Eating in Sync with Circadian Rhythms - PowerPoint Presentation

Slide1

Eating in Sync with Circadian Rhythms for Weight Loss and Metabolic Health

Tamara Duker Freuman, MS, RD, CDNMay 20, 2016Slide2

ObjectivesDescribe state of current scientific knowledge on meal timing as it pertains to metabolic health

Explain the “second meal phenomenon” and the potential benefit of circadian-synced eating patternsTranslate available research

into circadian-synced diet interventions/menu plans

Apply circadian-synced

dietary interventions

to appropriate patient

populationsSlide3

We’ve all met Patient XOverweight or obese, and struggling to lose Has pre-diabetes or diabetes, hyperlipidemia or high triglyceridesSkips or skimps on breakfast

Able to start off “good” each day, but things start to fall apart ~3-4pmOvereats at dinner, and grazes immediately after, well into the eveningHas been able to lose weight on “diets” in past, but always regains Slide4

Patient X diet historyTimeFood

Commentary7amCoffee

7:30

Either skip breakfast

OR has a Greek yogurt

OR a banana OR a granola bar

“I’m not so hungry when I get up, so I usually skip. I’ve found when I eat breakfast, it just makes me hungrier

in mid morning and then I have to eat again!”

12:00pm

Salad with grilled chicken OR

Chicken noodle soup

“I try to make a good, low calorie choice at lunch.”

3:00pm

Granola bar from office pantry, candy from vending machine or a cookie from Starbucks

“I get STARVING at around 3pm

and crave

something sweet.”

“I think I might be a binge eater. I’m so good all day up to this point, and then I can’t control myself!”

6:30/7pm

Meat and vegetable with a lot of rice

OR

Big bowl pasta with sauce, some salad too.

“I get to dinner starving—I

definitely eat too much at night. If there’s a bread basket, I often can’t control myself.”

8pm-11pm

Grazing

on ice cream, cookies, crackers/cheese, chips, a bowl of cereal…

“I just feel like I need something sweet… I’m not satisfied..”Slide5

Breakfast skipping associated with obesity, metabolic disturbancesNumerous observational studies have noted correlation between breakfast skipping, obesity in children and adults, e.g.:Szajewska

& Ruszczynski (2010): Review of 16 cross sectional studies (n= >60,000 subjects) of children/adolescents in Europe Eating breakfast associated with reduced risk of overweight and obesity and lower BMI compared to skipping

Timlin

et al

(2015): Prospective 5 year study of 2,200 teens

Inverse relationship between breakfast frequency and BMI after controlling for age, socioeconomic status, race, physical activity, baseline weight status and baseline breakfast status

Almoosawi

et al

(2013): Prospective

cohort of 1500 British men and women born in 1946CHO intake at breakfast or mid morning at age 43 had protective effect against abdominal adiposity at age 53Increased CHO intake in morning with reduced fat intake at age 43 associated with reduced risk of metabolic syndrome and lower TGs at age 53Cho et al (2003): NHANES III 1988-1994 data Eating CHO-rich breakfast associated with significantly reduced BMI among adults compared to breakfast skipping or low CHO (meat/egg) breakfasts

The above studies’

designs preclude ability to assess causation; lack of randomized intervention trials existedSlide6

Does a high CHO breakfast protect against obesity due to improved satiety?Link between breakfast skipping and obesity hypothesized to be over-compensation of kcals at subsequent meals due to excess hunger…d

e Castro J (2007): Review of food diaries from ~900 free living men and women When total proportion of daily CHOs relatively high in morning, there was lower total CHO and kcal intake for remainder of the day

Possibly due to increased satiety from CHO intake in the morning?

I

f breakfast skipping doesn’t necessarily lead to overeating later in the day, what might account for the widely observed relationship between breakfast skipping and obesity?

