Polymeric Diet Research Articles

Simultaneous determination of retinol and α-tocopherol in polymeric diets for enteral nutrition

Existing methods for simultaneous measurements of retinol and α-tocopherol in enteral formulas require large sample and solvent volumes and are time-consuming and costly. We have developed a simple, sensitive, cost-effective method for the determination of these vitamins in polymeric diets that can easily be applied to standard quality control of large numbers of samples. Our analytical procedure comprises deproteinization with pure ethanol, saponification with a 3.6 M KOH solution in a sonicator for 30 min at 65 °C under a nitrogen atmosphere, solubilization of samples in phosphate buffer and extraction with hexane. Vitamins are separated by reversed-phase HPLC and quantified by dual-wavelength spectrophotometry. The method gives satisfactory results, with recovery rates of 106.3 ± 1.5% for retinol and 102.3 ± 1.5% for α-tocopherol and RSDs ranging between 1.2 and 4.8% for precision. This method is suitable for the quality control of enteral formulas.

Formulation of enteral diets for use in jejunal enteral feeding

Nasogastric enteral feeding is not tolerated in patients with gastric atony and in many critically-ill patients in whom gastric emptying may be delayed and in whom gastro-oesophageal regurgitation may lead to pulmonary aspiration of enteral feed and the development of pneumonia. Initial attempts to overcome these problems led to the development of post pyloric enteral feeding techniques with the infusion port of the tubes positioned in the duodenum. In many centres this technique is still the most practised post-pyloric enteral feeding technique. Nasoduodenal feeding tubes often retroperistalse into the stomach. The technique of choice, therefore, in these difficult patients is to position the infusion port of the feeding tube well distal to the ligament of trietz (post ligament of trietz nasojejunal enteral tube feeding). While nasogastric and nasoduodenal enteral feeding techniques have been shown to elicit a stimulatory exocrine pancreatic response, distal jejunal enteral feeding does not. During this mode of feeding the ileal brake is activated and pancreatic exocrine pancreatic secretion inhibited by the action of the released peptide YY and glucagon-like peptide-1 hormones, in turn the inhibition of pancreatic secretion being the result of inhibition of trypsin secretion. In the light of the findings showing the absence of a stimulatory pancreatic exocrine response to nasojejunal enteral feeding these patients should receive a predigested rather than a polymeric enteral diet.

GLP‐2 Administration Results in Increased Proliferation but Paradoxically an Adverse Outcome in a Juvenile Piglet Model of Short Bowel Syndrome

The objective of the present study was to examine the effect of glucagon-like peptide-2 (GLP-2) administration in a piglet, juvenile model of short bowel syndrome. Four-week-old piglets underwent either a sham operation or 75% small bowel resection. Postoperatively, piglets received either polymeric infant formula diet or the diet and subcutaneous human recombinant GLP-2 (1600 microg/day for 7 days, 800 microg/day thereafter). Food intake was monitored throughout the experiment, and stool and serum samples obtained fortnightly. After the piglets were killed, tissues were obtained from the duodenum, jejunum, ileum, and terminal ileum, and used for morphological and functional analysis. Treatment with GLP-2 resulted in significantly increased numbers of proliferating and apoptotic cells in the ileum of sham and small bowel resection piglets (P < 0.05). GLP-2 administration resulted in decreased weight gain, serum albumin, and disaccharidases in both sham and small bowel resection piglets (P < 0.001 compared with polymeric infant formula diet alone). This is the first study to our knowledge to examine the effect of GLP-2 administration in a juvenile short bowel syndrome model. Contrary to adult rodent studies, administration of GLP-2 resulted in adverse outcomes including reduced ability to gain weight; decreased serum albumin, tissue maltase, and sucrase; and villous atrophy. We anticipate this information will have important implications for future paediatric clinical trials.

Nutritional therapy for active Crohn’s disease

Nutritional therapy for active Crohn's disease (CD) is an underutilised form of treatment in adult patients, though its use is common in the paediatric population. There is evidence that nutritional therapy can effectively induce remission of CD in adult patients. Enteral nutrition therapy is safe and generally well tolerated. Meta-analysis data suggest that corticosteroids are superior to nutritional treatment for induction of remission in active CD. However, the potential side effects of such pharmacotherapy must be taken into consideration. This review examines the evidence for the efficacy of elemental and polymeric diets, and the use of total parenteral nutrition in active CD.

Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn’s disease

Introduction: Nutritional therapy has been reported to have an almost equivalent efficacy to that of corticosteroids in achieving clinical remission in active Crohn’s disease (CD). However, the effects of both treatments on intestinal mucosal inflammation rarely are reported. In a randomized controlled trial in children with active CD, the authors compared the efficacy of nutritional therapy alone with that of corticosteroids on clinical variables and intestinal mucosal healing.

Review article: dietary and nutritional management of Crohn's disease

The value of dietary alteration and the nutritional management of Crohn's disease is assessed in this review. Lactose restriction, low-fat diets and low-residue diets may be of value in specifically indicated clinical situations. A fibre-rich, unrefined carbohydrate diet has not been shown to alter the course of the disease, and the value of 'exclusion diets' remains to be confirmed in controlled, prospective studies. Nutritional insufficiency of varying degrees is common in Crohn's disease and can be corrected by the efficient use of enteral diets (usually with polymeric preparations) or intravenous nutritional support. Growth retardation in adolescents with Crohn's disease can usually be improved by enteral nutrition. Nutritional support of various kinds may be of value in the management of local complications of Crohn's disease; sub-acute obstruction, anal, perianal and rectal lesions, fistulas and ileostomy complications, and the management of bile acid-induced diarrhoea. The use of nutrition as 'primary therapy; in Crohn's disease is considered. Theoretical reasons why nutritional support and bowel rest may possibly induce remission of the disease are discussed. The evidence to date suggests that intravenous nutrition and bowel rest may not be effective in inducing a primary remission of the disease, and the possible value of elemental diets and polymeric diets in this respect are assessed. Further prospective controlled studies of elemental diets as primary therapy in Crohn's disease are required.

Effect of exclusive enteral nutritional treatment on plasma antioxidant concentrations in childhood Crohn's disease

Oxidative stress and depletion of antioxidants may play a role in the pathogenesis of Crohn's disease (CD). The aim of this study was to determine the effect of exclusive enteral nutrition, which is increasingly being used as primary therapy for CD, on plasma antioxidant concentrations in children with active CD. In a double-blind randomised controlled trial, 15 children with active CD (mean age, 11.3 years, range 6.8-15.7) attending a paediatric gastroenterology referral centre, were assigned to receive either a standard polymeric diet (Group S, n=8) or a glutamine-enriched polymeric diet (Group G, n=7) as primary therapy for active CD. Plasma concentrations of selenium, urates, vitamin A, vitamin E, vitamin C, glutathione, and also malondialdehyde (MDA) were measured at baseline and after 4 weeks of exclusive enteral nutritional treatment. Mean (95% CI) selenium concentration of the cohort increased significantly from 0.82 micromol/l (0.72, 0.91) to 1.14 micromol/l (0.98, 1.3), P<0.001. There were, however, significant reductions in mean concentrations of vitamin C {11.8 mg/l (7.7, 15.8) to 6.5 mg/l (4.5, 8.7), P=0.01} and vitamin E {11.3 mg/l (10.3, 12.4) to 9.4 mg/l (8.7, 10.1), P=0.03}. The concentrations of vitamin A, urates, glutathione and MDA did not change significantly over the study period. Glutamine supplementation did not have any significant effect on plasma antioxidant concentrations. Significant changes in circulating antioxidant concentrations occurred in children with active CD receiving exclusive enteral nutritional treatment. Glutamine supplementation was not beneficial in improving plasma antioxidant status.

Effects of Intragastric L-Arginine Administration on Proximal Stomach Tone Under Basal Conditions and After an Intragastric Diet

Nitric oxide (NO) plays an important role as a nonadrenergic, noncholinergic inhibitory neurotransmitter in the GI tract. Our study aims were to investigate the effect of a single intragastric L-arginine (L-Arg) administration, as a source of NO, on proximal stomach tone in basal and postintragastric administration of a polymeric diet in humans and to evaluate concomitantly the effect on antral area as an indirect assessment of gastric emptying. Eight healthy volunteers were studied in a randomized double-blind crossover study after, respectively, 15 g L-Arg, 30 g L-Arg, or placebo administered in the stomach through a gastric tube. The drug administration was followed by a polymeric diet infusion (500 ml/500 kcal) at a rate of 250 ml/hr. Gastric tone variations were recorded with an electronic barostat, gastric emptying was concomitantly estimated by repeated ultrasound measurements of antral area, and symptoms were recorded throughout the experiment.L-Arg administration was associated with significantly higher increases in barostat bag volumes at both dosages, 30 g (117+/-16 ml) and 15 g (67+/-15 ml), compared to placebo (46+/-11 ml; P < 0.05). In response to the polymeric diet the 30-g L-Arg challenge was associated with a smaller increase in intrabag volume, whereas postinfusion final volumes did not differ in the three treatment conditions. Antral areas were not different at any time of measurement among the three challenges. Bloating and diarrhea were observed after 30-g L-Arg administration in five subjects of eight. Short-term L-Arg administration was able to induce proximal stomach relaxation that allowed a secondary response to enteral feeding only at the 15-g dosage. This 15-g dosage was as well tolerated as the placebo and was associated with no significant changes in gastric emptying patterns.

