The effect of a single, large bolus of vitamin D in healthy adults over the winter and following year: a randomized, double-blind, placebo-controlled trial.

BACKGROUND/OBJECTIVES: Although single, high doses of vitamin D effectively maintain vitamin D sufficiency in several populations, no studies have evaluated healthy adults over winter, during which vitamin D status declines. This study investigated whether high-dose vitamin D3 given once to healthy adults before winter will (1) prevent the wintertime decline in vitamin D status, (2) promote vitamin D sufficiency 1 year following the dose and (3) prevent the rise of parathyroid hormone (PTH) concentrations. SUBJECTS/METHODS: In this double-blind, placebo-controlled trial, we assessed plasma 25(OH)D and PTH concentrations at baseline, 5, 90 and 365 days after drug administration in 28 healthy adults. In all, >80% of subjects returned at each time point. RESULTS: At baseline, the young, healthy participants had a mean plasma 25(OH)D concentration of 17.5±6.1 ng/ml. Only two subjects exhibited plasma 25(OH)D concentrations >30 ng/ml. At 5 days, subjects randomized to vitamin D3 had a higher mean plasma 25(OH)D concentration compared with the placebo group (39.1 vs 19.1 ng/ml, P<0.001). Plasma 25(OH)D concentrations returned to baseline at 90 and 365 days in the vitamin D3 group and remained unchanged in the placebo group. PTH and calcium concentrations were unrelated to changes in 25(OH)D levels and similar between groups over time. CONCLUSIONS: A dose of 250,000 IU of vitamin D3 given once in November resulted in a robust increase in plasma 25(OH)D after 5 days, but it was unable to sustain this increase after 90 days. A larger or more frequent dosing regimen may be needed for long-term vitamin D sufficiency.

Effects of high-dose cholecalciferol on serum markers of inflammation and immunity in patients with early chronic kidney disease.

BACKGROUND/OBJECTIVES: Vitamin D has anti-inflammatory and immune-regulating properties. We aimed to determine if high-dose cholecalciferol supplementation for 1 year in subjects with early chronic kidney disease (CKD) improved circulating markers of inflammation and immunity. SUBJECTS/METHODS: In this double-blind, randomized, placebo-controlled trial, 46 subjects with early CKD (stages 2 and 3) were supplemented with oral cholecalciferol (50 000 IU weekly for 12 weeks followed by 50 000 IU every other week for 40 weeks) or a matching placebo for 1 year. Serum tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1 (MCP-1), interferon gamma-induced protein-10 and neutrophil gelatinase-associated lipocalin were measured at baseline, 12 weeks and 1 year. Serum cathelicidin (LL-37) was measured at baseline and 12 weeks. An in vitro experiment was performed to investigate the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment on MCP-1 secretion in THP-1 monocytes activated with lipopolysaccharide (LPS) and Pseudomonas aeruginosa. RESULTS: By 12 weeks, serum MCP-1 decreased in the cholecalciferol group (66.2±2.5 to 60.8±2.6 pg/ml, group-by-time interaction P=0.02) but was not different from baseline at 1 year. Other markers of inflammation and immunity did not change. In vitro, LPS- and Pseudomonas-activated monocytes treated with 1,25(OH)2D3 had significantly less MCP-1 secretion compared with untreated cells. CONCLUSIONS: High-dose cholecalciferol decreased serum MCP-1 concentrations by 12 weeks in patients with early CKD, although the decrease was not maintained for the remainder of the year. In vitro results confirm an MCP-1-lowering effect of vitamin D. Future studies should determine if vitamin D-mediated reductions in MCP-1 concentrations reflect improved clinical outcomes.

Glutamine supplementation in cancer patients receiving bone marrow transplantation and high dose chemotherapy.

Glutamine supplementation of enteral and parenteral nutrition support has received increased attention in the research community over the past decade. Glutamine may become a conditionally essential nutrient during certain catabolic states, including after bone marrow transplantation (BMT). The administration of enteral or parenteral glutamine seems safe and also potentially efficacious in some patient groups undergoing intensive treatment for cancer. Studies indicate that adjunctive glutamine treatment may improve nitrogen retention, decrease clinical infection and length of hospital stay and reduce the incidence and severity of mucositis after BMT and high dose chemotherapy. Although not all studies demonstrate benefit, there are sufficient positive data to suggest that this nutrient should be considered in the metabolic support of many individuals undergoing the catabolic process of marrow transplantation. Given the available data, randomized, double-blind, controlled clinical trials of glutamine-enriched nutrition in patients receiving BMT and high dose chemotherapy protocols are indicated to further define the utility of this amino acid as adjunctive therapy. Studies of glutamine nutrition combined with current combinations of cytoreductive agents and hematopoietic growth factors in BMT will be particularly pertinent.

