1. Melatonin as an antioxidant
One important feature, as a role as a pervasive and powerful antioxidant, Melatonin protect our body from free radicals by fighting against damage of the nuclear and mitochondrial DNA of the cells. In a study of "Free Radical-Mediated Molecular Damage Mechanisms for the Protective Actions of Melatonin in the Central Nervous System" by RUSSEL J. REITER, DARIO ACUÑA-CASTROVIEJO, DUN-XIAN TAN and SUSANNE BURKHARDT, researchers concluded that most recently, melatonin has been shown to increase the efficiency of the electron transport chain and, as a consequence, to reduce election leakage and the generation of free radicals. These multiple actions make melatonin a potentially useful agent in the treatment of neurological disorders that have oxidative damage as part of their etiological basis.
2. Melatonin (N-acetyl-5-methoxytryptamine) and Headaches
Over counter melatonin supplement has been proven to be effectively prevent and treat migraines and headaches. In a study of The therapeutic potential of melatonin in migraines and other headache types by Gagnier JJ., researcher found that melatonin may play a role in resynchronizing biological rhythms to lifestyle and subsequently relieve migraines and other forms of headaches. In addition, research testing the administration of melatonin found it safe in migraine sufferers, with few or no side effects. However, a larger, randomized control trial is needed to definitively determine if administration of melatonin to migraine patients is effective.
3. Melatonin (N-acetyl-5-methoxytryptamine) and Circadian disturbances
According to the article of Is Internal Timing Key to Mental Health? Published by AAAS, the article indicated that... psychiatrists working with small groups of patients have shown that
correcting abnormal circadian rhythms—through exposure to light, melatonin pills, or even sleep deprivation—can help treat some of these disorders,....
4. Melatonin (N-acetyl-5-methoxytryptamine) and Depression associated with the menopause
According to the study of "Effects of Melatonin in Perimenopausal and Menopausal Women: Our Personal Experience" by Bellipanni G, DI Marzo F, Blasi F, Di Marzo A., researchers concluded that At present we assert that the six-month treatment with MEL produced a remarkable and highly significant improvement of thyroid function, positive changes of gonadotropins towards more juvenile levels, and abrogation of menopause-related depression.
5. Melatonin (N-acetyl-5-methoxytryptamine) and Prolactin
In a study of Evening administration of melatonin enhances the pulsatile secretion of prolactin but not of LH and TSH in normally cycling women, by Massimo Terzolo, Alberto Revelli, Daniela Guidetti, Alessandro Piovesan, Paola Cassoni, Piero Paccotti, Alberto Angeli, Marco Massobrio, researchers found that Exogenous melatonin has a stimulatory effect on PRL release without affecting the temporal pattern of its pulsatile secretion in normal women. Melatonin has minor, if any, effect on TSH secretion whereas the effect on LH may depend on individual sensitivity.
6. Melatonin (N-acetyl-5-methoxytryptamine) and Fertility
Melatonin can enhance fertility of a woman by lowering Follicle stimulating hormones, according to the article of "You should know about Melatonin and Fertility" by Dr. Tanya Smith, TCM, ... at the 20th World Congress on Fertility and Sterility in September 2010 and found that the fertilization rate among women who took 3 mg tablets of melatonin (n = 56) during the second IVF cycle were improved compared with those achieved during their first failed cycle, at 50.0% versus 20.2%. Patients who did not take melatonin (n = 59) experienced no change in fertilization rates.
7. Melatonin (N-acetyl-5-methoxytryptamine) and Menopause
In a study of "Decrease in melatonin precedes follicle-stimulating hormone increase during perimenopause" Olli Vakkuri, Aarre Kivelä, Juhani Leppäluoto, Maija Valtonen and Antti Kauppila, researchers found that the inverse changes in melatonin and FSH secretion during the perimenopausal years, with the sharpest decline in nocturnal excretion of melatonin far before menopause, suggest that melatonin may be permissively linked to the initiation of menopause.
7. Melatonin (N-acetyl-5-methoxytryptamine) and Anxiety: the association with lower melatonin levels
In a study of "Perioperative effects of melatonin and midazolam premedication on sedation, orientation, anxiety scores and psychomotor performance" by Acil M, Basgul E, Celiker V, Karagöz AH, Demir B, Aypar U., researchers concluded that Melatonin premedication was associated with preoperative anxiolysis and sedation without postoperative impairment of psychomotor performance.
8. Anti-depressant action of melatonin
In the study to investigate the antidepressant effect of physiological and pharmacological doses of melatonin in the Porsolt forced swimming-induced behavioral despair test, showed that acute administration of higher doses of melatonin (2.5-10 mg/kg) failed to induce any anti-depressant activity in mice which were subjected to forced swimming test for the first time. However, daily administration of melatonin (2.5-10 mg/kg) prior to swimming test significantly reversed the increase in immobility period that was observed on chronic exposure to swimming test. This effect was comparable with the effect of GABA-benzodiazepine (BZ) receptor agonists. Similarly, like GABAergic drugs, acute administration of melatonin also showed anti-depressant activity in a mice which were exposed to chronic forced swimming test(8).