Factors Affecting Recurrence in Patients with Crohn's Disease Under Nutritional Therapy

This retrospective study was designed to determine risk factors for recurrence of Crohn's disease under enteral nutrition. The clinical course of 145 patients with Crohn's disease, who were primarily induced into remission by total parenteral nutrition, was reviewed. The patients were classified into two groups: enteral nutrition group (n = 98; >/=1,200 kcal/day of enteral nutrition), or nonenteral nutrition group (n = 47;<1,200 kcal/day of enteral nutrition) according to the amount of their daily elemental or polymeric diet. Contributions of enteral nutrition and other clinical variables to the recurrence were analyzed retrospectively. A Crohn's disease activity index of >150 plus an increase in Crohn's disease activity index of >70 from the baseline value was defined as recurrence. Forty-two patients in the enteral nutrition group and 29 patients in the nonenteral nutrition group recurred during periods ranging from 3 to 159 months. The cumulative rate of recurrence was significantly higher in the nonenteral nutrition group than in the enteral nutrition group (P = 0.047). Among the Crohn's disease patients in the enteral nutrition group, penetrating type (relative risk, 3.89; 95 percent confidence interval, 1.58-9.62), colonic involvement (relative risk, 3.10; 95 percent confidence interval, 1.39-6.9), and previous history of surgery (relative risk, 2.48; 95 percent confidence interval, 1.16-5.33) were factors that significantly affected recurrence. In contrast, penetrating type was the only possible factor associated with recurrence in the nonenteral nutrition group (relative risk, 2.75; 95 percent confidence interval, 0.96-7.81). Among patients with Crohn's disease under maintenance enteral nutrition, the risk of recurrence differs according to the disease type and the site of involvement. The maintenance treatment by enteral nutrition alone seems insufficient for patients with penetrating type or with colonic involvement.

Polymeric Diet Alone Versus Corticosteroids in the Treatment of Active Pediatric Crohn’s Disease: A Randomized Controlled Open-Label Trial

Nutritional therapy has been reported to have an almost equivalent efficacy of corticosteroids in achieving clinical remission in active Crohn's disease (CD). However, the effects of both treatments on intestinal mucosal inflammation rarely are reported. In a randomized controlled trial in children with active CD we compared the efficacy of nutritional therapy alone or corticosteroids on clinical variables and intestinal mucosal healing. In a prospective, 10-week open-label trial, children with active, naive CD were randomized to orally polymeric formula alone or oral corticosteroids. The clinical activity index and nutritional and activity serum variables were evaluated at week 0 and then every 2 weeks; intestinal mucosal inflammation was assessed through endoscopy and histology at weeks 0 and 10. Primary efficacy outcomes were clinical remission and mucosal healing. Of the 37 children randomized, 19 received polymeric formula and 18 received corticosteroids. At week 10, on an intention-to-treat basis, the proportion of patients achieving clinical remission was comparable between the 2 groups (polymeric formula: 15/19 [79%; 95% confidence interval (CI), 56%-92%]; corticosteroid group: 12/18 [67%; 95% CI, 44%-84%]; P = .4; not significant). On the contrary, the proportion of children showing mucosa healing was significantly higher in the polymeric (14/19; 74%; 95% CI, 51%-89%) than the corticosteroid group (6/18 [33%; 95% CI, 16%-57%]; P < .05). At week 10 both endoscopic and histologic scores significantly decreased only in the polymeric group (P < .001). In children with active and recently diagnosed CD, a short course of polymeric diet is more effective than corticosteroids in inducing healing of gut inflammatory lesions.

Enteral Nutrition as a Primary Therapy for Intestinal Lymphangiectasia: Value of Elemental Diet and Polymeric Diet Compared with Total Parenteral Nutrition

Enteral Nutrition as a Primary Therapy for Intestinal Lymphangiectasia: Value of Elemental Diet and Polymeric Diet Compared with Total Parenteral Nutrition

Continuous enteral nutrition during the early adaptive stage of the short bowel syndrome.

