It’s not the cholesterol that’s the issue, it’s the packaging.
High cholesterol is one of the most prevalent issues that Canadians face as they age. Many patients suffering from high cholesterol get recommended that they shouldn’t eat egg yolks because they have too much cholesterol and that there is good cholesterol and bad cholesterol. What does it even mean to have “high cholesterol” and what does the blood test actually measure? These questions are very important to answer and the science of cholesterol is so nuanced that it can be challenging for both physicians and patients to take the time to understand. However, there are many resources that can help people understand these concepts without getting lost in the woods of JAMA papers and seven hour podcasts with Tom Dayspring (I’ve done that for you). (Help.)
First let’s begin with what cholesterol looks like:
Cholesterol is absolutely necessary for you to live. It is a vital component of the cell membrane, aka the packaging, of every cell in your body. It’s also needed to make hormones in your body such as estrogen, testosterone and cortisol to name a few. It is used to make bile in the liver, an important substance that helps us digest fatty foods.
It’s so important, in fact, that every single cell in your body can make its very own cholesterol. Of our daily cholesterol turnover (800-1200mg), we make 75% and obtain the rest from our diet (300-500mg). Cholesterol is not the problem, it’s what it does sometimes is the issue. I know this is the issue you’re here for, but we’ll get to that.
The cholesterol in the picture is called a free or unesterified cholesterol. This is the only type of cholesterol that your body can absorb. When you eat food, the main type (>50%) of cholesterol found there is called cholesterol esterase which cannot be absorbed. The cholesterol you eat doesn’t make up a significant amount of the cholesterol in your blood. So then, how does frivolously eating bacon fat and egg yolks and hash browns and fatty steak (……wait, what was I talking about again?) contribute to the “bad cholesterol” that you sheepishly face when you get your blood test back? This requires an understanding of the actual blood test that’s done.
When you get a blood test done, it only tells you about the cholesterol in your blood. Since cholesterol is a hydrophobic substance, meaning it can’t dissolve in water, it has to be transported through your blood (which is mainly water) in a carrier called lipoprotein.
There are different types of lipoproteins such as LDL, HDL, and VLDL. “Hey!” You’re probably thinking, “I know some of these words!” LDL stands for low density lipoprotein and HDL stands for high density lipoprotein. They are the ones I will be focusing on but there are many different types.
The protein on the surface of this lipoprotein helps maintain structural integrity. LDL contains a protein on its surface called apoB and HDL contains apoAI. Sometimes, apoB can be found on other types of lipoproteins but mainly it’s with LDL. LDL and apoB have a pretty much one-to-one ratio. But since one HDL can have many different apoAI on its surface, you can’t figure out how many HDL there are by the number of apoAI. Like I said, this is kind of complicated.
But wait a minute, why do you care about these proteins? Because apoB sometimes does this thing, and I’m stealing this analogy from Peter Attia, where it parks illegally under the endothelium of, most famously, your carotid arteries along with the LDL molecule it was attached to. The immune system promptly arrives at the scene to manage this debauchery. White blood cells are generally pretty good at getting rid of the LDL from under the endothelium. When there is too much LDL there, however, the system gets overwhelmed and it crashes. The macrophages try to eat all the LDL to get rid of it and when they can’t digest it, they become foam cells. This turns into a clump which is called a plaque. When this plaque closes up the vessel so blood can’t get through, the downstream tissue (in this case the heart) can die. And this is atherosclerosis in a nutshell.
You’re probably thinking that it makes sense for your doctor to measure the amount of LDL that you have to figure out how likely you are for getting cardiovascular disease. But the blood test actually measures how much of your total cholesterol is found in LDL. Isn’t that the same thing? Nope. If we understand that LDL is just a car that carries cholesterol around and drops it off at different places, then we have to consider that sometimes the car could be empty. And for an apoB molecule on an LDL to violate the endothelium, it doesn’t need cholesterol passengers!! It follows that we actually care about how many LDL particles there are in the blood at any given time and not necessarily the amount of cholesterol. This is called your LDL-P, or LDL particle number.
In 2015, a study published in the Journal of Clinical Lipidology, they showed that when LDL-P>LDL-C then heart disease incidence was higher (n=511) than when LDL-P<LDL-C (n=553). When they were about the same the incidence was in the middle. Furthermore, in the Farmingham study of 2007 (J Clinical Lipidology), they followed 2500 patients for 15 years and found that LDL-C was only a good predictor of adverse cardiac events when LDL-P was also high. Here’s the craziest one though: a study of 136 000 patients hospitalized for coronary artery disease, HALF the patients had LDL-C of less than 104.9, and 17.6% had LDL-C less than 70mg/dl which is considered not at risk for cardiovascular disease. In a patient who was literally in the hospital for a cardiovascular disease related issue.
LDL-C can sometimes predict the number of particles floating around in your blood, but not always. Patients who have any kind of metabolic disease such as insulin resistance (contributing to diabetes) or obesity, have LDL-C values that correspond even less to the LDL-P values. This means LDL-C underestimates cardiovascular disease to a greater degree in these patients than in healthy ones!
There is the concept that increasing your “good cholesterol” aka HDL can somehow mitigate the risk for cardiovascular disease (CVD). There are many drugs that can increase HDL-C. In one trial niacin did just that, in 3000 people, it was able to increase HDL-C but it didn’t have any clinical benefit for CVD. There are many other such studies.
So what’s the actionable here? The Farmingham study showed that the more criteria you have along the spectrum of metabolic syndrome, the more difficult it is to predict your risk of CVD from your LDL-C. However, if ones improves their insulin resistance for example but eating less refined sugar, eating more whole foods (like whole eggs :p exercising, and managing your calories, one may be able to reduce the risk of CVD. It has been shown that the addition or removal of fat from the diet doesn’t really alter the lipid profile as profoundly as removing the refined sugar does.
We can’t eliminate the risk of cardiovascular disease completely because age is the most powerful risk factor. If you think about it, the more years you have, the more chances apoB has had to interact with your artery walls and the weaker your immune system is at dealing with it.
What I’ve learned from this is that there should be a shift to measure LDL-P in patients rather than just LDL-C, at least for those patients who have metabolic disease. Even though it is a more expensive measurement, it may be able to save lives with earlier intervention.
If this has inspired you to learn more about this topic, here are some links to some much smarter people who get into more juicy details:
- Peter Attia’s blog, a nerdier, more in-depth version of this.
- Goldberg AC et al. Journal of Clinical Lipidology 2011 vol 5
- Cromwell WC et al. Journal of Clinical Lipidology 2007 vol 1 (Farmingham study)
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