The Sugar “Maize”:Sugar, High Fructose Corn Syrup,

Obesity and Metabolic Risk: From Genes to Policy

Professor of Preventive Medicine; Physiology & Biophysics; and Pediatrics

Director, Childhood Obesity Research CenterCo-Director, Diabetes & Obesity Research Institute

Keck School of Medicine, USC

Michael I Goran, PhD

www.GoranLab.com

Brief History of Sugar (sucrose)

• 8,000 BC - first domestication of sugar cane

• 400 BC - first written mention of sugar in Indian literature referring to use in sweet puddings and drinks

• 500 AD - evidence of sugar making in India

• 400-800 AD - major production of sugar spreads west from India across the Persian Gulf to Arab countries

• 1000 AD - sugar spread to Europe through the Arab conquest

• 1200 - medicinal use of sugar

Brief History of Sugar (sucrose)• 16th century - production centered in the Mediterranean and

Atlantic Islands

• 1650 - Major sugar consumption among English nobility and wealthy

• 1800 - sugar has become a necessity of the diet

• 1900 - sugar supplies 20% of calories in the English diet

• 1957 - development of high fructose corn syrup

• 1970 onwards - proliferation of HFCS and sugar in the diet correlated with increases in obesity

$10 BILLION IS SPENT ANNUALLY ADVERTISING FOOD AND BEVERAGES TO CHILDREN; $500

MILLION ON SUGARY BEVERAGESIOM, 2005

FTC, 2008

17 teaspoonsAmount of sugar in a 20-oz

serving

41 percentKids age 2-11 that drink at

least 1 soda per day

62 percentKids aged 12-17 who drink

at least 1 soda per day

39 poundsAmount of sugar consumed in 1 year from 1 soda per

day

venti frappuccino with whipped cream

89g sugars(17 teaspoons)

if you stacked all the sugar as cubes from 1

day of sugar consumption in the US it would tower half way to

the moon

US sugar consumption = 70kg/person/year

Legislation - Soda Tax?10/21/09 3:20 PMNEJM -- Ounces of Prevention -- The Public Policy Case for Taxes on Sugared Beverages

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Volume 360:1805-1808 April 30, 2009 Number 18 Next

Ounces of Prevention — The Public Policy Case for Taxeson Sugared Beverages

Kelly D. Brownell, Ph.D., and Thomas R. Frieden, M.D., M.P.H.

Since this article has no abstract, we have provided an extractof the first 100 words of the full text and any section headings.

Sugar, rum, and tobacco are commodities which are nowhere

necessaries of life, which are become objects of almost universal

consumption, and which are therefore extremely proper subjects oftaxation.

— Adam Smith, The Wealth of Nations, 1776

The obesity epidemic has inspired calls for public health measures to prevent

diet-related diseases. One controversial idea is now the subject of publicdebate: food taxes.

Forty states already have small taxes on sugared beverages and snack foods,

but in the past year, Maine and New York have proposed large taxes on

sugared beverages, and similar discussions have begun in other states. The. . . [Full Text of this Article]

Source Information

Dr. Brownell is a professor and director of the Rudd Center for Food Policy and Obesity, Yale University, New Haven, CT. Dr.

Frieden is the health commissioner for the City of New York.

This article (10.1056/NEJMp0902392) was published at NEJM.org on April 8, 2009.

This article has been cited by other articles:

Brownell, K. D., Farley, T., Willett, W. C., Popkin, B. M., Chaloupka, F. J., Thompson, J. W.,Ludwig, D. S. (2009). The Public Health and Economic Benefits of Taxing Sugar-SweetenedBeverages. NEJM 361: 1599-1605 [Full Text] Halpern, S. D., Madison, K. M., Volpp, K. G. (2009). Patients as Mercenaries?: The Ethics of UsingFinancial Incentives in the War on Unhealthy Behaviors. Circ Cardiovasc Qual Outcomes 2: 514-516[Full Text] Lock, K., Stuckler, D., Charlesworth, K., McKee, M. (2009). Potential causes and health effects ofrising global food prices. BMJ 339: b2403-b2403 [Full Text]

FREE NEJM E-TOC

A couple of local ballot measures in the US have failedThe beverage industry has lobbied hard against them

One study has projected that even a 20% tax on sodas would only lead to a long-term weight loss of 3 pounds

mechanisms

sugars (esp fructose)

metabolicsyndrome

insulinresistance

fattyliver dyslipidemia

inflammation

obesity

metabolic disruption

Mechanisms Linking Increased Sugar to Negative Health Outcomes: The Double Edged Sword

why has high sugar become such an important issue in terms of obesity and metabolic

outcomes?1. trends in food and beverage consumption; related to

economics2. advent and proliferation of high fructose corn syrup

3. exacerbation of effects of sugars on metabolism in the obese state

4. earlier introduction of fructose in the diet from sugar (glucose + fructose) relative to breastfeeding (lactose =

glucose+galactose)

