Nutrition in the prevention and management of sarcopenia - A special focus on Asian Indians.

Sarcopenia, characterized by loss of muscle mass and strength, is common in advanced old age but can be accelerated by chronic disease, malnutrition and physical inactivity. Early initiation of intervention to achieve and maintain a higher peak muscle mass and strength may allow for prevention or delay of sarcopenia and facilitate independent living even in old age. In this context, malnutrition, a significant contributor to sarcopenia, is often overlooked among the Indian population. Maintenance of an optimal energy and protein balance with adequate physical activity level is essential to preserve physical function in the aging population. However, research on the role of micronutrients in muscle maintenance, is still in its infancy. This narrative review, therefore, aims to explore the current status of International and Indian research on the role of nutrition in sarcopenia mitigation and the way forward.

Nutrition as a modifiable factor in the onset and progression of pulmonary function impairment in COPD: a systematic review.

CONTEXT: Chronic obstructive lung disease (COPD) is a progressive lung disease characterized by persistent airflow limitation. An increasing amount of evidence suggests an effect of dietary quality on the risk of COPD in the general population and pulmonary function decline in patients with COPD. OBJECTIVE: The association of dietary intake and nutrient status with COPD risk and onset, as well as pulmonary function decline (change in forced expiratory volume in 1 second, forced vital capacity, or the ratio of the former to the latter) in patients with COPD was investigated in this systematic review. DATA SOURCES: The PubMed database was searched by combining terms of pulmonary function or COPD with diet, nutrient status, or nutritional supplementation. DATA EXTRACTION: Original studies and systematic reviews and meta-analyses were included. Articles obtained were independently screened for relevance on the bases of title and abstract by 2 researchers. Eventually, 89 articles were included in the analysis. RESULTS: The unhealthy Western-style diet is associated with an increased risk of COPD and an accelerated decline of pulmonary function. Intake of fruit, vegetables, dietary fibers, vitamins C and E, polyphenols, and ß-carotene were individually associated with lower COPD risk, whereas consumption of processed meat was associated with higher COPD risk. Data on the effect of dietary quality on pulmonary function decline in patients with COPD are limited and inconsistent. Strong evidence for beneficial effects on pulmonary function decline was found only for vitamin D supplementation. CONCLUSION: Considering the increasing burden of COPD, more attention should be given to dietary quality as a modifiable factor in disease development and progression in patients with COPD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021240183.

Gut microbial dysbiosis as a limiting factor in the management of primary and secondary sarcopenia: an Asian Indian perspective.

PURPOSE OF REVIEW: The article summarizes recent research advances on the role of gut microbiome in primary and secondary sarcopenia. This article also explores the potential contribution of gut dysbiosis to suboptimal sarcopenia management with special focus on factors contributing to gut dysbiosis among Asian Indians. RECENT FINDINGS: Aging and chronic diseases contribute to gut dysbiosis and intestinal barrier dysfunction allowing enhanced microbial translocation that may negatively affect muscle strength, physical function, and frailty. Gut microbiome of Asian Indians has shown a unique composition that is affected by multiple factors, such as socioeconomic status, poor hygiene, high rate of infection and infestations, antibiotic overuse and transition towards a westernized eating pattern. Current management approach for sarcopenia (exercise and/or protein supplementation) fails to address gut dysbiosis and intestinal barrier dysfunction. Incorporating a prebiotic or probiotic element to the intervention strategy may improve gut dysbiosis, inflammation and muscle function. SUMMARY: Gut dysbiosis and intestinal barrier dysfunction appear to be a significant limitation in sarcopenia management, thus gut centric intervention may be perceived as a (co)intervention strategy to be tested in appropriate clinical trials.

Safety and Tolerability of Targeted Medical Nutrition for Cachexia in Non-Small-Cell Lung Cancer: A Randomized, Double-Blind, Controlled Pilot Trial.

