Sugar andSugar andBody Weight ControlBody Weight Control

Ri h d D M tt MPH PhD RDRichard D. Mattes, MPH, PhD, RDPurdue University

W f IN USAWest Lafayette, IN, USA

WHO Monica Studyy(Multinational Monitoring of Trends and Determinants in Cardiovascular Disease)

Silventoinen et al., Intl J Obes 2004; 28: 710.

Dansinger et al., JAMA 2005;293:

There are now over 1 Billi i ht1 Billion overweight

and aboutand about800 million undernourished 800 o u de ou s ed

people in the world

CDC/NCHS, Health, United States, 2006

Venus of Willendorf (24,000-22,000BC)

"The Tuscan General" Alessandro del Borro, 1645.

When did this problem begin?When did this problem begin?

Fogel RW. Am Econ RevEcon Rev 1994;84:369-395.

When did this problem begin?When did this problem begin?

Data based on the Union Army Veterans data set (~15,000 white males who served in the Union Army during the Civil War (1861-1865) and who, after the

Helmchen, LA. http://home.uchicago.edu/~lahelmch. Sept 2001.

war, applied for a pension.

Costa & Steckel, In: Natl Bureau Econ Res 1997, Pp. 47-89.

Bua J, Olsen LW, Sorensen T. Obesity 2007 15(4):977-985.

Prevalence Trends of Overweight in Danish Children

Bua J, Olsen LW, Sorensen T. Obesity 2007 15(4):977-985.

How is it happening?How is it happening?How is it happening?How is it happening?

Obesity 2007;15:2365-2370.

Th tl b d t dThe recently observed trend in average BMI implies that the average U.S. adult over-gconsumes by ~10 kcals/d… To stop the epidemic, it suffices to decrease caloricsuffices to decrease caloric consumption by ~10kcals or walk and extra 2 to 3

i t dminutes per day on average.

Jebb et al., IJO 2006;30:1160-1162.

Yanovski et al., 2000;342:861-7.

What is the Primary Problem and Best Solution?

Feeding Regulation Target InterventionNon-homeostaticNon-homeostaticHomeostatic & functionalfunctionalHomeostatic & dysfunctionaldysfunctionalHomeostatic + non-homeostatichomeostatic

What is the Primary Problem and Best Solution?

Feeding Regulation Target InterventionNon-homeostatic Meal PatternNon-homeostatic Meal PatternHomeostatic & functionalfunctionalHomeostatic & dysfunctionaldysfunctionalHomeostatic + non-homeostatichomeostatic

Prentice A. & Jebb S. Nutr Rev 2004;62:S98-S104.

What is the Primary Problem and Best Solution?

Feeding Regulation Target InterventionNon-homeostatic Meal PatternNon-homeostatic Meal PatternHomeostatic & functional AccessibilityfunctionalHomeostatic & dysfunctionaldysfunctionalHomeostatic + non-homeostatichomeostatic

Macronutrient Intake Following PreloadPreload

200*

150 *

Low Energy, Non-Exerciser

High Energy, Non-Exerciser

100+

+

Low Energy, Exerciser

High Energy, Exerciser

50

0CARBOHYRDRATE FAT PROTEIN

* P<0.05, +P<0.025, P<0.01

Long SJ et al, British Journal of Nutrition (2002), 87, 517-523

Energy Intake

A B

20 20

15

10

!5

10

5

10

5

10

EE (MJ/d) EE (MJ/d)

5 55 10 2015 5 10 2015

Blundell JE, et al. Intl J Obes 22(2):S22-S29, 1998.

Excess Energy Intake and E iExercise

4

5

6

0

1

2

3

-1

0

4

No Exercise

1

2

3

-2

-1

0

ExerciseExercise

Racette S.B., et al. Am J Clin Nutr. 62:345-9 1995

What is the Primary Problem and Best Solution?

Feeding Regulation Target InterventionNon-homeostatic Meal PatternNon-homeostatic Meal PatternHomeostatic & functional AccessibilityfunctionalHomeostatic & dysfunctional Diet/LifestyledysfunctionalHomeostatic + non-homeostatichomeostatic

ERS. http://www.ers.usda.gov/briefing/CPIFoodandExpenditures/Data/table7.htm

What is the Primary Problem and Best Solution?