Plasma antioxidant status after high-dose chemotherapy: a randomized trial of parenteral nutrition in bone marrow transplantation patients.

BACKGROUND: Chemotherapy and radiation therapy result in increased free radical formation and depletion of tissue antioxidants. It is not known whether parenteral nutrition (PN) administered during bone marrow transplantation (BMT) supports systemic antioxidant status. OBJECTIVE: The aims of the study were to determine 1) whether high-dose chemotherapy decreases concentrations of major circulating antioxidants in patients undergoing BMT and 2) whether administration of standard PN maintains systemic antioxidant concentrations compared with PN containing micronutrients and minimal lipids alone. DESIGN: Twenty-four BMT patients were randomly assigned to receive either standard PN containing conventional amounts of dextrose, amino acids, micronutrients, and lipid (120 kJ/d) or a solution containing only micronutrients (identical to those in standard PN) and a small amount of lipid (12 kJ/d). Plasma antioxidant status was measured before conditioning therapy and serially at days 1, 3, 7, 10, and 14 after BMT. RESULTS: Plasma glutathione (GSH) and alpha- and gamma-tocopherol concentrations decreased and the GSH redox state became more oxidized after conditioning chemotherapy. Plasma cysteine concentrations were unchanged, whereas cystine concentrations increased. Plasma vitamin C and zinc concentrations and GSH peroxidase activity increased over time. Plasma alpha-tocopherol concentrations were lower in patients given standard PN. There were no differences in other plasma antioxidants between groups. CONCLUSIONS: A significant decline in GSH-glutathione disulfide, cysteine-cystine, and vitamin E status occurs after chemotherapy and BMT. Standard PN does not improve antioxidant status compared with administration of micronutrients alone. Further evaluation of PN formulations to support patients undergoing high-dose chemotherapy and BMT are needed.

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.

Glutamine in the support of patients following bone marrow transplantation.

Bone marrow transplantation is being utilized with increasing frequency in the treatment of patients with malignancy; it is also being applied to the treatment of patients with genetic diseases and as an adjunct to solid organ transplantation. The high dose cytotoxic chemotherapy, often accompanied by total body irradiation, results in severe catabolism, disruption of the gastrointestinal mucosa and marked immunosuppression. A variety of studies show that the supplementation of the amino acid glutamine, by the enteral or parenteral route, as either the free or dipeptide form, appears safe and efficacious in patients undergoing bone marrow transplantation. Further double-blind controlled clinical trials of glutamine supplementation in patients undergoing bone marrow transplantation and receiving more contemporary treatment, which often includes the administration of novel combinations of cytoreductive agents and hematopoietic growth factors, are warranted.

Effects of glutamine supplementation on circulating lymphocytes after bone marrow transplantation: a pilot study.

Glutamine (Gln) is an important nutrient substrate for lymphocytes and macrophages in vitro. This pilot study evaluated effects of Gln supplementation on circulating lymphocytes and lymphocyte subsets after allogeneic bone marrow transplantation (BMT). Adult patients received either parenteral nutrition supplemented by L-Gln (Gln-PN) or standard Gln-free PN after BMT. Leukocyte and total lymphocyte counts were determined during hospitalization, and flow cytometry studies of peripheral mononuclear cells were performed 1 to 2 weeks after hospital discharge. The Gln-PN group demonstrated a higher percentage of blood lymphocytes during hospitalization. At flow cytometry, patients who received Gln-PN had an increased total lymphocyte count (332 +/- 50 versus 590 +/- 71 cells/microL, P = 0.010); greater numbers of total T lymphocytes (54 +/- 19 versus 229 +/- 70 cells/microL, P = 0.030); and higher CD4+ and CD8+ T-lymphocyte counts in peripheral blood compared with controls. Gln-PN may support lymphocyte recovery after BMT.

Epidermal growth factor and human growth hormone accelerate adaptation after massive enterectomy in an additive, nutrient-dependent, and site-specific fashion.

