The Sugar Maize: Sugar, High Fructose Corn Syrup, Obesity And

The Sugar “Maize”: Sugar, High Fructose Corn Syrup, Obesity and Metabolic Risk: From Genes to Policy

Michael I Goran, PhD Professor of Preventive Medicine; Physiology & Biophysics; and Pediatrics Director, Childhood Obesity Research Center Co-Director, Diabetes & Obesity Research Institute Keck School of Medicine, USC

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 IOM, 2005 MILLION ON SUGARY BEVERAGES FTC, 2008 17 teaspoons Amount of sugar in a 20-oz serving

41 percent Kids age 2-11 that drink at least 1 soda per day

62 percent Kids aged 12-17 who drink at least 1 soda per day

39 pounds Amount of sugar consumed in 1 year from 1 soda per day venti frappuccino with whipped cream 89g sugars (17 teaspoons) US sugar consumption = 70kg/person/year

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

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

Ounces of Prevention — The Public Policy Case for Taxes on 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 extract A couple of localof the firstballot 100 words measuresof the full text and any insection the headings. US have failed Sugar, rum, and tobacco are commodities which are nowhere The beverage industry has lobbied hard against them necessaries of life, which are become objects of almost universal consumption, and which are therefore extremely proper subjects of taxation.

One study has— Adamprojected Smith, The Wealth that of Nations, even 1776 a 20% tax onFull Textsodas would only PDF

Thelead obesity epidemic to a has long-term inspired calls for public weight health measures lossto prevent of 3 PDApounds Full Text diet-related diseases. One controversial idea is now the subject of public debate: food taxes. Add to Personal Archive Forty states already have small taxes on sugared beverages and snack foods, Add to Citation Manager Notify a Friend but in the past year, Maine and New York have proposed large taxes on E-mail When Cited

sugared beverages, and similar discussions have begun in other states. The E-mail When Letters Appear . . . [Full Text of this Article]

PubMed Citation 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-Sweetened Beverages. NEJM 361: 1599-1605 [Full Text] Halpern, S. D., Madison, K. M., Volpp, K. G. (2009). Patients as Mercenaries?: The Ethics of Using Financial 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 of rising global food prices. BMJ 339: b2403-b2403 [Full Text]

http://content.nejm.org/cgi/content/short/360/18/1805 Page 1 of 2 mechanisms Mechanisms Linking Increased Sugar to Negative Health Outcomes: The Double Edged Sword

sugars (esp fructose) obesity

metabolic disruption

metabolic insulin fatty dyslipidemia syndrome resistance liver inﬂammation 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 economics 2. 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) Per Capita US Trends in Calories from Beverages

Duffey & Popkin: Obesity, 2007 advent of High Fructose Corn Syrup: different from sugar Consumer Price Index - Sodas are a good deal 10 teaspoons sugar

27 teaspoons sugar

6.5 oz 12 oz 20 oz 33 oz (1L) (1920s) (1960s) (1990s) Today Obesity/Economic Status in 128 LA Cities & Communities 50 )

% 40

( Walnut Park IrwindalWe est Compton e

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y 20 t i s Redondo Beach e Sierra Madre b Hidden Hills

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Economic Hardship of City 10,000

7,500 Hispanic,

Ethnicity

African American 5,000

Increasing 2,500 obesity

Insulin Insulin Response to Glucose Healthy Puberty/ Lean Pregnancy 0 1 2 3 4 5 6 7 8 9 10 Insulin Resistance As you become more obese and insulin resistant the demand on beta-cells to secrete insulin in response to glucose, rises exponentially Adjusted HOMA-IR by Intake of Added Sugars in US Adolescents

• 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 Intervention 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 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 Treatment Control 2 Treatment Follow-up 1.6 period period

1.2

0.8

0.4

Servings/day of CSB 0 93

91.4

89.8

88.2

86.6 Body weight (kg) 85 Baseline 1 Year 2 Year

Small treatment eﬀect at 1-year; not sustained aer 1-Year follow-up24 Hispanic Treatment Hispanic Control Non-Hispanic Treatment Non-Hispanic Control 100 98 Treatment Follow-up 96 period period 94 92 90 88 86 84

Body Weight (kg) 82 80 Baseline 1 Year 2 Year zero eﬀect in Non-Hispanics ~10kg reduced weight gain in Hispanics sustained over 2 years Ebbeling et al, NEJM 2012 25 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 Liver Fat Fraction by Ethnicity & Genotype

-ve for gene -/+ for gene +ve for gene 12

2 n=61 n=11 n=0 n=45 n=90 n=53 0 Liver Fat Fraction (%) African American Hispanic Liver Fat Fraction in 8-10 year olds

