Glycine increases fat-free mass in malnourished haemodialysis patients: a randomized double-blind crossover trial

Laurence Genton, Daniel Teta, Menno Pruijm, Catherine Stoermann, Nicola Marangon, Julie Mareschal, Isabelle Bassi, Arelene Wurzner-Ghajarzadeh, Vladimir Lazarevic, Luc Cynober, Patrice D Cani, François R Herrmann, Jacques Schrenzel, Laurence Genton, Daniel Teta, Menno Pruijm, Catherine Stoermann, Nicola Marangon, Julie Mareschal, Isabelle Bassi, Arelene Wurzner-Ghajarzadeh, Vladimir Lazarevic, Luc Cynober, Patrice D Cani, François R Herrmann, Jacques Schrenzel

Abstract

Background: Protein energy wasting is associated with negative outcome in patients under chronic haemodialysis (HD). Branched-chain amino acids (BCAAs) may increase the muscle mass. This post hoc analysis of a controlled double-blind randomized crossover study assessed the impact of BCAAs on nutritional status, physical function, and quality of life.

Methods: We included 36 chronic HD patient features of protein energy wasting as plasma albumin <38 g/L, and dietary intakes <30 kcal/kg/day and <1 g protein/kg/day. Patients received either oral BCAA (2 × 7 g/day) or glycine (2 × 7 g/day) for 4 months (Period 1), followed by a washout period of 1 month, and then received the opposite supplement (Period 2). The outcomes were lean body mass measured by dual-energy X-ray absorptiometry, fat-free mass index measured by bioelectrical impedance, resting energy expenditure, dietary intake and appetite rating, physical activity and function, quality of life, and blood parameters. Analyses were performed by multiple mixed linear regressions including type of supplementation, months, period, sex, and age as fixed effects and subjects as random intercepts.

Results: Twenty-seven patients (61.2 ± 13.7 years, 41% women) were compliant to the supplementations (consumption >80% of packs) and completed the study. BCAA did not affect lean body mass index and body weight, but significantly decreased fat-free mass index, as compared with glycine (coeff -0.27, 95% confidence interval -0.43 to -0.10, P = 0.002, respectively). BCAA and glycine intake had no effect on the other clinical parameters, blood chemistry tests, or plasma amino acids.

Conclusions: Branched-chain amino acid did not improve lean body mass as compared with glycine. Unexpectedly, glycine improved fat-free mass index in HD patients, as compared with BCAA. Whether long-term supplementation with glycine improves the clinical outcome remains to be demonstrated.

Trial registration: ClinicalTrials.gov NCT02962089.

Keywords: Amino acids; Body composition; Lean body mass; Malnutrition.

Conflict of interest statement

L.G. has received grants from the Swiss National Science Foundation, Alfred and Alice Lachmann Foundation, and Fresenius Kabi; speaker honoraria from Fresenius Kabi; advisory honoraria from Baxter and Abbott; and travel grants from Nestlé Health Science and Abbott. P.D.C. is a co‐founder of A‐Mansia Biotech S.A. (Belgium) and owner of several patents concerning the use of specific bacteria or components on the treatment of obesity, diabetes, and cardiometabolic disorders. D.T. has received grants from Fresenius Medical Care, Amgen, and Baxter; speaker honoraria from Fresenius Medical Care, B. Braun, Abbott International, Baxter, Genzyme, and Sanofi Aventis; travel grants for Fresenius Medical Care, Amgen, and Vifor; and a grant for teaching material from Abbott International. M.P., C.S., N.M., J.M., I.B., A.W.‐G., V.L., L.C., F.H., and J.S. have no conflicts of interest.

© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.

Figures

Figure 1
Figure 1
Line plot showing the evolution of (A) weight (kg), (B) lean body mass index (kg/m2), (C) fat mass index (DXA), (D) fat‐free mass index (kg/m2/day), and (E) fat mass index (BIA) (kg) in the BCAA–glycine group (black squares and line) and in the glycine–BCAA group (grey dots and line). The grey zone indicates the washout period, which occurred for each patient between Months 4 and 5.

