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n-6 Fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials

Ramsden CE, Hibbeln JR, Majchrzak SF, Davis JM. (2010) Br J Nutr. 2010 Dec;104(11):1586-600.PMID: 21118617   

Web URL: View this and other related abstracts on PubMed here


Randomised controlled trials (RCT) of mixed n-6 and n-3 PUFA diets, and meta-analyses of their CHD outcomes, have been considered decisive evidence in specifically advising consumption of 'at least 5-10 % of energy as n-6 PUFA'. Here we

(1) performed an extensive literature search and extracted detailed dietary and outcome data enabling a critical examination of all RCT that increased PUFA and reported relevant CHD outcomes;

(2) determined if dietary interventions increased n-6 PUFA with specificity, or increased both n-3 and n-6 PUFA (i.e. mixed n-3/n-6 PUFA diets);

(3) compared mixed n-3/n-6 PUFA to n-6 specific PUFA diets on relevant CHD outcomes in meta-analyses;

(4) evaluated the potential confounding role of trans-fatty acids (TFA).

n-3 PUFA intakes were increased substantially in four of eight datasets, and the n-6 PUFA linoleic acid was raised with specificity in four datasets. n-3 and n-6 PUFA replaced a combination of TFA and SFA in all eight datasets.

For non-fatal myocardial infarction (MI)+CHD death, the pooled risk reduction for mixed n-3/n-6 PUFA diets was 22 % (risk ratio (RR) 0·78; 95 % CI 0·65, 0·93) compared to an increased risk of 13 % for n-6 specific PUFA diets (RR 1·13; 95 % CI 0·84, 1·53). Risk of non-fatal MI+CHD death was significantly higher in n-6 specific PUFA diets compared to mixed n-3/n-6 PUFA diets (P = 0·02).

RCT that substituted n-6 PUFA for TFA and SFA without simultaneously increasing n-3 PUFA produced an increase in risk of death that approached statistical significance (RR 1·16; 95 % CI 0·95, 1·42).

Advice to specifically increase n-6 PUFA intake, based on mixed n-3/n-6 RCT data, is unlikely to provide the intended benefits, and may actually increase the risks of CHD and death.


These findings indicate that dietary advice to consume more 'polyunsaturated fats' (PUFA) by using vegetable oils to replace solid fats like butter, lard or hard margarines may actually increase the risk of heart disease if the vegetable oils only contain omega-6 PUFA. 

Previous studies relating dietary fat intake to heart health have failed to consider the very different effects of omega-6 versus omega-3 PUFA. (Broadly speaking, omega-6 PUFA tend to promote inflammation and blood clots, whereas omega-3 PUFA have the opposite effects).

These findings, published in the British Journal of Nutrition, are based on a detailed re-analysis of results from placebo-controlled treatment trials involving over 11,000 people in total.  This time, the scientists carefully separated the studies in which the dietary treatments contained omega-6 PUFA only, or a mixture of omega-3 and omega-6 PUFA. 

Only the 'mixed omega-3 and omega-6 PUFA' trials showed any benefits in reducing heart disease risk. By contrast, the use of omega-6 PUFA alone was associated with slightly worse heart disease outcomes. 

Omega-3 PUFA have repeatedly been shown to have benefits for heart health, but it is the longer-chain forms (EPA and DHA) - found in oily fish and seafood - which are the most valuable for heart health (as well as for the brain and immune system).  Only a few vegetable oils (such as flaxseed oil, rapeseed oil, or soybean oil) contain any omega-3 PUFA - although this is in a shorter-chain form (alpha-linolenic acid) that is not as beneficial to human health as EPA and DHA.  Many of the most commonly used vegetable oils (such as corn oil, sunflower oil or safflower oil) are high in omega 6 PUFA, and contain no omega-3 PUFA at all.