Advertisement

Amino Acids

, Volume 51, Issue 4, pp 647–659 | Cite as

Safety assessment of l-lysine oral intake: a systematic review

  • Kohsuke HayamizuEmail author
  • Ikuyo Oshima
  • Zesoku Fukuda
  • Yui Kuramochi
  • Yuki Nagai
  • Nobuo Izumo
  • Makoto Nakano
Original Article
First Online:
  • 289 Downloads

Abstract

Currently, the use of amino acids in supplements and functional foods is increasing globally. However, there are no guidelines for the upper limit of ingestion for the safe use of these amino acids. Safety evaluation of chemical substances is generally performed through non-clinical and clinical studies. However, amino acids that have these safety data are limited. Therefore, we used a systematic review approach for evaluating the safety of amino acids. In the present study, we evaluated the safety of l-lysine added to an ordinary diet in humans. Using PubMed, Cochrane Library, Ichushi Web, and EBSCOhost as search databases, we comprehensively searched human studies on oral ingestion of l-lysine. Ultimately, 71 studies were selected for evaluation. Of these, 12 studies were of relatively high quality with Jadad scores ≥ 3. The dose range of l-lysine in the selected studies was 16.8–17,500 mg/day, and the range of dosing period was 1–1095 days. The observed adverse events were mainly subjective symptoms related to the gastrointestinal tract such as nausea, stomachache, and diarrhea. The provisional no-observed-adverse-effect level obtained based on these gastrointestinal symptoms was 6000 mg/person/day. Integrated analysis of the risk for developing gastrointestinal symptoms revealed that the risk ratio was 1.02 (95% CI, 0.96–1.07; p = 0.49); thus, no significant increase was observed. (UMIN000028914)

Keywords

l-Lysine Systematic review Safety NOAEL Gastrointestinal symptom 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgements

This study was conducted with research funds provided by the International Council on Amino Acid Science (Grant no. ICAAS_4-4-19) (Brussels, Belgium).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with humans or animals. Authors make sure that the manuscript complies with the ethical rules applicable for this journal.

