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Nexx
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FIRSTLY NO MELATONIN DOESN'T CAUSE SUPPRESSION, ALSO IT WON'T MAKE U A GIGACHAD LIKE METRIBOLONE
MELATONIN AND SLEEP
MELATONIN MAKES YOU SLEEP LIKE A KID, BUT IF YOU TAKE SUDDEN RELEASE THEN YOU MAY WAKE UP AFTER A FEW HOURS
I'M NOT WASTING MY TIME ON EXPLAINING THE BENEFITS OF GOOD NIGHT SLEEP
MELATONIN AND BRAIN
A. Melatonin has neurotrophic effects. It co-localizes with the expression of BDNF and GDNF in some cells[20][21] and to stimulate their expression in stem cells, allowing them to diversify into mature cells[22].
B. For a review of melatonin’s neuroprotective character, see this citation[23].
C. There is much evidence for melatonin being particularly neuroprotective against the pathology of Parkinson’s disease[24].
D. Melatonin is being investigated for the treatment of Alzheimer’s disease [25]
E. Melatonin appears particularly useful for alleviating methamphetamine toxicity[26]. It may do the same for alcohol[27] (not just in the brain[28]).
MELATONIN AND AGING
A. Pharmacologic melatonin may improve aging[29].
B. Melatonin delays senescence[30].
C. Melatonin modulates sirtuin activity[31][32][33].
MELATONIN AND BLOOD PRESSURE
A. A meta-analysis of 5 controlled trials found that supplemental melatonin significantly reduced systolic and diastolic blood pressure[34]. This falls in line with theoretical evidence for melatonin and angiotensin modulating each other[35].
MELATONIN AND LIPIDS
A. A meta-analysis of 8 randomized controlled trials found that melatonin supplementation produced a large and significant reduction in serum triglycerides and a significant reduction in total serum cholesterol[36].
MELATONIN AND THE IMMUNE SYSTEM
A. Melatonin is immunomodulatory. It is synthesized by lymphocytes and the thymus. It stimulates natural killer cells and governs the release of T-helper 1 cells, B lymphocytes, and cytokine release[37].
B. In a randomized, double-blind, controlled study, 6 mg of melatonin reduced the TNF-alpha, interleukin-6, and C-reactive protein of obese women, indication a reduction in inflammation and oxidative stress[38].
MELATONIN AND CANCER
A. Melatonin is known to inhibit cancer development[39] and cancer metastasis[40].
B. Melatonin selectively triggers apoptosis in a variety of cancer cells[41].
C. Melatonin has been shown to inhibit breast cancer development, and it is thought that the reason night shift workers develop breast cancers more frequently is due to reduced melatonin synthesis[42].
D. Melatonin produces an anti-angiogenic effect by inhibits VEGF in liver cancer cells[43].
MELATONIN, INSULIN RESISTANCE, DIABETES, OBESITY, AND NAFLD
A. Melatonin regulates insulin sensitivity, producing insulin sensitivity early in the day and inducing insulin resistance when it is transmitted in the latter day[44]. It also influences GLUT4 expression, lipolysis, lipogenesis, fatty acid uptake, pancreatic islet function, and modulates IGF-1 activity.
B. A randomized, double-blind controlled trial found that 6 mg of melatonin significantly but minorly improved HbA1c, fasting blood glucose, and HDL-cholesterol among type 2 diabetics[45].
C. A randomized, double-blind controlled trial found that 10 mg of melatonin significantly improved insulin sensitivity, HDL-cholesterol, systolic and diastolic blood pressure, C-reactive protein, and metrics of oxidative stress among type 2 diabetics with coronary heart disease[46].
D. In a randomized, controlled trial, 10 mg of melatonin improved body weight reduction, antioxidant defense, and adipokine (cytokines released from adipose tissue, like leptin) secretion among obese dieters[47].
