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Finally a Well-designed Study of Saturated Fat & Heart Disease

Dean Pomerleau

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[Another one for the "Non-CR Health forum"...]


Recently there has been much hype in the popular press, including a Time Magazine story, with this provocative cover:




that claim we've been wrong about saturated fat (like butter) all along. These stories have been based on meta-analyses like this one [1], that purport to find no association between saturated fat and chronic diseases, even cardiovascular disease. One of my favorite nutrition bloggers, PlantPositive, did a thorough debunking of the Time story and the people & studies it uses as sources.


Among other faults of these previous meta-analyses outlined in PlantPositive's post, some of the biggest problems include:

  • Over correction by factoring out serum cholesterol in the analysis - which is elevated by saturate fat intake and so shouldn't be controlled for.
  • Failing to factor out the low cholesterol of saturated fat eaters who take statins to control their cholesterol.
  • Failing to account for the health effects of what people choose to eat instead when they don't eat saturated fat-rich foods.
As I recall (but an unable to verify due to the archives being down... :(xyz ), we talked about all these studies and their shortcomings on the CR email list before.


But now, we have something even better than critical analysis of flawed studies. We have a new prospective cohort study [2] of some of the best data available on diet, lifestyle and health from the Health Professionals and Nurses Health Studies. It appears to do a much better job, particularly with respect to the third confounder - food substitution effects. Here is popular press coverage of the new study. 


The Harvard researchers have followed these two cohorts of 42K men and 84K women for over 30 years, assessing their diet, lifestyle and health repeatedly during that time. This study looked at their fat consumption habits, and in particular changes in those habits over time and how those changes relate to coronary heart disease (CHD).


In a nutshell, they found that:


Replacing 5% of energy intake from saturated fats with equivalent 

energy intake from PUFAs, monounsaturated fatty acids, or carbohydrates from

whole grains was associated with a 25%, 15%, and 9% lower risk of CHD,

respectively (PUFAs, HR: 0.75, 95% CI: 0.67 to 0.84; p < 0.0001; monounsaturated 

fatty acids, HR: 0.85, 95% CI: 0.74 to 0.97; p = 0.02; carbohydrates from whole

grains, HR: 0.91, 95% CI: 0.85 to 0.98; p = 0.01). Replacing saturated fats with 

carbohydrates from refined starches/added sugars was not significantly associated

with CHD risk (p > 0.10).


Here is a graphical depiction of these results:




As you can see, trans fat is toxic relative to any other foods, including saturate fat - no surprise. More interestingly, it is about a wash to substitute saturated fat with refined carbohydrates when it comes to heart disease risk. But substituting any of the following for saturated fat results in significantly reduced CHD risk - MUFA, PUFA and whole grain carbohydrates. PUFAs appear particularly protective. Unfortunately the study did not address other healthy carbohydrate sources besides whole grains, like fruits, vegetables or legumes (which I willing to bet would do at least as well as whole grains at reducing CHD risk relative to saturated fat). They also didn't discriminate between the health effects of different types of saturated fats, some of which might not be as bad as others (i.e. those found in plants vs. animal sources). 


One concern is that when people clean up their diet by eliminating saturated fat, they might also undertake other health promoting lifestyle changes, making it appear that reducing saturated fat was beneficial when it actually was the other changes that made the difference. The authors addressed this potential problem by controlling for a host of other factors in their analysis, including:


The multivariable model was adjusted for total energy intake, the energy contribution from protein, cholesterol intake, alcohol intake, smoking status, body mass index, physical activity, use of vitamins and aspirin, family history of myocardial infarction and diabetes, and presence of baseline hypercholesterolemia and hypertension.


These results confirm what I think most people have believed all along - that saturated fat is detrimental to heart health, but probably no more so than what people will normally eat instead, crappy carbs. This explains those previous studies that found lower saturated fat intake was often not associated with lower risk of heart disease - people who ate less saturated fat were eating more refined carbs instead, and so weren't any better off. But when you replace saturated fat-rich foods with healthy fats or healthy carbs, you reduce your risk of heart disease dramatically.





[1] BMJ. 2015 Aug 11;351:h3978. doi: 10.1136/bmj.h3978.

Intake of saturated and trans unsaturated fatty acids and risk of all cause

mortality, cardiovascular disease, and type 2 diabetes: systematic review and

meta-analysis of observational studies.


de Souza RJ(1), Mente A(2), Maroleanu A(3), Cozma AI(4), Ha V(5), Kishibe T(6),

Uleryk E(7), Budylowski P(8), Schünemann H(9), Beyene J(10), Anand SS(11).


