Dr. Cromwell’s Take on Low Carb and High Cholesterol from Robb Wolf’s Wired To Eat Bonus Material

Posted on by BJJ Caveman

As a pre-order bonus to Robb Wolf’s latest book, Wired to Eat, he provided access to an interview with Dr. William Cromwell, a lipidologist who is the Director of Cardiovascular Disease at LabCorp where they discuss the ins and outs of various blood tests.

Their discussion naturally made its way to lipids and LDL-P which is of particular interest to me given my own history of having high LDL-Ps.

When Dr. Cromwell encounters a patient with an elevated LDL, he first likes to understand why it’s elevated.  

Potential causes include:

  • Genetics
  • Thyroid disorders
  • Impaired glucose metabolism
  • Renal disorders
  • Liver disorders
  • Chronic stress/hypervigilance

This makes sense to me and is the approach that I encountered when I first met my lipidologist, Dr. Dall.  Instead of just handing out a statin to treat the high LDL, both Dr. Cromwell and Dr. Dall try to understand what the cause behind it is.  This is one of the main points that separate lipidologists from conventional general practitioners.

In my case Dr. Dall felt that insulin resistance was at the heart of my cholesterol issues, mainly based on my LP-IR score and HbA1c.  Knowing what I do now, I’m not so sure this is the case, but at the time, given the information we had, it made sense.

Here’s a case study by Dr. Dall illustrating her approach to a particular case.

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Insulin Resistance and High Cholesterol

In the podcast, Dr. Cromwell goes on to explain that insulin resistance can lead to both overproduction and decreased clearance of LDL.  In early insulin resistance, the liver over-produces triglyceride rich lipoproteins from the liver called large VLDL particles.

As insulin resistance develops, our fat cells don’t do as good a job of holding onto trigylcerides and they start leaching out into the bloodstream.  Once these travel through the blood and enter the liver, the liver packages them up into VLDLs to remove them and place them in an appropriate package.

There are then an increased number of VLDL particles floating around that become metabolized into small LDL particles leading to an environment where there are elevated levels of both VLDL and small LDL particles.

Along with this, the number of large HDL particles go down.

The combination of high small LDL, high VLDL, and low large HDL are one of the earliest signals of insulin resistance and is used to calculate the LP-IR score (lipoprotein insulin resistance score).

What About Low Carb and High LDL-P?

My ears perked up when Robb asks about the situation where people who were previously unhealthy with poor lipid markers start working out, eating low carb paleo, and become healthier in terms of weight, blood pressure, how they feel, their blood markers, and pretty much every other aspect of their life EXCEPT for LDL-P which seems to go up.

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Robb asked about my specific situation!

I guess my question for you — maybe a couple of different questions — but is elevated lipoproteins the same in a truly insulin-resistant person versus, say, someone who’s eating a low carb or a ketogenic diet where you need a private detective to find their insulin secretion? Are those the same people? It’s that really the same risk factor? Do we have enough data or do we just have to play a conservative story on that until we better understand it?

Dr. Cromwell’s answer was very fascinating:

That’s a great observation and a great question. So let me take it in two steps. The actual observation, I think we’re still learning a lot about. And there are those people as you characterized who everything is better but LDL-P.

There was a very interesting study that was done a long time ago, back in the ’90s. And what they demonstrated was that for individuals who are in a fasting type of diet, a little different than a Paleo but a fasting diet, that they were subset of people who had this elevation in particle number, LDL cholesterol, and it was tightly associated, interestingly enough, with a decrease in insulin growth factor 1. So when IGF-1 went down particle number went up. And that was an observation that was made. And it was not persistent in a lot of people. So for various reasons, some individuals kind of hung in like that for a while and then it kind of went back down to a normal level.

So I think I think the first question is yes, there’s a mixture of individuals who respond to what you described, the vast majority of them with an improvement at everything including particle number, but a subset in whom particle number appears to go up counterintuitively, and at least there’s one population in whom those people are also characterized as having a decline in insulin growth factor 1.

So then the question is how long do they stay that way if you just leave them in their diet and exercise mode as you described. Some of those people will go up for a few months and come back down. We don’t really know how many of those people would stay persistently at that level if nothing were changed. So that’s the first question.

And the second question is if it is deleterious it’s deleterious because there is this dose exposure over time model for LDL. And what that means is that high LDL is problematic because it stays high for a long time. If LDL goes up and it’s transient we have no indication that that harbors a particular cardiovascular risk. So think of it in the case of a genetic disorder, for example, familial hypercholesterolemia. This is a disorder which affects about 1 in every 200 and 1 in every 250 kids born in the US. It’s a problem of clearing LDL particles. And when you can’t clear LDL particles you have lifelong high LDL levels. Now, if you don’t do anything for these folks who have high LDL from childhood they begin to experience cardiovascular events decades earlier than the average bear, in their 30s and 40s, and what’s their problem? They’ve had a high enough LDL for a long enough period of time to accelerate atherosclerosis in advance.

