The trouble with fructose

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The trouble with fructose The trouble with fructose Robert H. Lustig, M.D. Robert H. Lustig, M.D. Division of Endocrinology Division of Endocrinology Department of Pediatrics Department of Pediatrics University of California, San Francisco University of California, San Francisco STPHND, Madison, WI, June 8, 2008

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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. - PowerPoint PPT Presentation

Transcript of The trouble with fructose

Page 1: The trouble with fructose

The trouble with fructoseThe trouble with fructose

Robert H. Lustig, M.D.Robert H. Lustig, M.D.Division of EndocrinologyDivision of EndocrinologyDepartment of PediatricsDepartment of Pediatrics

University of California, San FranciscoUniversity of California, San Francisco

ASTPHND, Madison, WI, June 8, 2008

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Hill et al. Science 299:853, 2003

Prediction of BMI distribution in adults, 2008Prediction of BMI distribution in adults, 2008

The entire curve has shifted

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The First Law of ThermodynamicsThe First Law of Thermodynamics

CaloriesInCalories

Out

Weight Gain

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Children 2-17 yrs, CSFII (USDA) 1989-91 vs. 1994-95http://www.usda.gov/cnpp/FENR%20V11N3/fenrv11n3p44.PDF

Total Caloric IntakeTotal Caloric Intake

275 kcal in teen boys

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Fat Intake: GramsFat Intake: Grams

5 g (45 cal) in teen boys

Children 2-17 yrs, CSFII (USDA) 1989-91 vs. 1994-95

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Carbohydrate Intake: GramsCarbohydrate Intake: Grams

57 g (228 cal) in teen boys

Children 2-17 yrs, CSFII (USDA) 1989-91 vs. 1994-95

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0

10

20

30

40

50

60

1960 1970 1980 1990 2000

Obesity prevalence

Calories from fat

Year

Per

cen

tPrevalence of Obesity Compared to PercentPrevalence of Obesity Compared to Percent

Calories from Fat Among US AdultsCalories from Fat Among US Adults

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Beverage IntakeBeverage Intake

41% soft drinks

Children 2-17 yrs, CSFII (USDA) 1989-91 vs. 1994-95

35% fruit drinks

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Beverage IntakeBeverage Intake

41% soft drinks

Children 2-17 yrs, CSFII (USDA) 1989-91 vs. 1994-95

35% fruit drinks

One can of soda/day = 150 cal x 365 d/yr ÷ 3500 cal/lb = 15.6 lbs/yr!One can of soda/day = 150 cal x 365 d/yr ÷ 3500 cal/lb = 15.6 lbs/yr!

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“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

Are soft drinks the cause of obesity?Are soft drinks the cause of obesity?

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Meta-Analysis of Soft Drinks and ObesityMeta-Analysis of Soft Drinks and Obesity

88 cross-sectional and longitudinal studies regressing

soft drink consumption with —

• energy intake r = 0.16 (P < 0.001)

• body weight r = 0.08 (P < 0.001)

• milk and calcium intake r = -0.12 (P < 0.001)

• adequate nutrition 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

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Obesi

ty P

revale

nce

(%

)

James et al. BMJ 328:1237, 2004

Curtailing soft drinks limits childhood obesityCurtailing soft drinks limits childhood obesity

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High Fructose Corn Syrup

Current US annual consumption of HFCS

• 63 pounds per person

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High Fructose Corn SyrupHigh Fructose Corn Syrup

SucroseSucrose

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FructoseFructose 173173

invert sugar* 120

HFCS (42-55% fructose)HFCS (42-55% fructose) 120120

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

Relative sweetness of various carbohydratesRelative sweetness of various carbohydrates

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From the Corn Refiners AssociationFrom the Corn Refiners AssociationDecember, 2006December, 2006

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Unlikely Duo Opposes San Francisco Soft Drink Tax PlanCorn 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 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

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High Fructose Corn Syrup is 42-55% Fructose;High Fructose Corn Syrup is 42-55% Fructose;Sucrose is 50% FructoseSucrose is 50% Fructose

GlucoseGlucose FructoseFructose

SucroseSucrose

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Faith MS et al. Pediatrics 118:2066, 2006

Juice is sucrose:Juice is sucrose:Change in BMI z-score in lower socioeconomic status Change in BMI z-score in lower socioeconomic status children versus number of fruit juice servings per daychildren versus number of fruit juice servings per day

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High Fructose Corn SyrupHigh Fructose Corn Syrup

SucroseSucrose

JUICEJUICE

MOST FRUCTOSE ITEMS

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Fructose is not glucoseFructose 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, 2002Elliot et al. Am J Clin Nutr, 2002Bray et al. Am J Clin Nutr, 2004Bray et al. Am J Clin Nutr, 2004Teff et al. J Clin Endocrinol Metab, 2004Teff et al. J Clin Endocrinol Metab, 2004

Gaby, Alt Med Rev, 2005Gaby, Alt Med Rev, 2005Le and Tappy, Curr Opin Clin Nutr Metab Care, 2006Le and Tappy, Curr Opin Clin Nutr Metab Care, 2006Wei et al. J Nutr Biochem, 2006Wei et al. J Nutr Biochem, 2006

