Skip to main content
Top
Published in: BioPsychoSocial Medicine 1/2013

Open Access 01-12-2013 | Research

A randomized, double-masked, placebo-controlled crossover trial on the effects of L-ornithine on salivary cortisol and feelings of fatigue of flushers the morning after alcohol consumption

Authors: Takeshi Kokubo, Emiko Ikeshima, Takayoshi Kirisako, Yutaka Miura, Masahisa Horiuchi, Akira Tsuda

Published in: BioPsychoSocial Medicine | Issue 1/2013

Login to get access

Abstract

Background

Residual alcohol effects on physiological and psychological symptoms are commonly experienced the morning after alcohol consumption. The purpose of this study was to assess the effects of L-ornithine on subjective feelings and salivary stress markers the morning after alcohol consumption and to investigate whether L-ornithine acutely accelerates ethanol metabolism.

Methods

This study had a randomized, placebo-controlled, double-masked crossover design. Subjects were all healthy Japanese adults with the ‘flusher’ phenotype for alcohol tolerance. In experiment 1, 11 subjects drank 0.4 g/kg body weight alcohol 1.5 h before their usual bedtime. Half an hour after drinking, they ingested either a placebo or 400 mg ornithine. The next morning on awakening, subjects completed a questionnaire containing a visual analog scale (VAS), the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA), and a profile of mood states (POMS) and collected a saliva sample for measurement of salivary stress markers (cortisol, secretory immunoglobulin A, and α-amylase). In experiment 2, placebo or 400 mg ornithine were administrated to 16 subjects both before and after drinking, and the feeling of drunkenness, breath ethanol concentration and one-leg standing time were repeatedly investigated until 180 min after alcohol consumption.

Results

There were significant decreases in “awareness”, “feeling of fatigue” and “lassitude” VAS scores and in “anger-hostility” and “confusion” POMS scores and a significant increase in “sleep length” in the OSA-MA test. Salivary cortisol concentrations on awakening were reduced after ornithine supplementation. There were no differences between ornithine and placebo in any of the subjective or physiological parameters of acute alcohol metabolism.

