Thank you for the systematically written series on cholesterol, and in particular, meticulously addressing common concerns/criticisms/counterpoints. The reliability of certain blood markers like apoB is much easier to ascertain, at least in my opinion, than to come to conclusions on the epidemiological research available with the plethora of confounds present in many commonly-cited studies.
A few questions, if either of you have time:
-You mention the threshold of daily saturated fat % of total calories is important for comparison, but that the 12% vs 22% lower vs upper threshold in the Malmo study was still not under the recommended 10% (in addition to being confounded by dairy saturated fat). Via that line, I assume there isn’t a large difference between i.e. 10 and 12 or 13% (controlling for dairy intake) compared to other risk factors. Is that roughly correct?
Unrelated specifically to the article:
-Is there any longevity related benefit to limiting IGF-1 and mTOR, both in short-term bouts or long term? Limiting both/either seems to be at odds with building/maintaining muscle but there seem to be cases for doing this in cancer patients specifically.
-If yes, is there any precedent for periods of protein restriction (or i.e. animal protein restriction), or is there no evidence on that line specifically (aside from some mice studies)? Alternatively, is there any evidence that periodic fasting (24h+) can achieve the same goal, and if not, is there counterevidence or simply a lack of evidence?
Yes. The bolded is almost explicitly stated in Part III of the article series in section 9.
IGF-1 and mTOR stimulation can occur through multiple different mechanisms. Raising them via dietary protein and exercise is much different than raising them via cancer, for example. At present, it does not appear that limiting exercise and reducing lean body mass is a good strategy for both health- and lifespan.
The existing evidence shows that neither protein restriction nor fasting improves human health uniquely. In the case of protein restriction, it seems like there are multiple lines of evidence showing harm. For fasting, the existing evidence shows no improvement in any health marker (or outcome) compare to equivalent energy intake without fasting. Time restricted feeding with the feeding window in the early hours of the day may have some benefit for those with compromised blood sugar control.
As an aside, the dietary pattern is far more important than anything discussed in this reply.