The relationship between plasma amino acids and circulating albumin and haemoglobin in postabsorptive stroke patients

Roberto Aquilani, Roberto Maestri, Mirella Boselli, Maria Pia Achilli, Nadia Arrigoni, Mariella Bruni, Maurizia Dossena, Manuela Verri, Daniela Buonocore, Evasio Pasini, Annalisa Barbieri, Federica Boschi, Roberto Aquilani, Roberto Maestri, Mirella Boselli, Maria Pia Achilli, Nadia Arrigoni, Mariella Bruni, Maurizia Dossena, Manuela Verri, Daniela Buonocore, Evasio Pasini, Annalisa Barbieri, Federica Boschi

Abstract

Background: This retrospective study had two main aims: (1) to document possible correlations between plasma Amino Acids (AAs) and circulating Albumin (Alb) and Haemoglobin (Hb); and (2) to identify which AAs were predictors of Alb and Hb.

Methods: The study considered 125 stroke subjects (ST) (61.6% males; 65.6 +/- 14.9 years) who met the eligibility criteria (absence of co morbidities associated with altered plasma AAs and presence of plasma AAs determined after overnight fasting). Fifteen matched healthy subjects with measured plasma AAs served as controls.

Results: The best correlations of Alb were with tryptophan (Trp) and histidine (His) (r = + 0.53; p < 0.0001), and those of Hb were with histidine (r = +0.47) and Essential AAs (r = +0.47) (both p<0.0001). In multivariate analysis, Trp (p< 0.0001) and His (p = 0.01) were shown to be the best positive predictors of Alb, whereas glutamine (p = 0.006) was the best positive predictor of Hb.

Conclusions: The study shows that the majority of plasma AAs were positively correlated with Alb and Hb. The best predictors of circulating Alb and Hb were the levels of tryptophan and glutamine, respectively.

Conflict of interest statement

The author Roberto Aquilani is a scientific consultant at Professional Dietetics (Milano, Italy). This company had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. The other authors declare no conflict of interest.

Figures

Fig 1
Fig 1
Correlations between plasma tryptophan (panel A), plasma histidine (panel B) and serum albumin.
Fig 2
Fig 2
Correlations between plasma histidine (panel A), plasma essential amino acids (panel B) and plasma haemoglobin.