OBJECTIVE: To systematically review associations between intake of saturated fat

and trans unsaturated fat and all cause mortality, cardiovascular disease (CVD)

and associated mortality, coronary heart disease (CHD) and associated mortality,

ischemic stroke, and type 2 diabetes.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES: Medline, Embase, Cochrane Central Registry of Controlled Trials,

Evidence-Based Medicine Reviews, and CINAHL from inception to 1 May 2015,

supplemented by bibliographies of retrieved articles and previous reviews.


associations of saturated fat and/or trans unsaturated fat (total, industrially

manufactured, or from ruminant animals) with all cause mortality, CHD/CVD

mortality, total CHD, ischemic stroke, or type 2 diabetes.

DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and

assessed study risks of bias. Multivariable relative risks were pooled.

Heterogeneity was assessed and quantified. Potential publication bias was

assessed and subgroup analyses were undertaken. The GRADE approach was used to

evaluate quality of evidence and certainty of conclusions.

RESULTS: For saturated fat, three to 12 prospective cohort studies for each

association were pooled (five to 17 comparisons with 90 501-339 090

participants). Saturated fat intake was not associated with all cause mortality

(relative risk 0.99, 95% confidence interval 0.91 to 1.09), CVD mortality (0.97,

0.84 to 1.12), total CHD (1.06, 0.95 to 1.17), ischemic stroke (1.02, 0.90 to

1.15), or type 2 diabetes (0.95, 0.88 to 1.03). There was no convincing lack of

association between saturated fat and CHD mortality (1.15, 0.97 to 1.36; P=0.10).

For trans fats, one to six prospective cohort studies for each association were

pooled (two to seven comparisons with 12 942-230 135 participants). Total trans

fat intake was associated with all cause mortality (1.34, 1.16 to 1.56), CHD

mortality (1.28, 1.09 to 1.50), and total CHD (1.21, 1.10 to 1.33) but not

ischemic stroke (1.07, 0.88 to 1.28) or type 2 diabetes (1.10, 0.95 to 1.27).

Industrial, but not ruminant, trans fats were associated with CHD mortality (1.18

(1.04 to 1.33) v 1.01 (0.71 to 1.43)) and CHD (1.42 (1.05 to 1.92) v 0.93 (0.73

to 1.18)). Ruminant trans-palmitoleic acid was inversely associated with type 2

diabetes (0.58, 0.46 to 0.74). The certainty of associations between saturated

fat and all outcomes was "very low." The certainty of associations of trans fat

with CHD outcomes was "moderate" and "very low" to "low" for other associations.

CONCLUSIONS: Saturated fats are not associated with all cause mortality, CVD,

CHD, ischemic stroke, or type 2 diabetes, but the evidence is heterogeneous with

methodological limitations. Trans fats are associated with all cause mortality,

total CHD, and CHD mortality, probably because of higher levels of intake of

industrial trans fats than ruminant trans fats. Dietary guidelines must carefully

consider the health effects of recommendations for alternative macronutrients to

replace trans fats and saturated fats.


© de Souza et al 2015.


PMCID: PMC4532752

PMID: 26268692



[2] J Am Coll Cardiol. 2015 Oct 6;66(14):1538-48. doi: 10.1016/j.jacc.2015.07.055.

Saturated Fats Compared With Unsaturated Fats and Sources of Carbohydrates in

Relation to Risk of Coronary Heart Disease: A Prospective Cohort Study.


Li Y(1), Hruby A(1), Bernstein AM(2), Ley SH(1), Wang DD(1), Chiuve SE(3),

Sampson L(1), Rexrode KM(4), Rimm EB(5), Willett WC(5), Hu FB(6).



BACKGROUND: The associations between dietary saturated fats and the risk of

coronary heart disease (CHD) remain controversial, but few studies have compared

saturated with unsaturated fats and sources of carbohydrates in relation to CHD


OBJECTIVES: This study sought to investigate associations of saturated fats

compared with unsaturated fats and different sources of carbohydrates in relation

to CHD risk.

METHODS: We followed 84,628 women (Nurses' Health Study, 1980 to 2010), and

42,908 men (Health Professionals Follow-up Study, 1986 to 2010) who were free of

diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed by a

semiquantitative food frequency questionnaire every 4 years.