References

    1. Cano NJ, Aparicio M, Brunori G, Carrero JJ, Cianciaruso B, Fiaccadori E, et al. ESPEN Guidelines on Parenteral Nutrition: adult renal failure. Clin Nutr 2009;28:401–414.
    1. Fouque D, Kalantar‐Zadeh K, Kopple J, Cano N, Chauveau P, Cuppari L, et al. A proposed nomenclature and diagnostic criteria for protein‐energy wasting in acute and chronic kidney disease. Kidney Int 2008;73:391–398.
    1. Kalantar‐Zadeh K, Stenvinkel P, Bross R, Khawar OS, Rammohan M, Colman S, et al. Kidney insufficiency and nutrient‐based modulation of inflammation. Curr Opin Clin Nutr Metab Care 2005;8:388–396.
    1. Bonanni A, Mannucci I, Verzola D, Sofia A, Saffioti S, Gianetta E, et al. Protein‐energy wasting and mortality in chronic kidney disease. Int J Environ Res Public Health 2011;8:1631–1654.
    1. K/DOQI, National Kidney Foundation . Clinical practice guidelines for nutrition in chronic renal failure. Am J Kidney Dis 2000;35:S17–S140.
    1. National Kidney Foundation . Clinical practice guideline for nutrition in chronic kidney disease: 2019 update. . 2019.
    1. Mak RH, Ikizler AT, Kovesdy CP, Raj DS, Stenvinkel P, Kalantar‐Zadeh K. Wasting in chronic kidney disease. J Cachexia Sarcopenia Muscle 2011;2:9–25.
    1. Huang CX, Tighiouart H, Beddhu S, Cheung AK, Dwyer JT, Eknoyan G, et al. Both low muscle mass and low fat are associated with higher all‐cause mortality in hemodialysis patients. Kidney Int 2010;77:624–629.
    1. Combe C, Chauveau P, Laville M, Fouque D, Azar R, Cano N, et al. Influence of nutritional factors and hemodialysis adequacy on the survival of 1,610 French patients. Am J Kidney Dis 2001;37:S81–S88.
    1. Hiroshige K, Sonta T, Suda T, Kanegae K, Ohtani A. Oral supplementation of branched‐chain amino acid improves nutritional status in elderly patients on chronic haemodialysis. Nephrol Dial Transplant 2001;16:1856–1862.
    1. Cangiano C, Laviano A, Meguid MM, Mulieri M, Conversano L, Preziosa I, et al. Effects of administration of oral branched‐chain amino acids on anorexia and caloric intake in cancer patients. J Natl Cancer Inst 1996;88:550–552.
    1. Marchesini G, Bianchi G, Merli M, Amodio P, Panella C, Loguercio C, et al. Nutritional supplementation with branched‐chain amino acids in advanced cirrhosis: a double‐blind, randomized trial. Gastroenterology 2003;124:1792–1801.
    1. Cheng H, Kong J, Underwood C, Petocz P, Hirani V, Dawson B, et al. Systematic review and meta‐analysis of the effect of protein and amino acid supplements in older adults with acute or chronic conditions. Br J Nutr 2018;119:527–542.
    1. Komar B, Schwingshackl L, Hoffmann G. Effects of leucine‐rich protein supplements on anthropometric parameter and muscle strength in the elderly: a systematic review and meta‐analysis. J Nutr Health Aging 2015;19:437–446.
    1. Xu ZR, Tan ZJ, Zhang Q, Gui QF, Yang YM. The effectiveness of leucine on muscle protein synthesis, lean body mass and leg lean mass accretion in older people: a systematic review and meta‐analysis. Br J Nutr 2015;113:25–34.
    1. Cano NJ, Fouque D, Roth H, Aparicio M, Azar R, Canaud B, et al. Intradialytic parenteral nutrition does not improve survival in malnourished hemodialysis patients: a 2‐year multicenter, prospective, randomized study. J Am Soc Nephrol 2007;18:2583–2591.
    1. Genton L, Pruijm M, Teta D, Bassi I, Cani PD, Gaia N, et al. Gut barrier and microbiota changes with glycine and branched chain amino acids supplementation in chronic hemodialysis patients: a randomized double‐blind cross‐over trial. Submitted
