The sugar pandemic: policy vs. politics • no disclosures · Addiction medicine-Toxic substances that are abused • morphine • heroin • amphetamine • cocaine • ethanol •

The sugar pandemic:policy vs. politics

UCSF Sleep Apnea Symposium, Feb. 15, 2014

Robert H. Lustig, M.D., M.S.L.

Professor, Pediatric EndocrinologyMember, Institute for Health Policy Studies

University of California, San Francisco

President, Institute for Responsible Nutrition

• no disclosures

U.N. General AssemblySept 20, 2011

• Non-communicable disease is now a bigger problemthan acute infectious diseases worldwide

• Plan to target, tobacco, alcohol, and diet

• But exactly what about diet?Total calories?Fat?Red meat?Dairy?Carbohydrate?

U.N. General AssemblySept 20, 2011

• Non-communicable disease is now a bigger problemthan acute infectious diseases worldwide

• Plan to target, tobacco, alcohol, and diet

• But exactly what about diet?Total calories?Fat?Red meat?Dairy?Carbohydrate?

Addictive and hazardous to your health Addictive and hazardous to your health

New York Times,April 17, 2011

Nature 487:27-29, Feb 1, 2012

Criteria for societal intervention for substance control

• Unavoidability

• Toxicity

• Abuse

• Externalities-negative impact on society

Babor T, Caetano R, Casswell S, et al. Alcohol: no ordinary commodity - research and public policy. Oxford: Oxford University Press; 2003.

Unavoidability

The Fiction“Beating obesity will take action by all of us, based onone simple common sense fact: All calories count, nomatter where they come from, including Coca-Cola andeverything else with calories…”

-The Coca Cola Company, “Coming Together”, 2013

• Some Calories Cause Disease More than Others

• Different Calories are Metabolized Differently

• A Calorie is Not A Calorie

The Science High Fructose Corn Syrup

Current US annual consumption:

• 63 pounds per person

Current users:U.S.CanadaJapanParts of Europe (limited use)

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

Glucose Fructose

Sucrose

150150

125

100

75

50

25

0

Grams per day

U.S. Commerce Service 1822-1910, combined with Economic Research Service, USDA 1910-2010

150150

125

100

75

50

25

0

Grams per day


Growth ofSugar Industry

StabilizationHFCS +Sugar for Fat

WWII

150150

125

100

75

50

25

0

Grams per day



StabilizationHFCS +Sugar for Fat

WWII

Theoreticalthreshold based on EtOH

AHA threshold for CVD

150150

125

100

75

50

25

0

Grams per day



Stabilization

WWII

Emergence of CVD as health issue 1931

HFCS +Sugar for Fat



150150

125

100

75

50

25

0

Grams per day



Stabilization

WWII

Emergence of CVD as health issue 1931

HFCS +Sugar for Fat

Emergence of Adolescent T2DM as health issue 1988



Worldwide per capita sugar supply, 2007

FAOStat, 2007

Toxicity

Obesity is not the problem

People don’t die of obesity

Obesity is not the problem

People don’t die of obesity

Metabolic syndrome is the problem

In particular, diabetes:

because that’s where the money goes

“Exclusive” view of obesity and metabolic dysfunction

Obese (30%)

Normal weight (70%)240 million adults in U.S.

72 million168 million

Obese (30%)

Obese and sick(80% of 30%)



Total: 57 million sick

“Exclusive” view of obesity and metabolic dysfunction

Obese (30%)



“Inclusive” view of obesity and metabolic dysfunction

Obese (30%)


Normal weight,Metabolic dysfunction

(40% of 70%)

Obese and sick(80% of 30%)

57 million 67 million Total: 124 million sick


“Inclusive” view of obesity and metabolic dysfunction

Basu et al. PLoS One, 8:e57873, 2013

Imperfect correlation between obesity and diabetes worldwide

Obesity is rising at 1%/year, but diabetes at 4%/year Prevalence of diabetes, 2010

Toxicity :

The degree to which a substance can damage an organ ism

• Does not distinguish acute vs. chronic toxicity

Caveats:

• Exclusive of calories

• Exclusive of obesity

• Human data only

• In doses routinely consumed

Romaguera-Bosch et al. Diabetologia 56:1520, 2013

SSB’s and BMI-adjusted risk of diabetes in EPIC-Interact (Europe)

An international econometric analysis of diet and diabetes

Food and Agriculture Organization (FAO); FAOSTATFood Supply data in kcal/capita/day calculation: Food Supply= ∑Supply Elements - ∑Utilization Elements =

(Production + Import Quantity + Stock Variation – Export Quantity) - (Feed + Seed + Processing + Waste).

Only industrial waste factored in.

