Transcript Document

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
Prediction of BMI distribution in adults, 2008
The entire
curve has
shifted
Hill et al. Science 299:853, 2003
The First Law of Thermodynamics
Weight Gain
Calories
Out
Calories
In
Total Caloric Intake
 275 kcal in teen boys
Children 2-17 yrs, CSFII (USDA) 1989-91 vs. 1994-95
http://www.usda.gov/cnpp/FENR%20V11N3/fenrv11n3p44.PDF
Fat Intake: Grams
 5 g (45 cal) in teen boys
Children 2-17 yrs, CSFII (USDA) 1989-91 vs. 1994-95
Carbohydrate Intake: Grams
 57 g (228 cal) in teen boys
Children 2-17 yrs, CSFII (USDA) 1989-91 vs. 1994-95
Prevalence of Obesity Compared to Percent
Calories from Fat Among US Adults
60
Percent
50
40
30
Calories from fat
20
10
Obesity prevalence
0
1960
1970
1980
Year
1990
2000
Beverage Intake
41% soft drinks
35%
fruit drinks
Children 2-17 yrs, CSFII (USDA) 1989-91 vs. 1994-95
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!
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
Meta-Analysis of Soft Drinks and Obesity
88 cross-sectional and longitudinal studies regressing
soft drink consumption with —
• energy intake
• body weight
• milk and calcium intake
• adequate nutrition
r = 0.16 (P < 0.001)
r = 0.08 (P < 0.001)
r = -0.12 (P < 0.001)
r = -0.10 (P < 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
Obesity Prevalence (%)
Curtailing soft drinks limits childhood obesity
James et al. BMJ 328:1237, 2004
High Fructose Corn Syrup
Current US annual
consumption of
HFCS
• 63 pounds per
person
Sucrose
High Fructose Corn Syrup
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
From the Corn Refiners Association
December, 2006
Press Release, February 6, 2008
Unlikely Duo Opposes San Francisco Soft Drink Tax Plan
Corn Refiners and CSPI Agree High-Fructose Corn Syrup No Worse Than Sugar
WASHINGTON—The 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 highfructose 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.
High Fructose Corn Syrup is 42-55% Fructose;
Sucrose is 50% Fructose
Glucose
Fructose
Sucrose
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 118:2066, 2006
MOST FRUCTOSE ITEMS
Sucrose
JUICE
High Fructose Corn Syrup
Fructose is not glucose
• Fructose is 7 times more likely than glucose
to form Advanced Glycation End-Products (AGE’s)
• 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
24 kcal
Hepatocyte
96 kcal
Ethanol is a carbohydrate
CH3-CH2-OH
But ethanol is also a toxin
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
60 kcal
(+ 12 kcal
glucose)
48 kcal
Isganaitis and Lustig, Arterio Thromb Vasc Biol 25:2451, 2006
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
Chronic ethanol exposure
Chronic fructose exposure
• Hematologic disorders
• Electrolyte abnormalities
• Hypertension
• Hypertension
• Cardiac dilatation
• Cardiomyopathy
• Myocardial infarction
• Dyslipidemia
• Dyslipidemia
• Pancreatitis
• Pancreatitis (2o dyslipidemia)
• Malnutrition
• Obesity
• Obesity
• Hepatic dysfunction (ASH)
• Hepatic dysfunction (NASH)
• Fetal alcohol syndrome
• Fetal insulin resistance
• Addiction
• Habituation, if not addiction
UCSF Weight Assessment for Teen and Child Health
(WATCH) Clinic
294 patients 2003-2006
• Biochemistry
BMI
BMI z-score
FBG
Insulin
HOMA-IR
Maternal BMI
Paternal BMI
Median
33.2
2.5
87
20.7
4.3
28.9
28.9
Mietus-Snyder et al. (submitted)
Min
20.0
1.3
58
2
0.34
17.7
16.7
Max
