Response to Letters Regarding Article, “Dietary Linoleic Acid and Risk of Coronary Heart Disease: A Systematic Review and Meta-Analysis of Prospective Cohort Studies”
Authors: Maryam S. Farvid, Ming Ding, An Pan, Qi Sun, Stephanie E. Chiuve, Lyn M. Steffen, Walter C. Willett, Frank B. Hu
Journal: Circulation (2015)

We appreciate Lucas' and Hoenselaar's comments on our metaanalysis of linoleic acid (LA) and coronary heart disease (CHD) events. 1 Lucas pointed out that evidence from epidemiological studies, including our meta-analyses, contradicts the assertion that higher consumption of omega-6 polyunsaturated fats is harmful.Despite theoretical concern about the potential proinflammatory and thrombogenic properties of omega-6 polyunsaturated fats, evidence from human studies to support a positive association between intakes of these fatty acids and biomarkers of inflammation or risk of cardiovascular disease or cancer is limited.On the contrary, epidemiological studies and randomized, clinical trials have documented beneficial effects of replacing saturated fat with omega-6 polyunsaturated fats on blood lipids and cardiovascular disease risk.We agree with Lucas that the ratio of omega-6 to omega-3 is not particularly meaningful because both types of fatty acids are essential and confer health benefits and there is little evidence that the ratio per se is related to health outcomes.Hoenselaar argued that "Effects found were largely driven by results from 2 cohorts: the Nurses' Health Study [NHS] and the Health Professional Follow-Up Study [HPFS]."To address this issue, in a sensitivity analysis, we tested the influence of an individual study on the results.With systematic removal of 1 study at a time, the summary relative risks (RRs) for CHD events for the highest versus lowest categories of LA intake did not change materially.The summary RR was 0.89 (95% confidence interval [95% CI], 0.81-0.98)after the exclusion of data from NHS and 0.85 (95% CI, 0.77-0.93)after the exclusion of data from HPFS.We found a stronger association after excluding the Malmo Diet and Cancer Cohort Study (MDC; RR=0.81; 95% CI, 0.75-0.88).Similar results were observed for LA and CHD deaths (after the exclusion of NHS: RR=0.83; 95% CI, 0.73-0.94;after the exclusion of HPFS: RR=0.80; 95% CI, 0.70-0.92;and after the exclusion of MDC: RR=0.77; 95% CI, 0.67-0.87;all data included in this meta-analysis were presented in Tables IV through IV in the online-only Data Supplement of our article).Similar results were found for an increment of 5% energy from LA and risk of either CHD events or CHD deaths after the removal of 1 study at a time.Updated dietary data during follow-up, a large number of individuals followed up for a long time, and high rates of follow-up distinguished NHS and HPFS from other cohorts. 2 Stronger associations for LA and either CHD events or CHD deaths were observed in categorical analyses (ie, highest versus lowest categories) than continuous analyses.We used the median intake of LA in each tertile or quintile to calculate the RRs for each 5% energy from LA.Because the cut points for the categories of LA differed somewhat across different studies, the estimates from the categorical analyses were more approximate, whereas the estimates from continuous analyses were more comparable across studies and hence more accurate.Via direct investigator communication, we had a unique opportunity to evaluate the association between LA intake and CHD morbidity and mortality in the largest and most complete systematic review and meta-analysis to date.Based on a funnel plot and the Begg test, no significant publication bias was noted.In addition, these robust inverse associations were not dependent on an individual study.Overall, our results are consistent with an earlier pooled analysis of the primary individual data from 11 cohort studies on LA and CHD risk 3 and a meta-analysis of randomized, clinical trials that showed a 10% lower CHD risk (RR=0.90;95% CI, 0.83-0.97)for each 5% energy increment in polyunsaturated fat intake. 4Although different dietary sources of LA might affect the relation between LA and CHD events, the cardioprotective effect of specific foods high in LA was not the subject of this meta-analysis and should be addressed in future work.