What Causes Heart Disease, LDL or Seed Oils?

Hat tip to Dave Feldman for calling my attention to this podcast:

1/ I finished listening to the #SigmaNutrition podcast featuring Professor Chris Packard. This quote is worth it's own thread re #LMHRstudy

Alan asked the Prof about someone extolling an LDL of 13 mmol/L (~500 mg/dL) while having a CAC of 0, and this was his reply: pic.twitter.com/6oKgKpJ5JZ

— Dave Feldman (@DaveKeto) March 31, 2021

Which sounded interesting, so I downloaded it to listen to on my morning run.

Nevertheless he says something false in the first five minutes of the podcast. That didn't take long.

Why arguments from authority are fallacious. https://t.co/zAgEUvG2hQ

— Tucker Goodrich (@TuckerGoodrich) April 2, 2021

Given the comment by the interviewer, I had been hoping to get farther than a few minutes into my run before having to stop and tweet!

So to be correct, what he says (LDL is the "genetic", "primary cause" of CVD) is what got me. This can only be said by relying on a subset of the science, not, as the interviewer says, "the science".

But let's let Professor Packard put it in his own words (all transcriptions are mine, as are any errors therein. These are all taken from the tweet thread starting with my retweet above.).

He's discussing LDL, and a sub-type of LDL, Lp(a), which is a sub-type of oxidized LDL (oxLDL). He mentions that Lp(a) can be reduced by niacin (nicotinic acid), but that:

"...was put aside because of the THRIVE trial..." 

Huh, so what's the THRIVE trial?

"...participants who were assigned to extended-release niacin–laropiprant had an LDL cholesterol level that was an average of 10 mg per deciliter (0.25 mmol per liter as measured in the central laboratory) lower..."

So if you think LDL causes CVD, then a reduction of LDL must be a good thing, right? Unfortunately, the THRIVE trial was a "failed" trial, one which failed to show a benefit:

"...Among participants with atherosclerotic vascular disease, the addition of extended-release niacin–laropiprant to statin-based LDL cholesterol–lowering therapy did not significantly reduce the risk of major vascular events..."

So LDL is a "genetic" "primary cause" except when it has no effect whatsoever, apparently.

"Effects of Extended-Release Niacin with Laropiprant in High-Risk Patients"

Niacin also reduced Lp(a), among other seemingly beneficial things, "...lowering triglyceride and lipoprotein(a) levels and blood pressure." But all was for naught.

It's an odd cause, in my simple engineering view, that is only occasionally causal, as this is not the first time that reducing LDL has failed to show a benefit for CVD.

Next we come to this:

"...the classic exception is the guy in the [NEJM] who ate 40 eggs a day... and never got any problems with his LDL cholesterol... "

Seriously? We're back to eggs causing heart disease? This is the expert? This was considered debunked in the 1950s, for heaven's sake.

"From the animal experiments alone the most reasonable conclusion would be that the cholesterol content of human diets is unimportant in human atherosclerosis." — Ancel Keys, 1952https://t.co/fmMF82TiRT

— Tucker Goodrich (@TuckerGoodrich) May 9, 2018

Even the Dietary Guidelines dropped the recommendation against dietary cholesterol for lack of evidence.

"Normal Plasma Cholesterol in an 88-Year-Old Man Who Eats 25 Eggs a Day"

So ponder this: 

"LDL cholesterol is a marker of nutrition. So, that if you have a very poor diet, or you have existing disease, then you'll have a low LDL cholesterol."

Well, I agree with Prof. Packard! In fact, one of my major arguments for avoiding seed oils is the fact that they lower cholesterol, which seems to correlate with their negative effects on heart disease. 

So one would logically conclude a diet change that raised LDL would be good, and one that lowered it (like seed oils) would be bad, right?

He continues: 

"With the canakinumab trial we had a proof of concept, and absolutely correct that Paul [Ridker]... showed that lowering inflammation gave rise to a benefit [in CVD] without a reduction in LDL. And that does suggest that if you target the correct pathway, the correct inflammatory pathway, which is the IL-1β / IL-6 pathway... you end up probably stopping LDL having it's deleterious effects."

We won't get too into the details there, suffice to say that drug stops a cytokine from being produced, and this has a benefit for CVD that does not depend on LDL reduction. 

Now how could we do that to prevent people from getting CVD in the first place?

"The induction of [IL-1β] release from human monocyte-derived macrophages by 9-HODE and cholesteryl-9-HODE suggests a role for modified LDL, and its associated [linoleic acid] oxidation products, in vascular smooth muscle cell proliferation."

That's from 1992, which is shortly after it was shown that LDL alone did not induce the first step of atherosclerosis, it had to be "modified". The modification, it turned out, was the inclusion of linoleic acid from dietary seed oils, which would then become oxidized, and thus pathological, inducing the first step of atherosclerosis—and the rest, IMHO, and as suggested by the canakinumab trial.

"Induction of interleukin 1 beta expression from human peripheral blood monocyte-derived macrophages by 9-hydroxyoctadecadienoic acid."

So after assuring us that LDL is causal, Prof. Packard goes on to demonstrate, from the science, that it is not.

Yes, stop eating the precursor that causes that harmful inflammation, linoleic acid. 

Fix your poor diet: eat no seed oils. 

Don't worry about LDL.

Here's that podcast.

Listen to Prof. Packard explain (unwittingly) how a low seed oil diet could allow you to stop worrying about your LDL.

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Effects of Extended-Release Niacin with Laropiprant in High-Risk Patients. (2014). New England Journal of Medicine, 371(3), 203–212. https://doi.org/10.1056/NEJMoa1300955

Kern, F. (1991). Normal Plasma Cholesterol in an 88-Year-Old Man Who Eats 25 Eggs a Day. New England Journal of Medicine, 324(13), 896–899. https://doi.org/10.1056/NEJM199103283241306

Ku, G., Thomas, C. E., Akeson, A. L., & Jackson, R. L. (1992). Induction of interleukin 1 beta expression from human peripheral blood monocyte-derived macrophages by 9-hydroxyoctadecadienoic acid. Journal of Biological Chemistry, 267(20), 14183–14188. https://doi.org/10.1016/S0021-9258(19)49695-6

Ridker, P. M., Everett, B. M., Thuren, T., MacFadyen, J. G., Chang, W. H., Ballantyne, C., Fonseca, F., Nicolau, J., Koenig, W., Anker, S. D., Kastelein, J. J. P., Cornel, J. H., Pais, P., Pella, D., Genest, J., Cifkova, R., Lorenzatti, A., Forster, T., Kobalava, Z., … Glynn, R. J. (2017). Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. New England Journal of Medicine, 377(12), 1119–1131. https://doi.org/10.1056/NEJMoa1707914

Witztum, J. L., & Steinberg, D. (1991). Role of oxidized low density lipoprotein in atherogenesis. Journal of Clinical Investigation, 88(6), 1785–1792. https://doi.org/10.1172/JCI115499