Sleeping disorders - impact on health & nutrition interventions

1. SLEEPING
DISORDERS:
Impact on health & Nutrition
interventions
PRESENTED BY:
Supta Sarkar
HHM-2013-10
M.Sc Foods & Nutrition

2. SEE INSIDE…
 Introduction
 Sleepregulation
 Measuring sleep
 Types & stages of sleep
 Functional changes during sleep
 Types of sleeping disorders
 Healthrisk due to SD
 Nutrition intervention
 Conclusion
 Reference s

3. Introduction
• Sleep can be defined as a reversible behavioural state in which an
individual is perceptually disengaged from and unresponsive to the
environment (Carskadon & Dement,2011).
• People generally know little about the importance
of this essential activity.
• Sleep actually appears to be required for survival.
• The Guinness World Record for sleep deprivation is 11 days (Gillin,
2002).
• Rats deprived of sleep will die within two to three weeks, a time frame
similar to death due to starvation (Rechtschaffen, 1998).

4. • According to the International Classification of Sleep Disorders
(ICSD-2, 2005) there are around 90 distinct sleep disorders.
• The most common are obstructive sleep apnea, insomnia,
hypersomnia, parasomnia, narcolepsy, restless legs syndrome and
circadian rhythm disorder.
• Large numbers of individuals suffering from these sleep disorders are
unaware of—and have not been diagnosed or treated for—their
disorder (Strohl et al.,2000).
• Sleep disorders have been associated with fatigue, bad mood, poor
performance and also long-term health consequences like
hypertension, diabetes, obesity, depression, heart attack, stroke.
• Nutritional status of an individual could play a major role on sleep
quality (Partinen et al., 2014).

5. MISCONCEPTION ABOUT SLEEP:
Misconception 1:
Sleep is time for the body in general and the
brain specifically to shut down for rest.

6. Misconception 2:
Getting just one hour less sleep per night than
needed will not have any effect on daytime
functioning.

7. Misconception 3:
The body adjusts quickly to different sleep
schedules.

8. Misconception 4:
People need less sleep as they grow
older.

9. Misconception 5:
A “good night’s sleep” can cure problems
with excessive daytime sleepiness.

10. SLEEP REGULATION
How is sleep regulated?
 Under the brain’s control
 Internal factors drive sleep
 External factors influence sleep

11. A. BRAIN’S CONTROL
• A small number of brain cells are responsible for keeping
us awake or asleep—some cells promote wakefulness
and others promote sleep.
• Neurons that promote wakefulness or arousal:
Tuberomammillary Nucleus (TMN).
• Neurons that promote sleep:
Ventrolateral Preoptic Nucleus (VLPO).
• TMN release neurotransmitters histamine & orexin (also
known as hypocretin).

12. Wakefulnessorarousal:Tuberomammillary
nucleus(TMN)
Fig 1: Orexin neurons stimulate the brain’s
arousal centers.
Fig 2: Arousal centres send signals
that stimulate the cerebral cortex.

13. SLEEPINESS: VENTROLATERAL PREOPTIC NUCLEUS
(VLPO)
Fig: The VLPO promotes sleep by inhibiting activity in the brain’s arousal centers
(Neurotransmitters released from VLPO like GABA, galanin reduce activity in the
arousal regions, causing us to pass quickly into the unconscious state of NREM sleep)

14. B. Internal factors
• There are many internal factors: homeostatic
sleep drive and circadian rhythms.
• Homeostatic sleep drive: Drive to sleep that
accumulates during prolonged wakefulness &
minimize during sleeping.
• Circadian rhythms: Circadian rhythms are
endogenously generated, although they can be
modulated by external cues such as sunlight and
temperature.

15. CIRCADIAN RHYTHMS
 The term circadian comes from the Latin ‘circa’, meaning "around"
(or "approximately"), and ‘diem’ or ‘dies’, meaning "day”.
 A "master clock" in the brain controls circadian rhythms consists of a
group of nerve cells in the brain called the Suprachiasmatic
Nucleus, or SCN.

