The purpose of this site is to collect lab research by medical doctors about herbs that are proven to treat illnesses and counter the false attacks on herbs by the medical industry and false claims by alternative medicine. I let the science tell the facts.
 
index sitemap advanced
search engine by freefind
 
Melatonin

1. Wickipedia "Melatonin (pronounced /?m?l?'to?n?n/ ( listen)), also known chemically as N-acetyl-5-methoxytryptamine,[1] is a naturally occurring hormone found in most animals, including humans, and some other living organisms, including algae.[2] Circulating levels vary in a daily cycle, and melatonin is important in the regulation of the circadian rhythms of several biological functions.[3] Many biological effects of melatonin are produced through activation of melatonin receptors,[4] while others are due to its role as a pervasive and powerful antioxidant[5] with a particular role in the protection of nuclear and mitochondrial DNA.[6] Products containing melatonin have been available as a dietary supplement in the United States since 1993.[7] Foods may contain trace amounts of melatonin, but no food has been found to elevate plasma melatonin levels.[8] Over-the-counter sales of the hormone remain illegal in many other countries, and the U.S. Postal Service lists melatonin among items prohibited by Germany.[9]" http://en.wikipedia.org/wiki/Melatonin

2. "Protective Effects of Melatonin Against the Damages of Neuroendocrine-immune Induced by Lipopolysaccharide in Diabetic Rats. Zhong LY, Yang ZH, Li XR, Wang H, Li L. 1Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Chongwen District, Beijing, China.

The present study was to determine the protective effects of melatonin (MLT) against the damages of neuroendocrine-immune induced by lipopolysaccharide (LPS) in streptozotocin (STZ)-induced diabetic rats, and to analyze the parameters related to diabetes and oxidative stress. A total of 70 male Sprague-Dawley rats were assigned to this experiment. 10 of rats received STZ intraperitoneally (i.p.) alone as diabetic control; 40 of rats as the Diabetes+LPS received STZ plus LPS i.p. after induction of diabetes with STZ, then assigned to sub-groups as MLT (0.1) (mg), MLT (1) (mg), and Vehicle group, received two doses MLT and vehicle, i.p., respectively, q6 h for 12 h after LPS administration; and the remaining served as normal and LPS control. LPS significantly increased the serum levels of TNF-alpha and IL-6 in normal and diabetic rats; LPS also dramatically increased the plasma concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone. Both 0.1 and 1 mg/kg MLT doses significantly decreased the serum levels of TNF-alpha and IL-6. Significant inhibitory effects of MLT (1 mg/kg) were observed on the plasma concentrations of CRH, ACTH, and corticosterone of the HPA axis. The beneficial effects of MLT, such as the antioxidant activity and maintaining glucose homoeostasis, were also observed in this study, this resulted in a protective effect against the damages caused by LPS in STZ-induced diabetic rats. This finding probably provides a new approach for preventing the undesirable effects of the vicious cycle of hyperglycemia and stress factors such as severe infection in diabetic patients." PMID: 19449282

3. "Melatonin improves oxidative stress parameters measured in the blood of elderly type 2 diabetic patients. Kedziora-Kornatowska K, Szewczyk-Golec K, Kozakiewicz M, Pawluk H, Czuczejko J, Kornatowski T, Bartosz G, Kedziora J. Department and Clinic of Geriatrics, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.

An elevated oxidative status in the aging organism may be involved in the development of non-insulin dependent diabetes mellitus (NIDDM). Melatonin, a potent antioxidant agent, is essential for glucose homeostasis and regulation. The aim of this study was to determine the influence of melatonin supplementation on the oxidative stress parameters in elderly NIDDM patients. The malondialdehyde (MDA) concentration, Cu-Zn superoxide dismutase (SOD-1) activity in erythrocytes, the level of nitrate/nitrite in plasma and morning melatonin concentration and oxidase activity of ceruloplasmin (Cp) in serum in 15 elderly NIDDM patients at baseline and after the 30 days of melatonin supplementation (5 mg daily) in comparison with levels in 15 healthy elderly volunteers were determined. A significant increase of MDA level and decrease of SOD-1 activity and melatonin concentration were observed in NIDDM patients. Cp oxidase activity and nitrate/nitrite level were similar in both examined groups. Melatonin administration in NIDDM patients resulted in a significant increase in the morning melatonin concentration and SOD-1 activity, and a reduction in the MDA level and Cp oxidase activity. Statistically significant alterations in nitrate/nitrite levels were not observed. These results indicate an improvement of antioxidative defense after melatonin supplementation in the NIDDM individuals and suggest melatonin supplementation as an additional treatment for the control of diabetic complications."
PMID: 19317795

4. The following is written by two ghost writers who due to their vocations in the drug industry do not want their names attached.