References

    1. Abbott R.D.; Donahue R.P.; MacMahon S.W.; Reed D.M.; Yano K. Diabetes and the risk of stroke. The Honolulu Heart Program. JAMA.1987, February 20; 257(7):949–52.
    1. Mathers C.D.; Vos E.T.; Stevenson C.E.; Begg S.J. The Australian Burden of Disease Study: measuring the loss of health from diseases, injuries and risk factors. Med J Aust. 2000. June 19;172(12):592–6.
    1. Scholte O.P.; Reimer W.J.; de Haan R.J.; Rijnders P.T.; Limburg M.; van den Bos G.A. The burden of caregiving in partners of long-term stroke survivors. Stroke 1998. August;29(8):1605–11. 10.1161/01.str.29.8.1605
    1. Hata R.; Maeda K.; Hermann D.; Mies G.; Hossmann K.A. Dynamics of regional brain metabolism and gene expression after middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab. 2000. February;20(2):306–15. 10.1097/00004647-200002000-00012
    1. Lee J.M.; Zipfel G.J.; Park K.H.; He Y.Y.; Hsu C.Y.; Choi DW. Zinc translocation accelerates infarction after mild transient focal ischemia. Neuroscience 2002;115(3):871–8. 10.1016/s0306-4522(02)00513-4
    1. Aquilani R.; Scocchi M.; Iadarola P.; Viglio S.; Pasini E.; Condello S.; et al. Spontaneous neurocognitive retrieval of patients with sub-acute ischemic stroke is associated with dietary protein intake. Nutr Neurosci. 2010. June;13(3):129–34. 10.1179/147683010X12611460764002
    1. Aquilani R.; Scocchi M.; Iadarola P.; Franciscone P.; Verri M.; Boschi F.; et al. Protein supplementation may enhance the spontaneous recovery of neurological alterations in patients with ischaemic stroke. Clin Rehabil. 2008. December;22(12):1042–50. 10.1177/0269215508094244
    1. Aquilani R.; Baiardi P.; Scocchi M.; Iadarola P.; Verri M.; Sessarego P.; et al. Normalization of zinc intake enhances neurological retrieval of patients suffering from ischemic strokes. Nutr Neurosci. 2009. Oct;12(5):219–25.
    1. Aquilani R.; Boselli M.; D'Antona G.; Baiardi P.; Boschi F.; Viglio S.; et al. Unaffected arm muscle hypercatabolism in dysphagic subacute stroke patients: the effects of essential amino acid supplementation. Biomed Res Int. 2014; 2014:964365 10.1155/2014/964365 Epub 2014. November 9
    1. Belayev L.; Busto R.; Zhao W.; Clemens J.A.; Ginsberg M.D. Effect of delayed albumin hemodilution on infarction volume and brain edema after transient middle cerebral artery occlusion in rats. J Neurosurg. 1997. October;87(4):595–601. 10.3171/jns.1997.87.4.0595
    1. Belayev L.; Zhao W.; Pattany P.M.; Weaver R.G.; Huh P.W.; Lin B.; et al. Diffusion-weighted magnetic resonance imaging confirms marked neuroprotective efficacy of albumin therapy in focal cerebral ischemia. Stroke. 1998. December;29(12):2587–99. 10.1161/01.str.29.12.2587
    1. Belayev L.; Liu Y.; Zhao W.; Busto R.; Ginsberg M.D. Human albumin therapy of acute ischemic stroke: marked neuroprotective efficacy at moderate doses and with a broad therapeutic window. Stroke. 2001. February;32(2):553–60. 10.1161/01.str.32.2.553
    1. Yamasaki Y.; Matsuura N.; Shozuhara H.; Onodera H.; Itoyama Y.; Kogure K. Interleukin-1 as a pathogenetic mediator of ischemic brain damage in rats. Stroke. 1995. April;26(4):676–80; discussion 681. 10.1161/01.str.26.4.676
    1. Ginsberg M.D.; Zhao W.; Belayev L.; Alonso O.F.; Liu Y.; Loor J.Y.; et al. Diminution of metabolism/blood flow uncoupling following traumatic brain injury in rats in response to high-dose human albumin treatment. J Neurosurg. 2001. March;94(3):499–509. 10.3171/jns.2001.94.3.0499
    1. Boselli M.; Aquilani R.; Baiardi P.; Dioguardi F.S.; Guarnaschelli C.; Achilli M.P.; et al. Supplementation of essential amino acids may reduce the occurrence of infections in rehabilitation patients with brain injury. Nutr Clin Pract. 2012. February;27(1):99–113. 10.1177/0884533611431068
