A huge amount of animal research has been done on melatonin.  As of January, 2005, over 11,000 studies were listed on PubMed mentioning melatonin.  Melatonin increased longevity in rats and mice in 12 different studies, although in 8 others no difference was found. There is very strong evidence from 17 animal studies that melatonin helps reduce the severity of strokes, sub-arachnoid hemorrhages, closed head injury, and fetal asphyxia.  Animal research is also appears favorable for preventing and possibly treating Alzheimer's disease.  

Still more animal research showing benefit of melatonin in anesthesia, spastic bladder, cataracts, heart attacks, heavy metal brain damage, interstitial cystitis, cocaine and morphine withdrawal, medication side-effects including NSAID stomach ulcers, stress ulcers, colitis, age-related hearing loss, rejuvenation of the immune system, leukemia, cholestatic jaundice, umbilical cord occulsion, uterine adhesions after surgery, meningitis, obesity, scorpion bites, sepsis, spinal cord injury, skin aging, toxic damage to the kidney, liver, and heart, and x-ray damage.  

Many of the benefits appear due to melatonin's anti-oxidant ability, which in multiple studies has been shown to be stronger and more effective than other anti-oxidants.  Obviously, human research is needed.  Many are calling for such research, especially on stroke and heart attack victims.  However, since there are not big profits in melatonin, little human research is being done.

Aging: Melatonin-induced Reduction in Age-related Oxidative Damage in Mice. Lipid peroxidation, GSSG and acid phosphatase were reduced (P < 0.001) in melatonin-treated mice. Age-induced decline in the level of GSH, GSH-Px and alkaline phosphatase activity were inhibited significantly by melatonin for 3 months starting at age 16 months. Manda K, Bhatia AL. University of Rajasthan, Jaipur, India. Biogerontology. 2003;4(3):133-9

Aging: Melatonin and Acetyl-L-Carnitine Each Partially Reverse Exploratory Behavior Declines in Aged Mice: 8 weeks treatment of 25-month-old mice also lowered elevated nitic oxide synthase 1 to youthful levels with ALCAR and partially restored them with melatonin. Sharman EH, et al. University of California Irvine, Irvine, CA. Brain Res. 2002 Dec 13;957(2):223-30.

Alcohol Brain Damage Reduced: Protective effects of melatonin against ethanol-induced reactive gliosis in hippocampus and cortex of young and aged rats. Baydas G, Tuzcu M. Firat University, Turkey. Exp Neurol. 2005 Jul;194(1):175-81.

Alzheimer's: Inhibition of Melatonin Biosynthesis with Haloperidol Induces Neurofilament Hyperphosphorylation with Activation of Cyclin-dependent Kinase 5 in rats. Haloperidol, a specific inhibitor of 5-hydroxyindole-O-methyltransferase, resulted in significantly decreased level of serum melatonin with a concomitantly increased phosphorylation of neurofilament proteins. Wang S, et al. Tongji Medical College, Wuhan, China, . Neurochem Res 2007 Mar 31.

Alzheimer's: Melatonin Suppresses Amyloid-beta-induced Glial Activation in Rat Hippocampus: Growing evidence indicates that activated glia, as a result of chronic inflammation, are associated with amyloid-beta peptide (Abeta) deposits in the brain of Alzheimer's disease patients. Cells expressing IL-1alpha and C1q were significantly decreased in hippocampus by pretreatment with melatonin at doses of 0.1 mg/kg and 1 mg/kg, but not at the dose of 0.01 mg/kg. The data indicate that melatonin inhibited expressions of proinflammatory factors, which may contribute to improvement of learning and memory function in AD. Shen Y et al. Anhui Univ., Hefei, China. Arch Med Res 2007 Apr;38(3):284-90.

Alzheimer's: Memory of Older Rats, But Not Young or Adult Rats Helped: The chronic administration of melatonin ord epitalon (a synthetic tetrapeptide increasing melatonin production) was studied in LIO rats in the course of aging for 2 years. Melatonin did not influence the learning processes in young and adult animals but it was found to contribute to optimization of the brain cognitive function in rats in the course of aging, by improving the protracted memory process. Epitalon administered in a daily dose of 0.1 microg per animal beginning with the age of 4 months showed mnemotropic properties (decreasing the extent of memory disorders) in old rats under conditions of the shuttle labyrinth test. Comparative study of the effects of melatonin and epitalon on the protracted memory under the shuttle labyrinth test conditions in rats in the course of aging. Eksp Klin Farmakol 2006 Nov-Dec;69(6):13-6.

Alzheimer's: Mouse Model Helped: Melatonin alleviates behavioral deficits associated with apoptosis and cholinergic system dysfunction in the APP 695 transgenic mouse model of Alzheimer's disease. Feng Z, et al. J Pineal Res. 2004 Sep;37(2):129-36; Similar findings with increased survival. J Neurochem. 2003 Jun;85(5):1101-8. Similar, Feng Z et al. Free Radic Biol Med 2006 Jan;40:101-9.

Alzheimer's: Mouse Model Not Helped:  Tg2576 transgenic mice with heavy amyloid plaques not helped by 4 months of melatonin from age 14 months. Quinn J, et al. Portland, OR, VA , Brain Res. 2005 Mar 10;1037(1-2):209-13.

Alzheimer's: Inhibiting Melatonin Biosynthesis Reduced Spatial Memory and Increased Tau Phosphorylation in Rats. Zhu LQ, et al. Huazhong University, Wuhan, China.

Alzheimer's: Prevents of Isoproterenol-induced Tau Hyperphosphorylation in the Rat: Wang XC, et al. Huazhong University, Wuhan, China. Sheng Li Xue Bao. 2005 Feb 25;57(1):7-12

Alzheimer’s: Melatonin Blocks Haldol-Induced Hyperphosphorylation: Melatonin protects SH-SY5Y neuroblastoma cells from calyculin A-induced neurofilament impairment and neurotoxicity. Haloperidol is a specific inhibitor of 5-hydroxyindole-O-methyltransferase, a key enzyme in melatonin biosynthesis. Injection of haloperidol into the lateral ventricle and into peritoneal cavity compromises spatial memory retention of rats and induces hyperphosphorylation of microtubule-associated protein tau. Supplementation with melatonin by prior injection for 1 week and reinforcement during the haloperidol administration significantly improved memory retention deficits, arrested tau hyperphosphorylation and oxidative stress, and restored PP-2A activity. These results strongly support the involvement of decreased melatonin in Alzheimer-like spatial memory impairment and tau hyperphosphorylation, and PP-2A may play a role in mediating aberrant melatonin-induced lesions. J Pineal Res. 2004 Sep;37(2):71-7

Alzheimer’s: Melatonin Helped Mouse Model: A transgenic (Tg) mouse model for Alzheimer's disease mimics the accumulation of senile plaques, neuronal apoptosis and memory impairment. Melatonin reduces beta-amyloid (Abeta)-induced neurotoxicity. In this four month study of 8 month old Tg mice, melatonin alleviated learning and memory deficits. Choline acetyltransferase (ChAT) activity also decreased in the frontal cortex and hippocampus of APP 695 Tg mice compared with non-Tg littermates. Melatonin supplementation increased ChAT activity in the frontal cortex and hippocampus. Melatonin reduced the number of apoptotic neurons. Melatonin decreased the Abeta deposits. Melatonin alleviates behavioral deficits associated with apoptosis and cholinergic system dysfunction in the APP 695 transgenic mouse model of Alzheimer's disease. Feng Z, et al. Peking Union Medical College, Beijing, China. J Pineal Res. 2004 Sep;37(2):129-36 

Alzheimer's: Improves Cognitive Impairment: Long-term effects of melatonin or 17 beta-estradiol on improving spatial memory performance in cognitively impaired, ovariectomized adult rats. Feng Z, et al. J Pineal Res. 2004 Oct;37(3):198-206

Alzheimer’s: Melatonin May Help: Dietary supplementation results in a rise in endogenous melatonin in serum as well as other tissues. Elevated brain melatonin results in a significant reduction in levels of toxic cortical Abeta of both 40- and 42-amino-acid forms. Dietary melatonin supplementation may slow the neurodegenerative changes associated with brain aging and that the depletion of melatonin in the brain of aging mice may, in part, account for this adverse change. Lahiri DK, Chen D, et al. Indiana University. Ann N Y Acad Sci. 2004 Dec;1035:216-30

Alzheimer's: Isoproterenol-induced Tau Hyperphosphorylation Prevented by Melatonin Pretreatment in the rat. Wang XC, et al. Huazhong University, Wuhan, China. Sheng Li Xue Bao. 2005 Feb 25;57(1):7-12

Anesthesia: Melatonin Pretreatment Caused a Rapid Onset of Anesthesia after Ketamine and Thiopental administration while the duration of action of these agents was prolonged. Budhiraja S, et al. Haryana, India. [email protected]. Methods Find Exp Clin Pharm 2005 Dec;27(10):697-9.