Melatonin is extremely safe and there are some very interesting Melatonin Benefits that you may be interested in learning more about. Melatonin safety is well-documented, and in the past decade that melatonin has been used as a supplement it has received an amazingly low amount of reports of Side Effects of Melatonin- even at high dosages and even at EXTREMELY high dosages! http://www.easy-immune-health.com/melatonin-overdose.html#axzz18FUFBvog
 
Melatonin Safety
Except for the Melatonin Long Term Effects, melatonin safety is WELL documented and it's been found that a melatonin overdose is extremely hard to do- even when giving Melatonin for Children. In fact, it's so hard to give someone melatonin toxicity that scientists trying to find its toxicity level in mice couldn't do it. When scientists do preliminary studies on substances to try to find out levels of toxicity, they have developed a number called the LD 50. The LD 50 is the dose that will consistently kill half of the mice that they give the substance to. Well, Melatonin HAS NO LD 50 because no matter what dosage was given to mice, they just simply didn't die!

"When government scientists set out to find
melatonin’s “LD 50”- the dose that’s lethal to
50 percent of the animals receiving it - they
couldn’t make a rich enough concentrate to kill
a mouse. And when researchers fed human
volunteers 6 grams (6,000 mg) of the stuff every
night for a month stomach discomfort and some
residual sleepiness were the only reported
side effects."
Melatonin

In humans, while no one has gone experimenting trying to kill people with melatonin, people HAVE tried to kill themselves with it! There is a report of 3 people who tried to commit suicide by taking a melatonin overdose. 2 of the people took 20 tablets of 3 milligrams each and the other one took 50 tablets of 3 milligrams each. All 3 were completely fine, had almost no Side Effects of Melatonin, no symptoms and required no medical treatment!!
The Melatonin Benefits are that this makes perfect sense because these people trying to commit suicide took a lower dosage than the daily dosage given to volunteers in several different studies!! One study gave women 300 mg for 4 months in a row. They had no problems at all. One study gave people one GRAM, 1000 milligrams, for a month with no problems. And yet another study gave people 6 grams (6000 milligrams) every day for a month with only some sleepiness in the morning.
 
One Case of Melatonin Overdose
In all the literature, there has actually only been ONE true reported case of Melatonin Overdose and that was an elderly man who took melatonin the evening before a surgery and became temporarily confused, which resolved without medical treatment.
While the report called this as 'melatonin overdose', this gentleman only took 24 milligrams of Melatonin Supplements.
With all of the safe reports of melatonin being taken at dosages 50 TIMES greater than the dosage he took, it makes one wonder if maybe he became confused because he didn't sleep well, or because he became somewhat dehydrated or had low blood sugar from not being able to eat and drink before the surgery.
But an overdose on melatonin? It seems unlikely. In any case, melatonin is extremely safe and there is really no known dose that causes a melatonin overdose.
 

Read more: http://www.easy-immune-health.com/melatonin-overdose.html#ixzz15YG3rzHR

Toxicol Sci. 1999 Aug;50(2):271-9.
Maternal and developmental toxicity evaluation of melatonin administered orally to pregnant Sprague-Dawley rats.
Jahnke G, Marr M, Myers C, Wilson R, Travlos G, Price C.
Reproductive Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Jahnke@NIEHS.NIH.gov
Abstract
Melatonin (MEL) is a widely used, over-the-counter sleep aid, and it has putative contraceptive, antioxidant, antiaging, and anticancer effects. The developmental toxicity potential for repeated oral doses of MEL had not previously been evaluated. In the present studies, time-mated, Sprague-Dawley-derived (CD) rats were administered MEL or vehicle by gavage on gestation days (gd) 6-19. MEL-treated groups received 1-, 10-, 100-, 150-, or 200-mg/kg body weight/day in the screening study (15 rats/group), and 50, 100, or 200 mg/kg/day in the definitive study (25 rats/group). In both studies, maternal food/water consumption, body weight, and clinical signs were monitored at regular intervals throughout gestation. At termination (gd 20, both studies), maternal liver and gravid uterine weights, number of ovarian corpora lutea, conceptus survival, fetal sex, and fetal body weight were evaluated. Fetal morphological examination included external structures (both studies) as well as visceral and skeletal structures (definitive study). In the screening study, maternal serum levels of 17beta-estradiol, progesterone, prolactin, and luteinizing hormone were determined by radioimmunoassay, and mammary tissue was fixed, stained, and evaluated for percent glandular area within the fat pad. No maternal morbidity/mortality was found in either study. In the screening study, aversion to treatment (> or =100 mg/kg/day) and reduced maternal weight gain (> or =150 mg/kg/day) were noted, but reproductive/endocrine parameters and fetal development were not affected. In the definitive study, aversion to treatment was noted at > or =50 mg/kg/day, and mild sedation, reduced maternal food intake, and reduced body weight gain were found during initial treatment with 200 mg/kg/day. MEL had no effect on prenatal survival, fetal body weight, or incidences of fetal malformations/variations. Thus, in the definitive study, the maternal toxicity NOAEL and LOAEL were 100 and 200 mg/kg/day, respectively, and the developmental toxicity NOAEL was > or =200 mg/kg/day.
PMID: 10478864 [PubMed - indexed for MEDLINE]Free Article