16. • Retina also contains specialized ganglion cells which are
directly photosensitive, and contain the photopigment
melanopsin and their signals follow a pathway called the
retinohypothalamic tract, leading to the SCN.
• The SCN takes the information on the lengths of the day and
night from the retina, interprets it and passes it on to the pineal
gland, located on the epithalamus.
• In response, the pineal secretes the hormone melatonin.
• Secretion of melatonin peaks at night and ebbs during the day
and its presence provides information about night-length.
• The body's master clock, or SCN, controls the production of
melatonin, a hormone that makes one sleepy.

17. C. External factors
1. Sleeping environment: Light,
sound, temperature.
2. Jet leg
3. Shift worker
4. Pain, Anxiety, and Other Medical Conditions
5. Alcohol

18. HOW TO MEASURE SLEEP?
The commonly used methods to assess sleep.
1. Polysomnography: study body functions: brain activity
(electroencephalogram-EEG), eye movements
(electrooculogram-EOG), muscle activity
(electromyogram-EMG) are measured.
1. Actigraphy
3. Sleep diary.

19.  2 types: NREM & REM
 5 stages: NREM(4 stages) & REM
 NREM sleep is divided into four stages, which are
associated with a progressive increase in the depth
of sleep (Carskadon & Dement,2011).
 REM sleep is characterized by muscle atonia,
bursts of REM and dreaming.

20. Figure: First, the periods of
NREMand REMsleep alternateduring the night.
Stage-1-4 (NREM)
Stage-5 (REM)

21. Pattern of sleep in different stages

22. Brain waves formed in different stages

23. Indication of different Brain Waves:

24. • Sleep in particular slow-wave sleep (SWS) or deep
sleep, is important for recovery (Halson, 2004).
• The synchrony of growth hormone release with SWS
occurs in humans (Halson, 2004).
• The duration of SWS is proportional to preceding
wakefulness (Shapiro et al., 1981).
• When SWS is decreased by deprivation, an increase in
daytime sleepiness and a reduction in performance have
been observed (Dijk, 2010).

25. Changes in the functions of many organ
systems during sleep:
Endocrine system:
• Many hormones are secreted into the blood during
sleep.
• Growth hormone, follicle stimulating hormone and
luteinizing hormone are released during sleep.
• Thyroid-stimulating hormone, are released prior to
sleep.

26. Renal system:
• Kidney filtration, plasma flow, and the excretion of
sodium, chloride, potassium, and calcium all are reduced
during both NREM and REM sleep.
• These changes cause urine to be more concentrated
during sleep.
Alimentary activity:
• In a person with normal digestive function, gastric acid
secretion is reduced during sleep.
• In those with an active ulcer, gastric acid secretion is
actually increased.

27. TYPES OF SLEEPING DISORDERs
• According to the International Classification of Sleep
Disorders (ICSD-2, 2005) there are around 90 distinct sleep
disorders.
• The most common are:
-Obstructive Sleep Apnea(OSA),
-Narcolepsy,
-Restless Legs Syndrome(RLS),
-Insomnia,
-Parasomnias(Sleep walking & REM Behavior Disorder),
-Circadian rhythm disorders:
(Jet leg & shift work),
-Hypersomnia

28. IS IT A SLEEPING DISORDER?
Q. Do you…….
• feel irritable or sleepy during the day?
• have difficulty staying awake when sitting still, watching
television or reading?
• fall asleep or feel very tired while driving?
• have difficulty concentrating?
• often get told by others that you look tired?
• react slowly?
• have trouble controlling your emotions?
• feel like you have to take a nap almost every day?
• require caffeinated beverages to keep yourself going?

29. If you answered “yes” to any of the
previous questions, you may have a
sleep disorder.

30. Health risks associated with sleeping disorders:
• The cumulative effects of sleep loss and sleep disorders have been
associated with a wide range of deleterious health consequences
including an increased risk of diabetes, obesity, depression,
hypertension,heart attack, stroke and nutritional status of an
individual could play a major role on sleep quality (Partinen et
al.,2014).
• The exact mechanism by which decreased sleep influences glucose
metabolism is thought to be multifactorial and includes decreased
brain glucose utilization, alterations in sympathovagal balance,
increased evening cortisol, extended night-time growth hormone
secretion, and proinflammatory processes (Van Cauter et al., 2008).