-ve gene -/+ gene +ve gene 12

Goran et al; Diabetes 2010 PNPLA3 Gene*Diet Interaction Davis et al, AJCN 2010

) 40 )

40 %

( CG Genotype % CC Genotype ( n n o 30 i t o 30 i c t c a r a 20 r F

20 F t t a a F

10 F r

10 r e e v i v i

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L 0 0 10 20 30 40 50 0 10 20 30 40 50 Sugar Intake (% Kcal/d) Sugar Intake (% Kcal/d)

) 40 GG Genotype % (

o 30 i t c a r 20 F

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L 0 0 10 20 30 40 50 Sugar Intake (% Kcal/d) sugar in early life Combined Effects of Low Breastfeeding and High Sugar Consumption

• 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; AJCN 20012 Davis et al in review at Peds 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 versus HFCS

HFCS made from corn starch through sucrose = C12H22O11 conversion of sugars glucose-fructose typically 55% fructose, 40% glucose, puriﬁed from sugar 5% other sugars; cane or beets can be 90% fructose

advantages in food production: cheaper, more stable, makes food more appealing 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 Differential Effects of Fructose vs Glucose

Fructose Glucose

Fructose Insulin

Glucose Triose-P DNL

TG VLDL-TG Liver Fat Glucose Insulin resistance IMCL NEFA CO2 Fructose as a % of Sugars in Popular Drinks

Expected proporon if made with HFCS-55 55

Pepsi Sprite

Coca-Cola Dr Pepper AZ Iced Tea Fountain Coke Fountain pepsiFountain Sprite Suggests HFCS is 65:35 Fructose intake ~18% higher than assumed from label

and 30% higher than soda made with sucrose 41 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

15g Fructose 50g sugar 25g fructose/25g glucose (sucrose) + 28g fructose/22g glucose (HFCS 55) other dietary beneﬁts 33g fructose/17g glucose (HFCS 65) ﬁber, 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 & Diabetes

Goran et al Global Public Health, 2012 Global Implications: Data from 170 Countries

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 2711 + 510 1559 - 3781 per capita) Total Sugar (kg/day 29.8 + 16.0 2.2 - 68.6 per capita)

Goran et al; in preparation Global Inﬂuence of Sugar on Diabetes

20 Saudi r = 0.55; p<0.001 Arabia )

% 15 (

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Total Sugar (kg/capita per year)

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% 15 (

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0 0 5 10 15 20 25 Sugar (% of total calories) Dietary Sugar is Associated with Obesity and Diabetes

Obesity(

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

Sugar( Diabetes(

r=0.54,(p<0.0001( (Controlling(for(obesity:(r=0.23,(p=0.003)( Global Pattern in HFCS Use ) r

a 25 e y

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15 p u r y S

r 10 o C

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USA EgyptSpain urkey JapanKorea Poland Greece SerbiaT Mexicoaiwana Portugal Finland T BelgiumBulgariaCanadaSlovakiaHungary Germany Thailand Malaysia Argentina 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 Countries not Countries Using HFCS Using HFCS (n=21) (n=22)

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

Total Intake (kcal/day per 3230 + 377 3221 + 365 capita) Total Sugar (kg/day per 38.2 + 12.8 39.9 + 11.3 capita)

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 high fructose sugar obesity corn syrup

Diabetes HFCS Exports from the US to Mexico

1000000 All US Exports US Exports to Mexico All Imports to Mexico e v o

b 800000 a

d n a

5 600000 - S C F H

f 400000 o

s n o t

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0 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 Year 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

Cover story in Bloomberg Businessweek, Nov 1, 2010

• 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. Global Consumption of Coke

Mexico = 665 servings

(highest in the world) Hispanics: A “perfect storm” for Fatty Liver high prevalence of obesity high sugar GG Genotype consumption: in PNPLA3 Mexico has highest consumption of coca- cola in the world

1000000 All US Exports US Exports to Mexico All Imports to Mexico e v o

b 800000 a

d n a

5 600000 - S C F H

f 400000 o

s n o t

c i r

t 200000 e M

0 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 Year

exponential increase in PNPLA3*sugar HFCS export to interaction liver disease insulin resistance liver cancer type 2 diabetes Mexico 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) Acknowledgments

Marc Weigensberg Ryan Walker Krishna Assoc Prof, USC PhD Student Nayak, PhD

Jaimie Davis Hooman Allayee, Asst Prof USC USC Tanya Alderete PhD Student Funding:

NICHD (RO1 33064) NIDDK (RO1 59211) NCI (U54 116848) NCMHD (P60 002564) ADA Thrasher Foundation Atkins Foundation www.GoranLab.com