References

  1. Anderson SA, Raiten DJ (1992) Safety of amino acids used as dietary supplements 59. Life Science Research Office, FASEB, Special Publications Office, BethesdaGoogle Scholar
  2. Angeles-Agdeppa I, Magsadia CR, Capanzana MV (2011) Fortified juice drink improved iron and zinc status of school children. Asia Pac J Clin Nutr 20:535–543PubMedGoogle Scholar
  3. Azzarà A, Carulli G, Sbrana S, Rizzuti-Gullaci A, Minnucci S, Natale M, Ambrogi F (1995) Effects of lysine-arginine association on immune functions in patients with recurrent infections. Drugs Exp Clin Res 21:71–78PubMedGoogle Scholar
  4. Baier S, Johannsen D, Abumrad N, Rathmacher JA, Nissen S, Flakoll PJPENJ (2009) Year-long changes in protein metabolism in elderly men and women supplemented with a nutrition cocktail of beta-hydroxy-beta-methylbutyrate (HMB), l-arginine, and l-lysine. J Parenter Enteral Nutr 33:71–82CrossRefGoogle Scholar
  5. Baruffol C, Jordi J, Camargo S, Radovic T, Herzog B, Fried M, Schwizer W, Verrey F, Lutz TA, Steingoetter A (2014) l-lysine dose dependently delays gastric emptying and increases intestinal fluid volume in humans and rats. Neurogastroenterol Motil 26:999–1009CrossRefPubMedGoogle Scholar
  6. Bihuniak JD, Sullivan RR, Simpson CA, Caseria DM, Huedo-Medina TB, O’Brien KO, Kerstetter JE, Insogna KL (2014) Supplementing a low-protein diet with dibasic amino acids increases urinary calcium excretion in young women. J Nutr 144:282–288CrossRefPubMedPubMedCentralGoogle Scholar
  7. Cabacungan NB, Miles CW, Abernathy RP, Ritchey SJ (1973) Hydroxyproline excretion and nutritional status of children. Am J Clin Nutr 26:173–176CrossRefPubMedGoogle Scholar
  8. Chi CC, Wang SH, Delamere FM, Wojnarowska F, Peters MC, Kanjirath PP (2015) Interventions for prevention of herpes simplex labialis (cold sores on the lips). Cochrane Database Syst Rev 7:CD010095Google Scholar
  9. Chirita R, Sacuiu I, Burlea A, Chirita V (2012) The role of nitric oxide inhibitors in treatment on symptom severity and cognitive deficits in schizophrenia. Int J Neuropsychopharmacol 15:113Google Scholar
  10. Clark HE, Yang SP, Waltson W, Mertz ET (1960) Amino acid requirements of men and women. II. Relation of lysine requirement to sex, body size, basal caloric expenditure and creatinine excretion. J Nutr 71:229–234CrossRefPubMedGoogle Scholar
  11. Clark HE, Bailey LB, Brewer MF (1977) Lysine and tryptophan in cereal-based diets for adult human subjects. Am J Clin Nutr 30:674–680CrossRefPubMedGoogle Scholar
  12. Cochrane community (2014) http://community.cochrane.org/tools/review-production-tools/revman-5. Accessed 30 Oct 2014
  13. Contreras I, Reiser KM, Martinez N, Giansante E, Lopez T, Suarez N, Postalian S, Molina M, Gonzalez F, Sanchez MR, Camejo M, Blanco MC (1997) Effects of aspirin or basic amino acids on collagen cross-links and complications in NIDDM. Diabetes Care 20:832–835CrossRefPubMedGoogle Scholar
  14. Corpas E, Blackman MR, Roberson R, Scholfield D, Harman SM (1993) Oral arginine-lysine does not increase growth hormone or insulin-like growth factor-I in old men. J Gerontol 48:M128–M133CrossRefPubMedGoogle Scholar
  15. Deeks JJ, Higgins JPT (2010) Statistical algorithms in review manager 5. Cochrane training, http://training.cochrane.org/search/site/revman%20statistical. Accessed 10 Apr 2015
  16. DiGiovanna JJ, Blank H (1984) Failure of lysine in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Arch Dermatol 120:48–51CrossRefPubMedGoogle Scholar
