Cholesterol (Part I) - The Case For Correction
The word cholesterol is on everyone's mind when we talk about health problems related to the consumption of fatty foods. Since the beginning of the second half of the 20th century, when studies with significant impact were published in the USA, crusades against cholesterol have been waged, with awareness campaigns to reduce the consumption of foods high in cholesterol and, when necessary, to undergo targeted pharmacological therapy. All of this is due to the apparent negative consequences of high cholesterol levels on cardiovascular health, particularly in the role they play in the formation of fat plaques in our arteries (atherosclerosis) and the problems that can arise from this (e.g., acute myocardial infarctions).
Image 1 - Source: Time Magazine
The most common reasoning, conversely, is as follows: in order to avoid heart attacks caused by the deposition of fat plaques in our arteries (in people with high blood cholesterol levels), we should follow a diet that minimizes cholesterol consumption.
Is this reasoning correct? Only in part.
Being the dominant way of thinking for so long, both among professionals and non-professionals, it is ingrained in our culture. The medical community still explains things this way; drawing attention to patients regarding total cholesterol and helping distinguish "good cholesterol" from "bad cholesterol”. However, slowly, certain definitions and ways of thinking are changing.
What we commonly know as fats are a family of organic compounds scientifically referred to as lipids.
Lipids can take two easily identifiable forms for all of us:
Solid - fats
Liquid - oils
At a molecular level, the main types of lipids are three (1):
Triglycerides
Main constituent of body fat;
Play an important role in energy storage.
Phospholipids
Essential component of the cell membrane of our cells and their organelles.
Sterols (the most well-known is cholesterol)
Important substrate for hormone formation (e.g., testosterone, cortisol, progesterone); bile salts (which allow digestion); among others;
Facilitator in cell communication.
Some of these terms may be familiar to the reader of this text who, whether in more or less specialized readings, or even in conversations with their doctor, may have heard that we should try to have low levels of these through a healthy diet. However, here is where some confusion begins:
Of the 3 types of lipids that have been listed, triglycerides correspond to 95% of the total lipid quantity that comes from our diet. Phospholipids and cholesterol represent only 5% (1).
Thus, when we look at an analytical panel and see that a person's blood triglyceride concentration is high, we can review their diet. However, when on that same panel, the values of various types of cholesterol are altered, attributing that to the consumption of the same foods that caused the elevation of triglycerides is a flawed reasoning.
The terms commonly found in analytical reports related to cholesterol are known to anyone who has undergone a basic analytical check: total cholesterol, HDL cholesterol, and LDL cholesterol. These are the most frequent, and it is under the values of each that the medical community advises its patients. These values refer to one specific thing: the concentration of cholesterol in our blood (in a simplified way).
So, if the percentage of cholesterol we obtain from our diet is so low, why are we constantly concerned about its concentration in the blood and the potential consequences?
Despite this residual amount from what we ingest, given the importance of cholesterol functions, this compound is essential to the body, and our body is practically self-sufficient in its production, with cholesterol being synthesized in our liver and peripheral cells (2). Most of the time, these cells are self-sufficient, but when they need extra cholesterol, it has to travel from the liver to them through the "highway" of our bodies: the bloodstream. Here lies a problem: cholesterol (and triglycerides, which have been mentioned) are hydrophobic molecules, meaning they do not mix with water (we have all seen this when trying to mix oil and water without success). Since most of the blood is plasma ("water"), lipids have to be integrated into a carrier that can transport them from the liver to target cells. These carriers are called lipoproteins.
Image 2 - Source: Cleveland Clinic
These carriers can transport cholesterol and triglycerides inside them from point A to point B and are classified according to their density.
Image 3 - Source: Molecules
Two of these types of lipoproteins will be familiar to the reader:
HDL - "good cholesterol";
LDL - "bad cholesterol".