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Hepatocyte

24 kcal

96 kcal

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Ethanol is a carbohydrate

CH3-CH2-OH

But ethanol is also a toxin

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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

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60 kcal(+ 12 kcalglucose)

48 kcal

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Isganaitis and Lustig, Arterio Thromb Vasc Biol 25:2451, 2006

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Why is exercise important in obesity?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

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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

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UCSF Weight Assessment for Teen and Child Health (WATCH) Clinic

294 patients 2003-2006

• Race/Ethnicity Median Min Max Normal BMI 33.2 20.0 92.4 <25 BMI z-score 2.5 1.3 4.4 0 FBG 87 58 119 <100 Insulin 20.7 2 117.5 5-20 HOMA-IR 4.3 0.34 28.1 <4 Maternal BMI 28.9 17.7 58.6 <25 Paternal BMI 28.9 16.7 48.8 <25

• Biochemistry

Mietus-Snyder et al. (submitted)

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UCSF WATCH ClinicUCSF WATCH ClinicAssociations with the Metabolic SyndromeAssociations with the Metabolic Syndrome

Baseline Characteristic (mean ± SD)

HOMA-IR >5* N=124

HOMA-IR<5 N=147

P-value**

BMI 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 (mU/dl)

102, 69-138 83, 57-110 0.005

HDL-c (mU/dl)

41 ± 10 43 ± 10 0.04

Fasting Glc (mg/dl)

92 + 9

85 + 9

<0.001

Fasting Insulin (mU/ml)

33.7,28.6-47.1

15.2,11.2-19.8

<0.001

Creatinine (mg/dl)

0.64 + 0.14

0.58 + 0.15

0.003

ALT (U/L) 35, 23-50 23, 18-31 <0.001

MetS+ 52% 29% <0.001

Sugared Beverage Intake (kcal/d)

269, 100-423

129, 21-288

0.002

Breakfast (days/wk)

4, 0-7 7, 5-7 <0.001

Mietus-Snyder et al. (submitted)

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UCSF WATCH ClinicUCSF WATCH ClinicLifestyle InterventionLifestyle 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

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UCSF WATCH Clinic Lifestyle Intervention:UCSF WATCH Clinic Lifestyle Intervention:Median Change in BMI z-score from BaselineMedian Change in BMI z-score from Baseline

0 10 20 30Median Time (mos) from initial visit

Madsen et al. (submitted)

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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 > 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 P>|t| Beta-------------+---------------------------------------------------------------- sugared bev| .012786 .0048643 2.63 0.010 .2268616 HOMA| .0034239 .0018131 1.89 0.061 .1707474Baseline BMIZ| .0311507 .0199972 1.56 0.122 .1430862Baseline Age | .0027542 .0022543 1.22 0.224 .1055135 _cons | -.1475346 .0573037 -2.57 0.011 .------------------------------------------------------------------------------

Madsen et al. (submitted)

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The “fructosification” of AmericaThe “fructosification” of America

(and the world)(and the world)

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Can you name the seven foodstuffs atCan you name the seven foodstuffs at

McDonald’s that don’t have HFCS or sucrose?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

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Who’s really drinking this?Who’s really drinking this?

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The SFUSD School Milk Program

Courtesy ofM. Lustig

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J. Nutr. 136:1086, 2006

What about WIC?What about WIC?

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Could this be the reason for obesity with Could this be the reason for obesity with formula feeding?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

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Calories 150 150Percent 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

What’s the difference?What’s the difference?

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Fructose is a carbohydrate

Fructose is metabolized like fat

Fructose is also a toxin

(corollary: a low fat diet isn’t really low fat, because the fructose/sucrose doubles as fat)

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DESIGN, MANUFACTURING AND MARKETING OF DESIGN, MANUFACTURING AND MARKETING OF TOBACCO PRODUCTS: TOWARDS A SENSIBLE TOBACCO PRODUCTS: TOWARDS A SENSIBLE

REGULATORY FRAMEWORKREGULATORY FRAMEWORKBates Number: 2065346777/6799, Page 3Bates 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.

Philip Morris (Altria) Company: From the UCSF Legacy Tobacco Documents Library

HFCS has FDA GRAS status (Generally Regarded as Safe)

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… 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.

DESIGN, MANUFACTURING AND MARKETING OF DESIGN, MANUFACTURING AND MARKETING OF TOBACCO PRODUCTS: TOWARDS A SENSIBLE TOBACCO PRODUCTS: TOWARDS A SENSIBLE

REGULATORY FRAMEWORKREGULATORY FRAMEWORKBates Number: 2065346777/6799, Page 3Bates Number: 2065346777/6799, Page 3

Philip Morris (Altria) Company: From the UCSF Legacy Tobacco Documents Library

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SummarySummary• 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:

hypertensionde novo lipogenesis, dyslipidemia, and hepatic steatosisinflammationhepatic insulin resistance obesityCNS 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

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UCSF Dept. of PediatricsChaluntorn 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 BiostatisticsAnn Lazar, Ph.D.Peter Bacchetti, Ph.D.Saunak Sen, Ph.D.

UC Berkeley Dept. of Nutritional SciencesJean-Marc Schwarz, Ph.D.Sharon Fleming, Ph.D.Lorene Ritchie, Ph.D.

CollaboratorsCollaborators