Conclusions

Taking 400 mg ornithine after alcohol consumption improved various negative feelings and decreased the salivary stress marker cortisol the next morning. These effects were not caused by an increase in acute alcohol metabolism.
Appendix
Available only for authorised users
Literature
1.
go back to reference Uchisawa H, Sato A, Ichita J, Matsue H, Ono T: Influence of low-temperature processing of the brackish-water bivalve, Corbicula japonica, on the ornithine content of its extract. Biosci Biotechnol Biochem. 2004, 68: 1228-1234. 10.1271/bbb.68.1228.CrossRefPubMed Uchisawa H, Sato A, Ichita J, Matsue H, Ono T: Influence of low-temperature processing of the brackish-water bivalve, Corbicula japonica, on the ornithine content of its extract. Biosci Biotechnol Biochem. 2004, 68: 1228-1234. 10.1271/bbb.68.1228.CrossRefPubMed
2.
go back to reference Antoine FR, Wei CI, Littell RC, Quinn BP, Hogle AD, Marshall MR: Free Amino Acids in Dark- and White-muscle Fish as Determined by O-phthaldialdehyde Precolumn Derivatization. J Food Sci. 2001, 66: 72-77. 10.1111/j.1365-2621.2001.tb15584.x.CrossRef Antoine FR, Wei CI, Littell RC, Quinn BP, Hogle AD, Marshall MR: Free Amino Acids in Dark- and White-muscle Fish as Determined by O-phthaldialdehyde Precolumn Derivatization. J Food Sci. 2001, 66: 72-77. 10.1111/j.1365-2621.2001.tb15584.x.CrossRef
3.
go back to reference Frau M, Massanet J, Rosselló C, Simal S, Cañellas J: Evolution of free amino acid content during ripening of Mahon cheese. Food Chem. 1997, 60: 651-657. 10.1016/S0308-8146(97)00051-4.CrossRef Frau M, Massanet J, Rosselló C, Simal S, Cañellas J: Evolution of free amino acid content during ripening of Mahon cheese. Food Chem. 1997, 60: 651-657. 10.1016/S0308-8146(97)00051-4.CrossRef
4.
go back to reference Morris SM: Regulation of enzymes of the urea cycle and arginine metabolism. Annu Rev Nutr. 2002, 22: 87-105. 10.1146/annurev.nutr.22.110801.140547.CrossRefPubMed Morris SM: Regulation of enzymes of the urea cycle and arginine metabolism. Annu Rev Nutr. 2002, 22: 87-105. 10.1146/annurev.nutr.22.110801.140547.CrossRefPubMed
6.
go back to reference Staedt U, Leweling H, Gladisch R, Kortsik C, Hagmuller E, Holm E: Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis. A double-blind, randomized study using a four-fold crossover design. J Hepatol. 1993, 19: 424-430. 10.1016/S0168-8278(05)80553-7.CrossRefPubMed Staedt U, Leweling H, Gladisch R, Kortsik C, Hagmuller E, Holm E: Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis. A double-blind, randomized study using a four-fold crossover design. J Hepatol. 1993, 19: 424-430. 10.1016/S0168-8278(05)80553-7.CrossRefPubMed
7.
go back to reference Sugino T, Shirai T, Kajimoto Y, Kajimoto O: L-ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism. Nutr Res. 2008, 28: 738-743. 10.1016/j.nutres.2008.08.008.CrossRefPubMed Sugino T, Shirai T, Kajimoto Y, Kajimoto O: L-ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism. Nutr Res. 2008, 28: 738-743. 10.1016/j.nutres.2008.08.008.CrossRefPubMed
8.
go back to reference Ong JP, Oehler G, Kruger-Jansen C, Lambert-Baumann J, Younossi ZM: Oral L-ornithine-L-aspartate improves health-related quality of life in cirrhotic patients with hepatic encephalopathy: an open-label, prospective, multicentre observational study. Clin Drug Investig. 2011, 31: 213-220. 10.2165/11586700-000000000-00000.CrossRefPubMed Ong JP, Oehler G, Kruger-Jansen C, Lambert-Baumann J, Younossi ZM: Oral L-ornithine-L-aspartate improves health-related quality of life in cirrhotic patients with hepatic encephalopathy: an open-label, prospective, multicentre observational study. Clin Drug Investig. 2011, 31: 213-220. 10.2165/11586700-000000000-00000.CrossRefPubMed
