Monday, May 16, 2011

I'll Be on Chris Kresser's Podcast to Talk About Cholesterol -- Have Any Questions?

by Chris Masterjohn

Chris Kresser was once accused of being me.  This Friday, we are going to definitively falsify this hypothesis by both appearing on Chris's The Healthy Skeptic Podcast show at the same time.

The podcast won't be up until June 21st, but in just four days Chris and I will be discussing all things cholesterol:
Chris Masterjohn coming to talk about cholesterol
We won't have much time for questions, but if you have any burning ones leave a comment here or over on Chris's site and we'll try to get a few of the most popular or important ones.

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


  1. Chris you need to speak on the failed CETP trials and why lowering LDL to the levels cardiology wants is not biologically plausible based upon physiology and biochemistry

  2. The pro-statin camp is finding new ways to push them on to more populations. Attacking high HDL as a negative risk-factor is one such way. What do you have to say about the role of HDL and how one can use their high HDL to resist the pressure of starting a statin?

    Another manner in which docs are pushing statins is particle testing. I've heard Dr. Michael Richman out of Beverly Hills, CA go on the radio and tell people that even if their total cholesterol is below 200, they may have an overabundance of lipoprotein particles and need a statin. Here's the link:

  3. I would love to hear your BEST plan for those with familial hypercholesterolemia. If oxidation of overabundant LDL is the problem, what is the best solution for those of us with this genetic problem?

  4. Can you make a comment about what it might mean when the optometrist sees cholesterol deposited in the eyes.


  6. What did you eat the day before the podcast?

  7. I am 34 years old, weigh 227 pounds (started at 250), and my cholesterol has been as follows (mmol/L);

    1st September 2010
    HDL - 1.9
    LDL - 3.6

    29th December 2010
    HDL - 1.7
    LDL - 3.0

    9th May 2011
    HDL - 2.1
    LDL - 4.0

    From 1st January 2011 I have been on a pretty strict paleo diet (except that I have a few beers on weekends), however after my last test, the Dr freaked out and basically gave me a spiel about eating low fat and lots of grains etc (along with the usual pamphlets that I threw in the bin).

    Whilst my HDL has steadily gone up, it appears my LDL has as well.

    Since starting paleo I have been steadily losing a little weight, but lots of changes in clothes sizes. My Dr says this is irrelevant - my weight and cholesterol reading put me in the 50% risk range for cardiovascular disease.

    My research to date indicates that fish oil can produce this effect, however I am only on a maintenance dose which is a lot less than Robb Wolf recommends.

    My Dr is unlikely to order the test to check whether LDL is nice and puffy or oxidised (we argued about diet as it was).

    Is this increase in HDL and LDL normal when starting on paleo and is it something I should be worried about?

  8. What amounts of saturated fats and overll% fat would you recommend for ApoE4/4 genotypes?

  9. Thanks for sharing the links and this post! great job!

  10. Looking forward to the podcast w/Chris Kresser tomorrow. I've been pouring over your online writing for the last two days to see if I could find something already posted on the specific area, but without success [so far].

    My burning question has been a challenge to put together, but goes more or less like this:

    Is there a diet-related response to this whacked-lipid scenario? Near 50, male, always looked younger than his years, both parents alive in their 80s, athletic in his youth, has a physically active job, non-diet areas [stress/rest] could use tweaking, better than average diet, TC>300 TG 500-1000+ LDL/VLDL diff to calc HDL consistently <40. At best TC:HDL was 10.7. Liver/pancreas testing seems fine. Nothing out of the ordinary in any other labs. Slightly heavier than could be - 25.2 BMI w/17.7% body fat. Lipids are always better in non-fasting testing, but never great.

    ID'd hypertriglyceridemea by accident [first time lipid testing]. Siblings tend to have slightly elevated TC and slightly low HDL, but none have flagged the TG [at least yet].

    Wondering what to look at next [with a doc that is looking worried], but seriously not wanting to go with statins. He started CoQ10, Fish Oil, B6, Folate, Niacin in March and waiting on more recent labs. Sounds like he might want to drop the Fish Oil and seriously reduce or eliminate his s/r nut habit. Possibly increase the CoQ10. Push for testing pituitary/adrenals maybe, but there isn't a lot more to look at from what we can tell [haven't done the more elaborate lipid testing]... although we can still do a screening for CAD.

    And is there ever a lipid case where meds are the answer? Would love to hear a resounding "no," but curious for opinions.

  11. also... TSH was fine. Nothing flagging thyroid either.

  12. Here’s another kind of question, late, but not so suitable for a podcast anyway:

    It’s generally thought atherogenesis involves problems related to cholesterol transport through the arterial endothelium by LDL particles. It had been assumed that LDL particles normally diffuse passively through gaps in the endothelium, but this is wrong.

