Sleeping, obesity - PowerPoint Presentation

Slide1

Sleeping, obesity and metabolic balance

Importance of proper sleeping much higher than just having more oxygen for fat burning during the night

MUDr. Dana MaňaskováSlide2

Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies. Cappuccio FP

,

D'Elia L, Strazzullo P, Miller MA. Sleep. 2010 May;33(5):585-92.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864873/

Systematic search of publications using MEDLINE (1966-2009), EMBASE (from 1980), the Cochrane Library, and manual searches without language restrictions

Included studies: prospective, follow-up >3 years, duration of sleep at baseline, and all-cause mortality prospectively

1,382,999 male and female participants

Follow-up range 4 to 25 years, and 112,566 deaths

Sleep duration was assessed by questionnaire and outcome through death certification.

Short duration of sleep was associated with a greater risk of death

(RR: 1.12; 95% CI 1.06 to 1.18; P < 0. 01)

Short sleepers (commonly < 7 h per night, often < 5 h per night) have a 12% greater risk of dying

[1]

Long duration of sleep was also associated with a greater risk of death

(1.30; [1.22 to 1.38]; P < 0.0001)

Long sleepers (commonly > 8 or 9 h per night) a 30% greater risk of dying

[1]

than those sleeping 7 to 8 h per night

[1]

Effect was stronger in older cohorts, sleep of 10 h an more h per night, in follow-ups not longer than 19 years, and in East Asian cohorts.Slide3

Meta-analysis of short sleep duration and obesity in children and adults.

Cappuccio FP

1, Taggart FM, Kandala NB, Currie A, Peile E, Stranges S, Miller MA.Sleep.

2008

May;31(5):619-26.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2398753/

Children from 2 to 20 years

12 studies from the published articles were included in the pooled analysis.

30,002 participants from France, Tunisia, Japan, Germany, USA, Brazil, Portugal, United Kingdom, Canada, Taiwan, and China

Significant association between short duration of sleep and obesity.

The pooled OR was 1.89 (1.46 to 2.43

)

Adults from 15 to 102 years

17 studies included 604,509 participants from Spain, Japan, USA, France, Switzerland, Sweden, Brazil, Finland, Norway, Canada, Hong Kong, and United Kingdom

Significant association between short duration of sleep and obesity.

The pooled OR was 1.55 (1.43 to 1.68

) Slide4

Sweet/Dessert foods are more appealing to adolescents after sleep restriction.Simon SL

,

Field J, Miller LE, DiFrancesco M, Beebe DW. PLoS One. 2015 Feb 23;10(2):e0115434. doi: 10.1371/journal.pone.0115434. eCollection 2015

.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338308/

31 typically-developing adolescents aged 14–17 years

The 3-week protocol consisted of:

a baseline week

randomly 2 groups:

5 consecutive nights of SR (6.5 hours in bed)

5 nights healthy sleep duration (HS; 10 hours in bed)

a 2-night wash-out period

5-night cross-over intervention in that 2 groups

Sleep was monitored via actigraphy

Every morning teens rated their hunger, underwent a 24-hour diet recall interview, and rated the appeal of a series of pictures of sweet/dessert foods (e.g., ice cream, candy) and non-sweets (meat, eggs, fruits, vegetables)

Results:

Intake of overall calories was 11% higher

Consumption of sweet/dessert servings was 52% greater during SR than HS Slide5

Duration of sleep

Short sleep is associated with:

higher total mortality, poor self-rated health [1] hypertension, cardiovascular disease [1]metabolic syndrome [5], type 2 diabetes [1, 4] obesity in both children and adults

and respiratory disorders [1]

Microarousals during sleep were the best predictors of increased

morning cortisol levels and hyperlipidemia

[7]

reduced cognitive function [5]

unhappiness and symptoms of depression, suicidal ideation and attempts [5]

burnout syndrome, a syndrome characterized by emotional exhaustion, depersonalization and low personal accomplishment [7]

