Malnutrition in patients with COVID-19: assessment and consequences.

PURPOSE OF REVIEW: COVID-19 disease often presents with malnutrition and nutrition impact symptoms, such as reduced appetite, nausea and loss of taste. This review summarizes the most up-to-date research on nutritional assessment in relation to mortality and morbidity risk in patients with COVID-19. RECENT FINDINGS: Numerous studies have been published on malnutrition, muscle wasting, obesity, and nutrition impact symptoms associated with COVID-19, mostly observational and in hospitalized patients. These studies have shown a high prevalence of symptoms (loss of appetite, nausea, vomiting, diarrhea, dysphagia, fatigue, and loss of smell and taste), malnutrition, micronutrient deficiencies and obesity in patients with COVID-19, all of which were associated with increased mortality and morbidity risks. SUMMARY: Early screening and assessment of malnutrition, muscle wasting, obesity, nutrition impact symptoms and micronutrient status in patients with COVID-19, followed by pro-active nutrition support is warranted, and expected to contribute to improved recovery. There is limited research on nutritional status or nutrition impact symptoms in patients living at home or in residential care. RCTs studying the effects of nutrition intervention on clinical outcomes are lacking. Future research should focus on these evidence gaps.

Metabolic Consequences of Supplemented Methionine in a Clinical Context.

The central position of methionine (Met) in protein metabolism indicates the importance of this essential amino acid for growth and maintenance of lean body mass. Therefore, Met might be a tempting candidate for supplementation. However, because Met is also the precursor of homocysteine (Hcy), a deficient intake of B vitamins or excessive intake of Met may result in hyperhomocysteinemia (HHcy), which is a risk factor for cardiovascular disease. This review discusses the evidence generated in preclinical and clinical studies on the importance and potentially harmful effects of Met supplementation and elaborates on potential clinical applications of supplemental Met with reference to clinical studies performed over the past 20 y. Recently acquired knowledge about the NOAEL (no observed adverse effect level) of 46.3 mg · kg-1 · d-1 and the LOAEL (lowest observed adverse effect level) of 91 mg · kg-1 · d-1 of supplemented Met will guide the design of future studies to further establish the role of Met as a potential (safe) candidate for nutritional supplementation in clinical applications.

Clinical applications of body composition and functional status tools for nutrition assessment of hospitalized adults: A systematic review.

BACKGROUND: No global consensus exists on diagnostic criteria for malnutrition. Muscular deficits and functional impairments are major components of available malnutrition diagnostic frameworks because these facets of nutrition status significantly impact outcomes. The purpose of this review is to explore which body composition assessment (BCA) and functional status assessment (FSA) tools are being used for nutrition assessment (NA) and monitoring the response to nutrition interventions (RNIs) in adult inpatients. METHODS: A literature search of Embase, Medline (Ovid), Web of Science, and Cochrane Central was performed to identify studies that used BCA and/or FSA tools for NA (along with an accepted NA diagnostic framework) and/or for monitoring RNI in adult inpatients. RESULTS: The search yielded 3667 articles; 94 were included in the review. The number of studies using BCA and/or FSA tools for NA was 47 and also 47 for monitoring RNI. Seventy-nine percent of studies used bioimpedance for BCA, and 97% that included FSA utilized handgrip strength. When compared against sets of diagnostic criteria, many of the BCA and FSA tools showed promising associations with nutrition status. CONCLUSION: Bioimpedance methods are the most widely used bedside BCA tools, and handgrip strength is the most widely used FSA tool; however, these methods are being used with a variety of protocols, algorithms, and interpretation practices in heterogeneous populations. To create a standardized nutrition status assessment process there is a need for validation studies on bedside methods and the development of globally standardized assessment protocols in clinical inpatient settings.

Weight loss of 5% or more predicts loss of fat-free mass during palliative chemotherapy in patients with advanced cancer: a pilot study.