Background: This pilot, double-blind, comparator-controlled trial evaluated the safety and tolerability of an oral targeted medical nutrition (TMN) supplement for the management of cachexia in patients with non-small-cell lung cancer (NSCLC).Methods: Patients receiving first-line chemotherapy for NSCLC with weight loss or low BMI were randomized 1:1 to receive juice-based TMN (∼200 kcal; 10 g whey protein; ≥2.0 g eicosapentaenoic acid/docosahexaenoic acid in fish oil; and 10 µg 25-hydroxy-vitamin D3) or a milk-based isocaloric comparator twice daily for 12 weeks (ClinicalTrials.gov: NCT02515032). Primary endpoints included number/type of adverse events and changes in vital signs/laboratory parameters. Secondary endpoints included measures of clinical relevance. Survival was an exploratory endpoint.Results: The TMN group (n = 26; mean 64.4 years) experienced fewer adverse events (64 vs. 87) than the comparator group (n = 29; mean 66.0 years), including fewer cases of neutropenia (0 vs. 4). Compliance was slightly lower in the TMN (58.5%) vs. comparator group (73.6%). There were no statistically significant between-group differences in efficacy endpoints. Fewer (4 vs. 10) patients who received TMN than comparator had died by 1-year post baseline.Conclusions: TMN was well tolerated. Trends for improved clinical outcomes with TMN identified in this study warrant further investigation.

Clinical outcome and cost-effectiveness of a 1-year nutritional intervention programme in COPD patients with low muscle mass: The randomized controlled NUTRAIN trial.

BACKGROUND AND AIMS: The efficacy of nutritional intervention to enhance short- and long-term outcomes of pulmonary rehabilitation in COPD is still unclear, hence this paper aims to investigate the clinical outcome and cost-effectiveness of a 12-month nutritional intervention strategy in muscle-wasted COPD patients. METHODS: Prior to a 4-month pulmonary rehabilitation programme, 81 muscle-wasted COPD patients (51% males, aged 62.5 ± 0.9 years) with moderate airflow obstruction (FEV1 55.1 ± 2.2% predicted) and impaired exercise capacity (Wmax 63.5 ± 2.4% predicted) were randomized to 3 portions of nutritional supplementation per day (enriched with leucine, vitamin D and polyunsaturated fatty acids) [NUTRITION] or PLACEBO (phase 1). In the unblinded 8-month maintenance phase (phase 2), both groups received structured feedback on their physical activity level assessed by accelerometry. NUTRITION additionally received 1 portion of supplemental nutrition per day and motivational interviewing-based nutritional counselling. A 3-month follow-up (phase 3) was included. RESULTS: After 12 months, physical capacity measured by quadriceps muscle strength and cycle endurance time were not different, but physical activity was higher in NUTRITION than in PLACEBO (Δ1030 steps/day, p = 0.025). Plasma levels of the enriched nutrients (p < 0.001) were higher in NUTRITION than PLACEBO. Trends towards weight gain in NUTRITION and weight loss in PLACEBO led to a significant between-group difference after 12 months (Δ1.54 kg, p = 0.041). The HADS anxiety and depression scores improved in NUTRITION only (Δ-1.92 points, p = 0.037). Generic quality of life (EQ-5D) was decreased in PLACEBO but not in NUTRITION (between-group difference after 15 months 0.072 points, p = 0.009). Overall motivation towards exercising and healthy eating was high and did not change significantly after 12 months; only amotivation towards healthy eating yielded a significant between-group difference (Δ1.022 points, p = 0.015). The cost per quality-adjusted life-year after 15 months was EUR 16,750. CONCLUSIONS: Nutritional intervention in muscle-wasted patients with moderate COPD does not enhance long-term outcome of exercise training on physical capacity but ameliorates plasma levels of the supplemented nutrients, total body weight, physical activity and generic health status, at an acceptable increase of costs for patients with high disease burden.

Pulmonary rehabilitation, physical activity, respiratory failure and palliative respiratory care.

The CIRO Academy in Horn (the Netherlands) organised a 2-day meeting to present and discuss the studies published in 2017 pertaining to key priority areas of respiratory and critical care medicine. This review summarises studies focussing on pulmonary rehabilitation and exercise training, physical activity, chronic respiratory failure and palliative respiratory care published in 2017.

Stages of behavioural change after direct-to-consumer disease risk profiling: study protocol of two integrated controlled pragmatic trials.