Feeding Regulation Target InterventionNon-homeostatic Meal PatternNon-homeostatic Meal PatternHomeostatic & functional AccessibilityfunctionalHomeostatic & dysfunctional Diet/LifestyledysfunctionalHomeostatic + non-homeostatic Palatability/Rewardhomeostatic

Johnson et al., Am J Clin Nutr 2007;86:899-906.

n40

10

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Diet Soft Drinks

cons

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ion

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)

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10Obesity Prevalence

t Sof

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a

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1970 1980 1990 200015 0

31%23%15%14%13%

n40

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12Non-Diet Soft Drinks

Diet Soft Drinks

Percent of Intense Hurricanesco

nsum

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t Sof

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http://www.capmag.com/article.asp?ID=4418

“The mechanism was related to the inability of fructose to acutely stimulate insulin and leptin and to inhibit ghrelin, all factors that are known to affect the

Johnson et al., Am J Clin Nutr 2007;86:899-906.

insulin and leptin and to inhibit ghrelin, all factors that are known to affect the satiety center in the central nervous system.”

Neuroendocrine Factors inF di R l iFeeding Regulation

• Leptin • Corticosterone • TNF alpha• Leptin• Insulin• Amylin

• Corticosterone• Serotonin• Dopamine

• TNF-alpha• Beta-Endorphin• Dynorphin

• NPY• CRH• UCN

• MCH• Orexins• Ghrelin

• BDNF• PYY• IL-6UCN

• UCNII• Galanin• Neurotensin

Ghrelin• GLP-1• GLP-2• AgRP

IL 6• IL-1• IL-1RA• Norepinephrine• Neurotensin

• CART• Oxytocin

• AgRP• Beacon• Cannabinoids

• Norepinephrine• Amino Acids• PRL-RL

• Alpha-MSH • GAL-LP

Carbohydrate and Appetite, Food y pp ,Choice, Energy Balance and Body

WeightWeight

**Glu InsulinInsulin Glucose

**

Hunger Intake +EB Wt

Fruc InsulinInsulin Leptin**

Leptin and Food Intake

AN B d LeptinLeptin A d idAN Body LeptinLeptin Anandamide**Fat

BED B d L tiL ti A d id**

Intake

BED Body LeptinLeptin AnandamideFat Anandamide

( iti it )( sensitivity)

Monteleone et al., Neuropsychopharmacol 2005;30:1216-1221.

60

80

a

20

40

a

-20

0pg/m

l SIILII

-60

-40

1 3 5 7 9 11 13 15

Time points (30 minute increments)

Ghrelin profiles (calculated as change from baseline) standardized to lunch time by meal group. Arrows designate the lunch times for each group. “b” Time to from nadir to peak concentration is significantlyb Time to from nadir to peak concentration is significantly greater than SII, p<0.05

Frecka & Mattes Am J Physiol. 2008;294: G699.

0 400

Time Series Analysis for Ghrelin and Hunger

0.350

0.400Lag – Hunger precedes Ghrelin

0.250

0.300

0.150

0.200 All ParticipantsSII GroupLII Group

0 050

0.100

p

0.000

0.050

Lead 90 Lead 60 Lead 30 0 Lag 30 Lag 60-0.050 min. min. min. min. min.

McKiernan et al., Physiol & Behav 2008;93:975-983.

Properties of Sugar Associated with

Increased Energy IntakeIncreased Energy Intake

P l t bilit• Palatability• Sweetener• Sweetener• Sweetness• Sweetness

Looy H, & Weingarten HP, Chem Senses 1991;16:123-130.

Palatability Effects on AppetitePalatability Effects on Appetite

• Enhances motivation to eatEnhances motivation to eat– Hill et al., Appetite 1984;5:361– Yeomans et al., Appetite 1997;29:61Yeomans et al., Appetite 1997;29:61

• No Effect on motivation to eat– Yeoman & Symes Appetite 1999;32:383Yeoman & Symes Appetite 1999;32:383

• Diminishes motivation to eatWarwick et al Physiol Behav 1993;53:553– Warwick et al., Physiol Behav 1993;53:553

– DeGraaf et al., Physiol Behav 1999;66:681

Properties of Sugar Associated with

Increased Energy IntakeIncreased Energy Intake

P l t bilit• Palatability• Sweetener• Sweetener• Sweetness• Sweetness

Mechanisms By Which Sweeteners/Sweetness May

Stimulate Energy IntakeStimulate Energy Intake• Stimulate appetite• Informed use increases intake• Loss of signal fidelityLoss of signal fidelity• Water effects

A ti ti f d t• Activation of reward systems• Training the palate• Genetics

Positive AUC = 100; Total AUC = 100

200

;Positive AUC = 120; Total AUC = 92

160180200

)

100120140

se (m

g/dl

6080

100

Glu

cos

02040

0 30 60 90 120Time (min)

0

Chapman et al., Am J Physiol 1998;274:R596-R603.