Anxiety: Melatonin No Benefit: Melatonin, which does modify extracellular levels of 5-HT or noradrenaline, has been ineffective in all animal models of anxiolytic activity. In contrast to melatonin, and reflecting blockade of 5-HT(2C) receptors, agomelatine is active in several models of anxiolytic properties in rodents. The anxiolytic profile of agomelatine differs from that of benzodiazepines from which it may also be distinguished by its contrasting influence on corticolimbic monoaminergic pathways. Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT(2C) receptor blockade. Millan MJ, Brocco M, et al. Institut de Recherches Servier, Paris, France. Psychopharmacology (Berl). 2005 Feb;177(4):448-58

Bile Duct: Protected Against Cholestatic Liver Damage: Low dose of Melatonin Protected Against Cholestatic Oxidative Stress after Common Bile Duct Ligation in rats. Esrefoglu M, et al. Inonu University, Turkey. World J Gastroenterol. 2005 Apr 7;11(13):1951-6.

Bladder: Melatonin treatment improved age induced overactivity in bladder function, increasing bladder capacity. If similar effects can be demonstrated in humans, melatonin treatment may be a new approach to decrease the impact of age related bladder disorders. Gomez-Pinilla PJ et al, University of Extremadura, Caceres, Spain.
J Urol 2007 Apr;177(4):1558-61.

Bladder: Reduced Protamine sulfate induced Bladder Injury in Mice; May Help Interstitial Cystitis: An anti-oxidant effect reducing lipid peroxidation. Cetinel S, et al. Marmara University, Istanbul, Turkey. J Urol. 2003 Apr;169(4):1564-8

Brain: Protects Against Maternal Deprivation Damage: Protective effect of melatonin against maternal deprivation-induced acute hippocampal damage in infant rats. Tugyan K, et al. Dokuz Eylul University, Izmir, Turkey.

Brain Toxicity from Aluminum Protected Against by Melatonin in Rabbits: Aluminum-induced neurotoxicity and oxidative damage in rabbits: Protective effect of melatonin. Abd-Elghaffar SK, et al. Assiut University, Egypt. Neuro Endocrinol Lett. 2005 Oct 30;26(5)

Brain: Melatonin Reduces Iron, Aluminum, Lead Neuronal Death in rat Cerebral Cortex. Hayter CL, et al. Monash University, Victoria, Australia. Neurosci Lett. 2004 May 27;362(3):182-4; Similar with aluminum. J Pineal Res. 2003 Aug;35(1):32-9; Similar with lead. Cell Mol Biol Lett. 2003;8(2):461-70.

Brain: Melatonin Anti-convulsant Effect in Animals and Enhances Seizure Medications: Ray M, et al. Delhi, India. Methods Find Exp Clin Pharmacol. 2004 Apr;26(3):177-81.

Brain: Protects Against Viral Encephalitis Damage: Melatonin, a potent antioxidant, has shown to be beneficial in murine Venezuelan equine encephalomyelitis (VEE) virus infection. J Pineal Res 2007 Mar;42(2):107-12.

Brain: Melatonin Helped Blood Flow to Brain in Old Rats: Melatonin treatment of old rats induced hypertrophy of the arteriolar wall, prevented the age-linked decrease in cerebral arteriolar distensibility and decreased the lower limit of cerebral blood flow. Dupuis F, et al. Nancy, France. British Journal of Pharmacology (2004) 141, 399-406.

Brain: Helped Closed Head Injuries in Rats: The area of damage was cut in half. An anti-oxidant effect was thought to be the mechanism. Beni SM, et al. Hebrew University of Jerusalem. FASEB J. 2004 Jan;18(1):149-51. Similar results were found with 7-day older rats. The authors suggest melatonin may help human children with closed head injuries. Neurosci Lett. 2005 Jun 18. Ed: Currently, no treatment on humans has any proven beneficial impact at reducing the area of damage. In an extensive literature search of pharmacotherapy of behavior disorders in TBI, 63 papers were selected for data synthesis: 13 were randomized controlled trials, 8 prospective observational studies, 4 retrospective studies, 25 case series and 13 single case studies. There was no strong evidence to suggest that drugs are effective in the treatment of behavior disorders in patients with TBI. Weak evidence, primarily based on case studies, suggest that psychostimulants may be effective in the treatment of apathy, inattention and slowness; high dose beta-blockers in the treatment of agitation and aggression; anti-convulsants and anti-depressants (particularly SSRIs) in the treatment of agitation and aggression, particularly in the context of an affective disorder; and possibly a specific neuroleptic methotrimeprazine in the treatment of agitation in the post-acute stage of Acquired Brain Injury. Some drugs that are effective in some patients have been shown to be ineffective in others. Some drugs, particularly lithium and dopaminergic drugs could cause adverse effects and deterioration in some patients. The role of pharmacotherapy in the management of behaviour disorders in traumatic brain injury patients. Deb S, et al. University of Birmingham, UK. Brain Inj. 2004 Jan;18(1):1-31.

Brain: Melatonin against radiation induced damage in mouse cerebellum and Purkinje cells. Sisodia R, et al. University of Rajasthan, Jaipur, India. J Radiol Prot 2006 Jun;26(2):227-34.

Brain: Melatonin Protects Rats Against Alcohol Induced Memory Impairment: Especially older rats were protected. Hippocampus and neural cell adhesion molecules protected via anti-oxidant properties. Baydas, et al. Firat University, Turkey. J Pineal Res. 2005 Nov;39(4):346-52.

Brain: Melatonin Protects Rats Against Toluene-containing Thinner Intoxication by Reducing Reactive Gliosis: Baydas G, et al. Firat University, Turkey. Toxicol Lett. 2003 Feb 3;137(3):169-74.

Brain: Pinealectomy Causes Hippocampal Cell Loss; Melatonin Replacement Prevents and Leads to Neurogenesis: Rat study. Neurobiol Aging 2006 Jan 10.

Brain: Meningitis Damage Reduced: In experimental animal models, brain-derived neurotrophic factor protected against brain injury and improved hearing while melatonin, which has antioxidant properties among other effects, reduced neuronal death. Curr Opin Pediatr 2006 Apr;18(2):112-8.

Brain: Helps Various Animal Models of Alzheimer's: Melatonin had many beneficial effects in experimental models of AD, including improvement of cognitive function, anti-oxidative injury, anti-apoptosis, inhibition of beta-amyloid (Abeta) deposition and Abeta fiber formation. Several groups have shown that melatonin has an inhibitory effect on tau protein hyperphosphorylation. Acto Pharmacol Sin Feb 2006.

Cancer: Breast: Melatonin Lengthened Survival and Increased Latency in Induced Rat Cancer: Melatonin started one month before DMBA was applied to induce breast cancers. Saez MC, et al. University of Extremadura, Spain. Mol Cell Biochem. 2005 Jan;268(1-2):25-31.