The cutoff value of critical weight loss is still subject of discussion. In this pilot study, we investigated whether ≥ 5% weight loss in the past year predicts changes in nutritional status in patients with advanced cancer during treatment with palliative chemotherapy. In 20 patients with advanced cancer undergoing palliative (combination) chemotherapy, body weight, fat free mass (FFM), and cachexia were measured prior to the start and at 9 wk of treatment. History of weight loss was used to test differences in development of nutritional parameters during chemotherapy with use of independent sample t-tests. At baseline, 10 of 20 patients had lost ≥ 5% body weight during the past year and 5 patients were cachectic. The change in FFM in the first 9 wk of chemotherapy was significantly worse in patients with ≥ 5% weight loss compared to patients with <5% weight loss [mean difference: 3.5 kg (P = 0.001)]. Data also suggest that ≥ 5% weight loss predicts shorter survival (P = 0.03). We found that patients with ≥ 5% weight loss prior to chemotherapy have a deterioration in nutritional status during chemotherapy and may have a shorter survival. These results have to be confirmed in a larger study including a robust survival analysis.

Walking exercise alters protein digestion, amino acid absorption, and whole body protein kinetics in older adults with and without COPD.

Gut-related symptoms and an increase in markers of gut dysfunction have been observed in patients with chronic obstructive pulmonary disease (COPD). It remains unclear whether exercise, in relation to inducing hypoxia, plays a role in disturbances in protein digestion and amino acid absorption and whole body protein kinetics. Sixteen clinically stable patients with moderate-to-very severe COPD and 12 matched healthy subjects completed the study. Protein digestion and amino acid absorption, whole body protein kinetics were measured in the postabsorptive state via a continuous infusion of stable tracers in combination with orally administered stable tracer sips during 20 min of walking exercise and up to 4 h post exercise. In addition, concentrations of short-chain fatty acid (SCFA) and amino acids were measured. Patients with COPD completed one study day, walking at maximal speed, whereas healthy subjects completed two, one matched to the speed of a patient with COPD and one at maximal speed. The patients with COPD tolerated 20 min of vigorous intensity walking with an elevated heart rate (P < 0.0001) and substantial desaturation (P = 0.006). During exercise, we observed lower protein digestion (P = 0.04) and higher SCFA acetate (P = 0.04) and propionate (P = 0.02) concentrations on max speed study days, lower amino acid absorption (P = 0.004) in subjects with oxygen desaturation, and lower net protein breakdown (P = 0.03) and propionate concentrations (P = 0.04) in patients with COPD. During late recovery from exercise, amino acid absorption (P = 0.02) and net protein breakdown (P = 0.02) were lower in patients with COPD. Our data suggest that 20 min of walking exercise is sufficient to cause perturbations in gut function and whole body protein metabolism during and up to 4 h post exercise in older adults and in patients with COPD with exercise-induced hypoxia.NEW & NOTEWORTHY Gut function is disturbed in older adults with COPD. As exercise is the cornerstone of pulmonary rehabilitation in COPD, knowledge of the response of the gut to aerobic exercise is of importance.

Antioxidant-enriched enteral nutrition and immuno-inflammatory response after major gastrointestinal tract surgery.

Major surgery induces an immuno-inflammatory response accompanied by oxidative stress that may impair cellular function and delay recovery. The objective of the study was to investigate the effect of an enteral supplement, containing glutamine and antioxidants, on circulating levels of immuno-inflammatory markers after major gastrointestinal tract surgery. Patients (n 21) undergoing major gastrointestinal tract surgery were randomised in a single-centre, open-label study. The effects on circulating levels of immuno-inflammatory markers were determined on the day before surgery and on days 1, 3, 5 and 7 after surgery. Major gastrointestinal surgery increased IL-6, TNF receptor 55/60 (TNF-R55) and C-reactive protein (CRP). Surgery reduced human leucocyte antigen-DR (HLA-DR) expression on monocytes. CRP decrease was more pronounced in the first 7 d in the treatment group compared with the control group. In the treatment group, from the moment Module AOX was administered on day 1 after surgery, TNF receptor 75/80 (TNF-R75) level decreased until the third post-operative day and then stabilised, whereas in the control group the TNF-R75 level continued to increase. The results of the present pilot study suggest that enteral nutrition enriched with glutamine and antioxidants possibly moderates the immuno-inflammatory response (CRP, TNF-R75) after surgery.

Frailty, Sarcopenia, and Malnutrition Frequently (Co-)occur in Hospitalized Older Adults: A Systematic Review and Meta-analysis.

