The Role of Glutamine in Chronic Diseases

Year 2024, , 115 - 120, 30.01.2024

Yasemin Açar , Yasemin Akdevelioğlu

https://doi.org/10.61399/ikcusbfd.1148543

Abstract

Glutamine is a nutrient that is among the immunonutrition products such as arginine, omega-3 fatty acids and nucleotides. Besides being the most abundant amino acid in the human body, it becomes essential due to catabolic conditions such as stress, trauma, and sepsis. The release and availability of circulating glutamine is controlled by major metabolic organs such as the gut, liver, and skeletal muscles. Nitrogen balance, regulation of mucosal immune response, glucose metabolism, preservation of intestinal tissue integrity, and acid-base balance are included among the main functions of glutamine in the cell. In addition, glutamine has functions such as acting as a substrate for lymphocytes and enterocytes, regulating gluconeogenesis and protein synthesis, and suppressing proinflammatory cytokine release. With all these features, glutamine is very important in terms of its effects on health. Glutamine stores in plasma and skeletal muscles are depleted due to metabolic changes that occur in critical illness. It is important to supplement with glutamine to maintain a positive nitrogen balance during those periods. In the current studies, glutamine supplements were made in various ways, including oral, enteral, and/or parenteral, and different glutamine doses were used in the studies. In the literature, there is no definite recommendation for the disease-specific dose and for the most effective route of administration of glutamine. This review was written to examine the effects of glutamine on various diseases such as inflammatory bowel diseases, cardiovascular diseases, cancer, wounds, burns, stress, trauma, and sepsis in the light of data obtained from current studies.

Keywords

Glutamine, chronic disease, nutrition therapy

Glutaminin Kronik Hastalıklardaki Rolü

Abstract

Glutamin; arjinin, omega-3 yağ asitleri ve nükleotid gibi immünonütrisyon ürünleri arasında yer alan bir besin ögesidir. Aynı zamanda insan vücudunda en bol bulunan amino asit çeşidi olmakla birlikte stres, travma ve sepsis gibi katabolik koşullara bağlı olarak elzem hale gelmektedir. Dolaşımdaki glutamin salınımı ve bulunabilirliği bağırsak, karaciğer ve iskelet kasları gibi temel metabolik organlar tarafından kontrol edilmektedir. Glutaminin hücre içindeki başlıca görevleri arasında; nitrojen dengesinin sağlanması, mukozal immün yanıtın ve glukoz metabolizmasının düzenlenmesi, intestinal doku bütünlüğünün korunması ve asit baz dengesinin sağlanması yer almaktadır. Ayrıca glutaminin lenfosit ve enterositler için substrat görevi görme, glikoneogenezi ve protein sentezini düzenleme ve proinflamatuvar sitokin salınımını baskılama gibi görevleri de bulunmaktadır. Tüm bu özellikleri ile glutamin sağlık üzerindeki etkileri açısından oldukça önemlidir. Kritik hastalık durumunda meydana gelen metabolik değişiklikler nedeniyle, plazma ve iskelet kaslarındaki glutamin depoları tükenmektedir. Bu dönemlerde pozitif nitrojen dengesinin sağlanması adına glutamin takviyesinin yapılması önemlidir. Mevcut çalışmalarda glutamin destekleri oral, enteral ve/veya parenteral olmak üzere çeşitli yollarla yapılmış ve çalışmalarda farklı glutamin dozları kullanılmıştır. Literatürde, glutaminin hastalığa özgü dozu ve en etkin veriliş yolu için kesin bir öneri bulunmamaktadır. Bu derleme, güncel çalışmalardan elde edilen veriler ışığında glutaminin inflamatuvar bağırsak hastalıkları, kardiyovasküler hastalıklar, kanser, yara, yanık, stres, travma ve sepsis gibi çeşitli hastalıklar üzerindeki etkilerini incelemek amacıyla yazılmıştır.

