Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Communication
  • Published:

Glutamine-enriched total parenteral nutrition in patients with inflammatory bowel disease

European Journal of Clinical Nutrition volume 59, pages 1302–1309 (2005)Cite this article

Abstract

Background:

Studies in animal models of inflammatory bowel disease (IBD) suggest that supplementation of total parenteral nutrition with glutamine (gln), a conditionally essential amino acid in catabolic conditions, increases gln plasma concentrations, reduces intestinal damage, improves nitrogen balance and may improve the course of the disease. However, human data supporting this assumption are missing.

Methods:

A total of 24 consecutive patients with an acute exacerbation of IBD (19 Crohn's disease; five ulcerative colitis) and scheduled for total parenteral nutrition (TPN) (>7 days) were randomised. Parallel to a standardised anti-inflammatory therapy, the patients received either a TPN with 1.5 g/kg body weight of a standard amino acid or an isonitrogenic, isocaloric TPN with 1.2 g/kg body weight of a standard amino acid and 0.3 g/kg L-alanine-L-glutamine. Primary end points were gln plasma concentrations and intestinal permeability assessed by urinary lactulose and D-xylose ratio.

Results:

Gln plasma levels did not differ significantly in either group throughout the study. Intestinal permeability did not change within 7 days either with or without gln supplementation (Δ-lactulose/xylose ratio: 0.01±0.05 (gln+) vs 0.02±0.1 (gln−)). The observed changes in inflammatory and nutritional parameters, and also disease activity, length of TPN and hospital stay, were independent of glutamine substitution. Five (41%) patients in the gln+ group and three (25%) patients in the gln− group needed surgical intervention.

Conclusion:

Although limited by the sample size, these results do not support the hypothesis that glutamine substitution has an obvious biochemical or clinical benefit in patients with active IBD scheduled for total parenteral nutrition.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  • Akobeng AK, Miller V, Stanton J, Elbadri AM & Thomas AG (2000): Double-blind randomized controlled trial of glutamine-enriched polymeric diet in the treatment of active Crohn's disease. J. Pediatr. Gastroenterol. Nutr. 30, 78–84.

    Article  CAS  Google Scholar 

  • Ameho CK, Adjei AA, Harrison EK, Takeshita K, Morioka T, Arakaki Y, Ito E, Suzuki I, Kulkarni AD, Kawajiri A & Yamamoto S (1997): Prophylactic effect of dietary glutamine supplementation on interleukin 8 and tumour necrosis factor alpha production in trinitrobenzene sulphonic acid induced colitis. Gut 41, 487–493.

    Article  CAS  Google Scholar 

  • Bjarnason I, MacPherson A & Hollander D (1995): Intestinal permeability: an overview. Gastroenterology 108, 1566–1581.

    Article  CAS  Google Scholar 

  • Buchman AL, Moukarzel AA, Bhuta S, Belle M, Ament ME, Eckhert CD, Hollander D, Gornbein J, Kopple JD & Vijayaroghavan SR (1995): Parenteral nutrition is associated with intestinal morphologic and functional changes in humans. JPEN J. Parenter. Enteral Nutr. 19, 453–460.

    Article  CAS  Google Scholar 

  • Crenn P, Coudray-Lucas C, Thuillier F, Cynober L & Messing B (2000): Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. Gastroenterology 119, 1496–1505.

    Article  CAS  Google Scholar 

  • Den Hond E, Hiele M, Peeters M, Ghoos Y & Rutgeerts P (1999): Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn's disease. JPEN J. Parenter. Enteral Nutr. 23, 7–11.

    Article  CAS  Google Scholar 

  • Elia M (1999): Glutamine in parenteral nutrition: more food for thought. Gut 45, 6–7.

    Article  CAS  Google Scholar 

  • Fujita T & Sakurai K (1995): Efficacy of glutamine-enriched enteral nutrition in an experimental model of mucosal ulcerative colitis. Br. J. Surg. 82, 749–751.

    Article  CAS  Google Scholar 

  • Furst P, Pogan K & Stehle P (1997): Glutamine dipeptides in clinical nutrition. Nutrition 13, 731–737.

    Article  CAS  Google Scholar 

  • Gardiner KR & Rowlands BJ (1995): Efficacy of glutamine-enriched enteral nutrition in an experimental model of mucosal ulcerative colitis. Br. J. Surg. 82, 1278–1279.

    Article  CAS  Google Scholar 

  • Gassull MA & Cabre E (2001): Nutrition in inflammatory bowel disease. Curr. Opin. Clin. Nutr. Metab. Care 4, 561–569.