People reporting consistently sleeping 5 hours or less per night should be regarded as a higher risk group for all-cause mortality. [1] 2007 USA: More than 30% of adult men and women between the ages of 30 and 64 years report sleeping less than 6 hours per night. Has occurred over the same time period as the increase in the prevalence of obesity and diabetes. [4]

Long duration of sleep is associated with:

all different comorbidities and poor general health [1] depressive symptoms and using antidepressants / sedatives [5] low socioeconomic status and unemployment [1] low level of physical activity [1] undiagnosed health conditions [1] cancer-related fatigue [1] recent treatment for cancer [5] increased total cholesterol [5] higher total/HDL cholesterol ratio among the elderly [5] having had a heart attack or angina [5] poorer cognitive function [5] cardiovascular mortality and greater carotid intimal medial thickness [5, 6] esophageal cancer, pancreatic cancer, increased risk of urothelial cancer and non-Hodgkins lymphoma in women [6] decreased risk of prostate cancer [6] sleep apnea - compensating for the large degree of fragmentation associated with the disorder by spending more time asleep or excessive amounts of time in bed [6] Sleeping 9 h or more per night may represent a useful diagnostic tool for detecting subclinical or undiagnosed co-morbidity. [1]

Longer duration as compensation of poor sleep quality!Slide6

Short sleep side effects:

EEG and hormonal changes after acute total and recurrent partial sleep deprivation [4]

= depression, emotional lability etc... Decrease in cerebral glucose metabolism (PET studies) [4]Leptin low, ghrelin high [1]Increase appetite, caloric intake, reduce energy expenditure, facilitate obesity and impaired glycemic control [1]

= problems to keep on any diet and no real appetite to move

Sympathetic tone increased [4], elevated catecholamine secretion [6]

Short sleep = stressor in the acute and chronic setting [6] = lead to disease, neuronal damage, earlier aging [6]

Elevated heart rate variability [4]

Increased cortisol secretion [1]

= bad weight reduction...

Insulin resistance etc.

= strong hungers at the beginning of the low saccharide dietsivGTT protocol: after 5 days of restricted sleep in young people is similar to those in older adults with impaired glucose tolerance [4]Glycaemia higher after sleep restriction than after sleep recovery, insulin secretion non-significantly higher [4]HOMA curve for the breakfast meal more than 50% higher after 6 days of sleep restriction [4]Insulin resistance may develop progressively with increasing exposure to partial sleep loss [4]Accelerated by sleep-disordered breathing (SDB) (independent risk factor for insulin resistance) [4] Altered growth hormone metabolism [1] GH secretion peaks drop to baseline during recurrent sleep restriction [4]

= harder to grow muscles and regenerateTSHtotal sleep deprivation = TSH over 200% [4]

3-5 days of partial sleep deprivation = TSH markedly depressed [4] = low heat production, lower energy burning and bad weight reduction Lack of melatonin [hormone of youth, strong antioxidant !!!] = accelerated ageing !!!Low grade inflammation - activated during short sleep [1] Increased levels of inflammatory cytokines and low grade inflammation [4] esp.: interleukin-6 and tumor necrosis factor alpha [6] Elevated CRP concentrations have been reported in healthy subjects exposed to total and partial short-term sleep deprivation [6]Elevations of CRP [can bind leptin and cause it's lower function] [4] = higher taste to eat Slide7

Melatonine [N-acetyl-5- methoxytryptamine]

- key substance of regeneration

Quality of sleep and morning alertnessMetabolic adaptations - adipose and muscle tissues to physical training [16]

Broad-spectrum antioxidant

Scavenges: hydrogen peroxide, hydroxyl radical, nitric oxide, peroxynitrite anion, hypochlorous acid, singlet oxygen, superoxide anion, peroxyl radical and oxygen radicals [8]

Chain of metabolites effective free radical scavengers [8]

Elevate concentrations of antioxidating enzymes: superoxid dismutase, glutation peroxidase, glutation reductase and inhibit prooxidative enzymes [10]

