Dr Fernando Naclerio
Professor of Strength Training and Sports Nutrition; Director of the Centre for Exercise Activity and Rehabilitation, Institute for Lifecourse Development
School of Human Sciences
University of Greenwich
Abstract
Glutamine is the most abundant free amino acid in plasma and skeletal muscle. It is considered a conditionally essential amino acid during periods of physiological stress. It plays important roles in nitrogen transport, immune-cell metabolism and maintenance of intestinal integrity. Glutamine supplementation has attracted interest in physically active individuals because intense exercise, heat stress and training with high physical demands may temporarily increase glutamine requirements. This brief review aims to summarize the biological relevance of glutamine, evaluate current evidence on its use in healthy, physically active adults and provide practical recommendations for supplementation. Overall, current evidence does not support glutamine as a routine ergogenic aid for increasing muscle mass or improving physical performance in well-nourished athletes. Its most relevant application appears to be as a specific, short-term support strategy during periods of high physiological stress, especially when gastrointestinal integrity, recovery after muscle-damaging exercise or illness risk may be compromised. From a practical standpoint, current evidence recommends an intake of approximately 0.1 g/kg of body weight/day, increasing to around 0.3 g/kg/day during short phases focused on recovery after very demanding training. Glutamine should complement, not replace, adequate nutrition and appropriate recovery strategies.
Introduction
Glutamine is a neutral five-carbon amino acid and the most abundant free amino acid in both plasma and skeletal muscle [1,2]. Under normal conditions, it is synthesized primarily in skeletal muscle and is generally considered nonessential. However, during illness, injury, heat stress or high demands from physical training, endogenous production may not fully meet requirements, so glutamine can become conditionally essential [2]. In physically active individuals, glutamine is of interest not as a classic ergogenic aid, but as a nutrient that may help maintain intestinal-barrier integrity and immune function during periods of high physiological stress, with potential indirect benefits for recovery [1].
Biological Functions of Glutamine
Glutamine performs several important functions in human metabolism. It acts as a major nitrogen transporter between tissues, contributes to acid-base balance through renal ammoniagenesis and provides substrate for nucleotide and protein synthesis [3]. It is also a key source of metabolic energy for rapidly proliferating cells, especially small-intestinal enterocytes and immune cells such as lymphocytes and macrophages [4]. Because skeletal muscle is the main site of glutamine production and storage, prolonged or exhaustive exercise can reduce plasma concentrations, especially when recovery is inadequate or training stress is high [5]. These functions provide the main biological basis for considering glutamine supplementation in athletes and physically active individuals [6].
Glutamine Requirements and Dietary Sources
For most healthy, physically active individuals, glutamine requirements can be met through normal endogenous production together with an adequate intake of high-quality protein from foods such as meat, fish, eggs, dairy products, legumes and, when appropriate, protein supplements [1,7]. Although protein-rich foods provide glutamine, a substantial proportion of dietary glutamine is metabolized by the intestine before reaching systemic circulation [5]. Nevertheless, in healthy, physically active individuals, endogenous glutamine synthesis together with adequate energy and protein intake is usually sufficient to maintain glutamine availability and prevent clinical deficiency [3]. Even so, plasma glutamine concentrations may decline temporarily during periods of prolonged, exhaustive exercise, creating a temporary increase in glutamine demand rather than a state of chronic deficiency [6]. For this reason, glutamine supplementation may be more relevant during short periods of unusually high physiological stress, rather than as a routine strategy for every active individual [3,6].
When Glutamine Supplementation May Be Needed in Physically Active People
Current evidence does not support glutamine supplementation as an ergogenic aid for maximizing muscle-mass gains, improving body composition, or enhancing endurance or strength performance in well-nourished athletes [6]. A systematic review and meta-analysis of clinical trials concluded that glutamine supplementation generally had no significant effects on immune-cell counts, endurance performance or body composition (e.g., hypertrophy), although some subgroup analyses suggested that responses could vary according to supplementation protocols and the form of supplement used [6]. This interpretation is consistent with studies that found no improvements in resistance-exercise performance after acute ingestion of high doses of glutamine [8]. Consequently, glutamine should not be presented as a universal performance-enhancing supplement, especially for athletes whose total energy and protein intake is adequate.