Extracted Food Supply data for 2000 and 2007:Total Calories Roots & Tubers, Pulses, Nuts, Vegetables Fruits-Excluding Wine MeatOils CerealsSugar, Sugarcrops & Sweeteners

International Diabetes Federation (IDF)2000 (1st ed) and 2010 (3rd ed)

The World Bank World Development Indicators Databas eGDP expressed in purchasing power parity in 2005 US dollars for

comparability among countries Basu et al. PLoS One, e57873, 2013

Total 175 countries; complete data for 154 countrie s (21 not different)


Basu et al. PLoS One, e57873, 2013


Data monitoring and quality

Generalized estimating equations

Conservative fixed effects approach (Hausman test)

Hazard model to control for selection bias (Heckman selection model)

Longitudinal data to determine what preceded diabetes (Granger causality)

Period effects controlled for secular trends that may have occurred as a

result of changes diabetes detection capacity or importation policies.




Data monitoring and quality

Generalized estimating equations

Conservative fixed effects approach (Hausman test)

Hazard model to control for selection bias (Heckman selection model)

Longitudinal data to determine what preceded diabetes (Granger causality)

Period effects controlled for secular trends that may have occurred as a

result of changes diabetes detection capacity or importation policies.

Controlled for:

GDP per capita % population living in urban areas

Obesity % of population over age 65

physical inactivity




Diabetes prevalence rose from 5.5% to 7.0% for 175 countries 2000-2010



Diabetes prevalence rose from 5.5% to 7.0% for 175 countries 2000-2010

Sugar

Sugar+controls

Sugar+controls+period

Overall

Model # countries Effect (95% CI)





Only changes in sugar availability predicted change s in diabetes prevalence

Every extra 150 calories increased diabetes prevale nce by 0.1%

But if those 150 calories were a can of soda, diabe tes prevalence increased 11-fold, by 1.1% (95% CI 0.03 — 1.71%, p < 0.001)

This study meets the Bradford Hill criteria for Causal Medical Inference:

—dose —duration —directionality —precedence

We estimate that 25% of diabetes worldwide is expla ined by sugar


Figure 1. Adjusted Hazard Ratio of the Usual Percent of Calories from Added Sugar for CVD Mortality Among US Adults Aged >20 Years – NHANES Linked Mortalit y Files, 1988-2006

Histogram is the distribution of usual percent of calories from added sugar in population. Lines show the adjusted HRs from Cox models. Mid-value of quintile 1 (7.5%) was the reference standard. Model was adjusted for age, sex, race/ethnicity, educational attainment, smoking status, alcohol consumption, physical activity level, family history of CVD, antihypertensive medication use, health eating index score, body mass index, systolic blood pressure, total serum cholesterol and total calories. Solid line indicates point estimates ; dashed lines indicate 95% CIs. CVD indicates cardiovascular disease; HR, hazard ratio; NHANES, National Health and Nutrition Examination Survey.

Yang et al. JAMA Int. Med epub Feb 3, 2014

Hazard ratio for CV disease based on percent calories as sugarfor US adult population, 1988-2006 Foodstuffs and metabolic syndrome

• Transfats• Branched chain amino acids• Ethanol• Fructose

• Liver is the only site for energy metabolism• Not insulin regulated• No glycogen pop-off• Mitochondria are overwhelmed

A calorie is not a calorie

Abuse

Obesity and reward

Volkow et al. Philos Trans R Soc Lond B Biol Sci. 2008 363:3191, 2008

Dopamine binding correlates with glucose metabolism both in drug addiction and obesity

CTL Cocaine

D2receptors

CTL Obesity

Cocaine

Metamphet-amine

Cingulate

OFC

Is there really such a thing as sugar addiction?

Need to look for similarities to drugs of dependence

• nicotine• morphine

• amphetamine• cocaine• ethanol

Criteria for addiction

Cross-sensitizationIncreased

ConsumptionEnhanced locomotion

BINGEING

WITHDRAWAL

Tolerance

CRAVING

Negative emotion

Anticipation

Avena et al. Neurosci Biobehav Rev 32:20, 2008 (Courtesy Dr. B. Hoebel)

How about humans? The DSM-V criteria for addiction

2 of the 11 following criteria within a 12-month pe riod:

1.Tolerance2.Withdrawal3.Craving or a strong desire to use4.Use resulting in a failure to fulfill major role obligations (work, school, home); 5.Recurrent use in physically hazardous situations (e.g. driving); 6.Use despite social or interpersonal problems caused or exacerbated by use; 7.Taking the substance in larger amounts or over a longer period than intended; 8.Attempt to quit or cut down; 9.Time spent seeking or recovering from use; 10.Interference with life activities; 11.Use despite negative consequences.

