GSE
MELATONIN Health Benefits
Functions of MELATONIN
MELATONIN stimulates
immune system / immunomodulator
Evidence suggests an
immuno-enhancing function for MELATONIN
- stimulation of natural killer cell activity,
cytokine expression and inhibition of immune cell apoptosis have been reported.
A constant light
condition and drug-induced inhibition of MELATONIN synthesis in mice is associated with
suppressed humoral an cellular immunological responses
Guerrero
JM, Reiter RJ. MELATONIN-immune system relationships. Curr Top Med Chem
2002;2:167-79.
MELATONIN can interact with cells in lymphoid organs There is bidirectional
interaction between pineal gland and I.S. Since interleukins and cytokines (interferon
gamma) affect
MELATONIN synthesis/release
Withyachumnarnkul B, Nonaka KO, Santana
C, et al. Interferon-gamma modulates MELATONIN production in rat pineal glands
in organ culture. J Interferon Res 1990;10:403-11.
MELATONIN provides a link between the neuroendocrine
and immune systems. May be
explored in diseases that present daily rhythmic symptoms, such as rheumatoid
arthritis and nocturnal asthma.
Animal research has shown
that inhibition of MELATONIN synthesis
weakens cell-mediated immunity (acquired
immunity where T lymphocytes have predominant role)
and humoral immunity (immune response, mainly against bacterial
invasion, mediated by B cells).
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
MELATONIN increases production of interleukin 2 and 6 (IL-2 and IL-6).
MELATONIN receptors are found in lymphatic tissue, which supports the
premise that
MELATONIN has a direct regulating effect on the immune system. A study
evaluating IL-6 during nocturnal sleep,sleep deprivation and different sleep stages concluded that:
"Loss of sleep
may serve to decrease nocturnal IL-6 levels, with effects on the
integrity of immune system functioning . Alternatively, given the
association between sleep stages and IL-6 levels, depressed or
aged populations who show increased amounts of REM sleep and a
relative loss of slow wave sleep may have elevated nocturnal
concentrations of IL-6 with implications for inflammatory disease
risk ."
Laura Redwine,
Richard L.
Hauger, J. Christian
Gillin and Michael Irwin.
Effects of Sleep and Sleep Deprivation on
Interleukin-6, Growth Hormone, Cortisol, and MELATONIN Levels in Humans.
Home
Archive Oct 2000 85 (10): 3597
JCEM
MELATONIN is a powerful antioxidant
MELATONIN helps protect the body from cell damage caused by free radicals:
Direct scavenger of
OH• (hydroxyl radical), O2 •-(superoxide radical),
and NO•
(Nitric oxide) , ONOO- (Peroxynitrite
anion) , 1 O2
(singlet oxygen), and possibly
LOO• (peroxyl
radical); Neuroprotective - Can easily
cross cell membranes and the blood-brain barrier.
Kilic E, Özdemir
YG, Bolay H, Kelestimur H, Dalkara I. Pinealectomy aggravates and melatonin
administration attenuates brain damage in focal ischemia. J Cerebr Blood Flow Metab
19 511 -516,
1999 .Medline
Baydas, G., H. Canatan and A. Turkoglu, 2002.
Comparative analysis of the protective effects of melatonin and vitamin E on
streptozocin induced diabetes mellitus. J. Pineal Res., 32: 225-230.PubMed
"Suicidal
antioxidant "-
unlike other antioxidants (such as
vitamin C ),
MELATONIN can not be renewed antioxidant property).Demonstrated to prevent
some carcinogenic damage to DNA. Stops mechanism by which damaged DNA causes
cancer.Increases body's
"in-house" antioxidant
glutathione. Is equally effective
as this important antioxidantDebated as equal to
vitamin E as a chain-breaking antioxidant
against peroxyl radical.
Produced by lipid
peroxidation, which e.g. damages cell membranes altering cellular function. The
resulting cell membrane rigidity associated with aging;Scavenges initiating
radicals and breakdown products from lipid peroxidation.
Assured by the
fact that it scavenges 1 O2 ,
ONOO- and
OH• , all of which are
sufficiently reactive to initiate the peroxidative process. Prevents otherwise
harmful changes to membrane fluidity and function.Greatly reduced
inflammatory response. Both ONOO-
and NO• are believed
to be the mediators of the inflammation in animals treated with carrageenan
Beckman J.S., Koppenol W.H. Nitric oxide, superoxide, and peroxynitrite: The
good, the bad and ugly// Am. J. Physiol.-1996
Protected against
brain injury caused by ROS release in newborn rats - May reduce damage caused by some types of
Parkinson's disease
May play a role in preventing cardiac
arrhythmia May increase longevity.
Shown to increase
average life span of mice by 20% in some studies. Protects against sunburn.
