Sunday, November 24, 2013

The Rose Corn Oil Trial


Participants and Diets

80 patients with either a history of MI or angina, but < 70 years old and without heart failure and other non-cardiac disease were randomised to one of three groups: (1) a control group; (2) an olive oil group; and (3) a corn oil group 

“Patients in both oil groups were instructed to avoid fried foods, fatty meat, sausages, pastry, ice-cream, cheese, cakes (except plain sponge), etc. Milk, eggs, and butter were restricted. An oil supplement of 80 g./day was prescribed, to be taken in three equal doses at meal-times” 

While, “No advice on dietary fat was give to control patients.” 

Period
Olive Oil
Corn Oil
No. of Patients
g/day (Average)
No. of Patients
g/day (Average)
0-6 Months
24
73
28
74
6-12 Months
19
52
22
64
12-18 Months
16
47
19
62
18-24 Months
13
51
13
51
Mean
58
64

They were prescribed 80g of oil, but ended up consuming less (table 2).   Still, ~60 grams is a lot and I think they did pretty well.  Even though these oils supplied an additional several hundred calories, they adjusted their calorie intake and ended up eating a fairly similar amount when measured at 24 months (table 3). 

Group
No. of Patients
Carbs
Protein
Fat
Calories
Calories from Oil
Total Calories
Control
16
249
64
70
1,933
1,933
Olive Oil
12
216
49
45
1,505
540
2,045
Corn Oil
15
189
57
50
1,475
595
2,070

Results 

Total cholesterol levels significantly decreased in the corn oil group except during the 18-24 month period, which might be due to lower compliance (table 4).



Control
Olive Oil
Corn Oil
Mean
P
Mean
P
Mean
P
0-6m
4.4
> 0.5
3.5
> 0.7
-25.0
< 0.01
6-12m
0.3
> 0.8
12.0
> 0.4
-30.8
< 0.01
12-18m
-7.9
> 0.4
4.0
> 0.6
-30.3
< 0.01
18-24m
-2.8
> 0.8
-0.9
> 0.8
-19.9
< 0.20

When participants suffered a major cardiac event they were withdrawn from the study.  Therefore the total major cardiac events = the number of men with major cardiac events.  Participants who had other significant cardiac pain remained in the study

The following data is compiled from table 6.  The corn oil group had a higher incidence of major cardiac events (12 vs. 6), total CHD events (15 vs. 11) and CHD mortality/total mortality (5 vs. 1) compared to the control group.

Control
Olive
Corn
Sudden death
1
2
3
Fatal infarction
0
1
2
Definite infarction, non-fatal
3
4
3
Probable infarction, non-fatal
2
2
4
Total major cardiac events
6
9
12
Other significant cardiac pain
5
2
3
Removed from trial for other complications*
0
2
2
Lost to follow-up
2
3
1
Proportion in trial and free of major cardiac events, as percentage of those not removed from trial for other complications nor lost to follow-up**
75
57
52

Olive oil is generally considered healthy, so the results from that group are surprising.  The instruction to avoid certain junk food in the oil groups would be expected to improve diet quality.  However, both oil groups had a higher incidence of major CHD events than the control group suggesting this was offset by the oil supplements.  This may suggest an adverse effect of high refined oil consumption, perhaps compounded by the poor diet quality of the participants (indicated by low protein intake), making them more sensitive to nutrient dilution and any potential adverse effects of high oil consumption

* One patient in olive oil for gangrene, one in corn oil for pulmonary embolism and one each for type 2 diabetes.  The incidence of type 2 diabetes in the oil groups is only N of 2, but the temporal relationship deserves attention: "One of them already had mild diabetes, but glycosuria increased considerably soon after he started oil.  Oil was stopped and glycosuria disappeared.  Oil was restarted, but was stopped a month later because heavy glycosuria recurred.  The other patient, not a previously recognized diabetic, developed glycosuria with a diabetic glucose-tolerance test a few weeks after starting oil."  

** “The likelihood that the difference between the control and corn-oil groups was due to chance is 0.05-0.1”

Sunday, November 17, 2013

The Evidence Against Saturated Fat

The Heart Foundation’s Summary of Evidence 

Shortly after Catalyst aired the Heart Foundation responded to the program.  The response included links to a document called ‘Summary of evidence. Dietary fats and dietary cholesterol for cardiovascular health’ (2009). 

They discuss many things in this document and unfortunately their evidence often comes from studies where the endpoints are blood lipids rather than cardiovascular events, cardiovascular mortality or better still, total mortality.  I’m just going to keep it to SFA >> CVD and replacing SFA with PUFA for CVD. 

