Identifying Natural COX Inhibitors
Separating the wheat from the chaff…
Today I want to start drilling down into specific natural products and supplement ingredients that have the potential to help with microclots and platelet hyperactivation in Long Covid.
Remember the plan here is to try to identify natural products and supplement ingredients that have the same mechanisms of action as the pharmaceutical drugs that make up Triple Anticoagulant Therapy. As a reminder, here are those three drugs and their mechanisms of action:
Research Process
Over the past few months that I have been working to find natural products and supplement ingredients that have these mechanisms of action, my first goal was to compile a comprehensive list of compounds to research.
To create that list, I’ve done a lot of literature searching, Google searching, and even going through the textbooks that we use in the natural product course that I teach in (I wrote a few chapters in one of the textbooks).
Here’s the comprehensive list that I came up with:
Now keep in mind, these are compounds that are supposed to be “anticoagulants” or “platelet activation inhibitors” or “blood thinners”. But that might not be true.
So the next step in my work was to take each compound and find peer-reviewed scientific literature to confirm whether the compound is an anticoagulant or platelet activation inhibitor and if so, what is the specific mechanism of action.
That’s a long list of compounds, so it’s obviously taken me a long time.
And I’ll be honest and say once I got to the 5th or 6th compound that wasn’t panning out to meet the criteria for the mechanisms of action we need, I changed tactics a bit.
I started using advanced search techniques in the scientific databases like PubMed to search each component against those three specific mechanisms of action. That allowed me to segment the comprehensive list into three lists based on mechanism of action.
Then for each compound on each mechanism of action list, I had to dig through the scientific literature to find publications that actually showed the compounds had that effect.
That task alone was much harder than I thought it would be. It’s amazing how many publications refer to the supposed mechanism of action of a natural product or supplement ingredient without providing a reference or any supporting data.
COX-1 and COX-2 Inhibitors
After completing that research process, here are the natural products and supplement ingredients that are COX-1 or COX-2 inhibitors (highlighted in light blue):
Now something interesting and a bit unexpected happened as I went through the list researching the mechanisms of action.
ALL of the compounds in blue above are platelet activation inhibitors.
And ALL of them inhibit COX-1.
But only a couple of the compounds also inhibited COX-2. Here’s the table that I made showing this:
That led me to ask the question:
Do we want just a COX-1 inhibitor or a dual COX-1/COX-2 inhibitor in the natural version of Triple Anticoagulant Therapy?
When we think back to Triple Anticoagulant Therapy and the component that we are trying to replicate – aspirin – we know that aspirin is a dual COX-1/COX-2 inhibitor.
But when we look at molecular pathways in platelets, we see that only COX-1 is involved in the platelet activation mechanism.
So is there another benefit to including COX-2 inhibition in the formula?
The answer is actually YES. Inhibition of COX-2 is where aspirin gets its anti-inflammatory properties.
So by including a dual COX-1/COX-2 inhibitor in the natural version of Triple Anticoagulant Therapy, we will not only get the COX-1 inhibitor we need as a platelet activation inhibitor, but we will also get a bonus anti-inflammatory effect.
That’s a win-win scenario in my book.
So we have four candidates to use that are dual COX-1/COX-2 inhibitors:
White Willow
Boswellia
Cat’s Claw
Olive Oil Extract
Reviewing the data for each of these and thinking about formulating one of these components into a capsule with other ingredients, I chose White Willow Bark extract as the COX-1/2 inhibitor for the natural version of Triple Anticoagulant Therapy.
That fills in the first slot on our table:
White Willow Bark Extract as a COX-1/2 Inhibitor - The Data
Below is data from a great literature publication that evaluates White Willow Bark extract as both a COX-1 and COX-2 inhibitor in an in vivo inflammation model in rats. (Ref 1)
In this work, inhibition of COX-1 was determined by measuring the ability of the tested compounds to decrease thromboxane B2 (TXB2) levels in blood plasma after inflammation was induced.
Inhibition of COX-2 was determined by measuring the ability of the tested compounds to decrease Prostaglandin E2 (PGE2) levels in blood plasma after inflammation was induced.
The compounds tested in both experiments were:
Aspirin (abbreviated ASA) - a dual COX-1 & COX-2 inhibitor
Celecoxib - a selective COX-2 inhibitor
White Willow Bark extract (abbreviated STW 33-I)
Here’s the data from the experiments:
COX-1 Inhibition
COX-2 Inhibition
As you can see from the data above, White Willow Bark extract (STW 33-I) inhibits both COX-1 and COX-2 roughly the same amount as aspirin at roughly the same dosage.
To quote from this publication, “…it was found that on a mg/kg bases [aka the same dosage], White Willow Bark extract (STW 33-I) was as effective as aspirin (ASA) in inhibiting both COX-1 and COX-2 enzymes.”
That makes White Willow Bark extract a great choice for the COX-1/2 component of our natural version of Triple Anticoagulant Therapy!
In my next piece, we’ll be looking at the natural products on the list that are anticoagulants and which one I chose for the natural version of Triple Anticoagulant Therapy.
So stay tuned!
For now, if you’re interested in getting a bottle of the natural version of Triple Anticoagulant Therapy as soon as ordering opens, go to www.getLongCovidhelpnow.com and put your name on the notification list.
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Reference
Mechanisms Involved in the Anti-inflammatory Effect of a Standardized Willow Bark Extract. Arzneim.-Forsch./Drug Res. 2005, 55(11), 677−687. 10.1055/s-0031-1296917
I’m following this closely, Keith. Your posts are great - so clear and logically laid out. Thank you!