Free Shipping on All Orders $75 Or More!

Your Trusted Brand for Over 35 Years

Life Extension Magazine

<< Back to September 2013

Melatonin: The Brain Hormone

September 2013

By Stephen Fredericks



Melatonin has been ignored or trivialized as simply a “sleep aid” ever since Life Extension introduced it to the world in 1992. But a burst of new studies now reveals that melatonin can protect your brain from many of the ravages of aging.

When we’re young, melatonin protects our brains from free radical attack. But after middle age, melatonin levels drop precipitously, leaving our brains increasingly susceptible to the growing impact of oxidative damage. Such damage leads to increased risk of neurodegenerative diseases and stroke, and increased vulnerability to the effects of head trauma.

Studies now show that melatonin supplementation can normalize oxidative damage in brain tissue. It can protect against the pathological changes seen in Alzheimer’s and Parkinson’s diseases, can shrink the size of the brain area involved in a stroke and can minimize brain swelling and dysfunction following a head injury.

But, like all preventive measures, brain protection with melatonin requires early action. You likely won’t get much benefit from melatonin if you wait until after onset of symptoms of neurodegeneration or until after a stroke or head injury claims some of your brain cells.

In order to keep your brain functioning in top condition, you need to support your dwindling supplies of brain-protective melatonin now.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.


