Melatoninand
Lifestyle Diseases Dr. Fathi Neana, MD
Chief of OrthopaedicsDr. Fakhry & Alrajhy Hospital
Saudi ArabiaDecember, 11 – 2016
11 Lifestyle diseases you should take seriouslyRenita Tisha Pinto, Health Me Up | Oct 2, 2015
Globally 14.2 million people - 30-69 years olddie / year from these diseases.
These diseases emerged as bigger killers than infectious or hereditary ones.
Lifestyle diseases
Type II diabetes Arteriosclerosis Heart disease High blood pressure Swimmer's earCancer Stroke Chronic obstructive pulmonary disease CirrhosisNephritis Obesity & Metabolic syndrome
Lifestyle diseasesOrthopaedic complaints accounts for the epidemic proportions (cases of low back ache, joint disorders,
degenerative diseases that we find in our clinics and also around us)
Orthopedic disorders Metabolic syndromeNeck & LBPDeg Disc disorders - SpondylosisDeg Joint diseases - OAOsteoporosisOsteomalacia/RicketsInflammatory joint diseasesAuto immunityFracturesHost A B CSurgical difficultiesComplications
The common risk factors attributing to the orthopedic complaints are:
Lack of proper exercisesImproper posturesSedentary lifestyleChange in work methodsObesityLack of Nutritious diet (especially vitamins and minerals)Stress, Stress, Stress!!!
Healthy lifestyle vs medicines include:Regular exerciseHealthy eatingProper postureNo smokingManaging stress
سباتا ) نومكم لباسا( )9وجعلنا يل الل معاشا( 10وجعلنا هار الن وجعلنا(11)
النبإ سورة9. “And We made your sleep for repose,” 10. “And We made the
night as a covering” 11. “And We made the day for (seeking) livelihood,”
سباتا )و نومكم لباسا( )9جعلنا يل الل معاشا( 10وجعلنا هار الن وجعلنا(11)
النبإ سورة9. “And We made your sleep for repose,” 10. “And We made the
night as a covering” 11. “And We made the day for (seeking) livelihood,”
Blue light like from monitor screens suppress almost completely melatonin secretion
NB: Blue light from television, PC and laptop screens, smart phones are of the sources of the worst blue lights one can be exposed to and by leaving a television set or laptop
screen on during the night will suppress melatonin production significantly.
Melatonin, hormone secreted by the pineal gland
Melatonin was first isolated in 1958 by American physician Aaron B. Lerner and his colleagues at Yale
University School of Medicine
They gave the substance its name on the basis of its ability to lighten skin colour in frogs by reversing the skin-
darkening effects of melanocyte-stimulating hormone .
Melatonin, a derivative of the amino acid tryptophan ,In humans, melatonin plays an important role in the
regulation of sleep cycles (i.e., circadian rhythm).
