Melatonin administration

In humans, poor sleep correlates with low plasma melatonin and can be improved by melatonin administration. This therapeutic approach has been tried especially in individuals whose sleep rhythms are disrupted by shift-work, blindness or jet-lag but its benefits are as yet unconfirmed and, in any case, the mechanisms by which it might reset sleep patterns are unclear. Of course, it must be remembered that other body... 

Effects of exogenous melatonin administration on human sleep... 

A number of studies have investigated the potential of melatonin to alleviate the symptoms of jet lag. Melatonin has been found to be effective in 11 placebo-controlled studies in reducing the subjective symptoms of jet lag such as sleepiness and impaired alertness (Arendt 2005). The most severe health effects of jet lag occur following eastbound flights, since this requires a phase advancement of the biological clock. In a recent study, phase advancement after melatonin administration (using 3 mg doses just before bedtime) occurred in all 11... 

Hughes, R. J. Badia, P. (1997). Sleep-promoting and hypothermic effects of daytime melatonin administration in humans. Sleep 20, 124-31. 

Sachar EJ, Heilman L, Roffwarg HP, et al Disrupted 24 hour patterns of cortisol secretion in psychotic depressives. Arch Gen Psychiatry 28 19-24, 1973 Sack RL, Blood ML, Lewy AJ Melatonin administration to night shift workers an update. Sleep Research 24 539, 1995... 

There are several double-blind studies that support melatonin administration. For example, rapid deployment aviation groups sent to the Middle East demonstrated longer sleep duration and better test performance on melatonin than did the placebo group ( 174, 175). Arendt (173), who has had extensive experience with both controlled and uncontrolled studies, summarized the overall experience in 386 subjects, showing a 60% reduction in jet lag for eastern travel and a 40% reduction for western travel. 

In healthy men, chronic melatonin administration (> 6 months) decreased sperm quality, possibly by aromatase inhibition in the testes. Until more is known, melatonin should not be used by couples who are actively trying to conceive. 

Rogers NL, Phan O, Kennaway DJ, Dawson D. Effect of daytime oral melatonin administration on neurobehavioral performance in humans. J Pineal Res 1998 25(l) 47-53. 

Leibenluft E, Feldman-Naim S, Turner EH, Wehr TA, Rosenthal NE. Effects of exogenous melatonin administration and withdrawal in five patients with rapid-cycling bipolar disorder. J Clin Psychiatry 1997 58(9) 383-8. 

Cagnacci A, Arangino S, Renzi A, Paoletti AM, Melis GB, Cagnacci P, Volpe A. Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. Clin Endocrinol (Oxf) 2001 54(3) 339-46. 

Graw P, Werth E, Krauchi K, Gutzwiller F, Cajochen Co, Wirz-Justice A. Early morning melatonin administration impairs psychomotor vililance. Behavioral Brain Research 2001 121 167-172. 

One further treatment that has been studied extensively to achieve resynchronization of the circadian system is the administration of melatonin. Endogenous melatonin is secreted from the pineal gland, primarily across the nocturnal or dark period. It has been proposed to play a role in the control of the circadian system (reviewed in Ref. 174) and potentially in the initiation of sleep (175,176). Studies that have administered exogenous melatonin, primarily during the daytime, have reported both chronobiotic (177) and soporific effects (178). Melatonin administration has been successful in studies examining the reentrainment of the circadian system after transmeridian flight or shiftwork (179). Similarly, the effectiveness of melatonin in reentraining the circadian system of those with DSPS to a normal day has been studied. 

Phase advances of the circadian system and sleep-wake activity have been reported in a number of studies, with daily administration of melatonin (180-183). Termination of melatonin administration resulted in a reversal of the phase advances, with subjects reverting to their preadministration phase. Therefore, continued administration of melatonin may provide a means for those with DSPS to maintain a normal phase, and avoid the associated sleep deprivation due to having to live on a normal schedule. It is important to note, however, that at present the effective dose of melatonin to be administered and the safety of long-term melatonin administration have yet to be established (184). Therefore, melatonin should be thought of as a research compound and not a clinical solution to DSPS. 

