Heart Studyshould have been included despite the fact thatthe reduction in cardiovascular disease (CVD) events in this studyis virtually always attributed to the increased intake in alpha-linolenic acid, not the reduced intake of linoleic acid. It is unclearwhy confounding in Lyon is acceptable but confounding in Oslo isnot. The Sydney Heart Studywas excluded because it did notreport cardiovascular disease endpoints, only total mortality.Ramsden et al are correct that Rose et al.,should have beenincluded in the meta-analysis. In this 2-year study, 54 heartpatients were instructed to reduce animal fats and to substitute80g of either olive oil (
26) or corn oil (
28) per day. Acontrol group (
26) made no changes in their diets. Majorcoronary events occurred in 43%, 48% and 25% of each group,respectively. A chi-square test of these proportions gives a
0.31,and the most relevant comparison (between the two oil interven-tions) found no difference at all. Hence this study did not showincreased CV events associated with LA intake as Ramsden et al.indicate. Although Rose should have been included in the meta-analysis, it would not have altered the outcome because of both itslack of effect and its small sample size. In 1995, Gordonpublished a similar meta-analysis and reached the same conclusion:higher PUFA, lower saturated fat diets reduce CV events.The second issue raised by Ramsden et al. is that diets higher inLA lower the omega-3 index, an emerging erythrocyte-based markerof CV risk. Oddly, none of the three studies theyrefer to reported effects on the omega-3 index. Two were 30-daystudies in pigs examining the effects of varying LA:ALA ratioson cardiacand brainphospholipid fatty acid composition.
Neither assessed any CVD endpoint. The only human studycitedexamined the effects of 2,4-week treatment periods onplasma phospholipid fatty acid composition after recommendingdiets high (10% en) or low (3.8% en) in LA to healthy volunteers. If one uses the plasma phospholipid EPA+DHA content as a surrogateof the omega-3 index, concerns about the study design emerge.Presumablyowingtothe 2-weekpre-studyrestrictiononﬁshintake,phospholipid EPA+DHA levels were slowly decreasing throughoutthe study regardless of LA or ALA intake. With two variables (LA:ALAratios and EPA+DHA washout), the effects of the former alone aredifﬁcult to interpret. Nevertheless, others have reported that higherLA:ALA ratios do modestly lower membrane EPA and DHA levels. The relevant question in this context, however, is whether anLA-induced diminution of the omega-3 index increases risk for CVDor not; the other evidence cited in the review suggest that it maynot. CVD is a multifactorial disease, and changes in one risk factormay be offset by corresponding changes in others. The best way toraise the omega-3 index is by eating more EPA and DHA, not byeating less LA. The former has been shown to reduce risk for CVDwhereas the latter has not.
 J.M. Woodhill, A.J. Palmer, B. Leelarthaepin, et al., Low fat, lowcholesterol dietin secondary prevention of coronary heart disease, Adv. Exp. Med. Biol. 109(1978) 317–330. G.A. Rose, W.B. Thomson, R.T. Williams, Corn oil in the treatment of ischemicheart disease, Br. Med. J. 1 (1965) 1531–1533. M. de Lorgeril, P. Salen, J.L. Martin, et al., Mediterranean diet, traditional riskfactors, and the rate of cardiovascular complications after myocardialinfarction: ﬁnal report of the Lyon Diet Heart Study, Circulation 99 (1999)779–785. P. Leren, The effect of plasma cholesterol lowering diet in male survivors of myocardial infarction. A controlled clinical trial, Acta Med. Scand. Suppl. 466(1966) 1–92. D.J. Gordon, Lowering cholesterol and total mortality, in: B.M. Rifkin (Ed.),Lowering Cholesterol in High-Risk Individuals and Populations, MarcelDekker, Inc., New York, 1995, pp. 33–48. W.S. Harris, The omega-3 index as a risk factor for coronary heart disease, Am. J. Clin. Nutr. 87 (2008) 1997S–2002S. S. Ghosh, E.M. Novak, S.M. Innis, Cardiac proinﬂammatory pathways arealtered with different dietary n-6 linoleic to n-3 alpha-linolenic acid ratios innormal, fat-fed pigs, Am. J. Physiol. Heart Circ. Physiol. 293 (2007)H2919–H2927. E.M. Novak, R.A. Dyer, S.M. Innis, High dietary omega-6 fatty acidscontribute to reduced docosahexaenoic acid in the developingbrain and inhibit secondary neurite growth, Brain Res. 1237 (2008) 136–145. Y.A. Liou, D.J. King, D. Zibrik, et al., Decreasing linoleic acid withconstant alpha-linolenic acid in dietary fats increases (n-3) eicosapentaenoicacid in plasma phospholipids in healthy men, J. Nutr. 137 (2007) 945–952. E. Mantzioris, M.J. James, R.A. Gibson, et al., Dietary substitution with an
-linolenic acid-rich vegetable oil increases eicosapentaenoic acid concentra-tions in tissues, Am. J. Clin. Nutr. 59 (1994) 1304–1309.
William S. Harris
Sanford Research/USD, 1100 East 21st St, Suite 700, Sioux Falls,SD 57105, USAE-mail address:
What happened to do no harm? The issue of dietary omega-6fatty acids
In 1999, scientists from around the globe gathered to addressdietary recommendations for omega-3 and omega-6 fatty acids.Their recommendation emphasized the importance of reducingomega-6 fatty acids in order to reduce adverse health effects of excesses of arachidonic acid (AA) and its eicosanoid products.Therefore, they set an upper limit for linoleic acid (LA), to no morethan6.67g/day,basedona2000kcaldietof3.0%ofenergy.Yet,basedon the current series of papers published on LA[2–4], one might beled to believe there has been a substantial body of evidence to refutethe recommendation, which is not the case. The research cited istaken out of context and/or is based on very small studies, many of which were published over a decade ago, as described below.
Comments on three papers published in PLEFA September 2008(vol. 79, issue 3)
The health implications of changing linoleic acid intakes by JayWhelan (pp. 165–167).Linoleic acid and coronary heart disease by William S. Harris(pp. 169–171).Too much linoleic acid promotes inﬂammation
doesn’t it? byKevin L. Fritsche (173–175).
: Evelyn Tribole
1100 Quail Street, Suite 111,Newport Beach, CA 92660, USA.Fritschedescribes the CHIANTI study by Ferrucci et al.,
as an example of no adverse impact on inﬂammation from eatingtoo much LA. Subjects with the highest quartile of plasmaarachidonic acid levels had lower pro-inﬂammatory markers andhigher anti-inﬂammatory markers. But an important detail fromthis study is ignored
the subjects from this Mediterraneanregion eat a low LA diet, averaging 7g/day. In this context, it isnot surprising that plasma AA was associated with beneﬁcialinﬂammation biomarkers
because it does so in the presence of eating a balanced proportion of omega-6 and omega-3 fatty acids.The results of this study support the beneﬁts of eating a lower LAdiet!Harrisconcludes that, ‘‘Reducing LA intakes to less than 5%energy would be more likely to increase, not decrease, risk for
ARTICLE IN PRESS
Letters to the Editor / Prostaglandins, Leukotrienes and Essential Fatty Acids 80 (2009) 77–79