Abstract
Sleep and sleep medicine are in the limelight of the researchers for thousands of years. The definition of sleep started to change in the light of scientific experiments performed in the twentieth century, and the number of investigations on sleep medicine increased tremendously. Effects of nutritional factors on the regulation of the sleep-wake cycle and central nervous system triggered new developments in sleep medicine. Tryptophan is an essential amino acid and a precursor of serotonin, melatonin, and nicotinamide. More recently, the role of tryptophan played in the sleep-wake rhythm of newborns has been an interest of research. High levels of tryptophan are associated with the improvement in the total hours and the efficiency of sleep and increase in the duration of nocturnal immobility and decrease in both the number of nocturnal awakenings and the sleep latency of newborns. Serotonin is named as “neurohormone of sleep” after understanding the key role of serotonin in the mechanisms of the sleep-wake cycle. Inhibition of tryptophan hydroxylase enzyme decreases both the synthesis of serotonin from tryptophan and serotonin levels significantly leading to insomnia. The serotonergic system has a crucial impact on sleep and airway stabilization. Majority of investigations on serotonin have shown that serotonergic system is related to obstructive sleep apnea syndrome (OSAS). Melatonin is secreted by the pineal gland. It is synthesized from 5-HT by pinealocytes and then released into the blood and cerebrospinal fluid. It is well known that melatonin affects sleep, circadian rhythm, puberty, antioxidant status, aging, and blood pressure. Contrary to other sleep disorders, scarce data on the involvement of melatonin in OSAS are available. Investigators have shown that plasma melatonin levels are low in patients with newly diagnosed OSAS. Elaborate prospective studies should be conducted while bearing in mind the drawbacks of aforementioned studies to better delineate the role of tryptophan and its products in the pathogenesis, adverse outcome of sleep disorders and to answer whether consumption of tryptophan-rich foods and its products might be a novel pharmacological treatment or not in sleep medicine.
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References
American Academy of Sleep Medicine (2014) International classification of sleep disorders, 3rd edn. American Academy of Sleep Medicine, Darien
Aparicio S, Garau C, Esteban S, Nicolau MC, Rivero M, Rial RV (2007) Chrononutrition: use of dissociated day/night infant milk formulas to improve the development of the wake-sleep rhythms. Effects of tryptophan. Nutr Neurosci 10(3–4):137–143
Atkinson G, Jones H, Edwards BJ, Waterhouse JM (2005) Effects of daytime ingestion of melatonin on short-term athletic performance. Ergonomics 48:1512
Brown CC, Horrom NJ, Wagman AM (1979) Effects of L-tryptophan on sleep onset insomniacs. Waking Sleeping 3(2):101–108
Brzezinski A, Vangel MG, Wurtman RJ (2005) Effects of exogenous melatonin on sleep: a meta-analysis. Sleep Med Rev 9:41–50
Buscemi N, Vandermeer B, Hooton N (2005) The efficacy and safety of exogenous melatonin for primary sleep disorders. A meta-analysis. J Gen Intern Med 20:1151–1158
Buscemi N, Vandermeer B, Hooton N (2006) Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ 332:385–393
Carley DW, Radulovacki M (2008) Pharmacology of vagal afferent influences on disordered breathing during sleep. Respir Physiol Neurobiol 164:197–203
