Niloofar Bazargan

Glutamine and the gastrointestinal tract.

The amino acid glutamine has become one of the most intensively studied nutrients in the field of nutrition and metabolic support. A variety of studies in cell culture systems, animal models of gut mucosal atrophy, injury/repair and adaptation and a limited number of clinical trials demonstrate trophic and cytoprotective effects of glutamine in small bowel and colonic mucosal cells. Although the routine clinical use of glutamine-enriched parenteral and enteral nutrient solutions remains controversial, available data demonstrate both the safety and metabolic and clinical efficacy of glutamine treatment in selected patient groups. Basic investigations are elucidating underlying mechanisms of glutamine action in intestinal cells. These will inform preclinical and clinical investigations designed to determine glutamine efficacy in selected gastrointestinal disorders. Emerging clinical trials will further define the utility of adjunctive glutamine supplementation as a component of specialized nutrition support in gastrointestinal disease.

Efficacy of Parenteral Nutrition Supplemented With Glutamine Dipeptide to Decrease Hospital Infections in Critically Ill Surgical Patients

BACKGROUND Nosocomial infections are an important cause of morbidity and mortality in the surgical intensive care unit (SICU). Clinical benefits of glutamine-supplemented parenteral nutrition may occur in hospitalized surgical patients, but efficacy data in different surgical subgroups are lacking. The objective was to determine whether glutamine-supplemented parenteral nutrition differentially affects nosocomial infection rates in selected subgroups of SICU patients. METHODS This was a double-blind, randomized, controlled study of alanyl-glutamine dipeptide-supplemented parenteral nutrition in SICU patients requiring parenteral nutrition and SICU care after surgery for pancreatic necrosis, cardiac, vascular, or colonic surgery. Subjects (n = 59) received isocaloric/isonitrogenous parenteral nutrition, providing 1.5 g/kg/d standard glutamine-free amino acids (STD-PN) or 1.0 g/kg/d standard amino acids + 0.5 g/kg/d glutamine dipeptide (GLN-PN). Enteral feedings were advanced as tolerated. Nosocomial infections were determined until hospital discharge. RESULTS Baseline clinical/metabolic data were similar between groups. Plasma glutamine concentrations were low in all groups and were increased by GLN-PN. GLN-PN did not alter infection rates after pancreatic necrosis surgery (17 STD-PN and 15 GLN-PN patients). In nonpancreatic surgery patients (12 STD-PN and 15 GLN-PN), GLN-PN was associated with significantly decreased total nosocomial infections (STD-PN 36 vs GLN-PN 13, P < .030), bloodstream infections (7 vs 0, P < .01), pneumonias (16 vs 6, P < .05), and infections attributed to Staphylococcus aureus (P < .01), fungi, and enteric Gram-negative bacteria (each P < .05). CONCLUSIONS Glutamine dipeptide-supplemented parenteral nutrition did not alter infection rates following pancreatic necrosis surgery but significantly decreased infections in SICU patients after cardiac, vascular, and colonic surgery.

Are Plasma Citrulline and Glutamine Biomarkers of Intestinal Absorptive Function in Patients With Short Bowel Syndrome

Sensitive biomarkers for intestinal absorptive function would be clinically useful in short bowel syndrome (SBS). Citrulline (Cit) is a product of the metabolism of glutamine (Gln) and derived amino acids by enterocytes. Cit is produced almost exclusively by the gut, which is also a major site of Gln metabolism. The goals of this study were to examine whether plasma Cit and Gln concentrations are biomarkers of residual small intestinal length and nutrient absorptive functions in adult SBS patients followed prospectively. We studied 24 stable adults with severe SBS receiving chronic parenteral nutrition (PN) in a double-blind, randomized trial of individualized dietary modification +/- recombinant human growth hormone (GH). During a baseline week, intestinal absorption studies (% absorption of fluid, kcal, nitrogen, fat, carbohydrate, sodium, phosphorus, and magnesium) were performed and concomitant plasma Cit and Gln concentrations determined. Individualized dietary modification and treatment with subcutaneous injection of placebo (n = 9) or GH (0.1 mg/kg daily x 21 days, then 3 times/week; n = 15) were then begun. PN weaning was initiated after week 4 and continued as tolerated for 24 weeks. Repeat plasma amino acid determination and nutrient absorption studies were performed at weeks 4 and 12. Residual small bowel length at baseline was positively correlated with baseline plasma Cit (r = 0.467; p = .028). However, no significant correlations between absolute Cit or Gln concentrations and the percent absorption of nutrient substrates at any time point were observed. Similarly, no correlation between the change in Cit or GLN concentration and the change in % nutrient absorption was observed (baseline vs weeks 4 and 12, respectively). By weeks 12 and 24, 7 and 13 subjects were weaned completely from PN, respectively. However, baseline plasma Cit or Gln did not predict PN weaning at these time points. We concluded that plasma Cit (but not Gln) concentrations appeared to be an indicator of small intestinal length in adult SBS. However, neither plasma Cit nor Gln was a biomarker for intestinal absorptive function in this cohort of patients with SBS.

