Melatonin is a hormone that regulates sleep-wake cycles and is produced by the pineal gland. Lifestyle diseases such as diabetes, heart disease, and cancer have emerged as major global killers. Melatonin plays various roles in the body including as an antioxidant, immunomodulator, and in circadian rhythm regulation. It may help reduce the risk of lifestyle diseases by combating inflammation, protecting against cancer, and supporting brain and heart health. Melatonin levels decline with age and certain lifestyle factors like light exposure at night, and restoring optimal melatonin levels may support health.

1. Melatonin
and
Lifestyle Diseases
Dr. Fathi Neana, MD
Chief of Orthopaedics
Dr. Fakhry & Alrajhy Hospital
Saudi Arabia
December, 11 – 2016

2. 11 Lifestyle diseases you should take seriously
Renita Tisha Pinto, Health Me Up | Oct 2, 2015
Globally 14.2 million people - 30-69 years old
die / year from these diseases.
These diseases emerged as bigger killers than infectious or
hereditary ones.

3. Lifestyle diseases
Type II diabetes
Arteriosclerosis
Heart disease
High blood pressure
Swimmer's ear
Cancer
Stroke
Chronic obstructive
pulmonary disease
Cirrhosis
Nephritis
Obesity & Metabolic
syndrome

4. Lifestyle diseases
Orthopaedic 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 syndrome
Neck & LBP
Deg Disc disorders - Spondylosis
Deg Joint diseases - OA
Osteoporosis
Osteomalacia/Rickets
Inflammatory joint diseases
Auto immunity
Fractures
Host A B C
Surgical difficulties
Complications
The common risk factors attributing to the
orthopedic complaints are:
Lack of proper exercises
Improper postures
Sedentary lifestyle
Change in work methods
Obesity
Lack of Nutritious diet (especially vitamins and
minerals)
Stress, Stress, Stress!!!
Healthy lifestyle vs medicines include:
Regular exercise
Healthy eating
Proper posture
No smoking
Managing stress

5. ‫ا‬ً‫ت‬‫ا‬َ‫ب‬ُ‫س‬ ْ‫م‬ُ‫ك‬َ‫م‬ ْ‫َو‬‫ن‬ ‫َا‬‫ن‬ْ‫ل‬َ‫ع‬َ‫ج‬ َ‫و‬(9)‫ا‬ً‫س‬‫ا‬َ‫ب‬ِ‫ل‬ َ‫ل‬ْ‫ي‬َّ‫الل‬ ‫َا‬‫ن‬ْ‫ل‬َ‫ع‬َ‫ج‬ َ‫و‬(10)‫ا‬ً‫ش‬‫ا‬َ‫ع‬َ‫م‬ َ‫ار‬َ‫ه‬َّ‫ن‬‫ال‬ ‫َا‬‫ن‬ْ‫ل‬َ‫ع‬َ‫ج‬ َ‫و‬(11)
‫النبإ‬ ‫سورة‬
9. “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,”

6. ‫و‬‫ا‬ً‫ت‬‫ا‬َ‫ب‬ُ‫س‬ ْ‫م‬ُ‫ك‬َ‫م‬ ْ‫َو‬‫ن‬ ‫َا‬‫ن‬ْ‫ل‬َ‫ع‬َ‫ج‬(9)‫ا‬ً‫س‬‫ا‬َ‫ب‬ِ‫ل‬ َ‫ل‬ْ‫ي‬َّ‫الل‬ ‫َا‬‫ن‬ْ‫ل‬َ‫ع‬َ‫ج‬ َ‫و‬(10)‫ا‬ً‫ش‬‫ا‬َ‫ع‬َ‫م‬ َ‫ار‬َ‫ه‬َّ‫ن‬‫ال‬ ‫َا‬‫ن‬ْ‫ل‬َ‫ع‬َ‫ج‬ َ‫و‬(11)
‫النبإ‬ ‫سورة‬
9. “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,”

10. 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.

12. 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).

13. Serotonin N transferase: the rate-limiting enzyme
Melatonin synthesis
The pineal gland
The retina
Lymphocytes
The GI tract
Bone marrow cells
Platelets
Skin

14. 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

15. Central and peripheral clocks in mammals
Organized 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

16.  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 rhytm
1- 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 cycle
in the physiological processes of living beings

17. Melatonin:
Ubiquitously in nature (everywhere, same time)
One of the most phylogenetically ancient of all biological signaling mechanisms
A potent antioxidant (its primary function)
Antioxidant
Besides 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]

18. 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

19. 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 administration
Circadian rhytm sleep disorders (CRSD), insomnia, cancer, neurodegenerative diseases,
disorders of the immune function, oxidative damage

20. 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

21. Melatonin produces effects in:
Receptor-independent:
1. Free radical scavenging properties
2. Inhibition of calmodulin
-an attenuation of cAMP-dependent signaling cascades
-decrease ER binding and activation of ERE-containing genes
3. 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)

22. 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)

24. More efficient than other antioxidants; devoid of pro-
oxidant side-effects
1. Scavenging of free radicals
2. 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 antioxidant
Melatonin Combats Inflammation able to cross the blood-brain barrier

25. Melatonin Combats Inflammation, Offers Mood and Anti-Aging Brain Support
Melatonin 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 antioxidant
Melatonin Combats Inflammation able to cross the blood-brain barrier

26. 1. Antioxidant activity
2. 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 substance
Melatonin inhibits the carcinogenesis

27. 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

28. 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 Cancer
The greatest area of melatonin research to date has to do with breast
cancer.

