The recovery and re-evaluation of the old data on Sydney Diet Heart Study uncovers unexpected outcomes. However, interpret with care because things have changed since 1970s.

1. 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.
Page 1
[Updated February 2015]

2. 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

3. 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
Page 3

4. Methods (schematic)
Page 4
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”

5. 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
Page 5

6. Results, changes in diet
Page 6

7. Results, changes in cholesterol
Page 7
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

8. Results, coronary heart disease
mortality
Page 8
74 %
increased
risk in PUFA
group
PUFA
Safflower oil/margarine
Control Diet, high in SFA

9. Results, updated meta-analysis (1/2)
Page 9
When all PUFA studies are included, there is no difference in
cardiovascular disease mortality between the high SFA and the
PUFA groups

10. Results, updated meta-analysis (2/2)
Page 10
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

11. 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 result
Page 11

12. Why the reduction in cholesterol did not bring
about any benefit? My speculations (2/2)
Page 12
• 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?

13. 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.net13
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

14. Meta-analysis. My conclusions
Page 14
• 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

15. Welcome aboard!
15/02/201515
http://twitter.com/pronutritionist
http://www.facebook.com/pronutritionist
http://www.pronutritionist.net (Finnish)
http://www.pronutritionistblog.com (English)
Reijo Laatikainen, Authorized Nutritionist, MBA