Dear Mark: How Does LDL Even Penetrate the Arteries, New Zealand Farmed Salmon, Elevated Ferritin

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?

Let’s go:

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).

A free public textbook available on PubMed since last month called The Role of Lipids and Lipoproteins in Atherosclerosis tackles the topic head on. In the abstract, they say:

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.

Moving on:

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?

Last year, I explored the health effects of eating farmed salmon and found that it’s actually a pretty decent alternative to wild-caught salmon, at least from a personal health standpoint—the environmental impact may be a different story.

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.

Ferritin is also an acute phase reactant, a marker of inflammation—it goes up in response to infections (bacterial or viral) and intense exercise (an Ironman will increase ferritin). In fact, in obese and overweight Pakistani adults, elevated ferritin seems to be a reliable indicator of inflammatory status rather than iron status.

Thanks for reading, everyone. Take care and be well!


Birgegård G, Hällgren R, Killander A, Strömberg A, Venge P, Wide L. Serum ferritin during infection. A longitudinal study. Scand J Haematol. 1978;21(4):333-40.

Comassi M, Vitolo E, Pratali L, et al. Acute effects of different degrees of ultra-endurance exercise on systemic inflammatory responses. Intern Med J. 2015;45(1):74-9.

About the Author

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.

If you'd like to add an avatar to all of your comments click here!

18 thoughts on “Dear Mark: How Does LDL Even Penetrate the Arteries, New Zealand Farmed Salmon, Elevated Ferritin”

Leave a Reply

Your email address will not be published. Required fields are marked *

  1. I just realized that NZ King salmon is farmed last night. My local fish monger originally just listed it as King salmon. I assumed since it was kind, it had to be wild caught. Perhaps that is only if it is labeled Alaska. It tasted good, but way too expensive, nearly double the price of good old fashioned AK Sockeye. Thanks for the info.

    Oh, antibiotic free is also the case for Norwegian, per an article sent out by Costco’s shopping magazine.

  2. Mark, I have to imagine part 2 of the arterial integrity discussion will be about: sunlight! I’ve read ablut eNOS before, and it seems this is the direction you’re headed in? Could sunlight be that powerful? I think so.

    I’ve heard garlic is the best source of dietary sulfate. Curious about that too.

  3. What about antibiotics in farmed salmon though? (A comment made on that post from last year may not get a response)

    Don’t fish farms have similar practices of any other CAFO (antibiotics and hormones?)

  4. Australians have way fewer heart attacks than the English. Similar genetics, etc. The article sited sun exposure and increased NOs production as the reason due to vasodilatory effects.

    Evidence that the ApoB connection is related to high blood sugar sticking to LDL particles on ApoB receptor, and then our macrophages in the artery wall see that receptor with sugar and think it is a bacteria and eat it = foamy macrophages. So, LDLD damaged by excess sugar or infections (endotoxins) binding to ApoB create a target for plaque growth. That seems to be the bleeding edge evidence.

    1. Fascinating. Can you please recommend things to read on the matters addressed in your second paragraph. Thank you.

  5. Try to understand the attack on ones Arteries …as I have been diagnosed with a rare Coronary Artery Disease called Ectasia CAE….have it pronounced in left and right as well as 3 other Arteries…..bulging ..on a number of meds and just finished a round of Rituxan ….anyone familiar with this disease and how did I get it…and any treatment to reverse it…?Gary

  6. Increase ferritin with an iron man and an iron pan. That’s Mark’s iron plan.

  7. I am in Australia also, but travel to New Zealand frequently. In visiting the place where the actual Salmon are farmed I observed the fish being fed and was surprised (?) to see that they were being fed grains. Would that not affect the profile of the fish we are eating – in the same way the feed-lot beef has a poorer profile than grass-fed?

    1. This was exactly my concern, also the fact they often use factory farm offcuts in their feed pellets… I avoid tortured chicken at all costs so indirectly ingesting it doesn’t really appeal.

      1. Was there any mention of Faroe Island Salmon in this documentary. I have been told this is a very Eco sensitive and sustainable & humane practice.

      2. Time Travel, yeah farmed salmon in Norway, or Alaska (same) is pretty nasty most especially for the wild Salmon and local ocean wildlife.

    2. Maggie yes. i agree. i read a profile of wild and farmed salmon. same as CAFO”s, when animals/fish are fed corn and soy, their fatty acid, and nutritional profile is far worse than wild/grazed animals.

  8. Even though blood donors apparently live longer can you lose a substantial amount of any other nutrients with the iron?

  9. Two comments on the Atherosclerosis front:
    1) The process is long and slow and seems to start right after childhood – they say that fatty streaks are typically seen even in adolescents during autopsy.
    2) In the linked article it says:
    “Endothelial cell dysfunction is an initial step in atherosclerotic lesion formation and is more likely to occur at arterial curves and branches that are subjected to low shear stress and disturbed blood flow (atherosclerosis prone areas) (7,8). These mechanical stimuli activate signaling pathways leading to a dysfunctional endothelium lining that is barrier compromised, prothrombotic, and proinflammatory.

    So it seems that endothelial disfunction comes first, triggered by blood flow stresses. It’s common wear and tear in exposed areas. The patched knees on jeans. Managing endothelial health and healing may slow or diminish rate of progression or is it mostly too late for that?

  10. I found the Ldl information quite confusing. Do statins play any role in reducing this plaque in the arterial wall or do they prevent it from occurring?

  11. Ok- an add on question to the farmed salmon:

    After researching farmed NZ salmon on their website it list that their feed uses factory farm offcuts and vegetable oils. Surely this has an effect upon the nutritional profile of the fish? in fact it’s a mix of factory farmed meat, grains, corn, soy and vegetable oil. Even with the added small fish they mention as a supplementary protein added to their diets I imagine it is possibly not a great choice?

  12. Hi – I normally post at Malcolm Kendrick’s blog, but I saw a link to this blog.

    You wrote that raised LDL was a marker for CVD risk, but here is a list of studies that show that both total cholesterol and total LDL are slightly correlated with reduced mortality!

    Are these studies trustworthy?

    I know there is an argument that naturally low cholesterol is an indicator of disease, and that this distorts the picture, but doesn’t that sound more like an excuse to keep a failed hypothesis – the cholesterol hypothesis?