The strongest rationale for glutamine supplementation in sport appears to lie in specific situations associated with gastrointestinal and heat stress. Human studies have shown that oral glutamine can attenuate exercise-induced increases in intestinal permeability, including during prolonged exercise and running in the heat [9]. A more recent meta-analysis and systematic review reported no significant overall effect on intestinal permeability when all included adult studies were considered, although subgroup analyses suggested benefits with higher doses and shorter supplementation periods [10]. Importantly, that meta-analysis did not focus specifically on athletes and included heterogeneous adult populations, so it should not be extrapolated directly to physically active or athletic populations. Nevertheless, interpreted alongside studies whose participants exercised, the evidence supports a possible targeted use in endurance athletes, team-sport athletes training in hot environments, or athletes prone to gastrointestinal symptoms during periods of hard training, travel or congested competition schedules [9].
Evidence related to recovery and immune support is more limited and yields mixed results. In male judo athletes, a dose of 3 g/day for two weeks attenuated suppression of neutrophil function and markers of muscle damage during a period of intensive training [11]. In another study, a dose of 0.3 g/kg/day for 72 hours after eccentric exercise improved strength recovery and reduced muscle soreness [12]. However, not every study investigating glutamine's impact on the immune system supports protective effects. For example, an earlier study found that maintaining plasma glutamine availability did not prevent immune changes induced by repeated exercise [13]. More recently, a randomized study in combat-sport athletes reported that three weeks of glutamine supplementation improved salivary immunoglobulin A and hormonal status, and reduced the incidence of upper respiratory tract infections after intensive training [14]. Earlier work also suggested that glutamine intake could increase total-body glycogen storage during recovery [15], although later interpretations indicated that this effect probably occurred more in the liver than in muscle, limiting its practical relevance as a routine strategy for maximizing recovery [16].
In summary, glutamine should primarily be considered a supportive supplement in specific situations, especially when the main concerns are intestinal integrity, recovery under high physiological stress or illness risk, rather than as a consistently effective aid for improving physical performance or maximizing muscle-mass gains [6,16].
Forms of Glutamine Supplements
Most commercial glutamine products contain free L-glutamine, usually as powder or capsules. Powders are generally preferred because they allow flexible dosing and can be added easily to drinks or recovery shakes, whereas capsules are more convenient for travel and routine use. Research has also examined glutamine-containing beverages and dipeptide-based forms, although the current literature does not clearly support one supplemental form as universally superior in active populations [6]. The more stable, soluble dipeptide L-alanyl-L-glutamine has also been proposed, with potential hydration benefits; however, these findings should not be extrapolated directly to pure L-glutamine powders [17].
From a practical standpoint, standard free L-glutamine powder that is neutral in flavor and contains no added flavorings, preservatives, colorings or sweeteners remains the simplest and most widely recommended option.
Recommended Intake Protocols
From a practical perspective, glutamine should be reserved for short periods of increased physiological stress, such as hard, high-volume and intense training blocks, exercise in hot conditions, or phases associated with gastrointestinal stress. In healthy, physically active individuals, an intake of approximately 0.1- 0.3 g/kg of body mass per day would be recommended, taken as a single dose 1-2 hours before training or divided into two or three servings throughout the day on non-training days (for example, at breakfast, lunch and after dinner) [6]. Doses of up to 0.65 g/kg of body weight per day have been reported to be well tolerated, although this should be interpreted as a safety threshold rather than a target intake recommendation [5].
Safety and Possible Side Effects of Glutamine Supplementation in Humans
The most commonly reported side effects are mild gastrointestinal symptoms, such as bloating or stomach discomfort, especially when large single doses are consumed [18]. Consequently, prolonged or high-dose supplementation should be approached cautiously, because the safety of chronic use is less established than that of short-term supplementation [5].
Conclusions and Recommendations
In healthy, physically active adults, glutamine is best used as a short-term supportive supplement rather than as a routine ergogenic aid. Its practical use is most relevant during hard, intense training, prolonged exercise in hot conditions, gastrointestinal stress or periods with frequent competitions [6,9]. An evidence-based approach consists of taking approximately 0.1 g/kg of body weight/day for general support, increasing to around 0.3 g/kg/day during short phases focused on recovery between demanding training sessions [5,12]. Glutamine should complement, not replace, adequate personalized nutrition and appropriate recovery strategies.
Kyowa® L-Glutamine – Recovery, Immunity and Performance
Kyowa® L-Glutamine from Crown Sport Nutrition is a maximum-purity glutamine powder made with Kyowa® Quality raw material, the market's most demanding standard. It supports the immune system, promotes muscle recovery and optimizes nutrient absorption after intense training sessions. Informed Sport anti-doping certified, gluten-free, lactose-free and suitable for vegans.
