1. Sugar and
Body Weight Control
Richard D M tt
Ri h d D. Mattes, MPH PhD RD
MPH, PhD,
Purdue University
West Lafayette, IN, USA
W f IN

2. WHO Monica Study
y
(Multinational Monitoring of Trends and Determinants in Cardiovascular Disease)
Silventoinen et al., Intl J Obes 2004; 28: 710.

3. Dansinger et al., JAMA 2005;293:

4. There are now over
1 Billi overweight
Billion i ht
and about
800 million u de ou s ed
o undernourished
people in the world

5. CDC/NCHS, Health, United States, 2006

6. Venus of Willendorf "The Tuscan General"
(24,000-22,000BC) Alessandro del Borro,
1645.

7. When did this problem begin?
Fogel RW. Am
Econ Rev
1994;84:369-395.

8. 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
war, applied for a pension.
Helmchen, LA. http://home.uchicago.edu/~lahelmch. Sept 2001.

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

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

11. Prevalence Trends of Overweight in Danish Children
Bua J, Olsen LW, Sorensen T. Obesity 2007 15(4):977-985.

12. How is it happening?

13. Obesity 2007;15:2365-2370.
The
Th recently observed t d
tl b d trend
in average BMI implies that
the average U.S. adult over-
g
consumes by ~10 kcals/d…
To stop the epidemic, it
suffices to decrease caloric
consumption by ~10kcals or
walk and extra 2 to 3
minutes per day on average.
i t d

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

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

17. What is the Primary Problem
and Best Solution?
Feeding Regulation Target Intervention
Non-homeostatic
Homeostatic &
functional
Homeostatic &
dysfunctional
Homeostatic + non-
homeostatic

18. What is the Primary Problem
and Best Solution?
Feeding Regulation Target Intervention
Non-homeostatic Meal Pattern
Homeostatic &
functional
Homeostatic &
dysfunctional
Homeostatic + non-
homeostatic

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

20. What is the Primary Problem
and Best Solution?
Feeding Regulation Target Intervention
Non-homeostatic Meal Pattern
Homeostatic &
Accessibility
functional
Homeostatic &
dysfunctional
Homeostatic + non-
homeostatic

21. Macronutrient Intake Following
Preload
200
* Low Energy, Non-
Exerciser
150 High Energy, Non-
* Exerciser
Low Energy, Exerciser
100 High Energy, Exerciser
+
+
50
0
CARBOHYRDRATE FAT PROTEIN
* P<0.05, +P<0.025, P<0.01
Long SJ et al, British Journal of Nutrition (2002), 87, 517-523

22. Energy Intake
A B
20 20
15 !5
10 10
5 5
5 10 15 20 5 10 15 20
EE (MJ/d) EE (MJ/d)
Blundell JE, et al. Intl J Obes 22(2):S22-S29, 1998.

23. Excess Energy Intake and
6
Exercise
E i
5
4
3
2
1
0
-1
No Exercise
4
3
2
1
0
-1
-2
Exercise
Racette S.B., et al. Am J Clin Nutr. 62:345-9 1995

24. What is the Primary Problem
and Best Solution?
Feeding Regulation Target Intervention
Non-homeostatic Meal Pattern
Homeostatic &
Accessibility
functional
Homeostatic &
Diet/Lifestyle
dysfunctional
Homeostatic + non-
homeostatic

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

26. What is the Primary Problem
and Best Solution?
Feeding Regulation Target Intervention
Non-homeostatic Meal Pattern
Homeostatic &
Accessibility
functional
Homeostatic &
Diet/Lifestyle
dysfunctional
Homeostatic + non-
Palatability/Reward
homeostatic

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

28. 40 12
Non-Diet Soft Drinks
Diet Soft Drinks
10
Non-Diet Soft Drink consumption
n
Obesity Prevalence
35
nsumption
apita)
apita)
8
30
(gallons per ca
(gallons per ca
Diet So Drink con
c
6
25
oft
4
t
20
2
13% 14% 15% 23% 31%
15 0
1970 1980 1990 2000
Year

29. Percent of Intense Hurricanes
40 12
Non-Diet Soft Drinks
Diet Soft Drinks
10
Non-Diet Soft Drink consumption
n
Obesity Prevalence
35
nsumption
apita)
apita)
8
30
(gallons per ca
(gallons per ca
Diet So Drink con
c
6
25
oft
4
t
20
2
13% 14% 15% 23% 31%
15 0
1970 1980 1990 2000
Year
http://www.capmag.com/article.asp?ID=4418

30. “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
satiety center in the central nervous system.”
Johnson et al., Am J Clin Nutr 2007;86:899-906.