Scientists at
University of Zurich found that
MELATONIN protects against
UV radiation if topically applied before skin exposure; Role in repairing burned
skin. In a
study in Brain Research Bulletin,
MELATONIN levels rose six
hours after burn injury, then fell to normal.May prevent
cataract formation In small amounts, causes
skin cells to proliferate. In large amounts it stops proliferation.
People with psoriasis and atopic eczema have peak
MELATONIN in the day (instead of at night), and
low levels at night; not too surprising in that some scientists consider the
skin to be another gland.
MELATONIN enhances
bone mass
Bone health.
Bone resorption is
a process by which osteoclasts break down bone and release the minerals.
MELATONIN has been shown to inhibit bone
resorption and increase bone mass through its ability to down-regulate
activation of osteoclasts.
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
An adequate amount of
ESTRADIOL is also needed for MELATONIN to benefit bone (a salivary
ESTRADIOL test may be useful in cases where
MELATONIN is low and bone loss is a
concern).High CORTISOL levels also contribute to bone loss.
Raff H,
Raff JL,
Duthie EH,
Wilson CR,
Sasse EA,
Rudman I,
Mattson D.
Elevated salivary cortisol in the evening in healthy elderly men and women:
correlation with bone mineral density.
J Gerontol A
Biol Sci Med Sci. 1999 Sep;54(9):M479-83.
PubMed
MELATONIN is an anti-cancer agent
At present, the validity
of
MELATONIN
as an oncostatic agent seems well established.
The antitumor mechanisms of
MELATONIN have been identified, including:
Anti-proliferative actions
Immuno-stimulatory effects on host
anti-cancer defenses
Antioxidant
activity.
Circulating levels of MELATONIN are
depressed in a wide variety of cancers. Including breast, endometrial, prostate, lung, gastric and colon.
Bartsch C ,
Bartsch H .MELATONIN in
cancer patients and in tumor-bearing animals.
Adv Exp Med Biol.
1999;467:247-64.
PubMed
There are, however, isolated reports of tumor
growth stimulation, especially if
MELATONIN is administered in the morning.
Indicating a
circadian-stage dependency of antitumor action.
Bartsch H, Bartsch C. Effect of
MELATONIN on experimental tumors under
different photoperiods and times of administration. J Neural Transm
1981;52:269-79.
A recent controlled
trial shows the possibility to improve chemotherapy
- in terms of both survival and
quality of life of patients with advanced disease by a concomitant
administration of MELATONIN and cisplatinium etoposide in metastatic non small
cell lung cancer.
Lissoni P, Chilelli M, Villa S, et al. Five
years survival in metastatic non-small cell lung cancer patients treated with
chemotherapy alone or chemotherapy and MELATONIN :
Breast Cancer
Breast cancer risk was
increased among subjects who frequently did not sleep during the period of the
night when MELATONIN levels are typically at their
highest. There was also an
indication of increased risk among subjects with the brightest bedrooms.
Graveyard shiftwork was associated with increased breast cancer risk.
Night shift
work, Light at night, and Risk of breast cancer
Breast Cancer research
clearly shows solid links between low late-night MELATONINand increased breastcancer cell growth.
A study demonstrated that
MELATONIN -rich blood suppressed the growth of
human breast cancer xenografts and rat hepatomas.
No growth suppression occurred in tumors perfused with
MELATONIN -deficient blood
collected from the same women after short-term ocular exposure to bright light
at night.
Blask DE
et al. MELATONIN-depleted blood from premenopausal women exposed to light at
night stimulates growth of human breast cancer xenografts in nude rats.
Cancer Res.
2005 Dec 1;65(23):11174-84.
Pub Med
CORTISOL
levels are also tied to breast cancer risk.
Breast cancer
patients with high average CORTISOL throughout
the day and elevated CORTISOL at bedtime have
earlier mortality, lower natural killer (NK) cell counts and decreased activity
of NK cells The strength of the relationship between CORTISOL
and
MELATONIN levels
Sandra E. Sephton,
Robert M. Sapolsky,
Helena C. Kraemer,
David SpiegelDiurnal Cortisol Rhythm as a Predictor of Breast Cancer Survival.
Oxford Journals MedicineJNCI
Volume92, Issue12 Pp. 994-1000
JNCI
Reduced
MELATONIN
production has been proposed as a likely factor in the significantly higher
cancer rates in night workers. In 2007,
The World Health
Organization cited late night shift work as a probable cancer-causing agent .
When someone works
in artificial light, they generally have lower
MELATONIN , and without this
antioxidant and suppressant of tumor
development, they may be more likely to develop cancer.
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.
Lower nocturnal MELATONIN
levels
are associated withlarger tumors in patients with primary prostate cancer
Vijayalaxmi, Charles R. Thomas, Jr, Russel J. Reiter, Terence S. Herman.
