9 Benefits and Side Effects of L-glutamine (7 Contraindications To Be Noted)
Discover the science behind L-glutamine supplementation, including evidence for gut health, cancer treatment support, and athletic performance.
L-glutamine (often just called glutamine) is an amino acid that’s generated a lot of buzz in recent years. You’ll find it marketed for everything from gut health to muscle building to cancer treatment support. But what does the research actually show? The answer, as with many supplements, is more nuanced than the marketing suggests.
What is L-glutamine?
L-glutamine is the most abundant amino acid in the human body, making up roughly 60% of the free amino acid pool in your muscles and about 20% of what’s floating around in your blood plasma 1. Your body uses it for an impressive array of functions: producing energy and building nucleotides (the building blocks of DNA), maintaining redox balance, regulating acid-base balance, metabolising glucose, controlling gene expression, producing cytokines and hormones, maintaining muscle protein, and enabling cell proliferation.
Because your tissues can synthesise L-glutamine on their own, it’s classified as a “non-essential” amino acid. However, this label is a bit misleading. During periods of severe stress—think major surgery, serious illness, sepsis, or intense athletic training—your body’s demand for glutamine can outstrip its ability to produce it. When this happens, blood and cellular levels drop, potentially leading to problems with immune function, gut integrity, and recovery 2. This is why researchers often call glutamine a “conditionally essential” amino acid.
How much L-glutamine should you take?
Clinical studies have used doses ranging from around 5 grams daily up to approximately 6 grams per day for extended periods of up to 45 weeks. If you’re considering supplementation, starting with a conservative dose of around 3 grams daily is sensible.
For specific clinical applications, the research has used:
- Chemotherapy-related oral mucositis: 4 grams per day, starting with the first chemotherapy session and continuing until discharge or symptom resolution
- General supplementation: 5-10 grams daily in divided doses
- Athletic support: Typically 5 grams before or after training
The upper safe limit observed in studies where no adverse effects occurred was approximately 14 grams per day 3. Higher doses have been used and tolerated, but there simply isn’t enough evidence to confirm long-term safety at very high intakes.
What are the proven benefits of L-glutamine?
1. May support recovery after colorectal cancer surgery
Colorectal cancer is the fourth most common cancer globally, accounting for roughly 6% of all cancer diagnoses. For patients with localised tumours, the 5-year survival rate is around 93%—but this drops dramatically to just 5% for those with distant metastases 4.
Surgical resection remains the primary treatment, but not everyone is a candidate due to factors like extensive peritoneal spread or surgical comorbidities.
A meta-analysis examining 31 randomised controlled trials involving 2,201 colorectal cancer patients found that glutamine supplementation (either enteral or parenteral) improved immune function and reduced postoperative complications compared to controls. The complications that improved included surgical site infections, anastomotic leaks, and length of hospital stay 4.
My take: This is reasonably encouraging data, though the authors themselves noted potential bias and sample heterogeneity. If you’re facing colorectal surgery, it’s worth discussing with your surgical team—but don’t expect miracles.
2. May benefit severe acute pancreatitis
Acute pancreatitis is the most common gastrointestinal disorder requiring hospitalisation. The usual culprits are gallstones (28-38% of cases), alcohol (19-41%), and idiopathic causes (10-40%), with rarer triggers including high triglycerides, elevated calcium, family history, certain medications, trauma, and autoimmune conditions.
The disease ranges from mild inflammation to severe complications including acute peripancreatic effusion, pancreatic pseudocysts, acute necrotising collections, and walled-off necrosis.
A meta-analysis of 7 randomised controlled trials involving 433 patients with severe acute pancreatitis compared glutamine plus early enteral nutrition (EEN) against EEN alone 5. The combination increased serum albumin levels, reduced the inflammatory marker C-reactive protein, decreased the risk of death and multiple organ dysfunction syndrome, and shortened hospital stays. Importantly, adding glutamine didn’t increase infection rates or surgical interventions.
Worth noting: Early enteral nutrition itself is crucial in pancreatitis management. The glutamine appears to provide additional benefit on top of this foundation, not as a standalone treatment.
3. Mixed results for inflammatory bowel disease
Inflammatory bowel disease (IBD) encompasses Crohn’s disease and ulcerative colitis—two conditions characterised by chronic, recurring gut inflammation. Both share symptoms like diarrhoea, bloody stools, and abdominal pain, though they differ in where inflammation occurs and how deeply it penetrates the intestinal wall.
The theory behind glutamine supplementation is appealing: it’s the primary fuel source for intestinal cells (enterocytes), so extra glutamine might help repair and maintain the gut lining.
