In this episode we cover:
- The functional approach to high cholesterol
- Six underlying causes of high cholesterol
- Conventional markers are not accurate predictors of cardiovascular risk
- Other important cardiovascular risk markers
- How I approach familial hypercholesterolemia
Chris Kresser: Hey, everybody. It’s Chris Kresser. Welcome to another episode of Revolution Health Radio. This week, we’ve got a question from Tyler.
Tyler: Hey, Chris, really enjoy the podcast. I’ve been listening and interested in a Paleo diet ever since I heard you on the Joe Rogan Experience podcast last year. I’m somebody who takes statin medication for familial hypercholesterolemia. I’m wondering if you thought a Paleo diet would still work for somebody like me who’s on that statin medication, and I just wanted to get your thoughts on that. Thank you.
Chris Kresser: Thanks for sending in your question, Tyler. It’s a great one, but unfortunately, it’s difficult to answer in a short time. In a conventional paradigm, this is a really black and white, or binary, issue. You have total cholesterol and LDL cholesterol that are tested regularly, and if they are high, then the doctor will typically prescribe a statin and the patient is instructed to take it for the rest of his or her life and that’s the end of the story, but the reality is actually far more complex. We could do several podcasts on this topic. In fact, we could probably just dedicate a podcast to it and do it over and over again because there’s so much information to cover and there is so much new research that comes out that changes the landscape. Four out of 10 people that die each year die of a heart attack, so this is obviously a really big problem and one that doesn’t lend itself well to pat answers on a 20-minute podcast.
I’ve written a lot about this, and in fact, I got my start in this field writing about the relationship between cholesterol, lipids, and heart disease over 10 years ago now. Some of the earliest writings that I did were on this topic. More recently, I wrote an entire updated series on cholesterol and heart disease which we turned into a free ebook which you can download from chriskresser.com. If you haven’t already done that, then definitely check that out. One of the earliest digital programs that I put together was one called the High Cholesterol Action Plan, and if you Google “high cholesterol action plan” you’ll find it, and we can also put a link in the show notes, but this is a course that goes into much, much more detail than the ebook does because I got so many questions about this topic over the years, especially as I was writing about it early on. I just wanted to have a resource that I could direct people to that went into a lot more detail and provided a lot more assistance than I could ever do in a blog post or an ebook. So, if you haven’t checked all that stuff out, I would definitely do that.
In this show, I’m going to just provide an overview of what I think the key factors are to be thinking about with this particular question.
The Functional Approach to High Cholesterol
The first factor is to understand that a functional approach to dyslipidemia, high cholesterol, and even familial hypercholesterolemia is really different than the conventional approach. For those listeners who aren’t aware with familial hypercholesterolemia (or FH, as we’re going to call it so I don’t have to say that every time), FH is a disease that is—well, I mean, I don’t like the term disease but that’s what it’s referred to as—it’s a condition that is genetically mediated. There are genetic mutations involved that lead to very high cholesterol levels, often higher than 300 mg/dL. Believe it or not, it’s not that easy to test for. Some of the genetic testing that you have to do to completely be certain that you have it is very expensive and not widely available. In many cases, doctors will just—there are certain criteria called Simon Broome criteria that can be used to get a more accurate indication of whether FH is likely to be present. But I’ve seen that many clinicians in practice, if they see a total cholesterol above 300, they’ll often just diagnose the patient with FH on that basis alone, which is not a particularly accurate way of doing it, but there is certainly an argument to be made that FH is likely if total cholesterol is north of 300 mg/dL.
Six Underlying Causes of High Cholesterol
Anyways, back to the factors here. As I said, the first factor to consider is that the functional approach to dealing with this issue is very different than the conventional approach because in functional medicine, we view high cholesterol not as a disease but as a symptom. What is it a symptom of? Well, there at least six key underlying processes that can lead to hypercholesterolemia:
- One is metabolic dysfunction
- Another is chronic infections like H. pylori or even latent viral infections
- Another is gut dysbiosis permeability, that’s number three
- Number four is poor thyroid function, and this doesn’t have to be frank hypothyroidism, it can even be subclinical hypothyroidism or the thyroid is just—it’s not completely shut but it’s just underfunctioning, it’s not functioning optimally. In fact, back in the ’80s and prior to that, before statins came onto the scene in a big way, doctors used to use low doses of thyroid hormone to treat high cholesterol even when the patient had relatively normal thyroid numbers.
- The fifth cause is environmental toxins, especially heavy metals.
- And then the sixth cause would be genetic.
