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9 Benefits and SideEeffects of L-glutamine (7 Contraindications To Be Noted)

L-glutamine (or glutamine) is an important amino acid with a variety of functions in the human body, and has been commonly used in cancer radiotherapy and chemotherapy, after surgery and fitness supplementation in recent years.

Here’s why L-glutamine is important and discusses the benefits and contraindications of supplementation.

What is L-glutamine?

L-glutamine is the most abundant amino acid in the human body, accounting for about 60% of the muscle free amino acid pool and 20% of the plasma free amino acid pool. Note 10

L-glutamine is primarily involved in various physiological processes, including energy and nucleotide formation, redox balance, acid-base balance, glucose metabolism, gene expression, cytokines, hormone production, muscle protein metabolism, and cell proliferation.

Since most tissues synthesize L-glutamin, it is not an essential amino acid.

However, it is hypothesized that L-glutamine is a conditionally essential amino acid in catabolic and stressful states, and that once demand exceeds its own synthetic capacity, plasma and intracellular L-glutamine concentrations decline and lead to physiological dysfunction, for example, normalization of status through early exogenous supplementation can help improve clinical outcomes during intensive exercise and severe illness (trauma, surgery, sepsis).

How to eat L-glutamine (dosage)?

The doses used in the studies ranged from about 5 grams per day to high doses of about 6 grams per day for 45 weeks.

If you decide to take a L-glutamine supplement, it’s best to start with a conservative dose of around 3 grams per day.

Reduction of oral mucositis caused by chemotherapy: 4 g per day, starting with the first chemotherapy, until discharge or disappearance of symptoms.

What are the proven benefits of L-glutaminate?

1. Improve immunity and complications after radical surgery for colorectal cancer

Colorectal cancer is the fourth most common cancer, accounting for 6% of all cancer diagnoses, and the prognosis for staging varies widely, with a 5-year survival rate of 93% for localized tumors and 5% for distant metastases.

Surgical resection is the mainstay of treatment for colorectal cancer, however, not all patients are candidates for therapeutic surgery due to factors such as high-volume peritoneal spread or comorbidities of surgery.

A meta-analysis of 31 randomized controlled trials of 2,201 patients with colorectal cancer undergoing radical surgery found that glutamine/glutamine (enteral or parenteral nutrition) was effective in improving immune function (including humoral immune function and T-cell immune function) and reducing postoperative complications (including surgical site infection, anastomotic leak, and length of hospital stay) in patients undergoing radical colorectal cancer resection compared with controls. Note 1

*Conclusion: For patients with colorectal cancer who have undergone radical surgery, glutamine supplementation may bring positive help, but more studies are needed to verify it due to the possible risk of bias and heterogeneity of the samples

2. Beneficial severe acute pancreatitis

Acute pancreatitis is the most common gastrointestinal disorder, with the three most common causes of gallstone/biliary tract (28% to 38%), alcohol-related (19% to 41%), and idiopathic (10% to 40%), along with hypertriglyceridemia or hypercalcaemia, family history of pancreatic disease, prescription/over-the-counter medications, trauma, and autoimmune disease.

Disease can range from mild to severe with systemic complications (common complications include acute peripancreatic effusion, pseudocyst of the pancreas, acute necrotising effusion, and wallal necrosis). The basis of treatment includes aggressive fluid resuscitation, appropriate nutritional supplementation, and management of complications.

A meta-analysis (7 randomized controlled trials, 433 patients with severe acute pancreatitis) noted that glutamine + EEN increased serum albumin, reduced serum hypersensitivity C-reactive protein and the risk of death, multiple organ dysfunction syndrome (MODS), and shortened hospital stay compared with early enteral nutrition (EEN). Note 1

In addition, glutamine + EEN did not significantly increase infection-related morbidity, surgical intervention, or acute physiologic and chronic health assessment (APACHE II) scores.

*Conclusion: For acute pancreatitis, glutamine/glutamine + early enteral nutrition may bring positive benefits

3. Beneficial for inflammatory bowel diseases

Inflammatory bowel disease is a multifactorial immune disease characterized by chronic, recurrent bowel inflammation.

It is divided into two different diseases: Crohn’s disease and ulcerative colitis. Clinically, the two have similar symptoms, including diarrhoea, blood in the stool, and abdominal pain, but the location and depth of inflammation, as well as complications and prevalence, may differ.

Currently, the exact cause of inflammatory bowel disease is unknown. However, when certain environmental factors trigger genetically predisposed hosts, disturbances of the immune system interact with imbalances in microbes leading to the development of chronic intestinal inflammation.