BACKGROUND: The incidence and prevalence of chronic diseases have reached epidemic proportions during the last decades and are not expected to diminish. Chronic diseases increasingly affect younger individuals too, with over 40% of all deaths due to non-communicable diseases occurring before the age of 70. This has led to the development of information services aimed at preventive health care, such as Health Potential®. This counselling service estimates a personal disease risk of a carefully selected list of preventable common chronic diseases that have both a genetic and a lifestyle component of development. The results are delivered face-to-face by a lifestyle counsellor, simultaneously stimulating initial steps towards behaviour change. This information can assist in lifestyle decision-making. METHODS/DESIGN: The primary aim is to study the effect of the Health Potential® service on change in lifestyle behaviour in distinguishable customer populations. The secondary aims are (1) to study the effect of the Health Potential® service on determinants of behaviour change, (2) to study the effect of additional lifestyle counselling on behaviour change and determinants thereof, and (3) to describe the characteristics of the Health Potential® customer. The study consists of two integrated designs: (A) a two-armed non-randomised controlled pre-test/post-test trial (1.5:1 ratio), followed by (B) a two-armed randomised controlled pre-test/post-test trial (1:1 ratio), resulting in three study arms. Participants are clients of local prevention clinics, purchasing a personalised health check (PHC; intervention condition), consisting of Health Potential® and a general health check, or the general health check alone (GHC; control condition) (part A). PHC participants will be randomised to receive four additional lifestyle counselling sessions over a period of 3 months (part B). DISCUSSION: This research can provide valuable insights into the effectiveness of and possible ways forward in the field of personalised prevention making use of lifestyle interventions enriched with modern genetic advancements. TRIAL REGISTRATION: Nederlands Trial Register, NTR6289 and NTR6288 . Registered on 24 February 2017.

A randomized clinical trial investigating the efficacy of targeted nutrition as adjunct to exercise training in COPD.

BACKGROUND: Evidence regarding the efficacy of nutritional supplementation to enhance exercise training responses in COPD patients with low muscle mass is limited. The objective was to study if nutritional supplementation targeting muscle derangements enhances outcome of exercise training in COPD patients with low muscle mass. METHODS: Eighty-one COPD patients with low muscle mass, admitted to out-patient pulmonary rehabilitation, randomly received oral nutritional supplementation, enriched with leucine, vitamin D, and omega-3 fatty acids (NUTRITION) or PLACEBO as adjunct to 4 months supervised high intensity exercise training. RESULTS: The study population (51% males, aged 43-80) showed moderate airflow limitation, low diffusion capacity, normal protein intake, low plasma vitamin D, and docosahexaenoic acid. Intention-to-treat analysis revealed significant differences after 4 months favouring NUTRITION for body mass (mean difference ± SEM) (+1.5 ± 0.6 kg, P = 0.01), plasma vitamin D (+24%, P = 0.004), eicosapentaenoic acid (+91%,P < 0.001), docosahexaenoic acid (+31%, P < 0.001), and steps/day (+24%, P = 0.048). After 4 months, both groups improved skeletal muscle mass (+0.4 ± 0.1 kg, P < 0.001), quadriceps muscle strength (+12.3 ± 2.3 Nm,P < 0.001), and cycle endurance time (+191.4 ± 34.3 s, P < 0.001). Inspiratory muscle strength only improved in NUTRITION (+0.5 ± 0.1 kPa, P = 0.001) and steps/day declined in PLACEBO (-18%,P = 0.005). CONCLUSIONS: High intensity exercise training is effective in improving lower limb muscle strength and exercise performance in COPD patients with low muscle mass and moderate airflow obstruction. Specific nutritional supplementation had additional effects on nutritional status, inspiratory muscle strength, and physical activity compared with placebo.

Modifiable risk factors for the prevention of bladder cancer: a systematic review of meta-analyses.