Arch Gen Psychiatry. 2006 Oct;63(10):1149-57.
Ramelteon: a novel hypnotic lacking abuse liability and sedative adverse effects.
Johnson MW, Suess PE, Griffiths RR.
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Abstract
CONTEXT: Ramelteon is a novel MT1 and MT2 melatonin receptor selective agonist recently approved for insomnia treatment. Most approved insomnia medications have potential for abuse and cause motor and cognitive impairment.
OBJECTIVE: To evaluate the potential for abuse, subjective effects, and motor and cognitive-impairing effects of ramelteon compared with triazolam, a classic benzodiazepine sedative-hypnotic drug.
DESIGN: In this double-blind crossover study, each participant received oral doses of ramelteon (16, 80, or 160 mg), triazolam (0.25, 0.5, or 0.75 mg), and placebo during approximately 18 days. All participants received each treatment on different days. Most outcome measures were assessed at 0.5 hours before drug administration and repeatedly up to 24 hours after drug administration.
SETTING: Residential research facility.
PARTICIPANTS: Fourteen adults with histories of sedative abuse.
MAIN OUTCOME MEASURES: Subject-rated measures included items relevant to potential for abuse (eg, drug liking, street value, and pharmacological classification), as well as assessments of a broad range of stimulant and sedative subjective effects. Observer-rated measures included assessments of sedation and impairment. Motor and cognitive performance measures included psychomotor and memory tasks and a standing balance task.
RESULTS: Compared with placebo, ramelteon (16, 80, and 160 mg) showed no significant effect on any of the subjective effect measures, including those related to potential for abuse. In the pharmacological classification, 79% (11/14) of subjects identified the highest dose of ramelteon as placebo. Similarly, compared with placebo, ramelteon had no effect at any dose on any observer-rated or motor and cognitive performance measure. In contrast, triazolam showed dose-related effects on a wide range of subject-rated, observer-rated, and motor and cognitive performance measures, consistent with its profile as a sedative drug with abuse liability.
CONCLUSION: Ramelteon demonstrated no significant effects indicative of potential for abuse or motor and cognitive impairment at up to 20 times the recommended therapeutic dose and may represent a useful alternative to existing insomnia medications.
PMID: 17015817 [PubMed - indexed for MEDLINE]Free Article