A systematic review (seven randomized controlled trials of inflammatory bowel disease) noted that glutamamine had no significant effect on disease course, anthropometry, intestinal permeability and morphology, disease activity, intestinal symptoms, biochemical parameters, oxidative stress, and inflammatory markers, regardless of route of administration. Note 1

*Conclusion: To date, glutamine has not been clearly helpful in improving inflammatory bowel disease

4. Improve chemotherapy or radiotherapy-induced mucositis

The term mucositis was first introduced in 1980 to describe inflammation of the oral mucosa caused by radiotherapy (occurring in 80% of patients), chemotherapy (40-80% of patients), and bone marrow transplantation (more than 75% of patients).

Currently, oral mucositis is considered the most serious non-hematologic complication of cancer treatment, initially presenting as erythema of the oral mucosa and often progressing to erosions and ulcers that cause oral impairment such as difficulty speaking, swallowing saliva, or eating.

The consequences of mucositis may be mild and require little intervention, but they can be serious, such as causing hypovolemia, electrolyte abnormalities, malnutrition, and even death.

A systematic review (15 studies) suggests that oral levglutamine significantly reduces the incidence of grade 2, 3, or 4 mucositis after chemotherapy or radiotherapy, as well as the duration, timing, and severity of mucositis, and reduces weight loss (although nausea, vomiting, dry mouth, and anorexia did not differ significantly). Note 1

Another meta-analysis (5 clinical studies with 234 human head and neck cancer patients) pointed out that oral administration of levglutamine reduced the risk and severity of severe oral mucositis caused by radiotherapy or chemotherapy. Note 2

*Conclusion: L-glutamine administration initiated a few days before chemotherapy or radiotherapy has a positive effect on preventing and improving mucositis, but further prospective and large trials are needed to support these findings.

5. Improve peripheral neuropathy caused by chemotherapy

Chemotherapy-induced peripheral neuropathy is a common side effect of specific chemotherapy drugs (especially platinum, taxanes, vinca alkaloids, thalidomide, Vanke bortezomib).

The main symptoms are sensory abnormalities, pain or loss of motor control, which can sometimes lead to a reduction or cessation of chemotherapy doses, limiting the efficacy of cancer treatment.

The prevalence of peripheral neuropathy in the first month of chemotherapy was 68.1%, 3.60% at 0 months, and 6.30% at 0 months

A literature analysis (including 4 studies) pointed out that although oral levaroglutamine can reduce the pain of peripheral neuropathy caused by chemotherapy, it is not significantly helpful for indicators such as severity, numbness, and muscle weakness. Note 3

*Conclusion: For the symptoms of peripheral neuropathy caused by chemotherapy, oral administration of levuroglutamine has not brought significant improvement, and limited by the small sample size, more large studies are still needed to support it

6. Improve diarrhea caused by chemotherapy

Diarrhea is a common side effect of chemotherapy and is often seen in subjects treated with 5-fluorouracil and irinotecan.

The incidence of all grades of diarrhoea during chemotherapy has been reported to be up to 82%, with up to one third of patients experiencing severe (grade 3 or 4) diarrhoea.

Chemotherapy induced diarrhea severely interfered with anti-cancer treatment, resulting in a change in treatment in about 60% of patients, a dose reduction in 22 percent, a delayed dose in 28 percent, and a complete discontinuation of treatment in 15%.

Persistent and severe chemotherapy-related diarrhea is often associated with malnutrition and dehydration, resulting in accompanying weight loss (cachexia), fatigue, renal failure, infection, hemorrhoids, and rupture of perianal skin.

A meta-analysis (8 randomised controlled trials, 298 participants) noted that for chemotherapy-induced diarrhoea, levglutamine reduced the duration of diarrhoea (especially oral and intravenous, but did not) but did not improve its severity. Note 4

*Conclusion: Oral administration of levglutamine improves the duration of chemotherapy-induced diarrhoea, but more large, precisely designed randomized controlled trials are needed

7. Improve radiation enteritis caused by radiotherapy

Radiation therapy is the mainstay of a variety of malignant oncology treatments, commonly used for gastrointestinal, urinary tract and gynecologic cancers, and although it is more specific to the lesion, it still has side effects on normal organs or tissues.

Radiation enteritis, used to define damage to the small intestine as a result of radiation therapy, can lead to acute or chronic radiation enteritis, producing symptoms such as pain, bloating, nausea, stool urgency, diarrhea and rectal bleeding, which have a significant impact on a patient’s quality of life.

