elevated whole‐body protein breakdown in patients with cirrhosis was reduced with BCAA/LEU (P = 0.01). Fasting skeletal muscle molecular markers showed increased myostatin expression, impaired mTOR signaling, and increased autophagy in patients with cirrhosis compared to controls (P < 0.01). The BCAA/LEU supplement did not alter myostatin expression, but mTOR signaling, autophagy measures, and general control of nutrition 2 activation were consistently reversed in cirrhotic muscle (P < 0.01). Expression of SLC7A5 was higher in the basal state in patients with cirrhosis than controls (P < 0.05) but increased with BCAA/LEU only in controls (P < 0.001). Conclusions: Impaired mTOR1 signaling and increased autophagy in skeletal muscle of patients with alcoholic cirrhosis is acutely reversed by BCAA/LEU. (Hepatology 2015;61:2018‐2029)