However, a systematic review of seven randomised controlled trials found no significant effect of glutamine on disease progression, body measurements, intestinal permeability, gut structure, disease activity, symptoms, biochemical markers, oxidative stress, or inflammatory markers—regardless of whether it was given orally or intravenously 6.
The catch: The theory is sound, but the clinical evidence simply hasn’t materialised. If you have interstitial cystitis or painful bladder syndrome, where gut-bladder connections are increasingly recognised, you might wonder if glutamine could help—but based on current IBD evidence, I wouldn’t bet on it.
4. Helps reduce chemotherapy and radiotherapy-induced mucositis
Oral mucositis—severe inflammation and ulceration of the mouth lining—is arguably the most debilitating non-blood-related complication of cancer treatment. It affects around 80% of patients receiving head and neck radiotherapy, 40-80% of chemotherapy patients, and over 75% of bone marrow transplant recipients.
It starts as redness but often progresses to painful erosions and ulcers that make speaking, swallowing, and eating extremely difficult. Severe cases can lead to dehydration, electrolyte imbalances, malnutrition, and rarely, death.
A systematic review of 15 studies found that oral L-glutamine significantly reduced the incidence of grade 2, 3, and 4 mucositis following chemotherapy or radiotherapy 7. It also shortened how long mucositis lasted, delayed its onset, reduced its severity, and helped patients maintain their weight. (Though nausea, vomiting, dry mouth, and appetite loss weren’t significantly different.)
Another meta-analysis focusing on 234 head and neck cancer patients across 5 studies confirmed that oral L-glutamine reduced both the risk and severity of severe oral mucositis from cancer treatment 8.
This is probably the strongest evidence for L-glutamine supplementation. If you’re about to start chemotherapy or radiotherapy, particularly for head and neck cancers, there’s good reason to discuss glutamine with your oncologist. Starting a few days before treatment appears optimal.
5. Limited evidence for chemotherapy-induced peripheral neuropathy
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and distressing side effect of certain chemo drugs, particularly platinum compounds, taxanes, vinca alkaloids, thalidomide, and bortezomib. Symptoms include sensory abnormalities, pain, and sometimes loss of motor control—occasionally forcing dose reductions or treatment cessation, which obviously compromises cancer treatment effectiveness.
The prevalence is startlingly high: 68.1% of patients experience it within the first month of chemotherapy, with symptoms persisting in many patients months later.
A literature analysis of 4 studies examined whether oral L-glutamine could help 9. The results were mixed: while it appeared to reduce pain, it didn’t significantly improve other measures like severity, numbness, or muscle weakness.
Reality check: The sample sizes were small, and the evidence is far from compelling. If you’re dealing with chemotherapy-related neuropathy, glutamine might be worth trying for pain relief, but keep expectations modest. Other approaches like duloxetine have better evidence, so discuss options with your oncology team.
6. May shorten chemotherapy-induced diarrhoea
Diarrhoea is a frequent chemotherapy side effect, particularly with 5-fluorouracil and irinotecan regimens. Up to 82% of patients experience some degree of diarrhoea, with a third having severe (grade 3 or 4) symptoms.
The consequences extend beyond inconvenience: about 60% of affected patients need treatment modifications, 22% require dose reductions, 28% experience treatment delays, and 15% stop treatment entirely. Severe, persistent diarrhoea leads to malnutrition, dehydration, weight loss, fatigue, kidney problems, and secondary infections.
A meta-analysis of 8 randomised controlled trials with 298 participants found that L-glutamine reduced the duration of chemotherapy-induced diarrhoea—particularly when given orally or intravenously 10. However, it didn’t significantly improve diarrhoea severity.
In practice: If you’re experiencing persistent chemotherapy-related diarrhoea, glutamine might help you recover faster, though it won’t necessarily make the episodes less severe when they happen. This is useful, but not a game-changer.
7. Inconclusive for radiation enteritis
Radiation therapy is essential for treating many cancers of the gastrointestinal tract, urinary system, and gynaecological organs. While modern techniques target tumours more precisely than ever, radiation still damages healthy tissue—particularly the highly sensitive small intestine.
Radiation enteritis causes symptoms including pain, bloating, nausea, urgency, diarrhoea, and rectal bleeding. These significantly impact quality of life and, in patients with radiation cystitis or hemorrhagic cystitis, may compound bladder-related symptoms.
A meta-analysis of 13 randomised controlled trials involving 979 patients undergoing pelvic or abdominal radiation found that L-glutamine reduced the incidence of radiation enteritis and improved symptoms including urgency, abdominal cramps, and rectal bleeding compared to controls 11. However, the improvements weren’t statistically significant.
My assessment: The trend is positive, but the statistics don’t support a firm recommendation. More research with larger sample sizes is needed.
