Applied nutritional investigation The safety of oral use of L-glutamine in middle-aged and elderly individuals Siulmara Cristina Galera, M.D., Ph.D., M.Sc. a, *, FranciscoVagnaldo Fechine, M.D., Ph.D. b , Maria Ja ˆnia Teixeira, Ph.D. c , Zirlane Castelo Branco Coelho, M.Sc. d , Raquel Cavalcante de Vasconcelos e , and Paulo Roberto Leita ˜o de Vasconcelos, M.D., D.Phil. a a Department of Surgery, Federal University of Ceara ´, Fortaleza, Ceara ´, Brazil b Department of Physiology and Pharmacology, Federal University of Ceara ´ , Fortaleza, Ceara ´, Brazil c Department of Pathology and Forensic Medicine, Federal University of Ceara ´ , Fortaleza, Ceara ´, Brazil d Department of Clinical and Toxicologic Laboratory, Federal University of Ceara ´, Fortaleza, Ceara ´, Brazil e School of Medicine, Federal University of Ceara ´, Fortaleza, Ceara ´, Brazil Manuscript received December 8, 2008; accepted May 16, 2009. Abstract Objective: To evaluate the safety of nutraceutical oral administration of L-glutamine (L-Gln) in middle-aged and elderly individuals. Methods: In this randomized, crossover, double-blind clinical study, 30 residents of a long-term–care institution, selected according to a modified SENIEUR protocol (Working Party of the EURAGE Con- certed Action Programme on Ageing of the European Community), were studied. Fourteen subjects received orally 0.5 g $ kg 1 $ d 1 of L-Gln and 16 received calcium caseinate for 14 d, followed by a 5-d washout. Supplements were switched for the second 14-d trial. Laboratory tests for hepatic and renal functions and ammonemia were performed and the estimated glomerular filtration rate (eGFR) was calcu- lated. Results: Of the 30 subjects, 16 were men, mean age was 69 6 8.8 y, average weight was 61.8 6 14.2 kg, and mean serum albumin was 4.0 6 0.3 g/dL. Neither adverse clinical effects nor clin- ically significant laboratory changes were noted during L-Gln supplementation. There was no differ- ence in ammonemia between the groups. There were statistically but not clinically significant increases in plasma urea nitrogen and creatinine concentrations. There was no significant decrease in eGFR dur- ing calcium caseinate supplementation (2.9%). The eGFR decreased significantly after L-Gln supple- mentation (13.3%) but well below the 25% limit for biologic significance. Conclusion: Increases in serum urea nitrogen and creatinine and decrease in eGFR are probably due to difficulties by older kidneys in metabolizing the supplemented protein sources. Although not clin- ically significant, those alterations impose a rigorous control on the evaluation parameters of renal function during oral L-Gln supplementation, with doses of 0.5 g $ kg 1 $ d 1 in middle-aged and el- derly individuals. Ó 2010 Elsevier Inc. All rights reserved. Keywords: Glutamine; Elderly; Middle age; Safety Introduction Glutamine is the most abundant free amino acid in the human body, comprising about 20% of free amino acids in plasma and more than 50% of the amino acid pool in human skeletal muscle. It is not considered essential but a ‘‘conditionally essential’’ amino acid because its plasma concentration decreases by as much as 50% during stress, creating a deficiency condition [1–4]. In addition to multi- ple biochemical reactions, it participates in the maintenance The present study was supported by a grant from Conselho Nacional de De- senvolvimento Cientı ´fico e Tecnolo ´gico (CNPq), Ministe ´rio de Cie ˆncia e Tec- nologia, process no. 505304/04, and by the Coordenac ¸a ˜o de Aperfeic ¸oamento de Pessoal de Nı ´vel Superior (CAPES), Ministe ´rio da Educac ¸a ˜o, Brazil. *Corresponding author. Tel.: þ55-85-3366-9063; fax: þ55-85-3366- 8064. E-mail address: scgalera@uol.com.br (S. C. Galera). 0899-9007/10/$ – see front matter Ó 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.nut.2009.05.013 Nutrition 26 (2010) 375–381 www.nutritionjrnl.com