29. 1. Enhances the production of cytokines
2. 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 function
Melatonin has an immunomodulatory role

30. MT1 receptors in SCN
The treatment of insomnia (particularly in
individuals with melatonin deficiency)
Melatonin as a hypnotic
Melatonin promotes sleep in healthy humans

31. MT2 receptors in SCN
Implication in circadian rhythm sleep disorders
1. Shift-work disorder
2. Jet lag syndrom
3. Delayed sleep phase syndrome
4. Circadian rhythm disruption with ageing
Melatonin as a chronobiotic molecule
Melatonin acts as an endogenouos synchronizer of
bodily rhythms

32. 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 acid
2. High concentration in the bile-prevents oxidative
damage to the intestinal epithelium caused by bile acids
3. Gastroprotective efficacy: as an antioxidant
GIT melatonin

33. 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

34. 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?

35. 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 loss
lower 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?

36. Melatonin causes inhibition of bone resorption (protects
bone during treatment with gluococorticoids that affect
bone remodeling and cause osteoporosis)
1. Down-regulation of osteoclast activation
2. Direct inhibition of osteoclast function (antioxidant)
Melatonin effects on bone

37. 1. Via MT receptors
2. 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

38. Melatonin Regulates Our Cycles, Mood, Reproduction,
Weight and May Help Combat Cancer
October 10, 2013 | 279,344 views
01 AUG 2016
Melatonin – 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.

39. Disorders of melatonin
• Hypomelatonism
• Hypermelatonism
• Dysmelatonism

40. 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.

41. Drug induced hypomelatonism
• Beta blockers: Metaprolol->propranolol-
>Atenolol
• Alpha 2 blocker: Clonidine
• Naloxone
• NSAID ibuprofen
• Alcohol, tobacco, caffeine
• Benzodiazepine

42. Effects of hypomelatonism
Decreased immune function
Blood pressure instability
Increased plaques in the brain, like those seen with
Alzheimer's disease
Diabetic 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)

43. insomnia
difficulty getting to sleep
difficulty falling back to sleep when
awaken during the night
light sleeper/easy waking during the
night
early morning awakening
un-refreshing sleep
lack of dreaming
family history of insomnia
personal or family history of breast
cancer
personal or family history of prostate
cancer
prostate enlargement
fatigue
depression
irregular menstrual cycle
unusual menstrual flow (light or
heavy)
PMS
scoliosis
poor sleeping prior to menses
anxiety
sensitivity to stress
cataracts
neurodegerative disorder (MS,
Parkinson's, Alzheimer's, ALS, etc)
elevated cholesterol
high blood pressure
blood clots
heart attack
heart arrhythmias
Common symptoms and signs of melatonin deficiency
to many to remember

44. 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

45. Dysmelatonism
Circadian rhythm Syndrome
• Blind
• Jet lag
• Night shift workers ( Industrial
jet lag)
• Delayed sleep phase syndrome

46. • 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
Dysmelatonism
Clinical features of Circadian rhythm Syndrome (CRS)

47. 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)

48. Foods containing melatonin or induce
the natural production of melatonin
Improve your nights sleep with these
9 foods
Turkey
Oats
Almonds
Marmite
‫مارمايت‬/‫بخميرة‬ ‫أسود‬ ‫عسل‬
Warm milk
Bananas
Tart Cherries
Grapes
Whole Grain
Cereals

49. ‫ا‬ً‫ت‬‫ا‬َ‫ب‬ُ‫س‬ ْ‫م‬ُ‫ك‬َ‫م‬ ْ‫َو‬‫ن‬ ‫َا‬‫ن‬ْ‫ل‬َ‫ع‬َ‫ج‬ َ‫و‬(9)‫ا‬ً‫س‬‫ا‬َ‫ب‬ِ‫ل‬ َ‫ل‬ْ‫ي‬َّ‫الل‬ ‫َا‬‫ن‬ْ‫ل‬َ‫ع‬َ‫ج‬ َ‫و‬(10)‫ا‬ً‫ش‬‫ا‬َ‫ع‬َ‫م‬ َ‫ار‬َ‫ه‬َّ‫ن‬‫ال‬ ‫َا‬‫ن‬ْ‫ل‬َ‫ع‬َ‫ج‬ َ‫و‬(11)‫النبإ‬ ‫سورة‬
9. “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

50. Conclusions

51.  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

52. The New Lifestyle diseases is a Buzzle
searching for an answer

53. How to avoid Lifestyle diseases
My long life experience precious advice is
1- Trusted sources then Calibrate with the absolute truth
2- 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

54. How to Improve and Protect Your Melatonin Production
Improve 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.