The trouble with fructose

1
The trouble with fructose
Robert H. Lustig, M.D. Division of
Endocrinology Department of Pediatrics University
of California, San Francisco
ASTPHND, Madison, WI, June 8, 2008
2
Prediction of BMI distribution in adults, 2008
The entire curve has shifted
Hill et al. Science 299853, 2003
3
The First Law of Thermodynamics
CaloriesIn
Weight Gain
CaloriesOut
4
Quote 1
What happened to willpower? I love fat people.
Every fat person says its not their fault, that
they have gland trouble. You know which gland?
The saliva gland. They cant push away from the
table. Jesse Ventura (I), Former Governor of
Minnesota. Playboy, November 19994655.
5
Quote 2
A calorie is a calorie. -Anonymous
dietitian
6
Total Caloric Intake
? 275 kcal in teen boys
Children 2-17 yrs, CSFII (USDA) 1989-91 vs.
1994-95 http//www.usda.gov/cnpp/FENR20V11N3/fenr
v11n3p44.PDF
7
Fat Intake Grams
? 5 g (45 cal) in teen boys
Children 2-17 yrs, CSFII (USDA) 1989-91 vs.
1994-95
8
Carbohydrate Intake Grams
? 57 g (228 cal) in teen boys
Children 2-17 yrs, CSFII (USDA) 1989-91 vs.
1994-95
9
Prevalence of Obesity Compared to
Percent Calories from Fat Among US Adults
Percent
Year
10
Beverage Intake
?41 soft drinks
?35 fruit drinks
Children 2-17 yrs, CSFII (USDA) 1989-91 vs.
1994-95
11
Beverage Intake
?41 soft drinks
?35 fruit drinks
Children 2-17 yrs, CSFII (USDA) 1989-91 vs.
1994-95
One can of soda/day 150 cal x 365 d/yr 3500
cal/lb 15.6 lbs/yr!
12
(No Transcript)
13
Are soft drinks the cause of obesity?

• There is no association between sugar
  consumption and obesity.
• Richard Adamson
• Scientist for National Soft Drink Association
• BMJ 326, March, 2003
• Each additional sugar-sweetened drink increase
  over a 19 month follow-up
• BMI 0.24 kg/m2 (95 CI 0.1-0.39)
• OR for obesity 1.6 (95 CI 1.14-2.24)
• Ludwig et al. Lancet 2001

14
Meta-Analysis of Soft Drinks and Obesity

• 88 cross-sectional and longitudinal studies
  regressing
• soft drink consumption with
•  energy intake r 0.16 (P lt 0.001)
• body weight r 0.08 (P lt 0.001)
• milk and calcium intake r -0.12 (P lt 0.001)
•  adequate nutrition r -0.10 (P lt 0.001)
• Those studies funded by the beverage industry
  demonstrated smaller effects than independent
  studies

Vartanian et al. Am J Public Health epub March
2007 10.2105/AJPH.2005.083782
15
Curtailing soft drinks limits childhood obesity
Obesity Prevalence ()
James et al. BMJ 3281237, 2004
16
(No Transcript)
17
High Fructose Corn Syrup
Current US annual consumption of HFCS 63
pounds per person
18
Sucrose
High Fructose Corn Syrup
19
Relative sweetness of various carbohydrates
Fructose 173 invert sugar 120 HFCS
(42-55 fructose) 120 Sucrose 100 Xylitol
100 Tagatose 92 Glucose 74 high-DE
corn syrup 70 Sorbitol 55 Mannitol
50 Trehalose 45 regular corn syrup
40 Galactose 32 Maltose 32 Lactose
15
20
From the Corn Refiners Association December, 2006
21
Unlikely Duo Opposes San Francisco Soft
Drink Tax Plan Corn Refiners and CSPI Agree
High-Fructose Corn Syrup No Worse Than
Sugar WASHINGTONThe nonprofit Center for
Science in the Public Interest has long supported
small taxes on soft drinks to help pay for bike
paths, nutrition education, and other
obesity-prevention programs. But CSPI opposes a
measure proposed by San Francisco Mayor Gavin
Newsom because it would tax only drinks made with
high-fructose corn syrup and not drinks made with
other forms of sugar. Less surprisingly, the Corn
Refiners Association also opposes the measure,
but the two groups cosigned an unusual joint
letter to Mayor Newsom urging him to reconsider
his plan. We respectfully urge that the
proposal be revised as soon as possible to
reflect the scientific evidence that demonstrates
no material differences in the health effects of
high-fructose corn syrup and sugar, wrote CSPI
executive director Michael F. Jacobson and Corn
Refiners Association president Audrae Erickson.
The real issue is that excessive consumption of
any sugars may lead to health problems. The
letter goes on to explain that high-fructose corn
syrup and sucrose, or table sugar, are similar in
composition and that several studies have shown
that the two types of sugars are similarly
metabolized by the body.
Press Release, February 6, 2008
22
High Fructose Corn Syrup is 42-55
Fructose Sucrose is 50 Fructose
Glucose
Fructose
Sucrose
23
Juice is sucrose Change in BMI z-score in lower
socioeconomic status children versus number of
fruit juice servings per day
Faith MS et al. Pediatrics 1182066, 2006
24
MOST FRUCTOSE ITEMS
Sucrose
JUICE
High Fructose Corn Syrup
25
Fructose is not glucose
 Fructose is 7 times more likely than glucose
to form Advanced Glycation End-Products
(AGEs) Fructose does not suppress ghrelin
Acute fructose does not stimulate insulin (or
leptin) Hepatic fructose metabolism is
different Chronic fructose exposure promotes
the Metabolic Syndrome
Elliot et al. Am J Clin Nutr, 2002 Bray et al. Am
J Clin Nutr, 2004 Teff et al. J Clin Endocrinol
Metab, 2004
Gaby, Alt Med Rev, 2005 Le and Tappy, Curr Opin
Clin Nutr Metab Care, 2006 Wei et al. J Nutr
Biochem, 2006
26
24 kcal
Hepatocyte
96 kcal
27
(No Transcript)
28
Ethanol is a carbohydrate

