Cholesterol Stopped by Red Mold: The Blueprint for a Drug to Protect Blood Vessels Sleeping Within Mold
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Table of Contents
1. Why is cholesterol quietly scary?
2. The roots of discovery: The drug was sleeping inside mold
3. Red mold and blue-green mold
4. Mechanism of action: Statins stop the liver's factory
5. The real reason LDL levels drop
6. Current treatment: Statins remain at the center
7. Summary
8. References
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1. Why is cholesterol quietly scary?
Cholesterol is necessary for the body.
It builds cell membranes.
It becomes the material for hormones.
It also becomes the material for bile acids.
Therefore, cholesterol itself is not bad.
The problem is when a high level of LDL cholesterol persists in the blood.
LDL cholesterol enters the walls of blood vessels, and oxidation and inflammation trigger arteriosclerosis.
Moreover, this change is quiet.
It doesn't hurt.
You don't get a fever.
You won't collapse immediately today.
However, inside the blood vessels, future risks are accumulating little by little.
Myocardial infarction.
Cerebral infarction.
Angina pectoris.
The drug that confronts this invisible silence is the statin.
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2. The roots of discovery: The drug was sleeping inside mold
The story of statins did not begin with blood vessels.
It did not begin with the liver either.
The beginning was mold.
Japanese researcher Dr. Akira Endo thought that there might be substances produced by microorganisms that suppress cholesterol synthesis.
The background to this idea was the existence of penicillin.
Penicillin is an antibacterial drug discovered from blue mold.
If so, might there be hints for a cholesterol-lowering drug among the substances produced by microorganisms?
Thinking this, many molds and microorganisms were investigated.
And what was found was a substance produced by a mold called Penicillium citrinum.
It was compactin.
It was discovered that compactin inhibits HMG-CoA reductase, an important enzyme involved in cholesterol synthesis.
From here, the history of the drug called statin begins.
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3. Red mold and blue-green mold
The title of this article is,
Cholesterol Stopped by Red Mold
.
I will organize things a little here.
Famous as the root of statin discovery is compactin, which Dr. Akira Endo found from the blue-green mold Penicillium citrinum.
On the other hand, red yeast rice, known as red mold, sometimes contains a statin-like component called monacolin K.
Monacolin K is known as a component that has the same structure as lovastatin.
In other words, the story of statins involves mysterious chemical substances created by mold.
The first statin found from blue-green mold.
A statin-like component that also existed in red mold.
Mold did not create it to lower human cholesterol.
In the natural world, microorganisms create various chemical substances to survive against each other.
Those small chemical substances happened to stop an enzyme in the human body.
That changed the history of cholesterol treatment.
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4. Mechanism of action: Statins stop the liver's factory
Cholesterol does not just enter from food.
It is also made within the body.
The center of this is the liver.
In the liver, cholesterol is made from acetyl-CoA through several stages.
Within that synthesis pathway, there is an enzyme that acts as an important gateway.
It is HMG-CoA reductase.
Statins inhibit this HMG-CoA reductase.
In other words, it is a drug that weakens the switch of the cholesterol factory inside the liver.
What is important here is that statins do not directly grab and discard LDL cholesterol in the blood.
They are not sucking it up like a vacuum cleaner inside the blood vessels.
First, they make it harder to produce cholesterol in the liver.
From there, the body's reaction begins.
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5. The real reason LDL levels drop
Cholesterol synthesis in the liver is suppressed by statins.
Then the liver judges that there is not enough cholesterol.
If there isn't enough, let's take it in from the blood.
So, LDL receptors increase on the surface of the liver.
LDL receptors are the entrance for taking LDL cholesterol from the blood into the liver.
The number of entrances increases.
LDL in the blood is collected into the liver.
As a result, blood LDL cholesterol drops.
The flow is like this:
Statin inhibits HMG-CoA reductase
↓
Cholesterol synthesis in the liver decreases
↓
The liver increases LDL receptors
↓
LDL in the blood becomes easier to be taken into the liver
↓
LDL cholesterol decreases
Statins are not just drugs that lower cholesterol.
They are drugs that utilize liver metabolism and receptor regulation.
This is quite beautiful as pharmacology.
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6. Current treatment: Statins remain at the center
Even in current treatment for dyslipidemia, statins are the central drug.
For people with high LDL cholesterol, improvement of lifestyle habits is important first.
Diet.
Exercise.
Weight management.
Smoking cessation.
Management of other risks such as diabetes and hypertension.
However, for people with a high risk of atherosclerotic disease or those who have already had a myocardial infarction, angina pectoris, or cerebral infarction, drug treatment becomes important.
The representative drug used there is the statin.
Currently, if LDL cholesterol does not drop sufficiently with statins alone, other drugs may be combined.
For example, ezetimibe.
This is a drug that suppresses cholesterol absorption in the small intestine.
Furthermore, PCSK9 inhibitors.
This is a drug that makes it harder for LDL receptors to be broken down, further lowering LDL cholesterol in the blood.
In other words, current treatment is:
Improvement of lifestyle habits
Statins
Ezetimibe as needed
Consideration of PCSK9 inhibitors, etc., if at even higher risk
It is a form that is built up according to the patient's risk.
Even so, the foundation is the statin.
The small chemical substance found inside mold is still at the center of dyslipidemia treatment.
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7. Summary
Statins are drugs that lower cholesterol.
However, their beginning was not inside blood vessels.
The roots of the drug were inside mold.
Compactin, which Dr. Akira Endo found, opened the path to inhibiting HMG-CoA reductase and suppressing cholesterol synthesis.
Statins stop the liver's cholesterol factory.
Then the liver increases LDL receptors and makes it easier to take in LDL cholesterol from the blood.
As a result, LDL cholesterol drops.
Even now, statins are at the center of dyslipidemia treatment.
Red mold.
Blue-green mold.
The world of invisible microorganisms.
Within it, the blueprint for a drug to protect human blood vessels was sleeping.
It was not just a coincidence that it stopped cholesterol.
It was a code of mold born in a corner of the natural world.
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8. References
・Japan Atherosclerosis Society: Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2022 Edition
・Endo A. A historical perspective on the discovery of statins. Proc Jpn Acad Ser B Phys Biol Sci. 2010.
・From Fleming to Endo: The discovery of statins.
・Endotext: Cholesterol Lowering Drugs.
・ESC/EAS Guidelines for the management of dyslipidaemias.
・StatPearls: HMG-CoA Reductase Inhibitors.