Cancer: Ovarian Linked to Light; Slowed by Melatonin: The growth of solid ovarian tumors in the turkey breeder hen was promoted by long photoperiods and ceased, to the point of remission, on short photoperiods. Thus, ovarian adenocarcinoma in turkeys can be completely manipulated by photoperiod. In addition, treatment with melatonin attenuated tumor growth. Moore CB, NC State, Neuro Endocrinol Lett. 2004 Feb-Apr;25(1-2):94-101; 

Cancer: Epidemiological observations on increased risk of breast cancer in night shift workers, flight attendants, radio and telegraph operators and on decreased risk in blind women are in accordance with the results of experiments in rodents. Treatment with pineal indole hormone melatonin inhibits carcinogenesis in pinealectomized rats or animals kept at the standard light/dark regimen (LD) or at the constant illumination (LL) regimen. Neuro Endocrinol Lett. 2002 Jul;23 Suppl 2:28-36

Cancer: Breast: Rats with Advanced Tumors Live Longer with Melatonin: Melatonin increases the survival time of animals with untreated mammary tumours: Neuroendocrine stabilization. Saez MC, et al. University of Extremadura, Badajoz, Spain

Cancer: Leukemia: Increases Survival: In mice bearing mid-stage leukemia, daily administration of melatonin results in a survival index of 30-40% vs. 0% in untreated mice. Miller SC, et al. McGill. Int J Exp Pathol 2006 Apr;87(2):81-7.

Cancer: Prostate Cancer Slowed: Melatonin reduces prostate cancer cell growth leading to neuroendocrine differentiation via a receptor and PKA independent mechanism. Sainz RM, et al. Prostate. 2004 Sep 17

Cancer: Melatonin Causes Liver Cancer Cell Apoptosis: Melatonin significantly inhibited the growth of H22 hepatocarcinoma cells. Incubated with melatonin, the percentage of apoptotic cells was increased and cell cycle of the tumor cells extended. Inhibitory effect of melatonin on the growth of H22 hepatocarcinoma cells by inducing apoptosis. Qin L, Wang X, et al. Huazhong University, Wuhan. J Huazhong Univ Sci Technolog Med Sci. 2004;24(1):19-21, 31.

Cataracts Reduced by Melatonin in Rats: Use of melatonin to prevent selenite-induced cataract formation in rat eyes. Credited to anti-oxidant effect. Yagci R, et al. Ankara, Turkey. Curr Eye Res 2006 Oct;31(10):845-50.

Cell Phone Radiation Skin Damage Reduced in Rats: Most cell phones emit their radiation at 900 mHz. This can result in oxidative skin damage in rats.  Ayata A, et al. Suleyman Demirel University, Isparta, Turkey.

Cholesterol: Melatonin Increases Good HDL Cholesterol: Hussain et al.  University of Baghdad, Iraq.
Melatonin significantly reduced cholesterol absorption in rats fed a high cholesterol diet and caused significant decreases in total cholesterol, TG, VLDL- and LDL-cholesterol in the plasma and contents of cholesterol and TG in the liver. The level of HDL cholesterol was significantly increased after melatonin. J {ineal Res 2007 Apr;42(3):267-71.

Cholesterol: Melatonin Reduces Cholesterol Accumulation From High Cholesterol Diet in the Blood and Liver of Mice. Sener G, et al. Marmara University, Turkey. J Pineal Res. 2004 Apr;36(3):212-6

Cocaine-Induced Anxiety on Administration and Withdrawal Reduced in Rats. Zhdavona et al. MIT. Brain Res. 2002 Nov 29;956(2):323-31.

Colitis: Change of nitric oxide in experimental colitis and its inhibition by melatonin in vivo and in vitro. Mei Q, et al. Anhui Medical University, Hefei, China. Postgrad Med J. 2005 Oct;81(960):667-72.

Depression: Melatonin No Effect on Serotonin Receptors: Agomelatine (S 20098) is a novel antidepressant drug with melatonin receptor agonist and 5-HT(2C) receptor antagonist properties. Desensitization of 5-HT(1A) autoreceptors in the dorsal raphe nucleus (DRN) occurs after chronic administration of several classes of antidepressants. Neither acute nor chronic treatment with agomelatine changed the density of 5-HT(1A) receptors. Parallel experiments with melatonin and fluoxetine showed that the former was unable to affect 5-HT(1A) receptors whereas the latter decreased both the 5-HT(1A) receptor-mediated [(35)S]GTP-gamma-S binding and the potency of ipsapirone, a 5-HT(1A) receptor agonist, to inhibit neuronal firing in the DRN. Thus, the action of agomelatine is not mediated through the same mechanisms as SSRIs or tricyclics. Differential effects of the novel antidepressant agomelatine (S 20098) versus fluoxetine on 5-HT1A receptors in the rat brain. Hanoun N, et al. Pitie-Salpetriere, Paris, France. Neuropharmacology. 2004 Sep;47(4):515-26. 

Depression: Helped in Two Animal Models for Depression: Melatonin has been demonstrated to increase activity in the forced swim test (FST), a putative model of antidepressant efficacy, indicating that it may possess antidepressant-like qualities. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Sep;27(6):905-11; Melatonin also had an antidepressant type effect on the tail suspension test in mice. Mantovani M, et al. Universidade Federal de Santa Catarina, Florianopolis, Brazil. Neurosci Lett. 2003 May 29;343(1):1-4

Depression: Melatonin Receptor (MT1) Knockout Mice Display Depression-like behaviors and deficits in sensorimotor gating. Well ZM, et al. Ohio State University. Brain Res Bull 2006 Feb 15;68(6):425-9.

Diabetes: Protects Aorta Against Diabetic Damage: Melatonin treatment protects against diabetes-induced functional and biochemical changes in rat aorta and corpus cavernosum. Paskaloglu K, et al. Eur J Pharmacol. 2004 Sep 24;499(3):345-54

Diabetes: Protects Against Kidney Injury: Melatonin is more effective than taurine and 5-hydroxytryptophan against hyperglycemia-induced kidney-cortex tubules injury (. Derlacz RA, et al. Warsaw University, Poland. J Pineal Res 2007 Mar;42(2):203-9.

Eye: Melatonin Protective Against Nitric Oxide Retinal Damage: Effects of melatonin on the nitric oxide treated retina. Siu AW, et al. Centro de Investigacion Biomedical de Occidente, Guadalajara, Jalisco, Mexico. Br J Ophthalmol. 2004 Aug;88(8):1078-81

Eye: Melatonin Better than Vitamin E in Protecting Against Ischemia/Reperfusion Injury in Guinea Pigs: Yilmaz et al, Firat Univ. Turkey. Eur J Ophthalmol. 2002 Nov-Dec;12(6):443-9.

Fertility Downregulated: Melatonin appears to downregulate the production of kisspeptin which initiates the fertility process in seasonal species. Rev Endocrin Metab Disord.  2007 Mar 23

GI: Melatonin Helps Bowel Recovery After Massive Resection: Rats underwent 90% small bowel resection and suffered from diarrhea and weight loss between the first and the sixth postoperative days. The body weight of the SBR/melatonin group showed significant increases at the beginning of postoperative day 10 and day 21 in comparison to that of the SBR/untreated group. The rats treated with melatonin had significantly greater villus height and crypt cell mitosis, while the mucosal thickness was significantly increased. Effects of melatonin administration on intestinal adaptive response after massive bowel resection in rats. Ozturk H, et al. Diyarbakir, Turkey. Dig Dis Sci 2006 Feb;51(2):333-7.

