Background: The association between saturated fatty acid (SFA) intake and ischemic heart disease (IHD) risk is debated. Objective: We sought to investigate whether dietary SFAs were associated with IHD risk and whether associations depended on 1) the substituting macronutrient, 2) the carbon chain length of SFAs, and 3) the SFA food source. Design: Baseline (1993-1997) SFA intake was measured with a foodfrequency questionnaire among 35,597 participants from the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort. IHD risks were estimated with multivariable Cox regression for the substitution of SFAs with other macronutrients and for higher intakes of total SFAs, individual SFAs, and SFAs from different food sources. Results: During 12 y of follow-up, 1807 IHD events occurred. Total SFA intake was associated with a lower IHD risk (HR per 5% of energy: 0.83; 95% CI: 0.74, 0.93). Substituting SFAs with animal protein, cis monounsaturated fatty acids, polyunsaturated fatty acids (PUFAs), or carbohydrates was significantly associated with higher IHD risks (HR per 5% of energy: 1.27-1.37). Slightly lower IHD risks were observed for higher intakes of the sum of butyric (4: Conclusions:In this Dutch population, higher SFA intake was not associated with higher IHD risks. The lower IHD risk observed did not depend on the substituting macronutrient but appeared to be driven mainly by the sums of butyric through capric acid, the sum of pentadecylic and margaric acid, myristic acid, and SFAs from dairy sources. Residual confounding by cholesterol-lowering therapy and trans fat or limited variation in SFA and PUFA intake may explain our findings. Analyses need to be repeated in populations with larger differences in SFA intake and different SFA food sources.Am J Clin Nutr 2016;103:356-65.

Objective— We assessed whether the association between dietary saturated fatty acids (SFA) and incident coronary heart disease (CHD) depends on the food source, the carbon chain length of SFA, and the substituting macronutrient. Approach and Results— From the Rotterdam Study, 4722 men and women (≥55 years) were included. Baseline (1990–1993) SFA intake was assessed using a validated food frequency questionnaire. CHD (nonfatal myocardial infarction and fatal CHD) was ascertained by medical records. Using multivariable Cox regression analysis, we calculated CHD risks for higher intakes of total SFA, SFA from specific food sources, SFA differing in carbon chain length, and substituting other macronutrients instead of SFA. During a median follow-up of 16.3 years, 659 CHD events occurred. Total SFA intake was not associated with CHD risk (hazard ratio [HR] per 5 en%, 1.13; 95% confidence interval, 0.94–1.22), and neither was SFA from specific food sources. A higher CHD risk was observed for palmitic acid (16:0) intake (HR SD , 1.26; 95% confidence interval, 1.05–1.15) but not for SFA with other chain lengths. Except for a higher CHD risk for substitution of SFA with animal protein (HR 5en% , 1.24; 95% confidence interval, 1.01–1.51), substitution with other macronutrients was not associated with CHD. Conclusions— In this Dutch population, we observed that a higher intake of palmitic acid, which accounts for ≈50% of the total SFA intake, was associated with a higher CHD risk, as was substitution of total SFA with animal protein. Nevertheless, we found no association between total SFA intake and CHD risk, which did not differ by food source.

Background The effect of individual saturated fatty acids (SFAs) on serum cholesterol levels depends on their carbon-chain length. Whether the association with myocardial infarction (MI) also differs across individual SFAs is unclear. We examined the association between consumption of individual SFAs, differing in chain lengths ranging from 4 through 18 carbons, and risk of MI. Methods We used data from 22050 and 53375 participants from EPIC-Norfolk (UK) and EPIC-Denmark, respectively. Baseline SFA intakes were assessed through validated, country-specific food frequency questionnaires. Cox regression analysis was used to estimate associations between intakes of individual SFAs and MI risk, for each cohort separately. Results During median follow-up times of 18.8 years in EPIC-Norfolk and 13.6 years in Denmark, respectively, 1204 and 2260 MI events occurred. Mean (±SD) total SFA intake was 13.3 (±3.5) en% in EPIC-Norfolk, and 12.5 (±2.6) en% in EPIC-Denmark. After multivariable adjustment, intakes of C12:0 (lauric acid) and C14:0 (myristic acid) inversely associated with MI risk in EPIC-Denmark (HR upper versus lowest quintile: 0.80 (95%CI:0.66,0.96) for both SFAs). Intakes in the third and fourth quintiles of C4:0-C10:0 also associated with lower MI risk in EPIC-Denmark. Moreover, substitution of C16:0 (palmitic acid) and C18:0 (stearic acid) with plant proteins resulted in a reduction of MI risk in EPIC-Denmark (HR per 1 energy%: 0.86 (95%CI:0.78,0.95) and 0.87 (95%CI:0.79,0.96) respectively). No such associations were found in EPIC-Norfolk. Conclusion The results from the present study suggest that the association between SFA and MI risk depends on the carbon chain-length of the SFA.