…But research does not consistently show differences in of total energy intake among breakfast

skippers

Kant &

Graubard

(2015): NHANES data from

2,100

adults No significant difference in total daily energy intake or dinner intake among the same individuals on days in which they consumed or skipped breakfastLevitsky

& Pacanowski (2013): Randomized crossover trial of two dozen healthy undergrads, mostly female

Skipping breakfast did not result in compensatory overeating at subsequent meals compared to consuming a ~350 kcal high CHO or high fiber breakfast, or a larger, moderate CHO breakfastSlide7

Circadian Rhythms“Circadian rhythms are physical, mental and behavioral changes that follow a roughly 24-hour cycle, responding primarily to light and darkness in an organism's environment.”Source: National Institutes of Health, National Institute of General Medical Sciences

Circadian rhythms may be the causal link between breakfast skipping and metabolic dysregulationSlide8

Metabolic processes operate on a “biological clock”Variations in hormone levels, enzyme levels, glucose transporters at different dayparts differentially effect how calories, carbohydrates and fat are metabolizedGreen

et al (2008), Panda et al (2002): Diurnal variation in expression of genes coding for the hormones and rate limiting enzymes involved in metabolic pathways within liver, muscle and adipose tissues These so-called “rhythmic genes” are 5-20% of all genes expressed in these tissuesThe proteins these genes code for play roles relating to energy metabolism and storage

Examples: Insulin, glucagon, adiponectin,

ghrelin, leptin, and many others

Morgan et al (2003):

Plasma triglycerides also influenced by circadian rhythms, with higher levels at night

TG response to a standard meal higher in evening compared to daytime, and the day/night difference larger in men than in women

Diurnal/nocturnal variation in glucose tolerance has been observed in both humans and animals

VanCauter

et al (1991): Decreased insulin sensitivity in afternoon/evening vs. morning, no matter whether healthy human subjects were awake or asleep. Higher insulin secretion in evening and overnight compared to morning.

Versteeg

et al (2015): Better glucose tolerance and insulin sensitivity in early morning vs later in the daySlide9

The second meal phenomenonWhether an individual eats breakfast (and what they eat) affects his/her glycemic response to lunch

Specifically, CHO consumption at breakfast appears to impact glycemic response to subsequent meals favorably

Jakubowicz

D

et al

(2015): Breakfast consumption attenuates post-prandial hyperglycemia at lunch and this effect persists throughout the day in overweight patients with T2DM.

Lee

et al

(2011): Small group of middle aged Asians with T2DM: consuming mixed meal with 58g CHO at breakfast resulted in improved glucose tolerance following the same meal at lunch compared to skipping breakfast.

Chowdhury

et al

(2015): Small cohorts of lean AND obese adults without T2DM: glucose levels and insulin levels measured after a high carb pasta lunch significantly higher among breakfast skippers compared to those who ate a high GI, high CHO breakfast.Farshchi H et al (2005): Randomized crossover trial of healthy lean women: lower post-prandial insulin sensitivity to test meal (milkshake) after 2 wk period of breakfast skipping compared to same test meal after 2 wk period of regular high carb/high glycemic breakfast. Cholesterol and LDL levels were also higher after breakfast skipping period compared to breakfast eating period.Slide10

So where did Patient X go wrong?After fasting 7-8 hours overnight, patient has <100 calories in first 5 hours of waking

Skipping breakfast (or skimping on breakfast, especially carbs)

Missed

oppty

to mitigate glycemic effect of next meal via “second meal phenomenon”

Shifts greater proportion of daily intake to evening

Patient doubles down with a

low carb, low

calorie lunch

Limited % of total daily calories/carbs consumed in first daypart when glucose tolerance is the highest

Lower levels of satiety going into the eveningProlonged low blood sugar finally provokes intense cravings for simple carbs and sugar 3-4pm

Patient begins consuming majority of kcals and CHOs precisely when circadian-governed insulin sensitivity begins declining and lipogenesis increasing

Patient consumes >50% of day’s calories in short window of time in the evening

Lack of satiety from earlier in day results in strong cravings even when physiological hunger has been addressed

Pt continues grazing well past the 12-hour diurnal window of optimal glucose toleranceSlide11

Does timing of macronutrient intake actually affect metabolic markers in overweight humans?

