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Amino Acids

, Volume 50, Issue 9, pp 1215–1229 | Cite as

Safety of dietary supplementation with arginine in adult humans

  • Catherine J. McNeal
  • Cynthia J. Meininger
  • Colin D. Wilborn
  • Carmen D. Tekwe
  • Guoyao WuEmail author
Original Article

Abstract

Previous studies with animals and humans have shown beneficial effects of dietary supplementation with l-arginine (Arg) on reducing white fat and improving health. At present, a long-term safe level of Arg administration to adult humans is unknown. The objective of this study was to conduct a randomized, placebo-controlled, clinical trial to evaluate the safety and tolerability of oral Arg in overweight or obese but otherwise healthy adults with a body mass index of ≥ 25 kg/m2. A total of 142 subjects completed a 7-day wash-in period using a 12 g Arg/day dose. All the remaining eligible 101 subjects who tolerated the wash-in dose (45 men and 56 women) were assigned randomly to ingest 0, 15 or 30 g Arg (as pharmaceutical-grade Arg-HCl) per day for 90 days. Arg was taken daily in at least two divided doses by mixing with a flavored beverage. At Days 0 and 90, blood pressures of study subjects were recorded, their physical examinations were performed, and their blood and 24-h urine samples were obtained to measure: (1) serum concentrations of amino acids, glucose, fatty acids, and related metabolites; and (2) renal, hepatic, endocrine and metabolic parameters. Our results indicate that the serum concentration of Arg in men or women increased (P < 0.05) progressively with increasing oral Arg doses from 0 to 30 g/day. Dietary supplementation with 30 g Arg/day reduced (P < 0.05) systolic blood pressure and serum glucose concentration in females, as well as serum concentrations of free fatty acids in both males and females. Based on physiological and biochemical variables, study subjects tolerated oral administration of 15 and 30 g Arg/day without adverse events. We conclude that a long-term safe level of dietary Arg supplementation is at least 30 g/day in adult humans.

Keywords

Arginine Health Nutrition Obesity Safety Supplementation 

Abbreviations

ALT

Alanine transaminase

Arg

l-Arginine

AST

Aspartate transaminase

BMI

Body mass index

BW

Body weight

GI

Gastrointestinal

NO

Nitric oxide

OSL

Observed safe level

TSH

Thyroid stimulating hormone

Notes

Acknowledgements

We thank staff nurses at Baylor Scott & White Hospital, as well as Gilson D. Honvoh, Shengdi Hu, Katherine Kelly, Faqiang Liu, Yuanyuan Luan, Gayan I. Nawaratna, and Tapasree R. Sarkar for assistance in this study. This work was supported by a grant from International Council of Amino Acid Science (Brussels, Belgium).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

This study was approved by Baylor Scott & White Hospital and Texas A&M University Institutional Review Boards.

Informed consent

Informed consent was obtained from all study subjects.

Supplementary material

726_2018_2594_MOESM1_ESM.docx (33 kb)
Supplementary material 1 (DOCX 32 kb)
726_2018_2594_MOESM2_ESM.docx (33 kb)
Supplementary material 2 (DOCX 32 kb)