    1. Aquilani R.; Boselli M.; Baiardi P.; Pasini E.; Iadarola P.; Verri M.; et al. Is stroke rehabilitation a metabolic problem? Brain Inj. 2014;28(2):161–73. 10.3109/02699052.2013.860470
    1. Aquilani R.; Zuccarelli G.C.; Condino A.M.; Catani M.; Rutili C.; Del Vecchio C.; et al. Despite Inflammation, Supplemented Essential Amino Acids May Improve Circulating Levels of Albumin and Haemoglobin in Patients after Hip Fractures. Nutrients. 2017. June 21;9(6). E637 10.3390/nu9060637
    1. Mendez C.M.; McClain C.J.; Marsano L.S. Albumin therapy in clinical practice. Nutr Clin Pract. 2005. June;20(3):314–20. 10.1177/0115426505020003314
    1. De Feo P.; Horber F.F.; Haymond M.W. Meal stimulation of albumin synthesis: a significant contributor to whole body protein synthesis in humans. Am J Physiol. 1992. October;263(4 Pt 1):E794–9.
    1. Hunter K.A.; Ballmer P.E.; Anderson S.E.; Broom J.; Garlick P.J.; McNurlan M.A. Acute stimulation of albumin synthesis rate with oral meal feeding in healthy subjects measured with [ring-2H5]phenylalanine. Clin Sci (Lond). 1995. February;88(2):235–42.
    1. Volpi E.; Lucidi P., Cruciani G., Monacchia F., Reboldi G., Brunetti P., et al. Contribution of amino acids and insulin to protein anabolism during meal absorption. Diabetes. 1996. September;45(9):1245–52. 10.2337/diab.45.9.1245
    1. Caso G.; Feiner J.; Mileva I.; Bryan L.J.; Kelly P.; Autio K.; et al. Response of albumin synthesis to oral nutrients in young and elderly subjects. Am J Clin Nutr. 2007. February;85(2):446–51. 10.1093/ajcn/85.2.446
    1. Kirsch R.E.; Saunders S.J.; Frith L.; Wicht S.; Kelman L.; Brock J.F. Plasma amino acid concentration and the regulation of albumin synthesis. Am J Clin Nutr. 1969. December; 22(12):1559–62. 10.1093/ajcn/22.12.1559
    1. Flaim K.E.; Peavy D.E.; Everson W.V.; Jefferson L.S. The role of amino acids in the regulation of protein synthesis in perfused rat liver. I. Reduction in rates of synthesis resulting from amino acid deprivation and recovery during flow-through perfusion. J Biol Chem. 1982. March 25;257(6):2932–8.
    1. Flaim K.E.; Liao W.S.; Peavy D.E.; Taylor J.M.; Jefferson L.S. The role of amino acids in the regulation of protein synthesis in perfused rat liver. II. Effects of amino acid deficiency on peptide chain initiation, polysomal aggregation, and distribution of albumin mRNA. J Biol Chem. 1982. March 25;257(6):2939–46.
    1. John D.W.; Miller L.L. Regulation of net biosynthesis of serum albumin and acute phase plasma proteins. Induction of enhanced net synthesis of fibrinogen, alpha1-acid glycoprotein, alpha2 (acute phase)-globulin, and haptoglobin by amino acids and hormones during perfusion of the isolated normal rat liver. J Biol Chem. 1969. November 25;244(22):6134–42.
    1. Kelman L.; Saunders S.J.; Wicht S.; Frith L.; Corrigall A.; Kirsch R.E.; et al. The effects of amino acids on albumin synthesis by the isolated perfused rat liver. Biochem J. 1972. October;129(4):805–9. 10.1042/bj1290805
    1. Baumgartner R.N.; Koehler K.M; Romero L.; Garry P.J. Serum albumin is associated with skeletal muscle in elderly men and women. Am J Clin Nutr. 1996. October;64(4):552–8. 10.1093/ajcn/64.4.552
    1. Rothschild M.A.; Oratz M.; Schreiber S.S. Serum albumin. Hepatology. 1988. Mar-Apr;8(2):385–401.
    1. Anagnostou A.; Schade S.; Ashkinaz M.; Barone J.; Fried W. Effect of protein deprivation on erythropoiesis. Blood. 1977. December;50(6):1093–7.
    1. Mogoş T.; Popescu C.; Dumitrescu A.; Tănase I.; Mincu I. The relationship between aminoaciduria and plasma hemoglobin levels. Rom J Intern Med. 1993. Jul-Sep;31(3):223–8.