GI: Methotrexate Intestinal Injury Reduced: Methotrexate often causes diarrhea and malabsorption due to injury of the intestinal wall. Melatonin helped. Cell Biochem Funct. 2004 May-Jun;22(3):169-78

GI: Colitis From Acetic Acid or TNBS Helped in Mice: Two animal models of human colitis, i.e., induced by acetic acid and TNBS, were reduced with blockage of nitric oxide and prostaglandin E(2) and of activation of inducible nitric oxide synthetase (iNOS) and COX-2. Dong WG, et al. Wuhan University, China. World J Gastroenterol. 2003 Jun;9(6):1307-11

GI: Colitis From Dinitrobenzene sulfonic acid Helped in Rats: Cuzzocrea S, et al. University of Messina, Italy. J Pineal Res. 2001 Jan;30(1):1-12.

GI: Enteritis from Methotrexate Helped in Rats by Melatonin: Jahovic N, et al. Marmara University,  Istanbul, Turkey. Cell Biochem Funct. 2004 May-Jun;22(3):169-78

Hair: Helps Regrowth in Dog Alopecia: 29 dogs with hair arrest alopecia were treated with melatonin 3-6 mg twice a day for one year. 18 regrew partial or full coats of hair with 15 showing partial regrowth by 4 months. Frank et al. Univ. of Tennessee. Vet Dermatol. 2004 Oct;15(5):278-84 

Hearing: Melatonin, Vitamins C and E Reduced DNA Damage and Hearing Loss: Age-related hearing loss is accompanied by a reduction in blood flow to specific tissues, including the cochlea. Inadequate blood flow leads to the formation of reactive oxygen metabolites (ROM). ROM are highly toxic molecules that directly affect tissues including inner ear structures. In addition, ROM can damage mitochondrial DNA (mtDNA), resulting in the production of specific mtDNA deletions (mtDNA del4977 [human] or mtDNA del4834 [rat]; also known as the common aging deletion). In a rat study, 30% underfed rats had the least hearing loss and DNA damage by old age, followed by rats treated with either melatonin, or vitamins C or E. Those given placebos did least well. Seidman, MD. Henry Ford. Laryngoscope. 2000 May;110(5 Pt 1):727-38

Hearing: Protects Against Damage from Gentamycin or Tobramycin: Lopez-Gonzalez MA, et al. Virgen del Rocio University. J Pineal Res. 2000 Jan;28(1):26-33

Heart: Melatonin Increases 330% After Heart Attack: Sallinen, et al. Oulu Univ, Finland. J Pineal Res 2007 Apr;42(3):254-60.

Heart: Melatonin Protection in Heart Attack Attributed to Melatonin Receptor: Isolated perfused working rat heart was subjected to 20 min global ischemia or 35 min regional ischemia, and melatonin (25-50 mum) administered either before and during reperfusion, or before ischemia or during reperfusion after ischemia. The melatonin receptor was manipulated using luzindole and N-acetyltryptamine.Melatonin, when administered either before and during reperfusion after ischemia or during reperfusion only, significantly improved cardiac output and work performance and reduced infarct size compared with untreated controls. Luzindole, a melatonin receptor antagonist, abolished these cardioprotective effects. Long-term administration of melatonin (i.p. or orally for 7 days) caused a significant reduction in infarct size of hearts subjected to 35 min regional ischemia. The cardioprotection persisted for 2-4 days after discontinuation of treatment. Short- and long-term effects of melatonin on myocardial post-ischemic recovery. Lochner, et al. University of Stellenbosch, South Africa. J Pineal Research 2006 Jan;40(1):56-63.

Heart: Protects Heart and Lungs Against Fungal Toxin: Protective role of melatonin in ochratoxin a toxicity in rat heart and lung. Okutan H, Aydin G, Ozcelik N. J Appl Toxicol. 2004 Nov-Dec;24(6):505-12

Heart: Protected Against Cancer Drugs: Effect of melatonin on the cardiotoxicity of doxorubicin. Balli E, et al. Histol Histopathol. 2004 Oct;19(4):1101-8. Melatonin protects the heart against ischaemia-reperfusion injury and also against cardiotoxic effects of adriamycin and alloxan. Lack of melatonin was repeatedly reported in patients with coronary heart disease. Intake of this hormone leads to decrease of blood pressure in normotensive and hypertensive subjects, while pinealectomy induces hypertension. Vazan R, Beder I, Styk J. Cesk Fysiol. 2004;53(1):29-33; Similar, earlier report on adriamycin by Kocak, et al. Turkey. Can J Cardiol. 2003 Apr;19(5):535-41.

Heart: Melatonin Prolongs Cardiac Transplant Survival in Rats: Jung FJ, et al. University Hospital Zurich, Zurich, Switzerland J Pineal Res. 2004 Aug;37(1):36-41

Heart: Protects Mice and Rats Against Myocardial Infarction. Either pretreatment or at time of induced heart attack. Chen Z, et al. East Tennessee State University. Am J Physiol Heart Circ Physiol. 2003 May;284(5):H1618-24; Also, protects rats against ischemia/reperfusion injury. YM Lee et al. J Pineal Res. 2002 Sep;33(2):72-80. Also: Nitric oxide synthase inhibition in rats: Melatonin reduces blood pressure and ischemia/reperfusion-induced infarct size. Deniz E, et al. Firat University, Elazig, Turkey. Scand Cardiovasc J 2006 Aug;40(4):248-52.

Heart: Melatonin Reverses Urinary System and Aorta Damage in the rat due to Chronic Nicotine administration. Sener G, et al. Marmara University, Istanbul, Turkey. J Pharm Pharmacol. 2004 Mar;56(3):359-66

Heart: Melatonin Better than Lipoic Acid, Vitamins C and E, and Fish Oil for MDA and Homocysteine: Malondialdehyde (MDA) levels decreased in melatonin (p <0.01), lipoic acid (p <0.01), and vitamin E (p <0.05) groups but not significantly with vitamin C and VC6OP (p >0.05) and fish oil supplementation caused an insignificant increase in rats. Plasma lipid levels in animals treated with melatonin, vitamin E, vitamin C, lipoic acid, and fish oil were significantly lower than  controls; melatonin and fish oil significantly lowered homocysteine levels. Firat Univ. Turkey. Arch Med Res. 2002 Nov-Dec;33(6):515-9.

Heart: Protects Against Myocardial Injury of Isoproterenol in Rats: Acikel M, et al. Ataturk University. J Pineal Res. 2003 Sep;35(2):75-9. This effect appears to be due to protection of cardiolipins by melatonin from reactive oxygenation species for mitochondria due ischemic damage. FASEB 2006 Feb;20(2):269-76.

Heart: Atherosclerosis Increased in Aorta in One Study, But Not Another: Daily melatonin supplementation in hypercholesterolemic mice increases atherosclerosis in proximal aorta. Tailleux A, et al. Institut Pasteur, Lille, France. Biochem Biophys Res Commun. 2002 May 10;293(3):1114-23; However, in another study, a trend toward decreased cholesterol levels in the aorta was found with definite decreases in the liver and plasma. J Pineal Res. 2004 Apr;36(3):212-

Hyperthyroidism: Melatonin prevents oxidant damage in various tissues of rats with hyperthyroidism: Mogulkoc R, et al. Selcuk University, Konya, Turkey. Life Sci 2006 Feb 4

Immune System: Melatonin Protects Thymus Gland:. Pinealectomy decreases thymus weight and that long-term administration of melatonin restores thymus weight to normal levels. Oner H, et al. Akdeniz University, Burdur, Turkey. Neuro Endocrinol Lett. 2004 Feb-Apr;25(1-2):115-8; 60 days reversed age-related thymus involution, spleen weight, splenocytes, and mitogen responsiveness and NK cell immune activity. Tian et al. Tsinghua Univ. Immunol Lett. 2003 Aug 5;88(2):101-4

Immune System: Melatonin Restores Cellular Proliferation and DNA Synthesis in the Splenic and Thymic Lymphocytes of Old Rats: El-Sokkary GH, et al. Assiut University, Egypt. Neuro Endocrinol Lett. 2003 Jun-Aug;24(3-4):215-23

Intervertebral Disc Degeneration: Surgical pinealectomy accelerates intervertebral disc degeneration process in chicken. Turgut M, et al. Turkey. Eur Spine J. 2005 Sep 7

Kidney: Melatonin Protected Rat Kidneys Against Ochratoxin Oxidation: Ozcelik N, et al. Suleyman Demirel University, Isparta, Turkey. J Appl Toxicol. 2004 May-Jun;24(3):211-5; Another study found melatonin reduced kidney damage from gentamycin.