OBJECTIVES: The purpose of this systematic review and meta-analysis was to summarize the prevalence of, and association between, physical frailty or sarcopenia and malnutrition in older hospitalized adults. DESIGN: A systematic literature search was performed in 10 databases. SETTING AND PARTICIPANTS: Articles were selected that evaluated physical frailty or sarcopenia and malnutrition according to predefined criteria and cutoffs in older hospitalized patients. MEASURES: Data were pooled in a meta-analysis to evaluate the prevalence of prefrailty and frailty [together (pre-)frailty], sarcopenia, and risk of malnutrition and malnutrition [together (risk of) malnutrition], and the association between either (pre-)frailty or sarcopenia and (risk of) malnutrition. RESULTS: Forty-seven articles with 18,039 patients (55% female) were included in the systematic review, and 39 articles (8868 patients, 62% female) were eligible for the meta-analysis. Pooling 11 studies (2725 patients) revealed that 84% [95% confidence interval (CI): 77%, 91%, I2 = 98.4%] of patients were physically (pre-)frail. Pooling 15 studies (4014 patients) revealed that 37% (95% CI: 26%, 48%, I2 = 98.6%) of patients had sarcopenia. Pooling 28 studies (7256 patients) revealed a prevalence of 66% (95% CI: 58%, 73%, I2 = 98.6%) (risk of) malnutrition. Pooling 10 studies (2427 patients) revealed a high association [odds ratio (OR): 5.77 (95% CI: 3.88, 8.58), P < .0001, I2 = 42.3%] and considerable overlap (49.7%) between physical (pre-)frailty and (risk of) malnutrition. Pooling 7 studies (2506 patients) revealed a high association [OR: 4.06 (95% CI: 2.43, 6.80), P < .0001, I2 = 71.4%] and considerable overlap (41.6%) between sarcopenia and (risk of) malnutrition. CONCLUSIONS AND IMPLICATIONS: The association between and prevalence of (pre-)frailty or sarcopenia and (risk of) malnutrition in older hospitalized adults is substantial. About half of the hospitalized older adults suffer from 2 and perhaps 3 of these debilitating conditions. Therefore, standardized screening for these conditions at hospital admission is highly warranted to guide targeted nutritional and physical interventions.

Preserved anabolic threshold and capacity as estimated by a novel stable tracer approach suggests no anabolic resistance or increased requirements in weight stable COPD patients.

BACKGROUND & AIMS: Assessing the ability to respond anabolic to dietary protein intake during illness provides important insight in the capacity of lean body mass maintenance. We applied a newly developed stable tracer approach to assess in one session in patients with chronic obstructive pulmonary disease (COPD) and healthy older adults both the minimal amount of protein intake to obtain protein anabolism (anabolic threshold) and the efficiency of dietary protein to promote protein anabolism (anabolic capacity). METHODS: We studied 12 clinically and weight stable patients with moderate to very severe COPD (mean ± SE forced expiratory volume in 1 s: 36 ± 3% of predicted) and 10 healthy age-matched older adults. At 2-h intervals and in consecutive order, all participants consumed a mixture of 0.0, 0.04, 0.10 and 0.30 g hydrolyzed casein protein×kg ffm-1×2 h-1 and carbohydrates (2:1). We assessed whole body protein synthesis (PS), breakdown (PB), net PS (PS-PB) and net protein balance (phenylalanine (PHE) intake - PHE to tyrosine (TYR) hydroxylation) by IV primed and continuous infusion of L-[ring-2H5]PHE and L-[13C9,15N]-TYR. Anabolic threshold (net protein balance = 0) and capacity (slope) were determined on an individual basis from the assumed linear relationship between protein intake and net protein balance. RESULTS: We confirmed a linear relationship between protein intake and net protein balance for all participants (R2 range: 0.9988-1.0, p ≤ 0.0006). On average, the anabolic threshold and anabolic capacity were comparable between the groups (anabolic threshold COPD vs. healthy: 3.82 ± 0.31 vs. 4.20 ± 0.36 µmol PHE × kg ffm-1 × hr-1; anabolic capacity COPD vs. healthy: 0.952 ± 0.007 and 0.954 ± 0.004). At protein intake around the anabolic threshold (0.04 and 0.10 g protein×kg ffm-1×2 h-1), the increase in net PS resulted mainly from PB reduction (p < 0.0001) whereas at a higher protein intake (0.30 g protein×kg ffm-1×2 h-1) PS was also stimulated (p < 0.0001). CONCLUSIONS: The preserved anabolic threshold and capacity in clinically and weight stable COPD patients suggests no disease related anabolic resistance and/or increased protein requirements. TRIAL REGISTRY: ClinicalTrials.gov; No. NCT01734473; URL: www.clinicaltrials.gov.