31. HORMONAL IMBALANCE
 Sleep deprivation results in decreases in leptin and
increases in ghrelin (Van Cauter et al., 2008).
 Leptin and ghrelin are hormonal regulators of food intake,
with leptin exerting inhibitory effects on food intake and ghrelin
being an appetite-stimulating hormone (Van Cauter et al.,
2008).
 Sleep restriction has also been shown to increase hunger and
appetite, especially relating to carbohydrate-rich foods
(Spiegel et al., 2004).

32. FIG: Actions of and relationships between leptin and ghrelin

33. CORTISOL (the stress hormone):
• In studies on individuals who were sleep deprived (four hours
of sleep per night), evening cortisol levels were elevated
and the levels decreased six times slower when compared to
control subjects.
• These elevations in cortisol further increase the likelihood of
developing diabetes and obesity.
• Saliva cortisol has shown to decrease immediately after a
nap (Faraut et al., 2011).
INSULIN:
• Poor sleep is also associated with increases in the secretion
of insulin following a meal.
• Higher levels of insulin are associated with weight gain, a risk
factor for diabetes.

34. OBESITY
 Studies have shown that people who habitually sleep less than 7 hours
per night are much more likely to have a higher average BMI and more
likely to be obese (Gangwisch et al, 2005).
SLEEP
DEPRIVATION
Increased Hunger
Increased
opportunity to Eat
Altered
thermoregulation
Increased fatigue
Increased
caloric intake
Reduced
Energy
Expenditure
OBESITY
↑Ghrelin
↓Leptin

35. DIABETES
• Both laboratory and epidemiological
studies support the notion that chronic
partial sleep loss can increase the risk of obesity
and diabetes (Knutson et al.,2007).
• Potential mechanisms include changes in glucose regulation by
insulin resistance, dysregulation of neuroendocrine control of
appetite and/or increased energy intake (Knutson et al., 2007 &
Spiegel, 2005).
• In addition, researchers have correlated obstructive sleep apnea—a
disorder in which breathing difficulties during sleep lead to frequent
arousals—with the development of impaired glucose control similar
to that which occurs in diabetes.

36. Fig: Schematic diagram of the potential pathways leading from sleep loss to
diabetes risk.(Reproduced from Siegel et al.)
Acute sleep
deprivation
↑Glucose level
↓ Insulin level
Decreased
glucose
tolerance
Appetite
dysregulation &
risk of weight
gain
Normal glucose
level
↑Insulin levels
Chronic
sleep
deprivation
Insulin
resistance
Increased risk of
type II diabetes

37.  Even minor periods of inadequate sleep can cause an elevation
in blood pressure.
 Studies have found that a single night of inadequate sleep in
people who have existing hypertension can cause elevated blood
pressure throughout the following day.
 This effect may begin to explain the correlation between poor
sleep and cardiovascular disease and stroke.
 Sleeping too little (less than six hours) or too much (more than
nine hours) increased the risk of coronary heart disease (Ryu et
al., 2008).

38. MOOD DISORDERS
 Given that a single sleepless night can cause
people to be irritable and moody the following day,
it is conceivable that chronic insufficient sleep may
lead to long-term mood disorders.
 Sleeping four hours per night showed declining
levels of optimism and sociability as a function of
days of inadequate sleep (Haack and Mullington,
2005).

39. IMMUNE FUNCTION
• Increasing amounts of evidence suggest that sleep deprivation can have
detrimental effects on immune function, and that immune responses feed
back on sleep architecture (Bollinger et al., 2010).
• In a recent review examining the link between sleep and immunity, it was
concluded that sleep improves immune responses and that most immune
cells have their peak pro-inflammatory activity at night (Bollinger et al.,
2010).
• Short sleep duration(<7hr) was found to be associated with 30 % lower NK
cell activity when compared with normal sleep (Fondell et al., 2011).

