Sunday, December 15, 2013

The Medical Research Council Trial

Studies Associated with the Trial

Controlled trial of soya-bean oil in myocardial infarction: report of a research committee to the medical research council (1968) [1]
Dietary Aspects of a Controlled Trial of Soya-bean Oil in Myocardial Infarction (1969) [2]
Cancer among men on cholesterol-lowering diets: Experience from five clinical trials (1971) [3]
Letter: Are PUFA harmful? (1974) [4] 

Participants and Diets 

393 men who recently had a heart attack were randomised to two groups: an experimental group and a control group.  The groups were similar at baseline [1] 

The experimental group was asked to eat a diet low in SFA and take 85g of soybean oil daily, where “at least 43 g. of soya-bean oil daily had to be taken unheated, and it was often drunk with fruit juice”.  In addition “up to 35 g. of other fat per day was also allowed. 14 g. of this was taken as a moderately unsaturated margarine (’ Blue Band ’). Foods allowed daily included lean meat (up to 85 g.), any fish (which was encouraged), skimmed milk, and clear soups. Foods forbidden included butter, other margarines, cooking-fat, other oils, fat meat, whole milk, cheese, egg yolk, and most biscuits and cakes.” [1] [2] 

The control group remained on their regular diet, although they did seem to reduce fried foods after having their heart attack [1] 

73 in the experimental group and 90 in the control group were placed on a reduced carbohydrate diet to lose weight.  5 in the experimental group and 6 in the control group were placed on a very low calorie diet (1,000 calories) for weight loss. [1] 

On average, the experimental group consumed 80g of soybean oil per day and 40g from other fats.  The SFA:PUFA ratio was 1:2 in the experimental group and 6:1 in the control group.  Calories, protein, carbohydrate and sugar intakes were almost identical, and the experimental group was lower in cholesterol (258mg vs. 588mg) and slightly lower in calcium (808 mg vs. 930 mg) and vitamin A (by 1,000 IU) [1] 

Results 

Linoleic acid levels in adipose tissue were on average 19.0% among those in the experimental group with good adherence compared to 9.6 with poor adherence [2] 

Total Cholesterol (mg/dl)
Experimental
Control
Baseline
272
273
6 Months
213
259
6 Years
239
269
[1] 

The end-points in the trial were relapses, which included things like angina, heart attacks and deaths from cardiovascular disease.  There were no significant differences between the groups.  The difference in first relapses was due to non-major relapses like angina.  Unfortunately the number of major relapses wasn't reported, instead the number of 'men who had a major relapse at any time during trial' was, which is the closest measure and was slightly lower in the experimental group 

Experimental
Control
Number of men
199
194
First relapses
62
74
Major
40
39
Fatal
15
14
Non-fatal definite reinfarctions
25
25
Other non-fatal relapses
22
35
Men who had a major relapse at any time during trial
45
51
Fatal
25
25
Non-fatal definite reinfarctions
20
26
All deaths from cardiovascular disease
27*
25
* “1 death was from subarachnoid haemorrhage and 1 from cerebral embolism” [1] 

There were also 6 deaths from cancer in the control group compared to only 1 in the experimental group.  This resulted in total mortality being slightly lower in the experimental group (28 vs. 31) [1] [3]

It’s interesting that the experimental group had lower total CHD events, but not major CHD events and CHD mortality.  The authors suggested that: “One possibility is that the men in the control group themselves may have felt that they were having less active treatment, and might have been psychologically motivated both to complain more and more readily of cardiac symptoms. The other possibility, of course, is that the diet may have had a real effect in these cases of minor ischaemia.” [1]

No comments:

Post a Comment