There are, of course, others, but those are the six main ones that we look for in functional medicine. We explore all of these causes to determine and address whatever the underlying or root pathology is because if you treat the root, that will often fix the branch. If you think of the disease process like a tree, the roots are those core pathologies or underlying mechanisms that lead to the symptoms, which in this analogy are the branches. You can mess around with the branches and try to deal with things on that level, which is the conventional approach, or you can try to address the roots of the problem, which is what we’re doing in functional medicine.
In a conventional paradigm, it’s really a lot more about symptom suppression. If you have high cholesterol, you take a drug to lower it, a statin drug in this case. If you have high blood pressure, you take a drug to lower that, and it’s the same for many other conditions.
In your case, Tyler, you mentioned that you have FH, which means we know you have at least one of the six underlying factors present—the genetic predisposition, but that doesn’t mean that other factors aren’t also playing a role. In fact, I see this very often in my practice where the patients come in and they already know that they have FH but when we do a full comprehensive workup, we find that they also have poor thyroid function, SIBO and gut dysbiosis, maybe a latent chronic infection and heavy metal toxicity and all of those things are exacerbating the genetic predisposition to high cholesterol.
Conventional Markers Are Not Accurate Predictors of Cardiovascular Risk
The second factor to consider is that conventional lipid markers, which are the ones that we typically have tested for if you go to your doctor for routine blood work, so I’m talking about total cholesterol, LDL cholesterol, and HDL cholesterol, are not accurate predictors of cardiovascular risk. The most recent research has shown that these markers, total and LDL cholesterol, are not strongly associated with heart disease. The ratio of total-to-HDL cholesterol as well as non-HDL cholesterol, which is similar, are better predictors than total cholesterol or LDL cholesterol, but they are nowhere near as predictive as some of the newer markers like LDL particle number, which in turn itself isn’t as predictive as lipoprotein(a), or Lp(a). These markers, they tell us something different than the standard lipid markers.
The standard lipid markers tell us how much cholesterol is inside of the lipoproteins, so if we use an analogy in your bloodstream as like a highway, the passengers inside of a car are equivalent to cholesterol inside the lipoproteins, whereas the cars themselves would be equivalent to the lipoproteins. Extending this analogy, if you have a lot of cars on the road, there is a much greater likelihood that they’ll get into an accident, they’ll be off the road and slam into the side of the road, and the side of the road here would be the fragile lining of the artery, the endothelium. If you have a lot of LDL particles, which is reflected in the LDL particle number measurement, then because atherosclerosis is a gradient-driven process, there’s a much greater likelihood that one of these LDL particles is going to damage the fragile endothelium and initiate the process of plaque formation.
With lipoprotein(a), we know this is a different type of lipoprotein. I’m not going to go into a lot of detail here because it’s, I guess, pretty geeky, but it’s known as one of the most atherogenic lipoproteins that have been identified and it’s the single most significant lipid risk marker for heart disease. Of all of the things we could measure in terms of lipid markers, lipoprotein(a), or Lp(a), is the most predictive for future risk of heart disease.
The point of this second factor is that what we measure is important. Usually, doctors are only measuring total and LDL cholesterol, but what we really should be measuring as clinicians are things like LDL particle number, HDL particle number, and lipoprotein(a). These give us a much better idea of overall risk.
Other Important Cardiovascular Risk Markers
Third factor is that lipid markers, even the good ones, are only one part of the puzzle when it comes to quantifying overall risk. We need to look at things like family history, inflammatory markers like C-reactive protein, fibrinogen, Lp-PLA2, oxidized LDL, metabolic markers, so things like fasting insulin, fasting glucose, fasting leptin, post-meal blood sugar, hemoglobin A1c, and a variety of other markers that tell us what’s happening with metabolic function. Hypertension and smoking are two of the strongest risk factors for heart disease, hands down, so those of course should always be looked at. Diet, lifestyle, stress, nutritional status—either not enough of nutrients like vitamin D or too much of a nutrient like iron can increase the risk of heart disease. Status of the gut microbiota, there is an increasing amount of research that shows that this plays a significant role in heart disease pathogenesis.
There are certain calculators out there that are available for free online that use at least a small number of these risk factors. The Reynolds Risk Score, for example, uses C-reactive protein and systolic blood pressure in addition to age, total cholesterol, HDL cholesterol, and family history to determine the 10-year risk of heart disease expressed as a percentage. You enter all of your information in and it turns back up a percentage of what percent of the risk you have for having a heart attack in the next 10 years based on all of these validated criteria. The lowest it could be is 1 percent, and then it goes up from there, and you can put different numbers in there and play around and see what has the biggest impact on risk, and you’ll see that it’s not total cholesterol or even HDL cholesterol, but age actually is the biggest risk factor for heart disease. You’ll see changing the age around has the biggest impact on that risk prediction.