BACKGROUND: After massive enterectomy (ME), remnant intestine undergoes compensatory adaptation. Epidermal growth factor (EGF) and human growth hormone (hGH) have each been shown to enhance total length small intestine nutrient transport after ME. This study aims to determine the differential effects of EGF and hGH on proximal and distal small intestinal remnants after ME. METHODS: New Zealand white rabbits underwent 70% mid-jejunoileal resection. After 1 week, animals received hGH (0.2 mg/kg/day), EGF (1.5 micrograms/kg/hr), hGH + EGF, or vehicle (equal volume) for 7 days. Sodium-dependent uptake of glucose, glutamine, alanine, leucine, and arginine into brush border membrane vesicles was quantitated. Serum insulin-like growth factor-I concentrations as well as proximal and distal villus and microvillus heights were measured. IGF binding protein-3 and -4 mRNA expression was determined in full-thickness proximal and distal gut remnants. RESULTS: Concomitant hGH and EGF treatment up-regulates glucose (100%), glutamine (80%), and leucine (60%) transport in the proximal remnant; alanine (150%) and arginine (400%) transport in the distal remnant; and microvillus height (25% to 35%) both proximally and distally. Serum IGF-I levels and gross villus heights were not different among groups. CONCLUSIONS: Co-infusion of hGH and EGF accelerates intestinal adaptation after ME in an additive, nutrient-dependent, and site-specific fashion via enhanced nutrient transport as well as microvillus hypertrophy.

Adjunctive therapies in nutritional support.

The need for new therapeutic approaches to improve the metabolic and clinical efficacy of nutritional therapy has been increasingly emphasized. The field of nutrition support of catabolic, malnourished, or hospitalized patients is rapidly evolving in response to the beneficial effects observed with adjunctive therapies in animal models and in emerging clinical investigations. Enteral nutrition is being increasingly administered, and enteral diets are being tested to improve gut structure and function. Adjunctive therapies in enteral and parenteral nutrition are being actively investigated. These include administration of recombinant growth factors and anabolic steroid hormones (e.g., growth hormone, oxandrolone); conditionally essential amino acids (e.g., arginine, glutamine); novel lipid products (e.g., structured lipids, fish oils); nutrient antioxidants (e.g., vitamins C and E); and combinations of these approaches. It is likely that current methods of enteral and parenteral nutrition support will evolve in response to the results of these research studies.

Gut adaptation and the insulin-like growth factor system: regulation by glutamine and IGF-I administration.

Intestinal adaptation after extensive small bowel resection in rats is augmented by the provision of diets supplemented with the amino acid glutamine (Gln) or by administration of insulin-like growth factor-I (IGF-I). The goal of this study was to investigate potential synergistic effects of Gln and IGF-I on postresection ileal hyperplasia. Rats underwent 80% small bowel resection (SBR) and then were fed low-Gln or L-Gln-enriched diets and subcutaneously given recombinant human IGF-I or vehicle for 7 days. Gln and IGF-I each significantly enhanced adaptive ileal hyperplasia (DNA content) compared with rats receiving vehicle and low-Gln diet. Ileal DNA content was highest when IGF-I was administered together with Gln supplementation. Combined IGF-I plus Gln synergistically increased ileal weight and protein content. This was associated with higher plasma concentrations of IGF-I and Gln than observed when IGF-I or Gln was given individually. Ileal IGF-I mRNA expression rose nearly twofold during gut adaptation after SBR; this response was augmented with IGF-I administration but was unaltered by Gln feeding. In contrast, dietary Gln, but not IGF-I therapy, prevented a decrease in hepatic IGF-I mRNA induced by SBR. We conclude that parenteral IGF-I and enteral Gln have both individual and synergistic effects on ileal adaptation after massive small intestinal resection. These findings support the concept that specific gut-trophic nutrients and growth factors may be combined to enhance intestinal adaptation and possibly reduce the severity of short bowel syndrome after intestinal resection.

Glutamine: from basic science to clinical applications.

Glutamine (Gln) has been one of the most intensively studied nutrients in the field of nutrition support in recent years. Interest in provision of Gln derives from animal studies in models of catabolic stress, primarily in rats. Enteral or parenteral Gln supplementation improved organ function and/or survival in most of these investigations. These studies have also supported the concept that Gln is a critical nutrient for the gut mucosa and immune cells. Recent molecular and protein chemistry studies are beginning to define the basic mechanism involved in Gln action in the gut, liver and other cells and organs. Double-blind prospective clinical investigations to date suggest that Gln-enriched parenteral or enteral feedings are generally safe and effective in catabolic patients. Intravenous Gln (either as the L-amino acid or as Gln-dipeptides) has been shown to increase plasma Gln levels, exert protein anabolic effects, improve gut structure and/or function and reduce important indices of morbidity, including infection rates and length of hospital stay in selected patients subgroups. Additional blinded studies of Gln administration in catabolic patients and increasing clinical experience with Gln-enriched nutrient products will determine whether routine Gln supplementation should be given in nutrition support, and to whom. Taken together, the data obtained over the past decade or so of intensive research on Gln nutrition demonstrate that this amino acid is an important dietary nutrient and is probably conditionally essential in humans in certain catabolic conditions.

