ROUND-UP: Dietary fats and heart disease (BMJ*) – experts respond

Wed Feb 6, 2013

EMBARGOED LIFTED at 10.30am AEDT Wednesday 6 February, 2013

Advice from health authorities to replace animal fats with plant-based alternatives could be misguided, say US and Australian researchers who reanalysed data from the Sydney Diet Heart Study, originally conducted in the 1960s and 70s. The study of 458 men with heart problems suggests that replacing animal-derived saturated fats in the diet with omega 6 plant-derived polyunsaturated fats increases the risk of premature death.

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Bill Shrapnel is Deputy Chairman of the Sydney University Nutrition Research Foundation

“The authors state that the study assessed the effects of replacing saturated fat in the diet with omega 6 polyunsaturated fats, but it doesn’t.

The study used Miracle margarine as a source of polyunsaturated fat. In the 1960s, when this study began, Miracle margarine contained approximately 15% trans fatty acids, which have the worst effect on heart disease risk of any fat. The adverse effect of the intervention in this study was almost certainly due to the increase in trans fatty acids in the diet.

Recent, well conducted studies indicate that replacing saturated fat with polyunsaturated fats lowers heart disease risk and this is widely accepted. Trans fatty acids were largely removed from Australian margarines in the mid-1990s when their adverse effects on heart health became apparent.”

Disclosure: Bill Shrapnel consults to Goodman Fielder and the Australian Oilseeds Federation. He previously consulted to Unilever (14 years), makers of Miracle margarine.


Associate Professor Barbara Meyer is Director, Metabolic Research Centre, at the University of Wollongong and President of the Nutrition Society of Australia.

“This study highlights that excessive intakes (15% of energy) of linoleic acid (LA) increases all cardiovascular mortality.  Our research from the National Nutrition Survey (NNS) from 1995 (published in Meyer et al 2003; Howe et al 2006) has shown that Australians consume an average LA intake of 11 grams per day (approximately 5% of energy = one third of the excessive intakes) and that only a small proportion of Australians may be consuming LA intakes at the excessive intake level. Foods that are rich in LA are vegetable oils like safflower oil and margarines made from those oils and approximately 22% of LA intakes in the Australian diet comes from fats and oils. However, even though another food group called “cereal and cereal based products” (e.g. bread, cereals, cakes, biscuits, pies, pizza, muffins etc) contain lower amounts of LA per gram of food, approximately 30% of LA comes these processed foods in the diet. For Australians to reduce their consumption of LA, not only should they switch from using safflower oil to olive or canola oil (primarily monounsaturated fat), they should also reduce their intakes of processed foods like biscuits. The new NNS currently being conducted in Australia will enable us to see the current proportion of Australians that may be consuming these excessive LA intakes.”

Meyer BJ, Mann NJ, Lewis JL, Milligan GC, Sinclair AJ, Howe PRC. Dietary intakes and food sources of omega-6 and omega-3 polyunsaturated fatty acids.  Lipids 2003:38;391-398.

Howe PRC, Meyer BJ, Record S, Baghurst K. Dietary intake of long chain omega-3 polyunsaturated fatty acids: contribution of meat sources. Nutrition. 2006;22(1):47-53

Disclosure: no conflict of interest


Professor Peter Clifton is Baker IDI’s Head of Nutritional Interventions

“This is a very small study with only 63 total deaths. The 5.8% difference between groups for total mortality represents  a difference of 10 deaths between groups (p=0.051) computed from the %  deaths which does not meet conventional statistical significance. Figure 1 though only shows a difference in 6 deaths between groups.  Certainly there is no evidence of benefit  but the evidence of harm is relatively weak.

Although dismissed by the authors trans fats are likely to be responsible for the lack of benefit. The margarine would have contained  at least 20% trans fatty acids and if the participants were eating 25g/day of margarine then they would be consuming 5g of trans which might represent about 2% of calories. From the Nurses Health study this could reduce heart disease by 40-50% which would almost completely remove the apparent  increased risk from the N6 margarines. The more margarine eaten the greater the risk. The test margarine would have mostly supplanted butter rather than other margarines. The fall in total cholesterol seen not only reflects a fall in LDL cholesterol but also a trans induced fall in HDL cholesterol.

The fact that an increase in PUFA in the control group (90% of which would have been N6) was not associated with harm suggests  the findings in the intervention group are confounded by the trans fats.”