In a summary we get this: 

Evidence
Level of evidence
Saturated FA (SFA)
·         SFA intake is associated with CHD5
III–2
·         Replacing SFA with cis-unsaturated FA has a greater positive influence on CHD risk than replacing SFA with carbohydrates (CHO)6,7
I
·         Replacing SFA with n-6 PUFA to achieve a ratio of PUFA to SFA of greater than one will reduce the risk of CHD (1999 evidence statement retained)2
Good

The rest of the stuff in the table for SFA was about SFAs and LDL-C and a lack of evidence for associations between SFA with stroke and “the susceptibility to thrombosis and arrhythmia or blood pressure” 

Reference 5 is a review for FSANZ was only included observational studies looking at SFA and CVD and clinical trials looking at SFA and blood lipids.  No randomised controlled trials.  Also on their scale the level of evidence (III-2) is quite poor 

Reference 6 is a review by Mozzafarian.  The SFA section has some observational studies, some SFA >> LDL-C studies and a short section on clinical trials: 

“Results of randomized trials replacing saturated fat with polyunsaturated fat (including two trials that added a high proportion of alpha-linolenic acid, an omega-3 polyunsaturated fat) have been inconsistent; no significant effect was seen in four studies [40,41,43,44], CHD risk was reduced in one study [45,46], and total mortality was increased in another [42] (Table 1).” 

Reference 7 is a meta-analysis looking at how fatty acids and carbohydrates effect blood lipids.  Nothing on actual disease 

Reference 2 is to a previous evidence statement in 1999, which I can’t seem to find.  If it’s anything to go by, its referenced here as well: “The consumption of SFA and increased LDL-C levels are associated with an increase in CHD,2,24 although the strength of this association has recently been questioned.5.  Reference 24 is the Nutrient Reference Values (NRV) for Australia and New Zealand.  It has a small section on SFA and CVD, which only consists of the diet heart hypothesis: there is evidence that SFA increased LDL-C and evidence that LDL-C is associated with an increased risk of CVD.  Very appropriately they finish up with: “Whether dietary intervention would bring about equivalent lowering of CHD mortality is unknown.” 

On a somewhat related note, in the section ‘Limit intake of foods high in saturated fat’, the new Australian dietary guidelines just mention SFA >> LDL-C, but then there’s nothing about SFA >> CVD.  They then mention that omega 3s are therapeutic, which is not only irrelevant to the section but also irrelevant to the debate of whether to replace SFA with omega 6s 

So far, it’s just observational studies showing an association between SFA and CVD, studies that find SFA increases LDL-C and a short review of a few randomised trials with no significant effects and inconsistent results.  Not too persuasive. 

After 2009 

However, in the response to Catalyst the Heart Foundation mentioned that some further evidence in support of their position has been published since the 2009 Position Statement which includes: 

The Cochrane Database of Systematic Reviews (Hooper et al), 2011, Reduced or modified dietary fat for preventing cardiovascular disease.

Mozaffarian et al, 2010, Effects on Coronary Heart Disease of Increasing Polyunsaturated Fat in Place of Saturated Fat: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Jakobsen et al, 2009, Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies

But they didn’t reference the studies below, what a surprise 

Ramsden, et al., 2010. n-6 Fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials

Siri-Tarino, et al., 2010. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease.

The Meta-Analyses of Clinical Trials 

But let’s ignore Jakobsen et al and Siri-Tarino, et al because both are observational 

The Cochrane review found reducing saturated fat by reducing and/or modifying dietary fat reduced the risk of cardiovascular events by 14%” but “There were no clear effects of dietary fat changes on total mortality or cardiovascular mortality” 

Similarly, Mozzafarian, et al. found Combining all trials, the pooled risk reduction for CHD events was 19%” but “In secondary analyses restricted to CHD mortality alone, the pooled RR was 0.80 (95% CI 0.65–0.98). Evaluating total mortality due to all causes (2,472 events), the pooled RR was 0.98 (95% CI 0.89–1.08).” 

Whereas Ramsden, et al. found For non-fatal myocardial infarction (MI)+CHD death, the pooled risk reduction for mixed n-3/n-6 PUFA diets was 22% compared to an increased risk of 13% for n-6 specific PUFA diets. 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).” 

In other words neither study referenced by the Heart Foundation found that replacing SFA with PUFA lowered total mortality, whereas the findings of Ramsden, et al. suggest that replacing SFA with omega 6 is likely to increase total mortality (seeing as both SFA and TFA were replaced) 

Here are the trials (that replaced SFA with PUFA) the meta-analyses included.  I’m also aware of the Anti-Coronary Club and St. Vincent's Hospital Study, does anyone know of any others? 


Cochrane 2012
Mozzafarian 2010
Ramsden 2010
Rose Corn Oil 1965
X

X
Anti-Coronary Club 1966



Los Angeles Veterans 1968
X
X
X
Medical Research Council Trial 1968
X
X
X
Oslo Diet-Heart Study 1970
X
X
X
St. Vincent’s Hospital Study 1973



Sydney Diet Heart Study 1978
X

X
Finnish Mental Hospital 1983

X

Minnesota Coronary Survey 1989
X
X
X
Diet and Reinfarction Trial 1989
X
X

St. Thomas Atherosclerosis Regression Study 1992
X
X
X

I will discuss each of these trials in future blog posts