31. Neuroendocrine Factors in
Feeding R
F di Regulation
l i
• Leptin • Corticosterone • TNF-alpha
TNF alpha
• Insulin • Serotonin • Beta-Endorphin
• Amylin • Dopamine • Dynorphin
• NPY • MCH • BDNF
• CRH • Orexins • PYY
• UCN • Ghrelin • IL 6
IL-6
• UCNII • GLP-1 • IL-1
• Galanin • GLP-2 • IL-1RA
• Neurotensin • AgRP • Norepinephrine
• CART • Beacon • Amino Acids
• Oxytocin • Cannabinoids • PRL-RL
• Alpha-MSH • GAL-LP

32. Carbohydrate and Appetite, Food
y pp ,
Choice, Energy Balance and Body
Weight
*
Glu Insulin Glucose
Hunger Intake +EB Wt
Fruc Insulin Leptin
*

33. Leptin and Food Intake
AN B d
Body Leptin Anandamide
A d id
Fat *
Intake
*
BED B d
Body Leptin A d id
L ti Anandamide
Fat Anandamide
( sensitivity)
iti it )
Monteleone et al., Neuropsychopharmacol 2005;30:1216-1221.

34. 80
60 a
40
20
SII
pg/ml
LII
0
-20
-40
-60
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 significantly
b
greater than SII, p<0.05
Frecka & Mattes Am J Physiol. 2008;294: G699.

35. Time Series Analysis for Ghrelin and Hunger
0.400
0 400
Lag – Hunger precedes Ghrelin
0.350
0.300
0.250
0.200 All Participants
SII Group
0.150 LII Group
p
0.100
0.050
0 050
0.000
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.

36. Properties of Sugar
Associated with
Increased Energy Intake
• P l t bilit
Palatability
• Sweetener
• Sweetness

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

38. Palatability Effects on Appetite
• Enhances motivation to eat
– Hill et al., Appetite 1984;5:361
– Yeomans et al., Appetite 1997;29:61
• No Effect on motivation to eat
– Yeoman & Symes Appetite 1999;32:383
• Diminishes motivation to eat
– Warwick et al Physiol Behav 1993;53:553
al.,
– DeGraaf et al., Physiol Behav 1999;66:681

39. Properties of Sugar
Associated with
Increased Energy Intake
• P l t bilit
Palatability
• Sweetener
• Sweetness

40. Mechanisms By Which
Sweeteners/Sweetness May
Stimulate Energy Intake
• Stimulate appetite
• Informed use increases intake
• Loss of signal fidelity
• Water effects
• Activation f
A ti ti of reward systems
d t
• Training the palate
• Genetics

41. Positive AUC = 100; Total AUC = 100
;
Positive AUC = 120; Total AUC = 92
200
180
160
Glucos (mg/dl)
140
120
se
100
80
60
40
20
0
0 30 60 90 120
Time (min)

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

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

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

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

46. Mechanisms By Which
Sweeteners/Sweetness May
Stimulate Energy Intake
• Stimulate appetite
• Informed use increases intake
• Loss of signal fidelity
• Water effects
• Activation f
A ti ti of reward systems
d t
• Training the palate
• Genetics

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

48. Fig. 2. Effects of sweet taste on measures of cumulative energy Fig. 3. Effects of energy on measures of cumulative energy
intake across the day in HASB and LASB. Hashed bars intake across the day in HASB and LASB. Hashed bars
represent LASB solid bars represent HASB In each pair the
LASB, HASB. pair, represent LASB solid bars represent HASB In each pair the
LASB, HASB. pair,
dark bars on the left represent consumption after the W preload, pale bars on the left represent consumption after the AS
the pale bars on the right represent consumption after the AS preload, the dark bars on the right represent consumption after
preload. Significant differences ( pb0.05) between Wand AS the NS preload. #Significant differences (pb0.05) between LASB
preloads in LASB, no differences in HASB. #Significant and HASB, independent of preload.
differences ( pb0.05) between LASB and HASB, independent of
preload.
Appleton & Blundell. Physiol Behav 2007;92:479-486.

49. Mechanisms By Which
Sweeteners/Sweetness May
Stimulate Energy Intake
• Stimulate appetite
• Informed use increases intake
• Loss of signal fidelity
• Water effects
• Activation f
A ti ti of reward systems
d t
• Training the palate
• Genetics

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

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

52. Mechanisms By Which
Sweetness May Stimulate
Energy Intake
• Stimulate appetite
• Informed use increases intake
• Loss of signal fidelity
• Water effects
• Activation f
A ti ti of reward systems
d t
• Training the palate
• Genetics

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

54. Energy Intake
(
(N=40)
)
4000
Carbohydrate Fat Protein
3500
(Waterm ellon) (Coc onut) (Dairy ) Li ui
iq
*
3000
S o li d
2500
* *
L iq u i
K cals
2000
S o li d
1500
L iq u i
1000
S o li d
500
0

55. Summary
• The 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
adequately supported b scientific evidence.
d t l t d by i tifi id

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

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

58. Mechanisms By Which
Sweeteners/Sweetness May
Stimulate Energy Intake
• Stimulate fat intake
• Informed use increases intake
• Loss of signal fidelity
• Water effects
• Activation f
A ti ti of reward systems
d t
• Training the palate
• Genetics

59. Mattes Physiol Behav 1990;47:1037-1044.

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