Natural Products that are ACTUALLY Anticoagulants

...and meet the scientific definition

Last week, I started telling you about the work that I’d done to identify the natural products and supplement ingredients that matched the mechanisms of action of the pharmaceutical drugs in Triple Anticoagulant Therapy, the most promising treatment for Long Covid.

I told you briefly about the research process that I used. And we went through that process to identify natural COX-1 and COX-2 inhibitors to include in the natural version of Triple Anticoagulant Therapy I’m developing. At the end of that piece, I decided to choose White Willow Bark extract as the dual COX-1 and COX-2 inhibitor and a natural replacement for aspirin.

That filled in the first natural product on our table:

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Anticoagulants

Today, I want to tell you about the actual anticoagulants that I have identified using the same process and from the comprehensive list we’ve been examining:

As a reminder, we want to identify a natural anticoagulant that acts by a mechanism of action similar to apixaban in Triple Anticoagulant Therapy, to include as an ingredient in the supplement product to help with microclots.

Now before we get too far, I want to more precisely define what an anticoagulant actually is.

I have a very specific, very narrow definition, that is based on scientific mechanisms of action.

In order to precisely define an anticoagulant, we have to talk briefly about the Coagulation Cascade, which is the multi-step process by which clots are formed. Here’s the diagram of the Coagulation Cascade:

Now as you can see, this is a pretty complicated set of steps that are required to actually form a clot. The clot is the “Fibrin” formed in the bottom right-hand corner of the diagram.

To help simplify things, we subdivide the Coagulation Cascade into three parts: the Extrinsic pathway, the Intrinsic pathway, and the Common pathway. The Extrinsic and Intrinsic pathways are initiated in different ways:

• The Extrinsic Pathway is initiated by external trauma, like a cut or injury

• The Intrinsic Pathway is initiated by internal damage to the walls of the blood vessels, like from infection or inflammation

Both the Extrinsic and Intrinsic pathways funnel down into the Common pathway, which is where the clot is actually formed. 

When we look at all the enzymes in the Coagulation Cascade, we see many of them are named “Factor #” (abbreviated F#), where the # is a Roman Numeral. And once one of these Factor enzymes has been activated, an “a” is appended to the abbreviation, so the activated form is “Factor #a”.

On the one hand this is good because we see that there are a bunch of different enzymes that we can inhibit. But at the same time, it's super confusing. 

Regardless, these are the anticoagulant molecular targets that we have to work with.

So my definition, and the scientific definition, of an anticoagulant is a pharmaceutical drug or nutraceutical that inhibits one of the enzymatic steps in the Coagulation Cascade. 

And the best anticoagulants inhibit enzymatic steps in the Common pathway, so that they are effective at preventing clot formation regardless of how the clotting process was initiated (external trauma vs. internal damage).

So in trying to identify natural products and supplement ingredients that are anticoagulants, I did literature searches to determine if any of the compounds in the bullet list above inhibited enzymes in the Coagulation Cascade.

Surprisingly, very few natural product or supplement ingredients are true anticoagulants.

This was a huge surprise to me personally, because when I began this work and first had the idea of developing a nutraceutical version of Triple Anticoagulant Therapy, the initial thought I had was “I know there are a ton of natural products that are considered anticoagulants”.

But in reality, many of the natural product and supplement ingredients that are often referred to as anticoagulants are actually platelet activation or aggregation inhibitors. Meaning they don’t inhibit enzymes in the Coagulation Cascade at all.

So which compounds on our bullet list are actually anticoagulants? Here’s the very short list:

• Turmeric

• Red Clover

• Dong quai

And of these, we want to select the one that inhibits the same enzyme as apixaban in Triple Anticoagulant Therapy - Factor Xa.

Turns out that only ONE of the natural anticoagulants above inhibits Factor Xa: Turmeric.

So that is the anticoagulant that we are going to use in the natural version of Triple Anticoagulant Therapy to help with microclots.

That fills in a second block of our table:

Using Turmeric also has another bonus effect: It’s an extremely powerful antioxidant that can help fight the radical oxygen species (ROS) and oxidative damage to the mitochondria caused by Long Covid. 

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Turmeric as a Factor Xa Inhibitor - The Data

The active ingredient in Turmeric responsible for the anticoagulant, antioxidant, and anti-inflammatory activity is the polyphenol curcumin.

The effects of curcumin as an anticoagulant have been published. (Ref 3)

In vivo, it was shown that curcumin prolonged activated partial thromboplastin time (aPTT) and prothrombin time (PT) in human blood plasma, demonstrating that the natural product inhibits clot formation in the Coagulation Cascade.

To determine the mechanism of action, the ability of curcumin to inhibit Factor Xa enzyme activity was measured in vitro in a chromogenic assay. Curcumin does indeed inhibit Factor Xa with an IC50 of ~5 uM. Here the inhibition data from the paper:

To quote the findings from the paper:

• “The anticoagulant [curcumin] showed direct inhibitory effects on FXa activities at high concentrations” and

• “…these results suggested that the antithrombotic mechanism of curcumin…appears to be due to inhibition of fibrin polymerization and/or the intrinsic/extrinsic pathway”

Collectively, the data all shows that Turmeric, and its active ingredient curcumin, are a great choice Factor Xa inhibitor component of our natural version of Triple Anticoagulant Therapy.

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In my next piece, we’ll be looking at the natural products on the list that inhibit the P2Y1/12 receptor as the second platelet activation inhibitor to include in the natural version of Triple Anticoagulant Therapy to help with microclots and Long Covid recovery. 

So stay tuned!

For now, if you’re interested in getting a bottle of the natural version of Triple Anticoagulant Therapy when Presale Ordering opens on Nov 15th @ 12pm EST, go to www.getLongCovidhelpnow.com and put your name on the notification list.

If you want to hear more about this natural supplement, come join my email list or the Road to Long Covid Recovery Facebook Group.

Leave me a comment below and let me know what you think.

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Reference

1. Treatment of Long COVID symptoms with triple anticoagulant therapy. Research Square Preprint 2023, rs-2697680/v1. https://doi.org/10.21203/rs.3.rs-2697680/v1

2. Natural Products for Antithrombosis. Evidence-Based Complementary and Alternative Medicine 2015, Article ID 876426. http://dx.doi.org/10.1155/2015/876426.

3. Anticoagulant activities of curcumin and its derivative. BMB Reports 2012, 45(4), 221-226. http://dx.doi.org/10.5483/BMBRep.2012.45.4.221.