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April 2013

Reanalysis of clinical trial data resurrected from the 1960s by US researchers adds weight to arguments against simplistic dietary recommendations regarding fats and oils.

Christopher Ramsden of the US National Institutes of Health (NIH) and his team used modern statistical techniques to review data that were not included in the original 1978 publication of results from the Sydney Diet Heart Study (Advances in Experimental Medicine and Biology 109:317–330). That clinical trial, which was conducted from 1966–1973, followed 458 men, aged 30 to 59 years, with a history of heart disease. Roughly half of the subjects were told to replace the saturated fats in their diets (from dairy and animal sources) with linoleic acid (LA; 18:2n-6). The other subjects served as the control group and were told not to change anything.

The original researchers noted an increased risk of early death from any cause among the LA (omega-6 group), but did not mine the data for further information. Ramsden and his team, however, compared death rates from all causes, cardiovascular disease (CVD), and coronary heart disease.

The NIH researchers found that the omega-6 group had a higher risk of death from all causes and not just from CVD and coronary heart disease:

  • The risk of all-cause death was 17.6% in the omega-6 group compared with 11.8% in the controls (which constitutes a hazard ratio, or HR, of 1.62)
  • The risk of death from CVD was 17.2% for the omega-6 group vs. 11% for the controls (for an HR of 1.70)
  • The risk of death from coronary heart disease was 16.3% in the omega-6 group vs. 10.1 in the controls (for an HR of 1.74).

“Advice to substitute vegetable oils rich in polyunsaturated fatty acids (PUFA) for animal fats rich in saturated fatty acids has been a cornerstone of worldwide dietary guidelines for the past half century,” the scientists note in their article. “When this advice originated in the 1960s, PUFA were regarded as a uniform molecular category with one relevant biological mechanism—the reduction in blood cholesterol. Omega-6 [LA] was the best-known dietary PUFA at the time. Therefore, the terms “PUFA” and “LA” were often used interchangeably when interpreting clinical trial results and delivering dietary advice.”

The researchers further note that thinking about the general category of PUFA has changed, with an increased recognition that PUFA constitute “multiple species of omega-3 and omega-6 PUFA, each with unique biochemical properties and perhaps divergent clinical cardiovascular effects.”

Reaction to the new study, which appeared in the British Medical Journal, has been mixed. In an editorial accompanying the BMJ article, Philip Calder of the University of Southampton, UK, asserted that the new look at old data “provides important information about the impact of high intakes of omega-6 PUFA, in particular linoleic acid, on cardiovascular mortality at a time when there is considerable debate on this question.”

An article by quotes a number of health professionals who urged caution in interpreting the findings.

“We now know that reducing artery inflammation—by boosting monounsaturated fat intake—helps stabilize artery walls and make them more resistant to damage,” said Catherine Collins, principal dietitian at St. George’s Hospital in London. “Should we be concerned about our current intake of omega-6 polyunsaturates—LA in particular? As a dietitian, I think not.”

Inneke Herreman, secretary general of IMACE, the European Margarine Association, noted that the intake level of 15% of daily energy from PUFA used in the Sydney Diet Heart Study was greater than current dietary recommendations by many international health agencies. These recommendations suggest a total PUFA intake of up to 11% of daily energy, with a total omega-6 consumption of up to 9% of daily energy.

“Actually, the available clinical trial evidence demonstrates clear benefits of omega-6 consumption on blood lipids levels and large other well-designed and more recent prospective cohort studies demonstrate that higher intakes of omega-6 PUFA or total PUFA are associated with reduced risks of coronary heart disease events,” said Herreman.

The NIH authors suggested that benefits ascribed to PUFA in general might actually be due to n-3 PUFA. “Since n-6 LA is the most abundant dietary PUFA, and edible oil sources with markedly different contents of fatty acids are commercially available [see Table 1], it is important to ascertain the benefits and risks specific to n-6 LA.”

Table 1


Content of n-6 LA and n-3 α-LNA in commercially available edible oilsa

Cooking oil   LA (g per 100 g of cooking oil)  

α-LNA (g per 100 g of cooking oil)

Vegetable oil*   Depends on specific oil   Depends on specific oil
Safflower†   74.6   0.0
Sunflower†   65.7   0.0
Cottonseed   51.5   0.0
Corn   53.5   0.2
Soybean   50.3   7.0
Canola   18.6  


Olive   9.8   0.8
Butter oil   2.3   1.4
Coconut   1.8   0.0

aAdapted from Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis, British Medical Journal, 2013. Data are from the US Department of Agriculture Nutrient Database. Note: Fatty acid contents of oils vary to some extent by season, latitude, and other conditions.

Abbreviations: n-6 LA=omega-6 linoleic acid; n-3 α-LNA=omega-3 α-linolenic acid.

*Food items labeled “vegetable oil” may contain one or more of the above oils.

†Varieties of safflower and sunflower oils with lower LA content are commercially available.