Metabolic effects of enteral versus parenteral alanyl-glutamine dipeptide administration in critically ill patients receiving enteral feeding: a pilot study.

BACKGROUND Glutamine (Gln) may become conditionally indispensable during critical illness. The short-term metabolic effects of enteral versus parenteral Gln supplementation are unknown in this clinical setting. OBJECTIVES We studied metabolic effects of intravenous (i.v.) alanyl-Gln dipeptide (AG) supplementation and enteral (e.n.) AG supplementation on plasma Gln concentration, antioxidant status, plasma lymphocyte subset number, gut permeability and nitrogen balance in adult critically ill patients requiring tube feeding compared to a control group not receiving Gln supplementation. METHODS In a double-blind, pilot clinical trial, 44 medical and surgical ICU patients received identical Gln-free tube feedings 24 h/day and were randomized to either isonitrogenous control (n=15), e.n. AG (n=15) or i.v. AG (n=14) groups (AG). Twelve patients were discontinued from the study. The goal AG dose was 0.5 g/kg/day. Biochemical and metabolic endpoints were measured at baseline and on day 9 (plasma Gln, antioxidant indices, lymphocyte subsets; serum IGF-1 and IGF-binding protein-3; intestinal permeability). Nitrogen balance was determined between study days 6 and 8. RESULTS Illness severity indices, clinical demographics, enteral energy and nitrogen intake and major biochemical indices were similar between groups during study. Plasma Gln was higher in the i.v. AG (565+/-119 microM, mean+/-SEM) vs the e.n. AG (411+/-27 microM) group by day 9 (p=0.039); however, subjects in the i.v. AG group received a higher dose of AG (i.v. AG 0.50 versus e.n. AG 0.32+/-0.02 g/kg/day; p<0.001). E.n. AG subjects showed a significant increase in plasma alpha-tocopherol levels over time and maintained plasma gamma-tocopherol concentrations. There were no differences between groups for plasma concentrations of vitamin C, glutathione, malondialdehyde (MDA), T-lymphocyte subsets, intestinal permeability or nitrogen balance. CONCLUSIONS This study showed that alanyl-Gln administration by enteral or parenteral routes did not appear to affect antioxidant capacity or oxidative stress markers, T-lymphocyte subset (CD-3, CD-4, CD-8) number, gut barrier function or whole-body protein metabolism compared to unsupplemented ICU patients requiring enteral tube feeding. Enteral Gln appeared to maintain plasma tocopherol levels in this pilot metabolic study.

Growth Hormone Favorably Affects Bone Turnover and Bone Mineral Density in Patients With Short Bowel Syndrome Undergoing Intestinal Rehabilitation

BACKGROUND Patients with short bowel syndrome (SBS) have a high prevalence of metabolic bone disease due to nutrient malabsorption and potential effects of parenteral nutrition (PN). Human growth hormone (hGH) has been shown in some studies to have anabolic effects on bone, but hGH effects on bone in patients with SBS are unknown. METHODS Adults with PN-dependent SBS underwent a 7-day period of baseline studies while receiving usual oral diet and PN and then began receiving modified diets designed to improve nutrient absorption and daily oral calcium/vitamin D supplements (1500 mg elemental calcium and 600 IU vitamin D, respectively). Subjects were randomized to receive in a double-blind manner either subcutaneous (sc) saline placebo as the control or hGH (0.1 mg/kg/d for 3 weeks, then 0.1 mg/kg 3 days a week for 8 subsequent weeks). Open-label hGH was given from week 13 to week 24 in subjects who required PN after completion of the 12-week double-blind phase. Markers of bone turnover (serum osteocalcin and urinary N-telopeptide [NTX]), vitamin D nutriture (serum calcium, 25-hydroxyvitamin D [25-OH D] and parathyroid hormone [PTH] concentrations), and intestinal calcium absorption were measured at baseline and at weeks 4 and 12. Dual x-ray absorptiometry (DXA) of the hip and spine was performed to determine bone mineral density (BMD) at baseline and weeks 12 and 24. RESULTS The majority of subjects in each group exhibited evidence of vitamin D deficiency at baseline (25-OH D levels<30 ng/mL; 78% and 79% of control and hGH-treated subjects, respectively). Subjects treated with hGH demonstrated a significant increase from baseline in serum osteocalcin levels at 12 weeks (+62%; p<.05). The levels of NTX were increased over time in the hGH-treated group; however, this did not reach statistical significance. Both NTX and osteocalcin remained unchanged in control subjects. BMD of the spine and total hip was unchanged in subjects treated with placebo or hGH at 24 weeks. However, femoral neck BMD was slightly but significantly decreased in the placebo group at this time point but remained unchanged from baseline in the hGH-treated subjects. CONCLUSIONS hGH therapy significantly increased markers of bone turnover during the initial 3 months of therapy and stabilized femoral neck bone mass over a 6-month period in patients with severe SBS undergoing intestinal rehabilitation.

