HDL: What It Is, What It Isn’t, and What We Still Don’t Know
In the last post, we reviewed LDL and the family of ApoB-containing particles—the cholesterol-carrying particles that play a central role in atherosclerosis. HDL is often viewed as LDL’s counterpart, sometimes even its opposite. But HDL is frequently misunderstood, and its role in cardiovascular health is far more nuanced than the label “good cholesterol” suggests.
In This Article, We’ll Cover:
Vehicle vs. Cargo: Why "HDL" and "Cholesterol" are not the same thing.
The Smoke Alarm Analogy: Understanding HDL as a signal for metabolic health rather than a direct protector.
The Failure of HDL Medication: Why simply raising your HDL number doesn't necessarily lower your risk.
Causation vs. Association: What genetic studies tell us about the "Good Cholesterol" label.
The HDL-ApoB Relationship: Why a high HDL score cannot "cancel out" the risks of high particle burden.
HDL is not cholesterol
HDL stands for high-density lipoprotein.
It is a particle that circulates in your bloodstream. Cholesterol is one of the substances that particle can carry—but HDL itself is not cholesterol.
A helpful way to think about this is that HDL is the vehicle, and cholesterol is the cargo.
When you see HDL-C on a blood test, the lab is measuring how much cholesterol is being carried inside HDL particles—not the particles themselves. The “C” simply refers to the concentration being measured—the amount of cholesterol carried within HDL particles.
What HDL does (as far as we understand)
HDL particles are involved in several important biological processes, including:
Transporting cholesterol away from tissues and artery walls toward the liver
Participating in cholesterol recycling and removal
Interacting with inflammatory and oxidative processes in the body
These roles help explain why HDL has long been viewed as protective. But understanding HDL turns out to be more complicated than simply labeling it “good.”
Is High HDL Always Good? What Your HDL Number Actually Means.
The HDL value on a standard lipid panel reflects how much cholesterol is being carried by HDL particles.
It does not tell us:
How many HDL particles you have
How well those particles function
Whether they are behaving in a protective way
As a result, HDL-C is an imperfect snapshot of a much more complex system.
Association is not the same as causation
For decades, population studies have shown that people with lower HDL levels tend to have higher rates of cardiovascular and metabolic disease, while people with higher HDL levels often appear healthier.
But this does not prove that HDL itself is the reason.
More recent genetic research—looking at people who are born with lifelong differences in HDL levels—suggests that simply having higher or lower HDL cholesterol does not reliably change cardiovascular risk on its own.
In other words, HDL may be a marker of health rather than a direct driver of it.
An analogy that often helps: a smoke alarm does not cause a fire, but it can signal that something important may be happening.
Why raising HDL has not improved outcomes
This uncertainty is reinforced by clinical trials. Multiple medications have successfully raised HDL cholesterol levels, yet did not reduce heart attacks, strokes, or death.
The takeaway is not that HDL is unimportant. It is that raising the number alone does not fix the underlying biology.
If HDL is protective, that protection likely depends on how well the particles function—not on how much cholesterol they carry.
HDL as a signal, not a target
At Ikigai, we think about HDL as a signal.
Low HDL often travels alongside insulin resistance, sedentary behavior, and poorer metabolic health. This is not accidental—disrupted metabolic health changes how lipoproteins are produced and processed, which often results in lower HDL levels. In that context, HDL is pointing toward deeper physiological issues that do matter and are modifiable.
This is why we do not target HDL directly with medication. Instead, we focus on improving the underlying metabolic and cardiovascular health that HDL tends to reflect.
How HDL fits with ApoB (and why this matters)
As discussed in the prior post, ApoB reflects the number of cholesterol-carrying particles that can enter the artery wall and drive plaque formation.
This relationship is important to understand clearly:
A high HDL level does not cancel out risk from elevated ApoB
Improving HDL does not offset exposure to ApoB-containing particles
HDL can provide helpful context, but ApoB is far more directly tied to atherosclerosis and cardiovascular risk.
Both matter, but they play very different roles.
Common Question: How do you improve HDL?
Because HDL is a marker of metabolic health, it often improves through:
Vigorous physical activity: One of the few ways to reliably increase HDL-C.
Replacing refined carbs with healthy fats: Improving insulin sensitivity.
Smoking cessation: Which directly impacts HDL function.
Looking ahead
Many of the behaviors that consistently reduce cardiovascular risk—certain dietary patterns, regular physical activity, and improved metabolic health—also tend to be associated with higher HDL levels. That overlap is not accidental, but it does not mean HDL itself is the mechanism driving benefit.
In upcoming posts, we’ll focus directly on those behaviors and why they matter for long-term cardiovascular risk, rather than on trying to manipulate any single lab value.
A reassuring perspective
A low HDL number is not a diagnosis.
A high HDL number is not immunity.
HDL is one piece of a larger picture that includes particle burden, metabolic health, inflammation, blood pressure, physical fitness, and genetics.
Modern preventive and longevity medicine moves beyond “good” and “bad” labels and focuses instead on what truly drives disease risk—and what can meaningfully change it.
Understanding HDL is not about chasing a number.
It is about asking better questions.
Still have questions? Contact us to discuss what this means for you.