  1. Gutierrez-Cuesta J, Sureda FX, Romeu M, et al. Chronic administration of melatonin reduces cerebral injury biomarkers in SAMP8. J Pineal Res. 2007 Apr;42(4):394-402.
  2. Pandi-Perumal SR, BaHammam AS, Brown GM, et al. Melatonin antioxidative defense: therapeutical implications for aging and neurodegenerative processes. Neurotox Res. 2013 Apr;23(3):267-300.
  3. Gupta YK, Gupta M, Kohli K. Neuroprotective role of melatonin in oxidative stress vulnerable brain. Indian J Physiol Pharmacol. 2003 Oct;47(4):373-86.
  4. Bondy SC, Lahiri DK, Perreau VM, et al. Retardation of brain aging by chronic treatment with melatonin. Ann N Y Acad Sci. 2004 Dec;1035:197-215.
  5. De Rooij SE. Melatonin deficiency hypothesis in delirium. A synthesis of current evidence. Rejuvenation Res. 2013 Apr 19. [Epub ahead of print]
  6. Lahiri DK, Chen DM, Lahiri P, Bondy S, Greig NH. Amyloid, cholinesterase, melatonin, and metals and their roles in aging and neurodegenerative diseases. Ann N Y Acad Sci. 2005 Nov;1056:430-49.
  7. Feng Z, Qin C, Chang Y, Zhang JT. Early melatonin supplementation alleviates oxidative stress in a transgenic mouse model of Alzheimer’s disease. Free Radic Biol Med. 2006 Jan 1;40(1):101-9.
  8. Niranjan R, Nath C, Shukla R. The mechanism of action of MPTP-induced neuroinflammation and its modulation by melatonin in rat astrocytoma cells, C6. Free Radic Res. 2010 Nov;44(11):1304-16.
  9. Ma J, Shaw VE, Mitrofanis J. Does melatonin help save dopaminergic cells in MPTP-treated mice? Parkinsonism Relat Disord. 2009 May;15(4):307-14.
  10. Borah A, Mohanakumar KP. Melatonin inhibits 6-hydroxydopamine production in the brain to protect against experimental parkinsonism in rodents. J Pineal Res. 2009 Nov;47(4):293-300.
  11. Reiter RJ, Sainz RM, Lopez-Burillo S, Mayo JC, Manchester LC, Tan DX. Melatonin ameliorates neurologic damage and neurophysiologic deficits in experimental models of stroke. Ann N Y Acad Sci. 2003 May;993:35-47; discussion 48-53.
  12. Ayer RE, Sugawara T, Zhang JH. Effects of melatonin in early brain injury following subarachnoid hemorrhage. Acta Neurochir Suppl. 2008;102:327-30.
  13. Wang Z, Ma C, Meng CJ, et al. Melatonin activates the Nrf2-ARE pathway when it protects against early brain injury in a subarachnoid hemorrhage model. J Pineal Res. 2012 Sep;53(2):129-37.
  14. Chang HM, Wu UI, Lan CT. Melatonin preserves longevity protein (sirtuin 1) expression in the hippocampus of total sleep-deprived rats. J Pineal Res. 2009 Oct;47(3):211-20.
  15. Cristofol R, Porquet D, Corpas R, et al. Neurons from senescence-accelerated SAMP8 mice are protected against frailty by the sirtuin 1 promoting agents melatonin and resveratrol. J Pineal Res. 2012 Apr;52(3):271-81.
  16. Lahiri DK, Chen D, Lahiri P, Rogers JT, Greig NH, Bondy S. Melatonin, metals, and gene expression: implications in aging and neurodegenerative disorders. Ann N Y Acad Sci. 2004 Dec;1035:216-30.
  17. Fernandez-Tresguerres Hernandez JA. Melatonina: old molecule, new medicament. An R Acad Nac Med (Madr). 2008;125(4):681-96.
  18. Feng Z, Zhang JT. Long-term melatonin or 17-beta-estradiol supplementation alleviates oxidative stress in ovariectomized adult rats. Free Radic Biol Med. 2005 Jul 15;39(2):195-204.
  19. Bubenik GA, Konturek SJ. Melatonin and aging: prospects for human treatment. J Physiol Pharmacol. 2011 Feb;62(1):13-9.
  20. Wang JZ, Wang ZF. Role of melatonin in Alzheimer-like neurodegeneration. Acta Pharmacol Sin. 2006 Jan;27(1):41-9.
  21. Liu RY, Zhou JN, van Heerikhuize J, Hofman MA, Swaab DF. Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer’s disease, and apolipoprotein E-epsilon4/4 genotype. J Clin Endocrinol Metab. 1999 Jan;84(1):323-7.
  22. Wu YH, Swaab DF. The human pineal gland and melatonin in aging and Alzheimer’s disease. J Pineal Res. 2005 Apr;38(3):145-52.
  23. Cardinali DP, Furio AM, Brusco LI. Clinical aspects of melatonin intervention in Alzheimer’s disease progression. Curr Neuropharmacol. 2010 Sep;8(3):218-27.
  24. Cardinali DP, Brusco LI, Liberczuk C, Furio AM. The use of melatonin in Alzheimer’s disease. Neuro Endocrinol Lett. 2002 Apr;23 Suppl 1:20-3.
  25. Cardinali DP, Furio AM, Brusco LI. The use of chronobiotics in the resynchronization of the sleep/wake cycle. Therapeutical application in the early phases of Alzheimer’s disease. Recent Pat Endocr Metab Immune Drug Discov. 2011 May;5(2):80-90.