    Article  CAS  Google Scholar 

  • Geerling BJ, Badart-Smook A, Stockbrugger RW & Brummer RJ (1998): Comprehensive nutritional status in patients with long-standing Crohn disease currently in remission. Am. J. Clin. Nutr. 67, 919–926.

    Article  CAS  Google Scholar 

  • Hammarqvist F, Wernerman J, Ali R, von der Decken A & Vinnars E (1989): Addition of glutamine to total parenteral nutrition after elective abdominal surgery spares free glutamine in muscle, counteracts the fall in muscle protein synthesis, and improves nitrogen balance. Ann. Surg. 209, 455–461.

    Article  CAS  Google Scholar 

  • Harward TR, Coe D, Souba WW, Klingman N & Seeger JM (1994): Glutamine preserves gut glutathione levels during intestinal ischemia/reperfusion. J. Surg. Res. 56, 351–355.

    Article  CAS  Google Scholar 

  • Houdijk AP, Rijnsburger ER, Jansen J, Wesdorp RI, Weiss JK, McCamish MA, Teerlink T, Meuwissen SG, Haarman HJ, Thijs LG & van Leeuwen PA (1998): Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma. Lancet 352, 772–776.

    Article  CAS  Google Scholar 

  • Jeejeebhoy KN (2001): Total parenteral nutrition: potion or poison? Am. J. Clin. Nutr. 74, 160–163.

    Article  CAS  Google Scholar 

  • Jiang ZM, Wang LJ, Qi Y, Liu TH, Qiu MR, Yang NF & Wilmore DW (1993): Comparison of parenteral nutrition supplemented with L-glutamine or glutamine dipeptides. JPEN J. Parenter. Enteral Nutr. 17, 134–141.

    Article  CAS  Google Scholar 

  • Katz KD, Hollander D, Vadheim CM, McElree C, Delahunty T, Dadufalza VD, Krugliak P & Rotter JI (1989): Intestinal permeability in patients with Crohn's disease and their healthy relatives. Gastroenterology 97, 927–931.

    Article  CAS  Google Scholar 

  • Koga Y, Ikeda K, Inokuchi K, Watanabe H & Hashimoto N (1975): The digestive tract in total parenteral nutrition. Arch. Surg. 110, 742–745.

    Article  CAS  Google Scholar 

  • McAnena OJ, Moore FA, Moore EE, Jones TN & Parsons P (1991): Selective uptake of glutamine in the gastrointestinal tract: confirmation in a human study. Br. J. Surg. 78, 480–482.

    Article  CAS  Google Scholar 

  • McNurlan MA, Garlick PJ, Steigbigel RT, DeCristofaro KA, Frost RA, Lang CH, Johnson RW, Santasier AM, Cabahug CJ, Fuhrer J & Gelato MC (1997): Responsiveness of muscle protein synthesis to growth hormone administration in HIV-infected individuals declines with severity of disease. J. Clin. Invest. 100, 2125–2132.

    Article  CAS  Google Scholar 

  • Ockenga J, Bischoff SC, Tillmann H, Rifai K, Widjaja A, Böker K, Manns M & Brabant G (2000): Elevated bound leptin correlates with energy expenditure in cirrhotics. Gastroenterology 119, 1656–1662.

    Article  CAS  Google Scholar 

  • Ockenga J, Borchert K, Rifai K, Manns MP & Bischoff SC (2002): Effect of glutamine-enriched total parenteral nutrition in patients with acute pancreatitis. Clin. Nutr. 21, 409–416.

    Article  CAS  Google Scholar 

  • Oriishi T, Sata M, Toyonaga A, Sasaki E & Tanikawa K (1995): Evaluation of intestinal permeability in patients with inflammatory bowel disease using lactulose and measuring antibodies to lipid A. Gut 36, 891–896.

    Article  CAS  Google Scholar 

  • O'Riordain MG, Fearon KC, Ross JA, Rogers P, Falconer JS, Bartolo DC, Garden OJ & Carter DC (1994): Glutamine-supplemented total parenteral nutrition enhances T-lymphocyte response in surgical patients undergoing colorectal resection. Ann. Surg. 220, 212–221.

    Article  CAS  Google Scholar 

  • Parrilli G, Iaffaioli RV, Martorano M, Cuomo R, Tafuto S, Zampino MG, Budillon G & Bianco AR (1989): Effects of anthracycline therapy on intestinal absorption in patients with advanced breast cancer. Cancer Res. 49, 3689–3691.

    CAS  PubMed  Google Scholar 

  • Podolsky DK (2002): Inflammatory bowel disease. N. Engl. J. Med. 347, 417–429.

