Compendium of the most significant studies with reference to properties, intake, effects.

Holecek M. Side effects of long-term glutamine supplementation. JPEN J Parenter Enteral Nutr. 2013 Sep;37(5):607-16. doi: 10.1177/0148607112460682.

Abstract. Some people consume chronically glutamine (GLN) in high quantities (~40 g/d), although a number of biochemical pathways and cellular functions may be negatively affected. The following side effects of GLN supplementation are discussed...

Gleeson M. Dosing and efficacy of glutamine supplementation in human exercise and sport training. J Nutr. 2008 Oct;138(10):2045S-2049S. doi: 10.1093/jn/138.10.2045S.

Abstract. Some athletes can have high intakes of l-glutamine because of their high energy and protein intakes and also because they consume protein supplements, protein hydrolysates, and free amino acids. Prolonged exercise and periods of heavy training are associated with a decrease in the plasma glutamine concentration and this has been suggested to be a potential cause of the exercise-induced immune impairment and increased susceptibility to infection in athletes.

Reeds PJ, Burrin DG. Glutamine and the bowel. J Nutr. 2001 Sep;131(9 Suppl):2505S-8S; discussion 2523S-4S. doi: 10.1093/jn/131.9.2505S. 

Abstract. Since the pioneering work of Windmueller and Spaeth, the importance of glutamine to the support of intestinal mucosal metabolic function has become generally accepted. Nevertheless, the mechanisms underlying this role still remain obscure. This paper explores a number of questions...

Kim H. Glutamine as an immunonutrient. Yonsei Med J. 2011 Nov;52(6):892-7. doi: 10.3349/ymj.2011.52.6.892.

Abstract. Dietary supplementation with nutrients enhancing immune function is beneficial in patients with surgical and critical illness. Malnutrition and immune dysfunction are common features in hospitalized patients. Specific nutrients with immunological and pharmacological effects, when consumed in amounts above the daily requirement, are referred to as immune-enhancing nutrients or immunonutrients. Supplementation of immunonutrients is important especially for patients with immunodeficiency, virus or overwhelming infections accompanied by a state of malnutrition. Representative immunonutrients are arginine, omega-3 fatty acids, glutamine, nucleotides, beta-carotene, and/or branched-chain amino acids.

Cruzat V, Macedo Rogero M, Noel Keane K, Curi R, Newsholme P. Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients. 2018 Oct 23;10(11):1564. doi: 10.3390/nu10111564.

Abstract. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver, and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to the impairment of homeostasis in the inter-tissue metabolism of amino acids.

Wischmeyer PE. The glutamine debate in surgery and critical care. Curr Opin Crit Care. 2019 Aug;25(4):322-328. doi: 10.1097/MCC.0000000000000633.

Abstract. Purpose of review: Glutamine (GLN) is a versatile amino acid, long believed to have important implications in ICU and surgical patients. An extensive body of data examining GLN supplementation of TPN demonstrated a consistent signal of improved outcomes. However, recently signals of risk have come from two large-scale multicenter trials evaluating GLN (and other nutrients) at high dose and as primary pharmaconutrients, not as supplementation to complete nutrition. These trials indicate a risk of increased mortality when GLN is given to patients in shock, renal failure, and early in acute phase of critical care.

Kawakami I, Yoshino H, Fukumoto W, Tamai M, Okamura S, Osako Y, Sakaguchi T, Inoguchi S, Matsushita R, Yamada Y, Tatarano S, Nakagawa M, Enokida H. Targeting of the glutamine transporter SLC1A5 induces cellular senescence in clear cell renal cell carcinoma. Biochem Biophys Res Commun. 2022 Apr 20;611:99-106. doi: 10.1016/j.bbrc.2022.04.068.

Abstract. In recent years, cancer metabolism has attracted attention as a therapeutic target, and glutamine metabolism is considered one of the most important metabolic processes in cancer. Solute carrier family 1 member 5 (SLC1A5) is a sodium channel that functions as a glutamine transporter....

Glutamine: properties, uses, pros, cons, safety

Glutamine is an amino acid that is highly abundant in the human body. Under normal physiological conditions, it is not classified as strictly essential, because the body can synthesize it; however, in some situations of metabolic stress, trauma, intense catabolism, or illness, it is often considered conditionally essential. The form of greatest biological, nutritional, and technical interest is L-glutamine, with the formula C₅H₁₀N₂O₃ and a molecular weight of about 146.14 g/mol.

