Glutamine for Surgery and Post-Surgical Recovery

Surgery is a controlled injury, and the body responds to it the way it responds to any injury — by raiding its own reserves. Within hours of a major operation, skeletal muscle begins exporting glutamine to the gut, the immune system and the liver faster than it can make it, and plasma glutamine falls by 20–50%. That is the single clearest reason glutamine has been studied in surgical patients for forty years. The honest summary of those forty years is narrower than the supplement aisle suggests, and more interesting: in stable patients having planned abdominal operations, intravenous glutamine dipeptide given by the hospital shortens the stay by roughly two and a half days, with complication rates that move less convincingly. In critically ill patients already in multi-organ failure, the same nutrient at a high dose increased deaths. Those two sentences are not a contradiction — they describe different people, different doses and different delivery routes — and separating them is the whole job of this page.

Table of Contents

  1. Why an Operation Empties the Glutamine Tank
  2. What Glutamine Is Actually Doing While You Heal
  3. The Elective Surgery Evidence, Trial by Trial
  4. The REDOXS Warning: Where Glutamine Caused Harm
  5. Reconciling the Contradiction: Dose, Route, and Who Was in the Bed
  6. IV Dipeptide and Oral Powder Are Not the Same Intervention
  7. What the Evidence Says by Type of Operation
  8. A Practical Timeline: Before, During and After
  9. Dosing, Forms and What It Costs
  10. Who Should Not Take It
  11. Questions Worth Asking Your Surgical Team
  12. Key Research Papers
  13. External Authoritative Resources
  14. Connections
  15. Featured Videos

Why an Operation Empties the Glutamine Tank

Think of skeletal muscle as a warehouse. Roughly 60% of the free amino acids sitting inside your muscle cells are glutamine, and that store exists precisely so it can be spent in an emergency. Your body does not know the difference between a scheduled hernia repair and being hit by a car. Both trigger the same hormonal cascade — cortisol, catecholamines, glucagon — and that cascade has one metabolic instruction: break down muscle protein and ship the resulting amino acids to the tissues doing emergency work.

Three customers line up for that glutamine at once:

  1. The gut lining. Enterocytes — the cells carpeting your small intestine — burn glutamine as their primary fuel, not glucose. They turn over every three to five days at the best of times, and after surgery they are doing it while starved, handled and often not being fed by mouth.
  2. The immune system. Lymphocytes, neutrophils and macrophages consume glutamine at rates that rival their glucose consumption. After an operation they are multiplying hard, and every new cell is built from borrowed material.
  3. The liver and kidneys. Glutamine is a nitrogen shuttle and a precursor for glutathione, the body's main internal antioxidant. Both organs draw on it heavily during the stress response.

The warehouse cannot keep up. Muscle glutamine concentration falls measurably after major surgery and stays down for days — which is why glutamine is described as conditionally essential. Under ordinary circumstances your body makes all it needs. Under surgical stress, demand outruns supply, and the deficit has to come from somewhere: your own muscle.

That is the mechanism. The important thing to understand is that a mechanism this clean has repeatedly failed to translate into the clinical benefits people predicted from it — and the rest of this page is about why.

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What Glutamine Is Actually Doing While You Heal

Four jobs matter for recovery, and they are worth understanding separately because the evidence is much stronger for some than for others.

Keeping the gut barrier sealed

Your intestinal lining is one cell thick, held together by tight-junction proteins. When those cells are underfed, the seams loosen and bacterial products can cross into the bloodstream — the mechanism clinicians have long suspected links gut failure to post-operative infection. Glutamine is the fuel those cells prefer, and studies have measured its effect on intestinal permeability directly in critically ill patients, with an association between improved permeability and fewer systemic infections PubMed PMID: 15891348. The honest counterweight: a well-conducted trial in newborns and infants undergoing digestive-tract surgery found that glutamine-supplemented parenteral nutrition did not improve intestinal permeability, nitrogen balance or outcome PubMed PMID: 15798461. The mechanism is real; its clinical reach is contested.

Feeding the immune cells that prevent wound infection

The cells that clear bacteria from a fresh incision are among the most glutamine-hungry in the body. This is the rationale behind every trial that has used post-operative infection as an endpoint, and it is where the meta-analytic signal has been most consistent, if not overwhelming.