    1. U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute . Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. . November 27, 2017.
    1. Yoshikawa N, Shimizu N, Uehara M, Oda A, Matsumiya R, Matsubara E, et al. The effects of bolus supplementation of branched‐chain amino acids on skeletal muscle mass, strength, and function in patients with rheumatic disorders during glucocorticoid treatment. Mod Rheumatol 2017;27:508–517.
    1. Kyle UG, Genton L, Karsegard L, Slosman DO, Pichard C. Single prediction equation for bioelectrical impedance analysis in adults aged 20–94 years. Nutrition 2001;17:248–253.
    1. Genton L, Karsegard VL, Kyle UG, Hans DB, Michel JP, Pichard C. Comparison of four bioelectrical impedance analysis formulas in healthy elderly subjects. Gerontology 2001;47:315–323.
    1. Daugirdas JT, Depner TA, Greene T, Levin NW, Chertow GM, Rocco MV, et al. Standard Kt/Vurea: a method of calculation that includes effects of fluid removal and residual kidney clearance. Kidney Int 2010;77:637–644.
    1. Roberts HC, Denison HJ, Martin HJ, Patel HP, Syddall H, Cooper C, et al. A review of the measurement of grip strength in clinical and epidemiological studies: towards a standardised approach. Age Ageing 2011;40:423–429.
    1. Leong DP, Teo KK, Rangarajan S, Kutty VR, Lanas F, Hui C, et al. Reference ranges of handgrip strength from 125,462 healthy adults in 21 countries: a prospective urban rural epidemiologic (PURE) study. J Cachexia Sarcopenia Muscle 2016;7:535–546.
    1. Schneider PL, Crouter SE, Lukajic O, Bassett DR Jr. Accuracy and reliability of 10 pedometers for measuring steps over a 400‐m walk. Med Sci Sports Exerc 2003;35:1779–1784.
    1. Crouter SE, Schneider PL, Karabulut M, Bassett DR Jr. Validity of 10 electronic pedometers for measuring steps, distance, and energy cost. Med Sci Sports Exerc 2003;35:1455–1460.
    1. RAND 36‐Item Health Survey.
    1. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodology 1995;57:289–300.
    1. Dwan K, Li T, Altman DG, Elbourne D. CONSORT 2010 statement: extension to randomised crossover trials. BMJ 2019;l4378.
    1. Basolo A, Hohenadel M, Ang QY, Piaggi P, Heinitz S, Walter M, et al. Effects of underfeeding and oral vancomycin on gut microbiome and nutrient absorption in humans. Nat Med 2020;26:589–598.
    1. Abell TL, Johnson WD, Kedar A, Runnels JM, Thompson J, Weeks ES, et al. A double‐masked, randomized, placebo‐controlled trial of temporary endoscopic mucosal gastric electrical stimulation for gastroparesis. Gastrointest Endosc 2011;74:496–503, e3.
    1. Iversen VM, Mork PJ, Vasseljen O, Bergquist R, Fimland MS. Multiple‐joint exercises using elastic resistance bands vs. conventional resistance‐training equipment: a cross‐over study. Eur J Sport Sci 2017;17:973–982.
    1. Lis DM, Stellingwerff T, Kitic CM, Fell JW, Ahuja KDK. Low FODMAP: a preliminary strategy to reduce gastrointestinal distress in athletes. Med Sci Sports Exerc 2018;50:116–123.
    1. Herrmann FR. Geriatric epidemiology: practical considerations when involving elderly subjects in studies. Swiss Med Wkly 2004;134:117–125.
    1. Cederholm T, Jensen GL, Correia M, Gonzalez MC, Fukushima R, Higashiguchi T, et al. GLIM criteria for the diagnosis of malnutrition—a consensus report from the global clinical nutrition community. Clin Nutr 2019;38:1–9.
    1. Schutz Y, Kyle UU, Pichard C. Fat‐free mass index and fat mass index percentiles in Caucasians aged 18–98 y. Int J Obes Relat Metab Disord 2002;26:953–960.