References

  1. Barbul A (1986) Arginine: biochemistry, physiology, and therapeutic implications. J Parenter Enteral Nutr 10:227–238CrossRefGoogle Scholar
  2. 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–E896CrossRefGoogle Scholar
  3. 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
  4. Blachier F, Leclercq-Meyer V, Marchand J, Woussen-Colle MC, Mathias PC, Sener A, Malaisse WJ (1989) Stimulus-secretion coupling of arginine-induced insulin release. Functional response of islets to l-arginine and L-ornithine. Biochim Biophys Acta 1013:144–151CrossRefPubMedGoogle Scholar
  5. Blachier F, Davila AM, Benamouzig R, Tome D (2011) Channelling of arginine in NO and polyamine pathways in colonocytes and consequences. Front Biosci 16:1331–1343CrossRefGoogle Scholar
  6. Block G, Thompson FE, Hartman AM, Larkin FA, Guire KE (1992) Comparison of two dietary questionnaires validated against multiple dietary records collected during a 1-year period. J Am Diet Assoc 92:686–693PubMedGoogle Scholar
  7. Boger RH, Bode-Boger SM (2001) The clinical pharmacology of l-arginine. Annu Rev Pharmacol Toxicol 41:79–99CrossRefPubMedGoogle Scholar
  8. Brosnan JT, Brosnan ME (2007) Creatine: endogenous metabolite, dietary, and therapeutic supplement. Annu Rev Nutr 27:241–261CrossRefPubMedGoogle Scholar
  9. Buchman AL, O’Brien W, Ou CN, Rognerud C, Alvarez M, Dennis K, Ahn C (1999) The effect of arginine or glycine supplementation on gastrointestinal function, muscle injury, serum amino acid concentrations and performance during a marathon run. Int J Sports Med 20:315–321CrossRefPubMedGoogle Scholar
  10. 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–E539CrossRefGoogle Scholar
  11. 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
  12. Clarkson P, Adams MR, Powe AJ, Donald AE, McCredie R, Robinson J, McCarthy SN, Keech A, Celermajer DS, Deanfiled JE (1996) Oral l-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults. J Clin Invest 97:1989–1994CrossRefPubMedPubMedCentralGoogle Scholar
  13. Closs EI, Simon A, Vékony N, Rotmann A (2004) Plasma membrane transporters for arginine. J Nutr 134:2752S–2759SCrossRefPubMedGoogle Scholar
  14. Colgan M (1993) Optimum sports nutrition: your competitive edge. Advanced Research, RonkonkomaGoogle Scholar
  15. Creager MA, Gallagher SJ, Girerd XJ, Coleman SM, Dzau VJ, Cooke JP (1992) l-Arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans. J Clin Invest 90:1248–1253CrossRefPubMedPubMedCentralGoogle Scholar
  16. Cynober L (2007) Pharmacokinetics of arginine and related amino acids. J Nutr 137:1646S–1649SCrossRefPubMedGoogle Scholar
  17. Evans RW, Fernstrom JD, Thompson J, Morris SM, Kuller LH (2004) Biochemical responses of healthy subjects during dietary supplementation with l-arginine. J Nutr Biochem 15:534–539CrossRefPubMedGoogle Scholar
  18. FAO/WHO (Food and Agriculture Organization/World Health Organization) (2006) A model for establishing upper levels of intake for nutrients and related substances. Technical Workshop on Nutrient Risk Assessment, GenevaGoogle Scholar
  19. Flynn NE, Meininger CJ, Haynes TE, Wu G (2002) The metabolic basis of arginine nutrition and pharmacotherapy. Biomed Pharmacother 56:427–438CrossRefPubMedGoogle Scholar
  20. 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 135:714–721CrossRefPubMedGoogle Scholar
  21. Gornik HL, Creager MA (2004) Arginine and endothelial and vascular health. J Nutr 134:2880S–2887SCrossRefPubMedGoogle Scholar
  22. 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
  23. Grimble GK (2007) Advanced gastrointestinal effects of arginine and related amino acids. J Nutr 137:1693S–1701SCrossRefPubMedGoogle Scholar
  24. Haghikia A, Yanchev GR, Kayacelebi AA, Hanff E, Bledau N, Widera C, Sonnenschein K, Haghikia A, Weissenborn K, Bauersachs J, Bavendiek U, Tsikas D (2017) The role of L-arginine/L-homoarginine/nitric oxide pathway for aortic distensibility and intima-media thickness in stroke patients. Amino Acids 49:1111–1121CrossRefPubMedGoogle Scholar