Kidney: Partial suppressive effect of Melatonin on Indomethacin-induced Renal Injury in rat: Hemieda FA, et al. Mansoura University, Egypt. Indian J Exp Biol. 2004 Jan;42(1):63-7

Kidney: Chronic Renal Failure Oxidative Damage Reduced: Sener G, et al. J Pineal Res. 2004 May;36(4):232-41

Kidney: Melatonin Protects Kidney From Ischemia/reperfusion Injury: Rodriguez-Reynoso S, et al. Guadalajara, Jal. Mexico. J Surg Res. 2004 Feb;116(2):242-7; Similar, earlier report by Sahna, et al. Firat University, Turkey. Urol Res. 2003 Jul;31(3):188-93. Reduces oxidative changes.

Kidney: Reduces Cyclosporin A Nephrotoxicity in Rats. Esrefoglu M, et al.  Inonu University, Malatya, Turkey. J Int Med Res. 2003 Jan-Feb;31(1):42-4.

Kidney: Reduces Cisplatin Acute Renal Injury:  J Pineal Res. 2002 Oct;33(3):161-6

Kidney: Reduces Gentamycin Nephrotoxicity in Rats: Sener et al. Marmara University. Turkey. J Pineal Res. 2002 May;32(4):231-6.

Lead Toxicity: Melatonin Protects Blood Cells in Rats: Othman AI, Mansoura University, Egypt. 2004.

Lead Toxicity in Liver and Kidney Reduced: El-Sokkary, Assuit University, Egypt. Toxicology. 2005 Jun 16

Liver: Protected Against Acetaminophen Toxicity: This mouse study found dose related effectiveness.  Unfortunately, the melatonin was given subcutaneously or intraperitoneally. Melatonin protects on toxicity by acetaminophen but not on pharmacological effects in mice. Kanno S, et al. Tohoku Pharmaceutical University, Japan. Biol Pharm Bull 2006 Mar;29(3):472-6.

Liver: Melatonin protects Against Streptozotocin-induced diabetic liver injury in rats. Guven A, et al. Abant Izzet Baysal University, Duzce, Turkey. Acta Histochem 2006 May 19.

Liver: Protected Liver Against Carbon Tetrachloride Toxicity: Protective effects of melatonin against carbon tetrachloride hepatotoxicity in rats. Zavodnik LB, et al. Cell Biochem Funct. 2004 Oct 28

Liver: Protects Against Cholestasis: Melatonin prevents oxidative stress and hepatocyte cell death induced by experimental cholestasis. Padillo FJ, et al. Free Radic Res. 2004 Jul;38(7):697-704

Liver: Protective effect of melatonin against liver injury in mice induced by Bacillus Calmette-Guerin plus lipopolysaccharide. Wang H, et al. Anhui Medical University, Hefei, China. World J Gastroenterol. 2004 Sep 15;10(18):2690-6.

Liver: Melatonin Reduces Dimethylnitrosamine-induced Liver Fibrosis in Rats: Tahan V, et al. Istanbul University, Turkey. J Pineal Res. 2004 Sep;37(2):78-84

Liver and Kidney: Protects Against Acetaminophen Toxicity Better than Vit. E or N-Acetylcysteine: Pretreatment with 10 mg/kg melatonin or 30 of vit. E or 150 of NAC. Sener G, et al. Marmara University, Turkey. J Pineal Res. 2003 Aug;35(1):61-8.

Liver and Kidney: Protects Against Methotrexate Toxicity in Rats: Jahovic N, et al. Marmara University, Istanbul, Turkey. J Pineal Res. 2003 May;34(4):282-7.

Liver: Melatonin, but Not Lactulose, Prevented Damage in Obstructive Jaundice in Rats: Bulbuller N, et al. Firat Universty, Elazig, Turkey. Pediatr Surg Int. 2002 Dec;18(8):677-80.

Liver: Reduced Cholestatic Injury from Bile Duct Ligation in Rats:  Ohta Y, et al. Fujita Health University, Japan. J Pineal Res. 2003 Mar;34(2):119-26. Similar: World J Gastroenterol 2005 Apr 7;11(13):1951-6. 

Longevity: Caloric Restriction Increases Melatonin; Increases Mouse, Fruit Fly Lifespan: Food deprivation doubles melatonin in GI tract. It is a very potent scavenger of free radicals that has increased lifespan of mice in several studies. Bubenik, U Guelph, Science News 7/6/02. The pineal gland is smaller in obesity. In mice, long-term administration of melatonin was followed by an increase in their life span in 12 experiments and had no effect in 8 experiments. When melatonin was added to food throughout the life span, it increased the longevity of fruit flies. Anisimov. Toxicol Pathol. 2003 Nov-Dec;31(6):589-603. Increased longevity in mice. Vopr Onkol 2005;51(1):93-8.

Longevity: Fruit Flies Lived 33% Longer: Melatonin, added daily to the nutrition medium at a concentration of 100 microg/ml, increased significantly the life span of D. melanogaster (fruit fly). The maximum life span was 61.2 days in controls and 81.5 days in melatonin fed flies. The percentage increase in the melatonin fed flies was 33.2% in maximum life span, 19.3% in the onset of 90% mortality, and 13.5% in median life span. In a test of superoxide mediated toxicity it was shown that melatonin treatment increased the resistance of D. melanogaster to paraquat. The augmented resistance to an ambient temperature of 36 degrees C was also a demonstration of the antioxidative protection provided by the hormone. Extension of life span and stress resistance of Drosophila melanogaster by long-term supplementation with melatonin. Bonilla E, et al. Universidad del Zulia, Maracaibo, Venezuela. Exp Gerontol. 2002 May;37(5):629-38.

Lungs: Protects Against Bleomycin Oxidative Lung Fibrosis: Yildirim Z, et al. Inonu University, Malatya, Turkey. J Pineal Research 2006 Jan;40(1):27-33.

Lung: Melatonin limits lung injury (Pulmonary Fibrosis) in bleomycin treated mice. Genovese T, et al. University of Messina Torre Biologica, Italy. J Pineal Res 2005 Sep;39(2):105-12.

Lungs: Protects Somewhat Against Tobacco Smoke in Rabbits: Rabbits were exposed to cigarette smoke for 1 h daily for 1 month with or without intraperitoneal melatonin. Exposure to cigarette smoke causes severe histopathological changes and negatively affects the oxidant/antioxidant status in the lungs of rabbits. A low daily dose of melatonin has some protective effects on histopathological changes and oxidant/antioxidant status of the lungs in smoke exposed rabbits. Unly et al. Afyon, Turkey. Respirology 2006 Jul;11(4):422-8.

Kidney & Liver: Melatonin Protects Against Ochratoxin Toxicity in rat liver and kidney: Sutken E, et al. Osmangazi University. Eskisehir. Turkey.  Int J Toxicology 2007 Jan-Feb;26(1):81-7.

Medication Side-Effects Reduced: Reductions in side-effects by melatonin have been reported when combined with the following drugs: doxorubicin, cisplatin, epirubicin, cytarabine, bleomycin, gentamicin, ciclosporin, indometacin, acetylsalicylic acid, ranitidine, omeprazole, isoniazid, iron and erythropoietin, phenobarbital, carbamazepine, haloperidol, caposide-50, morphine, cyclophosphamide and L-cysteine, usually in animal studies. Reiter RJ, et al, Univ Texas. J Pharm Pharmacol. 2002 Oct;54(10):1299-321.

