Here are the basic mechanics – the first in a 3 part series on Cholesterol, Fats and Heart disease. The mis-information is too great, the beliefs are skewed, and the truth is that most of you can eat cheese and butter (and eggs!) and never get heart disease. But first you have to understand how you do get heart disease.
Cholesterol is essential to life. 50% of all cell membranes of all tissues are made of cholesterol. Most of the cholesterol our body uses to build these membranes comes from internal production, in the liver, about 75%. We get only about 25% from our diet, because much of the cholesterol in foods is not absorbable by the body – it is what is called esterified, and our gut lining is built to only absorb non-esterified cholesterol. Cholesterol is the precursor to all sex hormones. Babies need cholesterol to ensure brain growth – myelin and synapse formation need large amounts of cholesterol. Cholesterol maintains the intestinal wall, and is itself an antioxidant that protects against damage. The body tightly regulates the amount of cholesterol in the blood by regulating internal production. If you eat a lot, your body will produce less. So, dietary intake has much less impact on cholesterol levels than we have been led to believe.
Cholesterol travels through the blood on the back of proteins – “Apo” proteins, that bind to fats, and become “Apo lipoproteins”. Cholesterol comes in various forms, including Low Density and High Density, but because they are fat and do not mix with water, they are carried around the bloodstream attached to the Apo proteins, forming lipoprotein particles: LDL = Low Density Lipoprotein, HDL = High Density Lipoprotein.
Lipoproteins don’t only carry cholesterol. They transport triglycerides, fat-soluble vitamins and antioxidants to all cells. The body packs the cholesterol for its travel through the body with these vitamins and antioxidants with dual purpose – the antioxidants are carried around the body, but they also protect the cholesterol, which is prone to oxidation, and oxidation of cholesterol is dangerous. Lipoproteins also transport cholesterol back to the liver to be excreted. Although LDL has been vilified, the truth is that LDL cholesterol is actually necessary and useful in its proper form. It inactivates bacterial toxins to be taken out of the body, and also carries excess cholesterol back to the liver.
High cholesterol – is it bad for me?
Most people make the assumption that high cholesterol is bad, and low cholesterol is good, because this is what we have been told. But it is not necessarily the case. As I will explain, high LDL particle number, not cholesterol itself, is a risk, but simply because more particles make it more likely that an adverse event will occur. Cholesterol itself, in its healthy form, appears more beneficial than harmful at a higher number than prescribed by the US Dietary Committee.
The Framingham heart study had 50k participants. The information was used for many things, but one of the findings was a direct association between falling cholesterol levels and death. Long-term low cholesterol meant a greater risk of death. Another large scale study in Japan of 47k people found that the highest death rate was in those with lowest cholesterol. 200-260 total cholesterol was found to be the best range for the longest life.
It was also noted that those with the highest decline of levels were at the highest risk of cancer. Low cholesterol levels were correlated with 2x higher rates of violence and depression.
The US Dietary Committee recommendation for total cholesterol has been getting lower – it was 220, now it is 199.
But total cholesterol numbers are not universal. Traditional populations are generally free of heart disease, for example the Masai. Their diet consists predominantly of meat, milk and animal blood – and their average total cholesterol is very low – 130. The Kitav people eat fish, coconut, starchy tubers, and fruit their average numbers are 180 for men /240 for women. Eskimo Inuit people’s average total cholesterol runs 205-225 – and heart disease is very rare in their populations following traditional diet. So normal cholesterol numbers can vary greatly.
More importantly, we have been taught incorrectly about cholesterol risk.
Total and LDL cholesterol alone are only weakly correlated with risk.
This is why about half of the patients who have heart attacks have “normal” cholesterol. Many of the patients at highest risk will have even low LDL cholesterol, and those at low risk might have higher overall cholesterol numbers.
We have not been looking at the right correlations.