E. In a double-blind, controlled, crossover study, 8 mg of melatonin significantly improved some metrics of the metabolic syndrome[48].
F. Melatonin is particularly attractive for nonalcoholic fatty liver disease[49] and liver injury[50][51]. In a randomized, controlled trial, 10 mg of melatonin improved liver grade and C-reactive protein among sufferers of nonalcoholic fatty liver disease[52].
ALSO SOME PEOPLE MAY NOT EXPERIENCE ANYTHING FROM IT-
It is believed that a loss of response to melatonin supplementation is due to slow metabolism, particularly, to reduced activity of the CYP1A2 enzyme (found in 12-14% of people)[67].
A CONCERN-
H. Intuitively, twice a day dosing appears to damage sex hormone production by interfering with gonadotropin releasing hormone[66].
yes most of it is a copypasta ,I cba to write this much
MELATONIN AND SLEEP
MELATONIN MAKES YOU SLEEP LIKE A KID, BUT IF YOU TAKE SUDDEN RELEASE THEN YOU MAY WAKE UP AFTER A FEW HOURS
I'M NOT WASTING MY TIME ON EXPLAINING THE BENEFITS OF GOOD NIGHT SLEEP
MELATONIN AND BRAIN
A. Melatonin has neurotrophic effects. It co-localizes with the expression of BDNF and GDNF in some cells[20][21] and to stimulate their expression in stem cells, allowing them to diversify into mature cells[22].
B. For a review of melatonin’s neuroprotective character, see this citation[23].
C. There is much evidence for melatonin being particularly neuroprotective against the pathology of Parkinson’s disease[24].
D. Melatonin is being investigated for the treatment of Alzheimer’s disease [25]
E. Melatonin appears particularly useful for alleviating methamphetamine toxicity[26]. It may do the same for alcohol[27] (not just in the brain[28]).
MELATONIN AND AGING
A. Pharmacologic melatonin may improve aging[29].
B. Melatonin delays senescence[30].
C. Melatonin modulates sirtuin activity[31][32][33].
MELATONIN AND BLOOD PRESSURE
A. A meta-analysis of 5 controlled trials found that supplemental melatonin significantly reduced systolic and diastolic blood pressure[34]. This falls in line with theoretical evidence for melatonin and angiotensin modulating each other[35].
MELATONIN AND LIPIDS
A. A meta-analysis of 8 randomized controlled trials found that melatonin supplementation produced a large and significant reduction in serum triglycerides and a significant reduction in total serum cholesterol[36].
MELATONIN AND THE IMMUNE SYSTEM
A. Melatonin is immunomodulatory. It is synthesized by lymphocytes and the thymus. It stimulates natural killer cells and governs the release of T-helper 1 cells, B lymphocytes, and cytokine release[37].
B. In a randomized, double-blind, controlled study, 6 mg of melatonin reduced the TNF-alpha, interleukin-6, and C-reactive protein of obese women, indication a reduction in inflammation and oxidative stress[38].
MELATONIN AND CANCER
A. Melatonin is known to inhibit cancer development[39] and cancer metastasis[40].
B. Melatonin selectively triggers apoptosis in a variety of cancer cells[41].
C. Melatonin has been shown to inhibit breast cancer development, and it is thought that the reason night shift workers develop breast cancers more frequently is due to reduced melatonin synthesis[42].
D. Melatonin produces an anti-angiogenic effect by inhibits VEGF in liver cancer cells[43].
MELATONIN, INSULIN RESISTANCE, DIABETES, OBESITY, AND NAFLD
A. Melatonin regulates insulin sensitivity, producing insulin sensitivity early in the day and inducing insulin resistance when it is transmitted in the latter day[44]. It also influences GLUT4 expression, lipolysis, lipogenesis, fatty acid uptake, pancreatic islet function, and modulates IGF-1 activity.
B. A randomized, double-blind controlled trial found that 6 mg of melatonin significantly but minorly improved HbA1c, fasting blood glucose, and HDL-cholesterol among type 2 diabetics[45].
