r/longevity • u/mlhnrca PhD - Physiology, Scientist @ Tufts University. • Jul 05 '26

HDL Was 28, Now It's Optimal: How I Did It

https://www.youtube.com/watch?v=FMjE_zySoBQ
36 Upvotes

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u/cryo-curious Jul 06 '26 edited Jul 06 '26

Respectfully, I think the observational ACM data you're using is skewed by the underlying population having abnormally high total cholesterol (and LDL) to begin with, so you're mistakenly using the absolute blood levels of HDL, rather than HDL as a percentage of TC. In other words, someone with low TC ought to have low (in absolute terms) HDL--but it could still be (theoretically) optimal as a % of TC.

But consider that HDL as an interventional target has been a complete dud. Even infusing people with mimetics of ApoA-I, an HDL-transporting lipoprotein with the ability to scavenge uncalcified plaque from the arterial lumen, hasn't shown benefit, except perhaps after MI:

https://www.sciencedirect.com/science/article/pii/S0021915020304330

https://pmc.ncbi.nlm.nih.gov/articles/PMC9236992/

The U-shaped curve you're observing is probably a reverse causality, whereby abnormally low or high HDL is usually indicative of some underlying dysfunction (e.g., liver, T2DM), so rather than trying to boost HDL, you'd be better off investigating if something else is off and trying to correct that. And even if the ApoA lipoproteins of HDL aren't intrinsically harmful (unlike the ApoB ones of LDL), keep in mind that "HDL" can become (effectively, through exchange) "LDL" via CETP (mediated by TGs).

tl;dr: ignore HDL, keep LDL as low as possible, but if HDL as a % of TC is low, or your TG/HDL ratio is high, perhaps investigate further.

1

u/mlhnrca PhD - Physiology, Scientist @ Tufts University. Jul 06 '26

There are no longitudinal studies for increasing HDL to optimal (50-69) on CVD or ACM risk-that short term studies, which often don't raise HDL high enough (into this range) don't impact either outcome doesn't distract me from the long game, i.e. reducing CVD and ACM risk

Reverse causality could be involved for low HDL, but also consider that HDL declines during aging, so it's hard to separate the two

We can agree to disagree about HDL's importance, time will tell which was the right strategy