Description

Glutamine is a proteinogenic amino acid with an important role in nitrogen metabolism, tissue balance, and support for high-turnover cells, such as intestinal and immune cells. From an industrial point of view, it can be obtained through fermentation or other production processes suitable for the required grade.

For food and nutritional applications, the main factors are purity, the correct stereochemical profile, microbiological quality, and control of contaminants. In cosmetics, Glutamine is a relatively simple ingredient, used mainly in formulas that emphasize an amino acid profile and support the conditioning of skin and hair.

Production process

For food and nutraceutical use, L-glutamine is commonly produced through microbial fermentation, followed by purification, crystallization, drying, and analytical controls. This approach allows good selectivity and suitable quality for regulated applications.

For cosmetic or technical use, it may be supplied as a crystalline powder or as a component of amino acid blends or aqueous bases. Quality controls generally concern identity, assay, purity, moisture, contaminants, and batch stability.

Key constituents

In the case of Glutamine, the ingredient is essentially a single molecule and not a complex mixture. The main compound is therefore L-glutamine itself. Any accessory components of the commercial grade are limited to traces of process impurities, residual moisture, or possible excipients present in the finished raw material.

From a nutritional point of view, Glutamine is often discussed together with other amino acids involved in muscle, immune, and intestinal metabolism, but it has a distinct profile compared with the BCAAs.

Identification data and specifications

Physico-chemical properties (indicative)

Food focus

From a food perspective, Glutamine is naturally present in protein-rich foods such as meat, milk, dairy products, eggs, legumes, and other protein sources. Under normal conditions, an adequate diet and healthy physiology generally allow requirements to be covered without particular difficulty.

Glutamine is also widely used in the sports and nutraceutical sector, where it is proposed for recovery, support of muscle metabolism, or assistance under conditions of high physical load. However, its use as a supplement should be interpreted with balance: in many healthy individuals, the practical benefit is not always as marked as sometimes suggested by marketing, and the real usefulness depends on the nutritional context, the intensity of physical stress, and the overall quality of the diet.

In the clinical and metabolic field, Glutamine is of particular interest because it may become conditionally essential in catabolic states or under strong stress, but this does not mean that every healthy person necessarily needs to supplement it. In practice, supplementation should be evaluated in context and not assumed automatically.

Cosmetic focus

In the cosmetic sector, Glutamine is used mainly as an ingredient with hair conditioning, skin conditioning, and, according to some informative databases, also antistatic functions. In practice, it is included in formulations designed to highlight the amino acid content, improve the technical profile of the formula, and help maintain good skin and hair condition.

In skin formulations it may be used in light serums, hydrating products, gentle emulsions, and amino acid complexes. In hair products it may contribute to the conditioning profile and reduction of electrostatic effect, especially when associated with other amino acids, humectants, and conditioning agents.

From a formulation point of view, it is a relatively simple ingredient to handle, generally compatible with aqueous systems. Its cosmetic impact, however, is often more complementary than leading: the perceived value depends on the overall formula, the actual concentration, and the delivery system.

Cosmetics

Commonly reported INCI / informative functions: hair conditioning, skin conditioning, antistatic.

Pros

• It is an amino acid with an important and well-known metabolic role.

• In some physiological or catabolic contexts it may acquire conditionally essential relevance.

• It is widely available in protein foods and standardized nutritional products.

• In cosmetics it is a simple ingredient to incorporate into aqueous formulations and amino acid complexes.

• It may contribute to the conditioning profile of skin and hair products.

Cons

• Supplementation is not automatically necessary in healthy subjects with an adequate diet.

• Practical benefits in the sports context may be less evident than suggested by some commercial claims.

• In nutritional use, the real value depends greatly on the clinical, dietary, and metabolic context.

• In cosmetics, on its own it often has a more complementary than central role.

• In complex formulas, as with other hydrophilic actives, overall compatibility with pH, preservatives, and other ingredients should still be verified.

Safety, regulatory aspects and environment

From a safety perspective, Glutamine is a widely known and studied substance. For food use, the main issue is not so much toxicity at normal dietary quantities, but rather the appropriateness of the use context, the quality of the supplement, and the correct evaluation of the dose.

For cosmetic use, it is not considered a classic fragrance allergen. As with any ingredient, however, individual sensitivity in the finished product cannot be ruled out, especially if it is included in complex formulations or used on particularly reactive skin.