So in response to your question is it a problem, it’s a problem if it stays that way for a long time. But if it doesn’t stay that way for a long time we have no data suggest that it harbors the same degree of risk as, say, the insulin-resistant person who has had this undetected but high LDL level for a very long time.

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To summarize what Dr. Cromwell says:

  • In a subset of these people, going low carb paleo can lead to a decrease in IGF-1 (insulin like growth factor-1), which then leads to an elevation in LDL particles.  Eventually however, these tend to come back down to normal (mine stayed elevated so I don’t think this is the case in my situation).
  • Elevated LDL for a prolonged period corresponds to elevated cardiovascular risk due to the dose exposure over time model (Again, this is just a model that was developed on patients eating a standard diet.  I don’t think any data is available yet in the subset of people who are eating low carb paleo and are otherwise healthier in every other respect).

Reading between the lines of what Dr. Cromwell is pretty much echoing what Dr. Pokrywka, a lipidologist from Johns Hopkins University said:

No one knows what the CVD [cardiovascular disease] risk of increased LDL-C/ApoB/ LDL-P is in LCKD states, and the evidence for the long-term safety of this dietary approach is lacking.

Robb also shares his personal story with elevated LDL-p which:

The very first time that I had this advanced testing with Specialty Health I think I was 2200-2400, something like that. We dug around and we figured out that I had a thyroid issue going on. And so we did some Natroid and then some Synthroid and kind of bounced back and forth. And I also curtailed my travel. And about three months later I think I was at like 750 or something like that. So we were able to get that addressed. I felt like hell for a while. I’d been on the road a lot and had been pretty beaten down, again, sleep disorder, hypervigilant state. My whole physicality was beat down but then clearly my lipidology was reflecting that same problem.

It seems like he was able to treat it by addressing his thyroid issues, improving sleep, decreasing travel, and overall reducing stress.

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If you liked this and want to learn more about cholesterol, here are some posts you can check out:

I know that Dave Feldman is doing some really interesting stuff at CholesterolCode.com which I’ve been meaning to dive into, so that’s another resource.

And if you want to pick up Robb Wolf’s Wired To Eat you can get it here.  Writing a review of this book has also been on my to do list, but in short, I liked it!

Category: Cholesterol

3 thoughts on “Dr. Cromwell’s Take on Low Carb and High Cholesterol from Robb Wolf’s Wired To Eat Bonus Material”

  1. Very interesting indeed — especially the fasting part. My LDL-P numbers have been similar (though, sadly, worse) to yours so I follow your posts as well as Dave’s at Cholesterol Code closely. I have tried every supplement out there, vastly upped my cardio workouts, backed out of ketosis, greatly reduced my sat fat, and added back a higher quantity of carbs, but my particle profile has actually gotten worse.

    I have taken to skipping breakfast, and I’m wondering now if this ongoing “fasted” state is actually making matters worse. My inflammation markers are all fabulous, as are all other lab measures. I’m actually contemplating testing low carb veganism for a month just to see the impact.

    Reading this transcript makes me wonder if the other lifestyle factors could really have that kind of impact I travel heavily, don’t get enough sleep, and certainly deal with a great deal of stress and “vigilant” nervous system states. I have avoided genetic testing, since I’m not sure that I actually want to know my APOE 3/4 status. Perhaps the next step is to find a functional doc who will treat for sub-clinical hypothyroidism — my current doc is great, but very cautious on that front.

    I’ve got a coronary calcium scan and carotid ultrasound scheduled for next month just to see if any of this lipid madness is resulting in measurable, clinical outcomes.

    I must say, this is a genuinely frustrating situation. Have you found any new approaches since your last cholesterol update post?

    Thanks for continuing to track this topic – I know it impacts a pretty small population, but it’s good to know that others are on the case!

    1. I actually went and got a Carotid Ultrasound test which I’ll be writing about eventually. But this calmed a lot of my fears and decided to focus more of my efforts and getting my weight down and my fitness up without worrying too much about my cholesterol.

      I’m actually due to get it checked soon so we’ll see how it looks now, but I’ve essentially been doing the same thing, eating lowish carbs with occasional carb ups, training BJJ 3-4 x a week, supplements, trying to improve my sleep, and actually feeling better over all.

      The whole dose depending model of LDL-P is still a hypothesis and we’re still in uncharted territory. It’s not guaranteed to lead to CVD. They’re just extrapolating based on studies on standard patients.

  2. After recently getting some blood work done and seeing high cholesterol, I found your site and have been reading through your journey.

    Do you have an update on where you’re at and if you’ve been able to make any changes to get it under control?

    The thing about my blood work that perplexed me, was that for over four months I’ve been eating pretty strict keto, and yet I had an A1C of 5.6. While still normal, I’m shocked it was this high while barely eating any carbs.

    Atm, I’m leaning towards simply far too much dietary fat putting stress on my liver (as my ALT was elevated as well)

    I just wonder if long term (speaking only for myself) a keto diet could actually be more deleterious to insulin resistance than eating a lower fat diet with more whole fruits and vegetables and just no flour/sugar …

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