  26. Zhu LQ, Wang SH, Ling ZQ, Wang DL, Wang JZ. Effect of inhibiting melatonin biosynthesis on spatial memory retention and tau phosphorylation in rat. J Pineal Res. 2004 Sep;37(2):71-7.
  27. Wang S, Zhu L, Shi H, et al. Inhibition of melatonin biosynthesis induces neurofilament hyperphosphorylation with activation of cyclin-dependent kinase 5. Neurochem Res. 2007 Aug;32(8):1329-35.
  28. Daniels WM, van Rensburg SJ, van Zyl JM, Taljaard JJ. Melatonin prevents beta-amyloid-induced lipid peroxidation. J Pineal Res. 1998 Mar;24(2):78-82.
  29. Lahiri DK, Chen D, Ge YW, Bondy SC, Sharman EH. Dietary supplementation with melatonin reduces levels of amyloid beta-peptides in the murine cerebral cortex. J Pineal Res. 2004 May;36(4):224-31.
  30. Feng Z, Chang Y, Cheng Y, et al. Melatonin alleviates behavioral deficits associated with apoptosis and cholinergic system dysfunction in the APP 695 transgenic mouse model of Alzheimer’s disease. J Pineal Res. 2004 Sep;37(2):129-36.
  31. Cardinali DP, Vigo DE, Olivar N, Vidal MF, Furio AM, Brusco LI. Therapeutic application of melatonin in mild cognitive impairment. Am J Neurodegener Dis. 2012;1(3):280-91.
  32. Furio AM, Brusco LI, Cardinali DP. Possible therapeutic value of melatonin in mild cognitive impairment: a retrospective study. J Pineal Res. 2007 Nov;43(4):404-9.
  33. Capitelli C, Sereniki A, Lima MM, Reksidler AB, Tufik S, Vital MA. Melatonin attenuates tyrosine hydroxylase loss and hypolocomotion in MPTP-lesioned rats. Eur J Pharmacol. 2008 Oct 10;594(1-3):101-8.
  34. Gutierrez-Valdez AL, Anaya-Martinez V, Ordonez-Librado JL, et al. Effect of chronic L-dopa or melatonin treatments after dopamine deafferentation in rats: dyskinesia, motor performance, and cytological analysis. ISRN Neurol. 2012;2012:360379.
  35. Patki G, Lau YS. Melatonin protects against neurobehavioral and mitochondrial deficits in a chronic mouse model of Parkinson’s disease. Pharmacol Biochem Behav. 2011 Oct;99(4):704-11.
  36. Ono K, Mochizuki H, Ikeda T, et al. Effect of melatonin on alpha-synuclein self-assembly and cytotoxicity. Neurobiol Aging. 2012 Sep;33(9):2172-85.
  37. Sae-Ung K, Ueda K, Govitrapong P, Phansuwan-Pujito P. Melatonin reduces the expression of alpha-synuclein in the dopamine containing neuronal regions of amphetamine-treated postnatal rats. J Pineal Res. 2012 Jan;52(1):128-37.
  38. Brito-Armas JM, Baekelandt V, Castro-Hernandez JR, Gonzalez-Hernandez T, Rodriguez M, Castro R. Melatonin prevents dopaminergic cell loss induced by lentiviral vectors expressing A30P mutant alpha-synuclein. Histol Histopathol. 2013 Feb 27.
  39. Atanassova PA, Terzieva DD, Dimitrov BD. Impaired nocturnal melatonin in acute phase of ischaemic stroke: cross-sectional matched case-control analysis. J Neuroendocrinol. 2009 Jul;21(7):657-63.
  40. Kitkhuandee A, Sawanyawisuth K, Johns NP, Kanpittaya J, Johns J. Pineal Calcification is Associated with Symptomatic Cerebral Infarction. J Stroke Cerebrovasc Dis. 2013 Feb 20.
  41. Deykun K, Pometlova M, Schutova B, Mares J. Modulations of behavioral consequences of minor cortical ischemic lesion by application of free radicals scavengers. Gen Physiol Biophys. 2011 Sep;30(3):263-70.
  42. Sewerynek E. Melatonin and the cardiovascular system. Neuro Endocrinol Lett. 2002 Apr;23 Suppl 1:79-83.
  43. Manev H, Uz T, Kharlamov A, Joo JY. Increased brain damage after stroke or excitotoxic seizures in melatonin-deficient rats. FASEB J. 1996 Nov;10(13):1546-51.
  44. Shinozuka K, Staples M, Borlongan CV. Melatonin-based therapeutics for neuroprotection in stroke. Int J Mol Sci. 2013 Apr 25;14(5):8924-47.
  45. Pei Z, Ho HT, Cheung RT. Pre-treatment with melatonin reduces volume of cerebral infarction in a permanent middle cerebral artery occlusion stroke model in the rat. Neurosci Lett. 2002 Feb 1;318(3):141-4.
  46. Pei Z, Pang SF, Cheung RT. Pretreatment with melatonin reduces volume of cerebral infarction in a rat middle cerebral artery occlusion stroke model. J Pineal Res. 2002 Apr;32(3):168-72.
  47. Hung YC, Chen TY, Lee EJ, et al. Melatonin decreases matrix metalloproteinase-9 activation and expression and attenuates reperfusion-induced hemorrhage following transient focal cerebral ischemia in rats. J Pineal Res. 2008 Nov;45(4):459-67.
  48. de Courten Myers GM, Kleinholz M, Wagner KR, Myers RE. Stroke assessment: morphometric infarct size versus neurologic deficit. J Neurosci Methods. 1998 Sep 1;83(2):151-7.