From an environmental and industrial point of view, modern fermentation-based processes are generally consistent with well-controlled production; actual impact, however, depends on the specific process, purification, and energy management of the manufacturing site.

Conclusion

Glutamine is an amino acid of great biological and nutritional interest, with primary value in the food focus because of its role in nitrogen metabolism, in supporting high-turnover tissues, and in the response to metabolic stress conditions. Under ordinary conditions it is not strictly essential, but in some contexts it may become conditionally essential.

In the cosmetic focus, Glutamine has a more technical and complementary role, as a skin conditioning, hair conditioning, and amino acid complex support ingredient. Overall, it is a solid, well-known, and relatively easy-to-handle ingredient, whose value emerges especially when it is placed in a well-designed nutritional or formulation context.

Studies

Nutritional supplementation with glutamine is used by athletes because, due to its immunomodulatory role, it may help improve certain fatigue-related parameters (1).

This study calculated the amounts of glutamine derived from both dietary and endogenous processes and established that clinical doses of free glutamine for intestinal disorders should be comparable to the daily amount of glutamine metabolized by the small intestine rather than to the daily dietary intake (2).

Supplementation with immunonutrients (arginine, omega-3 fatty acids, glutamine, nucleotides, beta-carotene, and/or branched-chain amino acids) is particularly important for patients with immunodeficiency, viruses, or severe infections (3).

A detailed synthesis has been provided of the biochemical framework of glutamine metabolism in leukemia, the molecular mechanisms that promote glutamine dependency, the downstream functional consequences on proliferation, redox balance, and leukemic stem cell biology, as well as the current landscape of therapeutic strategies and emerging directions aimed at overcoming resistance and improving clinical efficacy (4).

For more information: 

  Glutamine studies

Typical commercial product characteristics Glutamine

• Molecular Formula  C₅H₁₀N₂O₃
• Linear Formula    H₂NCOCH₂CH₂CH(NH₂)CO₂H
• Molecular Weight    146.14
• Exact Mass   146.069138
• CAS  56-85-9
• UNII    0RH81L854J
• EC Number   200-292-1    230-006-0
• DSSTox Substance ID  DTXSID1023100
• IUPAC  (2S)-2,5-diamino-5-oxopentanoic acid
• InChI=1S/C5H10N2O3/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H2,7,8)(H,9,10)/t3-/m0/s1
• InChl Key      ZDXPYRJPNDTMRX-VKHMYHEASA-N
• SMILES   C(CC(=O)N)C(C(=O)O)N
• MDL number  MFCD00008044
• PubChem Substance ID    24895342
• ChEBI  18050
• eCl@ss    32160406
• Beilstein    1723797
• JECFA    1430   
• NACRES  NA.26
• FEMA   3684
• NSC   760081    759628
• RTECS   MA2275100
• RXCUI   4885  
• NCI   C522

Synonyms

• Levoglutamide
• L-Glutamic acid 5-amide
• (S)-2,5-Diamino-5-oxopentanoic acid

References________________________________________________________________________

(1) Coqueiro AY, Rogero MM, Tirapegui J. Glutamine as an Anti-Fatigue Amino Acid in Sports Nutrition. Nutrients. 2019 Apr 17;11(4):863. doi: 10.3390/nu11040863.

Abstract. Glutamine is a conditionally essential amino acid widely used in sports nutrition, especially because of its immunomodulatory role. Notwithstanding, glutamine plays several other biological functions, such as cell proliferation, energy production, glycogenesis, ammonia buffering, maintenance of the acid-base balance, among others. Thus, this amino acid began to be investigated in sports nutrition beyond its effect on the immune system, attributing to glutamine various properties, such as an anti-fatigue role. Considering that the ergogenic potential of this amino acid is still not completely known, this review aimed to address the main properties by which glutamine could delay fatigue, as well as the effects of glutamine supplementation, alone or associated with other nutrients, on fatigue markers and performance in the context of physical exercise. PubMed database was selected to examine the literature, using the keywords combination "glutamine" and "fatigue". Fifty-five studies met the inclusion criteria and were evaluated in this integrative literature review. Most of the studies evaluated observed that glutamine supplementation improved some fatigue markers, such as increased glycogen synthesis and reduced ammonia accumulation, but this intervention did not increase physical performance. Thus, despite improving some fatigue parameters, glutamine supplementation seems to have limited effects on performance.