9. Direct involvement of melatonin in modulation of ovarian steroidogenesis
In the study to investigate the gene expression of the two different forms of melatonin receptors in human granulosa-luteal cells, using RT-PCR. PCR products corresponding to the expected sizes of the melatonin receptor subtypes, mt(1)-R and MT(2)-R, which were obtained from granulosa-luteal cells, and the authenticity of the PCR products was confirmed by Southern blot hybridization with cDNA probes, showed that melatonin treatment alone had no effect on basal progesterone production but enhanced the effects of human CG-stimulated progesterone production. Because MAPKs are activated in response to a diverse array of extracellular stimuli leading to the regulation of cell growth, division, and differentiation, and because melatonin has been shown to modulate cellular proliferation and differentiation. But melatonin activated MAPK in a dose- and time-dependent manner can regulate progesterone production, LH receptor, GnRH, and GnRH receptor gene expression through melatonin receptors in human granulosa-luteal cells, which may be mediated via the MAPK pathway and activation of Elk-1(9).
10. Tryptophan-enriched cereal intake in elderly humans
In the study to analyze whether the consumption of cereals enriched with tryptophan, the precursor of both serotonin and melatonin, may help in the reconsolidation of the sleep/wake cycle and counteract depression and anxiety in 35 middle-aged/elderly (aged 55-75 year) volunteers in a simple blind assay, showed that the consumption of cereals containing the higher dose in tryptophan increased sleep efficiency, actual sleep time, immobile time, and decreased total nocturnal activity, sleep fragmentation index, and sleep latency. Urinary 6-sulfatoxymelatonin, 5-hydroxyindoleacetic acid levels, and urinary total antioxidant capacity also increased respectively after tryptophan-enriched cereal ingestion as well as improving anxiety and depression symptoms. Cereals enriched with tryptophan may be useful as a chrononutrition tool for alterations in the sleep/wake cycle due to age(10).
11.Melatonin and circadian rhythms and sleep
melatonin is an internal sleep "facilitator" in humans, and therefore useful in the treatment of insomnia and the readjustment of circadian rhythms. In the study of Role of melatonin in the regulation of human circadian rhythms and sleep, researchers found that administration of melatonin is able: (i) to induce sleep when the homeostatic drive to sleep is insufficient; (ii) to inhibit the drive for wakefulness emanating from the circadian pacemaker; and (iii) induce phase shifts in the circadian clock such that the circadian phase of increased sleep propensity occurs at a new, desired time(11).
12. Melatonin in the treatment of cancer
In a systematic review of randomized controlled trials between 1992 and 2003 and included 643 patients. All trials included solid tumor cancers. All trials were conducted at the same hospital network, and were unblinded. Melatonin reduced the risk of death at 1 yr (relative risk: 0.66, 95% confidence interval: 0.59-0.73, I2=0%, heterogeneity P<or=0.56). Effects were consistent across melatonin dose, and type of cancer. No severe adverse events were reported, according to the report of the Department of Clinical Epidemiology, McMaster University(12). Others suggested that Melatonin is effective in suppressing neoplastic growth in a variety of tumors like melanoma, breast and prostate cancer, and ovarian and colorectal cancer. As an adjuvant therapy, melatonin can be beneficial in treating patients suffering from breast cancer, hepatocellular carcinoma or melanoma(12a).
13. Melatonin in oral health and disease
According to the study of Faculty of Dentistry, Zonguldak Karaelmas University, melatonin has immunomodulatory and antioxidant activities, stimulates the proliferation of collagen and osseous tissue, and acts as a protector against cellular degeneration associated with aging and toxin exposure. Arising out of its antioxidant actions, melatonin protects against inflammatory processes and cellular damage caused by the toxic derivates of oxygen. As a result of these actions, melatonin may be useful as a coadjuvant in the treatment of certain conditions of the oral cavity. However, the most important effect of melatonin seems to result from its potent antioxidant, immunomodulatory, protective, and anticancer properties. Thus, melatonin could be used therapeutically for instance, locally, in the oral cavity damage of mechanical, bacterial, fungal, or viral origin, in postsurgical wounds caused by tooth extractions and other oral surgeries. Additionally, it can help bone formation in various autoimmunological disorders such as Sjorgen syndrome, in periodontal diseases, in toxic effects of dental materials, in dental implants, and in oral cancers(13). Other researchers suggested that strong reductions of circulating melatonin are also observed in numerous disorders and diseases, including Alzheimer's disease, various other neurological and stressful conditions, pain, cardiovascular diseases, cases of cancer, endocrine and metabolic disorders, in particular diabetes type 2(14). Clinical trials have shown that melatonin is efficient in preventing cell damage under acute (sepsis, asphyxia in newborns) and chronic states (metabolic and neurodegenerative diseases, cancer, inflammation, aging). The beneficial effects of melatonin can be explained by its properties as a potent antioxidant and antioxidant enzyme inducer, a regulator of apoptosis and a stimulator of immune functions(15).
