Can glutamine be given together with the amino acids arginine, lysine, citrulline, and proline?

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Last updated: June 12, 2025View editorial policy

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From the Guidelines

Glutamine can be safely given together with arginine, lysine, citrulline, and proline, as they are all amino acids that can be combined in supplementation regimens, with typical doses ranging from 0.2-0.4 g/kg/day of glutamine, and varying doses for the other amino acids. These amino acids have different metabolic pathways and functions in the body, allowing them to work complementarily rather than competitively. According to the ESPEN guidelines on parenteral nutrition, glutamine supplementation has been shown to reduce mortality and improve morbidity in critically ill patients, with a recommended dose of 0.2-0.4 g/kg/day 1.

Key Considerations

  • The combination of glutamine with other amino acids such as arginine, lysine, citrulline, and proline may support various physiological functions, including immune health, tissue repair, protein synthesis, and circulatory health.
  • Individuals with kidney or liver disease should consult healthcare providers before combining amino acid supplements, as these organs process amino acids and their metabolites.
  • Those taking medications should also check for potential interactions, particularly with immunosuppressants or certain antibiotics.
  • The ESPEN guidelines on nutrition in cancer patients suggest that glutamine levels drop in severe illness, but it has not been proven that this is caused by glutamine depletion, and long-term supplementation with glutamine in cancer cachexia should be avoided without dedicated studies 1.

Dosing and Administration

  • Typical supplementation doses vary: glutamine (5-10g daily), arginine (3-6g daily), lysine (1-3g daily), citrulline (3-6g daily), and proline (500mg-2g daily), though specific dosing should be tailored to individual needs.
  • When taking multiple amino acids, it's best to divide doses throughout the day to optimize absorption and utilization.
  • The nitrogen concentration ratio of the PN bags should be carefully considered to avoid administration of excessively high volumes 1.

From the Research

Amino Acid Interactions

  • Glutamine can be given together with other amino acids such as arginine, lysine, citrulline, and proline, but the effects of these combinations are not fully understood 2, 3.
  • The metabolism of glutamine and arginine are closely related, and their combined administration may result in additive or synergistic effects on gut barrier function and inflammatory response 2.
  • Glutamine serves as a precursor for the de novo production of arginine through the citrulline-arginine pathway, and its administration can influence arginine levels 3.
  • Citrulline supplementation has been shown to improve microcirculation in animal models with gut injury, but clinical studies are lacking 4.
  • Proline can be synthesized from glutamine catabolism in the intestine, and its supplementation has been studied in relation to glutamine metabolism and function 5.

Safety and Efficacy

  • Glutamine supplementation is generally well-tolerated, but high doses may be associated with increased proline oxidation and decreased proline synthesis 5.
  • The safety and efficacy of combining glutamine with other amino acids such as arginine, lysine, citrulline, and proline have not been fully established, and more research is needed to determine the potential benefits and risks of these combinations 2, 3, 4.
  • Glutamine supplementation has been shown to have beneficial effects on immune function, but the optimal dosage and timing of supplementation are not well-established 6.

Future Directions

  • Further studies are needed to fully understand the effects of combining glutamine with other amino acids such as arginine, lysine, citrulline, and proline, and to determine the potential benefits and risks of these combinations 2, 3, 4.
  • Research should focus on the clinical relevance of the different metabolic pathways involved in glutamine and amino acid metabolism, and on the development of evidence-based guidelines for the use of glutamine and other amino acid supplements in various clinical settings 3, 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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