Protecting the glutathione supply

Glutathione is made from three amino acids, and glutamine feeds the pathway that supplies one of them. Surgical trauma depletes muscle glutathione, and human muscle-biopsy work has shown that giving glutamine attenuates that post-traumatic depletion PubMed PMID: 12605586. This is a measured biochemical effect in people, not a theory.

Supporting nitrogen balance and the raw material for repair

After surgery you are in negative nitrogen balance — losing protein faster than you replace it. Trials of alanyl-glutamine in post-operative patients have used nitrogen balance as a primary measure and found it improved alongside acceptable clinical safety PubMed PMID: 10483898. Better nitrogen balance means more material available for collagen, the protein your body lays down to knit an incision together.

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The Elective Surgery Evidence, Trial by Trial

This is the section most relevant if you have an operation booked. Read the numbers rather than the headline: they are more modest, and more specific, than "glutamine speeds recovery".

The most directly relevant analysis

Sandini and colleagues pooled 19 randomised trials covering 1,243 patients — 640 given intravenous glutamine dipeptide, 603 controls — all undergoing major elective abdominal operations PubMed PMID: 25584966. What they found:

The authors were candid about two things: the individual trials were generally underpowered and of medium or low quality, and the shorter stay is genuinely hard to interpret when complication rates did not move. If glutamine is not preventing complications, why are patients going home sooner? Possibly better gut function and earlier tolerance of food; possibly unblinded discharge decisions in imperfectly blinded trials. Nobody has settled this.

The broader parenteral picture

Bollhalder and colleagues took a wider view — 40 randomised trials of parenteral glutamine given against a background of parenteral nutrition, in severely ill patients including surgical ones PubMed PMID: 23196117:

The authors added two warnings that deserve to travel with the numbers: the result was strongly influenced by one recent trial, and publication bias could not be excluded. Unlike earlier meta-analyses, they could not demonstrate a mortality benefit.

Wischmeyer and colleagues, restricting themselves to 26 trials of parenteral only glutamine in 2,484 ICU patients, found a significant reduction in hospital mortality (RR 0.68, 95% CI 0.51 to 0.90, p = 0.008) and hospital stay 2.56 days shorter (p = 0.02), with infectious complications showing a strong trend that fell just short (RR 0.86, p = 0.09) PubMed PMID: 24745648.

Notice how stable one number is across three independent analyses with different inclusion rules: roughly two to two and a half days off the hospital stay. That is the most reproducible finding in this literature.

The foundational review

Novak and colleagues published the systematic review that framed the field, concluding that glutamine supplementation was associated with reduced complications and mortality in surgical and critically ill patients PubMed PMID: 12352035. Everything published since has been, in one way or another, a test of whether that 2002 conclusion held up. Partly it did, and partly it did not — which is the next section.

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The REDOXS Warning: Where Glutamine Caused Harm

In 2013 the New England Journal of Medicine published a trial that changed intensive-care practice and that anyone reading about glutamine deserves to know about PubMed PMID: 23594003. It is usually called REDOXS.

The design: 1,223 critically ill adults across 40 intensive care units in Canada, the United States and Europe. Every one of them had multi-organ failure and was on a ventilator. They were randomised to glutamine, antioxidants, both or placebo, started within 24 hours of ICU admission and delivered both intravenously and enterally — a high total dose by two routes at once.

The results:

That result was not a fluke of one trial. The MetaPlus trial, published in JAMA the following year, tested a high-protein enteral formula enriched with immune-modulating nutrients including glutamine against standard high-protein feed in ICU patients, found no reduction in new infections, and reported higher six-month mortality in the medical subgroup PubMed PMID: 25096691.

And in 2022 the RE-ENERGIZE trial gave 0.5 g per kilogram per day of enteral glutamine to 1,200 patients with severe burns — mean burn size 33% of body surface area — and found no benefit at all: median time to discharge alive was 40 days with glutamine against 38 days with placebo (subdistribution hazard ratio 0.91, 95% CI 0.80 to 1.04, p = 0.17), and six-month mortality was 17.2% versus 16.2% PubMed PMID: 36082909. Burns had been glutamine's strongest historical indication. The largest trial ever run in that population found nothing.

