Rethinking Dietary Fats
Dariush Mozaffarian, MD DrPH
Dean
Jean Mayer Professor in Nutrition and Medicine
Controversiesand Advances in the Treatment of CVD
Los Angeles, CA
Nov 17, 2016
Disclosures
• Research support: National Institutes of Health, Gates
Foundation
• Ad hoc honoraria/consulting: Boston Heart Diagnostics,
Haas Avocado Board, Astra Zeneca, GOED, DSM, Life
Sciences Research Organization
• Royalties: UpToDate chapters on fish oil, dietary fats
Ca u s e s o f US De a th s in 2010
USBurden of Disease
Collaborators, JAMA 2013
Exp lo s io n o f In te re s t: P a s s io n & Co n fu s io n
Source: Google images
Diet & the Heart: Conventional Wisdom
Total Fat,
Saturated Fat
Serum Total and
LDL Cholesterol
Ecologic studies
(across nations
or populations)
Coronary Heart
Disease
Short-term studies
of single surrogate
outcomes
Number of Scientific
Publications
Exp lo s io n o f Nu tritio n S c ie n c e
Source: Pubmed/Medline
(through Aug 2016)
- 8.2 %E
total fat
- 2.9 %E
saturated fat
+ 4.4 %E (no change
total fat in sat. fat)
Diet & Health: Modern Science
Mozaffarian D, Circulation 2016
Dietar y Fats: Highly Bioactive
Mozaffarian & Wu, JACC2011
Dietar y Fats & Blood Lipids
No ApoB
0.10
0.06
0.02
-0.02
MUFA
-0.06
PUFA
0
1%
2%
3%
4%
? ApoCIII
MUFA
SFA
PUFA
-0.10
-0.15
2%
3%
4%
PUFA
0.03
0.02
0.01
0.00
0
-0.05
1%
MUFA
0.04
5%
0.00
0
0.05
∆ HDL-C, m m o l/L
0.14
-0.10
∆ Trig lyc e rid e s , m m o l/L
SFA
SFA
5%
∆ To ta l:HDL-C Ra tio
∆ LDL-C, m m o l/L
0.18
1%
2%
3%
4%
5%
0.04
SFA
0.00
-0.04
-0.08
MUFA
-0.12
-0.16
PUFA
-0.20
0
1%
2%
3%
4%
Meta-analysis of 60 randomized feeding trials. Mensink & Katan, AJCN 2003
5%
Satur ated Fat & CHD Events
16 p ro s p e c tive
c o h o rt s tu d ie s fro m
a ro u n d th e wo rld
No S ig n ific a n t As s o c ia tio n
Siri-Tarino et al, AJCN 2010
RR c o m p a rin g e xtre m e
c a te g o rie s (h ig h e s t vs . lo we s t)
o f s a tu ra te d fa t in ta ke
Polyunsatur ated Fat & CHD Events: RCTs
n6P UFA
n6
lab el
Clin ic a l Tria l
ev
n
Eve n ts n
%
(% e n e rg y)
con
Rx
Co n tro l Rx
8 randomized trials, 13,614
participants, 1,042 CHD events
RR (95 % CI)
RR (95% CI)
We ight
% We ig h t
LA Veteran s
12 4
846
4.0
14.9
0.74 (0 .53, 1.03)
13.44
MRC so y
96
393
4.4
20.4
0.86 (0 .61, 1.22)
12.48
Oslo Diet-Heart
14 2
412
5.2
20.7
0.75 (0 .57, 0.99)
16.87
Finn ish - Men
72
461
4.3
12.9
0.55 (0 .34, 0.88)
8.19
Finn ish - Women
73
357
4.3
12.9
0.64 (0 .41, 1.00)
8.69
Minn eso ta CS
25 2
905 7
5.2
14.7
1.08 (0 .84, 1.37)
18.79
DART
27 6
203 3
6.4
8.9
0.91 (0 .73, 1.14)
20.60
STARS
7
55
5.2
8.0
0.41 (0 .09, 1.96)
0.94
Ove rall
Ove
ra ll P o o le d Effe c t
0.81 (0.70,
(0 .70, 0.95)
0.81
0.95)
100.00
NOTE: Weights a re fro m random e ffects an alys is
.3 3
.5
1
2
Re la tive Ris k o f CHD
3
Mozaffarian et al,
PLoSMed 2010
SFA and CHD: Different Nutr ient Replacements
Die ta ry Ch a n g e (e a c h 5% e n e rg y)
RR (95% CI)
P o lyu n s a tu ra te d Fa t Re pla c in g S a tu ra te d Fa t
P re dicte d Effe ct from TC:HDL-C Cha nge
0.91 (0.87, 0.95)
Me ta -Ana lys is of 8 RCTs
0.90 (0.83, 0.97)
P oole d Ana lys is of 11 Obs e rva tiona l Cohorts
0.87 (0.77, 0.97)
Ca rb o h yd ra te Re p la c in g S a tu ra te d Fa t
P re dicte d Effe ct from TC:HDL-C Cha nge
1.01 (0.98, 1.04)
Wome n's He a lth Initia tive RCT
0.98 (0.88, 1.09)
