Gln in Short Bowel Syndrome
Use of Gln supplementation has also been studied in individuals with SBS following massive small bowel resection. Individuals with SBS may experience a period of intestinal adaptation following massive bowel resection, a time when need for PN support decreases and enteral tolerance increases as a result of structural or functional changes in the intestinal mucosa. These individuals are susceptible to systemic infections, often from gut-derived bacteria that may translocate through the bowel wall through a disrupted intestinal mucosa. Glutamine supplementation in those with SBS may therefore be helpful, given the trophic effects of Gln. Glutamine’s immunomodulatory effects may also be helpful in management of SBS, inasmuch as there may be an increased risk for bacterial gut translocation and subsequent systemic bacterial infection.
In animals, results of studies in which Gln was used to stimulate intestinal adaptation are conflicting, with some studies revealing improvement in mucosal mass and others revealing no improvement in intestinal mass with Gln supplementation (Tamada et al. 1992; Vanderhoof et al.
1992). Nevertheless, there may be immunoprotective effects attributable to Gln in animal models of SBS. In a rat model of SBS, the replacement of 20% of the dietary casein with Gln appeared to result in increased total serum antibodies, decreased serum antibody to bacterial LPS, and increased stool intestinal immunoglobulin A (Tian et al. 2009).
Despite these observations, human studies utilizing Gln in conjunction with conventional PN support have been disappointing. Scolapio et al. (2001) performed a randomized placebo controlled trial in eight adult patients with SBS with 8 weeks of oral Gln supplementation and noted no improvement in intestinal morphology, gastrointestinal transit, D-xylose absorption, or stool output with Gln. A recent Cochrane review in neonates with severe gastrointestinal disease found no obvious benefit with intravenous or enteral Gln supplementation although only two studies were deemed to be of methodologic quality for inclusion in this analysis (Wagner et al. 2012).
Glutamine has also been used in conjunction with growth hormone (GH) in patients with SBS (Ziegler et al. 2003). A pilot unblended study by Byrne et al. (1995) in patients with PN-dependent SBS showed that a 3-week regimen of GH administration, intravenous or oral Gln (30 g/day), and a high-carbohydrate/low-fat diet significantly improved intestinal sodium, fluid, nitrogen, and energy absorption and improved lean body mass. In a larger group of chronic SBS patients undergoing the same protocol of GH+Gln+diet modification for three weeks followed by maintenance on the modified diet and Gln supplementation alone, PN requirements were either eliminated or markedly decreased in a large proportion of the patients at follow-up 1 year later (Byrne et al. 1995). Later, a prospective, double-blind, randomized, placebo-controlled clinical trial performed in 41 adults dependent on PN with SBS indicated that only subjects receiving GH+Gln+diet maintained significant reductions in PN for at least 3 months (Byrne et al. 1995). However, both a Cochrane review as well as a statement by the European Society for Clinical Nutrition and Metabolism does not recommend GH with or without Gln use for routine use because there is no clear beneficial effect of this treatment (Van et al. 2009; Wales et al. 2010).
In summary, based on the available literature, there does not appear to be good evidence for recommending Gln for routine use in individuals with SBS, particularly in those receiving some enteral feedings. One possible explanation for the lack of efficacy of Gln in short bowel syndrome is that its serum levels are higher in these subjects because less Gln is metabolized by the intestine.