Each year, 430,000 people are diagnosed with bladder cancer. Due to the high recurrence rate of the disease, primary prevention is paramount. Therefore, we reviewed all meta-analyses on modifiable risk factors of primary bladder cancer. PubMed, Embase and Cochrane database were systematically searched for meta-analyses on modifiable risk factors published between 1995 and 2015. When appropriate, meta-analyses (MA) were combined in meta-meta-analysis (MMA). If not, the most comprehensive MA was selected based on the number of primary studies included. Probability of causation was calculated for individual factors and a subset of lifestyle factors combined. Of 1496 articles identified, 5 were combined in MMA and 21 were most comprehensive on a single risk factor. Statistically significant associations were found for current (RR 3.14) or former (RR 1.83) cigarette smoking, pipe (RR 1.9) or cigar (RR 2.3) smoking, antioxidant supplementation (RR 1.52), obesity (RR 1.10), higher physical activity levels (RR 0.86), higher body levels of selenium (RR 0.61) and vitamin D (RR 0.75), and higher intakes of: processed meat (RR 1.22), vitamin A (RR 0.82), vitamin E (RR 0.82), folate (RR 0.84), fruit (RR 0.77), vegetables (RR 0.83), citrus fruit (RR 0.85), and cruciferous vegetables (RR 0.84). Finally, three occupations with the highest risk were tobacco workers (RR 1.72), dye workers (RR 1.58), and chimney sweeps (RR 1.53). The probability of causation for individual factors ranged from 4 to 68 %. The combined probability of causation was 81.8 %. Modification of lifestyle and occupational exposures can considerably reduce the bladder cancer burden. While smoking remains one of the key risk factors, also several diet-related and occupational factors are very relevant.

Nutrition as a metabolic modulator in COPD.

COPD is an important global health problem. In addition to pulmonary impairment, systemic inflammation, musculoskeletal abnormalities, and cardiovascular comorbidity influence disease burden and mortality risk. Body weight and body composition are important discriminants in classifying disease heterogeneity. The rationale for and efficacy of caloric supplementation in preventing and treating involuntary weight loss is currently well established. For maintenance of muscle and bone tissue, appropriately timed, high-quality protein intake and addressing vitamin D deficiency must be considered. Specific nutrients (eg, n-3 polyunsaturated fatty acids and polyphenolic compounds) may have the pharmacologic potential to boost decreased muscle mitochondrial metabolism and enhance impaired physical performance, particularly when the metabolic stimulus of physical activity alone is limited. At this stage, evidence is insufficient to support an intake of high doses of single nutritional supplements to modulate respiratory pathology, but some small studies have identified micronutrient modulation via the diet as a promising intervention.

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.

Inflammatory signaling in skeletal muscle insulin resistance: green signal for nutritional intervention?

PURPOSE OF REVIEW: To review the evidence implying a role of inflammatory signaling pathways, specifically nuclear factor-κB and c-Jun NH2-terminal kinase, in fatty acid-induced skeletal muscle insulin resistance and to discuss the potential of dietary interventions to interfere with these processes. RECENT FINDINGS: Fatty acids can induce skeletal muscle insulin resistance via inflammatory signaling after binding Toll-like receptors at the cell membrane of muscle cells or after accumulating as intramyocellular lipid metabolites. In both processes, activation of intracellular inflammatory signaling is involved. The majority of literature addressing the causality of muscle nuclear factor-κB activation in skeletal muscle insulin resistance suggests that insulin resistance does not require muscle nuclear factor-κB activation. Recently, strong evidence was given that c-Jun NH2-terminal kinase signaling is an important inflammatory pathway involved in skeletal muscle insulin resistance. Furthermore, it is well established that proinflammatory cytokines originating from the enlarged adipose tissue or from activated adipose tissue macrophages can cause muscle insulin resistance. Recently, also macrophages resided in the muscle have been proposed to play an important role in muscle insulin resistance. Because of their anti-inflammatory characteristics, several dietary components like polyphenols may be interesting candidates for manipulating skeletal muscle insulin resistance. SUMMARY: Several dietary components, like polyphenols, have been reported to interfere with inflammatory signaling. To test whether these compounds can be used to prevent or reverse insulin resistance, well controlled human intervention studies have to be designed.

Nutritional recommendations for the management of sarcopenia.

The Society for Sarcopenia, Cachexia, and Wasting Disease convened an expert panel to develop nutritional recommendations for prevention and management of sarcopenia. Exercise (both resistance and aerobic) in combination with adequate protein and energy intake is the key component of the prevention and management of sarcopenia. Adequate protein supplementation alone only slows loss of muscle mass. Adequate protein intake (leucine-enriched balanced amino acids and possibly creatine) may enhance muscle strength. Low 25(OH) vitamin D levels require vitamin D replacement.