Sixty-two patients with the short bowel syndrome (30-150 cm) were managed by continuous enteral nutrition (CEN) in the early adaptive phase. In all, 82 per cent were referrals from other units and 85 per cent of referrals had failure of one or more organ systems on admission. There were intra-abdominal abscesses in 41 per cent of patients and 37 per cent had an enterocutaneous fistula. The diet included polysaccharides, medium chain triglycerides and protein hydrolysates, mixed with a high-viscosity tapioca suspension. An elemental diet was used initially in 15 per cent of patients. Thirty-three patients had an interruption of the gastrointestinal tract by a temporary enterostomy. Chyme was re-infused into the distal intestine in 20 cases. 'Zero-time' was taken as the time of operation or, for referred patients treated conservatively, the date of admission. CEN was commenced at a mean of 14 days from zero-time. Total parenteral nutrition could be discontinued at a mean of 36 days and exclusive oral alimentation was resumed at a mean of 87 days. Patients with small bowel longer than 80 cm attained enteral autonomy earlier than patients with a shorter length. Mean faecal volume did not increase following institution of CEN, suggesting tolerance to the high-viscosity diet. In cases with re-infusion of enteric content, the distal circuit (length of distal small intestine 46 cm) was able to absorb 70 per cent of the volume re-infused (mean volume 2700 ml). Body weight and nutritional markers increased significantly during the course of CEN. This study suggests that enteral autonomy can be attained early in the short bowel syndrome, even under challenging conditions. Elemental formulae do not appear to offer a benefit over polymeric diets.

Enteral Feeding Without Pancreatic Stimulation

All forms of commonly practiced enteral feeding techniques stimulate pancreatic secretion, and only intravenous feeding avoids it. In this study, we explored the possibility of more distal enteral infusions of tube feeds to see whether activation of the ileal brake mechanism can result in enteral feeding without pancreatic stimulation, with particular reference to trypsin, because the avoidance of trypsin stimulation may optimize enteral feeding in acute pancreatitis. The pancreatic secretory responses to feeding were studied in 36 healthy volunteers by standard double-lumen duodenal perfusion/aspiration techniques over 6 hours. Subjects were assigned to no feeding (n = 7), duodenal feeding with a polymeric diet (n = 7) or low-fat elemental diet (n = 6), mid-distal jejunal feeding (n = 11), or intravenous feeding (n = 5). All diets provided 40 kcal/kg ideal body weight/d and 1.5 g protein/kg ideal body weight/d. Plasma gut peptide responses were monitored in 15 subjects. In comparison with basal fasting trypsin secretion rates (mean = 134 [standard error = 22] U/h), duodenal feeding with the polymeric and elemental formulae stimulated trypsin secretion (mean = 408 [standard error = 51] U/h; P < 0.001), whereas intravenous feeding (mean = 171 [standard error = 34] U/h) and mid-distal jejunal (mean = 119 [standard error = 16] U/h) did not. Stimulation was associated with an increase in plasma cholecystokinin, whereas distal jejunal feeding resulted in an increase in plasma glucagon-like peptide-1 and peptide YY concentrations. Our results suggest that enteral feeding can be given without stimulating pancreatic trypsin secretion provided it is delivered into the mid-distal jejunum. The mechanism may involve activation of the ileal brake mechanism.

Enteral Nutrition as a Primary Therapy for Intestinal Lymphangiectasia: Value of Elemental Diet and Polymeric Diet Compared with Total Parenteral Nutrition

Intestinal lymphangiectasia (IL) is a rare disease requiring oral fat restriction. The aim of this study was to evaluate the efficacy of enteral nutrition compared to that of total parenteral nutrition (TPN). We retrospectively reviewed nine patients with IL presenting with protein-losing enteropathy. Of these, seven patients not responding to a low-fat diet were treated with elemental diet (ED), polymeric diet (PD) containing medium-chain triglycerides, or TPN. Improvement in serum total protein was observed in two of three on ED and in one of two on PD, compared with three of three on TPN. Enteric protein loss was improved in two of two on ED, one of two on PD, and two of two on TPN. Outpatients who continued to receive enteral nutrition maintained a total protein level. Enteral nutirition appears to be as effective as TPN for patients with IL, and it may provide a valid and safe alternative therapy.