    1. Alabi J .; Ng'ambi J.W.; Mbajiorgu E.F.; Norris D.; Mabelebele M. Growth and haematological response of indigenous Venda chickens aged 8 to 13 weeks to varying dietary lysine to energy ratios. J Anim Physiol Anim Nutr (Berl). 2015. June;99(3):436–41.
    1. Yap S.H.; Strair R.K.; Shafritz D.A. Effect of a short term fast on the distribution of cytoplasmic albumin messenger ribonucleic acid in rat liver. Evidence for formation of free albumin messenger ribonucleoprotein particles. J Biol Chem. 1978. July 25;253(14):4944–50.
    1. Austin S.A.; Clemens M.J. Control of the initiation of protein synthesis in mammalian cells. FEBS Lett. 1980. January 28;110(1):1–7. 10.1016/0014-5793(80)80009-3
    1. Rothschild M.A.; Oratz M.; Mongelli J.; Fishman L.; Schreiber S.S. Amino acid regulation of albumin synthesis. J Nutr. 1969. August;98(4):395–403. 10.1093/jn/98.4.395
    1. Chandran K.; Damodaran M. Amino-acids and proteins in haemoglobin formation. 2. Isoleucine. Biochem J. 1951. August;49(3):393–8. 10.1042/bj0490393
    1. Aquilani R.; Galli M.; Guarnaschelli C.; Fugazza G.; Lorenzoni M.; Varalda E.; et al. Prevalence of malnutrition and inadequate food intake in self-feeding rehabilitation patients with stroke. Europa Medicophysica 1999; 2:75–81
    1. Perry L. Eating and dietary intake in communication-impaired stroke survivors: a cohort study from acute-stage hospital admission to 6 months post-stroke. Clin Nutr. 2004. December;23(6):1333–43. 10.1016/j.clnu.2004.04.009
    1. Chumlea W.C., Roche A.F., Steinbaugh M.L. Estimating stature from knee height for persons 60 to 90 years of age. Journal of the American Geriatric Society 1985;33:116–120
    1. Aquilani R.; Tramarin R.; Pedretti R.F; Bertolotti G.; Sommaruga M.; Mariani P.; et al. Despite good compliance, very low fat diet alone does not achieve recommended cholesterol goals in outpatients with coronary heart disease. Eur Heart J. 1999. July;20(14):1020–9 10.1053/euhj.1999.1402
    1. Carnevale, E.; Marletta, L.; and Istituto Nazionale di Ricerca per gli alimenti e la nutrizione. Tabelle di composizione degli alimenti, Istituto Superiore Nazionale della Nutrizione Roma, Italy 1989.
    1. Quarta revisione dei livelli di assunzione di riferimento di nutrienti (LARN) e di energia per la popolazione italiana.
    1. Benjamini Y, Yekutieli D. (2001) The control of the false discovery rate in multiple testing under dependency. The Annals of Statistics. 2001. 29(4), 1165–1188.
    1. Deodhar S.D. C-reactive protein: the best laboratory indicator available for monitoring disease activity. Cleve Clin J Med. 1989. Mar-Apr;56(2):126–30.
    1. Zoico E.; Roubenoff R. The role of cytokines in regulating protein metabolism and muscle function. Nutr Rev. 2002. February;60(2):39–51. 10.1301/00296640260085949
    1. Norton J.A.; Gorschboth C.M.; Wesley R.A.; Burt M.E.; Brennan M.F. Fasting plasma amino acid levels in cancer patients. Cancer. 1985. September 1;56(5):1181–6. 10.1002/1097-0142(19850901)56:5<1181::aid-cncr2820560535>;2-8
    1. Kitagawa M.; Haji S.; Amagai T. High Serum Essential Amino Acids as a Predictor of Skeletal Muscle Depletion in Patients With Cachexia and Advanced Gastrointestinal Cancers. Nutr Clin Pract. 2017. October;32(5):645–651. 10.1177/0884533617724742
    1. Gabay C.; Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999. February 11;340(6):448–54. 10.1056/NEJM199902113400607
    1. Roth E. Immune and cell modulation by amino acids. Clin Nutr. 2007. October;26(5):535–44. Epub 2007 Jun 27. 10.1016/j.clnu.2007.05.007