Serotonin N transferase: the rate-limiting enzyme
Melatonin synthesis
The pineal glandThe retina
LymphocytesThe GI tract
Bone marrow cellsPlatelets
Skin
Melatonin's immediate precursor is the neurotransmitter Serotonin
A major player in regulating of the mood
Like serotonin, melatonin plays important roles in physical and
mental health
Physical and Mental health
Central and peripheral clocks in mammalsOrganized in a hierarchical manner
Central oscillator: controls the behavioral rhythm reset by external light signal
Peripheral oscillators : slave oscillators
regulate local rhythms reset by feeding
Circadian rhytms are endogenously generated; modulated by external signals (day/night rhytm)
Circadian rhytms – brain wave activity, hormone production, cell regeneration and other biological activities linked to this daily cycle
Regulation of a circadian rhytm1- The retinohypothalamic tract , the information about illumination from the retina (retinal
ganglion cells with melanopsin); 2. The circadian "clock" in the suprachiasmatic nucleus (SCN)3. The SCN interprets the information on day lenght and passes it on to the pineal gland which
then secretes the hormone melatonin (secretion of melatonin peaks at night)
Melatonin participates in various physiological functions according to 24-hour cycle
A circadian rhytm is 24-hour cyclein the physiological processes of living beings
Melatonin:
Ubiquitously in nature (everywhere, same time)One of the most phylogenetically ancient of all biological signaling mechanisms
A potent antioxidant (its primary function)
AntioxidantBesides its function as synchronizer of the biological clock, melatonin is a powerful free-radical scavenger and wide-spectrum antioxidant as discovered in 1993.[52] In many less-
complex life forms, this is its only known function.[27] Melatonin is an antioxidant that can easily cross cell membranes and the blood-brain barrier.[6][53] This antioxidant is a direct
scavenger of radical oxygen and nitrogen species including OH•, O•2
−, and NO•.[54][55]
Melatonin works with other antioxidants to improve the overall effectiveness of each antioxidant.[55] Melatonin has been proven to be twice as active as vitamin E, believed to be the most effective lipophilic antioxidant.[56] An important characteristic of melatonin that distinguishes it from other classic radical scavengers is that its metabolites are also
scavengers in what is referred to as the cascade reaction.[27] Also different from other classic antioxidants, such as vitamin C and vitamin E, melatonin has amphiphilic
properties. When compared to synthetic, mitochondrial-targeted antioxidants (MitoQ and MitoE), melatonin proved to be a comparable protector against mitochondrial oxidative
stress.[57]
Melatonin is involved in various physiological functions:
Circadian rhytm regulation, sleep propensity, control of sleep/wake rhytm,
blood pressure regulation, immune function, retinal functions,
detoxification of free radicals, control of tumor growth,
bone protection, the regulation of bicarbonate secretion in the GI tract
Melatonin in plants
in high concentrations (protection from oxidative damage) many plants represent an excellent dietary source of melatonin as an antioxidant
nutrient
The majority of herbs used in traditional Chinese medicine for retarding age-related changes and for treating diseases associated with the generation of free radicals
contain the highest levels of melatonin
Melatonin is primarily secreted by the pineal gland; synthesis also occurs in other cells and organs
secretion is synchronized to the light/dark cycle, with a nocturnal maximum
Exogenous administrationCircadian rhytm sleep disorders (CRSD), insomnia, cancer, neurodegenerative diseases,
disorders of the immune function, oxidative damage
Melatonin exerts actions in almost every cell in the body
1. Melatonin receptors-receptor mediated effects
2. Melatonin diffuses through membranes easily- receptor independent effects
Melatonin produces effects in:
Receptor-independent:
1. Free radical scavenging properties2. Inhibition of calmodulin
-an attenuation of cAMP-dependent signaling cascades-decrease ER binding and activation of ERE-containing genes3. Regulation of the quinone reductase 2 activity
Receptor-dependent:
1. G-protein coupled receptors (MT1 or MT2)- an attenuation of cAMP-dependent signaling cascades
- inhibition of ER 2. The mitogen activated protein kinase cascade (MEK/ERK)
Melatonin
Circadian pacemaker: suprachiasmatic nucleus
Seasonal breeding (hypothalamus and other
organs relevant to reproduction)
Vasomotor control: constriction via MT1 dilation via MT2
Immune system (B cells, T cells, NK cells, thymocytes,
bone marrow)
Scavenging of reactive oxygen species (ROS), reactive nitrogen species (RNS)
and organic radicals
Elimination of toxic quinones
CNS: antiexcitatory effects, avoidance of Ca2+ overload
Cytoskeletal effects: binding to calmodulin, activation of protein
kinase C
Upregulation of antioxidant and downregulation of prooxidant
enzymes
Attenuation of mitochondrial electron leakage
Decrease of free radicals and other oxidants
Prevention of apoptosis
Direct inhibition of mitochondrial permeability transition pore
opening
MT1, MT2
Quinone reductase 2 (MT3)
More efficient than other antioxidants; devoid of pro-oxidant side-effects
1. Scavenging of free radicals2. Up-regulation of antioxidant enzymes
3. Direct inhibition of free radical formation
Neurodegenerative diseases (Alzheimer‘s, Parkinson‘s and Huntington‘s disease) - potential role of
melatonin
Melatonin as an antioxidantMelatonin Combats Inflammation able to cross the blood-brain barrier
Melatonin Combats Inflammation, Offers Mood and Anti-Aging Brain SupportMelatonin is a powerful antioxidant and free radical scavenger that helps 'cool
down' excess inflammation.
