Мелатонин, липидный профиль крови и атеросклероз: обзор клинических исследований
Аннотация
Приводятся общие сведения о мелатонине – содержании в организме, регуляции секреции, действии. Учитывая антиоксидантные и противовоспалительные свойства мелатонина, выполнен аналитический обзор клинических исследований влияния мелатонина на липидные показатели крови и атеросклероз у человека. Результаты выполненных клинических исследований, в особенности плацебо-контролируемых (4 исследования), не позволяют сделать однозначный вывод об эффективности использования мелатонина для снижения уровня холестерина и нормализации липидного профиля крови.
Об авторе
К. В. Даниленко
РАМН
Россия
Россия
Константин Васильевич Даниленко, д-р мед. наук, ведущий научный сотрудник
СО РАМН
ФГБУ «НИИ терапии»
630089
ул. Бориса Богаткова, 175/1
Новосибирск
Список литературы
1. Radogna F., Diederich M., Ghibelli L. Melatonin: a pleiotropic molecule regulating inflammation // Biochem. Pharmacol. 2010. Vol. 80. P. 1844–1852.
2. Lerner A. B., Case J. D., Takahashi Y. et al. Isolation of melatonin, the pineal gland factor that lightens melanocytes // J. Am. Chem. Soc. 1958. Vol. 80. P. 2587–2589.
3. Tan D. X., Manchester L. C., Reiter R. J. et al. Identification of highly elevated levels of melatonin in bone marrow: its origin and significance // Biochim. Biophys. Acta. 1999. Vol. 1472. P. 206–214.
4. Bubenik G. A., Brown G. M., Bubenik A. B., Grota L. J. Immunohistological localization of testosterone in the growing antler of the white-tailed deer (Odocoileus virginianus) // Calcif. Tissue Res. 1974. Vol. 14. P. 121–130.
5. Князькин И. В. Пинеальная железа и экстрапинеальные источники мелатонина в висцеральных органах при естественном старении человека / И. В. Князькин // Успехи геронтологии. – 2008. – Т. 21. – С. 94–95.
6. Chen C. Q., Fichna J., Bashashati M. et al. Distribution, function and physiological role of melatonin in the lower gut // World J. Gastroenterol. 2011. Vol. 17. P. 3888–3898.
7. Klein D. С. The mammalian melatonin rhythm generating system // Light and Biolgical Rhythms in Man / Ed. L. Wetterberg. Oxford–New York–Seoul–Tokyo: Pergamon Press, 1993. P. 55–70.
8. Costa E. J. X., Shida C. S., Biaggi M. H. et al. How melatonin interacts with lipid bilayers: a study by fluorescence and ESR spectroscopies // FEBS Lett. 1997. Vol. 416. P. 103–106.
9. Shida C. S., Castrucci A. M. L., Lamy-Freund M. T. High melatonin solubility in aqueous medium // J. Pineal Res. 1994. Vol. 16. P. 198–201.
10. Iriti M., Varoni E. M., Vitalini S. Melatonin in traditional Mediterranean diets // J. Pineal Res. 2010. Vol. 49. P. 101–105.
11. Bonnefont-Rousselot D., Collin F. Melatonin: action as antioxidant and potential applications in human disease and aging // Toxicology. 2010. Vol. 278. P. 55–67.
12. Eriksson L., Valtonen M., Laitinen J. T. et al. Diurnal rhythm of melatonin in bovine milk: pharmacokinetics of exogenous melatonin in lactating cows and goats // Acta Vet. Scand. 1998. Vol. 39. P. 301–310.
13. Maldonado M. D., Moreno H., Calvo J. R. Melatonin present in beer contributes to increase the levels of melatonin and antioxidant capacity of the human serum // Clin. Nutr. 2009. Vol. 28. P. 188–191.
14. Burkhardt S., Tan D. X., Manchester L. C. et al. Detection and quantification of the antioxidant melatonin in montmorency and balaton tart cherries (prunus cer-asus) // J. Agric. Food Chem. 2001. Vol. 49. P. 4898–4902.
15. Lewy A. J., Emens J. S., Lefler B. J. et al. Melatonin entrains free-running blind people according to a physiological dose-response curve // Chronobiol. Int. 2005. Vol. 22. P. 1093–1106.
16. Howatson G., Bell P. G., Tallent J. et al. Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality // Eur. J. Nutr. 2011. Oct 30. [Epub ahead of print].
17. González-Flores D., Gamero E., Garrido M. et al. Urinary 6-sulfatoxymelatonin and total antioxidant capacity increase after the intake of a grape juice cv. Tempranillo stabilized with HHP // Food Funct. 2012. Vol. 3. P. 34–39.
