Study-Supported Benefits of MELATONIN Supplementation

Supplementing with MELATONIN is appropriate in certain situations

However, be aware that chronic use of supplemental MELATONIN in younger people can result in the pineal gland becoming lazy

For older people ( > 60 yrs) - daily MELATONIN supplementation can be useful, since their pineal gland is not producing enough .

To synchronize perturbed sleep and circadian rhythms - sustained desynchonisation of the "Biological Clock" has a profound impact on health and wellbeing, including suppressed immunity and increased risk of cancer. Also, frequently accompanying these disturbances are neuropsychiatric disorders, such as depression, schizophrenia and Alzheimer's. Desynchronisation occurs while the body's clocks struggle to adapt to an abruptly shifted external light/dark cycle. E.g.

• Frequent trans-meridian travel (Jet Lag).   E.g. Transcontinental flight personnel and frequent overseas fliers. Supplement MELATONIN on the day of the flight and continue for five days thereafter.
• Shift-workers.    MELATONIN supplements may simulate the MELATONIN production at different times that does not occur during regular sleeping hours for people who work night shifts.

Straif, Kurt; Baan, Robert; Grosse, Yann; Secretan, BéAtrice; Ghissassi, Fatiha El; Bouvard, VéRonique; Altieri, Andrea; Benbrahim-Tallaa, Lamia et al (2007). "Carcinogenicity of shift-work, painting, and fire-fighting". The Lancet Oncology 8 (12): 1065-6. doi:10.1016/S1470-2045(07)70373-X. PMID19271347.

Induces / Improves Sleep

MELATONIN Induces / Improves Sleep

Prevent ischemic damage - in rats, reduces tissue damage due to ischemia in brain and heart; (ischemia is a restriction in blood supply causing a shortage of oxygen delivery to target organs/tissues)

Against cardiovascular disease - Low nighttime MELATONIN has been reported in patients with coronary heart disease and heart failure. Similarly, thelinkbetween highCORTISOL andhypertension is well established.Supplementationwith MELATONINhas been shown to increase cardiac vagal tone, decrease circulating NOREPINEPHRINE, and reduce blood pressure.

Pandi-Perumal SR, Srinivasan V, Maestroni GJ, Cardinali DP, Poeggeler B, Hardeland R. MELATONIN: Nature's most versatile biological signal? FEBS J. 2006 Jul;273(13):2813-38. PubMed

Learning, memory and Alzheimer's - first published evidence that MELATONIN may be useful in Alzheimer's disease demonstrated that this neurotransmitter/hormone prevents neuronal death caused by exposure to the amyloid beta protein, a neurotoxic substance that accumulates in the brains of patients with the disorder.

Wang XC, Zhang J, Yu X, Han L, Zhou ZT, Zhang Y, Wang JZ. Prevention of isoproterenol-induced tau hyperphosphorylation by MELATONIN in the rat.Sheng Li Xue Bao. 2005 Feb 25;57(1):7-12 PubMed.

MELATONIN also inhibits the aggregation of the amyloid beta protein into neurotoxic microaggregates which seem to underlie the neurotoxicity of this protein, causing death of neurons and formation of neurofibrillary tangles, the other neuropathological landmark of Alzheimer's disease.

Pappolla MA, Sos M, Omar RA, Bick RJ, Hickson-Bick DL, Reiter RJ, Efthimiopoulos S, Robakis NK. MELATONIN prevents death of neuroblastoma cells exposed to the Alzheimer amyloid peptide. J Neurosci. 1997 Mar 1;17(5):1683-90. PubMed

ADHD - research shows that after MELATONIN is administered to ADHD patients on methylphenidate, the time needed to fall asleep is significantly reduced. Furthermore, the effects of the MELATONIN after three months showed no change from its effects after one week of use.

Tjon Pian Gi, Cecil V.; Broeren, Joris P. A.; Starreveld, J. Sander; A. Versteegh, Florens G (2003). "MELATONIN for treatment of sleeping disorders in children with attentiondeficit/hyperactivity disorder: a preliminary open label study". European Journal of Pediatrics 162(7-8): 554-5.

Migraines / Headaches - several clinical studies indicate that MELATONIN supplementation is an effective preventative and adjunct treatment for migraines and cluster headaches.

Treatment and Management of Cluster Headaches

The therapeutic potential of MELATONIN in migraines and other headache types.

Mood disorders - MELATONIN has been shown to be effective in treating seasonal affective disorder (SAD) and is being considered for bipolar and other disorders in which circadian disturbances are involved. Is Internal Timing Key to Mental Health?

• Depression - research shows that depressed patients have lower levels of MELATONIN than non-depressed patients, however, although MELATONIN supplementationhelps correctsleep disorders indepression,it does notimprove clinicalsymptoms of depression.

Pandi-Perumal SR, Srinivasan V, Maestroni GJ, Cardinali DP, Poeggeler B, Hardeland R. MELATONIN: Nature's most versatile biological signal? FEBS J. 2006 Jul;273(13):2813-38. PubMed.

High bedtime levels of CORTISOL are also associated with depression.