  17. Doraiswamy TR, Singh N, Daniel VA (1969) Effects of supplementing ragi (Eleusine coracana) diets with lysine or leaf protein on the growth and nitrogen metabolism of children. Br J Nutr 23:737–743CrossRefPubMedGoogle Scholar
  18. Duncan AM, Ball RO, Pencharz PB (1996) Lysine requirement of adult males is not affected by decreasing dietary protein. Am J Clin Nutr 64:718–725CrossRefPubMedGoogle Scholar
  19. Duparc C, André C, Ménard J, Godouet-Getti B, Wils J, Cailleux AF, Moreau-Grangé L, Louiset E, Lefebvre H (2017) l-lysine acts as a serotonin type 4 receptor antagonist to counteract in vitro and in vivo the stimulatory effect of serotonergic agents on aldosterone secretion in man. Horm Metab Res 49:269–275CrossRefPubMedGoogle Scholar
  20. Elango R, Humayun MA, Ball RO, Pencharz PB (2007) Lysine requirement of healthy school-age children determined by the indicator amino acid oxidation method. Am J Clin Nutr 86:360–365CrossRefPubMedGoogle Scholar
  21. Elango R, Humayun MA, Ball RO, Pencharz PB (2009) Indicator amino acid oxidation is not affected by period of adaptation to a wide range of lysine intake in healthy young men. J Nutr 139:1082–1087CrossRefPubMedGoogle Scholar
  22. Elango R, Ball RO, Pencharz PB (2012a) Recent advances in determining protein and amino acid requirements in humans. Br J Nutr 108:S22–30CrossRefPubMedGoogle Scholar
  23. Elango R, Chapman K, Rafii M, Ball RO, Pencharz PB (2012b) Determination of the tolerable upper intake level of leucine in acute dietary studies in young men. Am J Clin Nutr 96:759–767CrossRefPubMedGoogle Scholar
  24. FAO/WHO (2005) A model for establishing upper levels of intake for nutrients and related substances. Report of a joint FAO/WHO technical workshop on nutrient risk assessment WHO headquartersGoogle Scholar
  25. Flakoll P, Sharp R, Baier S, Levenhagen D, Carr C, Nissen S (2004) Effect of beta-hydroxy-beta-methylbutyrate, arginine, and lysine supplementation on strength, functionality, body composition, and protein metabolism in elderly women. Nutrition 20:445–451CrossRefPubMedGoogle Scholar
  26. Flodin NW (1997) The metabolic roles, pharmacology, and toxicology of lysine. J Am Coll Nutr 16:7–21CrossRefPubMedGoogle Scholar
  27. Fuller JC Jr, Baier S, Flakoll P, Nissen SL, Abumrad NN, Rathmacher JA (2011) Vitamin D status affects strength gains in older adults supplemented with a combination of β-hydroxy-β-methylbutyrate, arginine, and lysine: a cohort study. J Parenter Enteral Nutr 35:757–762CrossRefGoogle Scholar
  28. Ghosh S, Pellett PL, Aw-Hassan A, Mouneime Y, Smriga M, Scrimshaw NS (2008) Impact of lysine-fortified wheat flour on morbidity and immunologic variables among members of rural families in northwest Syria. Food Nutr Bull 29:163–171CrossRefPubMedGoogle Scholar
  29. Ghosh S, Smriga M, Vuvor F, Suri D, Mohammed H, Armah SM, Scrimshaw NS (2010) Effect of lysine supplementation on health and morbidity in subjects belonging to poor peri-urban households in Accra, Ghana. Am J Clin Nutr 92:928–939CrossRefPubMedGoogle Scholar
  30. Godard MP, Williamson DL, Trappe SW (2002) Oral amino-acid provision does not affect muscle strength or size gains in older men. Med Sci Sports Exerc 34:1126–1131CrossRefPubMedGoogle Scholar
  31. Graham GG, Placko RP, Acevedo G, Morales E, Cordano A (1969) Lysine enrichment of wheat flour: evaluation in infants. Am J Clin Nutr 22:1459–1468CrossRefPubMedGoogle Scholar
  32. Griffith RS, Walsh DE, Myrmel KH, Thompson RW, Behforooz A (1987) Success of l-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica 175:183–190CrossRefPubMedGoogle Scholar