Duffey & Popkin: Obesity, 2007

Per Capita US Trends in Calories from Beverages

advent of High Fructose Corn Syrup: different from sugar

Consumer Price Index - Sodas are a good deal

6.5 oz (1920s)

12 oz(1960s)

20 oz (1990s)

33 oz (1L) Today

10 teaspoonssugar

27 teaspoonssugar

Obesity/Economic Status in 128 LA Cities & Communities

0 20 40 60 80 100MEAN

0

10

20

30

40

50

Hermosa Beach

Manhatten Beach

Hidden Hills

MalibuPalos Verdes Estates

Sierra Madre

Redondo Beach

Calabasas

Rolling Hills Estate

Agoura Hills

LancasterLong Beach

Irwindale

Rosemead

West Compton

South San Jose Hills

South El Monte

Walnut Park

East LA

Westmont

LynwoodLA Dis 1MaywoodHuntington Park

Bell GardensLA Dis 9Florence-Graham

Economic Hardship of City

Obesity P

revale

nce (

%)

0

2,500

5,000

7,500

10,000

1 2 3 4 5 6 7 8 9 10

Insulin Resistance

Insu

lin R

espo

nse

to G

luco

se

HealthyLean

Incre

asing

obes

ity

Puberty/

Pregnancy

Hisp

anic

,A

fric

an A

mer

ican

Ethn

icity

As you become more obese and insulin resistantthe demand on beta-cells to secrete insulin in response to

glucose, rises exponentially

Welsh J A et al. Circulation 2011;123:249-257Copyright © American Heart Association

Adjusted HOMA-IR by Intake of Added Sugars in US Adolescents

Sugar and obesity: the evidence

• Ludwig et al Lancet 2001, 357:505-8– 19 month study of 548 middle school students– Every additional serving of per day increased risk of

obesity by 60%• Walsh et al. Pediatrics 2005, 115:223

– 1 year study of 10,904 children ages 2 to 3 years– Children were 2-times more likely to become or remain

overweight if they drank sugar-sweetened beverages

Sugar Sweetened Beverages and Obesity in Children:

Key Prospective Studies

James et al. British Med J 2004, 328:1237•Randomized controlled trial, 600 children 7 - 11 yr•Educational program designed to eliminate all “fizzy drinks” (including non-nutritively sweetened)•Consumption differed between groups by < 2 oz per day•Incidence of overweight/obesity significantly lower in the intervention group: 0.2 vs 7.7%

Sugar Sweetened Beverages and Obesity in Children:

Key Intervention Studies

Ebbeling, Ludwig. Pediatrics 2006, 117:673•6-month randomized controlled trial of 103 normal weight and overweight adolescents•Delivery of non-sugar sweetened beverages to participants homes (to replace regular beverages)•Sugar-sweetened beverages decreased by 82% vs no change among controls (p < 0.0001)•Among overweight/obese participants, BMI was 0.75 BMI units less in the intervention group, p = 0.03

Sugar Sweetened Beverages and Obesity in Children:

Key Intervention Studies

Ebbeling et al; NEJM 2012

• 224 overweight & obese adolescents (mean age ~15 years)

• 1-year intervention to reduce caloric-sweetened beverages followed by 1-year follow-up

• Main outcome body weight and BMI

24

0

0.4

0.8

1.2

1.6

2

Serv

ings

/day

of C

SB

Treatment ControlTreatment  period

Follow-­‐upperiod

85

86.6

88.2

89.8

91.4

93

Baseline 1 Year 2 Year

Body

wei

ght

(kg)

Small  treatment  effect  at  1-­‐year;  not  sustained  a7er  1-­‐Year  follow-­‐up

25

80

82

84

86

88

90

92

94

96

98

100

Baseline 1 Year 2 Year

Body

Wei

ght

(kg)

Hispanic Treatment Hispanic ControlNon-Hispanic Treatment Non-Hispanic Control

zero  effect  in  Non-­‐Hispanics~10kg  reduced  weight  gain  in  Hispanics  sustained  over  2  years

Treatment  period

Follow-­‐upperiod

Ebbeling  et  al,  NEJM  2012

sugar and fatty liver disease

Spectrum of NAFLD

Diet, genes, cellular factors and food policy

NAFLD in Children

• Autopsy study of 742 children aged 2-19 years by Schwimmer et al 2006

• Fatty liver defined by liver fat >5%• Overall prevalence = 13%• African American (1.5%); Whites (8.6%); Asian

(10.2%); Hispanic (11.8%)• Prevalence in obese children = 38%

Genetics of Fatty Liver

• A recent GWAS in adults from the Dallas Heart Study at UT Southwestern identified an amino-acid substitution (C to G) in the PNPLA3 gene associated with 2-fold higher liver fat