Jacubowitz et

al (2013)

Garaulet

et

al (2013)Slide12

Jakubowicz et al (2013)Among the first randomized intervention trials to test effect of differential daypart meal patterns in overweight humans

74 non-diabetic overweight/obese women with metabolic syndrome completed the 12 week study (BMI 32.4 kg/m2 +/- 1.8)All placed on 1400 calorie/d diet for 12 weeks, with bi-weekly RD assessment for diet compliance

Randomized into two groups:

Big breakfast group: 700 kcal breakfast, 500 kcal lunch, 200 kcal low carb dinner



86% of kcals before dinner

Big dinner group: 200 kcal low carb breakfast, 500 kcal lunch, 700 kcal dinner



50% of kcals before dinner

Groups similar in terms of

age, BMI

, waist circumference, baseline triglycerides, total cholesterol, blood pressure, fasting glucose, fasting ghrelin, OGTTSlide13

Jakubowicz test meals: 2 slices whole wheat bread 4oz light tuna in water

½ cup caprese salad (tomato/mozzarella/basil)Standard Hershey milk chocolate bar

2 cups skim milk

Americano coffee

50% of daily kcals

45% of kcals from CHO

30% of kcals from protein

36% of daily kcals

~25% of kcals from CHO

~50% of kcals from protein

14% of daily kcalsLow carb65% protein, 35% fat

Sample 700 kcal meal

Sample 500 kcal meal

(Lunch)

Sample 200 kcal meal

5oz grilled chicken breast

1 cup melon

1 TBSP lite mayo

1 can beef broth soup

1 cup green salad w/ balsamic vinaigrette

Diet coke

2 scrambled

eggwhites

5 slices turkey breast

Americano coffeeSlide14

Findings: Frontloading calories and carbs metabolically favorable (I)

Both groups lost statistically significant amount of weight

Big

breakfast group lost

2.5x

more weight

than

dinner group (

p < 0.0001)

19# vs. 8#, respectively (11# difference)

Big breakfast group had significantly greater reduction in BMI (p < 0.0001)10% reduction vs 5% reduction

32.2 kg/m2 29.2 kg/m2

and 30.9 kg/m2, respectively

Weight loss

Big breakfast group lost

1.9”

more off waist circumference than dinner group (p <

0.0001)

OGTT showed lower glucose and insulin levels in big breakfast group compared to big dinner group (p <

0.0001)

ISI index of insulin sensitivity improved in both groups, but

moreso

in the big breakfast group compared to big dinner group

(p < 0.0001)

Waist circumference/

insulin sensitivity

Fasting glucose

reduced

significantly more

in

big breakfast group compared to big dinner group

(11.5% versus 4.5%) (p

<

0.0001)

Fasting insulin levels significantly lower in big breakfast group at 12 weeks, despite starting off significantly higher at baseline

51% reduction from baseline, versus 29% reduction

At 12 weeks, 9.9



IU/mL

vs. 13.2

IU/mL

Glycemic controlSlide15

Findings: Frontloading calories and carbs metabolically favorable (II)

Mean triglycerides reduced by 33% in big breakfast group and INCREASED by 14.6% in big dinner group (p<0.0001)

179.7 mg/

dL

 119.4 mg/

dL

and 178.1 mg/dL204.1 mg/

dL

, respectively

HDL was slightly but significantly increased in the big breakfast group

No statistically significant change in LDL levels within or among the groups

Lipids

Ghrelin levels were high and steady throughout the day in big dinner group. In big breakfast group, they dropped during breakfast and increased throughout the day, but never reached levels of dinner group.