MELATONIN :
From Basic Research to Cancer Treatment Clinics.Journal of Clinical
Oncology , Vol 20, Issue 10 (May), 2002: 2575-2601JOCO
Endogenous
MELATONIN
stimulates anti-cancer defenses and exhibits anti-proliferative and antioxidant
activity
Claustrat B ,
Brun J ,
Chazot G .
The basic physiology and pathophysiology of
MELATONIN .Sleep Med Rev. PubMed
MELATONIN protects the GI tract and pancreas
MELATONIN
is
produced by enterochromaffin cells of the GI mucosa and discharged into the gut
lumen. Where, produced in amounts many times greater than the
pineal gland,
MELATONIN has several
surprising roles protecting the GI tract from damage and preventing forms of
gastritis.
Although
MELATONIN produced in the GI tract has a direct effect on GI
tissues, its major influence on GI organs seems to occur indirectly via the
brain-gut axis. Since the GI tract
source of
MELATONIN also contributes
to circulatory levels. Mechanisms affecting GI organs include peripheral
receptors, sensory afferent (vagal or sympathetic) pathways and the central
nervous system (CNS) acting on these organs via autonomic means.
MELATONIN protects gastrointestinal esophageal mucosa
and against various types of injury
Konturek SJ, Zayachkivska O, Havryluk XO, Brzozowski T, Sliwowski Z, Pawlik M,
Konturek PC, Cze?nikiewicz-Guzik M, Gzhegotsky MR, Pawlik WW.Protective
influence of MELATONIN against acute
esophageal lesions involves prostaglandins, nitric oxide and sensory nerves. J
Physiol Pharmacol. 2007 Jun;58(2):361-77.[PubMed ]
Jaworek J, Brzozowski T, Konturek SJ.
MELATONIN as an organoprotector in the
stomach and the pancreas. J Pineal Res. 2005;38:73-83. [PubMed ]
Thor PJ, Krolczyk G, Gil K, Zurowski
D, Nowak L. MELATONIN and serotonin effects
on gastrointestinal motility. J Physiol Pharmacol. 2007;58 Suppl 6:97-103.
[PubMed ]
MELATONIN protects duodenal
(1st part of small intestine)
epithelium against gastric H+
By stimulating
HCO3 - secretion from enterocytes.
Konturek PC, Konturek SJ, Hahn EG.
Duodenal alkaline secretion: its mechanisms and role in mucosal protection
against gastric acid. Dig Liver Dis. 2004;36:505-512. [PubMed ]
Low levels of
MELATONIN can lead to ulcers, gastroesophageal reflux
disease (GERD) and sleep disorders. Commonly, patients with GERD also have a sleep
disorder.
de Souza Pereira R. Regression of an
esophageal ulcer using a dietary supplement containing
MELATONIN . J Pineal Res. 2006;40:355-356.
[PubMed ]
Pereira Rde S. Regression of
gastroesophageal reflux disease symptoms using dietary supplementation with
MELATONIN , vitamins and aminoacids:
comparison with omeprazole. J Pineal Res. 2006;41:195-200. [PubMed ]
Stress / anxiety disorders.
May cause
tryptophan depletion, and as a consequence, low
MELATONIN levels, since
MELATONIN is a metabolite of this amino acid found in
certain protein foods.
Zimmermann RC, McDougle CJ,
Schumacher M, Olcese J, Mason JW, Heninger GR, Price LH. Effects of acute
tryptophan depletion on nocturnal MELATONIN secretion in
humans. J Clin Endocrinol Metab. 1993;76:1160-1164.
[PubMed ]
MELATONIN appears to
be implicated in stimulation of pancreatic enzyme secretion after eating.
Mediated byMELATONIN -induced
release of cholecystokinin, acting through entero-gastro-pancreatic reflexes.
Jaworek
J, Brzozowski T,
Konturek SJ.
MELATONIN
as an organoprotector in the stomach and the pancreas .
J Pineal Res.
2005 Mar;38(2):73-83.
MELATONIN's GI tract/ pancreas protective/healing
mechanisms. Increasing
MELATONIN levels should be considered for its
substantial role in prevention of gastric and pancreatic damage and in
accelerating healing of gastric ulcers.
Damage-protective
mechanisms of pancreas and GI tract. MELATONIN prevents various forms of gastritis and pancreatitis, via:
- Activation of specific MT2-receptors
- Scavenges
reactive oxygen species (ROS)
- MELATONIN cou nteracts the increase in the ROS- induced
lipid peroxidation and is partly responsible for preserving the activity of key
anti-oxidizing enzymes such as superoxide dismutase(SOD)
Accelerates the healing
of chronic gastric ulcerations
- By stimulating the microcirculation
- Interact ing withinflammation-controlling prostaglandins, nitric oxide released from vascular
endothelium, and/or sensory nerves and with their neuropeptides.