  33. Hanberg JS, Rao V, Ter Maaten JM, Laur O, Brisco MA, Perry Wilson F, Grodin JL, Assefa M, Samuel Broughton J, Planavsky NJ, Ahmad T, Bellumkonda L, Tang WH, Parikh CR, Testani JM (2016) Hypochloremia and diuretic resistance in heart failure: mechanistic Insights. Circ Heart Fail 9:e003180CrossRefPubMedGoogle Scholar
  34. Hecking E, Köhler H, Zobel R, Lemmel EM, Mader H, Opferkuch W, Prellwitz W, Keim HJ, Müller D (1978) Treatment with essential amino acids in patients on chronic hemodialysis: a double blind cross-over study. Am J Clin Nutr 31:1821–1826CrossRefPubMedGoogle Scholar
  35. Higgins JPT, Green S (2008) Cochrane handbook for systematic reviews of interventions. Wiley-Blackwell, ChichesterCrossRefGoogle Scholar
  36. Hlais S, Reslan DR, Sarieddine HK, Nasreddine L, Taan G, Azar S, Obeid OA (2012) Effect of lysine, vitamin B6, and carnitine supplementation on the lipid profile of male patients with hypertriglyceridemia: a 12-week, open-label, randomized, placebo-controlled trial. Clin Ther 34:1674–1682CrossRefPubMedGoogle Scholar
  37. Hussain T, Abbas S, Khan MA, Scrimshaw NS (2004) Lysine fortification of wheat flour improves selected indices of the nutritional status of predominantly cereal-eating families in Pakistan. Food Nutr Bull 25:114–122CrossRefPubMedGoogle Scholar
  38. Institute of Medicine for the National Academies (2002) Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. National Academic Press, Washinton DCGoogle Scholar
  39. Isidori A, Lo Monaco A, Cappa M (1981) A study of growth hormone release in man after oral administration of amino acids. Curr Med Res Opin 7:475–481CrossRefPubMedGoogle Scholar
  40. Iwasaki M, Ishihara J, Takachi R, Todoriki H, Yamamoto H, Miyano H, Yamaji T, Tsugane S (2016) Validity of a self-administered food-frequency questionnaire for assessing amino acid intake in Japan. J Epidemiol 26:36–44CrossRefPubMedGoogle Scholar
  41. Jadad AR, Moore RA, Carroll D, Jenkin-son C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12CrossRefPubMedGoogle Scholar
  42. Jamdar J, Rao B, Netke S, Roomi MW, Ivanov V, Niedzwiecki A, Rath M (2004) Reduction in tibial shaft fracture healing time with essential nutrient supplementation containing ascorbic acid, lysine, and proline. J Altern Complem Med 10:915–916PubMedGoogle Scholar
  43. Jezova D, Makatsori A, Smriga M, Morinaga Y, Duncko R (2005) Subchronic treatment with amino acid mixture of l-lysine and l-arginine modifies neuroendocrine activation during psychosocial stress in subjects with high trait anxiety. Nutr Neurosci 8:155–160CrossRefPubMedGoogle Scholar
  44. Kalogeropoulou D, LaFave L, Schweim K, Gannon MC, Nuttall FQ (2009) Lysine ingestion markedly attenuates the glucose response to ingested glucose without a change in insulin response. Am J Clin Nutr 90:314–320CrossRefPubMedGoogle Scholar
  45. Khan-Siddiqui L, Bamji MS (1983) Lysine-carnitine conversion in normal and undernourished adult men-suggestion of a nonpeptidyl pathway. Am J Clin Nutr 37:93–98CrossRefPubMedGoogle Scholar
  46. Kriengsinyos W, Wykes LJ, Ball RO, Pencharz PB (2002) Oral and intravenous tracer protocols of the indicator amino acid oxidation method provide the same estimate of the lysine requirement in healthy men. J Nutr 132:2251–2257CrossRefPubMedGoogle Scholar
  47. Kriengsinyos W, Wykes LJ, Goonewardene LA, Ball RO, Pencharz PB (2004) Phase of menstrual cycle affects lysine requirement in healthy women. Am J Physiol Endocrinol Metab 287:E489–E496CrossRefPubMedGoogle Scholar