No difference in fasting ghrelin levels

Lower hunger and higher satiety scores in big breakfast group compared to big dinner group

Satiety

Both groups decreased significantly, but no difference between the two groups (p>0.05)

Blood pressureSlide16

Case Study: Joseph F.57 yo AA male, multiple co-morbidities5’6”, ~300# (BMI >48kg/m2

)Type 2 diabetes, uncontrolledHypertensionHyperlipidemia

GERD

NAFLD

Night shift worker (works 11pm-7am)

Diet

hx

: A higher carb diet with most calories consumed in evening/overnight

Dinner at work: 2am (chicken/rice/veg OR turkey sandwich with lettuce/tomato)

Snack at work: 4-5am: Bagel with cream cheese & coffee or vending machine snack

“Not hungry… I snack to stay awake.”

Breakfast: 8-9am (eggs & 2 WW waffles or eggs & 4 sausages)Asleep by 10am… wakes anytime between 5:30pm and 9pmDoesn’t eat again until dinner at 2am7/15/15Wt (lbs)

299BMI

(kg/m2)48.3HgbA1c (%)

11.8 (H)

Glu

247 (H)

GGT

104 (H)

Total

Chol

211 (H)

HDL

56

LDL

130 (H)

TGs

123Slide17

Case study: Resolution7/15/15

10/29/1511/20/1512/9/15

2/22/16

Wt (lbs)

299

306

299

294

280

BMI

(kg/m2)48.349.348.347.645.2HgbA1c (%)

11.810.3

9.36.6

Glu

247

188

52

86

Waking finger sticks (mg/

dL

)

N/A

>200

Low 80s

GGT

104

118

87

82

Total

Chol

211

200

192

HDL

56

50

66

LDL

130

125

111

TGs

123

126

74

Patient given standard advice about reduced carb, lower glycemic diet:

Glycemic control improved, but he continued to gain weight at a rate of ~2#/month; liver enzymes worsened

Patient advised on circadian-synced reduced carb diet:

He began losing weight (2#/week), glycemic control improved quickly and dramatically, liver

enzymes and lipids enzymes

trending downSlide18

So… how do you actually implement this diet in real life?Slide19

Presenting the Circadian-Synced Low Glycemic DietAdapted for how free-living people live and eatALWAYS HAVE BREAKFAST!Minimum 300 kcals

Should always include a carbohydrate, preferably a high fiber/lower glycemic one (“slow carb”)Can be deferred a few hours after waking if not so hungry immediately, but not skipped

Ideally, satiating enough to preclude need for mid-morning snack

Lunch is most balanced, “main meal” of the day

Plate method of portion allocation: ¼ plate lean protein, ¼ plate “slow carb”, ½ plate non starchy veggies

Afternoon snack may be necessary if large gap between lunch/dinner (>5 hours)

No more than 200 kcals

High protein and fiber; no starches/grains (carb taper begins after lunch)

Defensive eating: Prevents patients from arriving at dinner feeling “starving”

Excess snacking, however, often compromises diet quality unless very well planned

Dinner is a small, low carb meal

Easier to control food choice and portions when not feeling excessively hungry!Slide20

BreakfastMin 300 kcals; Highest relative % of CHO of all meals1 cup cooked oatmeal/steel cut oats + 1oz nuts

2 slices Ezekiel bread + ½ mashed avocado + sliced tomato (+/- eggwhites)2 egg omelet with veggies + fruit + 1 slice WW toast1 plain Greek yogurt + 1/3-1/2 cup KIND granola + 1/3 cup pomegranate arils or 1 cup berries

3 Applegate Farms chicken sausages + 1 whole grain waffle + fruit

4

Wasa

whole grain crispbreads + tomato + cucumber + 3

oz

fish (tuna, lox, smoked mackerel) +

lowfat

cream cheese

Eggwhites

+1 slice cheese + tomato on WW 100-calorie sandwich flat (+/- fruit)…plus coffee with milk, modest amount sugar (or non caloric sweetener ) or no sweetenerSlide21