Growth hormone, glutamine, and a modified diet enhance nutrient absorption in patients with severe short bowel syndrome.

BACKGROUND: Massive loss of intestinal surface area results in the short bowel syndrome characterized by malabsorption of fluid, electrolytes, and other nutrients. Although the remaining bowel undergoes morphological and functional adaptation, often these changes are inadequate to support the individual by enteral feedings, and parenteral nutrition is required to prevent dehydration, electrolyte disturbances, and malnutrition. Substances such as growth hormone, glutamine, and fiber exert bowel-specific trophic effects and either directly or indirectly influence nutrient absorption. This study was undertaken to determine whether the co-administration of exogenous growth hormone, supplemental glutamine, and a modified fiber-containing diet could enhance nutrient absorption in patients who had undergone massive intestinal resection. METHODS: Ten patients (5 men, 5 women, aged 43 +/- 4 years) with short bowel syndrome were studied 6 +/- 1 years after surgical resection. All patients were admitted to the Clinical Research Center for a 28-day period; the first week served as a control period when nutritional (enteral and parenteral) and medical management simulated usual home therapy. Thereafter, eight patients received exogenous growth hormone, supplemental glutamine, and a modified high-carbohydrate, high-fiber diet. Two patients were treated with the modified diet alone. The efficiency of net nutrient absorption (percent absorbed) for total calories, protein, fat, carbohydrate, water, and sodium was calculated from the measured nutrient intake and stool losses. RESULTS: Three weeks of treatment with growth hormone, glutamine, and a modified diet increased total caloric absorption from 60.1 +/- 6.0% to 74.3 +/- 5.0% (p < or = .003), protein absorption from 48.8 +/- 4.8% to 63.0 +/- 5.4% (p < or = .006), and carbohydrate absorption from 60.0 +/- 9.8% to 81.5 +/- 5.3% (p < or = .02). Fat absorption did not change (61.0 +/- 5.3% to 60.3 +/- 7.9%, p = NS). Water and sodium absorption increased from 45.7 +/- 6.7% to 65.0 +/- 7.3% (p < or = .002) and from 49.0 +/- 9.8% to 69.6 +/- 6.5% (p < or = .04), respectively. These absorptive changes resulted in a decrease in stool output (1,783 +/- 414 g/d control period vs 1,308 +/- 404 g/d third week of treatment, p < or = .05). Treatment with diet alone did not influence nutrient absorption or stool output. CONCLUSIONS: The combined administration of growth hormone, glutamine, and a modified diet enhanced nutrient absorption from the remnant bowel after massive intestinal resection. These changes occurred in a group of patients that had previously failed to adapt to the provision of enteral nutrients. This therapy may offer an alternative to long-term dependence on total parenteral nutrition for patients with severe short bowel syndrome.

Adjunctive human growth hormone therapy in nutrition support: potential to limit septic complications in intensive care unit patients.

A large number of studies suggest that growth hormone (GH) modulates immune cell number and function. For example, GH administration in vitro or in animal models enhances antibody synthesis, increases T-lymphocyte proliferation, augments cytotoxic activity of natural killer cells, up-regulates priming of peritoneal and alveolar macrophages, and increases survival rates after infectious challenge. Similar effects on immune cells have been observed with insulinlike growth factor I (IGF-I), a major mediator of GH's anabolic actions. In critically ill patients, the administration of recombinant human GH improves nitrogen and mineral retention, enhances protein synthesis, and reduces urea generation. However, only limited data are available on the modulation of immune function and infection rates with GH treatment in catabolic patients. Limited studies in burn patients have shown improved wound healing and shortened hospital stay with GH therapy. Growth hormone was recently shown to improve cell-mediated immune responses and to maintain serum immunoglobulin concentrations after abdominal surgery in clinically stable patients. The immunomodulatory effects of GH administration may potentially limit septic complications in the intensive care unit setting. However, controlled studies in well-defined patient groups are needed to evaluate the potential beneficial effects of GH on immune function and infection risk in critically ill patients.

A cost-evaluation of glutamine-supplemented parenteral nutrition in adult bone marrow transplant patients.