Melatonin is so integral to the health of immune system . A lack of it causes thymus gland, a key component of immune system, to shrink in size
Because melatonin is a strong antioxidant and is able to cross the blood-brain barrier, it is thought to help protect against Alzheimer's disease as well as
brain aging.
Melatonin as an antioxidantMelatonin Combats Inflammation able to cross the blood-brain barrier
1. Antioxidant activity2. Modulation of the estrogen signalling pathway
Melatonin has demonstrated oncostatic effects against a variety of tumor cells: estrogen-positive breast cancer cell lines, ovarian carcinoma cell lines, endometrial carcinoma,
human uveal melanoma cells, prostate tumor cells, intestinal tumors
Melatonin ameliorates side effects of antitumoral therapeutic regimens (myelotoxicity, lymphocytopenia)
Melatonin as an oncostatic substanceMelatonin inhibits the carcinogenesis
1- melatonin has a calming effect on several reproductive hormones, which may explain why it seems to protect
against sex hormone-driven cancers
2- Causing cancer cells to self-destruct, melatonin boosts production of immune-optimizing substances such as
interleukin-2, which helps identify and attack the mutated cells that lead to malignant cancer
Melatonin's Role in Fighting Cancer
Some of the more impressive studies include the following:•The journal Epidemiology5 reported increased breast cancer risk among women who
work predominantly night shifts•Women who live in neighborhoods with large amounts of night time illumination are more likely to get breast cancer than those who live in areas where nocturnal darkness
prevails, according to an Israeli study6•From participants in the Nurses' Health Study, it was found that nurses who work
nights had 36 percent higher rates of breast cancer7•Blind women, whose eyes cannot detect light and so have robust production of
melatonin, have lower-than-average breast cancer rates8•When the body of epidemiological studies are considered in their totality, women who
work night shift are found to have breast cancer rates 60 percent above normal, even when other factors such as differences in diet are accounted for9
Melatonin's Role in Fighting CancerThe greatest area of melatonin research to date has to do with breast
cancer.
1. Enhances the production of cytokines2. Antiapoptotic and antioxidant actions
3. Direct effect on the regulation of the immune system (via receptors)
Inhibition of melatonin synthesis results in the attenuation of cellular and humoral responses: exogenous melatonin
counteracts immunodeficiences The role of melatonin in the pathogenesis of autoimmune
diseases: the increased prevalence of auto-immune diseases at winter (long nights, increased levels of melatonin)
Melatonin‘s immunomodulatory functionMelatonin has an immunomodulatory role
MT1 receptors in SCN
The treatment of insomnia (particularly in individuals with melatonin deficiency)
Melatonin as a hypnoticMelatonin promotes sleep in healthy humans
MT2 receptors in SCN
Implication in circadian rhythm sleep disorders1. Shift-work disorder
2. Jet lag syndrom3. Delayed sleep phase syndrome
4. Circadian rhythm disruption with ageing
Melatonin as a chronobiotic moleculeMelatonin acts as an endogenouos synchronizer of
bodily rhythms
Melatonin is synthesized in the enterochromaffin cells of the GI tract and can be released to the circulation
Functions in the GIT:1. Increase duodenal mucosal secretion of bicarbonate -
duodenal protection against gastric acid2. High concentration in the bile-prevents oxidative
damage to the intestinal epithelium caused by bile acids3. Gastroprotective efficacy: as an antioxidant
GIT melatonin
Melatonin reduces blood pressure in hypertensive patients
1. Peripheral mechanism: vasodilatation via MT2
vasoconstriction via MT1 (cerebral vessels)2. Central mechanism
Melatonin in cardiovascular diseases
Melatonin stimulates the appearance of 'beige' fat, which, similar to brown fat
The study… showed that chronic administration of melatonin sensitizes the thermogenic effect of exposure to cold, heightens
the thermogenic effect of exercise and, therefore, constitutes excellent therapy against obesity.