LunchMost balanced, “main meal” of the day (Plate method)Turkey/bean chili + side saladLarge turkey sandwich on WW bread with pile of baby carrots on the side (+/- side of soup)Baked salmon + ½ cup lentils + 2 cups cooked green veggies

Grilled chicken breast + ½ large sweet potato + steamed broccoli ad libLarge butternut squash soup + ½ grilled chicken or turkey sandwich on whole grain breadMushroom barley soup + tuna scoop on bed of greens

Mexican quinoa bowl: 1/2 cup quinoa + ½ cup black beans + 3

oz

chicken + 1/3 avocado + salsa + pile of greens

Shrimp/chicken with green beans/broccoli + 2/3 cup brown rice

I aim for 2/3 of daily kcals to be consumed by end of lunchtimeSlide22

Snacks100-200 kcals once/d if needed; protein + fiberApple with 1 TBSP peanut butterGrape tomatoes + 1 string cheese

Hard boiled egg +/- ½ avocado Whole piece of fruit +/- plain Greek yogurt or low sugar skyr (Siggi’s)

100 calorie pack nuts +

½

oz

semisweet chocolate chips

2oz hummus/raw vegetable

crudite

½ cup cottage cheese + fresh melon or pineapple

½ cup shelled edamame

3oz deli sliced turkey wrapped around mini cucumber or pickle spears + mustard

1 cup lentil or split pea soupTall skim latte +/- piece fruitSlide23

DinnerLight, low calorie (< 300-400 kcals), low carbSalad with fish, HB egg, or poultryCooked veggies with lean meat, fish, poultry

Spaghetti squash & turkey meatballs, marinara sauceLettuce wrap tacosTurkey burger and a salad, lite dressingOmelet or Frittata with side of haricot verts

Shakshouka

Chinese:

Shrimp or Chicken + veggie stir fry (no rice)

Mu Shu dish without pancakes/plum sauce

Japanese:

1-2

naruto

-style sushi rolls with miso soup or

hijiki

saladThai:Thai papaya salad + chicken satay appetizer (sauce on side, use sparingly)Slide24

Quality of carbs matters, but none off limits entirely

Beans, lentils, chickpeas, tofu, edamame

Dairy (milk, unsweetened yogurt, Greek yogurt)

Whole fruit

Cooked whole high fiber grains (steel cut/rolled oats, quinoa,

wheatberries

, barley, wild rice, whole grain pasta…)

Starchy fruits & vegetables (peas, winter squash, sweet potatoes); bananas

Processed whole grain foods (Whole grain breads, instant oatmeal) & lower fiber cooked grains (brown rice)

Lowest glycemic CHOs:

Make these the staples

White starchy carbs (White rice, white potatoes, white bread) & Candy

Processed/refined carbs: Low fiber cereals (Corn flakes, Rice Krispies, Special

K, etc

.), crackers, pancakes, bagels, pretzels, chips

Juice, soda, SSBs

Sweet snacks: Cookies, cakes, donuts, dried fruit

Highest glycemic CHOs:

Consume these least frequentlySlide25

Why it worksFrontloading kcals and CHOs is metabolically favorable in sync with circadian rhythmsIt is a low glycemic diet dietary pattern associated with long-term weight control

Improved satiety from mealsNot starving at dinner Improved portion control and ability to control food choice in evening

More meals, fewer snacks fewer empty calorie foods

Patients less likely to overeat CHOs at lunch than dinner restaurant portions smaller, patients fear afternoon “food coma”, less decision fatigue earlier in day

Completely adaptable to cultural food preferences

Anecdotally, pts report it doesn’t feel like a restrictive “diet”: nothing is entirely off limits long term compliance is good

Flexible enough to allow dining out at most types of restaurants

80/20 rule results generally achieved even if patients cheat 1-2 days/weekSlide26

When it might not workVegan/Paleo style diets (though these patients less likely to present as obese and diabetic..) carb restrictions unrealistic

Patients who travel a lot for work chronic jet lag disrupts circadian rhythms, minimal control over food availability

Shift workers who must eat overnight

 disturbed circadian rhythms and lack of continuity in wake/sleep/eating schedule

Though data suggest shift workers may be well advised to consume majority of kcals/CHOs during daylight hours and distort to smaller meals/protein when need to eat during nighttime hours.