  25. Harvard School of Public Health (2018) Nutrient tables. https://regepi.bwh.harvard.edu/health. Accessed 30 Jan 2018
  26. Hayashi Y (2003) Application of the concept of risk assessment to the study of amino acid supplements. J Nutr 133:2021S–2024SCrossRefPubMedGoogle Scholar
  27. Health Canada (2006) Canadian adverse drug reaction monitoring program. Health Canada, OttawaGoogle Scholar
  28. Hou YQ, Wu G (2017) Nutritionally nonessential amino acids: a misnomer in nutritional sciences. Adv Nutr 8:137–139CrossRefPubMedPubMedCentralGoogle Scholar
  29. Hou YQ, Yin YL, Wu G (2015a) Dietary essentiality of “nutritionally nonessential amino acids” for animals and humans. Exp Biol Med 240:997–1007CrossRefGoogle Scholar
  30. Hou Y, Jia S, Nawaratna G, Hu S, Dahanayaka S, Bazer FW, Wu G (2015b) Analysis of l-homoarginine in biological samples by HPLC involving precolumn derivatization with o-phthalaldehyde and N-acetyl-l-cysteine. Amino Acids 47:2005–2014CrossRefPubMedGoogle Scholar
  31. Hou YQ, Yao K, Yin YL, Wu G (2016a) Endogenous synthesis of amino acids limits growth, lactation and reproduction of animals. Adv Nutr 7:331–342CrossRefPubMedPubMedCentralGoogle Scholar
  32. Hou Y, Hu S, Jia S, Nawaratna G, Che D, Wang F, 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
  33. 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
  34. 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
  35. Jani B, Bulpitt CJ, Rajkumar C (2006) Blood pressure measurement in patients with rate controlled atrial fibrillation using mercury sphygmomanometer and Omron HEM-750CP deice in the clinic setting. J Hum Hypert 20:543–545CrossRefGoogle Scholar
  36. Jobgen WJ, Meininger CJ, Jobgen SC, Li P, Lee M-J, Smith SB, Spencer T, Fried SK, Wu G (2009a) 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
  37. Jobgen W, Fu WJ, Gao H, Li P, Meininger CJ, Smith SB, Spencer TE, Wu G (2009b) High fat feeding and dietary l-arginine supplementation differentially regulate gene expression in rat white adipose tissue. Amino Acids 37:187–198CrossRefPubMedGoogle Scholar
  38. 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
  39. Kayacelebi AA, Minović I, Hanff E, Frenay AS, de Borst MH, Feelisch M, van Goor H, Bakker SJL, Tsikas D (2017) Low plasma homoarginine concentration is associated with high rates of all-cause mortality in renal transplant recipients. Amino Acids 49:1193–1202CrossRefPubMedGoogle Scholar
  40. 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
  41. Li H, Meininger CJ, Wu G (2000) Rapid determination of nitrite by reversed-phase high-performance liquid chromatography with fluorescence detection. J Chromatogr B 746:199–207CrossRefGoogle Scholar
  42. Li H, Meininger CJ, Bazer FW, Wu G (2016) Intracellular sources of ornithine for polyamine synthesis in endothelial cells. Amino Acids 48:2401–2410CrossRefPubMedGoogle Scholar
  43. Liao SF, Regmi N, Wu G (2018) Homeostatic regulation of plasma amino acid concentrations. Front Biosci 23:640–655CrossRefGoogle Scholar
  44. 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
  45. 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
  46. Ma X, Han M, Li DF, Hu S, Gilbreath KR, Bazer FW, Wu G (2017) l-Arginine promotes protein synthesis and cell growth in brown adipocyte precursor cells via the mTOR signal pathway. Amino Acids 49:957–964CrossRefPubMedGoogle Scholar
  47. Marliss EB, Chevalier S, Gougeon R, Morais JA, Lamarche M, Adegoke OAJ, Wu G (2006) Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover. Diabetologia 49:351–359CrossRefPubMedGoogle Scholar
  48. McCreight LJ, Bailey CJ, Pearson ER (2016) Metformin and the gastrointestinal tract. Diabetologia 59:426–435CrossRefPubMedPubMedCentralGoogle Scholar
  49. McKnight JR, Satterfield MC, Jobgen WS, Smith SB, Spencer TE, Meininger CJ, McNeal CJ, Wu G (2010) Beneficial effects of l-arginine on reducing obesity: potential mechanisms and important implications for human health. Amino Acids 39:349–357CrossRefPubMedGoogle Scholar