Form several stable end-products which are excreted in the urine [8] = non toxic

Antiinflammatory functions

Down-regulates 5-lipooxygenase in B lymphocytes [12]AFMK (metabolite] inhibits IL-6, adhesion molecules [12], TNF alfa and IL-8 formation caused by LPS in neutrophils and mononuclear cells. [10] AFMK and AMK selectively inhibit gene expression of COX-2 [10] Anticancer effects - different pathwaysDirect augmentation of NK cells [13 ], stimulates production of IL-2, IL-6, IL-12, and IFN-gamma [13]

Suppress EGFR/MAPK mitogen activity (blocks linoleic acid uptake by tumor cells

and its conversion)Neurogenesis, neuroprotection and neuromodulation [12, 13]Inhibits NOS and dopamine release [12 ], potentiates GABA in CNS [12 ], modulates serotonin receptors, potentiates opioid analgesic [12], increases REM sleep continuity (dreams), increase CoQ9 in brain mitochondria(precursor to CoQ10) Immunomodulation - infection resistance [12] Intervening in lipid metabolism [12]Slide8

Melatonin for every cell

In all living organisms, also vegetables, fruits and herbs

Flowers and seeds (reproductive organs vulnerable to oxidative insults) [8] In ancient photosynthetic prokaryotes as receptor-independent free radical scavenger [10] Better growing of the corps [functional food - transgenic rice [17]] Substantial amounts found in: Tissues exposed to high stress: gut, bile, skin - keratinocytes

Organs with high oxygen consumption: brain, 3rd ventricular fluid, bone marrow [10]

Extrapineal production of melatonin !

[no light/dark regulation]:

Retina, ciliary body, lens, Harderian gland, brain, thymus, airway epithelium, bone marrow, gut [two orders greater than that produced by the pineal gland], ovary, testicle, placenta, lymphocytes, skin [10]

Intracellular melatonin much higher than that of the glutathione level in cells !!! [10]

Mitochondria contain high levels of melatonin

Strongly inhibit cytochrome C release from the mitochondria Suppress the activity of caspase 3 Stabilizes mitochondrial membrane part of the neuroprotection in oxygen–glucose–serum deprivation [10] Elevate ATP production by lowering electron leakage and inhibiting opening of the mitochondrial permeability transition pores [10] = Strong protection of mitochondria agg. ox. stress Slide9

Proved positive effects of melatonin as an adjuvant therapy in:

Macular degeneration, glaucoma, gastric ulcer, gastric reflux, irritable bowel syndrome, hemodialysis [11], Smith-Magenis syndrome, Sunburn prevention

Arterial hypertension, diabetes, androgenetic hair lossSide effects of chemotherapy and radiation in cancer patients !!Anti-aromatase effect of resveratrol and melatonin on hormonal positive breast cancer cells co-cultured with breast adipose fibroblasts.Melatonin sensitizes human breast cancer cells to ionizing radiation by downregulating proteins involved in double-strand DNA break repair.

Sleep deterioration, depression, premenstrual tension and postmenopausal hot flashes and irritability [14]

Agomelatine - new medicament for major depression and bipolar affective disorder

Alzheimer and other dementias, Parkinson disease, multiple sclerosis, stroke, brain ischemia/reperfusion, traumatic CNS injuries etc. !!! [12], Tinnitus

Anesthetic procedures

[9], some of the glucocorticoid indications [melatonin allows to use lower doses of glucocorticoids = less side effects] [12 ]

Malaria [10] and other inflammations [12], Septic shock and associated multi organ failure in critically ill patients [13]

Premature infants with severe respiratory distress syndrome and septic shock [13]

"Oral pulsatile system for potential delivery of melatonin to pediatric population" [2014] [ 20]Melatonin reduces the severity of disease conditions where free radicals are implicatedAccording to the: strong antioxidant activity up to now not known toxic effects of recommended melatonin doses / very rare effects of higher dosesnot known side effects of normal duration sleep

= PROFIT CAN BE EXPECTED IN EVERY ILNESS AND SITUATION - also in reducing weight !!! [my message]

The most complex therapy of the whole body ever known:During the day: have fun in the Sun and during the night: is the best to sleep and have a rest.Slide10