Insomnia?

Depression?Slide27

References (I)Almoosawi, S., Prynne, C. J., Hardy, R., & Stephen, A. M. (2012). Time-of-day and nutrient composition of eating occasions: Prospective association with the metabolic syndrome in the 1946 British birth cohort. International Journal of Obesity, 37(5), 725–731. http://doi.org/10.1038/ijo.2012.103 Arble, D. M., Bass, J., Laposky

, A. D., Vitaterna, M. H., & Turek, F. W. (2009). Circadian timing of food intake contributes to weight gain. Obesity, 17(11), 2100–2102. http://doi.org/10.1038/oby.2009.264 Brynes, A. E., Edwards, C. M., Ghatei

, M. A.,

Dornhorst

, A., Morgan, L. M., Bloom, S. R., & Frost, G. S. (2003). A

randomised

four-intervention crossover study investigating the effect of carbohydrates on daytime profiles of insulin, glucose, non-esterified fatty acids and

triacylglycerols

in middle-aged men. British Journal of Nutrition, 89(02), 207. http://doi.org/10.1079/bjn2002769

Challet

, E. (2015). Keeping circadian time with hormones. Diabetes, Obesity and Metabolism, 17, 76–83. http://doi.org/10.1111/dom.12516

Cho, S., Dietrich, M., Brown, C. J. P., Clark, C. A., & Block, G. (2003). The effect of breakfast type on total daily energy intake and body mass index: Results from the Third national health and nutrition examination survey (NHANES III). Journal of the American College of Nutrition, 22(4), 296–302. http://doi.org/10.1080/07315724.2003.10719307 Chowdhury, E. A., Richardson, J. D., Tsintzas, K., Thompson, D., & Betts, J. A. (2015). Effect of extended morning fasting upon ad libitum lunch intake and associated metabolic and hormonal responses in obese adults. International Journal of Obesity. http://doi.org/10.1038/ijo.2015.154Chowdhury, E. A., Richardson, J. D., Tsintzas, K., Thompson, D., & Betts, J. A. (2015). Carbohydrate-rich breakfast attenuates glycaemic, insulinaemic and ghrelin response to ad libitum lunch relative to morning fasting in lean adults. British Journal of Nutrition, 114(01), 98–107. http://doi.org/10.1017/s0007114515001506 de Castro, J. M. (2007). The time of day and the proportions of macronutrients eaten are related to total daily food intake. British Journal of Nutrition, 98(05). http://doi.org/10.1017/s0007114507754296 Farshchi, H., Taylor, M., & Macdonald, I. (2005). Deleterious effects of omitting breakfast on insulin sensitivity and fasting lipid profiles in healthy lean women. The American Journal of Clinical Nutrition., 2(81). Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15699226 Froy, O. (2010). Metabolism and Circadian Rhythms—Implications for obesity. Endocrine Reviews, 31(1), 1–24. http://doi.org/10.1210/er.2009-0014 Slide28

References (II)Garaulet, M., Gómez-Abellán, P., Alburquerque-Béjar, J. J., Lee, Y., Ordovás, J. M., & Scheer, F. A. (2013). Timing of food intake predicts weight loss effectiveness.