92.4
4.4
119
117.5
28.1
58.6
48.8
• Race/Ethnicity
Norm al
<25
0
<100
5-20
<4
<25
<25
Unknown
7%
Mi xed
10%
Caucasi an
30%
Asian
12%
AfricanAmerican
14%
Latino
27%
UCSF WATCH Clinic
Associations with the Metabolic Syndrome
Baseline
Characteristic
HOMA-IR >5* HOMA-IR<5
N=124
N=147
P-value**
BM I z-score
2.6, 2.3-2.8
2.5, 2.2-2.7
0.06
BP syst
125 ± 13
113 ± 15
<0.001
BP diast
68 ± 9
64 ± 8
<0.001
Triglyceride
102, 69-138
83, 57-110
0.005
41 ± 10
43 ± 10
0.04
92 + 9
85 + 9
<0.001
(mean ± SD)
(mU/dl)
HDL-c
(mU/dl)
Fasting Glc
(mg /dl)
Fasting Insulin
(mU /ml)
33.7,28.6-47.1 15.2,11.2-19.8 <0.001
Creatinine
(mg /dl)
ALT (U/L)
0.64 + 0.14
35, 23-50
0.58 + 0.15
23, 18-31
MetS+
52%
29%
269, 100-423
129, 21-288
0.002
4, 0-7
7, 5-7
<0.001
Sugared
Beverage
Intake (kcal/d)
Breakfast
(days/wk)
Mietus-Snyder et al. (submitted)
0.003
<0.001
<0.001
UCSF WATCH Clinic
Lifestyle Intervention
• Get rid of all sugared liquids—only 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
UCSF WATCH Clinic Lifestyle Intervention:
Median Change in BMI z-score from
Baseline
0
-.0
5
-.1
-.1
5
M
e
d
ia
n
C
ha
n
ge
in
B
M
Iz
-.2
0
Madsen et al. (submitted)
10
20
Median Ti me ( mos) fr om i ni tial visi t
30
UCSF WATCH Clinic
Predictors of Lifestyle Intervention
• Forward selection model, 4 variables
Source |
SS
df
MS
-------------+-----------------------------Model | .169200646
4 .042300161
Residual |
.81467663
125 .006517413
-------------+-----------------------------Total | .983877276
129 .007626956
Number of obs
F( 4,
125)
Prob > F
R-squared
Adj R-squared
Root MSE
=
=
=
=
=
=
130
6.49
0.0001
0.1720
0.1455
.08073
-----------------------------------------------------------------------------Delta z/yr |
Coef.
Std. Err.
t
P>|t|
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)
The “fructosification” of America
(and the world)
Can you name the seven foodstuffs at
McDonald’s that don’t have HFCS or sucrose?
1. French Fries (salt, starch, and fat)
2. Hash Browns (salt, starch, and fat)
3. Chicken McNuggets (salt, starch, and fat)
4. Sausage
5. Diet Coke
6. Coffee
7. Iced Tea
Who’s really drinking this?
The SFUSD School Milk Program
Courtesy of
M. Lustig
What about WIC?
J. Nutr. 136:1086, 2006
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
What’s the difference?
Calories
Percent CHO
Calories from
fructose
other carbs
alcohol
1st pass GI metabolism
Calories reaching liver
150
10.5% (sucrose)
75 (4.1 kcal/gm)
75 (glucose)
0%
90
150
3.6% (alcohol)
60 (maltose)
90 (7 kcal/gm)
10%
92
Fructose is a carbohydrate
Fructose is metabolized like fat
(corollary: a low fat diet isn’t really low fat,
because the fructose/sucrose doubles as fat)
Fructose is also a toxin
DESIGN, MANUFACTURING AND MARKETING OF
TOBACCO PRODUCTS: TOWARDS A SENSIBLE
REGULATORY FRAMEWORK
Bates Number: 2065346777/6799, Page 3
… Under the regulations governing food additives, it’s 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
DESIGN, MANUFACTURING AND MARKETING OF
TOBACCO PRODUCTS: TOWARDS A SENSIBLE
REGULATORY FRAMEWORK
Bates Number: 2065346777/6799, Page 3
… Although there is no existing regulatory framework permitting FDA to
restrict a consumer’s 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
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 (it’s “alcohol without the buzz”)
but FDA can’t and won’t regulate it
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.