    In normal endothelium, LDL is transported, not by diffusion, but by a tightly controlled process of transcytosis.

    What are the implications of finding that the normal-passive-diffusion hypothesis is bunk?

    (One may also wonder how a misconception about something this important, elementary, and observable could persist for so long. We’re not talking about puzzling correlations and confounders here, but about observing the behavior of cells in normal tissue!)

    Here are some papers and excerpts from before and after:

    Nature, 2000:

    “The endothelium, with its intercellular tight junctional complexes, functions as a selectively permeable barrier between blood and tissues… a primary initiating event in atherosclerosis is the accumulation of LDL in the subendothelial matrix. Accumulation is greater when levels of circulating LDL are raised…”

    Current Opinion in Lipidology, 2009:
    Transendothelial lipoprotein transport and regulation of endothelial permeability and integrity by lipoproteins

    “Previously, the endothelium was considered as a passive exchange barrier of lipoproteins between plasma and extravascular tissues. This dogma is challenged by recent findings... The endothelium actively controls the trafficking of lipoproteins between intravascular and extravascular compartments…”

    Cell and Tissue Research, 2009:
    Caveolae and transcytosis in endothelial cells: role in atherosclerosis

    “The endothelium plays an important role in the regulation of molecular exchanges between the blood and peripheral tissues. The transport of molecules between tissues must be tightly controlled in order to maintain homeostasis between the different organs of the body…This transport mode has been demonstrated to involve plasma-membrane vesicles that may be transferred with their cargo components from the apical to the basal side of endothelial cells…”

  13. Actually, this is not false. While transcytosis may occur, paracellular diffusion also occurs. Shear stress (parallel blood flow, which is increased by exercise and intrinsically lower at arterial branch points) decreases paracellular diffusion whereas inflammation increases it. Anitschkov did elegant experiments demonstrating this in rabbits at the beginning of the 20th century, and modern work has continued to demonstrate it and also to work out the molecular pathways. The central role for "cholesterol" in atherosclerosis is, in my view, bunk, but paracellular diffusion of LDL particles is not.


  14. We actually postponed the podcast a few days but it will air on schedule (June 21). Any questions that don't get addressed (likely most of them), I will try to turn into blog posts eventually. Thanks everyone!


  15. Yes, it occurs, but apparently as the result of damage, hence my perhaps opaque reference to the "normal-passive-diffusion hypothesis".

    I’d think that finding that LDL transport is normally tightly regulated would call for some reassessment of previous models.

    I see no reason why it would affect your own general lines of evidence and reasoning in any direct way, but transcytosis is part of the puzzle, and its normal role casts doubt on simplistic ideas about elevated LDL concentration directly and necessarily driving elevated LDL transport, cholesterol deposition, etc., etc. This indirectly supports your case.

  16. Anonymous,

    I will look into it in greater detail, but right now I do not believe it requires "damage" to occur, if "damage" is taken to mean an unusual case of damage, rather than the 'normal' levels of minor assaults a healthy person would see every day. Damage certainly enhances paracellular diffusion, but some seems to naturally occur, especially in the branch parts of arteries where shear stress is lower, and, consequently, gene transcription of junction complexes is not sufficiently upregulated. However, I agree with you that a "big picture" view should take into account transcytosis, and thank you for pointing that out.


  17. I should add that one could argue that the organism (human, rabbit, whichever one is considering) is designed to be very active, moreso than would occur for a rabbit in a lab or for a human in our society, and that this activity would cause sufficient blood flow to minimize paracellular diffusion even in branch points, and thus there is some "optimal" lifestyle where paracellular diffusion does not normally occur, or occurs very minimally. Although I think this would need some directly supportive evidence to be more than a speculation.


  18. Hi,

    I'd like you to address something that probably is quite common in the paleo/low carb community: raised LDL. From random searches on the internet, I have come to the conclusion that this isn't as uncommon as people might perceive. I myself never got myself tested while I was on a standard diet, but after about 6 months on a cyclic low carb diet (I would eat carbs on the weekend), this was my lipid profile:
    TC: 376
    HDL: 81
    TGs: 83
    LDL: 286 (calc)

    It came as a bit of a shock to me as I was under the impression that low carbing improved blood lipids. Now, there's no way of knowing what they were before, but I doubt my LDL would have been THAT high on a high carb diet. Granted, the HDL and TGs wouldn't have been this good either.