  49. Dietrichs E. Brain plasticity after stroke--implications for post-stroke rehabilitation. Tidsskr Nor Laegeforen. 2007 May 3;127(9):1228-31.
  50. Chen HY, Hung YC, Chen TY, et al. Melatonin improves presynaptic protein, SNAP-25, expression and dendritic spine density and enhances functional and electrophysiological recovery following transient focal cerebral ischemia in rats. J Pineal Res. 2009 Oct;47(3):260-70.
  51. Jang JW, Lee JK, Lee MC, Piao MS, Kim SH, Kim HS. Melatonin reduced the elevated matrix metalloproteinase-9 level in a rat photothrombotic stroke model. J Neurol Sci. 2012 Dec 15;323(1-2):221-7.
  52. Dong X, Song YN, Liu WG, Guo XL. Mmp-9, a potential target for cerebral ischemic treatment. Curr Neuropharmacol. 2009 Dec;7(4):269-75.
  53. Reiter RJ, Tan DX, Leon J, Kilic U, Kilic E. When melatonin gets on your nerves: its beneficial actions in experimental models of stroke. Exp Biol Med (Maywood). 2005 Feb;230(2):104-17.
  54. Tsai MC, Chen WJ, Tsai MS, Ching CH, Chuang JI. Melatonin attenuates brain contusion-induced oxidative insult, inactivation of signal transducers and activators of transcription 1, and upregulation of suppressor of cytokine signaling-3 in rats. J Pineal Res. 2011 Sep;51(2):233-45.
  55. Ismailoglu O, Atilla P, Palaoglu S, et al. The therapeutic effects of melatonin and nimodipine in rats after cerebral cortical injury. Turk Neurosurg. 2012;22(6):740-6.
  56. Flanagan SR, Cantor JB, Ashman TA. Traumatic brain injury: future assessment tools and treatment prospects. Neuropsychiatr Dis Treat. 2008 Oct;4(5):877-92.
  57. Sae-Teaw M, Johns J, Johns NP, Subongkot S. Serum melatonin levels and antioxidant capacities after consumption of pineapple, orange, or banana by healthy male volunteers. J Pineal Res. 2012 Oct 5.
  58. Thomas JN, Smith-Sonneborn J. Supplemental melatonin increases clonal lifespan in the protozoan Paramecium tetraurelia. J Pineal Res. 1997 Oct;23(3):123-30.
  59. Bonilla E, Medina-Leendertz S, Diaz S. Extension of life span and stress resistance of Drosophila melanogaster by long-term supplementation with melatonin. Exp Gerontol. 2002 May;37(5):629-38.
  60. Anisimov VN, Alimova IN, Baturin DA, et al. Dose-dependent effect of melatonin on life span and spontaneous tumor incidence in female SHR mice. Exp Gerontol. 2003 Apr;38(4):449-61.
  61. Rodriguez MI, Escames G, Lopez LC, et al. Improved mitochondrial function and increased life span after chronic melatonin treatment in senescent prone mice. Exp Gerontol. 2008 Aug;43(8):749-56.
  62. Kwon KJ, Kim JN, Kim MK, et al. Melatonin synergistically increases resveratrol-induced heme oxygenase-1 expression through the inhibition of ubiquitin-dependent proteasome pathway: a possible role in neuroprotection. J Pineal Res. 2011 Mar;50(2):110-23.
  63. Kwon KJ, Kim HJ, Shin CY, Han SH. Melatonin Potentiates the Neuroprotective Properties of Resveratrol Against Beta-Amyloid-Induced Neurodegeneration by Modulating AMP-Activated Protein Kinase Pathways. J Clin Neurol. 2010 Sep;6(3):127-37.
  64. Gallacher J, Elwood P, Pickering J, Bayer A, Fish M, Ben-Shlomo Y. Benzodiazepine use and risk of dementia: evidence from the Caerphilly Prospective Study (CaPS). J Epidemiol Community Health. 2012 Oct;66(10):869-73.
  65. McIntyre IM, Burrows GD, Norman TR. Suppression of plasma melatonin by a single dose of the benzodiazepine alprazolam in humans. Biol Psychiatry. 1988 May;24(1):108-12.
  66. McIntyre IM, Norman TR, Burrows GD, Armstrong SM. Alterations to plasma melatonin and cortisol after evening alprazolam administration in humans. Chronobiol Int. 1993 Jun;10(3):205-13.
  67. Billioti de Gage S, Begaud B, Bazin F, et al. Benzodiazepine use and risk of dementia: prospective population based study. BMJ. 2012;345:e6231.
  68. Potvin O, Hudon C, Forget H, et al. Prevalence of psychiatric disorders in community-dwelling older men and women with cognitive impairment no dementia: results from the ESA study. Aging Ment Health. 2012;16(2):218-27.
  69. Clay E, Falissard B, Moore N, Toumi M. Contribution of prolonged-release melatonin and anti-benzodiazepine campaigns to the reduction of benzodiazepine and z-drugs consumption in nine European countries. Eur J Clin Pharmacol. 2013 Apr;69(4):1-10.
  70. Mano H, Fukada Y. A median third eye: pineal gland retraces evolution of vertebrate photoreceptive organs. Photochem Photobiol. 2007 Jan-Feb;83(1):11-8.