40. • Increasing sleep duration (from 8 to 10 h) or napping (30 min)
following 1 night of sleep deprivation (only 2 h of sleep) both
resulted in a return of leukocyte values to normal ranges
(Faraut et al., 2011).
• Markers of the acute inflammatory system, such as interleukin
(IL)-1b, tumour necrosis factor-a, IL-6, and C-reactive protein
are all influenced following the manipulation of sleep (Mullington
et al., 2010).
• In addition, patients with insomnia and sleep apnea have
elevated inflammatory markers (Mullington et al., 2010).
***

41. RECOMMENDED AVERAGE SLEEP TIME:
AGE TOTAL SLEEP/DAY (hour)
1-15 days 16
3-5 months 14
6-23 months 13.5
2-3 years 12
3-5 years 11.5
5-9 years 11
10-13 years 10
14 – 18 years 8.5
19-30 years 8
33-45 years 7.5
50-70 years 7
70-80 years 6.5
Data source: Roffwang, H.P., Muzic, J.N and Dement,W.C. 1966. Ontogenic
development of human sleep-dream cycle. Science. 152: 604-619.

42. NUTRITION
INTERVENTIONS IN
SLEEPING DISORDERS

43.  Many different neurotransmitters, neuromodulators and
hormones have an important role in regulation of sleep and
wakefulness, and in eating behaviour.
 Research has identified a number of neurotransmitters
associated with the sleep–wake cycle. These include 5-HT,
gamma-aminobutyric acid (GABA), orexin, melanin-
concentrating hormone, cholinergic, galanin, noradrenaline, and
histamine (Saper et al., 2005).
 Dietary precursors can influence the rate of synthesis and
function of a small number of neurotransmitters, including 5-HT
(Silber & Schmitt, 2010).

45. • Ingestion of other forms of protein generally
decrease the uptake of Trp into the brain, as Trp is
the least abundant amino acid and therefore other
LNAA are preferentially transported into the brain
(Silber & Schmitt, 2010).
• Carbohydrate, however, increases brain Trp by
insulin stimulation of LNAA into skeletal muscle,
which results in an increase in free Trp (Fernstrom
& Wurtman,1971).

46. ROLE OF DIFFERENT NUTIENTS IN INFLUENCING
SLEEP

47. CARBOHYDRATE
Year Scientist Title STUDY & RESULT
1981 Porter &
Horne
Bed-time food
supplements
and sleep:
effects of
different
carbohydrate
levels
• Six male subjects with a high-carbohydrate meal
(130 g), a low-carb meal (47 g), or a meal
containing no carb was provided 45 min before
bedtime.
• The high-carbohydrate meal (130g) resulted in
increased REM sleep, decreased light sleep, and
wakefulness (Porter and Horne,1981).
2007 Afaghi et
al.
High-glycemic-
index
carbohydrate
meals shorten
sleep onset
• High or low glycemic index (GI) meals were given 4
h or 1 h before sleep
• The high GI meal significantly improved sleep-onset
latency above the low GI meal, and providing the
meal 4 h before sleep was better than providing the
meal 1 h before sleep.

48.  Sleepy patients with hypersomnias should avoid rapidly
absorbing carbohydrates at daytime to minimize
afternoon sleepiness. Adenosine is accumulating in the
brain, notably in the basal forebrain, during wake,
increasing the sleep pressure (Porkka-Heiskanen &
Kalinchuk, 2011).