Dawson D, Encel N, Lushington K. Improving adaptation to simulated night shift timed exposure to bright light versus daytime melatonin administration. Sleep 1995 18 11-21. 

The hormone melatonin is involved in the control of the circadian system, and has been implicated in the control of sleep [64], Several studies have examined the effectiveness of melatonin as a treatment of insomnia. While some researchers have reported a positive effect [65, 66], others have reported little or no effect [67,68], At present, the magnitude of beneficial effects following melatonin administration to insomniacs is unclear. Furthermore, the mechanism of action of this hormone with relation to sleep initiation, has not yet been fully described [69], Finally, exposure to bright light therapy during the early morning hours has been reported to relieve sleep onset insomnia, even in elderly patients [70], This may be due to the restoration of circadian rhythms in these insomniacs. 

James SP, Sack DA, Rosenthal NE, Mendelson WB (1990) Melatonin administration in insomnia. Neuropsychopharmacology 3 19-23... 

Dawson D, Rogers NL, va den Heuvel CJ, Kennaway DJ, Lushington K (1998) Effect of sustained nocturnal transbuccal melatonin administration on sleep and temperature in elderly insomniacs. J Biol Rhythms 13 532-538... 

In blind subjects with free-running rhythms, it has been possible to stabilize, or entrain, the sleep/wake cycle to a 24-hour period by giving melatonin, with resulting improvements in sleep and mood [42], In normal aged subjects [43],and in demented patients with desynchronization of sleep/wake cycle [44] melatonin administration is... 

Ozbek E, Turkoz Y, Sahna E, Ozugurlu F, Mizrak B, Ozbek M. Melatonin administration prevents the nephrotoxicity induced by gentamicin. BJU Int 2000 85(6) 742-6. 

The cardioprotective effect of melatonin is demonstrated in several studies in in vivo and ex vivo experimental rat models or cardiomyocytes, as reviewed by Reiter.30 Melatonin administration in perfused rat hearts subjected to ischemia and reperfusion increased postischemic recovery of function, reduced the duration of ventricular tachycardia and ventricular fibrillation and this was associated with decreased lipid peroxidation products and OH radical formation, indicating an antioxidant effect of melatonin.31 Furthermore, in pinealectomized rats, occlusion of the left coronary artery followed by reperfusion resulted in significant increase in infarct size than in intact animals.32 Melatonin acts as scavenger of oxygen or nitrogen based reactants, stimulates antioxidant enzymes, stabilizes cellular membrane, increases the efficiency of oxidative phosphorylation, reduces leukocyte recruitment and adhesion molecule expression and reduces homocysteine induced damage (reviewed by Duncker33). 

Gupta M, Gupta YK, Agarwal S, Aneja S, Kalaivani M, Kohli K. Effects of add-on melatonin administration on antioxidant enzymes in children with epilepsy taking carbamazepine monotherapy a randomized, double-blind, placebo-controlledtrial. Epilepsia (2004) 45,1636-9. 

Carneiro and Reiter (1998) have reported that the incubation of rat cerebral, hippocampal and cerebellar homogenates with 6-aminolaevulinic acid increases the formation of lipid peroxidation products presumably as a result of the induction of free radicals by 6-aminolaevulinic acid. Melatonin coincubation, in both a concentration-dependent and time-dependent manner, prevented the rises in the damaged lipid products malondialdehyde and 4-hydroxyalkenals. In vivo as well, acute melatonin administration reduced damaged lipid products in the brain of rats treated with 8-aminolaevulinic acid. Princ et al. (1997) in similar studies like Carneiro and Reiter (1998) felt that the ability of melatonin to protect against 6-aminolaevulinic acid toxicity relates to the free radical scavenging activity of the indolamine. Furthermore, Princ et al. (1998) showed that melatonin administered in vivo not only reduced lipid peroxidation in the brain of rats treated with 6-aminolaevulinic acid, but also increased enzyme activities of the heme pathway. 

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