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MELATONIN- Link to a decent web site about melatonin

It appears to be outstandingly useful and relatively safe. See the 2013 discovery about why sleep is so important.


Update Jan, 2013 from AGE: - Aging and vascular dysfunction: beneficial melatonin effects Luigi Fabrizio Rodella, Gaia Favero, Claudia Rossini, Eleonora Foglio, Francesca Bonomini, Russel J. Reiter & Rita Rezzani February 2013, Volume 35, Issue 1, pp 103-115 Melatonin is known to modulate oxidative stress-induced senescence and pro-survival pathways. 

There has been a lot of research on melatonin in recent years. Here is an update in June, 2010. It is suggested that taking 3mg at bedtime about 4 or 5 times per week is useful, especially if you are older. It appears to upregulate genes expressed by younger people, and downregulate genes of older people, based on gene screen experiments with people.   I am especially interested in sleep, because it is another of the areas of life that science has made little progress in understanding. For instance, we still do not understand why people need to sleep, though total sleep deprivation leads to serious harm.

Study states sleep disorders affect 50-70 million people in the US.  This multicener review by NIH concluded that " The magnitude of this effect appears to be clinically insignificant. There was evidence of possible
publication bias in the selection of studies that were analyzed; we found a greater number of studies reporting positive results compared to negative results...Melatonin increased sleep efficiency in normal sleepers"

One study announcement from MIT suggests that 0.3mg is an ideal dosage, and that 3 mg can have serious side effects, like hypothermia.
(link: Melatonin; added 6/2009) HOWEVER, IN 2010 AT THE AGE MEETING, it was reported that 3mg four or five times per week is safe.

added June 2007 - One study in people used a dosage range of 3-12 mg/night. J Clin Psychiatry. 2007 Feb;68(2):237-41
Search PubMed for  "J Pineal Res", melatonin, where a host of articles show the benefits of melatonin reduced oxidative damage and inflammation.

3. Reiter RJ, Paredes SD, Korkmaz A, Manchester LC, Tan DX: Melatonin in relation to the "strong" and "weak" versions of the free radical theory of aging. Adv Med Sci; 2008;53(2):119-29 "While the data supporting a role for melatonin in forestalling aging and prolonging life span per se is not compelling, the findings related to melatonin's ability to reduce the severity of a variety of age-related diseases that have as their basis free radical damage is convincing."

4. Melatonin: action as antioxidant and potential applications in human disease and aging. 
Bonnefont-Rousselot D, Collin F. Toxicology; 2010 Nov 28;278(1):55-67. "Therapeutic potential of melatonin relies either on increasing melatonin dietary intake or on supplementation with supraphysiological dosages. Clinical trials showed that melatonin could be efficient in preventing cell damage, as well under acute (sepsis, asphyxia in newborns) as under chronic (metabolic and neurodegenerative diseases, cancer, inflammation, aging). Its global action on oxidative stress, together with its rhythmicity that plays a role in several metabolic functions, lead melatonin to be of great interest for future clinical research in order to improve public health."

1) I first heard about it at the 2003 AGE meeting, where it was reported that melatonin may regulate many genes. In an RNA chip study of gene expression of 10,000 genes, it was found that elderly people had different gene expression levels in about 100 genes compared to young people. When the elderly were given melatonin, their gene expression pattern changed to that of youngsters.

The above link describes its effects on sleeping and other things.

2) AGE meeting notes; June, 2004: Presentation by Dr. Tomas Prolla, Univ of WI - reporting on gene expression profiling of aging in skeletal muscle -

Genes involved in: expression level change with age
stress response increase
energy metabolism decrease
neuronal injury increase

All of these changes are blocked by caloric restriction. Out of 7,000 genes tested, thirty one genes change expression dramatically with age. MELATONIN, COENZYME Q10 (CoQ10), and UBIQUINONE reverse some but not all of the gene expression changes.

3) Aging and oxygen toxicity: Relation to changes in melatonin - "Melatonin was recently found to be a free radical scavenger and antioxidant. It has been shown, in the experimental setting, to protect against both free radical induced DNA damage and oxidative stress-mediated lipid peroxidation. Pharmacologically, melatonin has been shown to reduce oxidative damage caused by such toxins as the chemical carcinogen safrole, carbon tetrachloride, paraquat, bacterial lipopolysaccharide, kainic acid, δ-aminolevulinic and amyloid β peptide of Alzheimer’s disease as well as a model of Parkinson’s disease involving the drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Additionally, the oxidative damage caused by agents such as ionizing radiation and excessive exercise is reduced by melatonin. Since free radical-induced molecular injury may play a significant role in aging, melatonin’s ability to protect against it suggests a potential function of melatonin in deferring aging and age-related, free radical-based diseases."

4) Correlation between night work and cancer rates © Copyright 2000 - 2007 The Hindu

Artificial light may lead to lower melatonin levels

LONDON: It was once scientific heresy to suggest that smoking contributed to lung cancer. Now, another idea initially dismissed as nutty is gaining acceptance: the graveyard shift might increase your cancer risk.

Next month, the International Agency for Research on Cancer, the arm of the World Health Organisation that is concerned with cancer, will classify shift work as a *probable* carcinogen. That will put shift work in the same category as cancer-causing agents such as anabolic steroids, ultraviolet radiation, and diesel engine exhaust.

If the shift work theory proves correct, millions of people worldwide could be affected. Experts estimate that nearly 20 per cent of the working population in developed countries work night shifts... IARC publishes the results of its analysis, the result of an expert panel convened in October, in the December [2007] issue of The Lancet Oncology...

The research suggests a correlation between people who work at night and increased cancer rates...Scientists suspect that shift work is dangerous because it disrupts the circadian rhythm, the bodyâ*?s biological clock. The hormone melatonin, which can suppress tumour development, is normally produced at night. Light shuts down melatonin production, so people working in artificial light at night may have lower melatonin levels, which scientists think can raise their chances of developing cancer.

Sleep deprivation may also be a factor...Not getting enough sleep makes your immune system vulnerable to attack, and less able to fight off potentially cancerous cells... Even worse than working the night shift would be to frequently flip between day and night shifts...



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