Antioxidant enriched enteral nutrition and oxidative stress after major gastrointestinal tract surgery.

AIM: To investigate the effects of an enteral supplement containing antioxidants on circulating levels of antioxidants and indicators of oxidative stress after major gastrointestinal surgery. METHODS: Twenty-one patients undergoing major upper gastrointestinal tract surgery were randomised in a single centre, open label study on the effect of postoperative enteral nutrition supplemented with antioxidants. The effect on circulating levels of antioxidants and indicators of oxidative stress, such as F2-isoprostane, was studied. RESULTS: The antioxidant enteral supplement showed no adverse effects and was well tolerated. After surgery a decrease in the circulating levels of antioxidant parameters was observed. Only selenium and glutamine levels were restored to pre-operative values one week after surgery. F2-isoprostane increased in the first three postoperative days only in the antioxidant supplemented group. Lipopolysaccharide binding protein (LBP) levels decreased faster in the antioxidant group after surgery. CONCLUSION: Despite lower antioxidant levels there was no increase in the circulating markers of oxidative stress on the first day after major abdominal surgery. The rise in F2-isoprostane in patients receiving the antioxidant supplement may be related to the conversion of antioxidants to oxidants which raises questions on antioxidant supplementation. Module AOX restored the postoperative decrease in selenium levels. The rapid decrease in LBP levels in the antioxidant group suggests a possible protective effect on gut wall integrity. Further studies are needed on the role of oxidative stress on outcome and the use of antioxidants in patients undergoing major abdominal surgery.

The route of administration (enteral or parenteral) affects the conversion of isotopically labeled L-[2-15N]glutamine into citrulline and arginine in humans.

BACKGROUND: Glutamine exhibits numerous beneficial effects in experimental and clinical studies. It has been suggested that these effects may be partly mediated by the conversion of glutamine into citrulline and arginine. The intestinal metabolism of glutamine appears to be crucial in this pathway. The present study was designed to establish the effect of the feeding route, enteral or parenteral, on the conversion of exogenously administered glutamine into citrulline and arginine at an organ level in humans, with a focus on gut metabolism. METHODS: Sixteen patients undergoing upper gastrointestinal surgery received an IV or enteral (EN) infusion of L-[2-(15)N]glutamine. Blood was sampled from a radial artery and from the portal and right renal vein. Amino acid concentrations and enrichments were measured, and net fluxes of [(15)N]-labeled substrates across the portal drained viscera (PDV) and kidneys were calculated from arteriovenous differences and plasma flow. RESULTS: Arterial [(15)N]glutamine enrichments were significantly lower during enteral tracer infusion (tracer-to-tracee ratio [labeled vs unlabeled substrate, TTR%] IV: 6.66 +/- 0.35 vs EN: 3.04 +/- 0.45; p < .01), reflecting first-pass intestinal metabolism of glutamine during absorption. Compared with IV administration, enteral administration of the glutamine tracer resulted in a significantly higher intestinal fractional extraction of [(15)N]glutamine (IV: 0.15 +/- 0.03 vs EN: 0.44 +/- 0.08 micromol/kg/h; p < .01). Furthermore, enteral administration of the glutamine tracer resulted in higher arterial enrichments of [(15)N]citrulline (TTR% IV: 5.52 +/- 0.44 vs EN: 8.81 +/- 1.1; p = .02), and both routes of administration generated a significant enrichment of [(15)N]arginine (TTR% IV: 1.43 +/- 0.12 vs EN: 1.68 +/- 0.18). This was accompanied by intestinal release of [(15)N]citrulline across the PDV, which was higher with enteral glutamine (IV: 0.38 +/- 0.07 vs EN: 0.72 +/- 0.11 micromol/kg/h; p = .02), and subsequent [(15)N]arginine release in both groups. CONCLUSIONS: In humans, the gut preferably takes up enterally administered glutamine compared with intravenously provided glutamine. The route of administration, enteral or IV, affects the quantitative conversion of glutamine into citrulline and subsequent renal arginine synthesis in humans.

Tolerance to increased supplemented dietary intakes of methionine in healthy older adults.

