Sydney Diet Heart Study

re-evaluation 2013

Ramsden CE, Zamora D, Leelarthaepin B, Majchrzak-Hong SF, Faurot KR, Suchindran

CM, et al. 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;346:e8707.

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[Updated February 2015]

Sydney Diet Heart Study ended 1973, the same year when Opera House was opened. Now after 40 years, the actual results of the study are presented.

Photo: BigStockPhoto

Background

• Sydney Diet Heart Study was one of the key studies in Diet Heart Hypothesis. It was a randomized controlled study (RCT) with disease and mortality end points.

• For some mysterious reason, the original investigators never reported the cardiovascular outcomes of the study, but total mortality rates only. This is rather puzzling as the purpose of the study was to examine the effects of saturated fat (SFA) and polyunsaturated fat (PUFA) on heart disease

• Chris Ramsden with coworkers and one original investigator, Dr. Boonseng Leelarthaepin, recovered the original data and analyzed the heart disease mortality

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Methods (schematic)

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Randomization of patients (MI survivors/angina, n = 458) Low in SFA, high in PUFA diet.

Safflower oil and safflower oil based margarine* n=221

Control (as at baseline)(normal Aussie diet during 1960s) n=237

Median follow up: 39 monthsy. 1966→1973

*) “Increase PUFA intake to about 15% of food energy and to reduce ntake of SFA and dietary cholesterol to less than 10% of food energy and 300 mg per day, respectively”

Methods

• N= 458, males only. • All participants had symptomatic coronary heart disease at the

baseline (secondary prevention)• ~ 70% were smokers at baseline• Total cholesterol was ~ 280 mg/DL, ie. 7,2 mmol/l at baseline• 8,1 % in PUFA group and 5,5 % in SFA group had diabetes at

baseline• Blood pressure was around 137/89 mmHg in both groups• BMI was around 25 in both groups • SFA intake at baseline in both groups was around 16 % of

energy and PUFA around 6 % in both groups• Intake of carbs was around 40 % of energy at baseline in both

groups

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Results, changes in diet

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Results, changes in cholesterol

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Δ 7,8%

Total cholesterol was 7,8 % lower (ie. 0,59 mmol/l, or 23 mg/DL) in the PUFA group at 12 months. No data at the end of the study is available

Results, coronary heart disease mortality

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74 %increased risk in PUFA group

PUFA Safflower oil/margarine

Control Diet, high in SFA

Results, updated meta-analysis (1/2)

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When all PUFA studies are included, there is no difference in cardiovascular disease mortality between the high SFA and the PUFA groups

Results, updated meta-analysis (2/2)

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In the PUFA studies where considerable increase in alfa-linolenic (ALA) was also achieved, PUFA+ALA/EPA/DHA interventions delivered 21 % decrease in cardiovascular mortality

Why the reduction in cholesterol did not bring about any benefit? My speculations (1/2)

• There role of trans fat in the margarine (intervention group)– Margarines during 1970s contained huge amount of trans fat.

Median content of trans fat was in one review 21.8% (Beare-Rogers 1979). Currently margarines in Europe contain trans fat less than 1%

– High TFA content of margarine is one likely contributing factor

• Role of inflammation (Ω-6 FAs → increase in arachidonic acid levels → inflammation story)– Ramsden dismisses the whole concept of inflammation in the

discussion even if he has previously been a keen supporter– A recent meta-analysis of RCTs in humans: diet very high in linoleic

acid do not cause the increase in inflammation markers in humans (Johnson & Fritsche 2012)

– If anything, high doses of SFA are pro-inflammatory according to many recent meal studies and prospective cohorts

– Low grade inflammation is unlikely explanation for the resultPage 11

Why the reduction in cholesterol did not bring about any benefit? My speculations (2/2)

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• There role of oxidatized linoleic acid metabolites in ox-LDL (OXLAMs)– The number one explanation offered by the authors– This theory is pretty new and non-established and represents a

major shift in the thinking of cholesterol sceptics– The theory contradicts the fact that nuts, high in linoleic acid, do

consistently decrease the risk of cardiovascular disease in prospective cohorts studies and improve lipid profile in humans (Mozaffarian et al. 2011)

• Perhaps, just a coincidence? • Perhaps, the recovery of the old data was not bullet-

proof?

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Different realities 1970s vs NOW

Omega-6 linoleic acid intake as of total calories

Trans fat content of margarines

At time of Sydney Diet Heart Study, ie. 1970s

15.4% 21.8%

Currently 5.5% <1% (at least in most European countries)

www.pronutritionist.net

Beare-Rogers JL et al. The linoleic acid and trans fatty acids of margarines. Am J Clin Nutr. 1979 Sep;32(9):1805-9.

Harika RK, Eilander A, Alssema M, Osendarp SJ, Zock PL. Intake of Fatty Acids in General Populations Worldwide Does Not Meet Dietary Recommendations to Prevent Coronary Heart Disease: A Systematic Review of Data from 40 Countries. Ann Nutr Metab. 2013 Oct 29;63(3):229-238

Meta-analysis. My conclusions

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• Increasing both n-6 fatty acids intake to >15% of daily calories (ie. 70 grams of safflower oil) and trans fat intake is not beneficial to heart, at least if no other healthy dietary modifications are done at the same time

• Vegetable oils, like canola oil (“rapeseed oil” in Europe) or soybean oil, are higher in ALA and lower in linoleic acid, and therefore likely to improve cardiovascular prognosis

• Modern margarine are devoid of trans fat, at least in most European countries

• Nuts are, in spite of their high linoleic acid content, consistently linked to improved health outcomes both randomized trials and prospective cohorts and should be used regularly

Welcome aboard!

11/04/202315

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Reijo Laatikainen, Authorized Nutritionist, MBA