Meningitis: Bacterial: Melatonin Helps: In experimental animal models, brain-derived neurotrophic factor protected against brain injury and improved hearing while melatonin, which has antioxidant properties among other effects, reduced neuronal death. Curr Opin Pediatr 2006 Apr;18(2):112-8.

Mitochondria: Melatonin Protects and Aids Mitochondria: Melatonin, or N-acetyl-5-methoxytryptamine is found in all organisms from unicells to vertebrates. Melatonin scavenges oxygen and nitrogen-based reactants generated in mitochondria. This limits the loss of the intramitochondrial glutathione and lowers mitochondrial protein damage, improving electron transport chain (ETC) activity and reducing mtDNA damage. Melatonin also increases the activity of the complex I and complex IV of the ETC, thereby improving mitochondrial respiration and increasing ATP synthesis under normal and stressful conditions. These effects reflect the ability of melatonin to reduce the harmful reduction in the mitochondrial membrane potential that may trigger mitochondrial transition pore (MTP) opening and the apoptotic cascade. Melatonin mitigates mitochondrial malfunction. Leon J, Acuna-Castroviejo D, et al. University of Texas, San Antonio. J Pineal Res. 2005 Jan;38(1):1-9.

Morphine Withdrawal Symptoms Reduced in Rats:  Reduced jumping latency and duration, and reduced nitric oxide in brain. Zhou YH, et al. Beijing Medical University. Yao Xue Xue Bao. 2002 Mar;37(3):175-7.

Muscle: Protected Against Ischemia Injury: Melatonin protects against ischemia/reperfusion injury in skeletal muscle. Erkanli K et al. Istanbul, Turkey. J Pineal Res. 2005 Oct;39(3):238-242.

Neurologic: Melatonin Increases Cell Proliferation in the Dentate Gyrus of Maternally Separated Rats: Kim MJ, et al. Dongduk Women's University, Seoul. J Pineal Res. 2004 Oct;37(3):193-7

Neurologic: Meningtitis: Melatonin is Neuroprotective in Experimental Streptococcus pneumoniae Meningitis. In rabbits infected with Streptococcus pneumoniae and given ceftriazone antibiotic 12 hours later, those given melatonin at the time of the infection had a lower density of apoptotic dentate granule cells (81 vs. 227 cells/mm(2); P=.002). The activity of superoxide dismutase in the hippocampal formation was higher (P=.04), and nitrite concentrations in cerebrospinal fluid were lower, after treatment with melatonin (P=.003). Melatonin reduced neuronal injury in vitro and in experimental meningitis, and it may be suitable as adjunctive therapy in human meningitis. Gerber J, et al. Georg-August-University, Gottingen, Germany. J Infect Dis. 2005 Mar 1;191(5):783-90

Obesity: Melatonin Reduces Weight Gain in Rats with Diet-induced Obesity. Melatonin had no effect on plasma insulin level, but it decreased plasma glucose (13%), leptin (28%), and triglyceride (28%) levels. In pinealectomized high-fat diet rats, body weight gain and feed efficiency were increased 4 wk after surgery. Adipose tissue weight, insulinemia, and glycemia had a tendency to increase. Treatment with melatonin prevented in part these changes. Melatonin may act as a regulator of body weight in a model of obesity and may prevent some of the side effects on glucose homeostasis such as decreased insulin sensitivity. Prunet-Marcassus B, et al. Universitaire Paul Sabatier, Toulouse, France. Endocrinology. 2003 Dec;144(12):5347-52. 

Obesity: Melatonin Reduces Olanzapine and Age Induced Fat Stores: The atypical antipsychotic drug olanzapine increases body weight and visceral adiposity in schizophrenia. In rats, aging-associated increased body weight and visceral adiposity are reversed by administration of the pineal hormone melatonin. Four groups (n=11/group) of female rats (240-250 g) were treated for 8 weeks with olanzapine, melatonin, olanzapine+melatonin, or vehicle alone. At week 8, olanzapine treatment reduced nocturnal plasma melatonin by 55% (p<0.001), which was restored to control levels by olanzapine+melatonin. Body weight increased 18% in rats treated with olanzapine alone, 10% with olanzapine+melatonin, 5% with melatonin alone, and 7% with vehicle control. Melatonin may be useful for the management of olanzapine-induced weight gain in humans. Olanzapine-Induced Weight Gain and Increased Visceral Adiposity is Blocked by Melatonin Replacement Therapy in Rats. Raskind MA, et al. University of Washington, Seattle. Neuropsychopharmacology 10 May 2006.

Obesity: Melatonin Signals Fat Storage Release in Animals during Winter’s Long Nights: Many animals show seasonal changes in adiposity that are triggered by changes in the photoperiod. In short "winterlike" days, the nocturnal duration of pineal melatonin (MEL) secretion increases resulting in body fat decreases. These decreases in body fat are mediated through increases in the sympathetic drive on white adipose tissue (WAT). The central nervous system (CNS) origins of the sympathetic outflow from brain to WATinclude the suprachiasmatic nucleus (SCN), an area necessary for the reception of season-encoded MELsignals in certain animals. The increased duration of MEL secretion in short days may increase MEL(1a)-receptor stimulation that, in turn, increases the sympathetic drive on WAT, thereby increasing lipolysis and decreasing adiposity. CNSsympathetic outflow neurons to white fat that express MEL receptors may mediate seasonal adiposity. Song CK, Bartness TJ. Georgia State University, Atlanta, GA.Am J Physiol Regul Integr Comp Physiol. 2001 Aug;281(2):R666-72

Osteoporosis: Melatonin Might Help: Inducible nitric oxide synthase (iNOS) is important in causing osteoporosis via its nitric oxide radical. Melatonin reduces both. In ovariectomized rats, 10 mg/kg/day reduced iNOS expression and the number of apoptitic cells. Authors state it may be effective in estrogen deficience states. Oktem G, et al. Surg Radiol Anat 2005 Dec 15; 1-6

Pancreatitis from Caerulein or Ischemia/Reperfusion Reduced by Melatonin or Tryptophan in Rats: Jaworek J, et al. Jagiellonian University, Krakow, Poland. J Pineal Res. 2003 Jan;34(1):40-52; Similar: J Pineal Res 2006 Apr;40(3):195-203

Pancreatitis from Caerulein Reduced Much More with Melatonin than with Ascorbic Acid + N-Acetyl Cysteine: World J Gastroenterol 2006 Jan 14;12(2):259-64.

Pancreatitis: Melatonin Reduced L-Arginine Induced Pancreatitis:  Might help acute necrotizing pancreatitis in humans. World J Gastroent 2006 Jan 14;12(2):251-8.

Parkinson's: Melatonin Protects against Rotenone-induced oxidative stress in a Hemiparkinsonian Rat Model: Saravanan KS, et al. Indian Institute of Chemical Biology, Calcutta, India."Our results strongly indicate melatonin's beneficial use in Parkinson's disease therapy as an antioxidant." J Pineal Res 2007 Apr;42(3):247-53.

Parkinson's Disease: Melatonin Protective in Mouse Model: Antolin I et al. Universidad de Oviedo, Spain. Brain Res. 2002 Jul 12;943(2):163-73. Mouse model uses a neurotoxin and melatonin helps prevent damage, perhaps as antioxidant.

Pregnancy: Side-Effects on Rat Embryos: Administration of MEL throughout pregnancy caused developmental alterations in offspring manifested by accelerated testes descent and delayed onset of negative geotaxia and startle reflex. Cent Eur J Public Health. 2004 Mar;12 Suppl:S23-5

Radiation: Protects Against Ionizing Radiation: Melatonin protects against ionizing radiation-induced oxidative damage in corpus cavernosum and urinary bladder in rats. Sener G, et al. J Pineal Res. 2004 Nov;37(4):241-6. Many other studies report protection against radiation damage.