P oole d Ana lys is of 11 Obs e rva tiona l Cohorts
1.07 (1.01, 1.14)
Mo n o u n s a tu ra te d Fa t Re p la c in g S a tu ra te d Fa t
P re dicte d Effe ct from TC:HDL-C Cha nge
0.93 (0.89, 0.96)
RCTs – None
--
P oole d Ana lys is of 11 Obs e rva tiona l Cohorts
0.7
1.19 (1.00, 1.42)
1.0
1.5
Re la tive Ris k o f CHD fo r Ea c h 5% En e rg y In ta ke
Mozaffarian et al., PLoS Med 2010
Aver age Sources of Calor ies in the US Diet
Oth e r c a rb s
Wh o le g ra in
P o ta to e s
S a t fa t
Mo n o fa t
Re fin e d g ra in
P o ly fa t
Ad d e d s u g a r
P ro te in
Tra n s fa t
Sources of Satur ated Fat in the U.S.
Based on NHANES2005-06. From USDA Dietary Guidelines 2010
Meats & CVD Mor tality
Among 448,568 European
men and women (EPIC),
including 5,556 CVD deaths
Total Red
Meat (100 g/d)
RR = 1.09
(1.00, 1.18)
Pr ocessed
Meat (100 g/d)
RR = 1.69
(1.37, 2.10)
Rohrmann et al., BMC Medicine 2013
Dair y & CVD
RR = 0.88
(0.81, 0.96)
Qin et al., Asia Pac Clin Nutr 2015
Cheese & CHD: RR 0.91 (0.84, 0.99)
Cheese & Stroke: RR 0.84 (0.71, 1.00)
Dairy and Diabetes: Complex Influences
340,234 Eu ro p e a n s , 8 c o u n trie s , 12,403 c a s e s
1.2
P-trend=0.50
Pr obiotics, Fer mentation ?
1.1
RR o f
Dia b e te s
P-trend=0.06
P-trend=0.01
1
0.9
0.8
0.7
Milk
Yogurt
Cheese
Qu in tile s o f Co n s u m p tio n
Sluijis et al., AJCN 2012
Dair y Fat & Diabetes
1.4
1.2
1.0
RR o f
In cid e n t
Dia b e te s
0.8
P tre n d < 0.001
0.6
0.4
0.2
0.0
Q1
Q2
Q3
Q4
Q5
Quintiles of Phospholipid Trans-16:1n-7 (palmitoleic acid)
Among 3,736 olde r US a dults .
Mozaffarian et al., Annals Intern Med 2010
Milk Fat Globule Membr ane
Rosqvist et al., AJCN 2016
Milk Fat Globule Membrane
Ch
f
bas
m
Rosqvist et al., AJCN 2016
Preventing Chronic Diseases: Food Patter ns
Dietar y Pr ior ities: Healthy Food Patter ns
Benefit
* Especially
extra-virgin olive oil,
oybean oil, canola oil
Eggs, Poultry, Milk
Butter
Har m
Mozaffarian D,
Circulation 2016
Calor ies, Fat, Single Nutr ients: Misleading
- 8.2 %E
total fat
- 2.9 %E
saturated fat
+ 4.4 %E (no change
total fat in sat. fat)
twitter: @DMozaffarian
www.nutritionletter.tufts.edu
Bar r ier s 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.
– Limits on phone use, texting.
• Car:
– Active: seat belts, child seats,
motorcycle helmets.
– Passive: padded interiors,
collapsible steering columns,
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 o h n S n o w, Lo n d o n Ch o le ra Ep id e m ic , 1854
Snow, J. On the Mode of Communication of Cholera, C.F. Cheffins, London 1855
WHI Tria l: Ho rm o n e Re p la c e m e n t Th e ra p y
Disease
WHI Tr ial RR
Obser vational RR
1.29 (1.02-1.63)
age<60: 0.59 (0.380.90) *
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)
Heart disease
* LaCroix et al., JAMA 2011
Cochr ane: Obser vational Studies vs. RCTs
• 15 reviews, totaling 1,583 meta-analyses of 228 medical
conditions
• Direct comparison of effects seen in RCTsvs.
observational studies:
– RCTs vs. all observational studies: ratio of RRs = 1.08
(0.96, 1.22)
– RCTsvs. prospective cohorts: ratio of RRs = 1.04
(0.89, 1.21)
Anglemyer A et al., 2014, The Cochrane Library
Satur ated Fat and Incident Diabetes
Micha & Mozaffarian, Lipids 2010
Dietar y Fat and Metabolic Health: RCTs
Imamura et al., Plos Med 2016
Dairy Fat and Diabetes: Benefits ?