Keywords

Glutamin, kronik hastalık, beslenme tedavisi

References

• Cruzat V, Macedo Rogero M, Noel Keane K, Curi R, Newsholme P. Glutamine: metabolism and immune function, supplementation and clinical translation. Nutrients. 2018;10(11):1564.
• Kim M, Wischmeyer PE. Glutamine. World Rev Nutr Diet. 2013;105:90-96.
• Coşkun T. İmmünonütrisyondan farmakonütrisyona. Çocuk Sağlığı ve Hastalıkları Dergisi. 2011;54:164-181.
• Bilski J, Mazur-Bialy A, Brzozowski B, Magierowski M, Zahradnik-Bilska J et al. Can exercise affect the course of inflammatory bowel disease? Experimental and clinical evidence. Pharmacol Rep. 2016;68(4):827-836.
• Kim MH, Kim H. The roles of glutamine in the intestine and its implication in intestinal diseases. Int J Mol Sci. 2017;18(5):1051.
• Hu X, Deng J, Yu T, Chen S, Ge Y, Zhou Z, et al. ATF4 deficiency promotes intestinal inflammation in mice by reducing uptake of glutamine and expression of antimicrobial peptides. Gastroenterology. 2019;156(4):1098- 1111.
• Shariatpanahi ZV, Eslamian G, Ardehali SH, Baghestani AR. Effects of early enteral glutamine supplementation on intestinal permeability in critically ill patients. Indian J Crit Care Med. 2019;23(8):356-362.
• Severo JS, da Silva Barros VJ, da Silva ACA, Parente JML, Lima MM, Lima AÂM, et al. Effects of glutamine supplementation on inflammatory bowel disease: A systematic review of clinical trials. Clin Nutr ESPEN. 2021;42:53- 60.
• Durante W. The emerging role of l-glutamine in cardiovascular health and disease. Nutrients. 2019;11(9):2092.
• Hasani M, Mansour A, Asayesh H, Djalalinia S, Mahdavi Gorabi A, Ochi F et al. Effect of glutamine supplementation on cardiometabolic risk factors and inflammatory markers: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2021;21(1):1-21.
• Wang X, Yang R, Zhang W, Wang S, Mu H, Li H et al. Serum glutamate and glutamine-to-glutamate ratio are associated with coronary angiography defined coronary artery disease. Nutr Metab Cardiovasc Dis. 2022;32(1):186-194.
• Papandreou C, Hernández-Alonso P, Bulló M, Ruiz-Canela M, Li J, Guasch-Ferré M et al. High Plasma Glutamate and a Low Glutamine-to-Glutamate Ratio Are Associated with Increased Risk of Heart Failure but Not Atrial Fibrillation in the Prevención con Dieta Mediterránea (PREDIMED) Study. J Nutr. 2020;150(11):2882-2889.
• Watanabe K, Nagao M, Toh R, Irino Y, Shinohara M, Iino T et al. Critical role of glutamine metabolism in cardiomyocytes under oxidative stress. Biochem Biophys Res Commun. 2021;534:687-693.
• Wang S, Yu X, Zhang W, Ji F, Wang M, Yang R et al. Association of serum metabolites with impaired fasting glucose/diabetes and traditional risk factors for metabolic disease in Chinese adults. Clin Chim Acta. 2018;487:60-65.
• Alipanah-Moghadam R, Molazadeh L, Jafari-Suha Z, Naghizadeh- Baghi A, Mohajeri M, Nemati A. Glutamine supplementation can reduce some atherosclerosis markers after exhaustive exercise in young healthy males. Nutrition. 2022;94:111506.
• Riley P, McCabe MG, Glenny AM. Oral cryotherapy for preventing oral mucositis in patients receiving cancer treatment. JAMA Oncol. 2016;2(10):1365-1366.
• Moslemi D, Nokhandani AM, Otaghsaraei MT, Moghadamnia Y, Kazemi S, Moghadamnia AA. Management of chemo/radiation-induced oral mucositis in patients with head and neck cancer: A review of the current literature. Radiother Oncol. 2016;120(1):13-20.
• Noé JE. L-glutamine use in the treatment and prevention of mucositis and cachexia: A naturopathic perspective. Integr Cancer Ther. 2009;8(4):409-15.
• Anderson PM, Lalla RV. Glutamine for amelioration of radiation and chemotherapy associated mucositis during cancer therapy. Nutrients. 2020;12(6):1675.
• Daniele B, Perrone F, Gallo C, Pignata S, De Martino S, De Vivo R et al. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial. Gut. 2001;48(1):28-33.
• Jebb S, Osborne R, Maughan T, Mohideen N, Mack P, Mort D et al. 5-fluorouracil and folinic acid-induced mucositis: no effect of oral glutamine supplementation. Br J Cancer. 1994;70(4):732-5.