    1. Grimble R.F.; Jackson A.A.; Persaud C.; Wride M.J.; Delers F.; Engler R. Cysteine and glycine supplementation modulate the metabolic response to tumor necrosis factor alpha in rats fed a low protein diet. J Nutr. 1992. November;122(11):2066–73. 10.1093/jn/122.11.2066
    1. Carubelli V.; Castrini A.I.; Lazzarini V.; Gheorghiade M.; Metra M.; Lombardi C. Amino acids and derivatives, a new treatment of chronic heart failure? Heart Fail Rev. 2015. January;20(1):39–51. 10.1007/s10741-014-9436-9
    1. Rothschild M.A.; Oratz M.; Schreiber S.S. Extravascular albumin. N Engl J Med. 1979. August 30;301(9):497–8. 10.1056/NEJM197908303010909
    1. Hennig B.; Honchel R.; Goldblum S.E.; McClain C.J. Tumor necrosis factor-mediated hypoalbuminemia in rabbits. J Nutr. 1988. December;118(12):1586–90. 10.1093/jn/118.12.1586
    1. Ferrando A.A.; Stuart C.A.; Sheffield-Moore M.; Wolfe R.R. Inactivity amplifies the catabolic response of skeletal muscle to cortisol. J Clin Endocrinol Metab. 1999. October;84(10):3515–21. 10.1210/jcem.84.10.6046
    1. Glass D.J. Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Nat Cell Biol. 2003. February;5(2):87–90. 10.1038/ncb0203-87
    1. Kirsch R.; Frith L.; Black E.; Hoffenberg R. Regulation of albumin synthesis and catabolism by alteration of dietary protein. Nature. 1968. February 10;217(5128):578–9. 10.1038/217578a0
    1. Rothschild M.A.; Oratz M.; Mongelli J.; Schreiber S.S. Effects of a short-term fast on albumin synthesis studied in vivo, in the perfused liver, and on amino acid incorporation by hepatic microsomes. J Clin Invest. 1968. December;47(12):2591–9. 10.1172/JCI105941
    1. Norberg Å.; Rooyackers O.; Segersvärd R.; Wernerman J. Leakage of albumin in major abdominal surgery. Crit Care. 2016. April 26;20(1):113 10.1186/s13054-016-1283-8
    1. Curzon G.; Friedel J.; Knott P.J. The effect of fatty acids on the binding of tryptophan to plasma protein. Nature. 1973. March 16;242(5394):198–200. 10.1038/242198a0
    1. Young V.R.; Marchini J.S. Mechanisms and nutritional significance of metabolic responses to altered intakes of protein and amino acids, with reference to nutritional adaptation in humans. Am J Clin Nutr. 1990. February;51(2):270–89. 10.1093/ajcn/51.2.270
    1. Kriengsinyos W.; Rafii M.; Wykes L.J.; Ball R.O.; Pencharz P.B. Long-term effects of histidine depletion on whole-body protein metabolism in healthy adults. J Nutr. 2002. November; 132(11):3340–8. 10.1093/jn/132.11.3340
    1. Sheng Y.B.; Badger T.M.; Asplund J.M.; Wixom R.L. Incorporation of 15NH4Cl into histidine in adult man. J Nutr. 1977. April;107(4):621–30. 10.1093/jn/107.4.621
    1. Visser M.; Kritchevsky S.B.; Newman A.B.; Goodpaster B.H.; Tylavsky F.A.; Nevitt M.C.; et al. Lower serum albumin concentration and change in muscle mass: the Health, Aging and Body Composition Study. Am J Clin Nutr. 2005. September;82(3):531–7. 10.1093/ajcn.82.3.531
    1. Bruns G.P.; London I.M. The evìffect of hemin on the synthesis of globin. Biochem Biophys Res Commun. 1965. January 18;18:236–42. 10.1016/0006-291x(65)90746-1
    1. Grayzel A.I.; Hörchner P., London I.M. The stimulation of globin synthesis by heme. Proc Natl Acad Sci U S A. 1966. March;55(3):650–5. 10.1073/pnas.55.3.650
    1. Nasset E.S.; Gatewood V.H. Nitrogen balance and hemoglobin of adult rats fed amino acid diets low in L- and D-histidine. J Nutr. 1954. June 10;53(2):163–76. 10.1093/jn/53.2.163
    1. Kopple J.D.; Swendseid M.E. Evidence that histidine is an essential amino acid in normal and chronically uremic man. J Clin Invest. 1975. May;55(5):881–91. 10.1172/JCI108016