9.
go back to reference Cascales C, Cascales M, Santos-Ruiz A: Effect of chronic ethanol or acetaldehyde on hepatic alcohol and aldehyde dehydrogenases, aminotransferases and glutamate dehydrogenase. Rev Esp Fisiol. 1985, 41: 19-27.PubMed Cascales C, Cascales M, Santos-Ruiz A: Effect of chronic ethanol or acetaldehyde on hepatic alcohol and aldehyde dehydrogenases, aminotransferases and glutamate dehydrogenase. Rev Esp Fisiol. 1985, 41: 19-27.PubMed
10.
go back to reference Rejniuk VL, Schafer TV, Ivnitsky JJ: Ammonia potentiates the lethal effect of ethanol on rats. Bull Exp Biol Med. 2008, 145: 741-743. 10.1007/s10517-008-0191-6.CrossRefPubMed Rejniuk VL, Schafer TV, Ivnitsky JJ: Ammonia potentiates the lethal effect of ethanol on rats. Bull Exp Biol Med. 2008, 145: 741-743. 10.1007/s10517-008-0191-6.CrossRefPubMed
11.
go back to reference Maier KP, Volk B, Hoppe-Seyler G, Gerok W: Urea-cycle enzymes in normal liver and in patients with alcoholic hepatitis. Eur J Clin Invest. 1974, 4: 193-195.CrossRefPubMed Maier KP, Volk B, Hoppe-Seyler G, Gerok W: Urea-cycle enzymes in normal liver and in patients with alcoholic hepatitis. Eur J Clin Invest. 1974, 4: 193-195.CrossRefPubMed
12.
go back to reference Goedde HW, Harada S, Agarwal DP: Racial differences in alcohol sensitivity: a new hypothesis. Hum Genet. 1979, 51: 331-334.CrossRefPubMed Goedde HW, Harada S, Agarwal DP: Racial differences in alcohol sensitivity: a new hypothesis. Hum Genet. 1979, 51: 331-334.CrossRefPubMed
13.
go back to reference Kokubo T, Ikeshima E, Komatsu M, Kirisako T, Miura Y, Horiuchi M, Tsuda A: L-ornithine-L-aspartate improves alcohol-derived fatigue feeling in flushers -A questionnaire study-. Jpn Pharmacol Ther. 2012, 40: 205-212. Kokubo T, Ikeshima E, Komatsu M, Kirisako T, Miura Y, Horiuchi M, Tsuda A: L-ornithine-L-aspartate improves alcohol-derived fatigue feeling in flushers -A questionnaire study-. Jpn Pharmacol Ther. 2012, 40: 205-212.
14.
go back to reference Yamamoto YTH, Takase M, Yamazaki K, Shirakawa S, Azumi K: Standardization of revised version of OSA sleep inventory for middle age and aged. Brain Sci Mental Disorders. 1999, 10: 401-409. Yamamoto YTH, Takase M, Yamazaki K, Shirakawa S, Azumi K: Standardization of revised version of OSA sleep inventory for middle age and aged. Brain Sci Mental Disorders. 1999, 10: 401-409.
15.
go back to reference McNair D, Lorr M: Dropleman L:Profile of Mood States. 1981, San Diego: Educational and Industrial Testing Service McNair D, Lorr M: Dropleman L:Profile of Mood States. 1981, San Diego: Educational and Industrial Testing Service
16.
go back to reference Suzuki K, Matsushita S, Ishii T: Relationship between the flushing response and drinking behavior among Japanese high school students. Alcohol Clin Exp Res. 1997, 21: 1726-1729. 10.1111/j.1530-0277.1997.tb04515.x.CrossRefPubMed Suzuki K, Matsushita S, Ishii T: Relationship between the flushing response and drinking behavior among Japanese high school students. Alcohol Clin Exp Res. 1997, 21: 1726-1729. 10.1111/j.1530-0277.1997.tb04515.x.CrossRefPubMed
17.
go back to reference Tsutaya S, Shoji M, Saito Y, Kitaya H, Nakata S, Takamatsu H, Yasujima M: Analysis of aldehyde dehydrogenase 2 gene polymorphism and ethanol patch test as a screening method for alcohol sensitivity. Tohoku J Exp Med. 1999, 187: 305-310. 10.1620/tjem.187.305.CrossRefPubMed Tsutaya S, Shoji M, Saito Y, Kitaya H, Nakata S, Takamatsu H, Yasujima M: Analysis of aldehyde dehydrogenase 2 gene polymorphism and ethanol patch test as a screening method for alcohol sensitivity. Tohoku J Exp Med. 1999, 187: 305-310. 10.1620/tjem.187.305.CrossRefPubMed