Lower levels of melatonine:

Lower

production: block of enzymes / lack of cofactors / substratesLow tryptophan [basic precursor] = low serotonin = also low melatonin !!!<300 kcal per day 2-7 days reduces melatonin in the blood by about 20%

Alcohol - dose dependent -

decreases TRP and glucose in blood5-hydroxylation

Decarboxylation - necessary coenzyme

vitamin B6

(=

serotonin)

N-acetylation by arylalkylamin N-acetyltransferase [AA-NAT] -

suppressed by lightChemical pinealectomy (constant light exposure) [10] Even a small light exposition [esp. blue light 460-480 nm] at night stops melatonin secretion !!!Light from small self-luminous displays [23] Exposure to room light before Bedtime suppresses melatonin onset and shortens melatonin duration [24] Stimulated by

adenosin (increases cAMP levels) - blocked by

caffeine, theobromine, xantineLow Zinc and magnesium - bind to AANAT [activating and increasing it's affinity to bind serotonin]O-methylation by hydroxyindol-O metyl transferase = cooperate with folate, B6, B12 pathway (methylation)Folate, magnesium and zinc deficiencies have been linked with lower melatonin levels in rodentsOther causes of lower secretion Epigallocatechin Gallate (EGCG) - Green Tea -antagonism High lesions of cervical spinal cord - miss of night melatonin peak, some brain tumors

Adrenergic agonists/antagonists

beta1 adrenergic blocators, alpha2 receptors -

clonidine

Stronger

electromagnetic field near the head !!!

Increased level of

insuline, proinfalmmatory cytokines, cortisol

etc.

Glucose, sodium, ethanol, caffeine

- phase-shifting circadian rhythms

Older people [pineal calcification etc.]

Higher liver metabolism - induction of CYP1A1, CYP1A2, [CYP2C19]:

Cigarette smoking, Carbamazepine, Rifampicin

Consumption higher than synthesis - by scavenging free radicals = low levels

Intensive oxidative stress [10] -toxic environmental contaminants

[10] etc.

Slide11

Higher levels of melatonin:

Higher production

Catecholamine elevation at the synapsis: MAO inhibitors and tricyclic antidepressants Some brain tumors Low intensity stressors such as

dietary restriction

and exercise, cold, UV-B irradiation etc.

activate AA-NAT

[10]

Glucocorticoids

upregulate stress-responsive transcriptional factor AP1 = upregulate gene expression for melatonin synthesis

Sources of: tryptophan, serotonin, B6, glycine, phytoestrogenes, folate,... Higher secretion Soon after the onset of darkness, peaks at 0-2-4 am and diminishes during rest of the night

Lower liver and extrahepatal metabolism / lower consumption by oxidative stress

In the elderly Liver cirrhosis - significantly increased melatonin during daylight hours Fluvoxamine - inhibits CYP1A2 and CYP2C19 - [17x increase in blood [10]] 5- or 8-methoxypsoralen (5 and 8-MOP) Cimetidine - CYP2D inhibitor Estrogens, oral contraceptives - inhibition of CYP1A1 and CYP1A2 Quinolones melatonin taken orally with 200 mg caffeine [large cup of coffee] - bioavailability increases 140% - both are substrates of CYP1A2 [10] Taken with vitamin E and vitamin C,

the bioavailability of melatonin increased

Folic acid

and many other

antioxidants from food

Caffeine, St. John's wort (Hypericum perforatum)

Exogenous melatonin

Pills

: [Circadine, Melatonex (Sun source); Mela-T (Alacer); Night Rest (Source Naturals), Regulin etc.]

FOOD

[next page]Slide12

W

hat to do keep proper melatonine

production and 7-8 hours of good quality sleep :Morning sun-light exposure

, ideal together with physical activity.

Work near a window. Hormetins [low prooxidative stressors that stimulate antioxidative protection of our body] - Moderate sport activity, small doses of alcohol, sauna, cryosauna, cold training, sun insolation,...

