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Amino Acids

, Volume 48, Issue 7, pp 1541–1552 | Cite as

Catabolism and safety of supplemental l-arginine in animals

  • Zhenlong Wu
  • Yongqing Hou
  • Shengdi Hu
  • Fuller W. Bazer
  • Cynthia J. Meininger
  • Catherine J. McNeal
  • Guoyao WuEmail author
Invited Review

Abstract

l-arginine (Arg) is utilized via multiple pathways to synthesize protein and low-molecular-weight bioactive substances (e.g., nitric oxide, creatine, and polyamines) with enormous physiological importance. Furthermore, Arg regulates cell signaling pathways and gene expression to improve cardiovascular function, augment insulin sensitivity, enhance lean tissue mass, and reduce obesity in humans. Despite its versatile roles, the use of Arg as a dietary supplement is limited due to the lack of data to address concerns over its safety in humans. Data from animal studies are reviewed to assess arginine catabolism and the safety of long-term Arg supplementation. The arginase pathway was responsible for catabolism of 76–85 and 81–96 % Arg in extraintestinal tissues of pigs and rats, respectively. Dietary supplementation with Arg–HCl or the Arg base [315- and 630-mg Arg/(kg BW d) for 91 d] had no adverse effects on male or female pigs. Similarly, no safety issues were observed for male or female rats receiving supplementation with 1.8- and 3.6-g Arg/(kg BW d) for at least 91 d. Intravenous administration of Arg–HCl to gestating sheep at 81 and 180 mg Arg/(kg BW d) is safe for at least 82 and 40 d, respectively. Animals fed conventional diets can well tolerate large amounts of supplemental Arg [up to 630-mg Arg/(kg BW d) in pigs or 3.6-g Arg/(kg BW d) in rats] for 91 d, which are equivalent to 573-mg Arg/(kg BW d) for humans. Collectively, these results can help guide studies to determine the safety of long-term oral administration of Arg in humans.

Keywords

Amino acids Nutrition Catabolism Health Dietary supplementation 

Abbreviations

AA

Amino acid(s)

Arg

l-arginine

AUC

Area-under-the curve

BW

Body weight

CAT

Cationic amino acid transporter

d

Day(s)

hArg

Homoarginine

MRSD

Maximum recommended starting dose

NO

Nitric oxide

NOS

Nitric oxide synthase

Notes

Acknowledgments

This work was supported by grants from International Council of Amino Acid Science (Brussels, Belgium), Texas A&M AgriLife Research (H-8200), National Basic Research Program of China (2012CB126305), National Natural Science Foundation of China (31172217 and 31272450), Natural Science Foundation of Hubei Province (2013CFA097 and 2013CFB325), and Hubei Hundred Talent program. We thank Drs. Robert Burghardt, Zhaolai Dai, Gregory Johnson, Xilong Li, Sidney Morris, and Stephen Smith for research collaboration.