  50. McNeal C, Wu G, Vasquez S, Wilson DP, Satterfield MC, McKnight JR, Malbari H (2010) The role of arginine for treating obese youth. In: Bagchi D (ed) Global perspectives on childhood obesity. Elsevier, New York, pp 433–442Google Scholar
  51. McNeal CJ, Meininger CJ, Reddy D, Wilborn CD, Wu G (2016) Safety and effectiveness of arginine in adults. J Nutr 146:2587S–2593SCrossRefPubMedGoogle Scholar
  52. Meijer AJ, Lof C, Ramos IC, Verhoeven AJ (1985) Control of ureogenesis. Eur J Biochem 148:189–196CrossRefPubMedGoogle Scholar
  53. Mertens IL, Van Gaal LF (2000) Overweight, obesity, and blood pressure: the effects of modest weight reduction. Obes Res 8:270–278CrossRefPubMedGoogle Scholar
  54. Morris SM Jr (2007) Arginine metabolism: boundaries of our knowledge. J Nutr 137:1602S–1609SCrossRefPubMedGoogle Scholar
  55. Muñoz-Garach A, Cornejo-Pareja I, Tinahones FJ (2017) Does metabolically healthy obesity exist? Nutrients 8:320CrossRefGoogle Scholar
  56. Paddon-Jones D, Borsheim E, Wolfe RR (2004) Potential ergogenic effects of arginine and creatine supplementation. J Nutr 134:2888S–2894SCrossRefPubMedGoogle Scholar
  57. Pahlavani N, Entezari MH, Nasiri M, Miri A, Rezaie M, Bagheri-Bidakhavidi M, Sadeghi O (2017) The effect of l-arginine supplementation on body composition and performance in male athletes: a double-blinded randomized clinical trial. Eur J Clin Nutr 71:544–548CrossRefPubMedGoogle Scholar
  58. Papageorgiou N, Androulakis E, Papaioannou S, Antoniades C, Tousoulis D (2015) Homoarginine in the shadow of asymmetric dimethylarginine: from nitric oxide to cardiovascular disease. Amino Acids 47:1741–1750CrossRefPubMedGoogle Scholar
  59. Pilz S, Meinitzer A, Gaksch M, Grübler M, Verheyen N, Drechsler C, Hartaigh BÓ, Lang F, Alesutan I, Voelkl J, März W, Tomaschitz A (2015) Homoarginine in the renal and cardiovascular systems. Amino Acids 47:1703–1713CrossRefPubMedGoogle Scholar
  60. Sase A, Nawaratna G, Hu S, Wu G, Lubec G (2016) Decreased hippocampal homoarginine and increased nitric oxide and nitric oxide synthase levels in rats parallel training in a radial arm maze. Amino Acids 48:2197–2204CrossRefPubMedGoogle Scholar
  61. Schneider JY, Rothmann S, Schröder F, Langen J, Lücke T, Mariotti F, Huneau JF, Frölich JC, Tsikas D (2015) Effects of chronic oral l-arginine administration on the l-arginine/NO pathway in patients with peripheral arterial occlusive disease or coronary artery disease: l-Arginine prevents renal loss of nitrite, the major NO reservoir. Amino Acids 47:1961–1974CrossRefPubMedGoogle Scholar
  62. Schulman SP, Becker LC, Kass DA, Champion HC, Terrin ML, Forman S, Ernst KV, Kelemen MD, Townsend SN, Capriotti A, Hare JM, Gernstenblith G (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
  63. Shao A, Hathcock JN (2008) Risk assessment for the amino acids taurine, l-glutamine and l-arginine. Regul Toxicol Pharmacol 50:376–399CrossRefPubMedGoogle Scholar
  64. Sidney S, Jacobs DR Jr, Haskell WL, Armstrong MA, Dimicco A, Oberman A, Savage PJ, Slattery ML, Sternfeld B, Van Horn L (1991) Comparison of two methods of assessing physical activity in the coronary artery risk development in young adults (CARDIA) Study. Am J Epidemiol 133:1231–1245CrossRefPubMedGoogle Scholar
  65. Stefan N, Häring HU, Hu FB, Schulze MB (2013) Metabolically healthy obesity: epidemiology, mechanisms, and clinical implications. Lancet Diabetes Endocrinol 1:152–162CrossRefPubMedGoogle Scholar
  66. Stockebrand M, Hornig S, Neu A, Atzler D, Cordts K, Böger RH, Isbrandt D, Schwedhelm E, Choe C (2015) Homoarginine supplementation improves blood glucose in diet-induced obese mice. Amino Acids 47:1921–1929CrossRefPubMedGoogle Scholar
  67. Tan BE, Li XG, Kong XF, Huang RL, Ruan Z, Yao K, Deng ZY, Xie MY, Shinzato I, Yin YL, Wu G (2009) Dietary l-arginine supplementation enhances the immune status in early-weaned piglets. Amino Acids 37:323–331CrossRefPubMedGoogle Scholar