    It's been a couple of months since and I made a few changes to my diet, namely making sure I kept my carb-ups clean on the weekend, since I was eating pizza and pastries earlier which I now know was far from ideal, also I've tried reducing the saturated fat by totally cutting out butter and cream, though I still have cheese occasionally. I also get some saturated fats from eggs, olive oil, nuts and dark chocolate, but that's about it since I don't eat red meat much. I've also increased my fish oil consumption to about 2700-3000mg of EPA/DHA per day. Previously, it was around 1800mg. Lastly, I've ensured I take a good multivitamin everyday, after reading Paul's blog post about micronutrient deficiencies. I was taking one earlier as well but have a more potent one now.
    Two months after incorporating these changes, my lipid profile looks like this:

    TC: 274
    HDL: 52
    TGs: 61
    LDL: 202 (calc)

    LDL is still high and the TC/HDL ratio has actually worsened because the HDL has dropped too. I exercise 6 days a week with weight with a couple of sessions of HIIT thrown in occasionally.

    I'm sure you would have come across such cases before but I am yet to read a definitive answer as to why people who adopt a healthier paleo lifestyle end up with high LDL numbers. If it happens, what's the best way to get it down? I know your stance on LDL is that it's oxLDL that's the bad guy, but I'm sure you don't suggest that an LDL over 200 is perfectly healthy either. My LDL calculates to be about 174 from the Iranian equation, but that's still enough to make everyone around me question my eating habits, even though I KNOW I'm healthier now than I was before. I would love some discussion on this as it's sorely needed, in my opinion. I've ended up cutting saturated fat from my diet simply to bring the LDL down, not really believing that it's going to make me any healthier. It's brought my LDL down but also brought my HDL down. What's a guy in my position to do? I know that if my LDL doesn't reach 'normal' levels soon, my family will basically force me to go back on a high carb diet. It's something I want to avoid at all costs.

  19. Chris,

    In case the interview hasn't happened yet...

    My daughter's studying to become a nurse and is taking a nutrition class this semester. I had a look at the section on saturated fat in her textbook and it says basically don't eat saturated fat because it raises your cholesterol. In support of this it sites "Effects of Dietary Fatty Acids and Carbohydrates on the Ratio of Serum total to HDL Cholesteral" by Mensink et al.

    I've read the study a good half-dozen times. It's a meta-analysis of 60 fat feeding trials with humans. I'm planning on at least spot-checking a few of the studies it relies on. Any chance this has been done already someplace?

    Even if all the studies were methodologically pristine and all the data unassailable, it's interesting that the study still says that replacing carbs with just about any type of fat will improve triglycerides and lower LDL particle size. Since the textbook overall harps on the benefits of a low-fat diet, I thought this paper an odd choice to support the contention.

    In any case, I'm wondering if you've seen the paper and if it provides anything worth bringing up in the podcast. I guess what I'm really getting at is how do we counter things like this when making presentations or in discussion? I've seen this paper referred to in other forums as "proof" that eating saturated fat worsens your cholesterol profile. (Total to HDL being the measure of choice in the paper.)

    Any thoughts?


  20. Hi Allen,

    Let me know if this helps:


  21. See. That's why I asked you. Because, in the parlance of the lab where I work, you are a smokin-awesome super-science beezitchinator!

    The post was quite helpful, thank you.

    So, if I'm reading the paper correctly, all forms of saturated fat, except stearic acid, improved (lowered) the Total:HDL ratio relative to carbohydrate. Further, dietary carbohydrate raises triglycerides relative to any type of fat and shifts LDL particle size down, which is bad.

    My arm is getting tired from flogging this study, however, I'm baffled by Figure 4. It lists a bunch of dietary fat sources and charts their impact on Total:HDL ratio if 10% calories from an "average" diet is replaced with one of the selected items.

    There seems to be a lot of things missing that would help put things in context with the rest of the paper. Shortening is listed, but there's no indication whether that's from lard or Crisco. Is shortening supposed to be a saturated fat in this chart? No idea. What's the difference between stick and tub margarine? What the hell is chocolate fat?

    Basically this chart seems to say if I stop eating carbohydrates and start drinking straight shots of rapeseed oil, I should live forever. Hmm.

    Also, I'm not good at figuring out what things on the list are trans-fats. If there's one thing they seem to say in this paper more than "carbohydrates make your triglycerides high" it's "trans-fats should never get into the human body even as massage oil or naughtiness lubricant."

    Okay, you don't really have to respond to this post. The more I read and discuss this paper, the more ridiculous it seems as support for the low-fat (especially low-sat-fat) diet my daughter's textbook recommends.

    Thanks for your response!


  22. Hi Chris,

    Did you complete a 14 day waterfast recently?

    (If yes)

    How did it go for you?

    Do you have any thoughts or resources on extended fasting? (whether water or protein sparing / low-reward)

    Thanks, and good luck on your WAPF speech :)


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