Compliance with ethical standards

The use of animals for our research described in this review article was approved by the Institutional Animal Care and Use Committee of Texas A&M University.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Agostinelli E (2014) Polyamines and transglutaminases: biological, clinical, and biotechnological perspectives. Amino Acids 46:475–485CrossRefPubMedGoogle Scholar
  2. Assaad H, Zhou L, Carroll RJ, Wu G (2014) Rapid publication-ready MS-Word tables for one-way ANOVA. Springerplus 3:474CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bazer FW, Johnson GA, Wu G (2015) Amino acids and conceptus development during the peri-implantation period of pregnancy. Adv Exp Med Biol 843:23–52CrossRefPubMedGoogle Scholar
  4. Beaumier L, Castillo L, Ajami AM, Young VR (1995) Urea cycle intermediate kinetics and nitrate excretion at normal and “therapeutic” intakes of arginine in humans. Am J Physiol Endocrinol Metab 269:E884–E896Google Scholar
  5. Benhar M (2015) Nitric oxide and the thioredoxin system: a complex interplay in redox regulation. Biochim Biophys Acta 1850:2476–2484CrossRefPubMedGoogle Scholar
  6. Bernstein HG, Jäger K, Dobrowolny H, Steiner J, Keilhoff G, Bogerts B, Laube G (2015) Possible sources and functions of l-homoarginine in the brain: review of the literature and own findings. Amino Acids 47:1729–1740CrossRefPubMedGoogle Scholar
  7. Böger RH (2014) The pharmacodynamics of l-arginine. Altern Ther Health Med 20:48–54PubMedGoogle Scholar
  8. Breuillard C, Cynober L, Moinard C (2015) Citrulline and nitrogen homeostasis: an overview. Amino Acids 47:685–691CrossRefPubMedGoogle Scholar
  9. Brosnan JT, Brosnan ME (2007) Creatine: endogenous metabolite, dietary, and therapeutic supplement. Annu Rev Nutr 27:241–261CrossRefPubMedGoogle Scholar
  10. Brown B, Roehl K, Betz M (2015) Enteral nutrition formula selection: current evidence and implications for practice. Nutr Clin Pract 30:72–85CrossRefPubMedGoogle Scholar
  11. Burrin DG, Ng K, Stoll B, Sáenz De Pipaón M (2014) Impact of new-generation lipid emulsions on cellular mechanisms of parenteral nutrition-associated liver disease. Adv Nutr 5:82–91CrossRefPubMedPubMedCentralGoogle Scholar
  12. Calabrò RS, Gervasi G, Bramanti P (2014) l-Arginine and vascular diseases: lights and pitfalls! Acta Biomed 85:222–2228PubMedGoogle Scholar
  13. Caldovic L, Tuchman M (2003) N-acetylglutamate and its changing role through evolution. Biochem J 372:279–290CrossRefPubMedPubMedCentralGoogle Scholar
  14. Castillo L, Chapman TE, Yu YM, Ajami A, Burke JF, Young VR (1993) Dietary arginine uptake by the splanchnic region in adult humans. Am J Physiol Endocrinol Metab 265:E532–E539Google Scholar
  15. Chin-Dusting JP, Alexander CT, Arnold PJ, Hodgson WC, Lux AS, Jennings GL (1996) Effects of in vivo and in vitro l-arginine supplementation on healthy human vessels. J Cardiovasc Pharmacol 28:158–166CrossRefPubMedGoogle Scholar
  16. Clarkson P, Adams MR, Powe AJ, Donald AE, McCredie R, Robinson J, McCarthy SN, Keech A, Celermajer DS, Deanfield JE (1996) Oral l-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults. J Clin Invest 97:1989–1994CrossRefPubMedPubMedCentralGoogle Scholar
  17. Closs EI, Simon A, Vékony N, Rotmann A (2004) Plasma membrane transporters for arginine. J Nutr 134:2752S–2759SPubMedGoogle Scholar
  18. Collins JK, Wu G, Perkins-Veazie P, Spears K, Claypool PL, Baker RA, Clevidence BA (2007) Watermelon consumption increases plasma arginine concentrations in adults. Nutrition 23:261–266CrossRefPubMedGoogle Scholar
  19. Dai ZL, Li XL, Xi PB, Zhang J, Wu G, Zhu WY (2012) Metabolism of select amino acids in bacteria from the pig small intestine. Amino Acids 42:1597–1608CrossRefPubMedGoogle Scholar