  48. Kurpad AV, Young VR (2003) What is apparent is not always real: lessons from lysine requirement studies in adult humans. J Nutr 133:1227–1230CrossRefPubMedGoogle Scholar
  49. Kurpad AV, El-Khoury AE, Beaumier L, Srivatsa A, Kuriyan R, Raj T, Borgonha S, Ajami AM, Young VR (1998) An initial assessment, using 24-h [13C]leucine kinetics, of the lysine requirement of healthy adult Indian subjects. Am J Clin Nutr 67:58–66CrossRefPubMedGoogle Scholar
  50. Kurpad AV, Raj T, El-Khoury A, Beaumier L, Kuriyan R, Srivatsa A, Borgonha S, Selvaraj A, Regan MM, Young VR (2001) Lysine requirements of healthy adult Indian subjects, measured by an indicator amino acid balance technique. Am J Clin Nutr 73:900–907CrossRefPubMedGoogle Scholar
  51. Kurpad AV, Regan MM, Raj T, El-Khoury A, Kuriyan R, Vaz M, Chandakudlu D, Venkataswamy VG, Borgonha S, Young VR (2002) Lysine requirements of healthy adult Indian subjects receiving long-term feeding, measured with a 24-h indicator amino acid oxidation and balance technique. Am J Clin Nutr 76:404–412CrossRefPubMedGoogle Scholar
  52. Kurpad AV, Regan MM, Nazareth D, Nagaraj S, Gnanou J, Young VR (2003a) Intestinal parasites increase the dietary lysine requirement in chronically undernourished Indian men. Am J Clin Nutr 78:1145–1151CrossRefPubMedGoogle Scholar
  53. Kurpad AV, Regan MM, Raj T, Vasudevan J, Kuriyan R, Gnanou J, Young VR (2003b) Lysine requirements of chronically undernourished adult Indian men, measured by a 24-h indicator amino acid oxidation and balance technique. Am J Clin Nutr 77:101–108CrossRefPubMedGoogle Scholar
  54. Maletzky BM (1978) The alcohol provocation test. J Clin Psychiatry 39:403–411PubMedGoogle Scholar
  55. McCune MA, Perry HO, Muller SA, O’Fallon WM (1984) Treatment of recurrent herpes simplex infections with l-lysine monohydrochloride. Cutis 34:366–373PubMedGoogle Scholar
  56. Michishita T, Kobayashi S, Katsuya T, Ogihara T, Kawabuchi K (2010) Evaluation of the antiobesity effects of an amino acid mixture and conjugated linoleic acid on exercising healthy overweight humans: a randomized, double-blind, placebo-controlled trial. J Int Med Res 38:844–859CrossRefPubMedGoogle Scholar
  57. Milman N, Scheibel J, Jessen O (1978) Failure of lysine treatment in recurrent herpes simplex labialis. Lancet 28:942CrossRefGoogle Scholar
  58. Milman N, Scheibel J, Jessen O (1980) Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. Acta Derm Venereol 60:85–87PubMedGoogle Scholar
  59. Mirmiranpour H, Khaghani S, Bathaie SZ, Nakhjavani M, Kebriaeezadeh A, Ebadi M, Gerayesh-Nejad S, Zangooei M (2016) The preventive effect of l-lysine on lysozyme glycation in type 2 diabetes. Acta Med Iran 54:24–31PubMedGoogle Scholar
  60. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PloS Med 6:e1000097CrossRefPubMedPubMedCentralGoogle Scholar
  61. Moja EA, Stoff DM, Gessa GL, Castoldi D, Assereto R, Tofanetti O (1988) Decrease in plasma tryptophan after tryptophan-free amino acid mixtures in man. Life Sci 42:1551–1556CrossRefPubMedGoogle Scholar
  62. Nilsson M, Holst JJ, Björck IM (2007) Metabolic effects of amino acid mixtures and whey protein in healthy subjects: studies using glucose-equivalent drinks. Am J Clin Nutr 85:996–1004CrossRefPubMedGoogle Scholar
  63. Pellett PL, Ghosh S (2004) Lysine fortification: past, present, and future. Food Nutr Bull 25:107–113CrossRefPubMedGoogle Scholar