Chan JS, Snoeren EM, Cuppen E, Waldinger MD, Olivier B, Oosting RS (2011) The serotonin transporter plays an important role in male sexual behavior: a study in serotonin transporter knockout rats. J Sex Med 8(1):97–108
Chauffard-Alboucq FA, Leathwood PD, Dormond CA (1991) Changes in plasma amino acid and subjective sleepiness ratings in humans after consuming L-tryptophan/maltodextrin mixes. Amino Acids 1:37–45
Chokroverty S (2003) An overview of normal sleep. In: Chokroverty S, Hening W, Walters A (eds) Sleep and movement disorders. Elsevier Butterworth, Philadelphia, p 23
Chokroverty S (2009) An overview of normal sleep. In: Chokroverty S (ed) Sleep disorders medicine: basic science, technical considerations, and clinical aspects. Elsevier Saunders, Philadelphia, p 19
Cole JO, Hartmann E, Brigham P (1980) L-tryptophan: clinical studies. In: Cole JO (ed) Pyschopharmacology update. The Callamore Press, Lexington, pp 119–148
Cubero J, Valero V, Sa’ nchez J, Rivero M, Parvez H, Rodrı’guez AB, Barriga C (2005) The circadian rhythm of tryptophan in breast milk affects the rhythms of 6-sulfatoxymelatonin and sleep in newborn. Neuroendocrinol Lett 26(6):657–661
Deacon S, Arendt J (1995) Melatonin-induced temperature suppression and its acute phase-shifting effects correlate in a dose-dependent manner in humans. Brain Res 688:77–85
Demisch K, Bauer J, Georgi K, Demisch L (1987) Treatment of severe chronic insomnia with L-tryptophan: results of a double-blind cross-over study. Pharmacopsychiatry 20(6):242–244
Deneris ES (2011) Molecular genetics of mouse serotonin neurons across the lifespan. Neuroscience 197:17–27
Dollins AB, Zhdanova IV, Wurtman RJ (1994) Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance. Proc Natl Acad Sci U S A 91:1824–1828
Douse MA, White DP (1996) Serotonergic effects on hypoglossal neural activity and reflex responses. Brain Res 726(1–2):213–222
Estaban S, Nicolaus C, Garmundi A, Rial RV, Rodriguez AB, Ortega E, Ibars CB (2004) Effect of orally administered L-tryptophan on serotonin, melatonin, and innate immune response in the rat. Mol Cell Biochem 267(1–2):39–46
European Food Safety Authority (2011) Scientific opinion on the substantiation of a health claim related to melatonin and reduction of sleep onset latency (ID 1698, 1780, 4080) pursuant to article 13(1) of regulation (EC) No 1924/2006. EFSA J 9:2241. http://www.efsa.europa.eu/en/efsajournal/doc/2241.pdf
Ferracioli-Oda E, Qawasmi A, Bloch MH (2013) Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS One 8(5):e63773
Galfi M, Radacs M, Juhasz A, Laszlo F, Molnar A, Laszlo FA (2005) Serotonin-induced enhancement of vasopressin and oxytocin secretion in rat neurohypophyseal tissue culture. Regul Pept 127(1–3):225–231
Garau C, Aparicio S, Rial RV, Nicolau MC, Esteban S (2012) Age related changes in the activity-rest circadian rhythms and c-fos expression of ringdoves with aging. Effects of tryptophan intake. Exp Gerontol 41(4):430–438
George CF, Millar TW, Hanly PJ, Kryger MH (1989) The effect of L-tryptophan on daytime sleep latency in normals: correlation with blood levels. Sleep 12(4):345–353
Hajak G, Huether G, Blanke J, Freyer B, Poeggeler P, Reimer A, Rodenbeck A, Schulz- Varszegi A, Ruether M (1991a) The influence of intravenous L-tryptophan on plasma melatonin and sleep in men. Pharmacopsychiatry 24(1):17–20
Hajak G, Huether G, Blanke J, Blomer M, Freyer C, Poeggler B, Reimer A, Rodenbeck A, Schulz-Varszegli M, Ruther E (1991b) The influence of intravenous L-tryptophan on plasma melatonin and sleep in men. Pharmacol Psychiatry 24:17–20