18.
go back to reference Collins WE, Schroeder DJ, Gilson RD, Guedry FE: Effects of alcohol ingestion on tracking performance during angular acceleration. J Appl Psychol. 1971, 55: 559-563.CrossRefPubMed Collins WE, Schroeder DJ, Gilson RD, Guedry FE: Effects of alcohol ingestion on tracking performance during angular acceleration. J Appl Psychol. 1971, 55: 559-563.CrossRefPubMed
19.
go back to reference Finnigan F, Hammersley R, Cooper T: An examination of next-day hangover effects after a 100 mg/100 ml dose of alcohol in heavy social drinkers. Addiction. 1998, 93: 1829-1838. 10.1046/j.1360-0443.1998.931218298.x.CrossRefPubMed Finnigan F, Hammersley R, Cooper T: An examination of next-day hangover effects after a 100 mg/100 ml dose of alcohol in heavy social drinkers. Addiction. 1998, 93: 1829-1838. 10.1046/j.1360-0443.1998.931218298.x.CrossRefPubMed
20.
go back to reference Stephens R, Ling J, Heffernan TM, Heather N, Jones K: A review of the literature on the cognitive effects of alcohol hangover. Alcohol Alcohol. 2008, 43: 163-170. 10.1093/alcalc/agm160.CrossRefPubMed Stephens R, Ling J, Heffernan TM, Heather N, Jones K: A review of the literature on the cognitive effects of alcohol hangover. Alcohol Alcohol. 2008, 43: 163-170. 10.1093/alcalc/agm160.CrossRefPubMed
21.
go back to reference Wilkinson DJ, Smeeton NJ, Watt PW: Ammonia metabolism, the brain and fatigue; revisiting the link. Prog Neurobiol. 2010, 91: 200-219. 10.1016/j.pneurobio.2010.01.012.CrossRefPubMed Wilkinson DJ, Smeeton NJ, Watt PW: Ammonia metabolism, the brain and fatigue; revisiting the link. Prog Neurobiol. 2010, 91: 200-219. 10.1016/j.pneurobio.2010.01.012.CrossRefPubMed
22.
go back to reference Mutch BJ, Banister EW: Ammonia metabolism in exercise and fatigue: a review. Med Sci Sports Exerc. 1983, 15: 41-50.PubMed Mutch BJ, Banister EW: Ammonia metabolism in exercise and fatigue: a review. Med Sci Sports Exerc. 1983, 15: 41-50.PubMed
23.
go back to reference Omori K, Kagami Y, Yokoyama C, Moriyama T, Matsumoto N, Masaki M, Nakamura H, Kamasaka H, Shiraishi K, Kometani T, et al: Promotion of non–rapid eye movement sleep in mice after oral administration of ornithine. Sleep Biol Rhythms. 2012, 10: 38-45. 10.1111/j.1479-8425.2011.00515.x.CrossRef Omori K, Kagami Y, Yokoyama C, Moriyama T, Matsumoto N, Masaki M, Nakamura H, Kamasaka H, Shiraishi K, Kometani T, et al: Promotion of non–rapid eye movement sleep in mice after oral administration of ornithine. Sleep Biol Rhythms. 2012, 10: 38-45. 10.1111/j.1479-8425.2011.00515.x.CrossRef
24.
go back to reference Yamane H, Tsuneyoshi Y, Denbow DM, Furuse M: N-Methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors involved in the induction of sedative effects under an acute stress in neonatal chicks. Amino Acids. 2009, 37: 733-739. 10.1007/s00726-008-0203-x.CrossRefPubMed Yamane H, Tsuneyoshi Y, Denbow DM, Furuse M: N-Methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors involved in the induction of sedative effects under an acute stress in neonatal chicks. Amino Acids. 2009, 37: 733-739. 10.1007/s00726-008-0203-x.CrossRefPubMed
25.