Soporte nutricional basado en la evidencia en la enfermedad inflamatoria intestinal

Patients with inflammatory bowel disease are at risk for malnutrition. Consequently all patients with inflammatory bowel disease should undergo nutritional screening to identify those who require thorough nutritional evaluation. When nutritional support is indicated, enteral nutrition (oral or through a tube) should be used. There are no significant differences between elemental and non-elemental enteral diets in inducing remission of Crohn's disease (CD). Nevertheless, given that non-elemental diets are better tolerated, most authors prefer polymeric diets. Enteral nutrition should not be used as the primary treatment of choice in patients with CD, since they are less effective in inducing remission than steroid therapy. Although dietary fat (quantity and type of fat) might influence the course of the disease, recommendations cannot be made on the basis of the available studies. Equally, there is insufficient evidence that glutamine is effective in inducing remission in CD. The use of probiotics presents a high level of evidence in maintenance treatment and in the prevention of postoperative pouchitis, although the level of evidence is lower in ulcerative colitis and CD. Further studies are required to investigate several issues such as dose, treatment duration, the separate or combined use of several strains, as well as the concomitant use of prebiotics, symbiotics or antibiotics.

Do Interventions Which Reduce Colonic Bacterial Fermentation Improve Symptoms of Irritable Bowel Syndrome?

Abnormal fermentation may be an important factor in irritable bowel syndrome (IBS). Gastroenteritis or antibiotic therapy may damage the colonic microflora, leading to increased fermentation and the accumulation of gas. Gas excretion may be measured by whole-body calorimetry but there has only been one such study on IBS to date. We aimed to assess the relationship between IBS symptoms and fermentation rates in IBS. A purpose-built, 1.4-m3, whole-body calorimeter was used to assess excretion of H2 and CH4 in IBS subjects while consuming a standard diet and, again, after open randomization on either the standard diet together with the antibiotic metronidazole or a fiber-free diet to reduce fermentation. Metronidazole significantly reduced the 24-hr excretion of hydrogen (median value compared to the control group, 397 vs 230 ml/24 hr) and total gas (H2 + CH4; 671 vs 422 ml/min) and the maximum rate of gas excretion (1.6 vs 0.8 ml/min), as did a no-fiber polymeric diet (hydrogen, 418 vs 176 ml/min; total gas, 564 vs 205 ml/min; maximum rate of gas excretion, 1.35 vs 0.45 ml/min), with a significant improvement in abdominal symptoms. IBS may be associated with rapid excretion of gaseous products of fermentation, whose reduction may improve symptoms.

Gastric tone variations during gastric infusion of fiber‐supplemented formulas

Despite gastric feeding being a common method of artificial nutritional support, little is known about the effects of enteral nutrition on fundic motor function. The objective of this study was to assess variations of fundic tone and their relation to antroduodenal motility before, during and after nasogastric feeding supplemented or not with fibers. Double-blinded studies were performed in random order with the three different diets (2100 kJ) in eight volunteers: fiber free (FF), insoluble fiber (IF) or mixed fiber (MF). Fundic tone was recorded by barostat concomitantly with antroduodenal manometry. Before the infusion, seven spontaneous fundic relaxations occurred during the 24 studies. Concomitantly or less than 2 min before these relaxations, phase III of the migrating motor complex (MMC) with a duodenal onset was recorded. Only the 17 studies without spontaneous fundic relaxation (4 FF, 6 MF, 7 IF) were suitable for the assessment of fundic response to infusion. Disappearance of the volume waves at the beginning and during the whole infusion was observed in 11/17 studies (FF 50%, MF 66% and IF 71%, NS), but a proximal gastric relaxation following the beginning of the infusion occurred in only three individuals, one with the FF and two with IF. When it occurred, fundic relaxation was observed within 2 min and was not different from those observed spontaneously. Gastric infusion of a polymeric diet, supplemented or not with fiber, did not promote fundic relaxation in most of the cases but often induced a disappearance of gastric volume waves.