Brown ES, Varghese FP, McEwen BS.Association of depression with medical illness: does cortisol play a role? Biol Psychiatry. 2004 Jan 1;55(1):1-9. PubMed

MELATONIN Controls Depression

Cancers - A systematic review of unblended clinical trials involving a total of 643 cancer patients using MELATONIN found a reduced incidence of death. MELATONIN in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. Reduced MELATONIN production has been proposed as a likely factor in the significantly higher cancer rates in night workers and breast cancer in women.

Supplemental MELATONIN has been shown to slow tumor progression in a variety of cancers - and provide subjective improvement in quality of life.

Pandi-Perumal SR, Srinivasan V, Maestroni GJ, Cardinali DP, Poeggeler B, Hardeland R. MELATONIN: Nature's most versatile biological signal? FEBS J. 2006 Jul;273(13):2813-38. PubMed

Gallbladder stones - in the gallbladder, MELATONIN converts cholesterol to bile, prevents oxidative stress and increases mobility of gallstones from the gallbladder. It also decreases the amount of cholesterol produced in the gallbladder by regulating the cholesterol that passes through the intestinal wall. In guinea pigs, MELATONIN administration restored normal function after induced cholecystitis, by reducing inflammation. Reactive Oxygen Species and the Hypomotility of the Gall Bladder as Targets for the Treatment of Gallstones with MELATONIN: A Review. Daytime MELATONIN concentration in mammalian bile is 2-3 times higher than daytime (very low) blood levels. High physiological levels of MELATONIN in the bile of mammals

ALS (Amytrophiic Lateral Sclerosis) In animal models, MELATONIN has been shown to ameliorate glutamate-induced neuronal death, presumed due to its antioxidanteffects. In a clinical safety study involving 31 ALS patients, high-dose rectal MELATONIN (300mg/day for 2 years) was shown to be tolerated well. Reduced oxidative damage in ALS by high-dose enteral MELATONIN treatment

Obesity - studies in experimental animals show that long-term MELATONIN supplementation in drinking water reduces body weight and abdominal fat, without changes to diet or being more active (especially in middle-aged rats) Daily MELATONIN administration to middle-aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat. A proposed mechanism is that MELATONIN promotes the recruitment and activity of brown adipose tissue as well as enhances its activity. , which would raise the basal metabolic rate by stimulating thermogenesis. Significance and application of MELATONIN in the regulation of brown adipose tissue metabolism: relation to human obesity

Protection from radiation - animal and human (2^nd Ref) studies have shown MELATONIN to provide more efficient protection from ionizing radiation than the commonly used drug amifostine. Its mechanism is thought due to the scavenging of harmful oxidants (E.g. free radicals), considered to be responsible for ~70% of ionizing damage to body tissues, especially the hydroxyl radical that attacks DNA, proteins, and cellular membranes. MELATONIN has the advantage of being broadly protective, readily available for oral supplementation, and without significant side effects.

Tinnitus - medical studies with adult patients show beneficial results in the treatment of tinnitus with MELATONIN

MELATONIN is associated with a statistically significant decrease in tinnitus intensity and improved sleep quality in patients with chronic tinnitus - MELATONIN is most effective in:

• Men
• Those without a history of depression
• Those who have not undergone prior tinnitus treatments
• Those with more severe and bilateral tinnitus
• Those with a history of noise exposure.

Hurtuk A, Dome C, Holloman CH, Wolfe K, Welling DB, Dodson EE, Jacob A (July 2011). "MELATONIN: can it stop the ringing?". Ann. Otol. Rhinol. Laryngol. 120(7): 433-40. Pubmed

The impact of MELATONIN on sleep was greatest among patients with the worst sleep quality, but its impact on tinnitus was not associated with the severity of the tinnitus

Megwalu UC, Finnell JE, Piccirillo JF (February 2006). "The effects of MELATONIN on tinnitus and sleep". Otolaryngol Head Neck Surg 134(2): 210-3.Pubmed

MELATONIN has been shown to be useful in the treatment of subjective tinnitus - Patients with high THI scores and/or difficulty sleeping are most likely to benefit from treatment with MELATONIN.

RosenbergSI, Silverstein H, Rowan PT, Olds MJ (March 1998). "Effect of MELATONIN on tinnitus". Laryngoscope 108(3): 305-10. Pubmed

One publication explores the possible mechanisms of how MELATONIN works against tinnitus:

• Its modulatory effect on central nervous system - resulting in a protective mechanism against an exaggerated sympathetic drive (sympathetic nervous system is responsible for regulating homeostatic conditions in the body);
• Its capacity to induce a more steady hemodynamic condition - through a multifactorial and multi-organ activity, resulting in more regular blood flow in the inner ear;
• A possible action on the skeletal muscle tending to a reduction of the muscular tone - which could relieve tinnitus of muscular origin deriving from contraction of tensor tympani muscles (located in the upper auditory canal) responsible for dampening sounds;
• Its possible reported anti-depressive effect - which could indirectly act on tinnitus;
• A direct regulation of inner ear immunity - as proposed in literature when melatonin was reported to be present in the inner ear.

Retrieved December 6, 2011. Exploring the reasons why MELATONIN can improve tinnitus, August 2010.

Studies site a typical dose for positive effect on tinnitus as 3 mg MELATONIN / day - usually taken in the evening