Dariush Mozaffarian, MD DrPHDean

Jean Mayer Professor in Nutrition and Medicine

Controversiesand Advancesin the Treatment of CVD

LosAngeles, CA

Nov 17, 2016

RethinkingDietary Fats

• Research support: National Institutes of Health, GatesFoundation

• Ad hoc honoraria/consulting: Boston Heart Diagnostics,Haas Avocado Board, Astra Zeneca, GOED, DSM, LifeSciences Research Organization

• Royalties: UpToDatechapterson fish oil, dietary fats

Disclosures

Caus es of US Deaths in 2010

USBurden of DiseaseCollaborators, JAMA2013

Explos ion of In te res t: Pas s ion & Confus ion

Source: Google images

Diet & the Heart: Conventional Wisdom

Total Fat,

Saturated Fat

Serum Total and

LDLCholesterol

Coronary Heart

Disease

Ecologicstudies(acrossnationsor populations)

Short-term studiesof single surrogate

outcomes

Explos ion of Nutrition Sc ience

Source: Pubmed/Medline(through Aug2016)

Num

ber

of

Scie

nti

fic

Public

atio

ns

- 8.2 %Etotal fat

- 2.9 %Esaturated fat

+ 4.4 %Etotal fat

(no changein sat. fat)

Diet & Health: Modern Science

Mozaffarian D, Circulation 2016

Mozaffarian & Wu, JACC2011

Dietary Fats: Highly Bioactive

Meta-analysis of 60 randomized feeding trials. Mensink & Katan, AJCN 2003

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LDietary Fats & Blood Lipids

PUFA

MUFA

SFA

PUFA

MUFA

SFA

PUFA

MUFA

SFA

PUFA

MUFA

SFA

No ApoB

? ApoCIII

Saturated Fat & CHD Events

Siri-Tarino et al, AJCN 2010

No Sign ifican t As s oc ia tion

16 pros pec tivecohort s tud ies from

around the world

RR comparing extremecategories (h ighes t vs . lowes t)

of s a tu ra ted fa t in take

NOTE: Weights a re from random effects analys is

Ove rall

Finnish - Women

MRC soy

STARS

DART

Finnish - Men

label

Oslo Diet-Heart

Minnesota CS

LA Veterans

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252

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846

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n6

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20.4

8.0

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12.9

Rx

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14.7

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n6

0.81 (0.70, 0.95)

0.64 (0.41, 1.00)

0.86 (0.61, 1.22)

0.41 (0.09, 1.96)

0.91 (0.73, 1.14)

0.55 (0.34, 0.88)

RR (95% CI)

0.75 (0.57, 0.99)

1.08 (0.84, 1.37)

0.74 (0.53, 1.03)

100.00

8.69

12.48

0.94

20.60

8.19

We ight

16.87

18.79

13.44

%

0.81 (0.70, 0.95)

0.64 (0.41, 1.00)

0.86 (0.61, 1.22)

0.41 (0.09, 1.96)

0.91 (0.73, 1.14)

0.55 (0.34, 0.88)

RR (95% CI)

0.75 (0.57, 0.99)

1.08 (0.84, 1.37)

0.74 (0.53, 1.03)

100.00

8.69

12.48

0.94

20.60

8.19

We ight

16.87

18.79

13.44

%

1.33 .5 1 2 3

0.81 (0.70, 0.95)Overall Pooled Effec t

RR (95% CI) % WeightClin ica l Tria l Events n Control Rx

PUFA(% energy) 8 randomized trials, 13,614

participants, 1,042 CHD events

Polyunsaturated Fat & CHD Events: RCTs

Mozaffarian et al,PLoSMed 2010

Rela tive Ris k of CHD

Mozaffarian et al., PLoS Med 2010

SFA and CHD: Different Nutr ient Replacements

Carbohydra te Replac ing Satura ted Fat

0.90 (0.83, 0.97)

RR (95% CI)

0.7 1.0 1.5

Rela tive Ris k of CHD for Each 5% Energy Intake

Women's Hea lth Initia tive RCT 0.98 (0.88, 1.09)

Polyuns atura ted Fat Replac ing Satura ted Fat

Meta -Ana lys is of 8 RCTs

Monouns atura ted Fat Replac ing Satura ted Fat

0.91 (0.87, 0.95)Predicted Effe ct from TC:HDL-C Change

0.87 (0.77, 0.97)Pooled Analys is of 11 Obse rva tiona l Cohorts

Predicted Effe ct from TC:HDL-C Change 1.01 (0.98, 1.04)

Pooled Ana lys is of 11 Observa tiona l Cohorts 1.07 (1.01, 1.14)

RCTs – None --

Predicted Effect from TC:HDL-C Change 0.93 (0.89, 0.96)

Pooled Ana lys is of 11 Observa tiona l Cohorts 1.19 (1.00, 1.42)

Dieta ry Change (each 5% energy)

Average Sources of Calor ies in the US Diet

Sat fa t

Mono fa t

Poly fa t

Trans fa tPro te in

Other carbs

Pota toes

Whole grain

Refined grain

Added s ugar

Sources of Saturated Fat in the U.S.

