Don't disregard the essential distinction between PUFA species.
Don't disregard the essential distinction between PUFA species.
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DOI：
10.1017/s0007114511001061
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发表时间：
2011-09
影响因子：
3.6
通讯作者：
Davis, John M.
中科院分区：
文献类型：
--
作者：
Ramsden, Christopher E.;Hibbeln, Joseph R.;Majchrzak-Hong, Sharon F.;Davis, John M.
Harris et al.(1) apparently overlooked the central finding of our analysis (2), that n-6 specific PUFA interventions and mixed n-3/n-6 PUFA interventions have significantly different effects on risk of non-fatal myocardial infarction (MI) and CHD death in heterogeneity analysis (P¼0· 02). Given this clear statistical distinction, it is not valid to assess these two heterogeneous interventions together as a single unit (3). This key finding of heterogeneity calls into question the validity of interpreting results of any pooled analysis of the effects of mixtures of n-3 and n-6 PUFA to support advice specific to n-6 PUFA. Yet Harris et al. have repeatedly cited (4–8) three such pooled analyses, that did not make this essential distinction, as the primary evidence base for American Heart Association (AHA) advice to maintain or increase intake of n-6 PUFA:(1) the meta-analysis of randomised controlled trials (RCT) and CHD outcomes by Mozaffarian et al.(8);(2) the analysis of prospective observational cohorts by Jakobsen et al.(9); and (3) the analysis of intermediate risk factors by Mensink et al.(10). Each of these analyses evaluated the effects of increasing n-3 and n-6 PUFA together (Tables 1 and 2), without specificity for n-6 linoleic acid (LA), as we recently reviewed in detail (11). In relying on these non-specific PUFA data, rather than data selective to n-6 LA, Harris et al.(1) and the AHA Advisory Group were willing to assume that the modest but ‘remarkably consistent’CHD benefits were attributable to n-6 LA, rather than to n-3 EPA þ DHA and/or a-linolenic acid (ALA). We were unwilling to make this assumption without valid data evaluating the effects of selectively increasing LA. Our meta-analysis of four n-6 specific PUFA RCT datasets with 9569 participants (2) is therefore unique because it is the first analysis to compile the detailed dietary fatty acid data necessary to evaluate the CHD effects of selectively increasing n-6 LA (in place of trans-fatty acids and SFA). These n-6 specific PUFA data, which were not available to Mozaffarian et al.(8), were obtained via an extensive search of published and unpublished data sources enabling identification of the specific study oils and n-3 and n-6 PUFA content of RCT diets. Of the total RCT participants (n 11 275), 85% were in the n-6 specific PUFA RCT (n 9569); therefore only 15% of all RCT participants (n 1706) were in the mixed n-3/n-6 PUFA RCT. Harris et al.(1) seem preoccupied with the results of the latter 15% of RCT participants, which they interpret as ‘confirming’that ‘vegetable oils rich in n-6 PUFA’lower CHD (1). However, they apparently dismiss our pivotal finding that there was no indication of benefit in any of the four n-6 specific PUFA datasets representing 85% of the total RCT participants.There was a non-significant, but relatively consistent, signal toward harm in each of these four n-6 specific PUFA datasets (Figs. 1 and 2), as well as a pooled analysis for both CHD outcomes and death from all causes, despite substitution of n-6 LA for trans-fatty acids and SFA, which are generally considered atherogenic. By highlighting only the two n-6 specific PUFA RCT (three datasets) that provided corn oil (12, 13), and ignoring the unfavourable results of the fourth n-6 specific PUFA RCT dataset that provided safflower-seed oil (14, 15), Harris et al. have inaccurately portrayed our n-6 specific PUFA evaluation of four datasets and 9569 participants as a ‘two-trial analysis’ with ‘limited statistical power’useful for ‘hypothesis generation but insufficient for deriving meaningful conclusions’. This fourth dataset, the Sydney Diet Heart Study (SDHS)(14), reported a 49% increase in risk of death in the n-6 specific intervention group that …