Disclosure: Peter previously consulted for Meadow Lea and Unilever on N6-rich margarines but has not worked with them in the last 10 years.


Professor Mark Wahlqvist is Emeritus Professor of Medicine, Monash University and Past President of the International Union of Nutritional Sciences

“The belated report of the outcomes of the Sydney Diet Heart Study of 1966-1973 is both welcome and disturbing. This is not only for  what it means for the findings about  a major characteristic of contemporary Western diets , but also of the medical science culture  in regard to  cardiovascular disease in  Australia (and elsewhere ) which prevailed  for a generation or moreAs  a young medical graduate at the time, who had ,as a student , developed an interest in the inflammatory basis of coronary heart disease , I  followed the work of the original investigators and  was impressed with their  reservations and call for well-designed  research  to evaluate the major shift in dietary fat intake being espoused  by lipid scientists and the non-dairy food industry of the day. Polyunsaturated fatty acids (PUFA) were promoted as an answer to the increase in coronary heart disease which had become epidemic.

“But in 1978, the chief investigator, Prof Ralph Blackett, and colleagues made clear and published that all-cause mortality was increased when the dietary PUFAs known as omega-6 or n-6 were increased. This was disregarded in favour of the unproven possibility that the particular omega-6 linoleic acid (and implicitly the omega-6 arachidonic acid) was responsible for the observed effects. The plausibility of this position was provided by evidence that these PUFAs could not be made by and were therefore essential for humans. The interpretive advantage of the SDHS was that safflower oil was used as a linoleic acid source and that it did not increase omega-3 fatty acids ; omega-3s  have, with time, been found to be essential in their own right and, as we now know, can offset adverse effects of omega-6  PUFA.

“As time went on, more Australian work raised questions about linoleic acid, particularly as a risk factor for the severity and extent of coronary artery disease assessed during coronary angiography in Melbourne published by Hodgson and colleagues. Hydrogenated margarines with their trans fatty acids derived from PUFAs were also implicated. But advice from the key expert committees was restricted to the trans fatty acids, circumventing the concerns about omega-6. The WHO regional committee for the Asia Pacific, which I chaired, recommended  in  a food-based approach to dietary fat, that it come preferably from a variety of sources and, when from plants, be unrefined from seeds, nuts or fruits (like olives and avocado); that the same should apply to oils produced from them; and that fats and oils should be labelled as to source. Yet apologists for omega-6 rich margarines and oils have lobbied against this, using Taiwan as an example of a population faring well in health with a high intake of linoleic acid. Studies which link linoleic acid itself to health outcomes are not available and, if they were, it would be in the context of a totally different diet to the West, with a high intake of fish and soy, not only with plentiful omega-3 fatty acids, but many other protective food components as well.

“Now the long unpublished data on linoleic acid from the SDHS has been analysed by an international team and linoleic acid found not only to increase all-cause, but cardiovascular mortality, and to be consistent with studies of a similar kind. Serious questions must now be asked about why it has taken so long to unearth and publish this crucial information about a major change in the human diet which took place as recently as the 1960s.”


[*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, Ramsden et al., BMJ 2013;346:e8707 doi: 10.1136/bmj.e8707]

Additional comments and analysis of statistical methods provided by our colleagues from the UK SMC:

Science Media Centre Round-Up


Expert reaction to research into dietary fats and heart disease as published in the BMJ*

Before The Headlines


Title, Date of Publication & Journal

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. BMJ 2013

Claim supported by evidence?

This paper takes a small study published in 1978 and adds some clarification of the original findings.


The paper does suggest the claim that data from the trial tend to indicate that a specific source of unsaturated fat (n-6 fatty acids) might lead to a slightly increased cardiovascular risk.


The paper does not provide evidence for the claim that substitution of “any polyunsaturated fatty acids in general” for saturated fats leads to a different cardiovascular risk.


Overall, there is no new base of evidence. The paper does not alter our understanding of the possible relationship between diet and cardiovascular risk.