Hartmann E, Greenwald D (1984) Tryptophan and human sleep: an analysis of 43 studies. In: Schlossberger HG, Kochen W, Linzen B, Steinhart H (eds) Progress in tryptophan and serotonin research. Walter de Gruyter, Berlin, pp 297–304
Heine WE (1999) The significance of tryptophan in infant nutrition. Adv Exp Med Biol 467:705–710
Herxheimer A, Petrie KJ (2002) Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev (2):CD001520
Hussain AM, Mitra AK (2000) Effect of aging on tryptophan hydroxylase in rat brain: implications on serotonin level. Drug Metab Dispos 28:1038–1042
Hussain AM, Mitra AK (2004) Effect of reactive oxygen species on the metabolism of tryptophan in rat brain: influence of age. Mol Cell Biochem 258(1–2):145–153
Johnson LC, Chernik DA (1982) Sedative-hypnotics and human performance. Psychopharmacology (Berl) 76(2):101–113
Kilbourne EM, Philen RM, Kamb ML, Falk H (1996) Tryptophan produced by Showa Denko and epidemic eosinophilia-myalgia syndrome. J Rheumatol 46(Suppl):81–88
Kubin L, Tojima H, Davies RO, Pack AI (1992) Serotonergic excitatory drive to hypoglossal motoneurons in the decerebrate cat. Neurosci Lett 139(2):243–248
Lucini V, Lucca A, Catalano M, Smeraldi E (1996) Predictive value of tryptophan/large neutral amino acids ratio to antidepressant response. J Affect Disord 36:129–133
Lynch HJ, Wurtman RJ, Moskowitz MA et al (1975) Daily rhythm in human urinary melatonin. Science 187:169
Lynch HJ, Jimerson DC, Ozaki Y (1978) Entrainment of rhythmic melatonin secretion in man to a 12-hour phase shift in the light/dark cycle. Life Sci 23:1557
Markus CR, Jonkman LM, Lammers J, Deutz N, Messer MH, Rigtering N (2005) Evening intake of a-lactalbumin increases plasma tryptophan availability and improves morning alertness and brain measures of attention. Am J Clin Nutr 81:1026–1033
Monti JM, Jantos H (2008) The roles of dopamine and serotonin, and of their receptors, in regulating sleep and waking. Prog Brain Res 172:625–646
Moruzzi G (1964) The historical development of the deafferentation hypothesis of sleep. Proc Am Philos Soc 108:19
Nicholson AN, Stone BM (1979) L-tryptophan and sleep in healthy man. Electroencephalogr Clin Neurophysiol 47(5):539–545
Oswald I, Ashcroft GW, Berger RJ, Eccleston D, Evans JI, Thacore VR (1966) Some experiments in the chemistry of normal sleep. Br J Psychiatry 112:391–399
Peigneux P, Laureys S, Fuchs S (2001) Generation of rapid eye movements during paradoxical sleep in humans. Neuroimage 14:701–706
Peker Y, Hedner J, Norum J, Kraiczi H, Carlson J (2002) Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea: a 7-year follow-up. Am J Respir Crit Care Med 166(2):159–165
Porter RJ, Mulder RT, Joyce PR, Luty SE (2005) Tryptophan and tyrosine availability and response to antidepressant in major depression. J Affect Disord 86:129–134
Sack RL (2010) Jet lag. N Engl J Med 362:440–447
Sánchez S, Sánchez CL, Paredes SD, Rodriguez AB, Barriga C (2008) The effect of tryptophan administration on the circadian rhythms of melatonin in plasma and the pineal glands of rats. J Appl Biomed 6:177–186
Schmidt HS (1983) L-tryptophan in the treatment of impaired respiration in sleep. Bull Eur Physiopathol Respir 19:625–629
Schneider-Helmert D (1981) Interval therapy with L-tryptophan in severe chronic insomniacs. A predictive laboratory study. Int Pharmacopsychiatry 16(3):162–173
Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Javier Nieto F, O’Connor GT, Boland LL, Schwartz JE, Samet JM (2001) Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 163(1):19–25
Shochat P, Haimov I, Lavie P (1998) Melatonin: the key to the gate of sleep. Ann Med 30(1):109–114