Supplementation of soy protein with branched-chain amino acids alters protein metabolism in healthy elderly and even more in patients with chronic obstructive pulmonary disease.

BACKGROUND: It is often suggested that chronic wasting diseases [eg, chronic obstructive pulmonary disease (COPD)] may benefit from branched-chain amino acid (BCAA) administration via improved protein metabolism. OBJECTIVE: The aim was to examine whether adding BCAAs to a soy protein meal would enhance protein anabolism in COPD patients and in healthy elderly persons. DESIGN: Eight normal-weight COPD patients and 8 healthy control subjects were examined on 2 test days. Simultaneous continuous intravenous infusion of l-[ring-(2)H(5)]phenylalanine (Phe) and l-[ring-(2)H(2)]tyrosine tracers was done postabsorptively and at 2 h of ingestion of a maltodextrin soy or maltodextrin soy + BCAA protein meal (rate of ingestion: 0.02 g protein.kg body weight(-1).20 min(-1)) in a crossover design. Together with the meal, oral ingestion of 1-[(13)C]Phe was performed to measure first-pass Phe splanchnic extraction (SPE(Phe)). The endogenous rate of Phe appearance [reflecting whole-body protein breakdown (WbPB)], whole-body protein synthesis (WbPS), and net WbPS (WbPS - WbPB) were calculated. Arterialized venous blood was sampled for amino acid enrichment and concentration analyses. RESULTS: Soy feeding induced a reduction in WbPB and an increase in WbPS. BCAA supplementation of soy protein resulted in a significantly higher (P < 0.05) increase in WbPS than did soy protein alone in COPD patients but not in the healthy elderly. BCAA supplementation did not significantly alter the change in WbPB or net WbPS. Furthermore, BCAA supplementation decreased (absolute) SPE(Phe) (P < 0.05) but did not change the percentage Phe hydroxylation in the splanchnic area, which indicates a BCAA-related reduction in splanchnic protein synthesis. CONCLUSION: BCAA supplementation to soy protein enhances WbPS in patients with COPD and alters interorgan protein metabolism in favor of the peripheral (muscle) compartment in healthy elderly and even more in COPD patients.

Effect of glutamate ingestion on whole-body glutamate turnover in healthy elderly and patients with chronic obstructive pulmonary disease.

OBJECTIVE: Decreased whole-body glutamate turnover is found in healthy elderly and in patients with chronic obstructive pulmonary disease (COPD). Glutamate supplementation as an option to increase whole-body glutamate turnover and, hence, glutamate availability has never been investigated. In the present study, we developed a protocol based on repeated glutamate ingestion to increase plasma glutamate concentration to a steady-state level without inducing toxic side effects and to evaluate the effect of repeated glutamate ingestion on whole-body glutamate turnover in patients with COPD and healthy elderly. METHODS: In part 1, the response of plasma glutamate concentration was determined in young healthy volunteers who repeatedly ingested a glutamate solution. The tolerance of the glutamate drink was evaluated in 26 healthy volunteers by a food tolerance questionnaire. In part 2, eight male patients with COPD and eight healthy elderly ingested the glutamate drink, an isomolar amount of a glutamine drink, or only water to test the effect on plasma glutamate concentration and whole-body glutamate turnover. RESULTS: In part 1, repeated ingestion of 30 mg of glutamate per kilogram of body weight every 20 min increased plasma glutamate concentration five-fold to steady-state level within 80 min and without any side effects. In part 2, repeated ingestion of glutamate significantly increased whole-body glutamate turnover in healthy controls and patients with COPD, although the increase was smaller in patients with COPD than in controls. CONCLUSION: We found that repeated ingestion of 30 mg of glutamate per kilogram of body weight every 20 min can increase glutamate availability in healthy elderly and patients with COPD, who are likely more dependent on external glutamate ingestion than are young adults.

Metabolic effects of glutamine and glutamate ingestion in healthy subjects and in persons with chronic obstructive pulmonary disease.

