Ask not what but how...
This information is taken from an interview with Dr. Malcolm Kendrick on the Nourish Balance Thrive podcast "The Clot Thickens", as well as the Primal Living podcast "What Causes a Heart Attack?".
Part 1 - “Impossible”
As described by the interviewer, experts are very vague when it comes to explaining the process of cholesterol in heart disease and are very quick to move to lipid metabolism and their favourite flavour of statin.
Kendrick recalls reading "the bible for cardiovascular disease” 30 years ago and looking for the explanation of how it happens and all he found was "LDL accumulates in the
arterial wall" which didn't help him understand anything!
I don’t think I need to explain this, but just in case, LDL is low-density lipoprotein or “bad cholesterol”.
After listening to 2 or 3 podcasts interviewing Kendrick his curiosity seems to stem from an offhand comment by a female researcher at Aberdeen university during a small group tutorial he attended.
She stated "LDL cannot get through the arterial wall".
While he didn't understand at the time, the way she said it made him think it had important implications.
He's spent the past 30+ years looking at Cardiovascular disease.
I think from here, it's best if I use Kendricks own words. "I found myself reading all about cells, cell membranes and receptors, gates and liposomes and cell transcytosis (transportation of molecules within a cell)...
but the one thing that stood out, for the LDL Hypothesis to work, you're having to transfer a molecule about the size of a virus (pretty large) out of the bloodstream and into the artery wall behind.
We know if you want to get LDL into a cell, you need
to have an LDL receptor. Once it's into the cell it's attacked by enzymes, the whole thing is broken down and it is used by the cell.
No receptor, no entry.
And yet the current thing seems to be LDL forces its way in, like osmotic pressure.
That can not be what happens.
Cells have to control very precisely what gets in and out. Cells can control entry of a single atom (sodium, calcium ions, etc).
What they are suggesting is that LDL will just pass through in some way.
That's not just unlikely, that is impossible.
Another possibility suggested is the LDL slips between the cells. Endothelial cells are joined together by tight junctions designed to let nothing through.
If you lose that barrier function of the endothelial cells, you are dead. You would die within 30 secs!
This is actually how the Ebola virus kills you, by opening up tight junctions and you bleed into your intracellular fluid
So it can't exist like that. That's the end of the LDL hypothesis"
Ok, wow! Dr Kendrick does go into even more detail and for the sake of time and sanity I've tried to keep it to the most important bits. Basically, there is no function of the cells in the arteries that would allow the LDL hypothesis to be plausible.
So if it isn't cholesterol or LDL that causes heart disease, what does?
Part 2 - The Clot Thickens
The Thrombogenic Hypothesis is very simple.
There is no 1 cause of heart disease but there is a single process.
It is purely damage to the endothelium (inner lining of blood vessels). That’s it. That’s the “cause” of heart disease according to this hypothesis.
When your endothelium is damaged, it then has to repair itself and it does this by creating a "micro" blood clot. It can then become a focal point for more damage and develop into an atherosclerotic plaque if the damage outpaces the repair process.
Examples of things that cause damage to the endothelium include high blood pressure (mechanical stress), high blood sugar, smoking and air pollution (microparticles) and sickle cell anemia.
All clearly very high risk factors for the condition in question. This is usually a sign your hypothesis is on the right track.
From there it gets a bit more complicated and of course I would recommend listening to the podcast, but I wanted to touch on a couple more key points and offer suggestions as to what you can do to accelerate repair
Maybe the big question I have left unanswered so far is why does cholesterol end up in the plaques inside the artery walls?
Kendrick explains that during the formation of a clot to repair damage many things are pulled from the blood to create the clot. In effect, I believe he is saying the cholesterol is there merely by coincidence, drawn in with other contents of the blood to form the clot. The clot is then shaved down by an enzyme called plasmin, converted from the protein plasminogen (which is in all blood clots) by tissue plasminogen activator and covered over with new cells, called endothelial progenitor cells which lay down a new layer of endothelium and seal the clot inside.
What about factors that seem to prove the cholesterol hypothesis?
Statins lower cholesterol and lower heart disease so cholesterol must play a role...
Statins also have anti-coagulation actions (stops blood clotting) and increase nitric oxide synthesis which has been shown to vastly reduce the risk of cardiovascular disease, among many other off-target effects.
So statins could theoretically be working by completely different mechanisms.
But you also have to explain the condition familial hypercholesterolemia’s (FH) association with cardiovascular disease - a genetic condition that makes you unable to remove LDL from the blood.
However, some studies show that they live just as long as anyone else, others have found that another condition is commonly linked with FH, high clotting factors. it seems you can find blood clotting and endothelial damage among all the risk factors for heart disease.
So if we're at risk of heart attacks and strokes through damaging artery walls, we obviously want to understand both how we can limit the damage but also improve the rate of repair.
Part 3 - Nitric Oxide Boost
We have already covered some of the main causes of damage, so you can protect yourself by doing obvious things like avoiding smoking, lowering blood pressure and keeping blood sugar and insulin low through avoiding processed foods and loads of carbs (for the most part). These are the main factors that we have lots of control over. What doesn't cause damage is cholesterol or saturated fat, although that isn't necessarily license to eat tubs of lard.
This is probably a good time to introduce you to a substance called glycocalyx. There’s a good chance you’ve never heard of it. It’s the same stuff that covers fish and makes them slippery. This sits on your endothelial lining and helps the components within the blood to flow freely.
Within the glycocalyx “fibrils” (Kendrick describes it as looking like a long lawn) sit anti-coagulant factors and all kinds of things to stop damage to the artery wall lining underneath.
High blood sugar for example, shrinks the glycocalyx down leaving the wall lining at greater exposure to damage.
So glycocalyx is pretty important.
“It also makes THE single most protective substance in your body, called nitric oxide”
Nitric oxide helps to open the arteries and also has powerful anti-coagulant effects, “anything that boosts nitric oxide, is good for cardiovascular health”.
So how do we get these levels up? One of the best things is sunshine. Exercise will increase your levels of nitric oxide. Foods naturally high in nitrates will convert to nitric oxide e.g. beetroot, celery, spinach, rocket, etc.
Also antioxidants like vitamin C, vitamin E and glutathione help to limit the breakdown of nitric oxide. Interestingly, certain bacteria in the mouth convert nitrate to nitric oxide and using mouthwash can kill these bacteria, meaning we can’t produce nitric oxide.
I’m sure there’s enough there to keep your mind spinning for a while. Of course, as always, I am only trying to offer an alternative view. It is entirely up to you how you use this information. But just to summarise, if we take this hypothesis to be correct, these are the recommendations:
Lower your blood pressure
Lower your blood sugar/insulin (low carb diet?)
Lower your stress levels
Avoid smoking
Get plenty of sunshine
Get plenty of exercise
Eat lots of vegetables
Get foods rich in antioxidants
No need to limit healthy fats, including naturally occurring saturated fats
So in essence, live a healthy lifestyle!
Maybe you still feel the cholesterol hypothesis is correct and saturated fat doesn’t belong in a healthy lifestyle, although I think even that is not contested as much as it once was, but no one will disagree with the rest of that list! Hopefully that encourages you to make any necessary changes and gain the incredible gift of health! What do you think, will this help you add some healthy habits into your lifestyle? Do you think the thrombogenic hypothesis has merit?
I’d love to hear your thoughts.
Stay healthy,
Ryan.
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