18. Iguchi H., Kato K. I., Ibayashi Y. Melatonin serum levels and metabolic clearance rate in patients with liver cirrhosis // J. Clin. Endocrinol. Metab. 1982. Vol. 54. P. 1025–1027.
19. Zeitzer J. M., Ayas N. T., Shea S. A. et al. Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia // J. Clin. Endocrinol. Metab. 2000. Vol. 85. P. 2189–2196.
20. Stoschitzky K., Sakotnik A., Lercher P. et al. Influence of beta-blockers on melatonin release // Eur. J. Clin. Pharmacol. 1999. Vol. 55. P. 111–115.
21. Weaver D. R. The suprachiasmatic nucleus: a 25-y retrospective // J. Biol. Rhythms. 1998. Vol. 13. P. 100–112.
22. Gaddy J. R., Rollag M. D., Brainard G. C. Pupil size regulation of threshold of light-induced melatonin suppression // J. Clin. Endocrinol. Metab. 1993. Vol. 77. P. 1398–1401.
23. Zeitzer J. M., Dijk D. J., Kronauer R. E. et al. Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression // J. Physiol. (Lond.). 2000. Vol. 526. P. 695–702.
24. Hatori M., Panda S. The emerging roles of melanopsin in behavioral adaptation to light // Trends Mol. Med. 2010. Vol. 16. P. 435–446.
25. Deacon S., Arendt J. Posture influences melatonin concentrations in plasma and saliva in humans // Neurosci. Let. 199. Vol. 167. P. 191–194.
26. Klerman E. B., Gershengorn H. B., Duffy J. F., Kronauer R. E. Comparisons of the variability of three markers of the human circadian pacemaker // J. Biol. Rhythms. 2002. Vol. 17. P. 181–193.
27. Benloucif S., Guico M. J., Reid K. J. et al. Stability of melatonin and temperature as circadian phase markers and their relation to sleep times in humans // J. Biol. Rhythms. 2005. Vol. 20. P. 178–188.
28. Rajaratnam S. M., Dijk D. J., Middleton B. et al. Melatonin phase-shifts human circadian rhythms with no evidence of changes in the duration of endogenous melatonin secretion or the 24-hour production of reproductive hormones // J. Clin. Endocrinol. Metab. 2003. Vol. 88. P. 4303–4309.
29. Mavroudis P. D., Scheff J. D., Calvano S. E., Lowry S. F. Entrainment of peripheral clock genes by cortisol // Physiol. Genomics. 2012. Apr 17. [Epub ahead of print]
30. Kiessling S., Eichele G., Oster H. Adrenal glucocorticoids have a key role in circadian resynchronization in a mouse model of jet lag // J. Clin. Invest. 2010. Vol. 120. P. 2600–2609.
31. Siepka S. M., Yoo S. H., Park J., Lee C., Takahashi J. S. Genetics and neurobiology of circadian clocks in mammals // Cold Spring Harb. Symp. Quant. Biol. 2007. Vol. 72. P. 251–259.
32. Danilenko K. V., Putilov A. A., Russkikh G. S. et al. Diurnal and seasonal variations of melatonin and serotonin in women with seasonal affective disorder // Arct. Med. Res. 1994. Vol. 53. P. 137–145.
33. Wehr T. A. Photoperiodism in humans and other primates: evidence and implications // J. Biol. Rhythms. 2001. Vol. 16. P. 348–364.
34. Kräuchi K., Cajochen C., Pache M. et al. Thermoregulatory effects of melatonin in relation to sleepiness // Chronobiol. Int. 2006. Vol. 23. P. 475–484.
35. Wirz-Justice A., Armstrong S. M. Melatonin: nature‘s soporific? // J. Sleep Res. 1996. Vol. 5. P. 137–141.
36. Wade A., Zisapel N., Lemoine P. Prolonged-release melatonin for the treatment of insomnia: targeting quality of sleep and morning alertness // Aging Health. 2008. Vol. 4. P. 11–21.
37. Kripke D. F., Kline L. E., Shadan F. F. et al. Melatonin effects on luteinizing hormone in postmenopausal women: a pilot clinical trial NCT00288262 // BMC Womens Health. 2006. Vol. 16, N 6. P. 8.
38. Puig-Domingo M., Webb S. M., Serrano J. et al. Brief report: melatonin-related hypogonadotropic hy-pogonadism // N. Engl. J. Med. 1992. Vol. 327. P. 1356–1359.
39. Cagnacci A., Arangino S., Angiolucci M. et al. Influences of melatonin administration on the circulation of women // Am. J. Physiol. 1998. Vol. 274. P. R335–R338.