  20. Dai ZL, Wu ZL, Yang Y, Wang JJ, Satterfield MC, Meininger CJ, Bazer FW, Wu G (2013) Nitric oxide and energy metabolism in mammals. Biofactors 39:383–391CrossRefPubMedGoogle Scholar
  21. Dashtabi A, Mazloom Z, Fararouei M, Hejazi N (2015) Oral l-arginine administration improves anthropometric and biochemical indices associated with cardiovascular diseases in obese patients: a randomized, single blind placebo controlled clinical trial. Res Cardiovasc Med 5(1):e29419CrossRefPubMedPubMedCentralGoogle Scholar
  22. Davis TA, Nguyen HV, Garcia-Bravo R, Fiorotto ML, Jackson EM, Lewis DS, Lee DR, Reeds PJ (1994) Amino acid composition of human milk is not unique. J Nutr 124:1126–1132PubMedGoogle Scholar
  23. Edmonds MS, Gonyou HW, Baker DH (1987) Effect of excess levels of methionine, tryptophan, arginine, lysine or threonine on growth and dietary choice in the pig. J Anim Sci 65:179–185PubMedGoogle Scholar
  24. Flynn NE, Meininger CJ, Kelly K, Ing NH, Morris SM Jr, Wu G (1999) Glucocorticoids mediate the enhanced expression of intestinal type II arginase and argininosuccinate synthase in postweaning pigs. J Nutr 129:799–803PubMedGoogle Scholar
  25. Flynn NE, Meininger CJ, Haynes TE, Wu G (2002) The metabolic basis of arginine nutrition and pharmacotherapy. Biomed Pharmacother 56:427–438CrossRefPubMedGoogle Scholar
  26. Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), U.S. Department of Health and Human Services (2005) Guidance for industry: estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. U.S. Department of Health and Human Services, Bethesda. http://www.fda.gov/cdev/guidance/index.htm
  27. Fu WJ, Haynes TE, Kohli R, Hu J, Shi W, Spencer TE, Carroll RJ, Meininger CJ, Wu G (2005) Dietary l-arginine supplementation reduces fat mass in Zucker diabetic fatty rats. J Nutr 135:714–721PubMedGoogle Scholar
  28. Getty CM, Almeida FN, Baratta AA, Dilger RN (2015) Plasma metabolomics indicates metabolic perturbations in low birth weight piglets supplemented with arginine. J Anim Sci 93:5754–5763CrossRefPubMedGoogle Scholar
  29. Grasemann H, Grasemann C, Kurtz F, Tietze-Schillings G, Vester U, Ratjen F (2005) Oral l-arginine supplementation in cystic fibrosis patients: a placebo-controlled study. Eur Respir J 25:62–68CrossRefPubMedGoogle Scholar
  30. Grimble GK (2007) Adverse gastrointestinal effects of arginine and related amino acids. J Nutr 137(Suppl 2):1693S–1701SPubMedGoogle Scholar
  31. Hatzoglou M, Fernandez J, Yaman I, Closs E (2004) Regulation of cationic amino acid transport: the story of the CAT-1 transporter. Annu Rev Nutr 24:377–399CrossRefPubMedGoogle Scholar
  32. Holecek M, Sispera L (2016) Effects of arginine supplementation on amino acid profiles in blood and tissues in fed and overnight-fasted rats. Nutrients 8(4). doi: 10.3390/nu8040206
  33. Hou YQ, Yin YL, Wu G (2015) Dietary essentiality of “nutritionally nonessential amino acids” for animals and humans. Exp Biol Med 240:997–1007CrossRefGoogle Scholar
  34. Hou YQ, Yao K, Yin YL, Wu G (2016a) Endogenous synthesis of amino acids limits growth, lactation and reproduction of animals. Adv Nutr 7:331–342CrossRefPubMedGoogle Scholar
  35. Hou YQ, Hu SD, Jia SC, Nawaratna G, Che DS, Wang FL, Bazer FW, Wu G (2016b) Whole-body synthesis of l-homoarginine in pigs and rats supplemented with l-arginine. Amino Acids 48:993–1001CrossRefPubMedGoogle Scholar
  36. Hu SD, Li XL, Rezaei R, Meininger CJ, McNeal CJ, Wu G (2015) Safety of long-term dietary supplementation with l-arginine in pigs. Amino Acids 47:925–936CrossRefPubMedGoogle Scholar
  37. Hurt RT, Ebbert JO, Schroeder DR, Croghan IT, Bauer BA, McClave SA, Miles JM, McClain CJ (2014) l-Arginine for the treatment of centrally obese subjects: a pilot study. J Diet Suppl 11:40–52CrossRefPubMedGoogle Scholar
  38. Jacquez JA (1996) Compartmental analysis in biology and medicine. BioMedware, Ann ArborGoogle Scholar