  64. Peltola K, Heinonen OJ, Näntö-Salonen K, Pulkki K, Simell O (2000) Oral lysine feeding in gyrate atrophy with hyperornithinaemia—a pilot study. J Inherit Metab Dis 23:305–307CrossRefPubMedGoogle Scholar
  65. Pillai RR, Elango R, Muthayya S, Ball RO, Kurpad AV, Pencharz PB (2010) Lysine requirement of healthy, school-aged Indian children determined by the indicator amino acid oxidation technique. J Nutr 140:54–59CrossRefPubMedGoogle Scholar
  66. Pillai RR, Elango R, Ball RO, Kurpad AV, Pencharz PB (2015) Lysine requirements of moderately undernourished school-aged Indian children are reduced by treatment for intestinal parasites as measured by the indicator amino acid oxidation technique. J Nutr 145:954–959CrossRefPubMedGoogle Scholar
  67. Prolla IR, Rafii M, Courtney-Martin G, Elango R, da Silva LP, Ball RO, Pencharz PB (2013) Lysine from cooked white rice consumed by healthy young men is highly metabolically available when assessed using the indicator amino acid oxidation technique. J Nutr 143:302–306CrossRefPubMedGoogle Scholar
  68. Rasmussen B, Gilbert E, Turki A, Madden K, Elango R (2016) Determination of the safety of leucine supplementation in healthy elderly men. Amino Acids 48:1707–1716CrossRefPubMedGoogle Scholar
  69. Renwick AG (1991) Safety factors and establishment of acceptable daily intakes. Food Addit Contam 8:135–149CrossRefPubMedGoogle Scholar
  70. Rose WC, Borman A, Coon MJ, Lambert GF (1955) The amino acid requirements of man. X. The lysine requirement. J Biol Chem 214:579–587PubMedGoogle Scholar
  71. Schmidt JA, Rinaldi S, Scalbert A, Ferrari P, Achaintre D, Gunter MJ, Appleby PN, Key TJ, Travis RC (2016) Plasma concentrations and intakes of amino acids in male meat-eaters, fish-eaters, vegetarians and vegans: a cross-sectional analysis in the EPIC-Oxford cohort. Eur J Clin Nutr 70:306–312CrossRefPubMedGoogle Scholar
  72. Scrimshaw NS, Taylor Y, Young VR (1973) Lysine supplementation of wheat gluten at adequate and restricted energy intakes in young men. Am J Clin Nutr 26:965–972CrossRefPubMedGoogle Scholar
  73. Simon CA, Van Melle GD, Ramelet AA (1985) Failure of lysine in frequently recurrent herpes simplex infection. Arch Dermatol 121:167–168CrossRefPubMedGoogle Scholar
  74. Smriga M, Ghosh S, Mouneimne Y, Pellett PL, Scrimshaw NS (2004) Lysine fortification reduces anxiety and lessens stress in family members in economically weak middle east communities. Proc Natl Acad Sci USA 101:8285–8288CrossRefPubMedGoogle Scholar
  75. Smriga M, Ando T, Akutsu M, Furukawa Y, Miwa K, Morinaga Y (2007) Oral treatment with l-lysine and l-arginine reduces anxiety and basal cortisol levels in healthy humans. Biomed Res 28:85–90CrossRefPubMedGoogle Scholar
  76. Spencer H, Samachson J (1963) Effect of lysine on calcium metabolism in man. J Nutr 81:301–306CrossRefPubMedGoogle Scholar
  77. Sulochana KN, Rajesh M, Ramakrishnan S (2001) Insulin receptor tyrosine kinase activity in monocytes of type 2 diabetes mellitus patients receiving oral l-lysine. Indian J Biochem Biophys 38:331–334PubMedGoogle Scholar
  78. Suminski RR, Robertson RJ, Goss FL, Arslanian S, Kang J, DaSilva S, Utter AC, Metz KF (1997) Acute effect of amino acid ingestion and resistance exercise on plasma growth hormone concentration in young men. Int J Sport Nutr 7:48–60CrossRefPubMedGoogle Scholar
  79. The R Project (2016) https://www.r-project.org. Accessed 29 Jun 2016
  80. Thein DJ, Hurt WC (1984) Lysine as a prophylactic agent in the treatment of recurrent herpes simplex labialis. Oral Surg Oral Med Oral Pathol 58:659–666CrossRefPubMedGoogle Scholar
