Vasanti Malik, ScD Research Scientist

Department of Nutrition

Harvard School of Public Health

Saturated Fatty Acids and Risk of

CHD: Modulation by Replacement

Nutrients

Cardiovascular Disease Prevention International Symposium,

Baptist Health South Florida

Thursday February 19, 2015

No conflicts of interest or disclosures

Conclusion from Chowdhury Abstract

“Current evidence does not clearly

support cardiovascular guidelines that

encourage high consumption of polyunsaturated fatty acids and low

consumption of total saturated fats.”

(Chowdhury R. et al. Ann Intern Med 2014:160:398-406)

Mark Bittman

Butter is Back

March 25, 2014

Julia Child, goddess of fat, is beaming

somewhere.

StudyType Strengths Limitations

Ecological Large numbers Confounding

Feeding Studies Control of diet

and confounding

Surrogate

outcomes

Cohort Studies Clinical

outcomes, better

control of

confounding

Potential

remaining

confounding

Randomized

Trials

Control of

confounding

Adherence to

diet, costly

Types of Studies of CHD

Fat type Cohorts, diet Cohorts, blood Randomized trials

Saturated fat RR=1.02

(0.97-1.07)

RR=1.06

(0.86-1.30)

MUFA RR=0.99

(0.89-1.09)

RR=1.06

(0.97-1.17)

N-6 PUFA RR=1.01

(0.96-1.07)

RR=0.94

(0.84-1.06)

RR=0.89

(0.71-1.12)

N-3 PUFA

(longchain)

RR=0.93

(0.84-1.02)

RR=0.84

(0.63-1.11)

RR=0.94

(0.86-1.03)

Trans fat RR=1.16

(1.06-1.27)

RR=1.05

(0.76-1.44)

Results from Chowdhury et al. (from Abstract) (RRs and 95% CIs for highest vs lowest category)

Fat type Cohorts, diet Cohorts, blood Randomized trials

Saturated fat RR=1.03

(0.98-1.07)

RR=1.06

(0.86-1.30)

MUFA RR=1.00

(0.91-1.10)

RR=1.06

(0.97-1.17)

N-6 PUFA RR=0.98

(0.90-1.06)

RR=0.94

(0.84-1.06)

RR=0.86

(0.69-1.07)

N-3 PUFA

(longchain)

RR=0.87

(0.78-0.97)

RR=0.84

(0.63-1.11)

RR=0.94

(0.86-1.03)

Trans fat RR=1.16

(1.06-1.27)

RR=1.05

(0.76-1.44)

Results from Chowdhury et al. (from revised Abstract) (RRs and 95% CIs for highest vs lowest category)

Randomized Control Trials of Omega 6

Study Intervention

Group

Control

Group RR (95% CI)

(Chowdhury et al., Ann Intern Med 2014)

Relationship of saturated fat intake to Coronary Heart

Disease Before 1970

Mancini and Stamler ; Nutr Metab Cardiovasc Dis (2004) 14:52-57

(Keys A Circulation (1970) 41 (Suppl. 1): 1-211)

Relationship of saturated fat intake to Cardiovascular

disease through 2010

Am J Clin Nutr 2010;91:535–46

HFCS

Whole grains

Whole grains

Corn syrup

% from fiber

Total

Carbohydrate

Gross et al. Am J Clin Nutr., 2004

Refined Carbohydrates and Added Sugar

Ecologic Data from the US

Mono fat

Poly fat

Trans fat Protein

Estimated Sources of Calories in US Diet Other carbs

Whole grain Potatoes Sat fat

Refined grain

Added sugar

(unpublished, compiled from NHANES)

Trans Fat

Saturated Fat

Unsaturated Vegetable Fats

--High monounsaturated vegetable fats

--High polyunsaturated vegetable fats

Refined Starch,

Sugar

Carbohydrates

Whole

Grains

Saturated fat

palm oil

Monounsaturated fats

olive, canola

almonds, peanuts

Polyunsaturated fats

w-6:

w-3: Linolenic-walnuts EPA, DHA- fatty fish, blue-green algae

Fats

Linoleic-soybean, rapeseed, sunflower oil

Nurses Health Study (121,701 women)

Health Professionals Follow-up Study (51,529 men)

Nurses Health Study II (116,686 young women)

1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 ....... 2010

Diet

Every Two Years: Weight, smoking, physical activity, CVD risk factors, diseases.

