Let us head back to the headwaters of HDL biology to find some more answers. If you did not read the original HDL piece or remember the basics of HDL biology, go back to Newsletter V13 #15 for a review. HDL as an associated biomarker of death risk has a U shaped curve with higher all cause mortality at very low and high levels of volume. Let us understand why? (Madsen et. al. 2017) Anything that causes more LDL, low density lipoproteins, to stay in circulation will raise one's risk of ASCVD or heart attack. The historical reality (as I have discussed for years) for why we would have these genomic mutations to have more LDL particles in circulation is 1) as a protection mechanism against bacterial infections which were common for thousands of years. The HDL and LDL particles have receptors on their surface to grab bacterial cell wall debris like LTE or LPS and remove them via the liver. This is a massive beneftit to the human species until recent times. 2) as a storage mechanism for calories/recirculation of metabolically expensive cholesterol. (Maile et. al. 2020)(Feng et. al.. 2019)(Trinder et. al. 2021)....... Enjoy, Dr. M

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