  81. Theytaz F, Noguchi Y, Egli L, Campos V, Buehler T, Hodson L, Patterson BW, Nishikata N, Kreis R, Mittendorfer B, Fielding B, Boesch C, Tappy L (2012) Effects of supplementation with essential amino acids on intrahepatic lipid concentrations during fructose overfeeding in humans. Am J Clin Nutr 96:1008–1016CrossRefPubMedGoogle Scholar
  82. Tipton KD, Ferrando AA, Phillips SM, Doyle D Jr, Wolfe RR (1999) Postexercise net protein synthesis in human muscle from orally administered amino acids. Am J Physiol 276:E628–E634CrossRefPubMedGoogle Scholar
  83. Torricelli P, Fini M, Giavaresi G, Giardino R (2003) Human osteopenic bone-derived osteoblasts: essential amino acids treatment effects. Artif Cells Blood Substit Immobil Biotechnol 31:35–46CrossRefPubMedGoogle Scholar
  84. Tsubuku S, Mochizuki M, Mawatari K, Smriga K, Kimura K (2004) Thirteen-week oral toxicity study of l-lysine hydrochloride in rats. Int J Toxicol 23:113–118CrossRefPubMedGoogle Scholar
  85. Tumilty L, Davison G, Beckmann M, Thatcher R (2013) Acute oral administration of a tyrosine and phenylalanine-free amino acid mixture. Eur J Appl Physiol 113:1511–1522CrossRefPubMedGoogle Scholar
  86. Unni US, Raj T, Sambashivaiah S, Kuriyan R, Uthappa S, Vaz M, Regan MM, Kurpad AV (2012) The effect of a controlled 8-week metabolic ward based lysine supplementation on muscle function, insulin sensitivity and leucine kinetics in young men. Clin Nutr 31:903–910CrossRefPubMedGoogle Scholar
  87. van Vliet S, Burd NA, van Loon LJ (2015) The skeletal muscle anabolic response to plant- versus animal-based protein consumption. J Nutr 145:1981–1991CrossRefPubMedGoogle Scholar
  88. van Vught AJ, Nieuwenhuizen AG, Brummer RJ, Westerterp-Plantenga MS (2008) Effects of oral ingestion of amino acids and proteins on the somatotropic axis. J Clin Endocrinol Metab 93:584–590CrossRefPubMedGoogle Scholar
  89. Vinod Kumar M, Rajagopalan S (2006) Impact of a multiple-micronutrient food supplement on the nutritional status of schoolchildren. Food Nutr Bull 27:203–210CrossRefPubMedGoogle Scholar
  90. Vinod Kumar M, Rajagopalan S (2008) Trial using multiple micronutrient food supplement and its effect on cognition. Indian J Pediatr 75:671–678CrossRefPubMedGoogle Scholar
  91. Wass C, Klamer D, Katsarogiannis E, Pålsson E, Svensson L, Fejgin K, Bogren IB, Engel JA, Rembeck B (2011) l-lysine as adjunctive treatment in patients with schizophrenia: a single-blinded, randomized, cross-over pilot study. BMC Med 9:40CrossRefPubMedPubMedCentralGoogle Scholar
  92. Zeinoddini A, Ahadi M, Farokhnia M, Rezaei F, Tabrizi M, Akhondzadeh S (2014) L-lysine as an adjunct to risperidone in patients with chronic schizophrenia: a double-blind, placebo-controlled, randomized trial. J Psychiatr Res 59:125–131CrossRefPubMedGoogle Scholar
  93. Zello GA, Pencharz PB, Ball RO (1993) Dietary lysine requirement of young adult males determined by oxidation of L-[1-13C]phenylalanine. Am J Physiol 264:E677–E685CrossRefPubMedGoogle Scholar
  94. Zhao W, Zhai F, Zhang D, An Y, Liu Y, He Y, Ge K, Scrimshaw NS (2004) Lysine-fortified wheat flour improves the nutritional and immunological status of wheat-eating families in northern China. Food Nutr Bull 25:123–129CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Laboratory of Food ChemistryYokohama University of PharmacyYokohamaJapan
  2. 2.General Health Medical CenterYokohama University of PharmacyYokohamaJapan

Personalised recommendations

Cite article

Buy options