40. Заславская Р. М. Мелатонин в комплексной терапии сердечно-сосудистых заболеваний / Р. М. Заславская [и др.] // Клиническая медицина. – 2010. – № 3. – С. 26–30.
41. Grossman E., Laudon M., Zisapel N. Effect of melatonin on nocturnal blood pressure: meta-analysis of randomized controlled trials // Vasc. Health Risk Manag. 2011. Vol. 7. P. 577–584.
42. Tan D. X., Chen L. D., Poeggeler B. et al. Melatonin: a potent, endogenous hydroxyl radical scavenger // Endocr. J. 1993. Vol. 1. P. 57–60.
43. Зенков Н. К. Ингибирование мелатонином окисления липопротеинов низкой плотности / Н. К. Зенков [и др.] // Бюл. эксперим. биол. мед. – 1996. – Т. 122, № 10. – С. 399–402.
44. Reiter R. J., Paredes S. D., Korkmaz A. et al. Melatonin combats molecular terrorism at the mitochondrial level // Interdiscip. Toxicol. 2008. Vol. 1. P. 137–149.
45. Джериева И. С. Оксидативный стресс и возможность его коррекции мелатонином / И. С. Джериева, Н. И. Волкова // Клиническая медицина. – 2011. – Т. 89. № 5. – С. 21–25.
46. Anisimov V. N., Popovich I. G., Zabezhinski M. A. et al. Melatonin as antioxidant, geroprotector and anticarcinogen // Biochim. Biophys. Acta. 2006. Vol. 1757. P. 573–589.
47. Bubenik G. A., Konturek S. J. Melatonin and aging: prospects for human treatment // J. Physiol. Pharmacol. 2011. Vol. 62. P. 13–19.
48. Sánchez-Barcelу E. J., Mediavilla M. D., Tan D. X., Reiter R. J. Clinical uses of melatonin: evaluation of human trials // Curr. Med. Chem. 2010. Vol. 17. P. 2070–2095.
49. Kunz D., Schmitz S., Mahlberg R. et al. A new concept for melatonin deficit: on pineal calcification and melatonin excretion // Neuropsychopharmacology. 1999. Vol. 21. P. 765–672.
50. Arendt J. Safety of melatonin in long-term use (?) // J. Biol. Rhythms. 1997. Vol. 12. P. 673–681.
51. Gooley J. J., Chamberlain K., Smith K. A. et al. Exposure to room light before bedtime suppresses melatonin onset and shortens melatonin duration in human // J. Clin. Endocrinol. Metab. 2011. Vol. 96. P. E463–E472.
52. Шварц Ш. Я. Фиброзный процесс при атеросклерозе / Ш. Я. Шварц, Е. А.. Чересиз // Атеросклероз. – 2011. – Т. 2, № 2. – С. 57–66.
53. Tailleux A., Torpier G., Bonnefont-Rousselot D. et al. Daily melatonin supplementation in mice increases atherosclerosis in proximal aorta // Biochem. Biophys. Res. Commun. 2002. Vol. 293. P. 1114–1123.
54. Tailleux A., Gozzo A., Torpier G. et al. Increased susceptibility of low-density lipoprotein to ex vivo oxidation in mice transgenic for human apolipoprotein B treated with 1 melatonin-related compound is not associated with atherosclerosis progression // J. Cardiovasc. Pharmacol. 2005. Vol. 46. P. 241–249.
55. Pita M. L., Hoyos M., Martin-Lacave I. et al. Long-term melatonin administration increases polyunsaturated fatty acid percentage in plasma lipids of hypercholesterolemic rats // J. Pineal Res. 2002. Vol. 32. P. 179–186.
56. ESC / EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) // Eur. Heart J. 2011. Vol. 32. P. 1769–1818.
57. Dominguez-Rodriguez A., Abreu-Gonzalez P., Garcia-Gonzalez M. et al. Elevated levels of oxidized low-density lipoprotein and impaired nocturnal synthesis of melatonin in patients with myocardial infarction // Atherosclerosis. 2005. Vol. 180. P. 101–105.
58. Tengattini S., Reiter R. J., Tan D. X. et al. Cardiovascular diseases: protective effects of melatonin // J. Pineal Res. 2008. Vol. 44. P. 16–25.
59. Aoyama H., Mori N., Mori W. Effects of melatonin on genetic hypercholesterolemia in rats // Atherosclerosis. 1988. Vol. 69. P. 269–272.