http://tnymed.com/?p=176

The medical world in general has a bad habit of finding one important function for a compound and paying little attention to other important functions.  Melatonin is a good example.  Every Dr. will know that it is made by our body and is so important for sleep that it is called the sleep hormone.  Some Drs. know that it’s levels drop with age and is an important antioxidant and anti-inflammatory.  Few know that it has powerful antidiabetic effects, can kill some cancers, will remove Amyloid Beta deposits from the brains of Alzheimer’s patients, reverse some types of kidney disease, protects the brain, is a major controller of colon health, can lower blood pressure, helps control the immune system, is important for healing and has many other important functions.  There are over 14,000 pieces of medical research readily available on melatonin and more for those who want to dig. Of importance to this presentation is that Melatonin has many powerful effects on Heart health.  Of importance here is that besides being a powerful antioxidant it has a strong influence on the entire antioxidant system, it has a powerful calming and controlling affect on the immune system (both important in stopping Heart Disease) and it can dramatically improve the repair of a damaged heart.The next report uses a lot of big words to explain how important Melatonin is to the heart and they only show a small part of what it does.  TNYMED
7: Cardiovasc Res.  2003 Apr 1;58(1):10-9. 
Melatonin: a novel protective agent against oxidative injury of the
ischemic/reperfused heart.
Reiter RJ, Tan DX.
Department of Cellular and Structural Biology, University of Texas Health
Science Center, San Antonio, TX 78229-3900, USA.  reiter@uthscsa.edu
This brief review summarizes the recently obtained evidence which illustrates
the beneficial effects of the endogenously produced antioxidant, melatonin, in
reducing tissue damage and reversing cardiac pathophysiology in models of
experimental ischemia/reperfusion.  
The report also describes the actions of other antioxidants, especially vitamin E and antioxidative enzymes, in altering the degree of ischemia/reperfusion damage in the heart. 
Based on the data available, melatonin seems to have advantages over other antioxidants tested in terms of ameliorating the hypoxia and reoxygenation-induced damage.  While the bulk of the studies that have used melatonin to overcome cardiac injury following transient arterial occlusion and subsequent reperfusion have used pharmacological doses to achieve protection, two recent reports have further shown that merely reducing endogenous circulating concentrations of melatonin (by surgical removal of a source of melatonin, i.e. the pineal gland) exaggerates the degree of injury and reduces survival of animals as a result of induced ischemia/reperfusion of the heart.
These findings are consistent with observations in other organs where the loss of physiological concentrations of melatonin results in increased oxidative damage during hypoxia and reoxygenation.
These findings have implications for the elderly since in the aged endogenous levels of melatonin are naturally reduced thereby possibly predisposing them to more severe cardiac damage during a heart attack.  To date, the bulk of the studies relating to the protective actions of melatonin in reducing cardiac ischemia/reperfusion injury have used the rat as the experimental model.  Considering the high efficacy of melatonin in limiting ischemia/reperfusion damage as well as melatonin’s low toxicity, the studies should be expanded to include other species and models of cardiac ischemia/reperfusion.  The results of these investigations would help to clarify the potential importance of the use of melatonin in situations of oxidative damage to the heart in humans.
Publication Types:
    Review
PMID: 12667942
This last piece of research shows more important functions of Melatonin on Heart health including a mention of it’s help in stabilizing Heart rhythms.  But, the section showing a major reduction of blood cholesterol levels and LDL artery deposits needs some explanation.  While the cholesterol lowering numbers are impressive and accurate, Melatonin works differently than dangerous statin drugs. 
Heart Disease always involves uncontrolled oxygen radicals.  These oxygen radicals interfere with the body’s tissues ability to absorb and properly use cholesterol and they oxidize the LDL cholesterol coming from the liver to the body tissues.  The body tissues do not want oxidized cholesterol and keep signaling for cholesterol they can use.  The liver keeps sending more cholesterol that gets oxidized.  The body is forced to use some of it but much of it builds up as unusable oxidized excess that adds to Heart Disease and raises LDL levels. 
Melatonin reduces oxygen radicals, protects the cholesterol from oxidation and improves the body’s tissues ability to use cholesterol efficiently.  The tissues get what they need and can use what they get so they stop demanding more and the cholesterol levels drop because the process begins to work.  This is what drops cholesterol and LDL levels.  Melatonin does not interfere with the production of cholesterol like statin drugs (which creates serious health problems).  Instead, melatonin helps the body to work in a healthy manor (pretty impressive for a safe natural compound that can be bought for a couple of bucks from several different discount department stores, huh!)   TNYMED
8: Neuro Endocrinol Lett.  2002 Apr;23 Suppl 1:79-83. 
Melatonin and the cardiovascular system.
Sewerynek E.
Department of Thyroidology, Institute of Endocrinology, Medical University of
Lodz, 91-425 Lodz, Sterlinga Str 5, Poland.  ewa@tyreo.am.lodz.pl
 
Melatonin concentrations in serum, as well as urinary levels of its main metabolite, 6-sulphatoxymelatonin, decrease with age.  In the course of aging, the frequency of Heart Diseases, both acute and chronic, systematically increases. 
The evidence from the last 10 years suggests that melatonin influences the cardiovascular system.  The presence of vascular melatoninergic receptors/binding sites has been demonstrated; these receptors are functionally linked with vasoconstrictor or vasodilatory effects of melatonin.  Melatonin can contribute in cardioprotection of the rat heart, following myocardial ischemia.
It has been shown that patients with coronary Heart Disease have a low melatonin
production rate, especially those with higher risk of cardiac infarction and/or sudden death.  There are clinical data reporting some alterations of melatonin in human stroke and coronary Heart Disease.  The suprachiasmatic nucleus and, possibly, the elatoninergic system may also modulate cardiovascular rhythmicity. 
Hypercholesterolemia and hypertension are the other age-related symptoms.  People with high levels of LDL-cholesterol have low levels of melatonin.  It has been shown that melatonin suppresses the formation of cholesterol by 38% and reduces LDL accumulation by 42%.  A 10-20% reduction of cholesterol concentration in women using the B-oval pill has been observed.  It is a very important because, even a 10-15% reduction in blood cholesterol concentration has been shown to result in a 20 to 30% decrease in the risk of
coronary Heart Disease.  People with hypertension have lower melatonin levels than those with normal blood pressure.  The administration of the hormone in question declines blood pressure to normal range.  It has been observed that melatonin, even in a dose 1 mg, reduced blood pressure and decreased catecholamine level after 90 min in human subjects. 
Melatonin may reduce blood pressure via the following mechanisms: 1) by a direct effect on the hypothalamus; 2) as an antioxidant which lowers blood pressure; 3) by decreasing the level of catecholamines, or 4) by relaxing the smooth muscle in the aorta wall.
Publication Types:
    Review
PMID: 12019357
 