• García-de-Lorenzo A, Zarazaga A, García-Luna PP, Gonzalez- Huix F, López-Martínez J, Miján A et al. Clinical evidence for enteral nutritional support with glutamine: A systematic review. Nutrition. 2003;19(9):805-11.
• Panigrahi P, Gewolb IH, Bamford P, Horvath K. Role of glutamine in bacterial transcytosis and epithelial cell injury. J Parenteral and Enteral Nutr. 1997;21(2):75-80.
• Çekici H, Tatar T, Akbulut G. Kanserde beslenme tedavisi. Ankara: Ankara Nobel Tıp Kitabevleri; 2019. 82 s.
• Tang G, Huang W, Zhang L, Wei Z. Role of Glutamine in the Management of Oral Mucositis in Patients with Cancer: A Meta- Analysis of Randomized Controlled Trials. Nutr Cancer. 2021;74(2):1- 14.
• Peng TR, Lin HH, Yang LJ, Wu T. W Effectiveness of glutamine in the management of oral mucositis in cancer patients: a meta-analysis of randomized controlled trials. Support Care Cancer. 2021;29(8):1-8.
• Sayles C, Hickerson SC, Bhat RR, Hall J, Garey KW, Trivedi MV. Oral glutamine in preventing treatment‐related mucositis in adult patients with cancer: a systematic review. Nutr Clin Pract. 2016;31(2):171-179.
• Gonzalez ACDO, Costa TF, Andrade ZDA, Medrado ARAP. Wound healing-A literature review. An Bras Dermatol. 2016;91(5):614-620.
• Leigh B, Desneves K, Rafferty J, Pearce L, King S, Woodward MC. The effect of different doses of an arginine-containing supplement on the healing of pressure ulcers. J Wound Care. 2012;21(3):150-156.
• Barchitta M, Maugeri A, Favara G, Magnano San Lio R, Evola G, Agodi A et al. Nutrition and wound healing: an overview focusing on the beneficial effects of curcumin. Int J Mol Sci. 2019;20(5):1119.
• Arribas-López E, Zand N, Ojo O, Snowden MJ, Kochhar T. The effect of amino acids on wound healing: a systematic review and meta-analysis on arginine and glutamine. Nutrients. 2021;13(8):2498.
• Wischmeyer PE. Glutamine in burn injury. Nutr Clin Pract. 2019;4(5):681-687.
• Yang YJ, Liu MM, Zhang Y, Wang ZE, Fan SJ, Wei Y et al. Effectiveness and mechanism study of glutamine on alleviating hypermetabolism in burned rats. Nutrition. 2020;79:110934.
• Singer P, Blaser AR, Berger MM, Alhazzani W, Calder PC, Casaer MP et al. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr. 2019;38(1):48-79.
• Cengiz M, Uysal BB, Ikitimur H, Ozcan E, Islamoğlu MS, Aktepe E et al. Effect of oral L-Glutamine supplementation on Covid-19 treatment. Clin Nutr Exp. 2020;33: 24-31.
• McRae MP. Therapeutic benefits of glutamine: An umbrella review of meta-analyses. Biomed Rep. 2017;6(5):576-584.
• Cotoia A, Cantatore LP, Beck R, De Gregorio A, Marchese F, Ferrara G et al. Immunological effects of glutamine supplementation in polytrauma patients in intensive care unit. BMC Immunol. 2022;2:41
• Stehle P, Ellger B, Kojic D, Feuersenger A, Schneid C, Stover J et al. Glutamine dipeptide-supplemented parenteral nutrition improves the clinical outcomes of critically ill patients: A systematic evaluation of randomised controlled trials. Clin Nutr ESPEN. 2017;17:75-85.
• Gorbalenya AE, Baker SC, Baric R, Groot RJD, Drosten C, Gulyaeva AA et al. The species severe acute respiratory syndromerelated coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020;5:536-544.
• World Health Organization. WHO Coronavirus (COVID-19) Dashboard. 2023. https://covid19.who.int/. (Erişim Tarihi: 7 Temmuz 2023).
• T.C. Sağlık Bakanlığı. Günlük COVID-19 Tablosu. 2022. https:// covid19.saglik.gov.tr/. (Erişim Tarihi: 13 Temmuz 2022).
• Naja F, Hamadeh R. Nutrition amid the COVID-19 pandemic: a multi-level framework for action. Eur J Clin Nutr. 2020;74(8):1117-1121.
• Mohajeri M, Horriatkhah E, Mohajery R. The effect of glutamine supplementation on serum levels of some inflammatory factors, oxidative stress, and appetite in COVID-19 patients: a case–control study. Inflammopharmacology. 2021;29(6):1769-1776.
• Soliman OM, Thabet AM, Abudahab GM, Kamel EZ. The impact of glutamine supplementation on the short-term mortality of COVID-19 diseased patients admitted to the ICU: A single-blind randomized clinical trial. Egypt J Anaesth. 2022;38(1):94-100.
• Aydın H, Tekin YK, Korkmaz İ, Tekin G, Yurtbay S, Keleş S et al. Glutamine-driven metabolic adaptation to COVID-19 infection. Ind J Clin Biochem. 2022;8:1-11.