OBJECTIVE: In a randomized, double-blind, prospective clinical trial, we evaluated the metabolic effects of glutamine-supplemented parenteral nutrition in patients with bone marrow transplants. We compared hospital charge and cost data for the two groups of patients in the trial. DESIGN: Retrospective review. SETTING: Bone Marrow Transplant Unit, Brigham and Women's Hospital, Boston, Mass. SUBJECTS: Forty-three patients admitted to the Bone Marrow Transplant Unit were assigned randomly to receive either standard parenteral nutrition or an isocaloric, isonitrogenous parenteral nutrition solution containing glutamine starting on day 1 after bone marrow transplant. The two groups were well matched for diagnosis, antineoplastic treatment, and sex. MEASURES: The primary clinical end points evaluated were nitrogen balance, length of hospitalization, incidence of infection, and results of microbial culture. After completion of the study, we compared the hospital charges for the categories of room and board, surgery, laboratory, pharmacy, radiology, ancillary, and miscellaneous between the two groups of patients. STATISTICAL ANALYSIS PERFORMED: The two groups were compared using the unpaired t test or Mann-Whitney test for nonparametric measurements. A P value of < .05 was considered significant. RESULTS: Nitrogen balance improved in the glutamine-supplemented group compared with control subjects (-1.4 +/- 0.5 g/day vs 4.2 +/- 1.2 g/day, respectively; P = .002). Length of hospitalization was significantly shorter in the glutamine-supplemented group than in the control group (29 +/- 1 day vs 36 +/- 2 days, respectively; P = .017). The incidence of positive microbial cultures and clinical infection was also significantly lower with glutamine supplementation. Hospital charges were $21,095 per patient less in the glutamine-supplemented group compared with charges for patients who received standard therapy. Room and board charges were significantly different: $51,484 +/- 2,647 for the glutamine-supplemented group vs $61,591 +/- 3,588 in the control group (P = .02). CONCLUSION: This intervention study using a new therapy demonstrated clinical and nutritional benefits to patients and cost savings to the hospital.

Growth hormone administration during nutritional support: what is to be gained?

Studies over the past three decades have documented the protein-anabolic effects of human growth hormone (GH) administration in malnourished or critically ill patients. The availability of recombinant GH has facilitated clinical investigation on the metabolic and clinical effects of this peptide in ICU settings. These studies demonstrate that GH improves nutrient utilization efficiency in critically ill patients. Recent randomized, controlled trials document improved wound healing with GH therapy in both adult and pediatric burn patients and reduced length of hospital stay in pediatric burn injury. However, little data have been published on functional or clinical outcome variables in other groups of catabolic patients treated with GH. Administration of growth factors in combination with specialized nutrition represents a novel strategy that may improve outcomes in critically ill patients. Additional clinical studies are needed to further define the safety, functional benefits, cost-effectiveness, and clinical utility of GH use in catabolic patients.

Anabolic therapy with growth hormone accelerates protein gain in surgical patients requiring nutritional rehabilitation.

OBJECTIVE: The authors investigated the effects of exogenous growth hormone (GH) on protein accretion and the composition of weight gain in a group of stable, nutritionally compromised postoperative patients receiving standard hypercaloric nutritional therapy. SUMMARY BACKGROUND DATA: A significant loss of body protein impairs normal physiologic functions and is associated with increased postoperative complications and prolonged hospitalization. Previous studies have demonstrated that standard methods of nutritional support enhance the deposition of fat and extracellular water but are ineffective in repleting body protein. METHODS: Fourteen patients requiring long-term nutritional support for severe gastrointestinal dysfunction received standard nutritional therapy (STD) providing approximately 50 kcal/kg/day and 2 g of protein/kg/day during an initial 7-day equilibrium period. The patients then continued on STD (n = 4) or, in addition, received GH 0.14 mg/kg/day (n = 10). On day 7 of the equilibrium period and again after 3 weeks of treatment, the components of body weight were determined; these included body fat, mineral content, lean (nonfat and nonmineral-containing tissue) mass, total body water, extracellular water (ECW), and body protein. Daily and cumulative nutrient balance and substrate oxidation studies determined the distribution, efficiency, and utilization of calories for protein, fat, and carbohydrate deposition. RESULTS: The GH-treated patients gained minimal body fat but had significantly more lean mass (4.311 +/- 0.6 kg vs. 1.988 +/- 0.2 kg, p < or = 0.03) and more protein (1.417 +/- 0.3 kg vs. 0.086 +/- 0.1 kg, p < or = 0.03) than did the STD-treated patients. The increase in lean mass was not associated with an inappropriate expansion of ECW. In contrast, patients receiving STD therapy tended to deposit a greater proportion of body weight as ECW and significantly more fat than did GH-treated patients (1.004 +/- 0.3 kg vs. 0.129 +/- 0.2 kg, p < 0.05). GH administration altered substrate oxidation (respiratory quotient = 0.94 +/- 0.02 GH vs. 1.17 +/- 0.05 STD, p < or = 0.0002) and the use of available energy, resulting in a 66% increase in the efficiency of protein deposition (13.37 +/- 0.8 g/1000 kcal vs. 8.04 g +/- 3.06 g/1000 kcal, p < or = 0.04). CONCLUSIONS: GH administration accelerated protein gain in stable adult patients receiving aggressive nutritional therapy without a significant increase in body fat or a disproportionate expansion of ECW. GH therapy accelerated nutritional repletion and, therefore, may shorten the convalescence of the malnourished patient requiring a major surgical procedure.