Every Four Years: Detailed dietary habits.

Diet Diet Diet Diet Diet

1986 1988 1990 1992 1994 1996 1998 2000 ........ 2010

Diet Diet Diet Diet

1989 1991 1993 1995 1997 1999 2001 ......... 2011

Diet Diet Diet

Diet

Diet

Harvard Prospective Cohort Studies

% C

ha

ng

e i

n C

HD

20

0 -20 -40

1%E 2%E 3%E 4%E 5%E

Sat

Mono Poly

Hu FB, et al. N Engl J Med 1997;337:1491-9

Type of Dietary Fat and Risk of Coronary Heart Disease

The Nurses' Health Study

14-Year Follow-up 100

Trans 80 60 40

-80 -60 -40 -20 0 20 40 60 80

Nurses’ Health Study

Dietary Fats and Risk of CHD Sat -->Carbo (5%E) Mono -->Carbo (5%E) Poly --> Carbo (5%E) Sat--> Mono (5%E) Sat--> Poly (5%E) Sat-->Unsat (5%E) Trans--> Mono (2%E) Trans --> Poly (2%E) Trans --> Unsat (2%E)

Change in CHD Risk (%)

Hu FB, et al. N Engl J Med 1997;337:1491-9

Coronary events per 5 E% increments: Pooled analysis of 11 cohorts

The model included intake of MUFA, PUFA, trans-fatty acids, CHs, protein expressed as percentage, TEI,

smoking, BMI, physical activity, highest attained educational level, alcohol intake, history of

hypertension, and energy-adjusted quintiles of fiber intake (g/d) and cholesterol intake (mg/d)

Am J Clin Nutr 2009;89:1425–32

Meta-analysis of RCTs evaluating effects of increasing PUFA consumption in place of SFA and occurrence of CHD events

PLoS Med 2010:7(3): e1000252. doi:10.1371

Ha

zard

Ra

tio

fo

r m

yo

card

ial

infa

rcti

on

1.08

1.64 1.33

0.6

0.8

1

1.2

1.6 1.4

Low-GI High-GI Medium-GI

Tertile of Glycemic Index

1.21

0.98

0.80

1.07

0.88

0.72

HR=1

Am J Clin Nutr 2010;91:1764–68

Substitution effect (5% of energy from carbohydrates for

saturated fatty acids differs by Glycemic Index

Danish prospective cohort study of Diet, Cancer and Health

Hazard ratios for CHD by intake of fatty acids and carbohydrates of

different quality as a percentage of total energy intake: Pooled results from

the NHS and HPFS

Unpublished

Two-to-4-year changes in percentage of energy intake from different fatty

acids and carbohydrate sources according to deciles of changes in saturated

fat as a percentage of energy intake: Pooled results from the NHS and HPFS

Unpublished

Multivariable hazard ratios for CHD with isocaloric (% of energy)

substitution of Saturated fat for other fats and different quality

carbohydrates: Pooled results from the NHS and HPFS

Unpublished

• A focus of dietary recommendations for CVD prevention and treatment has been a

reduction in saturated fat intake, primarily as a means of lowering LDL- cholesterol.

• The evidence that supports a reduction in saturated fat intake must be evaluated in the

context of replacement by other macronutrients.

• Based on prospective studies, replacement of saturated fat with carbohydrate is unlikely

to have an important effect on risk of CHD, but this depends on type of carbohydrate.

• Based on prospective studies and few RCTs, replacement of saturated fat with PUFA,

including a mix of N-6 and N-3 PUFA, will reduce risk of CHD.

• Data from prospective studies support an adverse effect of trans fat on

risk of CHD, which is consistent with feeding studies with intermediate endpoints.

• Findings for MUFA are complicated because main sources have been animal fats and

partially hydrogenated oils in the populations studied. Results of RCTs involving canola and

olive oil suggest likely benefits.

Conclusions

Acknowledgements:

Walter Willett

David Jenkins

Frank Hu

Yanping Li

Thank You