"Melatonin (pronounced /?m?l?'to?n?n/
( listen)), also known chemically as N-acetyl-5-methoxytryptamine,
is a naturally occurring hormone found in most animals,
including humans, and some other living organisms, including
algae. Circulating levels vary in a daily cycle,
and melatonin is important in the regulation of the
circadian rhythms of several biological functions.
Many biological effects of melatonin are produced through
activation of melatonin receptors, while others are
due to its role as a pervasive and powerful antioxidant
with a particular role in the protection of nuclear
and mitochondrial DNA. Products containing melatonin
have been available as a dietary supplement in the United
States since 1993. Foods may contain trace amounts
of melatonin, but no food has been found to elevate
plasma melatonin levels. 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." http://en.wikipedia.org/wiki/Melatonin
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
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,
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."
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
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
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!
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
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
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
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
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
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
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.
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
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
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.
7: Cardiovasc Res. 2003 Apr 1;58(1):10-9.
Melatonin: a novel protective agent against oxidative
injury of the
Reiter RJ, Tan DX.
Department of Cellular and Structural Biology, University
of Texas Health
Science Center, San Antonio, TX 78229-3900, USA.
This brief review summarizes the recently obtained evidence
the beneficial effects of the endogenously produced
antioxidant, melatonin, in
reducing tissue damage and reversing cardiac pathophysiology
in models of
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.
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!)
8: Neuro Endocrinol Lett. 2002 Apr;23 Suppl
Melatonin and the cardiovascular system.
Department of Thyroidology, Institute of Endocrinology,
Medical University of
Lodz, 91-425 Lodz, Sterlinga Str 5, Poland. firstname.lastname@example.org
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,
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.
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
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).
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.
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.