(2) McMullen MK. Glutamine: A misunderstood amino acid with therapeutic potential. Nutr Health. 2025 Dec;31(4):1325-1329. doi: 10.1177/02601060251356147.

Abstract. Background: Glutamine is an amino acid with trophic activity in the small intestine. The small intestine derives exogenous glutamine from foods and endogenous glutamine from arterial blood. Glutamine is vital for the rapidly proliferating enterocytes lining the intestinal mucosa and promotes the expression of proteins in the tight junctions, strengthening the barrier function and reducing gut permeability. With excessive physical activity, malnutrition, acute and chronic illnesses, sarcopenia or prolonged fasting, plasma levels drop. When glutamine is depleted, the small intestine atrophies causing increased gut permeability and bacterial dislocation. The use of intravenous glutamine is well established in critical medicine, by increasing depressed glutamine plasma levels intestinal atrophy is averted. Therefore, glutamine is classified as a conditionally essential amino acid. Aim: To calculate the amounts of glutamine derived from both food and endogenous processes and to establish a suitable dosage for oral supplementation. Methods: The contribution of dietary amino acids and endogenous glutamine was assessed and compared. The pharmacokinetics of glutamine supplementation was reviewed. Results: Approximately 88% of the glutamine metabolised daily is endogenously produced. Almost half of this comes from muscle protein breakdown. Studies with supplemental free-form glutamine for treating intestinal permeability, at doses based on dietary intake, have not yielded positive results, whereas doses of 30 g glutamine, similar to daily amount metabolised by the enterocytes yielded positive results. Discussion: Clinical doses of free-form glutamine for intestinal disorders should be akin to the daily amount of glutamine metabolised by the small intestine rather than the daily dietary intake.

(3) Kim H. Glutamine as an immunonutrient. Yonsei Med J. 2011 Nov;52(6):892-7. doi: 10.3349/ymj.2011.52.6.892.

Abstract. Dietary supplementation with nutrients enhancing immune function is beneficial in patients with surgical and critical illness. Malnutrition and immune dysfunction are common features in hospitalized patients. Specific nutrients with immunological and pharmacological effects, when consumed in amounts above the daily requirement, are referred to as immune-enhancing nutrients or immunonutrients. Supplementation of immunonutrients is important especially for patients with immunodeficiency, virus or overwhelming infections accompanied by a state of malnutrition. Representative immunonutrients are arginine, omega-3 fatty acids, glutamine, nucleotides, beta-carotene, and/or branched-chain amino acids. Glutamine is the most abundant amino acid and performs multiple roles in human body. However, glutamine is depleted from muscle stores during severe metabolic stress including sepsis and major surgery. Therefore it is considered conditionally essential under these conditions. This review discusses the physiological role of glutamine, mode and dose for glutamine administration, as well as improvement of certain disease state after glutamine supplementation. Even though immunonutrition has not been widely assimilated by clinicians other than nutritionists, immunonutrients including glutamine may exert beneficial influence on diverse patient populations.

(4) Silvestri G. Fueling the Fire: How Glutamine Metabolism Sustains Leukemia Growth and Resistance. BioMed (Basel). 2026 Mar;6(1):7. doi: 10.3390/biomed6010007. 

Abstract. Glutamine metabolism has emerged as one of the most critical bioenergetic and biosynthetic programs sustaining leukemic cell growth, survival, stemness and therapeutic resistance. In both acute and chronic leukemias, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), malignant cells display a strong dependency on extracellular glutamine to support mitochondrial respiration, anabolic biosynthesis and redox homeostasis. This dependency is reinforced by oncogenic signaling networks, post-transcriptional metabolic regulation and microenvironmental adaptation within the bone marrow niche. Therapeutic strategies targeting glutamine utilization, including glutaminase inhibition, transporter blockade and enzymatic glutamine depletion, have demonstrated robust antileukemic activity in preclinical models, and early clinical efforts have begun to explore glutamine-directed interventions in myeloid neoplasms. However, metabolic plasticity, microenvironment-derived nutrient buffering and systemic toxicity remain significant limitations to clinical translation. This review provides a detailed synthesis of the biochemical framework of glutamine metabolism in leukemia, the molecular mechanisms enforcing glutamine addiction, the downstream functional consequences on proliferation, redox balance and leukemic stem cell biology, the current landscape of therapeutic strategies and emerging directions aimed at overcoming resistance and improving clinical efficacy.