Chapman et al., Am J Physiol 1998;274:R596-R603.

Chapman et al., Am J Physiol 1998;274:R596-R603.

Chapman et al., Am J Physiol 1998;274:R596-R603.

Mechanisms By Which Sweeteners/Sweetness May

Stimulate Energy IntakeStimulate Energy Intake• Stimulate appetite• Informed use increases intake• Loss of signal fidelityLoss of signal fidelity• Water effects

A ti ti f d t• Activation of reward systems• Training the palate• Genetics

Swithers & Davidson Behav Neurosci 2008;122:161-173.

Fig. 3. Effects of energy on measures of cumulative energy intake across the day in HASB and LASB. Hashed bars represent LASB solid bars represent HASB In each pair the

Fig. 2. Effects of sweet taste on measures of cumulative energy intake across the day in HASB and LASB. Hashed bars represent LASB solid bars represent HASB In each pair the represent LASB, solid bars represent HASB. In each pair, the

pale bars on the left represent consumption after the AS preload, the dark bars on the right represent consumption after the NS preload. #Significant differences (pb0.05) between LASB and HASB, independent of preload.

represent LASB, solid bars represent HASB. In each pair, the dark bars on the left represent consumption after the W preload, the pale bars on the right represent consumption after the AS preload. �Significant differences ( pb0.05) between Wand AS preloads in LASB, no differences in HASB. #Significant differences ( pb0.05) between LASB and HASB, independent ofdifferences ( pb0.05) between LASB and HASB, independent ofpreload.

Appleton & Blundell. Physiol Behav 2007;92:479-486.

Mechanisms By Which Sweeteners/Sweetness May

Stimulate Energy IntakeStimulate Energy Intake• Stimulate appetite• Informed use increases intake• Loss of signal fidelityLoss of signal fidelity• Water effects

A ti ti f d t• Activation of reward systems• Training the palate• Genetics

De Araujo et al., Neuron 2008;57:930-941.

Davis & Fox. Appetite. 2008;50:43-49.

Mechanisms By Which Sweetness May Stimulate

Energy IntakeEnergy Intake• Stimulate appetite• Informed use increases intake• Loss of signal fidelityLoss of signal fidelity• Water effects

A ti ti f d t• Activation of reward systems• Training the palate• Genetics

Liem & de Graaf. Physiol & Behav 2004;83:421-429.

Energy Intake(N=40)

3 5 0 0

4 0 0 0

( )

L i i

Carbohydrate Fat Protein(Watermel lon) (Coconut) (Dairy )

2 5 0 0

3 0 0 0

L iq u i

So lid*(Watermel lon) (Coconut) (Dairy )

1 5 0 0

2 0 0 0

2 5 0 0

Kca

ls L iq u i

So lid* *

1 0 0 0

1 5 0 0 L iq u i

So lid

0

5 0 0

Summary• The roots of the obesity problem may be deeperThe roots of the obesity problem may be deeper

and stronger than currently recognized• The role of appetite in regulating energy intake pp g g gy

is uncertain• Positive energy balance reflects total energy gy gy

intake not macronutrient or sugar composition of the diet.

• Multiple mechanisms have been proposed that associated sugar with obesity, but few are

d t l t d b i tifi idadequately supported by scientific evidence.

Gatenby et al., AJCN 1997;65:1867-1873.

Franken & Muris. Appetite. 2005;45:198-201.

Mechanisms By Which Sweeteners/Sweetness May

Stimulate Energy IntakeStimulate Energy Intake• Stimulate fat intake• Informed use increases intake• Loss of signal fidelityLoss of signal fidelity• Water effects

A ti ti f d t• Activation of reward systems• Training the palate• Genetics

Mattes Physiol Behav 1990;47:1037-1044.

Naismith & Rhodes J Humn Nutr Dietet 1995;8:167-175.