  39. Jobgen WJ, Meininger CJ, Jobgen SC, Li P, Lee MJ, Smith SB, Spencer TE, Fried SK, Wu G (2009) Dietary l-arginine supplementation reduces white-fat gain and enhances skeletal muscle and brown fat masses in diet-induced obese rats. J Nutr 139:230–237CrossRefPubMedPubMedCentralGoogle Scholar
  40. Kayacelebi AA, Langen J, Weigt-Usinger K, Chobanyan-Jürgens K, Mariotti F, Schneider JY, Rothmann S, Frölich JC, Atzler D, Choe CU, Schwedhelm E, Huneau JF, Lücke T, Tsikas D (2015) Biosynthesis of homoarginine (hArg) and asymmetric dimethylarginine (ADMA) from acutely and chronically administered free l-arginine in humans. Amino Acids 47:1893–1908CrossRefPubMedGoogle Scholar
  41. Kim J, Song G, Wu G, Gao H, Johnson GA, Bazer FW (2013) Arginine, leucine, and glutamine stimulate proliferation of porcine trophectoderm cells through the MTOR-RPS6K-RPS6-EIF4EBP1 signal transduction pathway. Biol Reprod 88:113CrossRefPubMedGoogle Scholar
  42. King DE, Mainous AG, Geesey ME (2008) Variation in l-arginine intake follow demographics and lifestyle factors that may impact cardiovascular disease risk. Nutr Res 28:21–24CrossRefPubMedPubMedCentralGoogle Scholar
  43. Kong X, Tan B, Yin Y, Gao H, Li X, Jaeger LA, Bazer FW, Wu G (2012) l-Arginine stimulates the mTOR signaling pathway and protein synthesis in porcine trophectoderm cells. J Nutr Biochem 23:1178–1183CrossRefPubMedGoogle Scholar
  44. Lan A, Blachier F, Benamouzig R, Beaumont M, Barrat C, Coelho D, Lancha A Jr, Kong X, Yin Y, Marie JC, Tomé D (2015) Mucosal healing in inflammatory bowel diseases: is there a place for nutritional supplementation? Inflamm Bowel Dis 21:198–207CrossRefPubMedGoogle Scholar
  45. Lassala A, Bazer FW, Cudd TA, Li P, Li XL, Satterfield MC, Spencer TE, Wu G (2009) Intravenous administration of l-citrulline to pregnant ewes is more effective than l-arginine for increasing arginine availability in the fetus. J Nutr 139:660–665CrossRefPubMedPubMedCentralGoogle Scholar
  46. Lassala A, Bazer FW, Cudd TA, Datta S, Keisler DH, Satterfield MC, Spencer TE, Wu G (2010) Parenteral administration of l-arginine prevents fetal growth restriction in undernourished ewes. J Nutr 140:1242–1248CrossRefPubMedPubMedCentralGoogle Scholar
  47. Lassala A, Bazer FW, Cudd TA, Datta S, Keisler DH, Satterfield MC, Spencer TE, Wu G (2011) Parenteral administration of l-arginine enhances fetal survival and growth in sheep carrying multiple pregnancies. J Nutr 141:849–855CrossRefPubMedPubMedCentralGoogle Scholar
  48. Li XL, Rezaei R, Li P, Wu G (2011) Composition of amino acids in feed ingredients for animal diets. Amino Acids 40:1159–1168CrossRefPubMedGoogle Scholar
  49. Lucotti P, Setola E, Monti LD, Galluccio E, Costa S, Sandoli EP, Fermo I, Rabaiotti G, Gatti R, Piatti P (2006) Beneficial effect of a long-term oral l-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients. Am J Physiol Endocrinol Metab 291:E906–E912CrossRefPubMedGoogle Scholar
  50. Luiking YC, Ten Have GA, Wolfe RR, Deutz NE (2012) Arginine de novo and nitric oxide production in disease states. Am J Physiol Endocrinol Metab 303:E1177–E1189CrossRefPubMedPubMedCentralGoogle Scholar
  51. McCoard S, Sales F, Wards N, Sciascia Q, Oliver M, Koolaard J, van der Linden D (2013) Parenteral administration of twin-bearing ewes with l-arginine enhances the birth weight and brown fat stores in sheep. Springerplus 2:684CrossRefPubMedPubMedCentralGoogle Scholar
  52. Monné M, Miniero DV, Daddabbo L, Palmieri L, Porcelli V, Palmieri F (2015) Mitochondrial transporters for ornithine and related amino acids: a review. Amino Acids 47:1763–1777CrossRefPubMedGoogle Scholar
  53. Moretti M, Matheus FC, de Oliveira PA, Neis VB, Ben J, Walz R, Rodrigues AL, Prediger RD (2014) Role of agmatine in neurodegenerative diseases and epilepsy. Front Biosci (Elite Ed) 6:341–359CrossRefGoogle Scholar