  • The Sydney DHS had been performed between 1966 and 1973. Its data (e.g. death rates) had been reported, but not up to the current scientific standard. Therefore, this study had not been incorporated in existing meta-analyses.
  • There already exists a solid based of meta-analysis on the relationship between fatty acids and health. The inclusion of the Sydney DHS is a useful exercise, but it does not turn around the overall evidence that already existed.
  • In the new study, the use of n-6 fatty acids was related to increased cardiovascular risks. Previous meta-analysis suggested:
    • A small reduction in cardiovascular risk is observed when more unsaturated fat is digested; however the result appears to be driven by so called n-3 fatty acids.
    • When using n-6 fatty acids only, there was so far no evidence of cardiovascular risk reduction or risk increase. 
      There is a meta-analysis available from 2010 by the same authors as the current paper that concluded in 2010: “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.”
      Hence the new paper raises no new claim.
  • The authors describe a potential mechanistic model of how the n-6 fatty acids may contribute to cardiovascular risk. This model cannot be generalised to other unsaturated fatty acids.
  • I had no access to the supplementary material so could not perform a thorough review of the statistical methodology; but overall the description of the statistical methods appears to be adequate for the type of the paper.
  • It is generally desirable to make results from all clinical trials publically available. However the current paper is not an example of that as the reporting of the Sydney diet heart study was not intentionally hidden, as it is the case for some drug trials.


Study Conclusions

  • For reporting this new result, specific attention should be paid to the difference of available unsaturated fats, as the combined evidence suggests different impacts of n-3 vs. n-6 fatty acids on cardiovascular risks.



  • The new data, originating from an old study contribute to the overall evidence for the different portions of fats in the diet.
  • The study was performed in men, 30-59, with coronary heart disease. It is not clear whether the results can be generalised to other populations, specifically to healthy people.
  • The general scientific standard of the paper appears to be adequate.
  • The claims in the paper are not new or at odds with existing evidence. They may be different to existing nutrition guidances.


Before The Headlines is a service provided to the SMC by volunteer statisticians: members of the Royal Statistical Society (RSS), Statisticians in the Pharmaceutical Industry(PSI) and experienced statisticians in academia and research.  A list of contributors, including affiliations, is available at


Prof Iain Broom, Research Professor, Centre for Obesity Research and Epidemiology (CORE), Robert Gordon University, said:

“My comments are wider than the current paper’s focus, which is solely in n-6 PUFA intake, but I would say that the outcomes are not in the least surprising and the paper does carry out an exhaustive analyses of the data now available.  In addition the authors do come up with plausible explanations as to the reason for the increased CVD mortality in the shape of more easily oxidisable low density lipoprotein particles (LDL).  I find it incredible that the CVD data were not published in the original paper.  This paper could have repercussions amongst both Governments and the food industry where recommendations may not have been appropriate, and may also have implications for the American Heart Association’s recent suggestion of increasing n-6 PUFA dietary content.”

Prof David Spiegelhalter, Winton Professor of The Public Understanding of Risk, University of Cambridge, said:

“These are typically 50-year-old men, mainly smokers, who have had a heart attack already, and there were only 63 deaths altogether (35 in the control vs 28 in the intervention group) with barely statistically significant results.  So I would not want to get very excited about this study on its own, but it does add some evidence to a complex issue.”

Catherine Collins, Principal Dietitian, St George’s Hospital London, said:

“This article re-examines dietary information given 40years ago to young men who had had a major heart event at a young age (30-59y) despite being normal body weight. This re-analysis shows that a high intake of omega-6 polyunsaturated fat (derived from safflower oil – an oil rarely used in the UK but available in healthfood shops) – actually increased the risk of death from a second cardiac event, even though changing dietary fat choice reduced saturated fat intake and blood cholesterol levels.

“Our knowledge of diet and heart disease has become much more sophisticated over the intervening 40 years. We now know that reducing artery inflammation – by boosting monounsaturated fat intake (from rapeseed oil and olive oils) helps stabilise artery walls and make them more resistant to damage. More mono-unsaturates, with a modest amount of polyunsaturated fats, also helps to lower blood cholesterol levels. This together with other aspects of the Mediterranean diet – more dietary fibres, less salt, and more fruit and vegetable intake along with modest alcohol, are all part of the robust heart-healthy ‘portfolio’ of foods relatively unknown 40 years ago.

“Should we be concerned about our current intake of omega-6 polyunsaturates- linoleic acid in particular? As a Dietitian I think not. We already have a healthier diet than 40 years ago, and for those with resistant cholesterol levels medication can help regulate.