Background: l-Methionine (Met) is an essential amino acid for humans and is important for protein synthesis and the formation of polyamines and is involved in the synthesis of many metabolites, including homocysteine. Free-Met supplements have been claimed to have multiple positive effects; however, it remains unclear what the exact tolerance level is. With aging, Met metabolism changes, and increased plasma homocysteine is more apparent. High plasma concentrations of homocysteine are assumed to be associated with a high risk of developing atherosclerosis.Objective: We estimated the no-observed-adverse-effect level (NOAEL) and the lowest-observed-adverse-effect level (LOAEL) of supplemented, oral, free Met in healthy older adults by examining the increase in plasma homocysteine as the primary determinant.Design: We provided capsules with free Met to 15 healthy older adult subjects for 4 wk at climbing dosages of, on average, 9.2, 22.5, 46.3 and 91 mg · kg body weight-1 · d-1 with washout periods of 2 wk between each intake. Before, at 2 and 4 wk during, and 2 wk after each dosage, we studied a complete panel of biochemical blood variables to detect possible intolerance to increased Met intake. Plasma homocysteine and body composition were measured, and tolerance, quality of life, and cognitive function were assessed via questionnaires.Results: Plasma homocysteine was elevated with the highest dose of supplemented Met. The estimated NOAEL of supplemented Met was set at 46.3 mg · kg body weight-1 · d-1, and the estimated LOAEL of supplemented Met was set at 91 mg · kg body weight-1 · d-1 (on the basis of the actual intakes) in subjects independent of sex. No signs of intolerance were observed via questionnaires or other blood variables at the LOAEL. There were no meaningful changes in body composition.Conclusions: On the basis of plasma homocysteine, the NOAEL of supplemented Met intake is 46.3 and the LOAEL is 91 mg · kg body weight-1 · d-1 in healthy older adults. Both the NOAEL and LOAEL are not associated with meaningful effects on health and wellbeing. This trial was registered at clinicaltrials.gov as NCT02566434.

High Prevalence of Physical Frailty Among Community-Dwelling Malnourished Older Adults-A Systematic Review and Meta-Analysis.

BACKGROUND: Malnutrition and frailty are two geriatric syndromes that significantly affect independent living and health in community-dwelling older adults. Although the pathophysiology of malnutrition and physical frailty share common pathways, it is unknown to what extent these syndromes overlap and how they relate to each other. METHODS: A systematic review was performed resulting in a selection of 28 studies that assessed both malnutrition and frailty in community-dwelling older adults. Furthermore, a meta-analysis was performed on 10 studies that used Mini- Nutritional Assessment and the Fried frailty phenotype to estimate the prevalence of malnutrition within physical frailty and vice versa. RESULTS: In the systematic review, 25 of the 28 studies used the Mini-Nutritional Assessment (long or short form) for malnutrition screening. For frailty assessment, 23 of the 28 studies focused on the physical frailty phenotype, of which 19 followed the original Fried phenotype. Fifteen studies analyzed the association between malnutrition and frailty, which was significant in 12 of these. The meta-analysis included 10 studies with a total of 5447 older adults. In this pooled population of community-dwelling older adults [mean (standard deviation) age: 77.2 (6.7) years], 2.3% was characterized as malnourished and 19.1% as physically frail. The prevalence of malnutrition was significantly associated with the prevalence of physical frailty (P < .0001). However, the syndromes were not interchangeable: 68% of the malnourished older adults was physically frail, whereas only 8.4% of the physical frail population was malnourished. CONCLUSIONS: The systematic review and meta-analysis revealed that malnutrition and physical frailty in community-dwelling older adults are related, but not interchangeable geriatric syndromes. Two out of 3 malnourished older adults were physically frail, whereas close to 10% of the physically frail older adults was identified as malnourished.

Accurate perioperative flow measurement of the portal vein and hepatic and renal artery: a role for preoperative MRI?

BACKGROUND: Quantification of abdominal blood flow is essential for a variety of gastrointestinal and hepatic topics such as liver transplantation or metabolic flux measurement, but those need to be performed during surgery. It is not clear whether Duplex Doppler Ultrasound during surgery or MRI before surgery is the tool to choose. OBJECTIVE: To examine whether preoperative evaluation of abdominal blood flow using MRI could prove to be a useful and reliable alternative for the perioperative sonographic approach. METHODS: In this study portal and renal venous flow and hepatic arterial flow were sequentially quantified by preoperative MRI, preoperative and perioperative Duplex Doppler Ultrasound (DDUS). 55 Patients scheduled for major abdominal surgery were studied and methods and settings were compared. Additionally, average patient population values were compared. RESULTS: Mean (±SD) plasmaflow measured by perioperative DDUS, preoperative DDUS and MRI, respectively was 433±200/423±162/507±96 ml/min (portal vein); 96±70/74±41/108±91 ml/min (hepatic artery); 248±139/201±118/219±69 ml/min (renal vein). No differences between the different settings of DDUS measurement were detected. Equality of mean was observed for all measurements. Bland Altman Plots showed widespread margins. Hepatic arterial flow measurements correlated with each other, but portal and renal venous flow correlations were absent. CONCLUSIONS: Surgery and method (DDUS vs. MRI) do not affect mean flow values. Individual comparison is restricted due to wide range in measurements. Since MRI proves to be more reliable with respect to inter-observer variability, we recommend using mean MRI results in experimental setups.