Patients receiving glutamine-supplemented intravenous feedings report an improvement in mood.

Nutritional effects have traditionally focused on outcomes, such as nitrogen balance, wound healing, or muscle strength. Little emphasis has been placed on how biochemical or physical improvements translate into functional changes as perceived by the patient. Because glutamine (GLN)-supplemented nutrition promotes protein synthesis and improves nitrogen balance, we assessed the mood of individuals participating in a randomized controlled blinded trial receiving GLN solutions. Patients (n = 23) undergoing marrow transplantation were randomized by the research pharmacist to receive either standard total parenteral nutrition (TPN) (control) or GLN-containing TPN (40 g of glutamine total). The solutions were isocaloric and isonitrogenous and were administered until the patient was eating 50% of estimated requirements. Before TPN and on admission to the hospital, the patient completed the Profile of Mood States questionnaire, a standardized test quantifying the degree of tension, depression, anger, vigor, fatigue, and confusion. The patient completed the questionnaire again at the end of TPN near discharge. The tests were scored and the change from baseline for each mood for both groups of patients was calculated at the completion of TPN. The scores for vigor in the control group (delta scores) decreased over the course of hospitalization as would be expected with a serious illness. The group receiving glutamine TPN, however, essentially showed little change in vigor from baseline and the delta score was significantly different from the control group (delta vigor score -0.85 +/- 2.1 in the glutamine group vs. -5.90 +/- 1.7 in the control group; p = .07).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. A randomized, double-blind, controlled study.

OBJECTIVE: To determine whether glutamine-supplemented parenteral nutrition improves nitrogen retention and reduces hospital morbidity compared with standard parenteral nutrition after bone marrow transplantation. DESIGN: Double-blind, randomized, controlled clinical trial. SETTING: University teaching hospital. PATIENTS: Forty-five adults receiving allogeneic bone marrow transplants for hematologic malignancies. INTERVENTION: Parenteral nutrition was initiated the day after bone marrow transplantation (day 1). The experimental solution was supplemented with L-glutamine (0.57 g/kg body weight per day) and provided estimated requirements for energy and protein. The control solution was a standard, glutamine-free, isonitrogenous, isocaloric formula. MEASUREMENTS: Nitrogen balance was determined between days 4 and 11 in the initial 23 patients. The incidence of clinical infection and microbial colonization, time until bone marrow engraftment, indices of clinical care, and other data related to hospital morbidity were recorded for all patients. RESULTS: The glutamine-supplemented patients (n = 24) were clinically similar to the controls (n = 21) at entry. Nutrient intake was similar in both groups; however, nitrogen balance was improved in the glutamine-supplemented patients relative to the controls (-1.4 +/- 0.5 g/d compared with -4.2 +/- 1.2; P = 0.002). Fewer experimental patients developed clinical infection (three compared with nine in the control group; P = 0.041), and the incidence of microbial colonization was also significantly reduced. Hospital stay was shortened in patients receiving glutamine supplementation (29 +/- 1 d compared with 36 +/- 2 d; P = 0.017). CONCLUSION: Patients receiving glutamine-supplemented parenteral nutrition after bone marrow transplantation had improved nitrogen balance, a diminished incidence of clinical infection, lower rates of microbial colonization, and shortened hospital stay compared with patients receiving standard parenteral nutrition. These effects occurred despite no differences between groups in the incidence of fever, antibiotic requirements, or time to neutrophil engraftment.