Ramsden CE, Hibbeln JR, Majchrzak-Hong SF (2011) World Rev Nutr Diet. 2011;102:30-43. Epub 2011 Aug 5.
Advice to maintain or increase consumption of the omega-6 polyunsaturated fatty acid (n–6 PUFA) linoleic acid (LA) should be derived from interventional and observational trials evaluating the specific effects of dietary LA, rather than effects of n–3 PUFAs or total PUFAs. Failure to make a clear distinction among PUFA species may result in inadvertently attributing health effects of n–3 PUFAs to linoleic acid. Pooled analyses of randomized controlled trials (RCTs) of clinical CHD events  and intermediate risk factors  and pooled analyses of nonrandomized prospective observational trials of clinical CHD events  are often cited as providing strong concordant evidence [1, 4] that LA is cardioprotective. These pooled analyses [1–3] form the primary basis for recent population-wide advice to maintain or increase n–6 PUFA [5–7]. However, total PUFA rather than n–6 LA, was defined as the independent variable for statistical calculations in all three pooled analyses [1–3] (table 1), then interpreted as attributable to LA [4–8]. In this paper we: (1) establish that a clear distinction was not made between n–3 and n–6 PUFAs in pooled analyses of randomized and nonrandomized trials (tables 2, ?,3),3), (2) report whether a clear distinction was made between n–3 and n–6 PUFAs in each individual trial before pooling, (3) assess strengths and limitations of randomized and nonrandomized study designs for disentangling respective intakes of n–6 and n–3 PUFA species, and (4) highlight the necessity of making a clear distinction between PUFA species for interpreting the results of clinical trials and formulating dietary guidelines.