A trial-sequential meta-analysis of glutamine in severe adult burns reached a similarly deflationary conclusion about the earlier positive literature PubMed PMID: 37114912.

None of this describes a person recovering from a planned knee replacement or bowel resection. But it does mean that "glutamine is a harmless amino acid your body already makes" is not an adequate safety argument, and anyone telling you it is has not read the last fifteen years of this literature.

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Reconciling the Contradiction: Dose, Route, and Who Was in the Bed

How can the same nutrient shorten hospital stays in one literature and increase deaths in another? The most careful attempt to answer that came from Stehle and colleagues, and it is the single most useful paper on this page PubMed PMID: 28361751.

They applied deliberately strict eligibility rules, including only trials in which patients were:

Fifteen trials in 842 patients met that bar, with good average study quality. Within those boundaries the benefits held up.

Now compare that specification against REDOXS. Those patients were in multi-organ failure, many with kidney and liver impairment; they were enrolled within 24 hours, before stabilisation; and they received glutamine by both routes simultaneously at a high total dose, in patients who were often not being adequately fed. Every one of Stehle's boundaries was crossed. The published REDOXS paper also carries an erratum for a dosage error in the article text — worth knowing when you see the dose quoted second-hand.

The plain-language version: glutamine appears to help a body that is stressed but coping, and appears to harm a body that is failing. An organ in failure cannot process the extra nitrogen load, and a patient in shock is not in a state where feeding the repair machinery is the limiting problem. A planned operation in a reasonably healthy person sits at the first end of that spectrum, not the second.

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IV Dipeptide and Oral Powder Are Not the Same Intervention

This is the most commonly missed point in everything written about glutamine and surgery, and it has direct consequences for what you can act on.

Nearly all of the positive surgical evidence above used intravenous alanyl-glutamine dipeptide — a stabilised two-amino-acid molecule added to a bag of parenteral nutrition, given by hospital staff, usually starting the day of the operation. Free glutamine is unstable in solution, which is why the dipeptide form exists at all. That intervention is a hospital pharmacy decision, not a shopping decision. A trial of it in major abdominal surgery even measured the cost side, finding that the shorter stay offset the cost of the supplement PubMed PMID: 11104589.

What you can buy is oral L-glutamine powder. It is a genuinely different intervention:

So when a supplement label or a recovery blog cites "meta-analyses showing glutamine shortens hospital stay after surgery", the citation is real and the implied product is not the one that was tested. That is worth knowing before you spend money on it.

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What the Evidence Says by Type of Operation

Colorectal cancer surgery

The best-studied single indication. A meta-analysis of 26 randomised trials in 1,678 patients undergoing radical surgery for colorectal cancer found that glutamine significantly improved albumin, prealbumin and nitrogen balance, and significantly reduced TNF-α, CRP and infectious complications (RR 0.31, 95% CI 0.21 to 0.46) PubMed PMID: 37566134. Read that infection number with care: an RR of 0.31 is far larger than anything the broader surgical literature has produced, and the protein and inflammation outcomes carried very high statistical heterogeneity (I² between 75% and 90%), meaning the individual trials disagreed substantially with one another. A pooled figure built from trials that disagree that much is a hypothesis, not a settled effect size.

Major abdominal and upper gastrointestinal surgery

This is the population in Sandini's analysis above — shorter stay, complications not convincingly changed. Note that upper GI surgery is also where immunonutrition formulas have been tested: these combine arginine, omega-3 fatty acids and nucleotides, and sometimes glutamine, and have their own systematic-review literature PubMed PMID: 27020765. If your hospital offers a pre-operative immunonutrition drink, that is a different product from glutamine and should not be confused with it.

Liver surgery

A more recent systematic review and meta-analysis looked specifically at glutamine in patients undergoing hepatic surgery PubMed PMID: 42679488. Liver surgery deserves its own analysis precisely because the liver is the organ handling glutamine's nitrogen load — the same reason hepatic failure was an exclusion criterion in the trials that showed benefit.

Critically ill surgical patients

Distinct from elective surgery, and the subject of its own review and meta-analysis PubMed PMID: 32338020. This is the population where the REDOXS boundaries matter most.