    Article  CAS  Google Scholar 

  • Rachmilewitz D, Stamler JS, Bachwich D, Karmeli F, Ackerman Z & Podolsky DK (1995): Enhanced colonic nitric oxide generation and nitric oxide synthase activity in ulcerative colitis and Crohn's disease. Gut 36, 718–723.

    Article  CAS  Google Scholar 

  • Resnick RH, Royal H, Marshall W, Barron R & Werth T (1990): Intestinal permeability in gastrointestinal disorders. Use of oral [99mTc]DTPA. Dig. Dis. Sci. 35, 205–211.

    Article  CAS  Google Scholar 

  • Scheppach W, Loges C, Bartram P, Christl SU, Richter F, Dusel G, Stehle P, Fuerst P & Kasper H (1994): Effect of free glutamine and alanyl-glutamine dipeptide on mucosal proliferation of the human ileum and colon. Gastroenterology 107, 429–434.

    Article  CAS  Google Scholar 

  • Shinozaki M, Saito H & Muto T (1997): Excess glutamine exacerbates trinitrobenzenesulfonic acid-induced colitis in rats. Dis. Colon Rectum 40, S59–S63.

    Article  CAS  Google Scholar 

  • Smith RJ (1997): Glutamine-supplemented nutrition. JPEN J. Parenter. Enteral Nutr. 21, 183–184.

    Article  CAS  Google Scholar 

  • Stallmach A, Strober W, MacDonald TT, Lochs H & Zeitz M (1998): Induction and modulation of gastrointestinal inflammation. Immunol. Today 19, 438–441.

    Article  CAS  Google Scholar 

  • Stehle P, Zander J, Mertes N, Albers S, Puchstein C, Lawin P & Furst P (1989): Effect of parenteral glutamine peptide supplements on muscle glutamine loss and nitrogen balance after major surgery. Lancet 1, 231–233.

    Article  CAS  Google Scholar 

  • Swidsinski A, Ladhoff A, Pernthaler A, Swidsinski S, Loening-Baucke V, Ortner M, Weber J, Hoffmann U, Schreiber S, Dietel M & Lochs H (2002): Mucosal flora in inflammatory bowel disease. Gastroenterology 122, 44–54.

    Article  Google Scholar 

  • Thomas AG, Miller V, Taylor F, Maycock P, Scrimgeour CM & Rennie MJ (1992): Whole body protein turnover in childhood Crohn's disease. Gut 33, 675–677.

    Article  CAS  Google Scholar 

  • van Acker BA, Hulsewe KW, Wagenmakers AJ, von Meyenfeldt MF & Soeters PB (2000): Response of glutamine metabolism to glutamine-supplemented parenteral nutrition. Am. J. Clin. Nutr. 72, 790–795.

    Article  CAS  Google Scholar 

  • van der Hulst RR, van Kreel BK, von Meyenfeldt MF, Brummer RJ, Arends JW, Deutz NE & Soeters PB (1993): Glutamine and the preservation of gut integrity. Lancet 341, 1363–1365.

    Article  CAS  Google Scholar 

  • Wu G, Fang YZ, Yang S, Luptin JR & Turner ND (2004): Glutathione metabolism and its implications for health. J. Nutr. 134, 489–492.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Special thanks are given to the nutrition support team for preparing our TPN solutions and for assistance with patient management.

Author information

Author notes

  1. J Ockenga and K Borchert: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, Germany

    J Ockenga, K Borchert, M P Manns & S C Bischoff

  2. Department of Gastroenterology, Hepatology and Endocrinology, Humboldt University, Charité, Campus Mitte, Berlin, Germany

    J Ockenga & H Lochs

  3. 1st University Teaching Hospital, Kiel, Schittenhelstrasse 12, Kiel, 24105, Germany

    E Stüber

Authors
  1. J Ockenga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K Borchert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E Stüber
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H Lochs
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M P Manns
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S C Bischoff
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J Ockenga.

Additional information

Guarantor: J Ockenga.

Contributors: JO and KB were the daily project leaders, were involved in the study design, data interpretation and writing of the manuscript. JO and SCB were involved in design of the study and writing. ES carried out the investigation of the intestinal permeability and interpretation of the data. SCB, HL and MMP were involved in data interpretation and provided significant advice.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ockenga, J., Borchert, K., Stüber, E. et al. Glutamine-enriched total parenteral nutrition in patients with inflammatory bowel disease. Eur J Clin Nutr 59, 1302–1309 (2005). https://doi.org/10.1038/sj.ejcn.1602243

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1602243

Keywords

This article is cited by

Search

Advanced search

Quick links