A meta-analysis (13 randomized controlled trials, 979 patients undergoing pelvic or abdominal radiation therapy) found that the use of lev-glutamine reduced the incidence of radiation enteritis, increased response rates, and improved symptoms (including tenesmus, abdominal cramps, and blood loss in the stool) compared with controls, but the magnitude of improvement was not statistically significant. Note 5

*Conclusion: For radiation enteritis caused by radiotherapy, oral administration of levglutamine does not significantly improve severity and symptoms, and is limited by the number of samples included in the studies and related biases, which need to be further verified

8. Beneficial to critically ill patients

In most patients, critically ill occurs before physiological deterioration, characterized by strong metabolic changes leading to malnutrition and impaired immune function.

Malnutrition, including the depletion of essential micronutrients and weight loss, is common in severe cases, with 20% to 40% showing signs of protein-energy malnutrition.

Critically ill patients also often have spontaneous reduced food intake due to medical and surgical factors such as anorexia, gastrointestinal symptoms, depression, and anxiety.

A literature review and meta-analysis (11 randomized controlled trials with 1079 adults with severe disease) noted that enteral levaroglutamine supplementation only reduced length of hospital stay and was not significantly helpful in reducing hospital mortality, infectious complications, and intensive care unit stays. Note 6

In addition, the same analysis also pointed out that in a small proportion of burn patients, enteral levorramine supplementation can significantly reduce hospital mortality and length of stay.

*Conclusion: For critically ill patients, enteral levaroglutamine supplementation does not confer significant clinical benefit other than reducing length of hospital stay, and is limited by small sample sizes, which still needs to be supported by larger randomized trials.

9. Beneficial for fitness or athlete performance

With the rapid development of sports nutrition science and practice, nutrition is increasingly recognized as an important part of maintaining optimal exercise performance.

Proper nutrition promotes muscle regeneration, glycogen recovery, reduces fatigue, and supports physical and immune health, which helps athletes prepare for the next competition or training sessions throughout the season.

A literature review and meta-analysis pointed out that for exercise training, L-glutamine supplementation was only slightly helpful in reducing body weight, and other measures were not significantly improved, including: immune function (white blood cell, lymphocyte, and neutrophil count), maximum oxygen uptake (Vo2max), body composition (fat mass and lean body mass), plasma glucocreatine kinase, and growth hormone levels. Note 7

*Conclusion: In general, for fitness or exercise-related training, L-glutamine supplementation is not significantly helpful for the immune system, aerobic exercise performance and body composition, but limited by the small sample size, more large trials are still needed for further verification.

Does L-glutamine have side effects?

Since L-glutamine is an amino acid that occurs naturally in the human body and is present in many foods, proper supplementation is not obviously harmful to the human body.

Possible side effects or adverse reactions that have been reported after supplementation include: constipation, abdominal pain, nausea, headache, cough, pain in the extremities, shortness of breath, rash, chest tightness, wheezing, rapid heartbeat, chills, sudden decrease in urine output etc.

The upper safe value for no side effects observed in the study was about 14 g per day, and doses above this were well tolerated, but there was insufficient evidence that long-term high-dose supplementation was harmless and there was insufficient evidence to assume harm. Note 8

What are the safety precautions for L-glutaminate?

  1. Do not use during lactation in pregnant women (due to relevant safety is not known)
  2. Do not use if you have cirrhosis or hepatic encephalopathy (may worsen symptoms)
  3. People who have been sensitive to monosodium glutamate/monosodium glutamate should not use it (commonly known as Chinese restaurant syndrome), because the body will convert glutamine to sodium glutamate, thus promoting similar sensitivity symptoms.
  4. Do not use in people with epilepsy or mania (may increase the incidence of the disease)
  5. May interfere with the absorption and transport of other amino acids
  6. People taking anti-epileptic drugs should not use it, because glutamine affects the chemicals in the brain, which in turn affects the efficacy of the drug, the related drug names are: phenobarbital, primidone, valproic acid, gabapentin, carbamazepine, phenytoin
  7. Do not use it with lactulose (drugs to treat constipation and improve hepatic encephalopathy), which may affect the efficacy of the drug

What are the food sources of L-glutamine?

L-glutamine is synthesized from glutamic acid or glutamate in the body, and if the body does not produce sufficient amounts, it needs to be taken in increments from the diet.

Almost any food that contains protein will contain some glutamine, the difference is only in the content.

Glutamine is mainly found in animal proteins such as beef, chicken, tuna, cheese, shrimp, dairy products, as well as plant protein sources such as beans, spinach, kale, tree nuts, peanuts, etc. Note 9

It’s worth noting, though, that animal protein isn’t as easily digestible as plant protein.

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