Severe burns

Historically glutamine's strongest indication; now its most deflated one, after RE-ENERGIZE found no benefit in 1,200 patients PubMed PMID: 36082909.

Bone marrow transplant and high-dose chemotherapy

An adjacent literature with its own history, reviewed by Ziegler PubMed PMID: 11533316. Relevant if your operation sits inside a cancer treatment pathway rather than standing alone.

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A Practical Timeline: Before, During and After

Weeks before — where the real gains are

The single most evidence-backed thing you can do nutritionally before an operation is not glutamine. It is arriving well-nourished, with adequate total protein, and not fasted longer than necessary. The ESPEN practical guideline on clinical nutrition in surgery is explicit that early oral feeding is the preferred mode of nutrition for surgical patients, and that avoiding nutritional therapy carries a real risk of underfeeding after major surgery PubMed PMID: 34242915; the guideline was updated in 2025 PubMed PMID: 40957230.

Pre-operative oral carbohydrate loading — a clear carbohydrate drink a couple of hours before surgery instead of a midnight fast — has been studied in its own right and is part of Enhanced Recovery After Surgery protocols PubMed PMID: 33629128. If your hospital runs an ERAS pathway, that pathway is doing more for your recovery than any single supplement.

Practically: eat enough protein, keep eating normally until your team tells you to stop, and ask whether your hospital uses carbohydrate loading or an immunonutrition drink.

The admission itself — not your decision

If you receive intravenous nutrition, whether it contains alanyl-glutamine dipeptide is a clinical decision made by your surgical and nutrition team against their own protocols. It is reasonable to ask about. It is not something to arrange yourself, and oral powder is not a substitute for it.

The weeks after — the honest gap

This is the window most people are actually asking about when they search for glutamine and surgery: home, tired, incision healing, appetite poor, gut not quite right. It is also the window with the least direct trial evidence. Almost every trial cited on this page ran inside the hospital.

What can be said fairly: the mechanisms — gut lining repair, immune cell fuel, glutathione support, nitrogen balance — do not switch off at discharge, and oral glutamine has an established safety record at ordinary doses in people with normal liver and kidney function PubMed PMID: 11533313. What cannot be said is that a trial has shown oral glutamine speeds home recovery after surgery, because that trial has not been done. Anyone claiming otherwise is extrapolating from IV hospital data.

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Dosing, Forms and What It Costs

The hospital dose

The guideline-consistent parenteral dose used in the trials that showed benefit is 0.3 to 0.5 g of alanyl-glutamine dipeptide per kilogram of body weight per day, capped at 30% of the total prescribed nitrogen, given alongside adequate nutrition, in a patient who is stable and has working kidneys and liver. For an 80 kg adult that is roughly 24 to 40 g per day. Those boundaries are not decorative — they are precisely the boundaries within which the benefit has been demonstrated.

Oral forms

Timing

There is no trial-established timing for oral glutamine around surgery. Divided doses away from large protein meals is the conventional approach, on the reasoning that glutamine competes with other amino acids for transport. Treat that as convention, not evidence.

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Who Should Not Take It

These are not boilerplate. Each one traces to something specific above.

For everyone else with normal liver and kidney function, oral glutamine at ordinary doses has a long safety record PubMed PMID: 11533313. The caution above is about specific organ function and specific clinical states, not about the molecule being dangerous in general.

One more thing worth naming plainly: the broader critical-care nutrition literature has repeatedly found that interventions which looked promising in mechanism trials produced no difference in clinical outcomes when tested at scale. The 2022 ASPEN guideline update reviewed 36 trials in 20,578 patients across five foundational questions and found no differences for any outcome in any question, and lowered its energy recommendation over uncertainty about harm PubMed PMID: 34784064. That is the appropriate humility to bring to any single nutrient.

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Questions Worth Asking Your Surgical Team

You do not need to become an expert. You need five specific questions, and these are the ones that map onto the evidence above.