49. PROTEIN
Year Scientist Title RESULT
1978 Lacey et
al.
Effects of dietary
protein on sleep
EEG in normal
subjects
• Studied women for 7 days with either high
protein (>100 g), low protein (<15 g), or
normal daily protein intakes.
• Low-protein intakes resulted in lower amounts
of SWS.
2013 Lindseth
et al.
Nutritional effects
on sleep
• The diet of 44 adults were manipulated for 4
days.
• Diets were either high protein (56 % protein,
22 % carbohydrate,22 % fat), high
carbohydrate (22 % protein, 56 %
carbohydrate, 22 % fat), or high fat (22 %
protein, 22 % carbohydrate, 56 % fat).
• Diets higher in carbohydrate resulted in
shorter sleep-onset latencies, and diets
higher in protein resulted in fewer wake
episodes (Lindseth et al. ,2013).

50.  Grandner et al., 2013 examined the dietary intake (by
means of questionnaires) of 459 postmenopausal
women over 7 days.
 The only significant finding was that fat intake was
negatively associated with total sleep time.
 From the above study it appears that diets high in fat
may negatively influence total sleep time.

51. TRYPTOPHAN
 Synthesis of 5-HT is dependent on the availability of its
brain precursor, Trp.
 Furthermore, 5-HT is a precursor to melatonin in the pineal
gland.
 There have been numerous investigations of the effects of
tryptophan supplementation on sleep (Silber and Schmitt,
2010)
 Trp doses as low as 1 g can improve sleep latency and
subjective sleep quality (Silber and Schmitt, 2010).

52.  The ingestion of tart cherries may increase
exogenous melatonin, and when consumed
over a 2-week period was shown to improve
subjective insomnia symptoms when
compared with placebo (Pigeon, 2010).
 Tart cherries also contain antioxidant and
anti-inflammatory phytochemicals that may
influence sleep by means of cytokines
associated with the sleep–wake cycle
(Howatson, 2011).

53. CAFFEINE
• The stimulant and wake-producing properties of
caffeine depend on its ability to reduce adenosine
transmission in the brain.
• Caffeine acts as an antagonist to adenosine A1 and
especially to adenosine A2 receptors. (Fisone et al.,
2004; Burdakov et al., 2005).

54. FATTY ACIDS
• Fagioli et al.,1989 conducted a small study with
eight children.
• They were fed by total parenteral nutrition
without essential lipids and seven other
children who received a daily supplement of
essential lipids in their parenteral nutrition.
• Slow wave sleep was significantly decreased in
the group of children who did not receive fatty
acids as compared to those who did.

55. • Observational studies have shown a link between
sleep (Partinen ,2009) and vitamins and minerals,
whether taken in combination or individually.
• Unlike other dietary supplement ingredients,
vitamins and certain minerals are considered
essential nutrients for which standards of
adequacy are needed.
VITAMINS AND MINERALS

56. VITAMIN A
 Barcelo et al.,2006 reported that patients with obstructive sleep apnea
syndrome have a decreased antioxidant capacity of vitamin A and E levels.
 It has been suggested that retinoid signalling pathways are important for adult
neural function in health and disease (Sei, 2008).
 A definitive role for vitamin A signalling however is evident in the regulation of
delta oscillations which contribute to slow wave sleep (SWS). (Maret et
al.,2005)
 Study of sleep in mouse models of ageing shows involvement of vitamin A in
the regulation of delta oscillations (Ransom et al., 2013).
 Vitamin A deficiency is known to significantly reduce the power of the delta
oscillation in mice (Kitaoka et al., 2007).

57. VITAMIN B
 B vitamins have been advanced as a preventive for
insomnia based on research that suggests deficiencies
in vitamin B6 promote psychological distress and
ensuing sleep disturbances (Baldewicz et al., 1998).
 Vitamin B12 has been shown to modulate human
melatonin secretion (Yamazaki et al., 1991).

58.  The potential role of diet including vitamin C that
was associated independently with non-restorative
sleep has been reported which shows associations
between sleep symptoms and diet/metabolism,
potentially explaining associations between sleep
and CVD. (Grandneret al.,2013; Grandner et al.,
2014).
 In restless leg syndrome (RLS), vitamins C and E
and their combination are used as safe and
effective treatments for reducing the severity of
RLS in hemodialysis patients (Sagheb et al.,2012).