Weak warm light a few hours before going to sleep. Eliminate blue and other disturbing light waves (orange glasses while reading in the evening/working on PC).

Kayumov et al. showed that light wavelengths greater than 530 nm does not suppress melatonin in bright-light conditions.

No coffee or real tea [better in the morning] and no cigarettes in the evening. No alcohol - only some products have high melatonin content], meditation instead (25)

Sleep beginning ideal before 23h !!!

Electro free area near the head!!!

= No mobile under the pillow and within 2m, electric cables within 40cm, cook or fridge behind the wall, strong Wi-Fi,... = Switch it all off."Chronic exposures, there are now at least 11 studies in humans showing that magnetic fields as low as 0.2 μ T suppress or otherwise disrupt the nocturnal production of melatonin in the pineal gland" Sleep in 100% darkness !!! = Really dark curtains. No light on the way to the toilet etc.Control of used medicaments according to the quality of sleep and melatonin production:Sleep disturbancy: Diuretics, antiasthmatics, stimulating antidepressants, thyroideal hormones, nootropica etc.Melatonin synthesis lowered by: beta blockers, calcium channel blockers, anti-anxiety drugs, NSAIDs, steroids, some antidepressants, verapamil, FlumazenilTherapy of the depression [cave: depression as a symptom of food deficiency], inflammations and chronic pain [night doses more important than during the day]

Food supplements: B6, Vitamin E [14], C, glycine [14], L-tryptophan, phytoestrogens [resveratrol, soya beans, stevia, ...], B12, folate, melatoninLow serotonin may contribute to intense cravings for sugar. Insulin helps tryptophan to reach the brain.

Reduction of the chemicals in your home, food, clothes, cosmetics etc.: [melatonin consumption by oxidative stress due to chemical stress]Bedroom - toxic VOCs from matresses, viscofoam pillows, colors from the beddings, phtalates etc. from the floor, formaldehydes etc. from the furniture, dust with contaminants from air and ground pollution,... [prefer natural materials, wash dust and refresh air more often]Physics aspects of sleeping hygiene: Room temperature +- 18°C and less, moisture of the air at least 60%Slide13

METABOLIC BALANCE and quality of the sleep - involved steps to achieve higher concentrations of melatonin:

Not to eat after 21h - calm for stomachlow insulin, lower inflammatory signals form gut, higher glucagon for burning fats... Reduce inflammation and insulin levels on low-saccharide diet almost no fructose, restricted doses of coffee during the day

restriction of energy intake - stimulates melatonin production

Only fresh basic food - no unnecessary food additives and heat pre-preparations with too many preservatives - lower melatonin consumption

Rich on omega3-rich oils, fiber, vitamins E, A, C, folate and other antioxidants in food - synergic with melatonin = lower melatonin consumption

n-3 deficient diet reduces nighttime melatonin secretion, which returns to normal with supplemented DHA [seen in rodents]

Individual food list rich on necessary and synergic working substances for melatonin synthesis and its higher levels, especially if reported sleep or depressive disorders [I'd expected this...]

Tryptophan: turkey, cheese, nuts, sunflower seeds, pumpkin seeds

Vitamin B6: eggs, liver, spinach, turnip greens, garlic, cauliflower, mustard greens, celery, fish (especially tuna, halibut, salmon, cod and snapper), poultry (chicken and turkey], lean beef tenderloin, Quinoa

Serotonin: plantain,... Melatonin: Seeds and nuts - walnuts 3–4 ng/g, orange bell peppers, beverages - coffee 40 µg/cup, tea, wine 50–230 pg/ml, beer 52–170 pg/ml, crops - rice and barley 300–1,000 pg/g, corn, wheat, and oats, pineapple, banana and orange [15], Montmorency or tart cherry [Weichsel] [14], vegetable [16], Meats, eggs, colostrum [22] - but for sure as in humans drops by stress [me], Tomato 3–114 ng/g, Strawberry 1–11 ng/g, Olive oil 53–119 pg/ml, Cow's milk (unprocessed) 3–25 pg/ml, Nighttime milk 10–40 ng/ml Alcoholic fermentation of grapes, malt and pomegranate [19], yeast production during bear and bread [best 180 min.] fermentation etc. [18] Germination of lentils (Lens culinaris L.) and kidney beans (Phaseolus vulgaris L.) - max. melatonin 6th day when germinated in the dark [21] Heat [backing] consumes melatonin - in bread [19]Slide14

Sources:

[1]

Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies. Cappuccio FP, D'Elia L, Strazzullo P, Miller MA

.