BACKGROUND: Because low plasma glutamate and glutamine concentrations are often seen in chronic obstructive pulmonary disease (COPD), glutamine or glutamate supplementation may be a good option for preventing further metabolic disturbances in COPD patients. However, the metabolic effects of glutamate supplementation have never been compared with those of glutamine supplementation. OBJECTIVE: We compared the metabolic effects of repeated ingestion of glutamine and glutamate in COPD patients and in age-matched healthy control subjects. DESIGN: On 3 d separated by intervals of > or = 2 d, a protocol of primed constant and continuous infusion of [2H5]phenylalanine and [2H2]tyrosine was performed for 3 h in 8 stable male COPD patients and 8 healthy control subjects. After a 90-min tracer infusion, all subjects ingested a glutamine or glutamate drink or the same amount of water every 20 min for 80 min. Blood samples were taken at the end of the postabsorptive and ingestion periods to test for effects on plasma amino acid and substrate concentrations and whole-body protein turnover. RESULTS: Glutamate but not glutamine ingestion resulted in higher plasma ornithine concentrations than did water ingestion (P < 0.01). The change in plasma arginine, citrulline, and urea concentrations was significantly (P < 0.01) higher after glutamine ingestion than after water or glutamate ingestion. Whole-body protein turnover decreased overall, independent of the drink consumed. CONCLUSIONS: Repeated ingestion of glutamine and glutamate resulted in different effects on the plasma amino acid concentration. In both groups, ingestion of glutamine but not of glutamate increased the plasma concentrations of citrulline and arginine, substrates produced in the intestine and the liver.

Optimizing oral nutritional drink supplementation in patients with chronic obstructive pulmonary disease.

Nutritional support is indicated in some patients with chronic obstructive pulmonary disease to restore nutritional status and improve functional capacity. However, the efficacy of nutritional supplements is sometimes disappointing, partly owing to a compensatory drop in habitual food intake. We retrospectively studied the effect of nutritional drink supplements, differing in portion size and energy content, on weight gain and body composition. Thirty-nine patients with stable chronic obstructive pulmonary disease, participating in an 8-week pulmonary rehabilitation programme and eligible for nutritional support, were studied. Group A (n 19) received three portions of 125 ml (2380 kJ), whereas group B (n 20) received three portions of 200 ml (3350 kJ) daily. The macronutrient composition of the regimens was similar (20 % protein, 60 % carbohydrates and 20 % fat). Lung function, body weight, body composition (by bio-electrical impedance analysis), habitual dietary intake (by dietary history) and resting energy expenditure (by ventilated hood) were determined. Weight gain was compared with expected weight as predicted by a computer simulation model. Although patients in both groups significantly increased in weight, this increase was higher in group A (A, 3.3 (sd 1.9) kg; B, 2.0 (sd 1.2) kg; P=0.019), while receiving less energy. The observed weight gain in group A was similar to that expected, but in group B it was lower than expected (P<0.001). In both groups, fat-free mass and fat mass were gained in a ratio of 2:1, fat-free mass increasing primarily during the first 4 weeks. This study illustrates that there might be an optimum for the portion size of nutritional drink supplements in chronic obstructive pulmonary disease and that more is not always better.

Skeletal muscle glutamate metabolism in health and disease: state of the art.

PURPOSE OF REVIEW: Glutamate is an amino acid of interest because it participates in many metabolic pathways. However, there is evidence that skeletal muscle glutamate metabolism is disturbed in disease. This review presents current knowledge regarding the metabolic function and regulation of glutamate in skeletal muscle under physiological and pathophysiological circumstances. Furthermore, several options for modulating muscle glutamate concentration in order to improve glutamate metabolism are discussed. RECENT FINDINGS: The high correlation between muscle glutamate concentration and muscle glutathione concentration suggests that glutamate plays a determining role in the glutathione synthesis pathway. During exercise, glutamate plays a central role in energy provision because it participates in the tricarboxylic acid and the purine nucleotide cycles. However, a consistent finding in several diseases is reduced skeletal muscle glutamate. Remarkably, only few studies focused on modulation of muscle glutamate status either by exercise or by nutritional supplementation. There are several options for modulating glutamate metabolism, but the specific effects of the individual options require further elucidation. Nutritional supplementation of glutamate or its precursors glutamine, (ornithine) alpha-ketoglutarate, or the branched chain amino acids can influence muscle glutamate status. SUMMARY: Specific intervention studies must be conducted to investigate the effect of supplementation on skeletal muscle glutamate turnover and its related metabolic and functional consequences in healthy individuals and in patients with acute or chronic disease.