  68. Tan BE, Yin YL, Kong XF, Li P, Li XL, Gao HJ, Li XG, Huang RL, Wu G (2010) l-Arginine stimulates proliferation and prevents endotoxin-induced death of intestinal cells. Amino Acids 38:1227–1235CrossRefPubMedGoogle Scholar
  69. Tanghao O, Chalon S, Moreno H Jr, Hoffman BB, Blaschke TF (1999) Pharmacokinetics of l-arginine during chronic administration to patients with hypercholesterolaemia. Clin Sci (Lond) 96:199–207CrossRefGoogle Scholar
  70. Tsikas D, Wu G (2015) Homoarginine, arginine, and relatives: analysis, metabolism, transport, physiology, and pathology. Amino Acids 47:1697–1702CrossRefPubMedGoogle Scholar
  71. Tsikas D, Bollenbach A, Hanff E, Kayacelebi AA (2018) Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and homoarginine (hArg): the ADMA, SDMA and hArg paradoxes. Cardiovasc Diabetol 17(1):1CrossRefPubMedPubMedCentralGoogle Scholar
  72. 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
  73. Urbina SL, Roberts MD, Kephart WC, Villa KB, Santos EN, Olivencia AM, Bennett HM, Lara MD, Foster CA, Purpura M, Jäger R, Taylor LW, Wilborn CD (2017) Effects of twelve weeks of capsaicinoid supplementation on body composition, appetite and self-reported caloric intake in overweight individuals. Appetite 113:264–273CrossRefPubMedGoogle Scholar
  74. Wu G (1995) Urea synthesis in enterocytes of developing pigs. Biochem J 312:717–723CrossRefPubMedPubMedCentralGoogle Scholar
  75. Wu G (2013) Amino acids: biochemistry and nutrition. CRC, Boca RatonCrossRefGoogle Scholar
  76. Wu G, Meininger CJ (2000) Arginine nutrition and cardiovascular function. J Nutr 130:2626–2629CrossRefPubMedGoogle Scholar
  77. Wu G, Meininger CJ (2008) Analysis of citrulline, arginine, and methylarginines using high-performance liquid chromatography. Methods Enzymol 440:177–189CrossRefPubMedGoogle Scholar
  78. Wu G, Morris SM Jr (1998) Arginine metabolism: nitric oxide and beyond. Biochem J 336:1–17CrossRefPubMedPubMedCentralGoogle Scholar
  79. Wu G, Haynes TE, Li H, Meininger CJ (2000) Glutamine metabolism in endothelial cells: ornithine synthesis from glutamine via pyrroline-5-carboxylate synthase. Comp Biochem Physiol A 126:115–123CrossRefGoogle Scholar
  80. 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–1680SCrossRefPubMedGoogle Scholar
  81. Wu G, Collins JK, Perkins-Veazie P, Siddiq M, Dolan KD, Kelly KA, Heaps CL, Meininger CJ (2007b) Dietary supplementation with watermelon pomace juice enhances arginine availability and ameliorates the metabolic syndrome in Zucker diabetic fatty rats. J Nutr 137:2680–2685CrossRefPubMedGoogle Scholar
  82. 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
  83. Wu ZL, Hou YQ, Hu SD, Bazer FW, Meininger CJ, McNeal CJ, Wu G (2016) Catabolism and safety of supplemental l-arginine in animals. Amino Acids 48:1541–1552CrossRefPubMedGoogle Scholar
  84. 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
  85. Yao K, Yin YL, Chu WY, Liu ZQ, Deng D, Li TJ, Huang RL, Zhang JS, Tan BE, Wang W, Wu G (2008) Dietary arginine supplementation increases mTOR signaling activity in skeletal muscle of neonatal pigs. J Nutr 138:867–872CrossRefPubMedGoogle Scholar
  86. Zheng R, Liu C, Wang C, Zhou B, Liu Y, Pan F, Zhang R, Zhu Y (2016) Natural course of metabolically healthy overweight/obese subjects and the impact of weight change. Nutrients 8:430CrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Catherine J. McNeal
    • 1
  • Cynthia J. Meininger
    • 2
  • Colin D. Wilborn
    • 3
  • Carmen D. Tekwe
    • 4
  • Guoyao Wu
    • 2
    • 5
    Email author
  1. 1.Department of Internal MedicineBaylor Scott & White HealthTempleUSA
  2. 2.Department of Medical Physiology, College of MedicineTexas A&M Health Science CenterTempleUSA
  3. 3.Department of Exercise and Sport ScienceUniversity of Mary Hardin-BaylorBeltonUSA
  4. 4.Department of Epidemiology and Biostatistics, School of Public HealthTexas A&M Health Science CenterCollege StationUSA
  5. 5.Department of Animal Science and Faculty of NutritionTexas A&M UniversityCollege StationUSA

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