Authors Notes:
The preceding is a very simplified and condensed overview of Heart Disease.  It omits many important concepts and a vast amount of important information but it is an accurate outline of the process.  There is a flawed understanding of Heart Disease in the medical world today.  I knew it was impossible to correct all of the flaws in a short presentation so I picked several of the worst and tried to explain them simply and include a little research to illustrate them. 
I have a Heart Disease presentation that is the result of condensing many thousands of medical research papers down to about 400 pages (the absolute minimum of information needed to show how Heart Disease actually works).  It starts with a very basic explanation of the disease process, where I get my information from and why the Medical doctors do not have this information.
It uses hundreds of different pieces of medical research to show how the deadly trio that I call Metabolic Mayhem (uncontrolled oxygen radicals, an overactive immune system and defective metabolic processes) creates and drives Heart Disease and many other diseases. (To document Metabolic Mayhem and I have over 200,000 different pieces of medical research from some of the best medical centers in the world).
This condensed 400-page report also shows medical research on natural compounds that can stop and reverse the Heart Disease process and even improve the repair process of a damaged Heart. 
 
Obviously 400 pages (and I’m still adding important information) of highly technical medical research is more than most people will read so I made this introductory presentation with a simplified explanation of Heart Disease and only 8 pieces of medical research.  There is one for each of the three deadly processes of Metabolic Mayhem that cause Heart Disease (uncontrolled oxygen radicals, an overactive immune system and defective metabolic processes) and 5 that illustrate how two safe, natural and researched compounds can dramatically improve Heart health.
 
I have documented many more natural compounds that help but there is no room to elaborate here.  When I have time I want to condense the big report down to something more manageable of approximately 200 pages.
I believe the first step in becoming healthy is to understand how body systems are supposed to work.  The second step is to understand what isn’t working properly in a disease  condition and the third step is to find safe, natural and medically proven compounds that can help the body work the way it is supposed to work.The medical information I use comes directly from the best medical research centers worldwide including those in America (it is amazing what is known in some US medical centers that can’t be used by doctors).

MAYBE HELPFUL…

Pharmacology. 2001;62(3):151-6.
Acute antidepressant-like and antianxiety-like effects of tryptophan in mice.
Wong PT, Ong YP.
Department of Pharmacology, Faculty of Medicine, National University of Singapore, Kent Ridge, Singapore 119260. phcwth@nus.edu.sg
Abstract
The antidepressant-like, antianxiety-like and sedative effects of tryptophan (TRP), in the absence and presence of p-chlorophenylalanine (p-CPA), and melatonin were studied in mice using the forced-swimming test, open-field test and activity cage, respectively. Single-dose TRP caused an antidepressant-like effect dose dependently up to 125 mg/kg. No significant effect was observed, however, when the TRP dose was increased to 250 mg/kg, i.e. a reversal of effect occurred at high dose. With p-CPA pretreatment, the effects observed at 125 and 250 mg/kg TRP were similar to those obtained at 50 and 125 mg/kg without p-CPA pretreatment, respectively. Melatonin also caused an antidepressant-like effect in a similar manner, but appeared to be less potent than TRP. These results strongly indicate that the antidepressant-like effect of TRP was due to its conversion to 5-hydroxytryptamine (5-HT). An antianxiety-like effect was observed for TRP only at 250 mg/kg dose together with p-CPA pretreatment, while no sedative effect was observed at all. In contrast, melatonin did not produce any antianxiety-like effect, but produced sedation at 200 mg/kg dose. It may be concluded that the antianxiety-like effect of TRP is unrelated to 5-HT and melatonin formation, but associated with TRP itself or, perhaps, with other anxiolytic metabolites.

 

 

 
Recommended Information