Melatonin long-term effects

Recent studies in a model of ischemic stroke suggest that the acute neuro-protective effect of melatonin involves activation of the phosphatidylinositol-3-kinase/Akt pathway, whereas ERK-1/2 and c-Jun N-terminal kinase-1/2, in addition to Akt signaling, appear to be involved in its long-term effects (Kilic et al. 2005). These results indicate that melatonin can interact with multiple cellular pathways to produce its diverse physiological effects. Moreover, MTi and MT2 receptors can interact with divergent signaling pathways, as shown by their ability to... 

Researchers still need to learn a lot about what melatonin does and how it can be safely used. Scientists have not completed enough studies to know exactly what functions melatonin carries out in the human body. Similarly, physicians do not understand at what time during the day or night melatonin should be taken or what dose is most effective. Nor do physicians know enough about the long-term effects of taking melatonin since it has only became popular in the 1990s. 

While many commercially available preparations contain only melatonin, many others contain a combination of this hormone with other active ingredients. Some of these other ingredients may be vitamins such as pyri-doxine, while others are natural remedies such as kava root and valerian. It is even available combined with acetaminophen, a common over-the-counter pain reliever. Frequently, the long-term effects and safety of these other ingredients are not known. Even less is known about any possible interactions between these substances and melatonin, because melatonin has been available and used commercially for only a short period of time. Many experts have suggested that it would be preferable to test melatonin in controlled studies to determine if it is effective and safe before it was released on the market and used by millions of people. 

Melatonin is produced by the pineal gland in the body and is also available as a supplement in some parts of the world. However, the effects of longterm use of this supplement are unknown. From the above studies, it appears that caffeine significantly increases the levels of single doses of supplementary melatonin, however the long-term effects of caffeine and concurrent multiple dosing of melatonin do not appear to have been studied. Melatonin can cause drowsiness when taken on its own, so patients who take melatonin should be advised that this effect may be increased if they also take caffeine. This increased drowsiness may oppose the stimulating effect of caffeine. 

Russcher M, Koch BC, Nagtegaal JE, Ittersum FJ, Pasker-de Jong P, Hagen EC, et al. Long-term effects of melatonin on quality of life and sleep in haemodialysis patients (Melody study) a randomized controlled trial. Br J Clin Pharmacol 2013 76(5) 668-79. 

Melatonin may be an effective treatment for several conditions. Studies suggest that it may be helpful in treating sleep disorders, jet lag, and even cancer. However, research on this topic is still very limited and experts have warned consumers that very little is known about the effectiveness or long-term safety of taking melatonin supplements. 

Because melatonin is found in certain foods, the Food and Drug Administration considers it to be a dietary supplement instead of a drug. However, since melatonin has not been studied very extensively, it is still unknown if it causes long-term side effects. 

In addition to questions concerning the effectiveness of melatonin for any condition, researchers still do not know enough about the long-term consequences of taking melatonin on a regular basis. Many experts caution that until melatonin has been proven to be safe and not cause serious side effects, using it as a therapeutic agent is too risky. 

Currently, there are no treatment or rehabilitation options for people who use melatonin. It is not known if long-term users may have difficulty with sleeping or other side effects when they quit taking melatonin supplements. Discontinuing the use of melatonin after shortterm use, such as for adjusting to jet lag, has not proved to be difficult or to cause any side effects. 

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. 

Melatonin has side effects, but much less so than pharmaceutical sleeping pills. Long-term safety is not known. Prolonged use may have an influence on sex organs and reduce libido. It may slightly lower blood pressure. People with the symptoms of severe mental illness, severe allergies, autoimmune diseases, or immune system cancers such as leukemia should not... 

Diazepam is better indicated if insomnia is associated with daytime anxiety. Other benzodiazepines prescribed for insomnia include nitrazepam, flur-azepam, loprazolam, lormetazepam and temazepam. The non-benzodiazepine hypnotics zaleplon, zolpidem and zopiclone are not licensed for long-term use. The sedative antipsychotic promethazine hydrochloride is sometimes used to facilitate sleep, with a 25-50 mg recommended dose. Melatonin has proved effective for some clients, mostly in regulating the sleep/waking cycle. Although evidence of efficacy is limited, some clients use herbs such as valerian and chamomile. If Mr AB will finally be diagnosed with depression, a trial with an antidepressant will be indicated. 

Placebo-controlled studies Prolonged-release melatonin 2 mg at night (Circadin ) has been compared with placebo in a 6-month study of 791 adults with primary insomnia, of whom 534 took melatonin in the extension phase [45. The incidence and type of adverse events with melatonin and placebo were similar. Melatonin had no effect on vital signs, physical examination, electrocardiography, or laboratory tests, including prolactin, ACTH, T3, free T4, TSH, LH, FSH, estradiol in women, free and total testosterone in men, and cortisol before and after a Synacthen test. One patient taking melatonin had bouts of palpitation. There were no withdrawal effects after withdrawal of long-term melatonin. 

Literature reviews A review of the literature on the use of melatonin to treat sleep disorders concluded that treatment is not associated with any significant or serious short-term or long-term adverse side effects and that the headache, confusion, dizziness, cough and rashes sometimes reported are cormnon symptoms in children and are most... 

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