16. Melatonin and cancer theapies
In the searched 7 databases: MEDLINE (1966-February 2010), AMED (1985-February 2010), Alt HealthWatch (1995-February 2010), CINAHL (1982-February 2010), Nursing and Allied Health Collection: Basic (1985-February 2010), the Cochrane Database (2009), and the Chinese database CNKI (1979-February 2010). They included all trials that randomized patients to treatment, including MLT or a similar control group without MLT, researchers found that MLT may benefit cancer patients who are also receiving chemotherapy, radiotherapy, supportive therapy, or palliative therapy by improving survival and ameliorating the side effects of chemotherapy(16). Others found that the administration of melatonin alone or in combination with interleukin-2 in conjunction with chemoradiotherapy and/or supportive care in cancer patients with advanced solid tumors, has been associated with improved outcomes of tumor regression and survival. Moreover, chemotherapy has been shown to be better tolerated in patients treated with melatonin(17).
18. Melatonin and breast cancer prevention
In the reviews the usefulness of this indoleamine for specific aspects of breast cancer management, particularly in reference to melatonin's antiestrogenic and antioxidant properties, found that the clinical utility of melatonin depends on the appropriate identification of its actions. Because of its SERM (selective estrogen receptor modulators) and SEEM (selective estrogen enzyme modulators) properties, and its virtual absence of contraindications, melatonin could be an excellent adjuvant with the drugs currently used for breast cancer prevention (antiestrogens and antiaromatases)(18).
19. Melatonin in Children
In children and neonates, melatonin has been used widely, including for respiratory distress syndrome, bronchopulmonary dysplasia, periventricular leukomalacia (PVL), hypoxia-ischemia encephalopathy and sepsis. In addition, melatonin can be used in childhood sleep and seizure disorders, and in neonates and children receiving surgery, according to the study by Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine(19).
20. Shift work and cancer risk
About 15-20% of the employees in Europe and in the USA are engaged in shift work that involves night work. In the review of disruption in the melatonin synthesis and its effects on shift workers found that in six out of ten studies, a statistically significant association between night shift work and risk of breast cancer has been shown (OR = 2.2; 95% CI: 1.1-4.5 in nurses in Norway with > 30 years of night shift work). The increased cancer risk has been reported in nurses, radio-telephone operators, flight attendants, and women employed in the enterprises, in which 60% of employees work at night. Most of the analyses have been based on the data from the registries, with limited potential for the exposure assessment and confounders adjustment(20).
21. Melatonin and Drug-mediated ototoxicity and tinnitus
In the study to evaluate the published basic science and clinical reports related to the role of melatonin in reducing the side effects of aminoglycosides and the cancer chemotherapeutic agent cisplatin, in the cochlea and vestibule of the inner ear, suggested that the potential use of melatonin to combat the ototoxicity of aminoglycosides and cancer chemotherapeutic agents. Additional studies at both the experimental and clinical levels should be performed to further document the actions of melatonin at the cochlear and vestibular levels to further clarify the protective mechanisms of action of this ubiquitously-acting molecule. Melatonin's low cost and minimal toxicity profile supports its use to protect the inner ear from drug-mediated damage(21).
22. Melatonin in experimental seizures and epilepsy
Although melatonin is approved only for the treatment of jet-lag syndrome and some types of insomnia, clinical data also suggest that it is effective in the adjunctive therapy of osteoporosis, cataract, sepsis, neurodegenerative diseases, hypertension, and even cancer. In humans, melatonin may attenuate seizures, and it is most effective in the treatment of juvenile intractable epilepsy. Its additional benefits include improved physical, emotional, cognitive, and social functions. On the other hand, melatonin has been shown to induce electroencephalographic abnormalities in patients with temporal lobe epilepsy and increase seizure activity in neurologically disabled children. The hormone showed very low toxicity in clinical practice, according to the study by Department of Pathophysiology, Medical University, PL 20-090 Lublin, Jaczewskiego 8, Poland(22).
23. Melatonin and Treatment of Insomnia in elder
In 3-week and 6-month, randomized, double-blind clinical trials in patients with primary insomnia aged ≥55 years, melatonin PR 2 mg 1-2 h before bedtime was associated with significant improvements relative to placebo in many sleep and daytime parameters, including sleep quality and latency, morning alertness and health-related quality of life. Melatonin PR 2 mg was very well tolerated in clinical trials in older patients, with a tolerability profile that was similar to that of placebo. Short- or longer-term treatment with melatonin PR 2 mg was not associated with dependence, tolerance, rebound insomnia or withdrawal symptoms(23).