Mozaffarian D, EHJ2015
Bu tte r & CVD
Any CVD
CHD
Stroke
Total CVD
Pimpin et al., Plos One 2016
Milk Fat Globule Membr ane: Genetic Effects
Rosqvist et al., AJCN 2016
Benefit
Likely - needs
more study
Different
effects of
animal vs.
vegetable
sources ?
Different
effects of
various
fatty acids ?
Har m
Different
effects of
various
fatty acids ?
Why Our Infatuation with Single Nutr ients?
• In 1753, J a me s Lind te s te d whe the r e a ting citrus fruits pre ve nte d s curvy.
• In 1932, Vita min C is ola te d, confirme d a s the a ctive prote ctive nutrie nt.
On e n u trie n t → o n e d is e a s e !
• S oon: Thia mine (be ribe ri), nia cin (pe lla gra ), iron (a ne mia ),
iodine (goite r), vita min A (night blindne s s ), vita min D (ricke ts ).
• Ea rly 20th ce ntury die ta ry guide line s thus focus e d on p re ve n tin g n u trie n t d e fic ie n c y
d is e a s e s . Gre a t De pre s s ion a nd World Wa r II food s horta ge s → furthe r e mpha s is .
• Le a gue of Na tions , Britis h Me dica l As s ocia tion, a nd US DA forme d pa ne ls to cre a te
ne w minimum re quire me nts for ca lorie s , prote in, ca lcium, phos phorus , iron, va rious
vita mins → Na tio n a l Nu tritio n Co n fe re n c e fo r De fe n s e , Firs t RDAs in 1941.
• Mode rn die ta ry guide line s we re de ve lope d to me e t the s e ne w RDAs . S e t p re c e d e n t
to s ta rt with n u trie n t ta rg e ts a nd the n tra ns la te the s e into food re comme nda tions .
Mozaffarian D, Lancet Diabetes 2016
Nutr ient Focus: Recipe for Confusion
www.nhlbi.nih.gov/he a lth/public/he a rt/obe s ity/we ca n/downloa ds /go-s low-whoa .pdf
What is Dr iving Policy and Public Choices ?
• Total fat
• Clean labels
• Saturated fat
• Gluten-free
• Added sugar
• Organic
• Total calories
• Local
• Paleo
• Low-carb
• Vegetarian, vegan
Evidence-Based Policy Str ategies for Diet
Media and
Education
Sustained, focused media campaigns, especially as part of multicomponent strategies, focused on specific foodsor drinks.
Labeling and
Information
Mandated nutrition facts, front-of-pack labels, or menu labeling to
influence industry behavior.
Schools
Multicomponent nutrition programsincluding classes, teacher training,
supportive policies, environmental changes, and family components.
School garden programs.
Comprehensive worksite wellness programsfor diet and lifestyle.
Workplaces
Increased availability of healthier options and/or strong nutrition
standards, combined with on-site prompts, labels, or icons.
Economic
Incentives
Subsidy strategies to lower prices of more healthful foods.
Quality
Standards
Restrictionson marketingof lesshealthy foodsto childrens.
Agricultural
Policies
Long-term changes in agricultural policies for infrastructure to facilitate
production, transportation, and marketing of healthier foods.
Tax strategies to increase prices of less healthful foods.
Restrictions (e.g., salt, trans fat) or mandates (e.g., vegetable oils).
AHAScientific Statement: Population Approaches to Improve Diet, Physical Activity, and Smoking Habits.
Mozaffarian et al., Circulation 2012
The Real Cost of Food – Dietar y Taxes
and Subsidies to Improve Public Health
Packaged and
super mar ket foods
Restaur ant and other food
ser vice establishments
Simple Flat Tax
(10-30% )
Most packaged foods (e.g.,
nearly all foods with a
label).
Most chain restaurants,
large cafeteria vendors, and
other similar food service
establishments.
Subsidy
(from tax revenue)
Minimally processed
healthful foods, such as
fruits, nuts, vegetables,
beans, seafood, plain
yogurt, vegetable oils, and
minimally processed whole
grains.
School lunch and
afterschool programs.
Mozaffarian, Rogoff, & Ludwig, JAMA 2014