C. A randomized, double-blind controlled trial found that 10 mg of melatonin significantly improved insulin sensitivity, HDL-cholesterol, systolic and diastolic blood pressure, C-reactive protein, and metrics of oxidative stress among type 2 diabetics with coronary heart disease[46].
D. In a randomized, controlled trial, 10 mg of melatonin improved body weight reduction, antioxidant defense, and adipokine (cytokines released from adipose tissue, like leptin) secretion among obese dieters[47].
E. In a double-blind, controlled, crossover study, 8 mg of melatonin significantly improved some metrics of the metabolic syndrome[48].
F. Melatonin is particularly attractive for nonalcoholic fatty liver disease[49] and liver injury[50][51]. In a randomized, controlled trial, 10 mg of melatonin improved liver grade and C-reactive protein among sufferers of nonalcoholic fatty liver disease[52].
ALSO SOME PEOPLE MAY NOT EXPERIENCE ANYTHING FROM IT-
It is believed that a loss of response to melatonin supplementation is due to slow metabolism, particularly, to reduced activity of the CYP1A2 enzyme (found in 12-14% of people)[67].
A CONCERN-
H. Intuitively, twice a day dosing appears to damage sex hormone production by interfering with gonadotropin releasing hormone[66].
yes most of it is a copypasta ,I cba to write this much
[20] Niles, L. P., Armstrong, K. J., Castro, L. M. R., Dao, C. V., Sharma, R., McMillan, C. R., ... & Kirkham, D. L. (2004). Neural stem cells express melatonin receptors and neurotrophic factors: colocalization of the MT 1 receptor with neuronal and glial markers. BMC neuroscience, 5(1), 1-9. [21] Rincón Castro, L. M., Gallant, M., & Niles, L. P. (2005). Novel targets for valproic acid: up‐regulation of melatonin receptors and neurotrophic factors in C6 glioma cells. Journal of neurochemistry, 95(5), 1227-1236. [22] Kong, X., Li, X., Cai, Z., Yang, N., Liu, Y., Shu, J., ... & Zuo, P. (2008). Melatonin regulates the viability and differentiation of rat midbrain neural stem cells. Cellular and molecular neurobiology, 28(4), 569-579. [23] Alghamdi, B. S. (2018). The neuroprotective role of melatonin in neurological disorders. Journal of neuroscience research, 96(7), 1136-1149. [24] Srinivasan, V., Cardinali, D. P., Srinivasan, U. S., Kaur, C., Brown, G. M., Spence, D. W., ... & Pandi-Perumal, S. R. (2011). Therapeutic potential of melatonin and its analogs in Parkinson’s disease: focus on sleep and neuroprotection. Therapeutic advances in neurological disorders, 4(5), 297-317. [25] Shukla, M., Govitrapong, P., Boontem, P., Reiter, R. J., & Satayavivad, J. (2017). Mechanisms of melatonin in alleviating Alzheimer's disease. Current neuropharmacology, 15(7), 1010-1031. [26] Nopparat, C., Porter, J. E., Ebadi, M., & Govitrapong, P. (2010). The mechanism for the neuroprotective effect of melatonin against methamphetamine‐induced autophagy. Journal of pineal research, 49(4), 382-389. [27] Al Kury, L. T., Zeb, A., Abidin, Z. U., Irshad, N., Malik, I., Alvi, A. M., ... & Shah, F. A. (2019). Neuroprotective effects of melatonin and celecoxib against ethanol-induced neurodegeneration: a computational and pharmacological approach. Drug Design, Development and Therapy, 13, 2715. [28] Mishra, A., Paul, S., & Swarnakar, S. (2011). Downregulation of matrix metalloproteinase-9 by melatonin during prevention of