For today’s edition of Dear Mark, I’m answering three questions. First, can LDL actually infiltrate the arteries, or is there more to the story? Malcolm Kendrick says there’s more to the story, so I dig into some literature to see if they corroborate his position. Second, is New Zealand farmed salmon good to eat? And finally, what should you do about elevated ferritin levels—and why else might they be elevated if not because of your iron?
My reading of this post by Malcolm Kendrick MD is that LDL particles cannot infiltrate the endothelial lining of our arteries:
Great read. Malcolm Kendrick is consistently fascinating, insightful, and enlightening.
He’s basically suggesting that LDL particles can’t manhandle their way into the artery wall, which are equipped with tight junctions—the same kind that regulate passage through our gut lining. Something has to “allow” them in. The something he finds most plausible is injury, trauma, or insult to the endothelial lining (artery wall, for lack of a better phrase).
Population studies have demonstrated that elevated levels of LDL cholesterol and apolipoprotein B (apoB) 100 [note: ApoB is a stand-in for LDL particle number, as each LDL-P has an ApoB attached to it], the main structural protein of LDL, are directly associated with risk for atherosclerotic cardiovascular events (ASCVE). Indeed, infiltration and retention of apoB containing lipoproteins in the artery wall is a critical initiating event that sparks an inflammatory response and promotes the development of atherosclerosis.
This seems to posit that infiltration of the LDL particle into the artery wall is a critical initiating event. But is it the critical initiating event? Does something come before it? How does the infiltration happen, exactly? Moving on:
Arterial injury causes endothelial dysfunction promoting modification of apoB containing lipoproteins and infiltration of monocytes into the subendothelial space. Internalization of the apoB containing lipoproteins by macrophages promotes foam cell formation, which is the hallmark of the fatty streak phase of atherosclerosis. Macrophage inflammation results in enhanced oxidative stress and cytokine/chemokine secretion, causing more LDL/remnant oxidation, endothelial cell activation, monocyte recruitment, and foam cell formation.
If I’m reading this correctly, they’re saying that “arterial injury” is another critical initiating event—perhaps the critical initiating event, since the injury causes “endothelial dysfunction,” which in turn modifies (or oxidizes) the LDL particles. But wait: so they’re saying the LDL particles are already there when the arterial injury occurs. They’ve already made it into the endothelial walls, and they’re just…waiting around until the arteries get injured. Okay, okay, but, just like Malcolm Kendrick points out, nowhere in the abstract have the authors actually identified how the LDL particles enter the endothelial lining. Maybe it’s “common knowledge,” but I’d like to see it explained in full.
In atherosclerosis susceptible regions, reduced expression of eNOS and SOD leads to compromised endothelial barrier integrity (Figure 1), leading to increased accumulation and retention of subendothelial atherogenic apolipoprotein B (apoB)-containing lipoproteins (low-density lipoproteins (LDL)) and remnants of very low-density lipoproteins (VLDL) and chylomicrons)
Ah ha! So, in regions of the arteries that are prone to atherosclerosis, low levels of nitric oxide synthase (eNOS)—the method our bodies use to make nitric oxide, a compound that improves endothelial function and makes our blood flow better—and superoxide dismutase—an important antioxidant our bodies make—compromise the integrity of the arterial lining. The compromised arterial lining allows more LDL particles to gain entry and stick around. So, are low levels of nitric oxide and impaired antioxidant activity the critical initiators? That’s pretty much what Malcolm Kendrick said in his blog post.
Still—high LDL particle numbers are a strong predictor of heart disease risk, at least in the studies we have. They clearly have something to do with the whole process. They’re necessary, but are they sufficient? And how necessary are they? And how might that necessariness (yes, a word) be modified by diet?
I’ll explore this more in the future.
In regards to the oily fish article (and more indirectly given the omega 6 concern- the Israeli Paradox) What do you think of NZ farmed salmon? I’m in Australia, & occasionally like a fresh piece of salmon- there are no wild caught available here sadly, but I am wondering how it measures up as an alternative?
I wasn’t able to pull up any nutrition data for New Zealand farmed salmon, called King or Chinook salmon. Next time you’re at the store, check out the nutritional facts on a NZ farmed salmon product, like smoked salmon. The producer will have actually had to run tests on their products to determine the omega-3 content, so it should be pretty accurate. Fresh is great but won’t have the nutritional facts available. I don’t see why NZ salmon would be any worse than the farmed salmon I discussed last year.
According to the NZ salmon folks, they don’t use any pesticides or antibiotics. That’s fantastic if true.
I used to eat a lot of King salmon over in California, and it’s fantastic stuff. Very fatty, full of omega-3s. If your farmed King salmon comes from similar stock, go for it.
ok can someone tell me how to reduce ferritin? Is is just by giving blood?
Giving blood is a reliable method for reducing ferritin. It’s quick, effective, simple, and you’re helping out another person in need. Multiple wins.
Someone in the comment board recommended avoiding cast iron pans in addition to giving blood. While using cast iron pans can increase iron intake and even change iron status in severe deficiency, most don’t have to go that far. Giving blood will cover you.
Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.