    1. Gündoğdu R.H.; Temel H.; Bozkırlı B.O.; Ersoy E.; Yazgan A.; Yıldırım Z. Mixture of Arginine, Glutamine, and β-hydroxy-β-methyl Butyrate Enhances the Healing of Ischemic Wounds in Rats. JPEN J Parenter Enteral Nutr. 2017. August;41(6):1045–1050. 10.1177/0148607115625221
    1. Wilmore D.W. Food and Drug Administration Approval of Glutamine for Sickle Cell Disease: Success and Precautions in Glutamine Research. JPEN J Parenter Enteral Nutr. 2017. August;41(6):912–917. 10.1177/0148607117727271
    1. Curi R.; Lagranha C.J.; Doi S.Q.; Sellitti D.F.; Procopio J.; Pithon-Curi T.C.; et al. Molecular mechanisms of glutamine action. J Cell Physiol. 2005. August;204(2):392–401. 10.1002/jcp.20339
    1. Yang R.; Tan X.; Thomas A.M.; Steppacher R.; Qureshi N.; Morrison D.C.; Van Way C.W. 3rd. Alanine-glutamine dipeptide (AGD) inhibits expression of inflammation-related genes in hemorrhagic shock. JPEN J Parenter Enteral Nutr. 2007. Jan-Feb;31(1):32–6. 10.1177/014860710703100132
    1. Ohtani M.; Maruyama K.; Sugita M.; Kobayashi K. Amino acid supplementation affects hematological and biochemical parameters in elite rugby players. Biosci Biotechnol Biochem. 2001. September;65(9):1970–6. 10.1271/bbb.65.1970
    1. Li H.; Jiang W.; Liu Y.; Jiang J.; Zhang Y.; Wu P.; et al. The metabolites of glutamine prevent hydroxyl radical-induced apoptosis through inhibiting mitochondria and calcium ion involved pathways in fish erythrocytes. Free Radic Biol Med. 2016. March;92:126–140. 10.1016/j.freeradbiomed.2016.01.007
    1. Niihara Y.; Macan H.; Eckman J.R. L-glutamine therapy reduces hospitalization for sickle cell anemia and sickle ß-thalassemia patients at six months a phase II randomized trial. Clin Pharmacol Biopham 2014; 3:1–5.
    1. Morris C.R.; Suh J.H.; Haga r W.; Larkin S.; Bland D.A.; Steinberg M.H.; et al. Erythrocyte glutamine depletion, altered redox environment, and pulmonary hypertension in sickle cell disease. Blood. 2008. January 1;111(1):402–10. Epub 2007 Sep 11. 10.1182/blood-2007-04-081703
    1. Ioannou A.; Varotsis C. Modifications of hemoglobin and myoglobin by Maillard reaction products (MRPs). PLoS One. 2017. November 14;12(11):e0188095 10.1371/journal.pone.0188095
    1. Andrulis I.L., Chen J., Ray P.N. Isolation of human cDNAs for asparagine synthetase and expression in Jensen rat sarcoma cells. Mol Cell Biol. 1987. July;7(7):2435–43. 10.1128/mcb.7.7.2435
    1. Hankard R.G.; Haymond M.W.; Darmaun D. Effect of glutamine on leucine metabolism in humans. Am J Physiol. 1996. October;271(4 Pt 1):E748–54.
    1. Soeters P.B. Rationale for albumin infusions. Curr Opin Clin Nutr Metab Care. 2009. May;12(3):258–64. Review. 10.1097/MCO.0b013e32832a3e1a
    1. Means R.T. Jr. Pathogenesis of the anemia of chronic disease: a cytokine-mediated anemia. Stem Cells.1995. January;13(1):32–7. 10.1002/stem.5530130105
    1. Bacchetta J.; Zaritsky J.J., Sea J.L.; Chun R.F.; Lisse T.S.; Zavala K.; et al. Suppression of iron-regulatory hepcidin by vitamin D. J Am Soc Nephrol. 2014. March;25(3):564–72. 10.1681/ASN.2013040355
    1. Zughaier S.M.; Alvarez J.A.; Sloan J.H.; Konrad R.J.; Tangpricha V. The role of vitamin D in regulating the iron-hepcidin-ferroportin axis in monocytes J Clin Transl Endocrinol. 2014. Mar 21;1(1):19–25.
    1. Wischmeyer P.E. Glutamine: role in critical illness and ongoing clinical trials. Curr Opin Gastroenterol. 2008. March;24(2):190–7. 10.1097/MOG.0b013e3282f4db94
    1. Hu Y.M.; Hsiung Y.C.; Pai M.H.; Yeh S.L. Glutamine administration in early or late septic phase. Downregulates lymphocyte PD-1/PD-L1 expression and the inflammatory response in mice with polymicrobial sepsis. JPEN J Parenter Enteral Nutr. 2017. March 1:148607117695245 10.1177/0148607117695245 [Epub ahead of print]

Source: PubMed

3
Subscribe