What you're describing is basically the same as what is called the "healthy user bias", where healthy behaviours or behaviours that are socially percieved as healthy tend to associate to each other, and the same happens with unhealthy behaviours. I agree it is probably the only explanation for the positive results of PUFA in obseravtional studies.

@Kasper
Is there a reason to believe stress levels would be higher among people consuming less PUFAs? Because that's what you're implying here.

If you have a large enough sample, there's no reason to assume stress levels would be significantly different between those at low vs high intakes of PUFA, thus it's pointless to account for chronic stress in such an analysis. The point of these studies is precisely to isolate the effect of PUFA specifically on health outcomes.

Ecological studies like the Israeli or Japanese ones are arguably far more confounded and less relevant than the meta analysis I posted. Is it the lack of PUFA that made Tokelauans healthy or the myriad of other factors that distinguishes them from the average westerner?

Researchers obviously control for relevant variables such as energy intake, socioeconomic status etc. What reason is there to believe work stress or social life would significantly differ between thosa at low vs high PUFA intake?

I agree that looking at biomarkers such as cholesterol is not a reliable way of assessing a persons health. But studies looking at hard outcomes paint the same picture in favor of PUFA.

Ray Peat was against both omega 3 and 6...

Did anyone try eliminating starch entirely and relying exclusively on simple sugars? Did it make a difference?

Also, did you experience problems with reintroducing starch?

Thanks for sharing your thoughts. From what I gather, you seem to agree with me on healthy user bias being the main reason for the association.

"The healthy user effect is best described as the propensity for patients who receive one preventive therapy to also seek other preventive services or partake in other healthy behaviors.18 Patients who choose to receive preventive therapy may exercise more, eat a healthier diet, wear a seatbelt when they drive, and avoid tobacco. As a result, an observational study evaluating the effect of a preventive therapy (e.g., statin therapy) on a related outcome (e.g., myocardial infarction) without adjusting for other related preventive behaviors (e.g., healthy diet or exercise) will tend to overstate the effect of the preventive therapy under study. The healthy user effect has been widely cited as a likely source of bias in observational studies of HRT. Studies indicate that women who took HRT were more likely to engage in healthy behaviors such as regular exercise, a healthy diet, abstinence from alcohol, and maintenance of a healthy weight as compared to non-users.2 The apparent protective effect of HRT on cardiovascular disease likely reflects these unmeasured differences in patient characteristics."

In this case, the "preventive therapy" would be eating more PUFAs.

Underreporting alcohol and energy intake could be thought of as an extension of healthy (or in this case unhealthy) user bias

@JulofEnoch Thanks for the elaborate answer. I will focus on the second study since it's more general.

I agree that food frecuency questionnaries are extremely limited, but they should probably be good enough to at least discriminate between those at the highest vs lowest perecentiles of PUFA intake.

By its very nature, I doubt MR is a valid way to assess the impact of dietary exposures. Serum omega 6 is not the same as tissue omega-6, and high omega-6 intake doesn't always lead to high serum omega-6.

We know that observational epidemiology cannot make causal inferences, but one has to wonder why high PUFAs, if they truly are the problem Ray Peat outlines them to be, rarely associate with worse health outcomes.

I agree that healthy user bias is probably explaining part or maybe all of the effect of PUFAs on different outcomes. Another possible explanation is over-adjustment for variables such as BMI.

But I still wonder if Peat or the community have found better explanations.

@dan-saintdominic Isn't PUFA being the scourge of the modern diet a main tenet of the Ray Peat philosohpy?

@thyroidchor27 I read the conclusion, obviously. What are you trying to state?

@skylark How are the examples I provided not "real life"?

In pretty much every retrospective, cohort study or RCT I happen to take a look at, higher PUFA consumption, especially linoleic acid, almost always leads to better outcomes than lower PUFA consumption.

Example of a study I came upon by chance: https://pubmed.ncbi.nlm.nih.gov/35170737/

Higher n-6 PUFA consumption cuts the risk of dying by half in newly diagnosed head/neck cancer patients.

Example 2:
https://pubmed.ncbi.nlm.nih.gov/34434952/

Highest vs lowest PUFA quartile associated with 20% decreased all-cause mortality

Is healthy user bias enough to explain this?