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Peter Attia MD#24 – Tom Dayspring, M.D., FACP, FNLA – Part V of V: Lp(a), inflammation, oxLDL, remnants, and more
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At a glance
WHAT IT’S REALLY ABOUT
Dayspring and Attia Close Lipidology Course: Lp(a), Oxidation, Remnants, Omega-3s
- Dayspring explains that statins don't lower Lp(a) because apo(a) production in the liver, not receptor clearance, is the main determinant, and that apo(a) may camouflage the LDL receptor binding domain on apoB.
- The two discuss inflammation-targeting trials (an IL-1 inhibitor, methotrexate, colchicine) and oxidation biomarkers such as oxLDL, F2-isoprostanes, myeloperoxidase and Lp-PLA2, with Dayspring stressing that these markers have never been adjusted for apoB or LDL particle number.
- They cover ADMA and SDMA as endothelial and renal function markers tied to nitric oxide and homocysteine, along with a push for cystatin C over creatinine alone for kidney assessment.
- Dayspring argues that remnants are poorly defined, that LDL particle number drives most cholesterol delivery into the artery wall, and that apoC-III content of apoB particles may matter more than triglyceride levels.
- The episode ends with an omega-3 discussion (DHA versus EPA, red blood cell levels, an upcoming EPA outcome trial) and Dayspring's story of his friend Earl, who avoided medical care and died of a heart attack in his mid-50s.
IDEAS WORTH REMEMBERING
5 ideasLp(a) is poorly served by current tests and drugs
Dayspring says Lp(a) mass is a weak metric because apo(a) size varies, and an electrophoresis-based particle count is better. Statins lower the non-Lp(a) LDL particles but not Lp(a), so residual risk remains.
Apo(a) production, not clearance, likely drives Lp(a) levels
Dayspring cites data that liver production is the main determinant and suggests apo(a) camouflages the LDL receptor binding domain on apoB. That is why an apo(a) synthesis inhibitor under investigation is seen as the logical therapy.
Oxidation markers must be interpreted with caution
Dayspring notes that plasma oxLDL really reflects minimally oxidized apoB, and that outcome trials of oxidative markers were never adjusted for apoB. He mainly uses these markers to motivate nutritional change, and advises against Lp-PLA2 because Mendelian randomization and inhibitor trials showed no outcome benefit.
ADMA and SDMA link homocysteine and renal function to nitric oxide
Both markers point to reduced arginine and nitric oxide, so they give a view of endothelial function. SDMA is cleared by the kidneys, while homocysteine impairs clearance of ADMA and SDMA, and both speakers favor cystatin C alongside creatinine.
Particle number matters more than the remnant label
Dayspring says remnants exist in every lipoprotein class and that LDL particles vastly outnumber them, so most cholesterol entering the artery wall is LDL-delivered. He adds that small VLDLs high in apoE and low in apoC-III are cleared quickly.
WORDS WORTH SAVING
5 quotesWhich would you rather have, 1,000 guys coming at you or one guy? I'd take my odds that I could beat one guy rather than 1,000 guys, you know?
— Dr. Tom Dayspring
I've been around too long seeing, seeing lower this and lowers that, and they don't work.
— Dr. Tom Dayspring
The field is infinitely more complex than you ever imagined.
— Dr. Tom Dayspring
I find this subject matter to be as complicated as any I have ever tried to learn. And unfortunately, every time I have a brilliant idea just based on first principles, I still have to go and check if it's grounded in the foundation of science.
— Dr. Peter Attia
As a biologist sitting in the bath, he always realized there was one more fact he needed to remember before he could draw a conclusion, and so he had to keep getting out of the bathtub to go and look up a certain fact
— Dr. Peter Attia
High quality AI-generated summary created from speaker-labeled transcript.