• CH3-CH2-OH

But ethanol is also a toxin
29
Acute ethanol exposure
CNS depression Vasodilatation,
decreased BP Hypothermia
Tachycardia Myocardial
depression Variable pupillary
responses Respiratory depression
Diuresis Hypoglycemia
Loss of fine motor control
Acute fructose exposure

30
(No Transcript)
31
(No Transcript)
32
60 kcal ( 12 kcal glucose)
48 kcal
33
(No Transcript)
34
Isganaitis and Lustig, Arterio Thromb Vasc Biol
252451, 2006
35
Why is exercise important in obesity?

• Because it burns calories?
• Because it improves skeletal muscle insulin
  sensitivity
• Because it reduces stress, and resultant cortisol
  release
• Because it makes the TCA cycle run faster, and
  detoxifies fructose, improving hepatic insulin
  sensitivity

36
Chronic ethanol exposure
Hematologic disorders Electrolyte
abnormalities Hypertension
Cardiac dilatation
Cardiomyopathy Dyslipidemia
Pancreatitis Malnutrition
Obesity Hepatic dysfunction
(ASH) Fetal alcohol syndrome
Addiction
Chronic fructose exposure
Hypertension
Myocardial infarction
Dyslipidemia Pancreatitis (2o
dyslipidemia)
Obesity Hepatic dysfunction (NASH)
Fetal insulin resistance
Habituation, if not addiction
37
UCSF Weight Assessment for Teen and Child Health
(WATCH) Clinic294 patients 2003-2006

• Race/Ethnicity

• Biochemistry

Mietus-Snyder et al. (submitted)
38
UCSF WATCH ClinicAssociations with the Metabolic
Syndrome
Mietus-Snyder et al. (submitted)
39
UCSF WATCH ClinicLifestyle Intervention

• Get rid of all sugared liquidsonly water and
  milk
• Eat your carbohydrate with fiber
• Wait 20 minutes for second portions
• Buy your screen time minute-for-minute with
• physical activity
• Pts are followed every 3 months

40
UCSF WATCH Clinic Lifestyle InterventionMedian
Change in BMI z-score from Baseline
Madsen et al. (submitted)
41
UCSF WATCH Clinic Predictors of Lifestyle
Intervention

• Forward selection model, 4 variables

Source SS df MS
Number of obs 130 --------------------
----------------------- F( 4, 125)
6.49 Model .169200646 4
.042300161 Prob gt F 0.0001
Residual .81467663 125 .006517413
R-squared 0.1720 ------------------------
------------------- Adj R-squared
0.1455 Total .983877276 129
.007626956 Root MSE
.08073 ------------------------------------------
------------------------------------ Delta z/yr
Coef. Std. Err. t Pgtt
Beta ---------------------------------
--------------------------------------------
sugared bev .012786 .0048643 2.63
0.010 .2268616 HOMA
.0034239 .0018131 1.89 0.061
.1707474 Baseline BMIZ .0311507 .0199972
1.56 0.122 .1430862 Baseline
Age .0027542 .0022543 1.22 0.224
.1055135 _cons -.1475346
.0573037 -2.57 0.011
. ------------------------------------------------
------------------------------
Madsen et al. (submitted)
42
The fructosification of America (and the world)
43
Can you name the seven foodstuffs at McDonalds
that dont have HFCS or sucrose?