59. VITAMIN D
 Vitamin D enhance the synthesis and transmission of
serotonin, leading to improvement in mood & sleep. (Privette
et al, 1991)
 Persistent inadequacy of vitamin D may also increase the risk
for obstructive sleep apnea by promotion of adenotonsillar
hypertrophy, airway muscle myopathy, and/or chronic rhinitis
(McCarty et al.,2013).

60. VITAMIN E
 Vitamin E normalize chronic sleep deprivation (Alzoubi, et
al, 2012).
 Decreased levels of antioxidants and lower performance on
the neuropsychological tasks were observed in patients with
obstructive sleep apnea (Sales et al.,2013).
 Limited research indicates that supplemental vitamin E may
reduce symptom occurrence in restless leg syndrome
(Sagheb et al.,2012).

61.  Zinc is an important cofactor for metabolism relevant
to neurotransmitters, prostaglandins, and melatonin,
and indirectly affects dopamine metabolism
(Prasad,1985).
 Magnesium has beneficial effects on mood and is
crucial, together with zinc, in the endogenous
synthesis of melatonin (Nordlander,1953).
 The administration of nightly melatonin, magnesium,
and zinc appears to improve the quality of sleep and
the quality of life in long-term care facility residents
with primary insomnia (Nowak et al., 2002).

62. IRON
In restless legs syndrome S-ferritin is often
low, in which case, giving iron per os, or
intravenously in more severe cases, should
be part of the treatment.
In patients with RLS 45 μg/L is usually used
as a limit when one should consider giving
iron supplement even if hemoglobin is
normal (Partinen et al., 2009).

63. SELENIUM
• Selenium may have some role in regulation of sleep and
in development of insomnia as lack of selenium was
statistically significantly associated with difficulty falling
asleep in a recent large survey (Chiu et al., 2003).
• Infusion of tetravalent selenium compounds, reversibly,
time- and dose-dependently inhibited both nonrapid
eye movement (NREM) and rapid eye movement (REM)
sleep during the daytime (Gumustekin et al., 2004).

64. DIETARY GUIDELINES:
Several practical recommendations may be suggested
(Halson,2004):
• High GI foods may promote sleep.
• Diets high in carbohydrate may result in shorter sleep
latencies.
• Diets high in protein may result in improved sleep quality.

65. • Diets high in fat may negatively influence total sleep
time.
• When total caloric intake is decreased, sleep quality may
be disturbed.
• Small doses of tryptophan (1 g) may improve both sleep
latency and sleep quality.
• The hormone melatonin and foods that have a high
melatonin concentration may decrease sleep onset time.

66. CONCLUSION

67. REFERENCE
 Afaghi, A., O’Connor, H., Chow, C.M. 2007. High-glycemic-index carbohydrate meals shorten sleep onset. Am J
Clin Nutr.85(2):426–30.
 Alzoubi KH, Khabour OF, Rashid BA, Damaj IM, Salah HA. 2012. The neuroprotective effect of vitamin E on
chronic sleep deprivation-induced memory impairment: the role of oxidative stress. Behav Brain Res.
226(1):205-10.
 Baldewicz et el,1998 vitB and insomnia*
 Bollinger T, Bollinger A, Oster H. 2010. Sleep, immunity, and circadian clocks: a mechanistic model.
Gerontology. 56(6):574–80.
 Burdakov D, Gerasimenko O, Verkhratsky A. 2005. Physiological changes in glucose differentially modulate
the excitability of hypothalamic melanin-concentrating hormone and orexin neurons in situ. J Neurosci .
25(9): 2429-33.
 Carskadon MA, Dement WC. 2011. Normal human sleep: an overview. In: Kryger MH, Roth T, Dement WC,
editors. Principles and practice of sleep medicine. 5th ed. St. Louis: Elsevier. 16–26.
 Chiu C-C, Huang S-Y, Shen Winston W, Su K-P. 2003. Omega-3 fatty acids for depression in pregnancy.
American journal of psychiatry. 160((2)): 385.
 Dijk DJ. 2010. Slow-wave sleep deficiency and enhancement: implications for insomnia and its management.
World J Biol Psychiatry. 11(Suppl. 1):22–8.
 Fagioli I, Baroncini P, Ricour C, Salzarulo P. 1989. Decrease of slow-wave sleep in children with prolonged
absence of essential lipids intake. Sleep . 12(6): 495-9.
 Faraut B, Boudjeltia KZ, Dyzma M. 2011. Benefits of napping and an extended duration of recovery sleep on
alertness and immune cells after acute sleep restriction. Brain Behav Immun. 25(1):16–24.