Therapeutic efficacy of infliximab on active Crohn's disease under nutritional therapy

Objective. The aim of this investigation was to elucidate retrospectively the therapeutic effect of infliximab in patients with active Crohn's disease (CD) under nutritional therapy. Material and methods. Using a review of the clinical records in 24 nationwide institutions specializing in inflammatory bowel disease, the short-term effect of infliximab in 97 patients with active CD was retrospectively investigated. The Crohn's disease activity index (CDAI) at baseline and after 2 weeks of a single infliximab administration (5 mg/kg) was compared among patients under total parenteral nutrition (TPN group, n=36), those following an elemental or polymeric diet (EN group, n=49) and those without TPN and EN (NN group, n=12). A decrease in CDAI ≥ 70 or a CDAI value <150 at 2 weeks was regarded as effective. Results. There was no difference in CDAI at baseline among the three groups. In each group, CDAI decreased significantly (from 250 (195–290) [median (interquartiles)] to 152 (123–233) in the TPN group, p<0.0001; from 259 (200–325) to 180 (130–238) in the EN group, p<0.0001; from 278 (222–291) to 164 (132–196) in the NN group, p=0.003). Infliximab was effective in 63.9% of patients in the TPN group, in 55.1% of those in the EN group and in 75% of the NN group. There was no statistical difference in efficacy among the three groups (p=0.4). Multivariate logistic regression analysis revealed younger age to be a significant factor related to the efficacy of infliximab. Conclusions. Infliximab is effective in patients with CD under TPN or EN. Age at infliximab administration may be predictive of response to infliximab.

Colostrum Protein Concentrate Enhances Intestinal Adaptation After Massive Small Bowel Resection in Juvenile Pigs

Short bowel syndrome (SBS) usually results from the surgical removal of a large segment of small intestine. Patient outcome depends on the extent of intestinal resection and adaptation of the remaining intestine. We evaluated the impact of colostrum protein concentrate (CPC) on intestinal adaptation after massive small bowel resection in a porcine model of infant SBS. Four-week-old piglets underwent an approximate 75% small bowel resection (R, n = 23) or a control transection operation (C, n = 14). Postoperatively, animals from both groups received either pig chow (R = 6, C = 5), polymeric infant formula (R = 6, C = 3) or polymeric infant formula supplemented with CPC (R = 11, C = 6) for 8 weeks until sacrifice. Clinical outcome measures included weight gain and stool consistency. Morphologic measures were intestinal villus height and crypt depth. Functional outcome measure was mucosal disaccharidase activity. Resected animals fed polymeric infant formula alone had reduced weight gain compared with controls fed the same diet (P < 0.005). Despite massive small bowel resection, animals fed pig chow or polymeric infant formula supplemented with CPC grew at an equivalent rate to controls fed polymeric infant formula alone. Resected animals supplemented with CPC had increased villus length and crypt depth in the jejunum (P < 0.001) and ileum (P < 0.001) compared with resected animals fed either pig chow or polymeric infant formula alone. In an animal model of SBS, CPC supplementation of polymeric infant formula resulted in normal weight gain and features of enhanced morphologic adaptation.

Dose dependency of the effect of ornithine α-ketoglutarate on tissue glutamine concentrations and hypercatabolic response in endotoxaemic rats

The optimal dosage of ornithine alpha-ketoglutarate (OKG) for repleting tissue glutamine (Gln) concentrations and maintaining N homeostasis after injury is unknown. We set out to perform 'dose-ranging' of OKG supplementation after an endotoxaemic challenge. Sixty-one male Wistar rats were injected with 3 mg lipopolysaccharide (LPS) from Escherichia coli/kg (n 50) or saline vehicle (9 g NaCl/l; controls n 11). After a 24 h fast, survivors were fed by gavage for 48 h with a polymeric standard diet (879 kJ/kg per d and 1.18 g N/kg per d) supplemented with non-essential amino acids (control, n 11; LPS-OKG-0.0, n 9), or with 0.5 g OKG/kg per d (LPS-OKG-0.5, n 12), 1.5 OKG/kg per d (LPS-OKG-1.5, n 11) or 4.5 g OKG/kg per d (LPS-OKG-4.5, n 10). The diets for all groups were made isonitrogenous with the LPS-OKG-4.5 diet by adding an appropriate amount of non-essential amino acids. Rats were killed on day 3 for blood and tissue sampling (muscle, jejunum mucosa, liver). Urine was collected daily for 3-methylhistidine and total N assays. The OKG dose was correlated with Gln concentrations in every tissue and with cumulative N balance (Spearman test, P<0.01). 3-Methylhistidine excretion was increased in endotoxaemic groups compared with controls (ANOVA, P<0.05) except in the LPS-OKG-4.5 group. Only the LPS-OKG-4.5 group achieved a positive post-injury N balance (t test, P<0.05). In conclusion, OKG exerted a dose-dependent effect on tissue Gln concentration and N balance, but only the highest dosage counteracted myofibrillar hypercatabolism and caused a positive N balance.