Nutrient Intake From Habitual Oral Diet in Patients With Severe Short Bowel Syndrome Living in the Southeastern United States

OBJECTIVES Little data are published on the habitual home oral diet of patients with short bowel syndrome (SBS). METHODS We assessed nutrient intake from oral food and beverages in 19 stable patients with severe SBS who live in the southeastern United States. Intestinal absorption of energy, fat, nitrogen (N), and carbohydrate (CHO) was determined in a metabolic ward. RESULTS We studied 12 women and 7 men, age 48 +/- 3 y of age (mean +/- SE) receiving parenteral nutrition for 31 +/- 8 mo following massive small bowel resection (118 +/- 25 cm residual small bowel). The patients demonstrated severe malabsorption of energy (59 +/- 3% of oral intake), fat (41 +/- 5%), N (42 +/- 5%) and CHO (76 +/- 3%). Oral energy intake was 2656 +/- 242 kcal/d (39 +/- 3 kcal/kg/d) and oral protein intake was 1.4 +/- 0.1 g/kg/d. Food/beverage intake constituted 49 +/- 4% of total (enteral plus parenteral) daily fluid intake, 66 +/- 4% of total daily kcal and 58 +/- 5% of total daily N intake. Oral fat intake averaged 92 +/- 11 g/day ( approximately 35% of total oral energy). Oral fluid intake averaged 2712 +/- 240 ml/d, primarily from water, soft drinks, sweet tea and coffee. Simple sugars comprised 42 +/- 3% of oral CHO intake. Usual dietary intake of multiple micronutrients were below the Recommended Dietary Allowances (RDA) in a large percentage of patients: vitamin A (47%), vitamin D (79%), vitamin E (79%), vitamin K (63%), thiamine (42%), vitamin B6 (68%), vitamin B12 (11%), vitamin C (58%), folate (37%), iron (37%), calcium (63%), magnesium (79%) and zinc (68%). Only seven patients (37%) were taking oral multivitamin-mineral supplements and only six subjects (32%) were taking oral iron and calcium supplements, respectively. CONCLUSION In these SBS patients, an oral diet provided a significant proportion of daily nutrient intake. The types of foods and fluids consumed are likely to worsen malabsorption and thus increase PN requirements. Oral intake of essential micronutrients was very low in a significant proportion of these individuals.

Prospective analysis of serum carotenoids, vitamin A, and tocopherols in adults with short bowel syndrome undergoing intestinal rehabilitation.

OBJECTIVE Carotenoids, vitamin A, and tocopherols serve important roles in many key body functions. However, availability of these compounds may be decreased in patients with short bowel syndrome (SBS) due to decreased oral intake of fruits and vegetables and/or decreased intestinal absorption. Little information is available on serum concentrations of carotenoids, vitamin A, and tocopherols during chronic parenteral nutrition (PN) or during PN weaning. The aim of this study was to prospectively examine serum concentrations of a wide variety of carotenoids, vitamin A, and tocopherols in patients with SBS undergoing an intensive 12-wk intestinal rehabilitation program. METHODS Twenty-one PN-dependent adult patients with SBS were enrolled in a 12-wk intestinal rehabilitation program, which included individualized dietary modification, multivitamin supplementation, and randomization to receive subcutaneous placebo (n = 9) or human growth hormone (0.1 mg . kg(-1) . d(-1); n = 12). PN weaning was initiated after week 4 and advanced as tolerated. Serum concentrations of carotenoids, vitamin A, and tocopherols were determined at baseline and at weeks 4 and 12. RESULTS A significant percentage of subjects exhibited low serum concentrations for carotenoids and alpha-tocopherol at study entry, and a few subjects had low concentrations of retinol (5%). Carotenoid and vitamin A valves did not improve over time, while alpha-tocopherol levels rose. Serum alpha-tocopherol concentration was negatively associated with PN lipid dose (r = -0.34, P < 0.008). CONCLUSION Patients with SBS are depleted in diet-derived carotenoids despite oral and intravenous multivitamin supplementation and dietary adjustment during intestinal rehabilitation and PN weaning. Reduction of PN lipid infusion may improve serum alpha-tocopherol concentrations.