*Free shipping on orders over 25€
References
1. Cruzat V, Rogero MM, Keane KN, Curi R, Newsholme P. Glutamine: Metabolism and immune function, supplementation and clinical translation. Nutrients. 2018;10:1–31. https://doi.org/10.3390/nu10111564
2. Hankard R, Mauras N, Hammond D, Haymond M, Darmaun D. Is glutamine a “conditionally essential” amino acid in Duchenne muscular dystrophy? Clinical Nutrition. 1999;18:365–9. https://doi.org/10.1016/S0261-5614(99)80017-X
3. Xi P, Jiang Z, Zheng C, Lin Y, Wu G. Regulation of protein metabolism by glutamine: implications for nutrition and health. Front Biosci. 2011;1:578–97. https://doi.org/10.1109/leoswt.2008.4444364
4. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. United States; 1999;4:239–48.
5. Gleeson M. Dosing and efficacy of glutamine supplementation in human exercise and sport training. J. Nutr.; 2008;138:2045S-2049S. https://doi.org/10.1093/jn/138.10.2045s
6. Ramezani Ahmadi A, Rayyani E, Bahreini M, Mansoori A. The effect of glutamine supplementation on athletic performance, body composition, and immune function: A systematic review and a meta-analysis of clinical trials. Clin Nutr. 2019;38:1076–91. https://doi.org/10.1016/j.clnu.2018.05.001
7. Labow BI, Souba WW. Glutamine. World J Surg. 2000;24:1503–13. https://doi.org/10.1007/s002680010269
8. Antonio J, Sanders MS, Kalman D, Woodgate D, Street C. The effects of high-dose glutamine ingestion on weightlifting performance. J Strength Cond Res. United States; 2002;16:157–60.
9. Pugh JN, Sage S, Hutson M, Doran DA, Fleming SC, Highton J, et al. Glutamine supplementation reduces markers of intestinal permeability during running in the heat in a dose-dependent manner.
Eur J Appl Physiol. 2017; https://doi.org/10.1007/s00421-017- 3744-4
10. Abbasi F, Haghighat Lari MM, Khosravi GR, Mansouri E, Payandeh N, Milajerdi A. A systematic review and meta-analysis of clinical trials on the effects of glutamine supplementation on gut permeability in adults. Amino Acids. Springer Vienna; 2024;56. https://doi.org/10.1007/s00726-024-03420-7
11. Sasaki E, Umeda T, Takahashi I, Arata K, Yamamoto Y, Tanabe M, et al. Effect of glutamine supplementation on neutrophil function in male judoists. Luminescence. http://www.ncbi.nlm.nih.gov/pubmed/23348981
12. Legault Z, Bagnall N, Kimmerly DS. The Influence of Oral L-Glutamine Supplementation on Muscle Strength Recovery and Soreness Following Unilateral Knee Extension Eccentric Exercise. Int J Sport Nutr Exerc Metab; 2015;25:417–26. https://doi.org/10.1123/ijsnem.2014-0209
13. Rohde T, MacLean DA, Pedersen BK. Effect of glutamine supplementation on changes in the immune system induced by repeated exercise. Med Sci Sports Exc. 1998;30:856–62.
14. Lu TL, Zheng AC, Suzuki K, Lu CC, Wang CY, Fang SH. Supplementation of L- glutamine enhanced mucosal immunity and improved hormonal status of combat-sport athletes. J Int Soc Sports Nutr; 2024;21. https://doi.org/10.1080/15502783.2023.2300259
15. Bowtell JL, Gelly K, Jackman ML, Patel A, Simeoni M, Rennie MJ. Effect of oral glutamine on whole body carbohydrate storage during recovery from exhaustive exercise. J Appl Physiol. 1999;86:1770–7. https://doi.org/10.1152/jappl.1999.86.6.1770
16. Rennie MJ, Bowtell JL, Bruce M, Khogali SEO. Interaction between glutamine availability and metabolism of glycogen, tricarboxylic acid cycle intermediates and glutathione. J. Nutr.; 2001;131:2488S-2490S. https://doi.org/10.1093/jn/131.9.2488s
17. Hoffman JR, Ratamess NA, Kang J, Rashti SL, Kelly N, Gonzalez AM, et al. Examination of the efficacy of acute L-alanyl-L-glutamine ingestion during hydration stress in endurance exercise. J Int Soc Sports Nutr. 2010; https://doi.org/10.1186/1550- 2783-7-8
18. Ogden HB, Child RB, Fallowfield JL, Delves SK, Westwood CS, Millyard A, et al. Gastrointestinal tolerance of low, medium and high dose acute oral L-glutamine supplementation in healthy adults: A pilot study. Nutrients. 2020;12:1–13. https://doi.org/10.3390/nu12102953