'beige fat' cell mitochondria express levels of UCP1 protein, responsible for burning calories and generating heat."
Melatonin Help You Fight Fat?
Beneficial effects for heart disease, including reducing the severity of high blood pressure, limiting the frequency of heart
failure and protecting against drug-related damage to the heart.Useful for restoring imbalances in bone remodeling to prevent
bone losslower levels of melatonin have double the risk of developing type
2 diabetes Reduced the frequency of migraine headaches by half (or more)
after three months
Help for Heart Disease, Headaches, Diabetes and Osteoporosis?
Melatonin causes inhibition of bone resorption (protects bone during treatment with gluococorticoids that affect
bone remodeling and cause osteoporosis)
1. Down-regulation of osteoclast activation2. Direct inhibition of osteoclast function (antioxidant)
Melatonin effects on bone
1. Via MT receptors2. Via nuclear receptors
Melatonin inhibits the hypothalamic-pituitary-gonadal axis (important for sexual maturation)
The decline in melatonin concentration is very important for the initiation of puberty
Melatonin down-regulates GnRH gene in a cyclicyl pattern over a 24-h period; the pulsatile secretion of GnRH controls
LH a FSH
Melatonin in sexual maturation and in reproduction
Melatonin Regulates Our Cycles, Mood, Reproduction, Weight and May Help Combat Cancer
October 10, 2013 | 279,344 views
01 AUG 2016Melatonin – health and repair mechanisms
By Robert Gorter, MD, PhD,
Melatonin help us to sleep. This benefit is only one of many.
Melatonin protect against heart disease, diabetes, Alzheimer's & migraine headaches? It help with weight control , strengthening the immune system?
It play a role in cancer prevention.
Artificial lighting, laptop & TV monitors , smart phones disrupts melatonin production . Many Americans may be lacking this 'wonder hormone.
Disorders of melatonin
• Hypomelatonism
• Hypermelatonism
• Dysmelatonism
Hypomelatonism
• Old age• Pineal tumors• Psychiatric
disorders: depression, schizophrenia
• Mentally retarded and autistic
• Alcohlism
• Autonomopathy• Klinefelder's and Turner's
syndrome• Neoplasm: liver, kidney,
upper respiratory tract, breast, skin and prostate
• Some cases of coronary heart disease.