  54. Morris SM Jr (2006) Arginine: beyond protein. Am J Clin Nutr 83:508S–512SPubMedGoogle Scholar
  55. Pilz S, Meinitzer A, Gaksch M, Grübler M, Verheyen N, Drechsler C, Hartaigh BÓ, Lang F, Alesutan I, Voelkl J et al (2015) Homoarginine in the renal and cardiovascular systems. Amino Acids 47:1703–1713CrossRefPubMedGoogle Scholar
  56. Popolo A, Adesso S, Pinto A, Autore G, Marzocco S (2014) l-Arginine and its metabolites in kidney and cardiovascular disease. Amino Acids 46:2271–2286CrossRefPubMedGoogle Scholar
  57. Reynolds LP, Wulster-Radcliffe MC, Aaron DK, Davis TA (2015) Importance of animals in agricultural sustainability and food security. J Nutr 145:1377–1379CrossRefPubMedGoogle Scholar
  58. Ritschel WA (1986) Handbook of basic pharmacokinetics. Drug Intelligence Publications, HamiltonGoogle Scholar
  59. Rose WC (1957) The amino acid requirements of adult man. Nutr Abstr Rev Ser Hum Exp 27:631–647PubMedGoogle Scholar
  60. Satterfield MC, Dunlap KA, Keisler DH, Bazer FW, Wu G (2012) Arginine nutrition and fetal brown adipose tissue development in diet-induced obese sheep. Amino Acids 43:1593–1603CrossRefGoogle Scholar
  61. Satterfield MC, Dunlap KA, Keisler DH, Bazer FW, Wu G (2013) Arginine nutrition and fetal brown adipose tissue development in nutrient-restricted sheep. Amino Acids 45:489–499CrossRefPubMedGoogle Scholar
  62. Sawant OB, Wu G, Washburn SE (2015) Maternal l-glutamine supplementation prevents prenatal alcohol exposure-induced fetal growth restriction in ewes. Amino Acids 47:1183–1192CrossRefPubMedGoogle Scholar
  63. Schulman SP, Becker LC, Kass DA, Champion HC, Terrin ML, Forman S, Ernst KV, Kelemen MD, Townsend SN, Capriotti A et al (2006) l-Arginine therapy in acute myocardial infarction: the vascular interaction with age in myocardial infarction (VINTAGE) randomized clinical trial. JAMA 295:58–64CrossRefPubMedGoogle Scholar
  64. Shao A, Hathcock JN (2008) Risk assessment for the amino acids taurine, l-glutamine and l-arginine. Regul Toxicol Pharmacol 50:376–399CrossRefPubMedGoogle Scholar
  65. Suryawan A, Davis TA (2014) Regulation of protein degradation pathways by amino acids and insulin in skeletal muscle of neonatal pigs. J Anim Sci Biotechnol 5(1):8CrossRefPubMedPubMedCentralGoogle Scholar
  66. Tan BE, Yin YL, Liu ZQ, Li XG, Xu HJ, Kong XF, Huang RL, Tang WJ, Shinzato I, Smith SB, Wu G (2009) Dietary l-arginine supplementation increases muscle gain and reduces body fat mass in growing-finishing pigs. Amino Acids 37:169–175CrossRefPubMedGoogle Scholar
  67. Tan BE, Li XG, Yin YL, Wu ZL, Liu C, Tekwe CD, Wu G (2012) Regulatory roles for l-arginine in reducing white adipose tissue. Front Biosci 17:2237–2246CrossRefGoogle Scholar
  68. Tsikas D, Wu G (2015) Homoarginine, arginine, and relatives: analysis, metabolism, transport, physiology, and pathology. Amino Acids 47:1697–1702CrossRefPubMedGoogle Scholar
  69. Tsubuku S, Hatayama K, Mawatari K, Smriga M, Kimura T (2004) Thirteen-week oral toxicity study of l-arginine in rats. Int J Toxicol 23:101–105CrossRefPubMedGoogle Scholar
  70. Wang XQ, Frank JW, Little DR, Dunlap KA, Satterfiled MC, Burghardt RC, Hansen TR, Wu G, Bazer FW (2014a) Functional role of arginine during the peri-implantation period of pregnancy. I. Consequences of loss of function of arginine transporter SLC7A1 mRNA in ovine conceptus trophectoderm. FASEB J 28:2852–2863CrossRefPubMedGoogle Scholar
  71. Wang XQ, Frank JW, Xu J, Dunlap KA, Satterfield MC, Burghardt RC, Romero JJ, Hansen TR, Wu G, Bazer FW (2014b) Functional role of arginine during the peri-implantation period of pregnancy. II. Consequences of loss of function of nitric oxide synthase NOS3 mRNA in ovine conceptus trophectoderm. Biol Reprod 91:59CrossRefPubMedGoogle Scholar
