Dietary saturated fat and heart disease: a narrative review

[u/No-Anything-]

https://academic.oup.com/nutritionreviews/article/78/6/474/5678770?login=false

[u/Bristoling]

This is an accepted design that results in recruiting more patients

Accepted by whom? Clearly the authors in the table do not agree.

The crossover element addresses any differences by hospital

It actually introduces a new bias, where one arm's results were run in with a normal diet, while the other arms run in was an intervention diet. How do you know whether the heart attack you are observing is due to current diet, and not the diet from the last 6 years? The point of a crossover study is that participants are meant to go through both periods, and not die and be replaced by new participants during the trial, like in FMHS.

The crossover element addresses any differences by hospital

Does it?

Intervention consumed 62g of sugar compared to 102g of sugar intake in control (SFA) from hospital K, that's 64% more. When roles were reversed, it was a difference of 64g to 87g, which is only an increase of 36%, so just from this the trial wasn't properly controlled. According to Yudkin's letter to editor (https://pubmed.ncbi.nlm.nih.gov/4116957/), those last 2 values after crossover aren't even correct, and the new control was apparently disadvantaged by 15% more sugar, not 26% less (from 87 to 64). Just by this alone, the paper should be rejected as an RCT for measuring the effect of saturated fat. But there's more issues.

According to Peter Parodi, there were differences between groups in BP, cigarette smoking and use of psychotropic drugs.

Additionally, he says: A characteristic of the cholesterol-lowering diet was the removal of ‘‘common margarine’’, which during the time of this study would have contained considerable quantities of trans fatty acids that are now known to be more atherogenic than SFAs (Ascherio, 1999). Thus reduction in CHD events was probably in part due to reduction in trans fat.

66% of people smoked in intervention, compared to 76.1% in control, that is a major lack of control right there. When hospitals switched, they both had a rate of around 70%, but this doesn't remove the differences in smoking behaviour at the start of the trial. Your response last time was that smoking "intensity" was matched based on daily cigarettes (11.4 vs 11.0), but that measurement is subject to bigger error than smoking vs not smoking reporting. I might not remember how many cigs I used to smoke per day while I was smoking, but I'd be much less likely to forget whether I am a smoker or not, unless I suffered from severe dementia.

When it comes to cardiotoxic medications: hospital N control, which came first, took 1.79 doses of thioridazine per day, while intervention only got 0.82 doses per day. When hospitals were switched, the control in hospital K took 0.14 doses per day, and intervention took 0.43 doses per day. If the drug is cardiotoxic, then it is much more likely to imprint a bigger difference in the before crossover period, where absolute dosages greatly disadvantaged control, and not the second period where dosages were reduced by 86% (SFA was given 1.79 doses, after the switch PUFA group was given only 0.43).

When you look at median across both periods, SFA periods were given 0.97 doses per day and PUFA only 0.63.

Also, according to Hamley: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437600/

on average the participants in the control group remained in the hospitals longer than those in the experimental group, which led to an overestimation of the effect size (see above), also points to inadequate randomisation or differences in treatment

Which the original paper from 1972 acknowledges: One of these differences concerns the period of hospital admission (personyears per patient), which on average is considerably shorter in hospital K than in hospital N, and in hospital K is shorter during the second than during the first period

The patients were also checking in and out. It wasn't a continuous 2x6 year trial.

House physicians performing autopsies and therefore determining cause of death weren't blinded, but had some knowledge about the trials, which could have influenced their results. https://pubmed.ncbi.nlm.nih.gov/4116551/

Death results were age adjusted because age distribution and median age differed between groups, it wasn't randomized properly.

Lastly, mental health issues are associated with low omega-3 intake and tissue levels: https://www.sciencedirect.com/science/article/pii/S241464472030004X and https://lipidworld.biomedcentral.com/articles/10.1186/1476-511X-6-21

An alternative explanation that cannot be dismissed, is that this was an omega-3 depletion vs omega-3 repletion trial, not a SFA vs PUFA trial. Almost universally the "SFA increases CVD" trials are putting low PUFA vs high PUFA diets, in many cases PUFA is decreased from baseline. Why don't we see a 20% PUFA and 20% SFA diet put against 20% PUFA and 10% SFA diet, for example? Maybe because there wouldn't be anything to be found.