go back to reference Hamasu K, Shigemi K, Tsuneyoshi Y, Yamane H, Sato H, Denbow DM, Furuse M: Intracerebroventricular injection of L-proline and D-proline induces sedative and hypnotic effects by different mechanisms under an acute stressful condition in chicks. Amino Acids. 2010, 38: 57-64. 10.1007/s00726-008-0204-9.CrossRefPubMed Hamasu K, Shigemi K, Tsuneyoshi Y, Yamane H, Sato H, Denbow DM, Furuse M: Intracerebroventricular injection of L-proline and D-proline induces sedative and hypnotic effects by different mechanisms under an acute stressful condition in chicks. Amino Acids. 2010, 38: 57-64. 10.1007/s00726-008-0204-9.CrossRefPubMed
26.
go back to reference Suenaga R, Yamane H, Tomonaga S, Asechi M, Adachi N, Tsuneyoshi Y, Kurauchi I, Sato H, Denbow DM, Furuse M: Central L-arginine reduced stress responses are mediated by L-ornithine in neonatal chicks. Amino Acids. 2008, 35: 107-113. 10.1007/s00726-007-0617-x.CrossRefPubMed Suenaga R, Yamane H, Tomonaga S, Asechi M, Adachi N, Tsuneyoshi Y, Kurauchi I, Sato H, Denbow DM, Furuse M: Central L-arginine reduced stress responses are mediated by L-ornithine in neonatal chicks. Amino Acids. 2008, 35: 107-113. 10.1007/s00726-007-0617-x.CrossRefPubMed
27.
go back to reference Stratakis CA, Chrousos GP: Neuroendocrinology and pathophysiology of the stress system. Ann N Y Acad Sci. 1995, 771: 1-18. 10.1111/j.1749-6632.1995.tb44666.x.CrossRefPubMed Stratakis CA, Chrousos GP: Neuroendocrinology and pathophysiology of the stress system. Ann N Y Acad Sci. 1995, 771: 1-18. 10.1111/j.1749-6632.1995.tb44666.x.CrossRefPubMed
28.
go back to reference Hellhammer DH, Wust S, Kudielka BM: Salivary cortisol as a biomarker in stress research. Psychoneuroendocrinology. 2009, 34: 163-171. 10.1016/j.psyneuen.2008.10.026.CrossRefPubMed Hellhammer DH, Wust S, Kudielka BM: Salivary cortisol as a biomarker in stress research. Psychoneuroendocrinology. 2009, 34: 163-171. 10.1016/j.psyneuen.2008.10.026.CrossRefPubMed
29.
go back to reference Buchanan TW, Bagley SL, Stansfield RB, Preston SD: The empathic, physiological resonance of stress. Soc Neurosci. 2011, 7: 191-201.CrossRefPubMed Buchanan TW, Bagley SL, Stansfield RB, Preston SD: The empathic, physiological resonance of stress. Soc Neurosci. 2011, 7: 191-201.CrossRefPubMed
30.
go back to reference McGraw LK, Out D, Hammermeister JJ, Ohlson CJ, Pickering MA, Granger DA: Nature, correlates, and consequences of stress-related biological reactivity and regulation in Army nurses during combat casualty simulation. Psychoneuroendocrinology. 2012, 38: 135-144.CrossRefPubMed McGraw LK, Out D, Hammermeister JJ, Ohlson CJ, Pickering MA, Granger DA: Nature, correlates, and consequences of stress-related biological reactivity and regulation in Army nurses during combat casualty simulation. Psychoneuroendocrinology. 2012, 38: 135-144.CrossRefPubMed
31.
go back to reference Kurata K, Nagasawa M, Tomonaga S, Aoki M, Morishita K, Denbow DM, Furuse M: Orally administered L-ornithine elevates brain L-ornithine levels and has an anxiolytic-like effect in mice. Nutr Neurosci. 2012, 14: 243-248.CrossRef Kurata K, Nagasawa M, Tomonaga S, Aoki M, Morishita K, Denbow DM, Furuse M: Orally administered L-ornithine elevates brain L-ornithine levels and has an anxiolytic-like effect in mice. Nutr Neurosci. 2012, 14: 243-248.CrossRef
Metadata
Title
A randomized, double-masked, placebo-controlled crossover trial on the effects of L-ornithine on salivary cortisol and feelings of fatigue of flushers the morning after alcohol consumption
Authors
Takeshi Kokubo
Emiko Ikeshima
Takayoshi Kirisako
Yutaka Miura
Masahisa Horiuchi
Akira Tsuda
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BioPsychoSocial Medicine / Issue 1/2013
Electronic ISSN: 1751-0759
DOI
https://doi.org/10.1186/1751-0759-7-6

Other articles of this Issue 1/2013

BioPsychoSocial Medicine 1/2013 Go to the issue