Schistosomiasis Reduced by Melatonin: Melatonin reduces oxidative damage and increases survival of mice infected with Schistosoma mansoni. El-Sokkary GH et al. Assiut University, Egypt. Free Radic Biol Med. 2002 Feb 15;32(4):319-32

Scorpion Bites Helped by Melatonin:  Scorpion venom causes oxidative stress in the rat, and damages the heart and other organs. Sahnoon Z, et al. Sfax, Tunisia. Clin Exp Pharmacol Physiol 2007 Apr;34(4):263-8.

Seizures: Melatonin Reduced Theophylline-Induced: Possible role of free radicals in theophylline-induced seizures in mice. Gulati K, et al. University of Delhi, India. Theophylline is prone to induce seizures. Free radicals have considerable neurotoxic potential. Aminophylline (50-250 mg/kg) induces convulsions and mortality in mice in a dose-dependent manner and the anti-oxidants, melatonin (25-100 mg/kg) and N-actylcysteine (100 and 200 mg/kg) attenuated aminophylline seizures and mortality.

Sepsis: Melatonin Protects Against Oxidative Organ Injury in a Rat Model of Sepsis. Sener G, et al. Marmara University, Istanbul, Turkey. Surg Today. 2005 Jan;35(1):52-59. Several other studies have similar findings.

Skin: Low Melatonin Increases Aging; Replacement Helps: Researchers reported a significant reduction in the thickness of epidermis and epidermis + dermis in the back, abdominal and thoracic skin of the long-term pinealectomized rats and the potent therapeutic effect of melatonin on the pinealectomy-induced morphometric changes. Melatonin was given at 4 mg/kg. Fundament Clin Pharmacol 2006 Dec;20(6):605-611.

Skin: Topical Protected Pressure Damage Ischemia and Intraperitoneal Protected Internal Organs: Melatonin protects against pressure ulcer-induced oxidative injury of the skin and remote organs in rats. Sener G, et al. Marmara University, Istanbul, Turkey. J Pineal Res 2006 Apr;40(3):280-7.

Skin: Protects Against Aging Effects: Potent therapeutic effect of melatonin on aging skin in pinealectomized rats. Esrefoglu M et al. Inonu Univ. Turkey. J Pineal Res. 2005 Oct;39(3):231-237.

Skin: Protects from X-Ray Damage: Melatonin can protect albino rats from the skin damage of x-rays. Hussein MR, et al. Assuit Univ. Int J Exp Pathol. 2005 Feb;86(1):45-55. Melatonin topically also protected against UV redness.

Stomach: Protects Against Alendronate Damage: Protective effect of melatonin and omeprazole against alendronate-induced gastric damage in rats. Each did equally well with pretreatment and attributed to anti-oxidant effect. Sener G, et al. Marmara University, Istanbul, Turkey. Dig Dis Sci. 2005 Aug;50(8):1506-12.

Stomach: Melatonin Protects Against Piroxicam, Indomethacin-induced Ulcers: This study with piroxicam in rats. Authors says protection probably true for other NSAIDs. Bandyopadhyay D, et al. Indian Institute of Chemical Biology, Kolkata, India. J Pineal Res. 2004 Apr;36(3):195-203; Similar results against indomethacin ulcers. Singh, et al. Indian J Physiol Pharmacol. 2002 Apr;46(2):229-34.

Stomach: Protects Against Stress-Induced Gastric Ulcers and Helps Ranitidine and Omeprazole: By self did better than ranitidine but not as well as omeprazole in study with rats. D Bandylpadhyay et al. Kolkata, India. J Pineal Res. 2002 Aug;33(1):1-7.

Stomach: Protects Against Alcohol-Induced Ulcers: Bilici et al. Ataturk University. Turkey. Dig Dis Sci. 2002 Apr;47(4):856-61

Stomach & GI: Gastric ulcers are common in pigs.  The addition of 2.5 mg of melatonin per kilogram of food decreased stomach ulcers by 25% and larger amounts had no added benefit. Univ of Guelph, Canada. http://www.omafra.gov.on.ca/english/livestock/swine/facts/info_n_dietary.htm 

Stroke: Melatonin Works by Blocking COX-1: Melatonin reduced volume of cerebral infarct induced by photothrombosis in wild-type mice, not in Cyclooxygenase-1 gene knockout mice. Zou et al. Hong Kong Univ. Conf Proc IEEE Eng Med Biol Soc 2004;7:4748-50.

IV Melatonin Reduced Intracerebral Cellular Inflammatory of focal cerebral ischemia in rats. Exogenous melatonin improves the preservation of the blood-brain barrier (BBB) and neurovascular unit following cerebral ischemia-reperfusion. The melatonin-mediated decrease in the cellular inflammatory response was accompanied by both reduced brain infarction and improved neurobehavioral outcome by 43% (P < 0.001) and 50% (P < 0.001), respectively. Its pleuripotent neuroprotective actions is suited either as a monotherapy or an add-on to the thrombolytic therapy for ischemic stroke patients. Lee MY, et al. Natl Cheng Kung Univ. Tainan, Taiwan. J Pineal Res 2007 Apr;42(3):297-309.

Stroke: Melatonin Neuroprotective for Ischaemic Stroke: In a meta-analysis of fourteen studies involving 432 animals, melatonin improved the outcome by an average of 43%. Systematic review and meta-analysis of the efficacy of melatonin in experimental stroke. Macleod MR, et al. National Stroke Research Institute, Melbourne, Australia. J Pineal Res. 2005 Jan;38(1):35-41

Stroke: Melatonin decreases neurovascular oxidative/nitrosative damage and protects against early increases in the blood-brain barrier permeability after transient focal cerebral ischemia in mice. Chen HY, et al. Taiwan. J Pineal Res 2006 Sep;41(2):175-82.

Stroke: Melatonin reduces infarction volume in a photothrombotic stroke model in the wild-type but not cyclooxygenase-1-gene knockout mice. Zou LY, et al. Univ Hong Kong. J Pineal Res 2006 Sep;41(2):150-6.

Stroke: Protects Blood-Brain Barrier and Damage: Melatonin attenuates the postischemic increase in blood-brain barrier permeability and decreases hemorrhagic transformation of tissue-plasminogen activator therapy following ischemic stroke in mice. Chen TY, et al. National Cheng Kung University, Tainan, Taiwan. J Pineal Res 2006 Apr;40(3):242-50.

Stroke: Melatonin Reduces Vasospasm following experimental Subarachnoid Hemorrhage: Rabbits given 5 mg/kg of melatonin either after the time of a SAH or two hours after an SAH had 33% and 26% constriction vs. 57% constriction of basilar arteries in untreated group. There was also less apoptosis of endothelial cells with melatonin. Aydin MV, et al. Baskent University, Turkey. Neurol Res. 2005 Jan;27(1):77-82

Stroke: Helped Injured Nerve: Beneficial effects of melatonin on reperfusion injury in rat sciatic nerve. Sayan H, et al. J Pineal Res. 2004 Oct;37(3):143-8 

Stroke Model Helped: Pretreatment with melatonin exerts anti-inflammatory effects against ischemia/reperfusion injury in a rat middle cerebral artery occlusion stroke model. Pei Z, et al. J Pineal Res. 2004 Sep;37(2):85-91.