Human taurine metabolism: fluxes and fractional extraction rates of the gut, liver, and kidneys.

Taurine is involved in numerous biological processes. However, taurine plasma level decreases in response to pathological conditions, suggesting an increased need. Knowledge on human taurine metabolism is scarce and only described by arterial-venous differences across a single organ. Here we present taurine organ fluxes using arterial-venous concentration differences combined with blood flow measurements across the 3 major organ systems involved in human taurine metabolism in patients undergoing hepatic surgery. In these patients, we collected blood from an arterial line, portal vein, hepatic vein, and renal vein, and determined blood flow of the hepatic artery, portal vein, and renal vein using Doppler ultrasound. Plasma taurine was determined by high-performance liquid chromatography, and net organ fluxes and fractional extraction rates were calculated. Seventeen patients were studied. No differences were found between taurine concentrations in arterial, portal venous, hepatic venous, and renal venous plasma. The only significant finding was a release of taurine by the portally drained viscera (P = .04). Our data show a net release of taurine by the gut. This probably is explained by the enterohepatic cycle of taurine. Future studies on human taurine metabolism are required to determine whether taurine is an essential aminosulfonic acid during pathological conditions and whether it should therefore be supplemented.

Gastric emptying, glucose metabolism and gut hormones: evaluation of a common preoperative carbohydrate beverage.

OBJECTIVE: To study the gastric-emptying rate and gut hormonal response of two carbohydrate-rich beverages. A specifically designed carbohydrate-rich beverage is currently used to support the surgical patient metabolically. Fruit-based beverages may also promote recovery, due to natural antioxidant and carbohydrate content. However, gastric emptying of fluids is influenced by its nutrient composition; hence, safety of preoperative carbohydrate loading should be confirmed. Because gut hormones link carbohydrate metabolism and gastric emptying, hormonal responses were studied. METHODS: In eight volunteers, gastric emptying rates of both 400 mL of a ready-to-use beverage (A: Nutricia preOp; 50.4 g carbohydrates-mainly polysaccharides; 260 mOsm/kg) and 400 mL over-the-counter fruit-based lemonade (B: Roosvicee Original; 48 g carbohydrates--mainly fruit-associated saccharides; 805 mOsm/kg) were determined scintigraphically (using hepatate Tc-99(m)) according to a crossover design. Plasma glucose, insulin, C-peptide, glucagon-like peptide (GLP-1), peptide YY, total glucagon, and ghrelin were studied. RESULTS: Gastric emptying showed no differences in residual volumes. Earlier onset in emptying for beverage A versus B was observed (trend), with significantly higher glucose, insulin, C-peptide, and glucagon responses at 15-90 min. GLP-1 was inversely related to residual volume. CONCLUSION: Fruit-based lemonade is a safe alternative for preoperative purposes. It induces a more limited glucose, insulin, and C-peptide response. Later onset in gastric emptying (B versus A: trend), lower glucagon release, and differences in beverage content and osmolarity may have contributed to those differences. Efficient emptying was reflected by early GLP-1 levels.

Enteral administration of alanyl-[2-(15)N]glutamine contributes more to the de novo synthesis of arginine than does intravenous infusion of the dipeptide in humans.