Smith I, Lasserson TJ, Wright JJ (2006) Drug therapy for obstructive sleep apnoea in adults. Cochrane Database Syst Rev CD003002. doi:10.1002/14651858
Spinweber CL, Ursin R, Hilbert RP, Hilderbrand RL (1983) L-tryptophan: effects on daytime sleep latency and the waking EEG. Electroencephalogr Clin Neurophysiol 55(6):652–661
Tang JP, Melethil S (1995) Effect of aging on the kinetics of blood-brain barrier uptake of tryptophan in rats. Pharm Res 12(7):1085–1091
Tufik S, Santos-Silva R, Taddei JA, Bittencourt LR (2010) Obstructive sleep apnea syndrome in the Sao Paulo Epidemiologic Sleep Study. Sleep Med 11(5):441–446
Vaneck J (1998) Cellular mechanisms of melatonin action. Physiol Rev 78(3):687–721
Varvarigau V, Dahabreh IJ, Malhotra A, Kales SN (2011) A review of genetic association studies of obstructive sleep apnea: field synopsis and meta-analysis. Sleep 34(11):1461–1468
Vermeeren A (2004) Residual effects of hypnotics: epidemiology and clinical implications. CNS Drugs 18(5):297–328
Volgin DV, Stettner GM, Kubin L (2013) Circadian dependence of receptors that mediate wake-related excitatory drive to hypoglossal motoneurons. Respir Physiol Neurobiol 188:301–307
Waldhauser F, Lieberman HR, Lynch HJ (1987) A pharmacological dose of melatonin increases PRL levels in males without altering those of GH, LH, FSH, TSH, testosterone or cortisol. Neuroendocrinology 46:125–130
Walsh J (1986) Sleep disorders medicine. Association of Professional Sleep Societies, Rochester
Weaver TE, Grunstein RR (2008) Adherence to continuous positive airway pressure therapy: the challenge to effective treatment. Proc Am Thorac Soc 5:173–178
Witt-Enderby PA, Bennett J, Jarzynka MJ et al (2003) Melatonin receptors and their regulation: biochemical and structural mechanisms. Life Sci 72:2183–2198
Wu Y, Liu HB, Ding M, Liu JN, Zhu FX, Gu JH, Lu G (2013) Association between the -1438G/A and T102C polymorphisms of 5-HT2A receptor gene and obstructive sleep apnea: a meta-analysis. Mol Biol Rep 40:6223–6231
Yao K, Fang J, Yin YL, Feng ZM, Tang ZR, Wu G (2011) Tryptophan metabolism in animals: important roles in nutrition and health. Front Biosci (Schol Ed) 1(3):386–397
Young SN (1986) The clinical psychopharmacology of tryptophan. Nutr Brain 7:49–88
Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S (1993) The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 328(17):1230–1235
Zhdanova IV, Wurtman RJ, Lynch HJ (1995) Sleep-inducing effects of low doses of melatonin ingested in the evening. Clin Pharmacol Ther 57:552–558
Zhdanova IV, Wurtman RJ, Morabito C (1996) Effects of low oral doses of melatonin, given 2–4 hours before habitual bedtime, on sleep in normal young humans. Sleep 19:423–431
Zhdanova IV, Wurtman RJ, Regan MM (2001) Melatonin treatment for age-related insomnia. J Clin Endocrinol Metab 86:4727–4730
Zirlik S, Hildner KM, Targosz A, Neurath MF, Fuchs FS, Brzozowski T, Konturek PC (2013) Melatonin and omentin: influence factors in the obstructive sleep apnoea syndrome? J Physiol Pharmacol 64(3):353–360
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Kokturk, O., Kanbay, A. (2015). Tryptophan Metabolism and Sleep. In: Engin, A., Engin, A. (eds) Tryptophan Metabolism: Implications for Biological Processes, Health and Disease. Molecular and Integrative Toxicology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-15630-9_10
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DOI: https://doi.org/10.1007/978-3-319-15630-9_10
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