LDL vs HDL
LDL was given a bad name when it was thought that HDL was the component that returned extra cholesterol to the liver for excretion, but it is now known that LDL is also responsible for this. LDL is the low density protein, of which 50% of the weight is cholesterol, and 25% protein. HDL is 20% cholesterol and 50% protein. The protein is more dense, so the HDL particle is “High Density”. LDL contain B-proteins, HDL contain mostly A-I and A-II proteins.
As noted, the LDL particle is made up of cholesterol and ApoB protein. This particle is constructed in the liver and sent out to deliver the cholesterol to where it is needed in the body, through the bloodstream. The ApoB protein is not only a structural component or a facilitator in helping carry the fat through water-based blood. It is also the maître d. In order for the cholesterol to get into the cell, the ApoB presents the cholesterol to the cell via a receptor on the cell.
So, receptors are important, or the LDL particle will remain in the bloodstream. And this is where the danger comes.
The longer the LDL particle remains in the bloodstream, the more likely it is to suffer oxidative damage, and the more chance it has to affect the wall of the artery. So the more LDL particles you have floating around your bloodstream, the more risk you have. Each particle has exactly one ApoB protein. So the number of ApoB proteins represents the number of particles. It is the LDL particle number, and the state of the cholesterol in that particle that is the risk factor.
How do LDL particles cause heart disease?
Here is the situation in which LDL particles can initiate heart disease:
Our patient, patient X, has bad eating habits, and the gene that tells the body to create LDL receptors is off because his thyroid hormone is low so no receptors are being made.
His liver is busy packaging and sending the cholesterol and protein particles out, including LDL particles. Unfortunately because there are not enough receptors, the particles are rejected from the cells and sent back out into the bloodstream.
LDL particles come in various sizes depending on how much cholesterol is present and how much triglyceride, and it has been found that the smaller more dense LDL particle is the most dangerous – this is the “unhealthy” form of LDL cholesterol. The smaller denser more dangerous LDL particles appear to be correlated to higher levels of triglycerides.
So patient X is eating a lot of pastry and bread and sugar, and his body turns this into triglycerides. And so now he has a higher concentration of smaller LDL particles, in constant contact with the artery lining.
One of these small “unhealthy” LDL particles, which stays in the bloodstream because it can’t find a receptor, gets stuck – it accidentally lodges into the artery wall, the space under the lining – the arterial lining is only one cell deep, so easy to damage. The body knows this particle isn’t supposed to be there, so it triggers immune cells and an inflammatory response. Maybe the LDL particle has already become oxidized from being in the blood, or maybe it happens now, but the particle becomes oxidized, and easier for the proteoglycans in the artery wall to hang on to. Oxidized LDL also impairs the release of artery-protective endothelial substance, and so the artery cannot protect itself from inflammation. One of the cells the immune system sends to help is called a macrophage, and this cell surrounds the LDL particle in an attempt to destroy it. But the LDL-particle laden macrophages get stuck, and start to form fatty streaks of cells in the lining. This aggregation is cemented as the body stimulates collagen formation as a repair, and this forms a fibrous cap over the fat-laden macrophages. Deposits form the blood attach to this in the form of plaque. Oxidized LDL also stimulates something in the body called MMP. Unfortunately, although this measure is meant to help, MMP actually ends up weakening the cap plaque deposits. If this cap ruptures, this oxidized and dangerous material travels through the blood to the arteries of the heart, and causes a cardiovascular event such as a heart attack.
So, it is not LD cholesterol that is the problem, nor is it the Low Density Lipoprotein particle itself that is the problem.
It is the number of LDL particles overall, the size of those particles, and oxidation, or health, of those particles.
Now you can see the situation – perhaps someone is on statins, so they have low LDL cholesterol. They also have a lower number of particles most likely. But maybe the particles, the cholesterol in the particles themselves, is not in the healthy form – the particle is full of triglycerides, and oxidized. This person, although having “low” cholesterol, is at high risk for a cardiovascular event.
In the next installment I will explain how dietary cholesterol and fats affect blood levels.