“Our diet is now naturally higher in mono-unsaturates which is protective against omega-6 fats, but for the older generation who still choose polyunsaturated margarines, and fry foods regularly in corn or sunflower oils, a change to ‘vegetable oil’ (rapeseed oil ) is all that is necessary to limit risk from linoleic acid. After all, it’s all about proportion of each fat in the diet, not absolute amounts.

“Almost 70% of subjects in both groups were smokers, which was common at the time but less so now with only 20% of the population smoking Why is this important? Smoking damages your arteries, and so in these subjects having a high polyunsaturated fat intake – naturally less stable than other fats – the risk of damage and health effects from the combination of smoking and linoleic acid intake would have been enhanced.”

Prof Tom Sanders, Head of Diabetes & Nutritional Sciences Division, King’s College London, said:

“This is data dredging of a study conducted many years ago in Australia. It has little relevance to diets today. It reports the results of a study conducted in Sydney where subjects were asked to consume large amounts of safflower oil. The study was stopped because of adverse effects – I heard about this from a colleague whose brother was involved in the trial more than 30 years ago! Hopefully science has moved on. Firstly, the study was enormously underpowered to detect any meaningful outcome with only 458 men. Assuming a high mortality of 12% per year, the chances of detecting meaningful differences in mortality are small, particularly when follow-up is short.

“A meta-analysis of other randomised controlled trials including n–6 PUFA which has been published in the last few years refutes this (including a Cochrane review by Lee Hooper). It shows that dietary advice to replace saturated fatty acids with polyunsaturated fatty acids reduces incident coronary heart disease (CHD; Mozaffarian et al. Plos Med The prospective cohort studies also show benefit of replacing saturated fatty acids with polyunsaturated fatty acids (mainly linoleic acid).

“Safflower oil is rather unusual in that it contains mainly linoleic acid whereas commonly used vegetable oils such as soybean oil and rapeseed oil contain both linoleic and linolenic acid. The evidence for the benefits of long-chain n-3 PUFA have also received a drubbing by the systematic reviewers in JAMA in September. Furthermore, in support of the benefits of n-6 PUFA is a current report from the Oxford EPIC group which shows a 32% reduction in incident CHD in vegetarians (published in the current AJCN). Vegetarians have high intakes of n-6 PUFA, much lower blood cholesterol concentrations and slightly lower blood pressure.

“You need to look carefully at the paper because the dietary intervention was as a supplement of margarine and oil rather than the type of dietary modification currently advocated for cardiovascular disease (CVD) prevention such as the DASH diet or the NICE guidelines. We do not know the level of trans fatty acids in the margarine, which are now known to increase risk of heart disease. Current advice should be based on present knowledge and not veered off course by this new study. Taking extra fat on board in patients with CHD is not a good idea. Current dietary guidelines focus on decreasing sources of saturated fat and partially replacing saturated with unsaturated fatty acids i.e. vegetable oils rather than animal fats.”

Prof Brian Ratcliffe, Professor of Nutrition, Robert Gordon University, Aberdeen, said:

“This paper does not provide evidence for changes to the current recommendations for a healthy diet.  It provides interesting additional information regarding the role of dietary fats in the development of cardiovascular diseases.  The study was specifically a secondary prevention and it may have limited relevance to primary prevention. 

“Nevertheless, it is worth pointing out that current advice in the UK (dating back to the COMA report of 1994) does not recommend replacing saturated fatty acids with n-6 PUFA.  It was recommended that there should be no increase in the average intake of n-6 PUFA and that the proportion of the population consuming this type of fat in excess of 10% of energy intake should not increase, and the target is about 6% of energy intake.  Subjects in this study achieved PUFA levels of 15% of food energy.  Also, it is recommended not to exceed a PUFA:SFA ratio of 1 whereas in this study, in the intervention group at follow up, the ratio was 1.7. 

“It has been known for some time that there is potentially a problem with high intakes of linoleic acid leading to oxidised linoleic acid metabolites that would be potentially atherogenic.  The authors of this latest paper suggest that this may indeed be the mechanism that has contributed to the increased mortality from cardiovascular diseases seen in the study. 

“It is generally assumed that eating a healthy diet involves achieving a balance of n-6 and n-3 PUFA and many authorities have suggested that diets in developed countries are too imbalanced in favour of n-6 PUFA.  It is also worth pointing out that this study used a safflower oil with a particularly high content of linoleic acid (n-6 PUFA) and the level of this fatty acid varies considerably in commercially available safflower oils.”