    1. Cynober L, Moinard C, De Bandt JP. The 2009 ESPEN Sir David Cuthbertson. Citrulline: a new major signaling molecule or just another player in the pharmaconutrition game? Clin Nutr 2010;29:545–551.
    1. Gropper SS, Gropper DM, Acosta PB. Plasma amino acid response to ingestion of l‐amino acids and whole protein. J Pediatr Gastroenterol Nutr 1993;16:143–150.
    1. Wang W, Wu Z, Dai Z, Yang Y, Wang J, Wu G. Glycine metabolism in animals and humans: implications for nutrition and health. Amino Acids 2013;45:463–477.
    1. Ham DJ, Caldow MK, Chhen V, Chee A, Wang X, Proud CG, et al. Glycine restores the anabolic response to leucine in a mouse model of acute inflammation. Am J Physiol Endocrinol Metab 2016;310:E970–E981.
    1. Ham DJ, Murphy KT, Chee A, Lynch GS, Koopman R. Glycine administration attenuates skeletal muscle wasting in a mouse model of cancer cachexia. Clin Nutr 2014;33:448–458.
    1. Koopman R, Caldow MK, Ham DJ, Lynch GS. Glycine metabolism in skeletal muscle: implications for metabolic homeostasis. Curr Opin Clin Nutr Metab Care 2017;20:237–242.
    1. Caldow MK, Ham DJ, Trieu J, Chung JD, Lynch GS, Koopman R. Glycine protects muscle cells from wasting in vitro via mTORC1 signaling. Front Nutr 2019;13:172.
    1. Adeva‐Andany M, Souto‐Adeva G, Ameneiros‐Rodriguez E, Fernandez‐Fernandez C, Donapetry‐Garcia C, Dominguez‐Montero A. Insulin resistance and glycine metabolism in humans. Amino Acids 2018;50:11–27.
    1. Alves A, Bassot A, Bulteau AL, Pirola L, Morio B. Glycine metabolism and its alterations in obesity and metabolic diseases. Nutrients 2019;11:1536. 10.3390/nu11061356
    1. Wang WW, Qiao SY, Li DF. Amino acids and gut function. Amino Acids 2009;37:105–110.
    1. Wang W, Wu Z, Lin G, Hu S, Wang B, Dai Z, et al. Glycine stimulates protein synthesis and inhibits oxidative stress in pig small intestinal epithelial cells. J Nutr 2014;144:1540–1548.
    1. Howard A, Tahir I, Javed S, Waring SM, Ford D, Hirst BH. Glycine transporter GLYT1 is essential for glycine‐mediated protection of human intestinal epithelial cells against oxidative damage. J Physiol 2010;588:995–1009.
    1. Genton L, Mareschal J, Charretier Y, Lazarevic V, Bindels LB, Schrenzel J. Targeting the gut microbiota to treat cachexia. Front Cell Infect Microbiol 2019;9:305.
    1. Dai ZL, Li XL, Xi PB, Zhang J, Wu G, Zhu WY. Metabolism of select amino acids in bacteria from the pig small intestine. Amino Acids 2012;42:1597–1608.
    1. Mehta SJ, Roche Recinos A, Saggi SJ, Oh MS. A hypothesis for mechanism for brain oedema due to glycine. Med Hypotheses 2017;103:58–61.
    1. Newgard CB. Interplay between lipids and branched‐chain amino acids in development of insulin resistance. Cell Metab 2012;15:606–614.
    1. Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, et al. Metabolite profiles and the risk of developing diabetes. Nat Med 2011;17:448–453.
    1. Rand WM, Pellett PL, Young VR. Meta‐analysis of nitrogen balance studies for estimating protein requirements in healthy adults. Am J Clin Nutr 2003;77:109–127.
    1. Brown RO, Compher C, American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors . A.S.P.E.N. clinical guidelines: nutrition support in adult acute and chronic renal failure. JPEN J Parenter Enteral Nutr 2010;34:366–377.
    1. von Haehling S, Morley JE, Coats AJS, Anker SD. Ethical guidelines for publishing in the Journal of Cachexia, Sarcopenia and Muscle: update 2019. J Cachexia Sarcopenia Muscle 2019;10:1143–1145.

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