• Effect strongest in Hispanics in whom the frequency of the variant was much higher (49%) than African Americans (10%)

• Aim was to examine if the effect of this gene was manifested in a pediatric population

0

2

4

6

8

10

12

African American Hispanic

-ve for gene -/+ for gene +ve for gene

n=61 n=11 n=45 n=90 n=53

Liver Fat Fraction by Ethnicity & Genotype

n=0

Live

r Fa

t Fra

ctio

n (%

)

0

3

6

9

12

Liver Fat Fraction in 8-10 year olds

-ve gene -/+ gene +ve gene

Goran et al; Diabetes 2010

0 10 20 30 40 500

10

20

30

40 GG Genotype

Sugar Intake (% Kcal/d)

Liv

er

Fat F

raction (

%)

0 10 20 30 40 500

10

20

30

40

CG Genotype

Sugar Intake (% Kcal/d)

Liv

er

Fat F

raction (

%)

0 10 20 30 40 500

10

20

30

40 CC Genotype

Sugar Intake (% Kcal/d)

Liv

er

Fat F

raction (

%)

PNPLA3 Gene*Diet InteractionDavis et al, AJCN 2010

sugar in early life

• 1483 Latino children (2 to 4 yrs) from WIC LA County

• Completed early life nutrition measures on breastfeeding and SSB intake - 2008

• height/weight/BMI data

• Multinominal regressions – differences in prevalence of ow/ob in children between BF and SSB categories

Combined Effects of Low Breastfeeding and High Sugar Consumption

Davis et al in review at Peds

Combined Effects of Low Breastfeeding and High Sugar Consumption

Davis et al; AJCN 20012

Other Animal Studies

• Sugars and especially fructose programs for obesity and metabolic risk starting with exposure in utero and during breastfeeding

• Fructose affects fat cell and hypothalamic development in ways that favor obesity

high fructose corn syrup (HFCS)

HFCS magnifies many of the worst aspects of table sugar

(sugar on steroids)

sucrose = C12H22O11

glucose-fructose

purified from sugar cane or beets

HFCSmade from corn starch through

conversion of sugarstypically 55% fructose,

40% glucose, 5% other sugars;

can be 90% fructose

advantages in food production: cheaper, more stable, makes food

more appealing

Sucrose versus HFCS

Glucose versus Fructose

• Glucose and fructose are structurally very similar but functionally very different sugars

• Fructose is much sweeter

• has a specific absorption in the gut; in high doses can get fructose malabsorption with GI symptoms

• it is metabolized almost entirely in the liver where it can be a substrate for new fat synthesis in the liver

• does not stimulate insulin release therefore less well regulated

Fructose

Triose-­‐P

TG

Liver  FatVLDL-­‐TG

Glucose

Glucose

Insulin

NEFA

IMCL

CO2

Fructose Glucose

DNL

Insulin  resistance

Differential Effects of Fructose vs Glucose

Fructose  as  a  %  of  Sugars  in  Popular  Drinks

50

55

60

65

Pepsi

Coca-C

ola

Sprit

e

Founta

in C

oke

Dr P

epper

Founta

in p

epsi

Founta

in S

prite

AZ Ic

ed T

ea

41

Expected  proporPon  if  made  with  HFCS-­‐55

Suggests HFCS is 65:35Fructose intake ~18% higher than assumed from label

and 30% higher than soda made with sucrose

Other Sugars

• Agave - mostly all fructose

• Fructose itself being used as a sweetener now in many yoghurts

• “Fruit sugar” on a label probably means fructose

• Juices from fruit probably very high in fructose and likely to have a higher fructose load than a soda made with HFCS

Fructose versus Glucose in Foods

50g sugar25g fructose/25g glucose (sucrose)

28g fructose/22g glucose (HFCS 55)33g fructose/17g glucose (HFCS 65)

15g Fructose+

other dietary benefitsfiber, antioxidants

Implication:fructose consumption might be higher than we think and

contributing to obesity and obesity complications like NAFLD

Policy Implication:Need better label information on fructose content of

foods and bevrages

Global Influence of Dietary Sugar & HFCS on Obesity &

DiabetesGoran et al

Global Public Health, 2012

Global Implications:Data from 170 Countries

Goran et al; in preparation

Mean + SD Range

Diabetes Prevalence (%)

6.8 + 3.0 1.6 - 18.7

BMI (kg/m2) 24.9 + 2.3 20.1 - 31.1

Total Intake (kcal/day per capita)

2711 + 510 1559 - 3781

Total Sugar (kg/day per capita)

29.8 + 16.0 2.2 - 68.6

Global Influence of Sugar on Diabetes

0 20 40 60 800

5

10

15

20

Total Sugar (kg/capita per year)