RESULTS: During 24 to 30 years of follow-up, we documented 7,667 incident cases

of CHD. Higher intakes of polyunsaturated fatty acids (PUFAs) and carbohydrates

from whole grains were significantly associated with a lower risk of CHD

comparing the highest with lowest quintile for PUFAs (hazard ratio

: 0.80,

95% confidence interval [CI]: 0.73 to 0.88; p trend <0.0001) and for

carbohydrates from whole grains (HR: 0.90, 95% CI: 0.83 to 0.98; p trend =

0.003). In contrast, carbohydrates from refined starches/added sugars were

positively associated with a risk of CHD (HR: 1.10, 95% CI: 1.00 to 1.21; p

trend = 0.04). Replacing 5% of energy intake from saturated fats with equivalent

energy intake from PUFAs, monounsaturated fatty acids, or carbohydrates from

whole grains was associated with a 25%, 15%, and 9% lower risk of CHD,

respectively (PUFAs, HR: 0.75, 95% CI: 0.67 to 0.84; p < 0.0001; monounsaturated

fatty acids, HR: 0.85, 95% CI: 0.74 to 0.97; p = 0.02; carbohydrates from whole

grains, HR: 0.91, 95% CI: 0.85 to 0.98; p = 0.01). Replacing saturated fats with

carbohydrates from refined starches/added sugars was not significantly associated

with CHD risk (p > 0.10).

CONCLUSIONS: Our findings indicate that unsaturated fats, especially PUFAs,

and/or high-quality carbohydrates can be used to replace saturated fats to reduce

CHD risk.


Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier

Inc. All rights reserved.


PMCID: PMC4593072 [Available on 2016-10-06]

PMID: 26429077

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This isn't an actual meta-analysis: it's a prospective study using combined datasets from two different cohorts studied by overlapping grouups of scientists using similar methods.
The best actual meta-analysis so far is (1), which unlike the misleading Siri-Tarino, Chowdhury, and de Sousa meta-analyses (which are behind most of the "Butter is Back" headlines and Atkins triumphalism of the last 5 y or so) (a) took into account the substitution effects that those other meta-analyses neglected, and (b) actually dug down into individual patient data, getting the actual grams of saturated fat (rather than pooling all the extremes in populations with differing ranges of intake) and actual rates of cardiovascular events and mortality (rather than pooling relative risks across populations with different risk rates). It found the same thing (tho' it didn't look at carb quality): substitution of the general pool of carb in western diets (which is largely crap: refined grains, sugar, and processed starchy vegetables) for SaFA is neutral, whereas substitution of PUFA reduces risk. (2) gave further nuance by providing evidence that the kind of PUFA matters: a mixture of n3 and n6 is (surprisingly weakly) better than n6 alone.
MUFA comes out neutral, or only very slightly beneficial, or even slightly harmful in well-done meta-analyses, presumably because of unavoidable confounding of MUFA with SaFA and its deleterious confounders in the Western diet:

the major sources of monounsaturated fatty acids in the United States and Scandinavia were dairy, meat, and partially hydrogenated oils.  A high intake of fat from these foods typifies an unhealthy lifestyle. Correction for confounders such as smoking, body mass index, and activity cuts the excess risk associated with high monounsaturated fatty acid intake in half, and therefore monounsaturated fatty acids may have acted as a surrogate for other risk factors. In countries in which olive oil is the main source, a high monounsaturated fatty acid intake is associated with lower rates of coronary heart disease.(3)

Certainly, both the epidemiological evidence within Mediterranean countries where olive oil is used in meaningful quantities, as well as now large-scale clinical trials, demonstrate that plant-based MUFA, and especially real extra-virgin olive oil (or, though less celebrated, canola) reduces cardiovascular events and mortality, likely total mortality, and mortality from some cancers.
1: Jakobsen MU, O'Reilly EJ, Heitmann BL, Pereira MA, Bälter K, Fraser GE, Goldbourt U, Hallmans G, Knekt P, Liu S, Pietinen P, Spiegelman D, Stevens J, Virtamo J, Willett WC, Ascherio A. Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies. Am J Clin Nutr. 2009 May;89(5):1425-32. Epub 2009 Feb 11. PubMed PMID: 19211817; PubMed Central PMCID: PMC2676998.
2: Ramsden CE, Hibbeln JR, Majchrzak SF, Davis JM.
n-6 Fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials.
Br J Nutr. 2010 Dec;104(11):1586-600.
PMID 21118617
3:  Katan MB. Omega-6 polyunsaturated fatty acids and coronary heart disease. Am J
Clin Nutr. 2009 May;89(5):1283-4. Epub 2009 Mar 25. PubMed PMID: 19321556.

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This isn't an actual meta-analysis: it's a prospective study using combined datasets from two different cohorts studied by overlapping grouups of scientists using similar 


Sorry, you're right. I assumed it was another meta-analysis when I started writing the post (hence the title), and then forgot to change the title when I recognized it was a prospective study. I've edited the title from "Meta-Analysis" to "Study" to correct this error.


I agree with you (and more importantly, the data) that suggests that MUFA sometimes gets a bad rap in studies because of its frequent correlation (in many western countries) with dairy meat and partially hydrogenated oil consumption, which in turn correlate with other unhealthy lifestyle factors. 



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