These definitions of "good" and "bad" are slowly falling out of use because they are incorrect. As mentioned earlier, HDL and LDL are a type of lipoproteins (cholesterol carriers) and not cholesterol itself. The cholesterol each of them carries, or that each of the other lipoproteins listed in the chart carries, is always the same: cholesterol. What differentiates them is the destination for which they transport that cholesterol:
HDL (2)
Can transport excess cholesterol from cells to the liver, where it is eliminated as bile (reverse cholesterol transport);
Allows, when further input is not needed, regulation of the absorption of dietary cholesterol through the intestine.
LDL (1)
Primary transporter of cholesterol from the liver to cells, and in pro-inflammatory states such as obesity or situations of excessive consumption of triglyceride-rich foods, increases the number of smaller and denser LDL in circulation, with greater potential for atherosclerosis development.
In other words, cholesterol is always the same, but the transport promoted by HDL aims to regulate its levels, while that carried out by LDL can lead to atherosclerosis.
When, in our blood panels, we see the definition c-HDL (cholesterol-HDL) and c-LDL (cholesterol-LDL), the results refer to the blood concentration of cholesterol transported in each of these lipoproteins. On the other hand, the total cholesterol value, as it encompasses the concentration of cholesterol in all types of lipoproteins in circulation, is a value whose utility is very limited and, fortunately, has fallen out of use.
Considering that LDL has great potential for atherosclerosis formation, the LDL-c value should be sufficient to inform us about our risk; however, this is not the only particle with this capacity: VLDL, IDL, and chylomicrons also contribute to this phenomenon.
Thus, it is essential to have a measure that is even more precise in assessing this risk.
The mentioned lipoproteins can be divided into two distinct families, considering an essential component in their formation and metabolism found in their outer layer, called apolipoprotein (1):
Apolipoprotein A (ApoA) - present in HDL;
Apolipoprotein B (ApoB) - present in LDL, VLDL; IDL and chylomicrons.
Since ApoB is present in all atherogenic lipoproteins (one ApoB for each lipoprotein), the laboratory quantification of these is a much more precise measure to understand the number of carriers with the potential to develop fat plaques in our bodies, compared to simply the blood concentration of cholesterol transported in LDL.
While most doctors still use the other metrics, such as c-LDL, these more precise methods are slowly gaining traction into our daily practice, and worldwide major institutions and publications are supporting them (link 1).
Within this group of lipoproteins, there is also a type of lipoprotein (similar to LDL) called lipoprotein (a) - LP(a) - which has an apoprotein - Apo(a) - linked to ApoB. Apo(a) is similar to a procoagulant component of our body (plasminogen), which means that elevated levels of circulating Lp(a) increase the potential for thrombotic events (1). The levels of this lipoprotein are related to genetic polymorphisms, not other factors, so its assessment should be done only once in a lifetime to decide if there should be any intervention, but it represents one more factor that needs to be assessed in a lipid profile panel.
For all these reasons, as doctors, we need to get the message straight, in order to convey to our patients in terms of diet (we should be moderate in the consumption of foods rich in triglycerides, especially saturated fats - and not rich in cholesterol, specifically) and in terms of blood panels (the amount of cholesterol transported in particles with atherogenic potential should be assessed through ApoB measurement, and the amount of cholesterol transported in particles that help regulate cholesterol levels in the blood should be assessed through ApoA - instead of discussing "good" and "bad" cholesterol).
These two topics will be the themes of the next chapters of this piece on cholesterol: the correct diet and the appropriate analytical evaluation.
It is of utmost importance that the general population understands these definitions, and doctors have a clear message with no room for confusion.
Only then our common goals will be achieved.
1 - Manual De Lípidos - Sociedade Portuguesa de Aterosclerose, coord. Francisco Araújo (1ª edição, 2021);
2 - Tom Dayspring, M.D., FACP, FNLA – Part II of V: Lipid metrics, lipid measurements, and cholesterol regulation - The Drive Podcast (Peter Attia)