Based on NHANES2005-06. From USDADietary Guidelines 2010

Meats & CVD Mortality

Total RedMeat (100 g/d)

RR = 1.09(1.00, 1.18)

ProcessedMeat (100 g/d)

RR = 1.69(1.37, 2.10)

Rohrmann et al., BMC Medicine 2013

Among 448,568 Europeanmen and women (EPIC),

including 5,556 CVD deaths

Dairy & CVD

RR = 0.88(0.81, 0.96)

Qin et al., Asia Pac Clin Nutr 2015Cheese & CHD: RR 0.91 (0.84, 0.99)

Cheese & Stroke: RR 0.84 (0.71, 1.00)

0.7

0.8

0.9

1

1.1

1.2

Milk Yogurt Cheese

P-trend=0.50

Quintile s of Cons umption

Sluijis et al., AJCN 2012

340,234 Europeans , 8 countries , 12,403 cas es

P-trend=0.06 P-trend=0.01RR of

Diabe tes

Probiotics, Fermentation ?

Dairy and Diabetes: Complex Influences

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

Q1 Q2 Q3 Q4 Q5

RR of

Inciden t

Diabetes

Quintilesof Phospholipid Trans-16:1n-7 (palmitoleic acid)

Mozaffarian et al., AnnalsIntern Med 2010

P trend < 0.001

Among 3,736 older US adults .

Dairy Fat & Diabetes

Rosqvist et al., AJCN2016

Milk Fat Globule Membrane

Chf

basm

Milk Fat Globule Membrane

Rosqvist et al., AJCN2016

Preventing Chronic Diseases: Food Patterns

Mozaffarian D,Circulation 2016

Dietary Pr ior ities: Healthy Food Patterns

Benefit

Harm

Eggs, Poultry, Milk

Butter

*Especiallyextra-virgin olive oil,oybean oil, canola oil

Calor ies, Fat, Single Nutr ients: Misleading

- 8.2 %Etotal fat

- 2.9 %Esaturated fat

+ 4.4 %Etotal fat

(no changein sat. fat)

twitter: @DMozaffarian www.nutritionletter.tufts.edu

Barr iers and Oppor tunities for Healthy Eating

Afshin A et al, The Handbook for Global Health Policy, 2014

Lessons From Past Public Health Successes

USCenters for Disease Control and Prevention, MMWRMorb Mortal Wkly Rep, 1999

Lessons From Past Public Health Successes

•Driver:– Education.– Licensing.– Limitson phone use, texting.

•Car:– Active: seat belts, child seats,

motorcycle helmets.– Passive: padded interiors,

collapsible steeringcolumns,shatterproof glass, air bags.

– Crash safety standards.– Safety inspections.

Road:– Road engineering, guard rails,

rumble strips.– Speed limits.– Stop signs, stop lights, caution

signs.

•Culture:– Designated driver campaign.– Drunk-drivinglegislation.– Private advocacy, e.g. MADD.

Mozaffarian D, Circulation 2016

J ohn Snow, London Cholera Epidemic , 1854

Snow, J. On the Mode of Communication of Cholera , C.F. Cheffins, London 1855

WHI Tria l: Hormone Replacement Therapy

Disease WHI Trial RR Observational RR

Heart disease 1.29 (1.02-1.63)

age<60: 0.59 (0.38-0.90) *

0.61 (0.45-0.82)

Stroke 1.41 (1.07-1.85) 1.45 (1.10-1.92)

Pulm. embolism/DVT 2.13 (1.39-3.25) 2.10 (1.20-3.80)

Breast cancer 1.26 (1.00-1.59) 1.15 (<5 yrs)

1.53 (5+ yrs)

Colorectal cancer 0.63 (0.43-0.92) 0.66 (0.59-0.74)

Hip fracture 0.66 (0.45-0.98) 0.75 (0.68-0.84)