8. May benefit critically ill patients—but mainly burn victims
Critical illness triggers dramatic metabolic changes leading to rapid malnutrition and compromised immunity. Between 20-40% of intensive care patients show signs of protein-energy malnutrition, often exacerbated by poor appetite, gastrointestinal symptoms, depression, and anxiety.
A meta-analysis of 11 randomised controlled trials with 1,079 critically ill adults found that enteral L-glutamine supplementation reduced hospital stay length but didn’t significantly reduce mortality, infectious complications, or ICU duration 12.
However, the same analysis noted something interesting: in the subset of burn patients specifically, enteral glutamine significantly reduced both mortality and length of stay.
Worth noting: For general critical illness, glutamine offers marginal benefit at best. But burn patients appear to be a special case where supplementation makes a meaningful difference. If you’re caring for someone with severe burns, this is worth raising with the medical team.
9. Disappointing evidence for athletic performance
Sports nutrition has evolved dramatically, and proper nutrition is now recognised as crucial for performance, recovery, and immune function during intense training.
L-glutamine is heavily marketed to athletes with claims about muscle recovery, immune support, and performance enhancement. A meta-analysis examined these claims systematically 13. The results were underwhelming: glutamine supplementation was only slightly helpful for reducing body weight. It didn’t significantly improve immune markers (white blood cells, lymphocytes, neutrophils), maximal oxygen uptake (VO2max), body composition (fat mass or lean mass), muscle damage markers (creatine kinase), or growth hormone levels.
My take: If you’re taking L-glutamine hoping it’ll boost your gym performance or help you recover faster from training, the evidence suggests you’re probably wasting your money. The marketing vastly outpaces the science here. Better options for athletic performance include creatine, BCAAs, and adequate protein intake.
What are the side effects of L-glutamine?
Since L-glutamine occurs naturally in your body and in many foods, supplementation at reasonable doses generally doesn’t cause problems. However, reported side effects include:
- Constipation or bloating
- Abdominal discomfort
- Nausea
- Headache
- Cough
- Pain in arms or legs
- Shortness of breath
- Skin rash
- Chest tightness or wheezing
- Rapid heartbeat
- Chills
- Decreased urine output
The observed safe upper limit from clinical studies is around 14 grams daily 3. While higher doses have been used without obvious harm, there’s insufficient long-term safety data for chronic high-dose supplementation.
Safety precautions and contraindications
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Pregnancy and breastfeeding: Avoid use, as safety hasn’t been established.
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Liver disease: Don’t use if you have cirrhosis or hepatic encephalopathy—glutamine may worsen symptoms by contributing to ammonia buildup.
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MSG sensitivity: If you react to monosodium glutamate (sometimes called “Chinese restaurant syndrome”), be cautious. Your body converts glutamine to glutamate, which may trigger similar reactions.
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Neurological conditions: Avoid if you have epilepsy or mania, as glutamine may increase seizure risk or worsen manic episodes.
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Amino acid absorption: High-dose glutamine may interfere with absorption and transport of other amino acids.
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Anti-epileptic medications: Don’t use with phenobarbital, primidone, valproic acid, gabapentin, carbamazepine, or phenytoin. Glutamine affects brain chemistry in ways that may reduce these drugs’ effectiveness.
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Lactulose: Avoid combining with lactulose (used for constipation and hepatic encephalopathy), as glutamine may interfere with the medication’s action.
Food sources of L-glutamine
Your body synthesises L-glutamine from glutamic acid, but when demand exceeds supply, dietary sources become important. Almost any protein-containing food provides some glutamine—the difference is mainly quantity.
Rich animal sources include beef, chicken, fish (particularly tuna), cheese, prawns, and dairy products. Plant sources include beans, spinach, kale, nuts (especially tree nuts), and peanuts 14.
If you’re eating adequate protein from varied sources, you’re likely getting 3-6 grams of glutamine daily from food alone. For most healthy people, this is sufficient. Supplementation becomes relevant mainly during illness, surgery recovery, or potentially during very intense athletic training—though as discussed, the athletic benefits are poorly supported by evidence.
The bottom line
L-glutamine has genuine therapeutic potential in specific clinical contexts—particularly supporting cancer patients through chemotherapy and radiotherapy side effects, and possibly helping burn patients and those recovering from major surgery. For these uses, discussing supplementation with your medical team is reasonable.
However, the heavily marketed claims around gut health for the general population and athletic performance simply aren’t supported by current evidence. If you’re healthy and eating adequate protein, your body produces all the glutamine it needs. Save your money for supplements with stronger evidence for whatever your specific health goals might be.
Medical Disclaimer: The information provided is for educational purposes only and should not be considered as medical advice. Always consult with a qualified healthcare professional before making any changes to your diet, supplement regimen, or treatment plan.