Thursday, June 9, 2011

My Healthy Skeptic Podcast Interview With Chris Kresser is Now Up

by Chris Masterjohn
My interview with Chris Kresser on his Healthy Skeptic podcast show is now up:

If you've been following my blogs and interviews on cholesterol and are familiar with most of my cholesterol material, you may find yourself in familiar territory at first, in which case you can skip ahead to the 60 minute mark where we discuss some of my criticisms about undue focus on LDL particle size, my suggestions about managing familial hypercholesterolemia, and my thoughts on the role of leptin and thyroid hormone in regulating LDL receptor activity by communicating energy and nutrient availability to our body for the purposes of strength, virility, and fertility.  This will serve as a comprehensive introduction and I'll be back a second time just to answer questions.

I'm a bit jammed for time but will try to write more soon.  Enjoy!

Read more about the author, Chris Masterjohn, PhD, here.


  1. Chris,

    This was an excellent interview for verbalizing your thoughts regarding dietary lipids and CVD and the role of oxLDL in this context. It was weaker when you talked about tNF and Leptin. Perhaps the latter could be explained at greater length at another opportunity.

  2. Chris,

    I know you wrote a post about FH mortality in the 19th Century, but what I didn't see you address is: if FH causes higher mortality, why it is so common (incidence of about 1 in 500 for heterozigotos FH; over 900 mutations in the LDLR gene cause FH)? Why natural selection did not eliminated FH?

  3. Anonymous, thanks, I'll get more into that in the future.

    Mario, check out the survival curve here (have to scroll down a bit):

    You can see that most people with heterozygous FH live through their reproductive years, so I don't think the fact that it hasn't been eliminated needs any explanation at all.

    That said, as I noted here:'s possible the risk was lower or, perhaps, there was some benefit when rates of infectious diseases were much higher.


  4. Chris:
    I think you also said that magnitude of LDL particle count not a worry if at acceptable levels? What did you mean by that? What would be an unacceptable level of LDL particles? Also, is it generally seen that for any LDL measurement, the number of particles is always higher, ie LDL of 120, but particle count of LDL of 2000.

    Thanks much.

  5. Steve, no one goes to the doctor and gets their "LDL" measured. They get LDL-C or LDL-cholesterol measured. LDL particle count is a totally different measurement than the concentration (mass per volume) of LDL-associated cholesterol and they can't be legitimately compared (e.g. higher, lower).

    I'm not sure if I said anything about "acceptable" levels -- I think what I said was in most cases, the sheer number of particles is not going to overwhelm the LDL recpetor, althogh this is theoretically possible if the number gets high enough. That is in fact what happens in the cholesterol-fed rabbit. But even in levels seen in FH, the levels go up because of decreased clearance. You don't generally see levels that high in people without FH or thyroid disorders.


  6. Amazing podcast Chris!

    It seems to me that the absolute number of LDL particles must directly correlate with their mean lifetime, and therefore their chances of oxidizing.

    As an engineer I'm inclined to model the median time of LDL in blood as a particle half-life in a mix tank. Consider two different steady state systems with the same rate of LDL production and degradation (in particles/time), but one has a much higher amount of free LDL particles in solution (blood) than the other. The biological half-life of the particles present at any given time will be much greater for the system with a higher particle count.

    This is consistent with your statement about LDLR activity being critical, because for a given rate of LDL production the steady state blood particle count will be determined by the degradation rate constant:

    0=d[LDL]/dt=production rate - (degradation rate constant)*[LDL]

    solving for particle count ([LDL]):
    [LDL]=production rate/(degradation rate constant)

    It seems like particle count then (independent of size) would be an accurate measure of both mean particle lifetime and LDLR function (degradation rate with dimensions 1/time) and therefore of atherosclerosis risk.

    As a side-note your thoughts on leptin really got me thinking, because I've been working on a project trying to figure out how leptin resistance at the blood brain barrier works biochemically. I wonder if the same (unknown) mechanism of leptin resistance is occurring in the liver.

    Looking forward to your talk at UCLA!

  7. One clarification... I don't mean to imply that the degradation rate of LDL actually is constant, just that it has a particular value in a given person at steady state. I know it's a saturable receptor-mediated endocytosis system, and therefore has hyperbolic relationship between blood LDL levels and degradation rate.

  8. Just a tip of the hat here for the clarity of your explanations. Rarely have I been able to visualize and comprehend such stuff so easily. Nice job.

    FWIW Dept: You are the person/thinker who convincingly persuaded me away from a low-fat diet which I had faithfully adhered to for 30 years. During that three decade stretch I adhered to something very close to the Dean Ornish's prescription (although the original inspiration was the now nearly forgotten Nathan Pritikin model.) I was hoping to avoid the fate of both parents who had heart disease in their early sixties, killing my father at 61. So I ate nothing but whole foods for years: tons of brown rice and vegetables, very little fruit (triglycerides), and moderate legumes. And plenty of beer here and there. And amazingly it seems to have worked. Four years ago, just before my 57th birthday I had a calcium score of zero. Yes, N=1, of course, but it tells you something I suspect: a diet of whole foods can keep heart disease at bay no matter what the macro nutrient levels. I finally switched to a much lower carb diet because my blood sugar was drifting up higher and higher and, after all, the logical understanding that saturated fat played a decisive role in shaping our genome is very persuasive all by itself. It can't be poison.

    In any event, brother, you put the picture together for me a few years back and ever since I've never felt better. The food is sooo much better! Thanks.

    Peter M.

  9. Chris - Great podcast. Towards the end you mention three strategies for dealing with FH, in descending order: 1) reducing inflammation and the clotting cascade; 2) eating an antioxidant rich diet from unrefined whole foods; and 3) reducing cholesterol. Can you expand on #1 a little with the kinds of things one can do to address this? Seems like 1 & 2 are related, but I'm wondering what factors outside of diet are important.

    Also you stress working with a physician. I raised FH as a possibility with my doctor and he said he wasn't inclined to test because his clinical response would be the same - statin therapy. Any thoughts on how best to navigate this?


  10. First, a big thank you for that interview Chris. I learned a lot and have a question.

    You stated that you are skeptical of the hypothesis that small, dense LDL particles fit into the artery lining and oxidize because the LDL can already be partially oxidized in the blood.

    What I did not hear explained (or I missed it) is what happens to the oxidized LDL particle already in the blood? How does it contact the artery lining?



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