Sleep. 2010 May;33(5):585-92.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864873/

[2]

Meta-analysis of short sleep duration and obesity in children and adults.

Cappuccio FP

1, Taggart FM, Kandala NB, Currie A, Peile E, Stranges S, Miller MA.Sleep. 2008 May;31(5):619-26. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2398753/[3] Sweet/Dessert Foods Are More Appealing to Adolescents after Sleep Restriction,

Stacey L. Simon,1,* Julie Field,

2 Lauren E. Miller,3 Mark DiFrancesco,2 and Dean W. Beebe2,4, Ralph E Mistlberger, Academic Editor[4] The Metabolic Consequences of Sleep Deprivation, Kristen L. Knutson, PhD,1 Karine Spiegel, PhD,2 Plamen Penev, MD, PhD,1 and Eve Van Cauter, PhD1http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1991337/[5] Sleep duration and all-cause mortality: a critical review of measurement and associations, Lianne M. Kurina, PhD,a,* Martha K. McClintock, PhD,b Jen-Hao Chen, PhD,a Linda J. Waite, PhD,c Ronald A. Thisted, PhD,a and Diane S. Lauderdale

, PhDa

[6] Mortality

Associated with Short Sleep Duration: The Evidence, The Possible Mechanisms, and The Future,

Michael A. Grandner

, PhD,1

Lauren Hale

, PhD,2

Melisa Moore

, PhD,1,3 and

Nirav P. Patel

, MD1,4

[7] Sleep loss: a novel risk factor for insulin resistance and Type 2 diabetes, Karine Spiegel , Kristen Knutson , Rachel Leproult , Esra Tasali , Eve Van Cauter , Journal of Applied Physiology Published 1 November 2005 Vol. 99 no. 5, 2008-2019 DOI: 10.1152/japplphysiol.00660.2005, http://jap.physiology.org/content/99/5/2008

[8] Significance of Melatonin in Antioxidative Defense System: Reactions and Products, Tan D.-X.a · Manchester L.C.a · Reiter R.J.a · Qi W.-B.a · Karbownik M.b · Calvo J.R.a, Biol Signals Recept 2000;9:137–159 (DOI:10.1159/000014635),

http://www.karger.com/Article/Abstract/14635

[9] Clinical uses of melatonin: evaluation of human trials.

Curr Med Chem.

2010;17(19):2070-95.

Sánchez-Barceló EJ

1,

Mediavilla MD

,

Tan DX

,

Reiter RJ

.

[10]

One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species?

J Pineal Res.

2007 Jan;42(1):28-42.

Tan DX

1,

Manchester LC

,

Terron MP

,

Flores LJ

,

Reiter RJ

. http://onlinelibrary.wiley.com/doi/10.1111/j.1600-079X.2006.00407.x/full

[11] Implications of melatonin therapy in irritable bowel syndrome: a systematic review.

Curr Pharm Des.

2010;16(33):3646-55.

Mozaffari S

1,

Rahimi R

,

Abdollahi M

.

[12] Antiinflammatory Activity of Melatonin in Central Nervous System,

Emanuela Esposito

1 and

Salvatore Cuzzocrea

1,2,*

[13] Melatonin

in bacterial and viral infections with focus on sepsis: a review.

Srinivasan V

1,

Mohamed M

,

Kato H

.

[14] Resveratrol, tryptophanum, glycine and vitamin E: a nutraceutical approach to sleep disturbance and irritability in peri- and post-menopause.

Parazzini F

1.