68. • Fernstrom JD, Wurtman RJ. 1971.Brain serotonin content: physiological dependence on plasma
tryptophan levels. Science. 173(3992):149–52.
• Fisone G, Borgkvist A, Usiello A. 2004. Caffeine as a psychomotor stimulant: mechanism of* 2004
• Fondell E, Axelsson J, Franck K. 2011. Short natural sleep is associated with higher T cell and lower
NK cell activities. Brain Behav Immun. 25(7):1367–75.
• Gangwisch JE; Malaspina D; Boden-Albala B et al. 2005. Inadequate sleep as a risk factor for
obesity: analyses of the NHANES I. SLEEP .28(10): 1289-1296.
• Gillin,2002
• Grandner MA, Jackson N, Gerstner JR, Knutson KL. 2013. Dietary nutrients associated with short
and long sleep duration. Data from a nationally representative sample. Appetite. 64:71-80.
• Grandner MA, Jackson N, Gerstner JR, Knutson KL. 2013. Sleep symptoms associated with intake of
specific dietary nutrients. J Sleep Res. 23(1):22-34. doi: 10. 1111/jsr.12084. Epub 2013 Sep 2.
• Grimmett A, Sillence MN. 2004. Calmatives for the excitable horse: a review ofL-tryptophan. Vet J.
2005;170(1):24–32.
• Gumustekin et al, 2004, selenium* REM N NREM*
• Kaack,M and Mullington,JM. 2005. Sustained sleep restriction reduces emotional & physical well-being.
Pain. 119(1-3): 56-64.
• Halson,S.L. 2004, Sleep in Elite Athletes and Nutritional Interventions to Enhance Sleep.
• Howatson G, Bell PG, Tallent J. 2011. Effect of tart cherry juice(Prunus cerasus) on melatonin levels
and enhanced sleep quality. Eur J Nutr. 51(8):909–16.

69. • International Classification of Sleep Disorders – Second Edition (ICSD-2), 298
pages.©2005 American Academy of Sleep Medicine, ISBN 0965722023
ISBN 978-0965722025
• Kitaoka K, Hattori A, Chikahisa S, Miyamoto K, Nakaya Y, Sei H. 2007. Vitamin
A deficiency induces a decrease in EEG delta power during sleep in mice.
Brain Res. 1150:121-30.
• Knutson KL, Spiegel K, Penev P. 2007. The metabolic consequences of sleep
deprivation. Sleep Med Rev. 11(3):163–78.
• Lacey JH, Hawkins C, Crisp AH. 1978. Effects of dietary protein on sleep EEG
in normal subjects. Adv Biosci. 21:245–7.
• Lindseth G, Lindseth P, Thompson M. 2013. Nutritional effects on sleep. West
J Nurs Res. 35:497–513.
• Maret S, Franken P, Dauvilliers Y, Ghyselinck NB, Chambon P, Tafti M. 2005.
Retinoic acid signaling affects cortical synchrony during sleep. Science.
310(5745):111-3.
• Markku Partinen, Tuomas Westermarck and Faik Atroshi,2014, Nutrition, Sleep
and Sleep Disorders – Relations of Some Food Constituents and Sleep,
http://dx.doi.org/10.5772/58345
• McCarty DE, Chesson AL Jr, Jain SK, Marino AA. 2013. The link between
vitamin D metabolism and sleep medicine. Sleep Med Rev. pii: S1087-
0792(13)00073-7.