  1. “Does this hospital use an ERAS or enhanced recovery pathway for my operation?” This single question captures carbohydrate loading, early feeding, early mobilisation and shorter fasting — collectively far more impactful than any supplement.
  2. “Will I be on intravenous nutrition, and if so does it include alanyl-glutamine?” This is the intervention the trial evidence actually supports, and it is entirely in their hands.
  3. “Is there a pre-operative nutrition drink I should be taking?” Distinguishes immunonutrition and carbohydrate loading from glutamine, which people routinely conflate.
  4. “Are my liver and kidney function normal on my pre-op bloods?” This is the question that determines whether oral glutamine is reasonable for you at all, and the answer is already in your chart.
  5. “I'm considering oral glutamine powder after discharge — any reason not to?” Framed this way it is a two-second answer for them, and it keeps your total intake visible to the people managing your recovery.

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Key Research Papers

  1. Sandini M, Nespoli L, Oldani M, Bernasconi DP, Gianotti L (2015). Effect of glutamine dipeptide supplementation on primary outcomes for elective major surgery: systematic review and meta-analysis. Nutrients 7(1):481-99. — PubMed PMID: 25584966 (the most directly relevant analysis for planned abdominal surgery)
  2. Heyland D, Muscedere J, Wischmeyer PE, et al.; Canadian Critical Care Trials Group (2013). A randomized trial of glutamine and antioxidants in critically ill patients. New England Journal of Medicine 368(16):1489-97. — PubMed PMID: 23594003 (REDOXS; increased in-hospital and 6-month mortality in multi-organ failure)
  3. Stehle P, Ellger B, Kojic D, et al. (2017). Glutamine dipeptide-supplemented parenteral nutrition improves the clinical outcomes of critically ill patients: A systematic evaluation of randomised controlled trials. Clinical Nutrition ESPEN 17:75-85. — PubMed PMID: 28361751 (the reconciliation: benefit holds within guideline dose, route and patient boundaries)
  4. Heyland DK, Wibbenmeyer L, Pollack J, et al.; RE-ENERGIZE Trial Team (2022). A Randomized Trial of Enteral Glutamine for Treatment of Burn Injuries. New England Journal of Medicine 387(11):1001-1010. — PubMed PMID: 36082909
  5. Bollhalder L, Pfeil AM, Tomonaga Y, Schwenkglenks M (2013). A systematic literature review and meta-analysis of randomized clinical trials of parenteral glutamine supplementation. Clinical Nutrition 32(2):213-23. — PubMed PMID: 23196117
  6. Wischmeyer PE, Dhaliwal R, McCall M, Ziegler TR, Heyland DK (2014). Parenteral glutamine supplementation in critical illness: a systematic review. Critical Care 18(2):R76. — PubMed PMID: 24745648
  7. Novak F, Heyland DK, Avenell A, Drover JW, Su X (2002). Glutamine supplementation in serious illness: a systematic review of the evidence. Critical Care Medicine 30(9):2022-9. — PubMed PMID: 12352035
  8. van Zanten AR, Sztark F, Kaisers UX, et al. (2014). High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition and nosocomial infections in the ICU: a randomized clinical trial. JAMA 312(5):514-24. — PubMed PMID: 25096691 (MetaPlus)
  9. Xiong K, Li G, Zhang Y, et al. (2023). Effects of glutamine on plasma protein and inflammation in postoperative patients with colorectal cancer: a meta-analysis of randomized controlled trials. International Journal of Colorectal Disease 38(1):212. — PubMed PMID: 37566134 (note the high heterogeneity on the protein and inflammation outcomes)
  10. Weimann A, Braga M, Carli F, et al. (2021). ESPEN practical guideline: Clinical nutrition in surgery. Clinical Nutrition 40(7):4745-4761. — PubMed PMID: 34242915
  11. Weimann A, Bezmarevic M, Braga M, et al. (2025). ESPEN guideline on clinical nutrition in surgery — Update 2025. Clinical Nutrition 53:222-261. — PubMed PMID: 40957230
  12. Compher C, Bingham AL, McCall M, et al. (2022). Guidelines for the provision of nutrition support therapy in the adult critically ill patient: The American Society for Parenteral and Enteral Nutrition. JPEN Journal of Parenteral and Enteral Nutrition 46(1):12-41. — PubMed PMID: 34784064