[15] Association of vegetable intake with urinary 6-sulfatoxymelatonin level.

Nagata C

1,

Nagao Y

,

Shibuya C

,

Kashiki Y

,

Shimizu H

.

[16]

J Pineal Res.

2013 Oct;55(3):229-39. doi: 10.1111/jpi.12065. Epub 2013 May 28. Adaptations of the aging animal to exercise: role of daily supplementation with melatonin.

Mendes C

1,

Lopes AM

,

do Amaral FG

,

Peliciari-Garcia RA

,

Turati Ade O

,

Hirabara SM

,

Scialfa Falcão JH

,

Cipolla-Neto J

.

[17]

J Pineal Res.

2014 Jan;56(1):31-8. doi: 10.1111/jpi.12093. Epub 2013 Sep 30. Alcoholic fermentation induces melatonin synthesis in orange juice.

Fernández-Pachón MS

1,

Medina S

,

Herrero-Martín G

,

Cerrillo I

,

Berná G

,

Escudero-López B

,

Ferreres F

,

Martín F

,

García-Parrilla MC

,

Gil-Izquierdo A

.

[18]

J Pineal Res.

2014 Apr;56(3):275-82. doi: 10.1111/jpi.12120. Epub 2014 Feb 8. Elevated production of melatonin in transgenic rice seeds expressing rice tryptophan decarboxylase.

Byeon Y

1,

Park S

,

Lee HY

,

Kim YS

,

Back K

.

[19] Formation of Melatonin and Its Isomer during Bread Dough Fermentation and Effect of Baking

Cemile Yılmaz

,

Tolgahan Kocadağlı

, and

Vural Gökmen

*

Department of Food Engineering, Hacettepe University, 06800 Beytepe, Ankara, Turkey

[20]

Int J Pharm.

2014 Jul 20;469(1):67-79. doi: 10.1016/j.ijpharm.2014.04.055. Epub 2014 Apr 24. Formulating SLMs as oral pulsatile system for potential delivery of melatonin to pediatric population.

Albertini B

1,

Di Sabatino M

2,

Melegari C

2,

Passerini N

2.

[21]

J Agric Food Chem.

2014 Nov 5;62(44):10736-43. doi: 10.1021/jf503613w. Epub 2014 Oct 23. Effect of illumination on the content of melatonin, phenolic compounds, and antioxidant activity during germination of lentils (Lens culinaris L.) and kidney beans (Phaseolus vulgaris L.).

Aguilera Y

1,

Liébana R

,

Herrera T

,

Rebollo-Hernanz M

,

Sanchez-Puelles C

,

Benítez V

,

Martín-Cabrejas MA

.

[22]

J Pineal Res.

2014 Sep;57(2):213-8. doi: 10.1111/jpi.12152. Epub 2014 Jul 8. Melatonin identified in meats and other food stuffs: potentially nutritional impact.

Tan DX

1,

Zanghi BM

,

Manchester LC

,

Reiter RJ

. http://www.ncbi.nlm.nih.gov/pubmed/24942090

[23] Light level

and duration of exposure determine the impact of self-luminous tablets on melatonin suppression

Brittany Wood

,

Mark S.

Rea

,

Barbara Plitnick

,

Mariana G

.

Figueiro

,

[24] J Clin Endocrinol Metab. 2011 Mar; 96(3): E463–E472. Published online 2010 Dec 30. doi:

10.1210/jc.2010-2098

PMCID: PMC3047226 Exposure to Room Light before Bedtime Suppresses Melatonin Onset and Shortens Melatonin Duration in Humans

Joshua J. Gooley

,

Kyle Chamberlain

,

Kurt A. Smith

,

Sat Bir S. Khalsa

,

Shantha M. W. Rajaratnam

,

Eliza Van Reen

,

Jamie M. Zeitzer

,

Charles A. Czeisler

, and

Steven W. Lockley

[25]

Acute increases in night-time plasma melatonin levels following a period of meditation. Biol Psychol. 2000 May;53(1):69-78. Tooley GA1, Armstrong SM, Norman TR, Sali A.