alcohol-induced liver injury in mice. Biochimie, 93(5), 854-866. [29] Poeggeler, B. (2005). Melatonin, aging, and age-related diseases. Endocrine, 27(2), 201-212. [30] Wang, P., Yin, L., Liang, D., Li, C., Ma, F., & Yue, Z. (2012). Delayed senescence of apple leaves by exogenous melatonin treatment: toward regulating the ascorbate–glutathione cycle. Journal of pineal research, 53(1), 11-20. [31] Mayo, J. C., Sainz, R. M., Gonzalez Menendez, P., Cepas, V., Tan, D. X., & Reiter, R. J. (2017). Melatonin and sirtuins: a “not‐so unexpected” relationship. Journal of pineal research, 62(2), e12391. [32] Cristòfol, R., Porquet, D., Corpas, R., Coto‐Montes, A., Serret, J., Camins, A., ... & Sanfeliu, C. (2012). Neurons from senescence‐accelerated SAMP8 mice are protected against frailty by the sirtuin 1 promoting agents melatonin and resveratrol. Journal of pineal research, 52(3), 271-281. [33] Dezfouli, M. A., Zahmatkesh, M., Farahmandfar, M., & Khodagholi, F. (2019). Melatonin protective effect against amyloid β-induced neurotoxicity mediated by mitochondrial biogenesis; involvement of hippocampal Sirtuin-1 signaling pathway. Physiology & behavior, 204, 65-75. [34] Hadi, A., Ghaedi, E., Moradi, S., Pourmasoumi, M., Ghavami, A., & Kafeshani, M. (2019). Effects of melatonin supplementation on blood pressure: a systematic review and meta-analysis of randomized controlled trials. Hormone and Metabolic Research, 51(03), 157-164. [35] Campos, L. A., Cipolla-Neto, J., Amaral, F. G., Michelini, L. C., Bader, M., & Baltatu, O. C. (2013). The angiotensin-melatonin axis. International Journal of Hypertension, 2013. [36] Mohammadi-Sartang, M., Ghorbani, M., & Mazloom, Z. (2018). Effects of melatonin supplementation on blood lipid concentrations: a systematic review and meta-analysis of randomized controlled trials. Clinical Nutrition, 37(6), 1943-1954. [37] Mohamed, M., Srinivasan, V., Maestroni, G., Rosenstein, R. E., & Oter, S. (2014). Melatonin and immune function: clinical significance. In Melatonin and Melatonergic Drugs in Clinical Practice (pp. 143-157). Springer, New Delhi. [38] Alamdari, N. M., Mahdavi, R., Roshanravan, N., Yaghin, N. L., Ostadrahimi, A. R., & Faramarzi, E. (2015). A double-blind, placebo-controlled trial related to the effects of melatonin on oxidative stress and inflammatory parameters of obese women. Hormone and Metabolic Research, 47(07), 504-508. [39] Reiter, R. J., Rosales-Corral, S. A., Tan, D. X., Acuna-Castroviejo, D., Qin, L., Yang, S. F., & Xu, K. (2017). Melatonin, a full service anti-cancer agent: inhibition of initiation, progression and metastasis. International journal of molecular sciences, 18(4), 843. [40] Su, S. C., Hsieh, M. J., Yang, W. E., Chung, W. H., Reiter, R. J., & Yang, S. F. (2017). Cancer metastasis: Mechanisms of inhibition by melatonin. Journal of pineal research, 62(1), e12370. [41] Bizzarri, M., Proietti, S., Cucina, A., & Reiter, R. J. (2013). Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer: a review. Expert opinion on therapeutic targets, 17(12), 1483-1496. [42] Hill, S. M., Belancio, V. P., Dauchy, R. T., Xiang, S., Brimer, S., Mao, L., ... & Frasch, T. (2015). Melatonin: an inhibitor of breast cancer. Endocrine-related cancer, 22(3), R183-R204. [43] Carbajo-Pescador, S., Ordoñez, R., Benet, M., Jover, R., García-Palomo, A., Mauriz, J. L., & González-Gallego, J. (2013). Inhibition of VEGF expression through blockade of Hif1α and STAT3 signalling mediates the anti-angiogenic effect of melatonin in HepG2 liver cancer cells. British journal of cancer, 109(1), 83-91. [44] Cipolla‐Neto, J., Amaral, F. G., Afeche, S. C., Tan, D. X., & Reiter, R. J. (2014). Melatonin, energy metabolism, and obesity: a review. Journal of pineal research, 56(4), 371-381. [45] Rezvanfar, M. R., Heshmati, G., Chehrei, A., Haghverdi, F., Rafiee, F., & Rezvanfar, F. (2017). Effect of bedtime melatonin consumption on diabetes control and lipid profile. International Journal of Diabetes in Developing Countries, 37(1), 74-77. [46] Raygan F, Ostadmohammadi V, Bahmani F et al. Melatonin administration lowers biomarkers of oxidative stress and cardio-metabolic risk in type 2 diabetic patients with coronary heart disease: A randomized, double-blind, placebo-controlled trial [47] Szewczyk-Golec, K., Rajewski, P., Gackowski, M., Mila-Kierzenkowska, C., Wesołowski, R., Sutkowy, P., ... & Woźniak, A. (2017). Melatonin supplementation lowers oxidative stress and regulates adipokines in obese patients on a calorie-restricted diet. Oxidative medicine and cellular longevity, 2017. [48] Goyal, A., Terry, P. D., Superak, H. M., Nell-Dybdahl, C. L., Chowdhury, R., Phillips, L. S., & Kutner, M. H. (2014). Melatonin supplementation to treat the metabolic syndrome: a randomized controlled trial. Diabetology & metabolic syndrome, 6(1), 124. [49] Zhou, H., Du, W., Li, Y. E., Shi, C., Hu, N., Ma, S., ... & Ren, J. (2018). Effects of melatonin on fatty liver disease: The role of NR 4A1/DNA‐PK cs/p53 pathway, mitochondrial fission, and mitophagy. Journal of Pineal Research, 64(1), e12450. [50] Zhang, J. J., Meng, X., Li, Y., Zhou, Y., Xu, D. P., Li, S., & Li, H. B. (2017). Effects of melatonin on liver injuries and diseases. International Journal of Molecular Sciences, 18(4), 673. [51] Mortezaee, K., & Khanlarkhani, N. (2018). Melatonin application in targeting oxidative‐induced liver injuries: A review. Journal of Cellular Physiology, 233(5), 4015-4032. [52] Pakravan, H., Ahmadian, M., Fani, A., Aghaee, D., Brumanad, S., & Pakzad, B. (2017). The effects of melatonin in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Advanced biomedical research, 6.
[66] Amano, M., Iigo, M., Ikuta, K., Kitamura, S., Okuzawa, K., Yamada, H., & Yamamori, K. (2004). Disturbance of plasma melatonin profile by high dose melatonin administration inhibits testicular maturation of precocious male masu salmon. Zoological science, 21(1), 79-85. [67] Braam, W., Van Geijlswijk, I., Keijzer, H., Smits, M. G., Didden, R., & Curfs, L. M. (2010). Loss of response to melatonin treatment is associated with slow melatonin metabolism. Journal of Intellectual Disability Research, 54(6), 547-555
[66] Amano, M., Iigo, M., Ikuta, K., Kitamura, S., Okuzawa, K., Yamada, H., & Yamamori, K. (2004). Disturbance of plasma melatonin profile by high dose melatonin administration inhibits testicular maturation of precocious male masu salmon. Zoological science, 21(1), 79-85. [67] Braam, W., Van Geijlswijk, I., Keijzer, H., Smits, M. G., Didden, R., & Curfs, L. M. (2010). Loss of response to melatonin treatment is associated with slow melatonin metabolism. Journal of Intellectual Disability Research, 54(6), 547-555
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