Physiologic

Psychologic

Externalities-

Negative impact on society

Societal intervention requires ““““externalities ””””


If you smoke, drink, or take drugs, it ’’’’s bad for me• second hand smoke• car accidents• declining housing prices• altered work productivity and absenteeism



How does your obesity affect me?• $274 million extra for jet fuel (?)• discomfort on the subway (?)• sinking of boats due to the weight (?)



How does your obesity affect me?• $274 million extra for jet fuel (?)• discomfort on the subway (?)• sinking of boats due to the weight (?)• $65B reduction in work productivity • 50% increase in absenteeism• 50% increase in health insurance premiums• $150B waste of health care resources• Obesity is a ““““threat to national security ””””

• The Government pays ““““twice ””””

Toxic substances that are not abused

• Iron• Vitamin D• Pseudoephedrine (not turned into meth)

Toxic substances that are not abused

• Iron• Vitamin D• Pseudoephedrine (not turned into meth)

Abused substances that are not toxic

• caffeine• nicotine (but the tars in the cigarettes are)

A vicious cycle: Addiction medicine-

Toxic substances that are abused

• morphine• heroin• amphetamine• cocaine• ethanol• sugar

Recognition at the American Heart Association

Circulation 120:1011, 2009

Recommends reduction in sugar intake from 22 tsp/da y to 9 tsp/day (males) and 6 tsp/day (females)

Response of the sugar industry

Response of the sugar industry1. Fructose for glucose exchange studies show no sig. difference

B. Hypercaloric trialsFavors fructose Favors any CHO

0%0.01 (-0.42, 0.44)212IHCLNon-alcoholic fatty liver (NAFL)

0.04 (-0.43, 0.50)

-0.39 (-0.93, 0.16)-0.68 (-1.23, -0.14)-0.64 (-1.19, -0.10)

-0.33 (-0.63, -0.02)0.06 (-0.29, 0.45)-0.27 (-0.67, 0.14)

-0.27 (-0.49, -0.04)-0.46 (-0.95, 0.03)-0.16 (-0.90, 0.58)

0%

31%47%*97%*

0%0%0%

66%*63%*13%

390

352

352352

121598458

172176

57

sBP

dBPMAP

GBPFBGFBI

GBPFBGFBI

18

13

1313

62824

1316

7

Uric acid

Blood pressure 4

Glycemic control in non-diabetes

Glycemic control in diabetes

0%0.01 (-0.42, 0.44)212IHCLNon-alcoholic fatty liver (NAFL)

0.04 (-0.43, 0.50)

-0.39 (-0.93, 0.16)-0.68 (-1.23, -0.14)-0.64 (-1.19, -0.10)

-0.33 (-0.63, -0.02)0.06 (-0.29, 0.45)-0.27 (-0.67, 0.14)

-0.27 (-0.49, -0.04)-0.46 (-0.95, 0.03)-0.16 (-0.90, 0.58)

0%

31%47%*97%*

0%0%0%

66%*63%*13%

390

352

352352

121598458

172176

57

sBP

dBPMAP

GBPFBGFBI

GBPFBGFBI

18

13

1313

62824

1316

7

Uric acid

Blood pressure 4

Glycemic control in non-diabetes

Glycemic control in diabetes

-4 -3 -2 -1 0 1 2 3 4

1.07 (0.27, 1.87)1.41 (0.43, 2.39)

-0.40 (-1.79, 0.98)0.57 (-0.82, 1.96)

1.24 (0.61, 1.85)

Standardized Mean Differences (SMD) with 95% CI

96%*84%*96%*0%

30%

I2

127

59

2828

119

N

TG

TC

LDL-CHDL-C

6

4

22

10

No. trials

Body weight 2

Cardiometabolic endpoint

Lipids in non-diabetes 1.07 (0.27, 1.87)1.41 (0.43, 2.39)

-0.40 (-1.79, 0.98)0.57 (-0.82, 1.96)

1.24 (0.61, 1.85)

Standardized Mean Differences (SMD) with 95% CI

96%*84%*96%*0%

30%

I2

127

59

2828

119

N

TG

TC

LDL-CHDL-C

6

4

22

10

No. trials

Body weight 2

Cardiometabolic endpoint

Lipids in non-diabetesDolan et al. 2010;Sievenpiper et al.Ann Int Med 2012


2. Fructose doesn’t raise the blood sugar, has low glycemic index• It’s all taken up by the liver, causes insulin resistance• A fructose receptor has been identified on beta-cells

(Kyriasis et al. Proc Natl Acad Sci 109:E524, 2012)

Rizkalla, Livesey


2. Fructose doesn’t raise the blood sugar, has low glycemic index• It’s all taken up by the liver, causes insulin resistance• A fructose receptor has been identified on beta-cells

(Kyriasis et al. Proc Natl Acad Sci 109:E524, 2012)