• French Fries (salt, starch, and fat)
• Hash Browns (salt, starch, and fat)
• Chicken McNuggets (salt, starch, and fat)
• Sausage
• Diet Coke
• Coffee
• Iced Tea

44
Whos really drinking this?
45
The SFUSD School Milk Program
Courtesy of M. Lustig
46
What about WIC?
J. Nutr. 1361086, 2006
47
Could this be the reason for obesity with
formula feeding?

• INGREDIENTS (Powder)
• ((U) Pareve)
• 43.2 Corn syrup solids, 14.6 soy protein
  isolate, 11.5 high oleic safflower oil,
• 10.3 sugar (sucrose),
• 8.4 soy oil,
• 8.1 coconut oil

Courtesy of M. Walker
48
Whats the difference?
Calories 150 150 Percent CHO 10.5
(sucrose) 3.6 (alcohol) Calories from
fructose 75 (4.1 kcal/gm) other carbs 75
(glucose) 60 (maltose) alcohol 90 (7
kcal/gm) 1st pass GI metabolism 0
10 Calories reaching liver 90 92
49
Fructose is a carbohydrate
Fructose is metabolized like fat
(corollary a low fat diet isnt really low fat,
because the fructose/sucrose doubles as fat)
Fructose is also a toxin
50
DESIGN, MANUFACTURING AND MARKETING OF TOBACCO
PRODUCTS TOWARDS A SENSIBLE REGULATORY
FRAMEWORKBates Number 2065346777/6799, Page 3

• Under the regulations governing food additives,
  its required that additives be safe, defined
  as a reasonable certainty by competent scientists
  that no harm will result from the intended use of
  the additive. 21 C.F.R. Sec. 170(3)(I)(1998).
  Using this standard, numerous additives generally
  thought of as fat, including fatty acids, cocoa
  butter substitute, epoxidized soybean oil and the
  like are permitted to be used in ordinary course.
  

HFCS has FDA GRAS status (Generally Regarded as
Safe)
Philip Morris (Altria) Company From the UCSF
Legacy Tobacco Documents Library
51
DESIGN, MANUFACTURING AND MARKETING OF TOBACCO
PRODUCTS TOWARDS A SENSIBLE REGULATORY
FRAMEWORKBates Number 2065346777/6799, Page 3

• Although there is no existing regulatory
  framework permitting FDA to restrict a consumers
  choice to consume high fat foods, such products
  are, like all food products, subject to general
  FDA requirements regarding adulteration and
  misbranding. See e.g. 21 U.S.C. Sec 402(a) A
  food shall be deemed to be adulterated if it
  bears of contains any poisonous or deleterious
  substance which may render it injurious to
  health.Thus, under existing law the agency is
  charged with the responsibility of ensuring that
  consumption of high fat (and all other) food
  products does not result in acute injuries such
  as poisoning, and with preventing consumers from
  being misled, but not with the prevention of
  chronic diseases even though its own regulations
  explicitly postulate the connection between such
  products and such diseases.

Philip Morris (Altria) Company From the UCSF
Legacy Tobacco Documents Library
52
Summary
Fructose (sucrose vs. HFCS) consumption has
increased in the past 30 years, coinciding with
the obesity epidemic Fructose is everywhere
A calorie is not a calorie, and fructose is not
glucose Hepatic fructose metabolism leads to
all the manifestations of the Metabolic
Syndrome hypertension de novo lipogenesis,
dyslipidemia, and hepatic steatosis inflammation
hepatic insulin resistance obesity CNS leptin
resistance, promoting continuous consumption
Fructose ingestion interferes with obesity
intervention Fructose is a chronic hepatotoxin
(its alcohol without the buzz) but FDA
cant and wont regulate it
53
Collaborators
UCSF Dept. of Pediatrics Chaluntorn
Preeyasombat, M.D. Elvira Isganaitis,
M.D. Michele Mietus-Snyder, M.D. Andrea Garber,
Ph.D., R.D. Joan Valente, Ph.D. Cam-Tu Tran,
M.D. Kristine Madsen, M.D., M.P.H. Stephanie
Nguyen, M.D. Carolyn Jasik, M.D., M.P.H. UCSF
Dept. of Epidemiology and Biostatistics Ann
Lazar, Ph.D. Peter Bacchetti, Ph.D. Saunak Sen,
Ph.D. UC Berkeley Dept. of Nutritional
Sciences Jean-Marc Schwarz, Ph.D. Sharon
Fleming, Ph.D. Lorene Ritchie, Ph.D.