International Journal of Obesity, 37(4), 604-611. doi:10.1038/ijo.2012.229Green, C. B., Takahashi, J. S., & Bass, J. (2008). The meter of metabolism. Cell

,

134

(5), 728–742. http://doi.org/10.1016/j.cell.2008.08.022

Jakubowicz

, D., Wainstein, J.,

Ahrén

, B., Bar-Dayan, Y., Landau, Z.,

Rabinovitz

, H. R., &

Froy, O. (2015). High-energy breakfast with low-energy dinner decreases overall daily hyperglycaemia in type 2 diabetic patients: A randomised clinical trial. Diabetologia, 58(5), 912–919. http://doi.org/10.1007/s00125-015-3524-9Jakubowicz, D., Wainstein, J., Ahren, B., Landau, Z., Bar-Dayan, Y., & Froy, O. (2015). Fasting until noon triggers increased Postprandial Hyperglycemia and impaired insulin response after lunch and dinner in individuals with type 2 diabetes: A Randomized clinical trial. Diabetes Care, 38(10), 1820–1826. http://doi.org/10.2337/dc15-0761Jakubowicz, D., Barnea, M., Wainstein, J., & Froy, O. (2013). High caloric intake at breakfast vs. Dinner differentially influences weight loss of overweight and obese women. Obesity, 21(12), 2504–2512. http://doi.org/10.1002/oby.20460Kant, A. K., & Graubard, B. I. (2015). Within-person comparison of eating behaviors, time of eating, and dietary intake on days with and without breakfast: NHANES 2005-2010. American Journal of Clinical Nutrition, 102(3), 661–670. http://doi.org/10.3945/ajcn.115.110262

Kumar Jha, P., Challet, E., & Kalsbeek, A. (2015). Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals.

Molecular and Cellular Endocrinology. http://doi.org/10.1016/j.mce.2015.01.024 Lee, S. ., Tura, A., Mari, A., Ko, S. ., Kwon, H. ., Song, K. ., … Ahn, Y. . (2011). Potentiation of the early-phase insulin response by a prior meal contributes to the second-meal phenomenon in type 2 diabetes.

AJP: Endocrinology and Metabolism

,

301

(5), E984–E990.

http://doi.org/10.1152/ajpendo.00244.2011

Levitsky

, D. A., &

Pacanowski

, C. R. (2013). Effect of skipping breakfast on subsequent energy intake.

Physiology & Behavior

,

119

, 9–16. http://doi.org/10.1016/j.physbeh.2013.05.006

Morgan, L., Hampton, S., Gibbs, M., & Arendt, J. (2003). Circadian aspects of postprandial metabolism.

Chronobiology International.

,

5

(20). Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/14535354

Panda, S.,

Antoch

, M. P., Miller, B. H., Su, A. I.,

Schook

, A. B.,

Straume

, M., …

Hogenesch

, J. B. (2002). Coordinated transcription of key pathways in the mouse by the Circadian clock.

Cell

,

109

(3), 307–320. http://

doi.org/10.1016/s0092-8674(02)00722-5Slide29

References (III)Szajewska, H., & Ruszczyński, M. (2010). Systematic review demonstrating that breakfast consumption influences body weight outcomes in children and adolescents in Europe. Critical Reviews in Food Science and Nutrition, 50(2), 113–119. http://doi.org/10.1080/10408390903467514

Timlin, M. T., Pereira, M. A., Story, M., & Neumark-Sztainer, D. (2008). Breakfast eating and weight change in a 5-Year prospective analysis of adolescents: Project EAT (eating among teens). PEDIATRICS, 121(3), e638–e645. http://doi.org/10.1542/peds.2007-1035

Van

Cauter

, E., Blackman, J., Roland, D., Spire, J.,

Refetoff

, S., &

Polonsky

, K. (1991). Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep.

The Journal of Clinical Investigation.

,

3(88). Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/1885778 Versteeg, R. I., Serlie, M. J., Kalsbeek, A., & la Fleur, S. E. (2015). Serotonin, a possible intermediate between disturbed circadian rhythms and metabolic disease. Neuroscience, 301, 155–167. http://doi.org/10.1016/j.neuroscience.2015.05.067