BACKGROUND: We previously confirmed in humans the existence of a pathway of glutamine into citrulline and arginine, which is preferentially stimulated by luminally provided glutamine. However, because glutamine is unstable, we tested this pathway with a stable dipeptide of glutamine. OBJECTIVES: The objectives were to explore whether alanyl-glutamine contributes to the synthesis of arginine in humans and whether this depends on the route of administration. DESIGN: The study was conducted under postabsorptive conditions during surgery. Sixteen patients received alanyl-[2-(15)N]glutamine enterally or intravenously together with intravenously administered stable-isotope tracers of citrulline and arginine. Blood was collected from an artery, the portal vein, a hepatic vein, and the right renal vein. Arterial and venous enrichments and (tracer) net balances of alanyl-glutamine and glutamine, citrulline, and arginine across the portal-drained viscera, liver, and kidneys were determined. Parametric tests were used to test results (mean +/- SEM). P < 0.05 was considered significant. RESULTS: Twice as much exogenous glutamine was used for the synthesis of citrulline when alanyl-glutamine was provided enterally (5.9 +/- 0.6%) than when provided intravenously (2.8 +/- 0.3%) (P < 0.01). Consequently, twice as much exogenous glutamine was used for the synthesis of arginine when alanyl-glutamine was provided enterally (5 +/- 0.7%) than when provided intravenously (2.4 +/- 0.2%) (P < 0.01). However, results at the organ level did not explain the differences due to route of administration. CONCLUSIONS: Alanyl-glutamine contributes to the de novo synthesis of arginine, especially when provided enterally. A stable-isotope study using a therapeutic dose of alanyl-glutamine is needed to investigate the clinical implications of this finding.

Glutamine is an important precursor for de novo synthesis of arginine in humans.

BACKGROUND: A metabolic relation exists between glutamine and arginine, 2 amino acids with properties that enhance the recovery of seriously ill patients. It is possible that glutamine exerts part of its beneficial effects by enhancing the availability of arginine. OBJECTIVES: We aimed to quantify under postabsorptive conditions the metabolic pathway of plasma glutamine into arginine via the intermediate citrulline and to establish the contribution of the kidneys to the synthesis of arginine. DESIGN: The study was conducted in patients during surgery. The metabolism of glutamine, citrulline, and arginine was studied by using intravenous administration of stable isotope tracers of the amino acids. Results were interpreted by using established equations. Parametric tests were used to test and correlate results. P < 0.05 was regarded as significant. RESULTS: Mean (+/-SE) whole-body plasma turnover rates of glutamine, citrulline, and arginine were 240 +/- 14, 6.2 +/- 0.6, and 42 +/- 2.9 micromol x kg(-1) x h(-1), respectively (P < 0.01). Plasma turnover of citrulline derived from glutamine was shown to be 5.1 +/- 0.7 micromol x kg(-1) x h(-1), and arginine derived from citrulline was shown to be 4.9 +/- 0.9 micromol x kg(-1) x h(-1) (P < 0.01). The contribution of plasma glutamine to plasma arginine derived from plasma citrulline was calculated to be 64%. The kidneys were observed to take up >50% of circulating plasma citrulline and to release equimolar amounts of arginine into plasma. CONCLUSIONS: This study shows that glutamine is an important precursor for the synthesis of arginine in humans. It also provides a firm basis for future studies exploring the effect of a treatment dose and the route of administration (enteral or parenteral) of glutamine.

The gut does not contribute to systemic ammonia release in humans without portosystemic shunting.

The gut is classically seen as the main source of circulating ammonia. However, the contribution of the intestines to systemic ammonia production may be limited by hepatic extraction of portal-derived ammonia. Recent data suggest that the kidney may be more important than the gut for systemic ammonia production. The aim of this study was to quantify the role of the kidney, intestines, and liver in interorgan ammonia trafficking in humans with normal liver function. In addition, we studied changes in interorgan nitrogen metabolism caused by major hepatectomy. From 21 patients undergoing surgery, blood was sampled from the portal, hepatic, and renal veins to assess intestinal, hepatic, and renal ammonia metabolism. In seven cases, blood sampling was repeated after major hepatectomy. At steady state during surgery, intestinal ammonia release was equaled by hepatic ammonia uptake, precluding significant systemic release of intestinal-derived ammonia. In contrast, the kidneys released ammonia to the systemic circulation. Major hepatectomy led to increased concentrations of ammonia and amino acids in the systemic circulation. However, transsplanchnic concentration gradients after major hepatectomy were similar to baseline values, indicating the rapid institution of a new metabolic equilibrium. In conclusion, since hepatic ammonia uptake exactly equals intestinal ammonia release, the splanchnic area, and hence the gut, probably does not contribute significantly to systemic ammonia release. After major hepatectomy, hepatic ammonia clearance is well preserved, probably related to higher circulating ammonia concentrations.