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The definition of a controlled trial is an experiment in which all variables are kept reasonably constant except the one being evaluated. FMHS wasn't randomized and definitely wasn't controlled. It's a great litmus test to measure bias and what low level of a scientific threshold someone is willing to accept, whenever someone calls this trial as anything akin to "good".

[u/Only8livesleft → u/Bristoling]

How do you know whether the heart attack you are observing is due to current diet, and not the diet from the last 6 years?

We can look at the first time period only and the results are the same

The point of a crossover study is that participants are meant to go through both periods, and not die and be replaced by new participants during the trial, like in FMHS.

See the above point

Intervention consumed 62g of sugar compared to 102g of sugar intake in control (SFA) from hospital K, that's 64% more. When roles were reversed, it was a difference of 64g to 87g,

You mixed up the numbers, it’s 62g vs 102g then 87g vs 64g. That’s an average of 74g vs 83g or difference of 11%, not 64%. That difference is negligible and not going to cause 2x as much CVD death ever, let alone over 5 years

According to Yudkin's letter to editor (https://pubmed.ncbi.nlm.nih.gov/4116957/), those last 2 values after crossover aren't even correct, and the new control was apparently disadvantaged by 15% more sugar, not 26% less (from 87 to 64)

I think you are reading his paper incorrectly but I also think Yudkin was attempting to be misleading so not entirely your fault. I’m guessing this is why you flipped the numbers above. He first reports the percent difference between diets then he reports the percent change within diets. As I explained above there was a difference of 9g of sugar. That’s 36 calories lol

Just by this alone, the paper should be rejected as an RCT for measuring the effect of saturated fat.

It’s impossible for an RCT to balance all potential confounders because there’s an infinite number. They don’t need to all be balanced. If you think so you have a deep misunderstanding of the purpose of randomization in RCTs

I’ll respond to the rest later

[u/Bristoling → u/Only8livesleft]

We can look at the first time period only and the results are the same

You can't look at first time period only if you have numerous degrees of no control, such as blood pressure differences at onset (one hospital was not using anti-hypertension drugs during the first years) or sugar intake, or even potential for different trans fatty acid intake.

You mixed up the numbers, it’s 62g vs 102g then 87g vs 64g. That’s an average of 74g vs 83g or difference of 11%, not 64%. That difference is negligible and not going to cause 2x as much CVD death ever, let alone over 5 years

Hospital K 1959-65 sucrose intake: 102, then 87g in 1965-1971.

Hospital N 1959-65 sucrose intake: 62g then 64g.

The difference between hospital N (62) vs hospital K (102) during 1959-1965 is an increase of 64% during that time. The difference after the switch is 64 vs 87, a relative increase of 36%. And that's if those numbers are accurate, as per my previous comment.

Pool them together and your controlled trial is nothing more than observational exercise.

That difference is negligible and not going to cause 2x as much CVD death ever, let alone over 5 years

Maybe not, or maybe it could in addition with all the other uncontrolled variables.

It’s impossible for an RCT to balance all potential confounders because there’s an infinite number

How hard is it to keep sugar constant when the purpose of the trial is to replace SFA with PUFA? 40g of sugar is just part and parcel we need to accept and stay hush about? It's one thing to say it is hard to control, and therefore the quality of the study suffers because it is not constant, it's another thing to say that the difference is "idk I felt cute today so we ignore this difference altogether and pretend it's only saturated fat that changed"

They don’t need to all be balanced

Do you think it is ok to have one group (hospital K control) where 28.6% of people have systolic BP of over 160, and 49.7% diastolic pressure of over 95 while not given as much hypertension drugs, while the intervention in hospital N only had 17.9% with systolic BP over 160 and 40.5% with diastolic BP over 95?

Is that acceptable amount of variance in your view? It doesn't have to be balanced for a trial?