Dia

bete

s P

reva

lenc

e (%

)

r = 0.55; p<0.001

0 5 10 15 20 250

5

10

15

20 r = 0.55; p<0.001

Sugar (% of total calories)

Dia

bete

s P

reva

lenc

e (%

)

Saudi Arabia

USA

Dietary Sugar is Associated with Obesity and Diabetes

Obesity(

Diabetes(Sugar(

r=0.70,(p<0.0001( r=0.58,(p<0.0001(

r=0.54,(p<0.0001((Controlling(for(obesity:(r=0.23,(p=0.003)(

German

y

Poland

Thaila

nd

Greece

Portug

al

Malays

iaEgy

ptSpa

in

Finlan

dSerb

ia

Turke

y

Mexico

Taiw

anaJa

panKore

a

Argenti

na

Belgium

Bulgari

a

Canad

a

Slovak

ia

Hunga

ryUSA

0

5

10

15

20

25

Zero or < 0.5kg per capita/year: Australia, China, Cyprus, Czech Republic, Denmark, Estonia, France, India, Indonesia, Ireland, Italy, Latvia, Lithunia, Luxemburg, Malta, Netherlands, Romania, Slovenia, Sweden, United Kingdom, Uraguy

Hig

h Fr

ucto

se C

orn

Syru

p (k

g/ca

pita

per

yea

r)

Global Pattern in HFCS Use

Countries not Using HFCS

(n=22)

Countries Using HFCS (n=21)

BMI (kg/m2) 25.5 + 1.6 25.9 + 1.4

Total Intake (kcal/day per capita)

3230 + 377 3221 + 365

Total Sugar (kg/day per capita)

38.2 + 12.8 39.9 + 11.3

HFCS (kg/day per capita) 0.1 + 0.2 5.8 + 6.1

Diabetes Prevalence (%) 6.7 + 1.3 7.9 + 1.8

Fasting Glucose (mmol/L) 5.23 + 0.17 5.33 + 0.17

Diabetes

obesitysugar high fructosecorn syrup

HFCS Exports from the US to Mexico

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 20100

200000

400000

600000

800000

1000000All US Exports US Exports to Mexico All Imports to Mexico

Year

Met

ric to

ns o

f HFC

S-55

and

abo

ve

Policy Implications:EU policy on HFCS quotas and their trading between

countries may be a factor influencing that countries public health

Trade policy between countries in sugar and HFCS may be a factor driving public health

Africa: Coke’s Last Frontier

• Per Capita consumption of coke in Kenya = 39 servings

• Mexico = 665 servings (highest in the world)

• Coke sales stagnant in developed countries (in the US: $2.6b in 1989 vs $2.9b in 1999)

• Coke plans to invest $12b in Africa in next 10 years.

Cover story in Bloomberg Businessweek, Nov 1, 2010

Global Consumption of Coke

Mexico = 665 servings

(highest in the world)

Hispanics:A “perfect storm” for Fatty Liver

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 20100

200000

400000

600000

800000

1000000All US Exports US Exports to Mexico All Imports to Mexico

Year

Met

ric to

ns o

f HFC

S-55

and

abo

ve

high prevalence of GG Genotype

in PNPLA3

PNPLA3*sugar interaction

exponential increase in

HFCS export to Mexico

high sugar consumption:

Mexico has highest consumption of coca-

cola in the world

obesity

liver diseaseliver cancer

insulin resistancetype 2 diabetes

Simple  Tips

• Avoid  products  with  high  fructose  corn  syrup• Replace  sugary  drinks  with  water  or  dilute  juice  with  water  (50:50)

• Avoid  foods  with  >10g  sugar  per  serving• Avoid  flavored  milk• Watch  for  “hidden”  sugar  which  can  be  high  in  surprising  products  (eg  yogurts,  breads)

57

Summary• Sugar is a contributing factor to obesity and related outcomes

• Double-edged sword: effects of sugar on obesity and separate effects on metabolic outcomes like diabetes

• Not all sugars are equal in their health effects - fructose is more damaging because of the way it is metabolized

• Dietary fructose is increasing because of HFCS - fructose content of foods made with HFCS is higher than we think

• The more we tip the balance towards increasing fructose, the greater the metabolic problems (diabetes, gout, hypertension)

Hooman Allayee, USC

Krishna Nayak, PhD

Jaimie DavisAsst Prof USC

Marc WeigensbergAssoc Prof, USC

Ryan WalkerPhD Student

Tanya AlderetePhD Student

Acknowledgments

Funding:

NICHD (RO1 33064)NIDDK (RO1 59211)NCI (U54 116848)

NCMHD (P60 002564)ADA

Thrasher FoundationAtkins Foundation

www.GoranLab.com