Drug induced hypomelatonism
• Beta blockers: Metaprolol->propranolol->Atenolol
• Alpha 2 blocker: Clonidine• Naloxone• NSAID ibuprofen • Alcohol, tobacco, caffeine• Benzodiazepine
Effects of hypomelatonismDecreased immune function
Blood pressure instabilityIncreased plaques in the brain, like those seen with
Alzheimer's diseaseDiabetic microangiopathy (capillary damage)
Accelerated cancer cell proliferation and tumor growth (including leukemia)
Decreased free radical scavenging Increased risk of osteoporosis
Depression and/or seasonal affective disorder (SAD)
insomniadifficulty getting to sleepdifficulty falling back to sleep when awaken during the nightlight sleeper/easy waking during the nightearly morning awakeningun-refreshing sleeplack of dreamingfamily history of insomniapersonal or family history of breast cancerpersonal or family history of prostate cancerprostate enlargementfatigue
depressionirregular menstrual cycleunusual menstrual flow (light or heavy)PMSscoliosispoor sleeping prior to mensesanxietysensitivity to stresscataractsneurodegerative disorder (MS, Parkinson's, Alzheimer's, ALS, etc)elevated cholesterolhigh blood pressureblood clotsheart attackheart arrhythmias
Common symptoms and signs of melatonin deficiencyto many to remember
Hypermelatonism
Seasonal affective disorder (SAD)
• Extreme fatigue and lack of energy• Increased need for sleep• Carbohydrate cravings• Weight gain• Reduced work productivity• Withdrawal from social contacts• Exposure to light improve
Dysmelatonism
Circadian rhythm Syndrome• Blind• Jet lag• Night shift workers ( Industrial
jet lag)• Delayed sleep phase syndrome
• Disruption of sleep• Decreased attention
span– Decreased work
efficiency – Work- and non-work
related accidents• Irritability• Headaches
• Fatigue
• Substance abuse• Depression• Reduced Immunity
• Cardiovascular and • Gastrointestinal
disorders
DysmelatonismClinical features of Circadian rhythm Syndrome (CRS)
Natural way to increase melatonin
• Early to bed and early to rise• Food: Oats, sweet corn, rice, barley,
tomatoes and bananas• Vitamin B3, B6 (dried apricots, barley,
whole wheat, tuna and turkey, rice, bananas, lentils, shrimp and carrots)
Foods containing melatonin or induce the natural production of melatoninImprove your nights sleep with these
9 foods Turkey Oats Almonds Marmite
بخميرة/ أسود عسل مارمايت Warm milk Bananas Tart CherriesGrapes Whole Grain Cereals
سباتا ) نومكم لباسا( )9وجعلنا يل الل معاشا( )10وجعلنا هار الن النبإ( 11وجعلنا سورة9. “And We made your sleep for repose,” 10. “And We made the night as a covering” 11. “And We
made the day for (seeking) livelihood,”
Deep sleep in the dark is the cheapest source of Melatonin
Conclusions
Melatonin is distributed widely in nature; it acts as a photoperiod messenger molecule, transducing photoperiod changes to various
cyclic function in organism (reproduction, sleep-wake rhythms)
Melatonin is very important antioxidant (primary function in evolution)
Melatonin influences various cell mechanisms via receptors (plasmatic, nuclear)
Melatonin play a role in many pathological states: neurodegenerative disorders, circadian rhythm sleep disorders, depression, cardiovascular
diseases, tumor growth, immune pathologies, bone resorption (potential therapeutic agent)
Summary
The New Lifestyle diseases is a Buzzlesearching for an answer
How to avoid Lifestyle diseases
My long life experience precious advice is
1- Trusted sources then Calibrate with the absolute truth2- Live a Biological, Anti inflammatory and Natural Life style
Attach to the absolute truths in the sayings of almightly ALLAH and his Messenger (peace and
blessings be upon him)
Avoid Mankind processed deviations & inherited Myths
How to Improve and Protect Your Melatonin ProductionImprove your sleep hygiene, article "33 Secrets to a Good Night's Sleep.”
Avoid watching TV or using computer in the evening, at least an hour before going to bed.
Make sure you get BRIGHT sun exposure regularly. Sleep in complete darkness, or as close to it as possible.
Install a low-wattage yellow, orange or red light bulb if you need a source of light for navigation at night.
Keep the temperature in your bedroom no higher than 70 degrees F. optimal room temperature for sleep is 60 to 68 degrees F.
Take a hot bath 90 to 120 minutes before bedtime. Avoid using loud alarm clocks. Regular enough sleep, not even need an alarm.
Get some sun in the morning, Circadian system needs bright light to reset itself. Be mindful of electromagnetic fields in your bedroom. EMFs can disrupt your
pineal gland and its melatonin production, and may have other negative biological effects as well.