There are other types of testing that look for objective evidence of plaque accumulation, like a calcium score and CIMT, and these are tests that a doctor can do when/if they are warranted, and they provide a different angle. The lipid markers are just looking at blood markers that are typically associated with heart disease, but a calcium score and carotid intima-media thickness test can tell you what’s actually happening in terms of plaque accumulation.
How I Approach Familial Hypercholesterolemia
Those are three factors to consider, and here’s how I would approach someone with FH: I’ve had many patients with FH, so this is what I actually do. I would start with a more advanced testing to determine what their LDL particle number, lipoprotein(a), and other important markers are like—fasting insulin, fasting post-meal glucose, inflammatory markers etc.—and then I do a thorough history and get a thorough family history as well. We do then an entire functional medicine workup to determine if they have other contributing factors like SIBO, dysbiosis, infections, heavy metal toxicity, hypothyroidism, etc. We address all of those factors that we discover in that extensive workup. Then we retest all of these markers, and if they are then normal, great, our work is finished.
If the markers are still elevated, we’ll move onto a more detailed risk quantification. We may refer them out for calcium score, a CIMT, and we may look at some of the other risk factors, lifestyle, stress, etc. Then if we deem that the risk is still significant, we’ll try more advanced diet modification strategies. If they are a hyper-responder to saturated fat and that increases their LDL particle number, we might put them on more of what I call a Mediterranean Paleo approach, which is Paleo that’s lower in fat and higher in Paleo-friendly carbohydrates, whole-food carbohydrates like starchy plants, and even whole fruits, non-starchy vegetables, and then we’ll emphasize monounsaturated fat more than saturated fat. Then, we might use some supplements that have been shown to reduce LDL particle number and address inflammatory processes like delta and tocotrienols, pantethine, curcumin, etc., and these will often lead to a significant reduction in these various biomarkers that are risk factors for heart disease, even lipoprotein(a), which is in the conventional paradigm, thought to be almost entirely genetically mediated and not really amenable to diet and lifestyle change. Furthermore, it’s not typically affected by statins.
If the numbers are still high after all of that, which is a lot, that process takes typically several months if not longer because of all of the testing and all of the dietary intervention and the retesting, exploring, and investigating all of those various underlying causes, then if the numbers are still high and the patient is in a very high risk group, only then would I, especially if it were me, consider statins and other medications. Statins are not effective, as I mentioned, for reducing lipoprotein(a) in many patients, and so if that’s the primary marker that’s still elevated after all of this workup and treatment, those patients may need new drugs called antisense nucleotides, or ASOs, that specifically target lipoprotein(a). That’s just one example of how even the pharmaceutical aspect of the treatment, if it’s determined that it’s needed, can be more individually tailored based on the patient’s unique circumstances and based on the most recent evidence rather than just using a one-size-fits-all, black-and-white approach, which is the typical way that it’s done in the conventional paradigm.
Tyler, I realize this may have raised more questions than an answer perhaps. Unfortunately, that’s what happens when you dig into some of these topics. And this is, as I said at the outset of the show, certainly one of the most complex and nuanced areas of medicine and treatment. There are so many different things to consider and I think the big public health campaign during the latter part of the 20th century was oriented around making this message as simple as possible, so that people would comply with the diet and lifestyle recommendations that were being made. This really oversimplified the message of “cholesterol is bad and if you have high cholesterol you need to bring it down and you should take a statin to do that” is really out of date and not in sync with the most recent scientific evidence, and the lipidologists, the folks out there like Dr. Tom Dayspring and others, are way, way ahead of how they approach cardiovascular disease and have been for many many years but that has not trickled down into the mainstream understanding at lexicon and to the average primary care doctor’s office. The training for primary care doctors is really out of date unless someone is really taking an initiative to stay on top of all of this stuff or if they are lipidologists themselves. Even a lot of cardiologists are not current with this information and so it’s a problem for patients who are trying to get help. It is really difficult to do that from your local doctor unless they are really staying abreast of all of these more recent developments. At least this podcast can give you some food for thought and places to look for further information and discussion with your practitioner.
We’ll put some links to all of the resources that I mentioned here in the show notes, and for everybody else, keep sending in your questions. Tyler, thanks again for sending your question in, and that’s it for today. I’ll see you next time. Take care everybody.