  13. Ortiz-Reyes L, Lee ZY, Chin Han Lew C, et al. (2023). The Efficacy of Glutamine Supplementation in Severe Adult Burn Patients: A Systematic Review With Trial Sequential Meta-Analysis. Critical Care Medicine 51(8):1086-1095. — PubMed PMID: 37114912
  14. van Zanten AR, Dhaliwal R, Garrel D, Heyland DK (2015). Enteral glutamine supplementation in critically ill patients: a systematic review and meta-analysis. Critical Care 19:294. — PubMed PMID: 26283217
  15. Pimentel RFW, Fernandes SL (2020). Effects of parenteral glutamine in critically ill surgical patients: a systematic review and meta-analysis. Nutrición Hospitalaria 34(3):616-621. — PubMed PMID: 32338020
  16. Meng X, Zhang M, Wang X, et al. (2026). Efficacy of glutamine supplementation in postoperative patients undergoing hepatic surgery: a systematic review and meta-analysis of randomized controlled trials. Clinics (São Paulo) 81:101086. — PubMed PMID: 42679488
  17. Jian ZM, Cao JD, Zhu XG, et al. (1999). The impact of alanyl-glutamine on clinical safety, nitrogen balance, intestinal permeability, and clinical outcome in postoperative patients: a randomized, double-blind, controlled study of 120 patients. JPEN Journal of Parenteral and Enteral Nutrition 23(5 Suppl):S62-6. — PubMed PMID: 10483898
  18. Mertes N, Schulzki C, Goeters C, et al. (2000). Cost containment through L-alanyl-L-glutamine supplemented total parenteral nutrition after major abdominal surgery: a prospective randomized double-blind controlled study. Clinical Nutrition 19(6):395-401. — PubMed PMID: 11104589
  19. De-Souza DA, Greene LJ (2005). Intestinal permeability and systemic infections in critically ill patients: effect of glutamine. Critical Care Medicine 33(5):1125-35. — PubMed PMID: 15891348
  20. Albers MJ, Steyerberg EW, Hazebroek FW, et al. (2005). Glutamine supplementation of parenteral nutrition does not improve intestinal permeability, nitrogen balance, or outcome in newborns and infants undergoing digestive-tract surgery: results from a double-blind, randomized, controlled trial. Annals of Surgery 241(4):599-606. — PubMed PMID: 15798461 (an important negative trial)
  21. Fläring UB, Rooyackers OE, Wernerman J, Hammarqvist F (2003). Glutamine attenuates post-traumatic glutathione depletion in human muscle. Clinical Science (London) 104(3):275-82. — PubMed PMID: 12605586
  22. Wong CS, Aly EH (2016). The effects of enteral immunonutrition in upper gastrointestinal surgery: A systematic review and meta-analysis. International Journal of Surgery 29:137-50. — PubMed PMID: 27020765
  23. Cheng PL, Loh EW, Chen JT, Tam KW (2021). Effects of preoperative oral carbohydrate on postoperative discomfort in patients undergoing elective surgery: a meta-analysis of randomized controlled trials. Langenbeck's Archives of Surgery 406(4):993-1005. — PubMed PMID: 33629128
  24. Garlick PJ (2001). Assessment of the safety of glutamine and other amino acids. Journal of Nutrition 131(9 Suppl):2556S-61S. — PubMed PMID: 11533313
  25. Ziegler TR (2001). Glutamine supplementation in cancer patients receiving bone marrow transplantation and high dose chemotherapy. Journal of Nutrition 131(9 Suppl):2578S-84S. — PubMed PMID: 11533316

PubMed Topic Searches

  1. PubMed: Glutamine in elective surgery, randomized controlled trials
  2. PubMed: Alanyl-glutamine dipeptide parenteral nutrition in surgery
  3. PubMed: Glutamine and postoperative infectious complications
  4. PubMed: Glutamine and length of hospital stay after surgery
  5. PubMed: Enhanced Recovery After Surgery nutrition protocols
  6. PubMed: Glutamine, wound healing and collagen synthesis
  7. PubMed: Glutamine and intestinal permeability in surgical patients
  8. PubMed: Glutamine safety in hepatic and renal impairment

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External Authoritative Resources

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Connections

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