Stroke: Delayed Melatonin Reduced Infarct Size: In rats given experimental strokes with 1.5 hour interruption of blood flow, melatonin 72 hours after the stroke was still beneficial in minimizes the stroke damage by 35%. Lee EJ, et al. National Cheng Kung University, Taiwan. J Pineal Res. 2004 Jan;36(1):33-42

Stroke: Brain Edema Helped with Reduced Infarct Size:  Brain edema was produced in rats by creating a lesion via cortical freezing. Melatonin was administered (50 mg/kg intraperitoneally) 15 minutes after the cold injury was induced. In 24 hours, melatonin reduced edema (86% for placebo versus 80% for melatonin, P < 0.001) and blood-brain barrier permeability (45% in the control versus 38% with melatonin, P < 0.001) at the periphery of cold injury. Area of infarct reduced from 5.8% in the control group to 3.3% in the melatonin treatment group (P < 0.001). Gorgulu A et al. Univ Trakya, Turkey. Neurosurgery. 2001 Dec;49(6):1434-41

Testicular Torsion: Melatonin Better than Allopurinol for Testicular or Ovarian Torsion: Beneficial effects of melatonin compared with allopurinol in experimental testicular torsion. Abasiyanik A, et al. J Pediatr Surg. 2004 Aug;39(8):1238-41; Same with the ovary. J Pineal Res. 2004 Sep;37(2):137-41

Toxoplasmosis: Melatonin Increased CD4+ and CD8+ Lymphocyte Response Activating Cell Immunity: Zinc had similar effects. Baltaci AK, et al. Selcuk University, Turkey. Biol Trace Elem Res. 2003 Winter;96(1-3):237-45

Umbilical Cord Occlusion: Fetal Asphyxia Helped in Sheep: Oxygen free radicals, including the highly toxic hydroxyl radical (*OH), initiate lipid peroxidation and DNA/RNA fragmentation and damage cells. The pineal hormone melatonin is an antioxidant and powerful scavenger of *OH. In 10 fetuses, asphyxia was induced by umbilical cord occlusion for 10 min using an inflatable cuff - the ewes of these fetuses received either intravenous melatonin (1 mg bolus, then 1 mg/h for 2 h; n = 5) or vehicle (1% ethanol in saline; n = 5), and results were compared to fetuses with sham cord occlusion and vehicle-infused ewes (n = 5). Hypoxemia, acidemia, hypertension and bradycardia produced by cord occlusion was similar in the melatonin- and vehicle-treated groups. In the vehicle-treated group, cord occlusion resulted in a significant increase in *OH in gray matter at 8-9.5 h after occlusion (p < 0.05); in contrast, there was no *OH change in the melatonin-treated group. After cord occlusion, lipid peroxidation (4-hydroxynonenal immunoreactivity) found throughout the brain of vehicle-infused ewes was significantly less in the melatonin-infused group. Melatonin provides neuroprotection in the late-gestation fetal sheep brain in response to umbilical cord occlusion. Miller SL, et al. Monash University, Clayton, Australia. Dev Neurosci. 2005 Mar-Aug;27(2-4):200-10

Uterine Adhesions Prevented: Both melatonin and hyaluronate/carboxymethylcellulose membrane were effective in prevention of adhesion formation in a rat uterine horn model in this animal model of human post-operative adhesions. Demirbag S, et al. Ankara, Turkey. Hum Reprod. 2005 Mar 31

Viral Infections: Helped: Melatonin prevents paralysis and death in mice infected with the encephalomyocarditis virus and decreases viremia. Melatonin postpones the onset of Semliki Forest virus disease and reduces the mortality of stressed West Nile virus-infected mice. Melatonin protects some strains of mink against Aleutian disease, and prevents the reduction of B- and T-cells as well as Th1 cytokine secretion in mice infected with leukemia retrovirus. In VEE-infected mice, melatonin reduces the mortality rate by an increase in the production of interleukin-1beta (IL-1beta). Bonilla E, et al. J Pineal Res. 2004 Mar;36(2):73-9

Wound Healing: Melatonin May Slow Healing; But Increased Skin-Flap Viability: Melatonin decreased collagen synthesis and epithelium proliferation and had negative effects on wound healing in both normal and pinealectomized rats. Effect of melatonin on wound healing in normal and pinealectomized rats. Bulbuller N, et al. Firat University, Elazg, Turkey.. J Surg Res. 2005 Jan;123(1):3-7. However, melatonin increases skin-flap viability in pinealectomized rats. J Pineal Res. 2004 Jan;36(1):58-63. And neovascularization and hydroxyproline levels were helped by melatonin. Surg Today. 2003;33(12):896-901.

Wound Healing: Prevented Adhesions After Uterine Surgery in Rats:  Ozcelik B, et al. Erciyes University. Hum Reprod. 2003 Aug;18(8):1703-6

X-Ray Damage: Melatonin prevents X-ray irradiation induced oxidative damage in peripheral blood and spleen. Sharma S, et al. Banaras Hindu University, Varanasi, India. 

X-Ray Damage: Melatonin Protects Against Roentgen irradiation of the testis. Hussein MR, et al. King Khlid University, Saudi Arabia. Fertil Steril 2006 Jul 17.

Zinc Important for Melatonin: Zinc deficiency decreases the melatonin levels and zinc supplementation may increase the plasma melatonin levels in rats. Bediz CS, et al. Dokuz Eylul University, Turkey. Acta Physiol Hung. 2003;90(4):335-9. Ed: Since zinc is still being debated as to whether it is good or bad for Alzheimer's, I do not recommend a zinc supplement other than zinc lozenges for upper respiratory tract infections (colds).

Lab Studies

N-acetyl-serotonin is the immediate precursor of melatonin in the tryptophan metabolic pathway in the pineal gland.  Whether 5-HTP (5-hydroxytryptophan) supplements increase melatonin production similar to its effect on serotonin production has not been reported, but is likely since tryptophan supplementation has been shown to have this effect.  The body turns tryptophan from food into 5-HTP and then into serotonin.  The next step in the pineal gland is N-acetyl-serotonin, and finally melatonin.  5-HTP is a somewhat useful treatment for depression, but this is probably on its effect on brain serotonin levels and not via melatonin, since melatonin has no effect on serotonin receptors and is of no benefit in animal models of anxiety.

Antioxidant Value of Melatonin High: In comparing the peroxyl radical scavenger ability of melatonin, vitamin E, ascorbic acid (As.A.), reduced glutathione (GSH) and mannitol, all, except mannitol, prevented the lysis of human erythrocytes exposed to an azo-initiator of peroxyl radicals. The efficiency was greatest with melatonin > vitamin E > As.A. > GSH. Based on the assumption that each molecule of vitamin E scavenges two peroxyl radicals, the scavenging capacity of melatonin was four peroxyl radicals/molecule. Melatonin is an efficient antioxidant. Pieri C, et al. Ancona, Italy. Arch Gerontol Geriatr. 1995 Mar-Apr;20(2):159-65

Melatonin is a natural compound synthesized by a variety of organs. It has been shown to function as a cell-protective agent. Since 1994, when the first paper was published documenting the role of melatonin in apoptosis, the number of reports in this area has increased rapidly. Much of the research conducted falls into three major categories: first, the role of melatonin in inhibiting apoptosis in immune cells; second, the role of melatonin in preventing neuronal apoptosis and finally, the role of melatonin in increasing apoptotic cell death in cancer cells. Sainz RM,, et al, Univ Texas. Cell Mol Life Sci. 2003 Jul;60(7):1407-26

Skin can produce serotonin and transform it into melatonin.  Both have receptors in keratinocytes, melanocytes, and fibroblasts which effect cell proliferation and differentiation.  Serotonin can be pro-edema, dilate vessels, increase inflammation and itching, melatonin is involved in the hair growth cycle, pigment and melanoma control (Slominski, A. et al. Univ. of Tennessee, FASEB J. 2005 Feb;19(2):176-94).  Melatonin acts by melanogenesis inhibition, melanocyte growth inhibition, regulation of seasonal changes in the fur.  It is a potent free radical scavenger.  There are two types of high-affinity membrane melatonin receptors, MT1 and MT2, which inhibit adenylate cyclase activity to decrease the intracellular level of cAMP. A low-affinity membrane receptor MT3/QR2 has also been identified. Melatonin is ligand of nuclear transcription factor ROR, so it may regulate cell cycle negatively via a target gene such as p21(WAF/CIP1). Due to its lipophilic structure and anti-oxidant character, melatonin enters through both the plasma and nuclear membrane, and protects macromolecules, in particular DNA (Kobayashi H, Paus R. University of Hamburg. Exp Dermatol. 2005 Feb;14(2):157).

Thomas E. Radecki, M.D., J.D.

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