70.  Mullington JM, Simpson NS, Meier-Ewert HK. 2010. Sleep loss and inflammation. Best Pract Res Clin
Endocrinol Metab.. 24(5):775–84.
 Norlander, 1953, zinc and magnesium*
 Nowak G, Szewczyk B. 2002. Mechanisms contributing to antidepressant zinc actions. Pol J
Pharmacol.. 54(6):587-92.
 Partinen M. 2009. Nutrition and sleep. Sleep Disorders Medicine, ed SC (Butterworth/Elsevier),
3rd Ed, pp:307-318.
 Pigeon,2010-melatonin*
 Porkka-Heiskanen T, Kalinchuk AV. 2011. Adenosine, energy metabolism and sleep homeostasis.
Sleep Med Rev . 15(2): 123-35.
 Porter JM, Horne JA.1981. Bed-time food supplements and sleep:effects of different carbohydrate
levels. Electroencephalogr Clin Neurophysiol. 51(4):426–33.
 Prasad AS. 1985. Clinical and biochemical manifestation zinc deficiency in human subjects.
 Privette TH, Stumpf WE, Mueller RA, Hollis BW. 1991. Serum 1,25 dihydroxyvitamin D3 (soltriol) levels
influenceserotonin levels in the hypothalamus of the rat Abstr. Soc Neurosci . 17:498 (197. 9).
 Ransom J, Morgan PJ, McCaffery PJ, Stoney PN. 2013. The rhythm of retinoids in the brain. J
Neurochem. doi: 10. 1111/jnc.12620.
 Rechtschaffen, A. 1998. Current perspectives on the function of sleep. Perspectives in Biological
Medicine, 41: 359–390.

71. • Roffwang, H.P., Muzic J.N and Dement,W.C. 1966. Ontogenic development of human sleep-dream cycle.
Science. 152: 604-619.
• Ryu,SY., Kim,KS and Han MA. 2008. Factors Associated with Sleep Duration in Korean Adults: Results of a 2008
Community Health Survey in Gwangju Metropolitan City, Korea. J Korean Med Sci. 26(9): 1124–1131.
• Sagheb MM, Dormanesh B, Fallahzadeh MK, Akbari H, Sohrabi Nazari S, Heydari ST, Behzadi S. 2012.
Efficacy of vitamins C, E, and their combination for treatment of restless legs syndrome in hemodialysis
patients: a randomized, double-blind, placebocontrolled trial. Sleep Med. 13(5):542-5.
• Sales LV, Bruin VM, D'Almeida V, Pompéia S, Bueno OF, Tufik S, Bittencourt L. 2013. Cognition and
biomarkers of oxidative stress in obstructive sleep apnea. Clinics (SaoPaulo). 68(4):449-55.
• Saper CB, Scammell TE, Lu J. 2005. Hypothalamic regulation of sleep and circadian rhythms. Nature.
437(7063):1257–63.
• Sei H. 2008. Vitamin A and sleep regulation. J Med Invest. 55(1-2):1-8. Pharmacology and Nutritional
Intervention in the Treatment of Disease 214
• Shapiro CM, Bortz R, Mitchell D. 1981. Slow-wave sleep: a recovery period after exercise. Science.
214(4526):1253–4.
• Silber BY, Schmitt JA. 2010. Effects of tryptophan loading on human cognition, mood, and sleep. Neurosci
Biobehav Rev. 34(3):387–407.
• Spiegel K, Tasali E, Penev P. 2004. Brief communication: sleep curtailment in healthy young men is
associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann
Intern Med. 141(11):846–50.
• Strohl, K.P., Haponik, E.E., Sateia, M.J.,Veasey, S., Chervin, R.D., Zee, P., and Papp,K. 2000. The need for a
knowledge system in sleep and chronobiology. Academic Medicine, 75: 819–21.
• Van Cauter E, Spiegel K, Tasali E.2008. Metabolic consequences of sleep and sleep loss. Sleep Med.
9(Suppl. 1):S23–8.
• Yamazaki et al,1991 vit B12 modulte melatonin secretn*