A role for anabolic steroids in the rehabilitation of patients with COPD? A double-blind, placebo-controlled, randomized trial.

STUDY OBJECTIVES: Skeletal muscle weakness commonly occurs in patients with COPD. Long-term use of systemic glucocorticosteroids further contributes to muscle weakness. Anabolic steroids could be an additional mode of intervention to improve outcome of pulmonary rehabilitation by increasing physiologic functioning, possibly mediated by increasing erythropoietic function. PATIENTS AND METHODS: We randomly assigned 63 male patients with COPD to receive on days 1, 15, 29, and 43 a deep IM injection of 50 mg of nandrolone decanoate (ND) [Deca-Durabolin; N.V. Organon; Oss, The Netherlands] in 1 mL of arachis oil, or 1 mL of arachis oil alone (placebo) in a double-blind design. All patients participated in a standardized pulmonary rehabilitation program. Outcome measures were body composition by deuterium and bromide dilution, respiratory and peripheral muscle function, incremental exercise testing, and health status by the St. George's Respiratory Questionnaire. RESULTS: Treatment with ND relative to placebo resulted in higher increases in fat-free mass (FFM; mean, 1.7 kg [SD, 2.5] vs 0.3 kg [SD, 1.9]; p = 0.015) owing to a rise in intracellular mass (mean, 1.8 kg [SD, 3.1] vs - 0.5 kg [SD, 3.1]; p = 0.002). Muscle function, exercise capacity, and health status improved in both groups to the same extent. Only after ND were increases in erythropoietic parameters seen (erythropoietin: mean, 2.08 U/L [SD, 5.56], p = 0.067; hemoglobin: mean, 0.29 mmol/L [SD, 0.73], p = 0.055). In the total group, the changes in maximal inspiratory mouth pressure (PImax) and peak workload were positively correlated with the change in hemoglobin (r = 0.30, p = 0.032, and r = 0.34, p = 0.016, respectively), whereas the change in isokinetic leg work was correlated with the change in erythropoietin (r = 0.38, p = 0.013). In the patients receiving maintenance treatment with low-dose oral glucocorticosteroids (31 of 63 patients; mean, 7.5 mg/24 h [SD, 2.4]), greater improvements in PImax (mean, 6.0 cm H(2)O [SD, 8.82] vs - 2.18 cm H(2)O [SD, 11.08], p = 0.046), and peak workload (mean, 20.47 W [SD, 19.82] vs 4.80 W [SD, 7.74], p = 0.023) were seen after 8 weeks of treatment with ND vs placebo. CONCLUSIONS: In conclusion, a short-term course of ND had an overall positive effect relative to placebo on FFM without expanding extracellular water in patients with COPD. In the total group, the improvements in muscle function and exercise capacity were associated with improvements in erythropoietic parameters. The use of low-dose oral glucocorticosteroids as maintenance medication significantly impaired the response to pulmonary rehabilitation with respect to respiratory muscle function and exercise capacity, which could be restored by ND treatment.

Energy balance in depleted ambulatory patients with chronic obstructive pulmonary disease: the effect of physical activity and oral nutritional supplementation.

Patients with chronic obstructive pulmonary disease (COPD) often suffer from weight loss. The aim of the present study was to gain insight into the energy balance of depleted ambulatory COPD patients, in relation to their habitual level of physical activity and consumption of oral nutritional supplements. Clinically stable and weight-stable patients (n 20; BMI 19.8+/- SD 2.0 kg/m2) were studied 1 and 3 months after rehabilitation or recovery in the clinic and were at random assigned to a control or intervention group with regard to nutritional supplementation. Energy intake was measured with a 7 d food record. Energy expenditure was estimated from a simultaneous 7 d assessment of physical activity with a tri-axial accelerometer for movement registration in combination with measured BMR. Body mass was measured at several time points. The body mass remained stable in both groups after 1 or 3 months and mean energy balances were comparable for both groups. The mean body-mass change between month 1 and 3 was negatively related to the mean physical activity level (r -0.49; P=0.03). Weight change over the 3 months was negatively associated with the physical activity level. These results suggest that knowledge about the individual physical activity level is necessary for the estimation of the energy need of the COPD patient.