60. Kitagawa A., Ohta Y., Ohashi K. Melatonin improves metabolic syndrome induced by high fructose intake in rats // J. Pineal Res. 2012. Vol. 52. P. 403–413.
61. Ríos-Lugo M. J., Cano P., Jiménez-Ortega V. et al. Melatonin effect on plasma adiponectin, leptin, insulin, glucose, triglycerides and cholesterol in normal and high fat-fed rats // J. Pineal Res. 2010. Vol. 49. P. 342–348.
62. Pawlikowski M., Kolomecka M., Wojtczak A., Karasek M. Effects of six months melatonin treatment on sleep quality and serum concentrations of estradiol, cortisol, dehydroepiandrosterone sulfate, and somatomedin C in elderly women // Neuro Endocrinol. Lett. 2002. Suppl 1. P. 17–19.
63. Wakatsuki A., Okatani Y., Ikenoue N. et al. Effects of short-term melatonin administration on lipoprotein metabolism in normolipidemic postmenopausal women // Maturitas. 2001. Vol. 38. P. 171–177.
64. Tamura H., Nakamura Y., Narimatsu A. et al. Melatonin treatment in peri- and postmenopausal women elevates serum high-density lipoprotein cholesterol levels without influencing total cholesterol levels // J. Pineal Res. 2008. Vol. 45. P. 101–105.
65. Koziróg M., Poliwczak A. R., Duchnowicz P. et al. Melatonin treatment improves blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome // J. Pineal Res. 2011. Vol. 50. P. 261–266.
66. Коркушко О. В. Пептидный геропротектор из эпифиза замедляет ускоренное старение пожилых людей: результаты 15-летнего наблюдения / О. В. Коркушко [и др.] // Биогеронтология. – 2011. – Т. 151, № 3. – С. 343–347.
67. Seabra M. L., Bignotto M., Pinto L. R. Jr., Tufik S. Randomized, double-blind clinical trial, controlled with placebo, of the toxicology of chronic melatonin treat ment // J. Pineal Res. 2000. Vol. 29. P. 193–200.
68. Rindone J. P., Achacoso R. Effect of melatonin on serum lipids in patients with hypercholesterolemia: a pilot study // Am. J. Ther. 1997. Vol. 4. P. 409–411.
69. Gonciarz M., Gonciarz Z., Bielanski W. et al. The pilot study of 3-month course of melatonin treatment of patients with nonalcoholic steatohepatitis: effect on plasma levels of liver enzymes, lipids and melatonin // J. Physiol. Pharmacol. 2010. Vol. 61. P. 705–710.
70. Gonciarz M., Gonciarz Z., Bielanski W. et al. The effects of long-term melatonin treatment on plasma liver enzymes levels and plasma concentrations of lipids and melatonin in patients with nonalcoholic steatohepatitis: a pilot study // J. Physiol. Pharmacol. 2012. Vol. 63. P. 35–40.
71. Cichoz-Lach H., Celinski K., Konturek P. C. et al. The effects of L-tryptophan and melatonin on selected bio-chemical parameters in patients with steatohepatitis // J. Physiol. Pharmacol. 2010. Vol. 61. P. 577–580.
72. Robeva R., Kirilov G., Tomova A., Kumanov P. Melatonin-insulin interactions in patients with metabolic syndrome // J. Pineal Res. 2008. Vol. 44. P. 52–56.
73. Masue T., Wada K., Hayashi M. et al. Associations of urinary 6-sulfatoxymelatonin with biomarkers related to cardiovascular disease in Japanese women // Metabolism. 2012. Vol. 61. P. 70–75.
74. Maldonado M. D., Manfredi M., Ribas-Serna J. et al. Melatonin administrated immediately before an intense exercise reverses oxidative stress, improves immunological defenses and lipid metabolism in football players // Physiol. Behav. 2012. Vol. 105. P. 1099–1103.
75. Sandyk R., Awerbuch G. I. The relationship between melatonin secretion and serum cholesterol in patients with multiple sclerosis // Int. J. Neurosci. 1994. Vol. 76. P. 81–86.
76. Dominguez-Rodriguez A., Abreu-Gonzalez P., Reiter R. J. Melatonin and cardiovascular disease: myth or reality? // Rev. Esp. Cardiol. 2012. Vol. 65. P. 215–218.
Рецензия
Для цитирования:
Даниленко К.В. Мелатонин, липидный профиль крови и атеросклероз: обзор клинических исследований. Атеросклероз. 2012;8(1):36-42.
For citation:
Danilenko K.V. Melatonin, serum lipids, and atherosclerosis: a review of clinical studies. Ateroscleroz. 2012;8(1):36-42. (In Russ.)
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