*LaCroix et al., JAMA2011

• 15 reviews, totaling1,583meta-analysesof 228 medicalconditions

• Direct comparison of effectsseen in RCTsvs.observational studies:

–RCTsvs. all observational studies: ratio of RRs=1.08(0.96, 1.22)

–RCTsvs. prospective cohorts: ratio of RRs=1.04(0.89, 1.21)

Cochrane: Observational Studies vs. RCTs

Anglemyer A et al., 2014, The Cochrane Library

Micha & Mozaffarian, Lipids 2010

Saturated Fat and Incident Diabetes

Imamura et al., Plos Med 2016

Dietary Fat and Metabolic Health: RCTs

Dairy Fat and Diabetes: Benefits?

Mozaffarian D, EHJ2015

Butte r & CVD

Pimpin et al., Plos One 2016

Any CVD

CHD

Stroke

Total CVD

Rosqvist et al., AJCN2016

Milk Fat Globule Membrane: Genetic Effects

Benefit

Harm

Differenteffects ofanimal vs.vegetablesources ?

Differenteffects ofvarious

fatty acids ?

Likely - needsmore study

Differenteffects ofvarious

fatty acids ?

Why Our Infatuation with Single Nutr ients?

• In 1753, James Lind tes ted whether ea ting citrus fruits prevented scurvy.

• In 1932, Vitamin C isola ted, confirmed as the active protective nutrient.

One nu trien t → one dis eas e!

• Soon: Thiamine (beriberi), niacin (pe llagra ), iron (anemia),

iodine (goite r), vitamin A (night blindness ), vitamin D (ricke ts ).

• Early 20th century die ta ry guide lines thus focused on preventing nutrien t defic iency

dis eas es . Grea t Depres s ion and World War II food shortages → further emphas is .

• League of Nations , British Medica l Associa tion, and US DA formed panels to create

new minimum requirements for ca lories , prote in, ca lcium, phosphorus , iron, various

vitamins → Nationa l Nutrition Conference for Defens e , Firs t RDAs in 1941.

• Modern die ta ry guide lines were deve loped to meet these new RDAs . Se t precedent

to s ta rt with nu trien t ta rge ts and then trans la te these into food recommendations .

Mozaffarian D, Lancet Diabetes 2016

Nutr ient Focus: Recipe for Confusion

www.nhlbi.nih.gov/health/public/heart/obes ity/wecan/downloads /go-s low-whoa .pdf

What is Driving Policy and Public Choices ?

• Clean labels

• Gluten-free

• Organic

• Local

• Paleo

• Low-carb

• Vegetarian, vegan

• Total fat

• Saturated fat

• Added sugar

• Total calories

Evidence-Based Policy Strategies for Diet

AHAScientific Statement: Population Approaches to Improve Diet, Physical Activity, and Smoking Habits.Mozaffarian et al., Circulation 2012

Media andEducation

Sustained, focused media campaigns, especially aspart of multi-component strategies, focused on specific foodsor drinks.

Labeling andInformation

Mandated nutrition facts, front-of-pack labels, or menu labeling toinfluence industry behavior.

SchoolsMulticomponent nutrition programsincludingclasses, teacher training,supportive policies, environmental changes, and family components.

School garden programs.

WorkplacesComprehensive worksite wellnessprogramsfor diet and lifestyle.

Increased availability of healthier optionsand/or strongnutritionstandards, combined with on-site prompts, labels, or icons.

EconomicIncentives

Subsidy strategiesto lower pricesof more healthful foods.

Tax strategiesto increase pricesof lesshealthful foods.

QualityStandards

Restrictionson marketingof lesshealthy foodsto childrens.

Restrictions(e.g., salt, transfat) or mandates(e.g., vegetable oils).

AgriculturalPolicies

Long-term changesin agricultural policies for infrastructure to facilitateproduction, transportation, and marketingof healthier foods.

The Real Cost of Food –Dietary Taxesand Subsidies to Improve Public Health

Mozaffarian, Rogoff, & Ludwig, JAMA2014

Packaged andsupermarket foods

Restaurant and other foodservice establishments

Simple Flat Tax(10-30% )

Most packaged foods (e.g.,nearly all foods with alabel).

Most chain restaurants,large cafeteria vendors, andother similar food serviceestablishments.

Subsidy(from tax revenue)

Minimally processedhealthful foods, such asfruits, nuts, vegetables,beans, seafood, plainyogurt, vegetable oils, andminimally processed wholegrains.

School lunch andafterschool programs.