  72. Wang XQ, Ying W, Dunlap KA, Lin G, Satterfield MC, Burghardt RC, Wu G, Bazer FW (2014c) Arginine decarboxylase and agmatinase: an alternative pathway for de novo biosynthesis of polyamines for development of mammalian conceptuses. Biol Reprod 90:84CrossRefPubMedGoogle Scholar
  73. Windmueller HG, Spaeth AE (1981) Source and fate of circulating citrulline. Am J Physiol 241:E473–E480PubMedGoogle Scholar
  74. Wu G (2013) Amino acids: biochemistry and nutrition. CRC Press, Boca RatonCrossRefGoogle Scholar
  75. Wu G (2014) Dietary requirements of synthesizable amino acids by animals: a paradigm shift in protein nutrition. J Anim Sci Biotechnol 5:34CrossRefPubMedPubMedCentralGoogle Scholar
  76. Wu G, Meininger CJ (2000) Arginine nutrition and cardiovascular function. J Nutr 130:2626–2629PubMedGoogle Scholar
  77. Wu G, Morris SM Jr (1998) Arginine metabolism: nitric oxide and beyond. Biochem J 336:1–17CrossRefPubMedPubMedCentralGoogle Scholar
  78. Wu G, Knabe DA, Flynn NE, Yan W, Flynn SP (1996a) Arginine degradation in developing porcine enterocytes. Am J Physiol Gastrointest Liver Physiol 271:G913–G919Google Scholar
  79. Wu G, Meier SA, Knabe DA (1996b) Dietary glutamine supplementation prevents jejunal atrophy in weaned pigs. J Nutr 126:2578–2584PubMedGoogle Scholar
  80. Wu G, Davis PK, Flynn NE, Knabe DA, Davidson JT (1997) Endogenous synthesis of arginine plays an important role in maintaining arginine homeostasis in postweaning growing pigs. J Nutr 127:2342–2349PubMedGoogle Scholar
  81. Wu G, Flynn NE, Flynn SP, Jolly CA, Davis PK (1999) Dietary protein or arginine deficiency impairs constitutive and inducible nitric oxide synthesis by young rats. J Nutr 129:1347–1354PubMedGoogle Scholar
  82. Wu G, Bazer FW, Cudd TA, Jobgen WS, Kim SW, Lassala A, Li P, Matis JH, Meininger CJ, Spencer TE (2007a) Pharmacokinetics and safety of arginine supplementation in animals. J Nutr 137:1673S–1680SPubMedGoogle Scholar
  83. Wu G, Bazer FW, Davis TA, Jaeger LA, Johnson GA, Kim SW, Knabe DA, Meininger CJ, Spencer TE, Yin YL (2007b) Important roles for the arginine family of amino acids in swine nutrition and production. Livest Sci 112:8–22CrossRefGoogle Scholar
  84. Wu G, Bazer FW, Davis TA, Kim SW, Li P, Rhoads JM, Satterfield MC, Smith SB, Spencer TE, Yin YL (2009) Arginine metabolism and nutrition in growth, health and disease. Amino Acids 37:153–168CrossRefPubMedGoogle Scholar
  85. Wu G, Bazer FW, Dai ZL, Li DF, Wang JJ, Wu ZL (2014) Amino acid nutrition in animals: protein synthesis and beyond. Annu Rev Anim Biosci 2:387–417CrossRefPubMedGoogle Scholar
  86. Wu G, Cross HR, Gehring KB, Savell JW, Arnold AN, McNeill SH (2016) Composition of free and peptide-bound amino acids in beef chuck, loin, and round cuts. J Anim Sci. doi: 10.2527/jas.2016-0478 Google Scholar
  87. Yang Y, Wu ZL, Jia SC, Dahanayaka S, Feng S, Meininger CJ, McNeal CJ, Wu G (2015) Safety of long-term dietary supplementation with l-arginine in rats. Amino Acids 47:1907–1920Google Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Zhenlong Wu
    • 1
  • Yongqing Hou
    • 2
  • Shengdi Hu
    • 3
  • Fuller W. Bazer
    • 3
  • Cynthia J. Meininger
    • 4
  • Catherine J. McNeal
    • 5
  • Guoyao Wu
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.State Key Laboratory of Animal NutritionChina Agricultural UniversityBeijingChina
  2. 2.Hubei Key Laboratory of Animal Nutrition and Feed Science, Hubei Collaborative Innovation Center for Animal Nutrition and Feed SafetyWuhan Polytechnic UniversityWuhanChina
  3. 3.Department of Animal ScienceTexas A&M UniversityTexasUSA
  4. 4.Department of Medical PhysiologyTexas A&M Health Science CenterTempleUSA
  5. 5.Department of Internal MedicineBaylor Scott and White HealthTempleUSA

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