3. A little fructose has been shown to improve insulin secretion

• Like alcohol, it’s dose-dependent (50 gm/day threshold)

Rizkalla, Livesey

Response of the sugar industry4. Information on total sugars is available on the food label for each consumer to make his or her own choice

• NLEA of 1990 lists total sugars (glucose, galactose, fructose)• no information of “added” sugars, which is the problem• food industry petitioned FDA; information on added ingredients was “proprietary”

• 56 names for sugar – that’s on purpose

Wilkening, Popkin

Fat Chance

Response of the sugar industry4. Information on total sugars is available on the food label for each consumer to make his or her own choice

• NLEA of 1990 lists total sugars (glucose, galactose, fructose)• no information of “added” sugars, which is the problem

• food industry petitioned FDA; information on added ingredients was “proprietary”

• 56 names for sugar – that’s on purpose

5. We were wrong about fat; what makes you think you’re right now? WE NEED MORE RESEARCH

• Pessimistic meta-induction theory• Moving the goalposts

• What level of proof do we need? Scientific or Causal Inference?

Wilkening, Popkin


6. Regulation is tantamount to the “Nanny State” • We’re already told what to eat, with lack of access and choice• Of the 600,000 items in the American supermarket,

80% have added sugar

Wilkening, Popkin

And how do they stay that way?Co-opting dieticians

October 17, 2009American Academy of Pediatrics (Washington, DC)

Welcome Reception Sponsored by

And how do they stay that way?Co-opting medical professionals

And how do they stay that way?Co-opting politicians

Washington Post, Dec. 9, 2013

Philpott, Mother Jones 2012 (from Bureau of Labor Statistics)

How our food dollars have been reallocated Who’s wealthy?• Despite the economic downturn of 2008,McDonald ’’’’s revenues and stock price continues to rise; and Coke and Pepsi still fared better than the S&P 500

Pepsi

McDCoke

S&P 500

Stock prices of various food companies comparedto the S&P500 2007-2013

Who’’’’s winning the war?

Archer Daniels Midland Proctor & Gamble

Kraft

Monsanto

General Mills

ConAgra

Hormel

S&P500

Kraft

Old medicine: infections microbes

New medicine: chronic multinationaldisease corporations

Lancet 381:670, 2013

Personal responsibility vs. public health

• Syphilis• Cholera• Lead poisoning

• TB• Food-borne illnesses• Vitamin deficiencies• AIDS• Pollution• Guns?

Personal responsibility vs. public health

• Syphilis• Cholera• Lead poisoning

• TB• Food-borne illnesses• Vitamin deficiencies• AIDS• Pollution• Guns?• Sugar?

The ““““Let’’’’s Move ”””” Campaign

Focus on the IndividualFocus on the Family

Focus on the CommunityBut leaves government and the food industry out

Anita Dunn (founder of Let’s Move) —now lobbying for the food industry

Question 1:

Can our ““““toxic food environment ”””” be changed

without government/societal intervention?

Especially when there are potentially addictive

substances involved?

Question 2:

Can we afford to wait to enact public health measur es

when health care will be bankrupt due to

chronic metabolic disease?

We believe higher taxation on “sugary” food and drinks would be the best option to reduce sugar intake and help fund the fast-growing healthcare costs associated with diabetes type II and obesity.

We have started a non-profit to provide

medical, nutritional and legal analysis and consult ation

to promote personal and public health vs. Big Food

INSTITUTE FOR RESPONSIBLE NUTRITION

www.responsiblefoods.orgPlease let me know if you would like more informati on!

[email protected]

UCSF Andrea Garber, Ph.D., R.D.Patrika Tsai, M.D., M.P.H.Emily Perito, M.D.Jung Sub Lim, M.D., Ph.D.

Touro University Dept. of BiochemistryJean-Marc Schwarz, Ph.D.Alejandro Gugliucci, Ph.D.

SFGH Depts. of Medicine & RadiologySusan Noworolski, Ph.D.Kathleen Mulligan, Ph.D.

Stanford Prevention InstituteSanjay Basu, M.D., Ph.D.

Collaborators

UCSF Clinical/TranslationalScience Institute

Laura Schmidt, Ph.D.Claire Brindis, Dr.P.H.Cristin Kearns, D.D.S.Stanton Glantz, M.D.

UC HastingsDavid Faigman, J.D.Marsha Cohen, J.D.John Diamond, J.D.Patricia Davidson, J.D.

UC Berkeley Dept. of Nutr. SciencesPat Crawford, R.D., Ph.D.Kristine Madsen, M.D., M.P.H.Lorrene Ritchie, Ph.D.Paula Yoffe, B.A.

Documents

The sugar pandemic: policy vs. politics • no disclosures · Addiction medicine-Toxic substances that are abused • morphine • heroin • amphetamine • cocaine • ethanol •