Friday, October 30, 2015

Addressing Some Questions from my Presentation: Part 1

Monounsaturated Fat and Coronary Heart Disease

My presentation (and the meta-analysis) is about saturated fat (SFA) and polyunsaturated fat (PUFA), but what about monounsaturated fat (MUFA)?  Despite the promotion of MUFA as being heart healthy (because it reduces LDL-C and the total-C:HDL-C ratio) it actually received very little attention until much later on with the promotion of the Mediterranean diet.  As a result, my understanding is that there is only one clinical trial that has manipulated MUFA intake without also altering several other dietary variables, which is what occurs in the Mediterranean diet trials and as a result the Mediterranean diet trials are inappropriate to test the effect of MUFA on the incidence of coronary heart disease (CHD)

The only clinical trial is the ‘Rose Corn Oil Trial’ (RCOT; hat tip to Zahc for reminding me).  RCOT had a control/saturated fat group, an olive oil group and a corn oil group.  The control group performed slightly better than both oil groups, but the differences between the groups was hardly significant as the number of participants and events in the groups was very small.  So I wouldn’t want make much of a conclusion on MUFA and CHD to for a few reasons: (1) there seems to be only one relevant trial; (2) the trial was very small; and (3) the fact that both oil groups did slightly worse may indicate an unfavourable health effect of the ‘oil advice’ per se, rather than being related to MUFA and PUFA

Saturated Fat
(N = 26)
Olive Oil
(N = 26)
Corn Oil
(N = 28)
Major Coronary Events
Total Coronary Events
Coronary and Total Mortality
Participants who Completed the Trial

Regarding observational studies, 3 out of 4 meta-analyses of observational studies have found no association between MUFA and CHD, including Jakobsen [1], Skeaff [2] and Chowdhury [3].  The Mente meta-analysis was the only one to find a significant association between MUFA and CHD, with MUFA being inversely associated with CHD [4]

The reason why MUFA were not well researched until recently is likely because the original diet heart hypothesis related to total cholesterol, rather than LDL-C or the total-C to HDL-C ratio, likely due to limitations in measurement.  MUFA doesn’t affect total-C as it increases HDL-C to the same extent as it reduces LDL-C [5], so it was considered neutral and largely ignored

Is Nutrition Science Bad?

In order to accurately convey the evidence regarding saturated fat and coronary heart disease I had to point out some of the problems with the saturated fat vs. polyunsaturated fat trials as well as in relying on mechanisms/risk factors and observational studies.  I can understand how someone could come away from my presentation with a negative attitude towards nutrition science, but I don’t think it’s as bad that

One of the problems is that the early to mid-20th century was like the dark ages of epidemiology.  Diet and disease relationships were only beginning to be explored in observational studies and tested in clinical trials and some of the limitations of certain study designs didn’t appear to be well understood at the time

Regarding observational studies, prospective cohort studies are the most reliable*, however such cohorts had not yet been set up.  Instead a lot of observational epidemiology at the time was based on ecological studies – comparing the dietary patterns and incidence of coronary heart disease between different countries.  Ecological studies are some of the most susceptible to confounding variables and it seems the early ecological studies didn’t adjust to adjust for confounding variables.  This is understandable considering the lack of evidence at the time to identify confounders and perhaps the lack of software to execute such adjustments

There were some issues with the early clinical trials.  Some of them weren’t randomised like the Anti-Coronary Club and the Finnish Mental Hospital Study.  It was not uncommon to put participants on a diet, and then after a year or so allocate the good adherers to the ‘experimental group’ and the poor adherers to the ‘control group’.  Not to mention that the health effects of trans fats were not widely understood at the time and the investigators preferred to test a ‘cholesterol lowering diet’ rather than rigorously testing the effects of replacing SFA with PUFA

The design and execution of observational studies and clinical trials appears to be much better these days.  I think we need to recognise the issues in certain earlier studies and not disregard modern and better designed epidemiological evidence based on the faults of their predecessors

With the diet heart story the main problem is that so few people have actually read the papers and have relied on reviews and meta-analyses, which in turn seemed to assume everything is ok with the trials, and many simply take some participant characteristics and the results then leave it at that

* Prospective cohorts are the most reliable because they avoid the issue of reverse ‘causality’.  For example in a cross-sectional design it could be possible to have a positive association between calcium intake and fracture risk.  This is because the people with the highest intake of calcium may be those who are taking calcium supplements because they are at high risk of osteoporosis or have been diagnosed with osteoporosis or osteopenia 

** Although adherence may be a bit worse and using patients in mental hospitals to achieve very high adherence and a double-blind design is probably unethical in most countries these days


  1. Steven, I am not convinced that monounsaturated fat per se lowers LDL. I've seen far too many studies where higher monounsaturated intakes had little to no effect on LDL. Therefore, I think that the old idea that monounsaturated fat is neutral still holds true (excluding HDL). Some foods rich in monounsaturated do appear to lower LDL consistently (e.g. some nuts, avocado), but perhaps there are other components in these foods that modulate LDL.

    BTW, I'm looking forward to your presentation and the publication of your meta-analysis!

    1. Hi Zahc, that's interesting, I've not looked into how fats affect cholesterol that much. What are some of those studies? I would be interested to have a look at them

    2. Sure, would collect and summarize some of the evidence and get back to you this weekend.

  2. I've put together something here -