What actually determines how many particles you have?
Up to this point, the system has started to take shape.
Particles move through circulation.
They are cleared by the liver.
And over time, the number of particles determines exposure.
But that raises a more important question.
If particle number matters…
what determines how many particles are there in the first place?
For a long time, most of the focus has been on clearance.
Statins, PCSK9 inhibitors, and other therapies all work, at least in part, by helping the liver remove particles more efficiently. When clearance improves, particle levels fall. That relationship is consistent and predictable.
But clearance is only half of the system.
Particles Okaydon’t just circulate.
They are constantly being produced.
Every ApoB-containing particle originates in the liver.
Triglycerides and cholesterol are packaged together and released into circulation as very low-density lipoproteins. Each of these particles represents a new unit entering the system.
So at any moment, particle number reflects two forces:
- how many particles are being removed
- how many particles are being produced
Think of it this way.
Not as a number.
As a system you can actually see.
At any moment, what you measure is simply the balance between these two flows.
Under normal conditions, these two processes stay balanced.
Particles enter circulation and are cleared at a similar rate. The system remains stable, even though it is always in motion.
But that balance can shift.
In certain metabolic states, the liver begins producing more particles.
One of the most common examples is insulin resistance.
In this setting, the liver continues to produce triglycerides even when energy is already abundant. Those triglycerides cannot remain in the liver indefinitely, so they are exported into circulation.
And the only way to export them…
is by creating more particles.
As production increases, particle number rises.
And this happens before you even consider clearance.
At the same time, the same metabolic environment can impair clearance, reducing the efficiency of particle removal.
So the system is being pushed in both directions:
- more particles entering
- fewer particles leaving
This helps explain a familiar clinical pattern.
Triglycerides increase.
HDL decreases.
LDL-C may not look dramatically elevated.
But underneath that, particle number is rising.
From a cholesterol perspective, the system can still look “acceptable.”
From a particle perspective, it is not.
This is where the model shifts again.
Particle number is not just about clearance.
It is also about production.
And in many individuals, production is the dominant force.
Which leads to a different kind of question.
If we want to reduce particle burden over time…
are we only focusing on how particles leave the system?
Or are we also considering how they enter it?
That’s where the system starts to become actionable.
Continue reading - When Both Sides of the System Start to Fail
Or start here - The LIV System