24. Melatonin treatment in children with ADHD and chronic sleep onset insomnia
In the study to assess long-term melatonin treatment course, effectiveness and safety in children with attention-deficit/hyperactivity disorder (ADHD) and chronic sleep onset insomnia (CSOI), researchers at the Department of Neurology, Elisabeth Hospital, Tilburg, The Netherlands, found that long-term melatonin treatment was judged to be effective against sleep onset problems in 88% of the cases. Improvement of behaviour and mood was reported in 71% and 61% respectively. We conclude that melatonin remains an effective therapy on the long term for the treatment of CSOI in children with ADHD and has no safety concerns regarding serious adverse events or treatment related co-morbidity. Discontinuation of melatonin treatment usually leads to a relapse of sleep onset insomnia and in resuming melatonin treatment, even after several years of treatment(24).
25. Melatonin treatment in the circadian sleep disorders: delayed sleep phase syndrome (DSPS) and non-24-hour sleep wake disorder
In the study to evaluate the effect of Melatonin treatment in the circadian sleep disorders: delayed sleep phase syndrome (DSPS) and non-24-hour sleep wake disorder, researchers at the School of Biological Sciences, University of Surrey, Guildford, U.K, showed that compared with placebo, melatonin advanced the sleep period in subjects with DSPS. Melatonin also improved a number of sleep parameters in blind subjects suffering from non-24-hour sleep wake disorder(25).
26. Melatonin and sleep problems in children with neurodevelopmental disorders
In a 12 week double masked randomised placebo controlled phase III trial to test for the efficacy of melatonin in treating sleep problems in children with neurodevelopmental disorders, found that children gained little additional sleep on melatonin; though they fell asleep significantly faster, waking times became earlier. Child behaviour and family functioning outcomes did not significantly improve. Melatonin was tolerable over this three month period. Comparisons with slow release melatonin preparations or melatonin analogues are required(26)
27. Effects of melatonin on ovarian follicles
In the study to evaluate the histomorphometry and expression of Ki-67 and c-kit in ovarian follicles of pinealectomized or melatonin-treated pinealectomized rats, researchers at the São Paulo Federal University (UNIFESP), showed that melatonin exerts a role on the maintenance of a proper follicular function, and is thus important for ovulation and progesterone production(27).
28. Melatonin on angiogenesis and wound healing
In the study to investigate the effects of melatonin hormone on angiogenesis in wound healing on 100 Wistar-Albino rats, with melatonin dissolved in 0.9% NaCl administered to the study group in a dose of 0.4 mg/kg/rat per day (0.25 cc/rat per day), and 0.9% NaCl to the control group in a dose of 0.25 cc/rat per day. Incisions 5 cm in length were made on the back skin of the rats and the wounds were closed with a skin stapler found that melatonin may have a positive effect on both angiogenesis and wound healing(28).
Sources
(8) http://www.ncbi.nlm.nih.gov/pubmed/11115737
(9) http://www.ncbi.nlm.nih.gov/pubmed/11600542
(10) http://www.ncbi.nlm.nih.gov/pubmed/22622709
(11) http://www.ncbi.nlm.nih.gov/pubmed/12622846
(12) http://www.ncbi.nlm.nih.gov/pubmed/16207291
(12a) http://www.ncbi.nlm.nih.gov/pubmed/22074586
(13) http://www.ncbi.nlm.nih.gov/pubmed/22792106
(14) http://www.ncbi.nlm.nih.gov/pubmed/22724080
(15) http://www.ncbi.nlm.nih.gov/pubmed/22511571
(16) http://www.ncbi.nlm.nih.gov/pubmed/22019490
(17) http://www.ncbi.nlm.nih.gov/pubmed/22753734
(18) http://www.ncbi.nlm.nih.gov/pubmed/22500582
(19) http://www.ncbi.nlm.nih.gov/pubmed/22370283
(20) http://www.ncbi.nlm.nih.gov/pubmed/21870422
(21) http://www.ncbi.nlm.nih.gov/pubmed/21673362
(22) http://www.ncbi.nlm.nih.gov/pubmed/21441606
(23) http://www.ncbi.nlm.nih.gov/pubmed/23044640
(24) http://www.ncbi.nlm.nih.gov/pubmed/19486273
(25) http://www.ncbi.nlm.nih.gov/pubmed/10721041
(26) http://www.ncbi.nlm.nih.gov/pubmed/23129488
(27) http://www.ncbi.nlm.nih.gov/pubmed/23102587
(28) http://www.ncbi.nlm.nih.gov/pubmed/14669079
