Reply to P Scarborough et al

Dear Sir:

We agree with Scarborough et al that it is appropriate to consider the possibility that inclusion of serum cholesterol concentrations in multiple regression models may attenuate the relation of saturated fat to cardiovascular disease (CVD) in observational cohort studies. However, using data from the subset of studies in our meta-analysis in which the models did not include blood cholesterol concentration [9 coronary heart disease (CHD) studies and 6 stroke studies; n = 291,126], the results did not differ significantly from those that we reported for all 21 studies (n = 347,747) (1). The calculated relative risk estimates and 95% CIs for saturated fat intake in the subset were 1.13 (0.96, 1.33) for CHD, 0.84 (0.63, 1.10) for stroke, and 1.02 (0.86, 1.19) for total CVD. This secondary analysis suggests that the overall results from the meta-analysis are robust and are not affected by different analytic strategies. They corroborate a recent pooled analysis of 11 American and European cohort studies (n = 344,696 persons) that showed that replacement of saturated fat by carbohydrate was not associated with decreased risk of CHD; on the contrary, such a replacement was associated with a slightly increased risk of CHD (2).