Supplements that Share A Key Pathway With Hydroxychloroquine for Coronavirus
Of all places, NPR.
Driving home the other day (essential travel - grocery store), I was struck by a news program on NPR.
There were some snarky remarks on hydroxychloroquine and how it's not FDA studied, etc.
We've already covered in detail how hydroxychloroquine works for coronavirus here and fully expect that the NY trial starting yesterday will deliver game-changing results by the time you're reading this.
The host and guest (Kaiser Foundation) we're basically poo-pooing the buzz on hydroxychloroquine with the clear aim of dissuading the public from seeking it out.
They then showed their cards.
When asked why there was a shortage or run on it by the host, the Kaiser foundation rep stated:
"Doctors are writing scripts for themselves, their families, and friends".
It totally erased the prior 15-minute warnings of frivolous thoughts about hydroxychloroquine being a potential agent of change with coronavirus.
The Kaiser guest's main argument is that it hasn't been FDA approved for coronavirus.
Read the review on hydroxychloroquine here with supporting research and determine for yourself.
Our goal isn't to wax political but really to look at whether there are other safe and effective supplements that mirror the key pathway of hydroxychloroquine.
It turns out that there are and it all centers around zinc.
Taking zinc supplements or increasing zinc in the blood won't help here.
It's zinc absorption into the cell down to the very machinery that coronavirus uses to replicate.
There's also an interesting tie in with cancer (anti-cancer effects).
We'll cover these topics:
- A quick review of how hydroxychloroquine works
- Hydroxychloroquine as a zinc ionophore
- Zinc PH effects and coronavirus
- Quercetin and EGCG as zinc ionophore for coronavirus
It may sound really technical but we'll walk through it and decipher along the way.
This just may be a discount way to get access to a key hydroxychloroquine pathway in case the medication is "sold out".
A very real possibility based on the doctor's and dentist's initial response.
A quick review of how hydroxychloroquine works
It really helps to see the lay of the land here.
The primary effect of hydroxychloroquine appears to result from increasing the PH levels within the cell at a specific spot needed by coronavirus to make more of itself.
PH is just the level of acid to base. Like with a swimming pool.
There's an assembly line going on within each of your cells and two key players are fast at work.
- Endosomes - work like material separators and shippers
- Lysosomes - works like the stomach of your cell
Once the coronavirus gains access to your cell, it will put these to work to make more viruses that then spreads out into the body.
Here's the deal...coronaviruses (especially the SARS variety like covid19) require the low PH end of the endosome to thrive.
The "late" endosome is just further down the assembly line.
PH is really important as it shifts from higher (early endosome) to lower (late endosome) in a typical cellular function.
Okay, before we lose you...here's the deal.
Hydroxychloroquine raises the PH levels in the cell including the endosome!
Don't take our word for it:
Both CQ and HCQ are weak bases that are known to elevate the pH of acidic intracellular organelles, such as endosomes/lysosomes, essential for membrane fusion.
The net effect of this PH shift is a reduction in virus production!
In brand new research, they could actually see a 10 fold drop in the virus (technically called virion for the individual players) coming out the late endosome after hydroxychloroquine.
Again, check out the hydroxychloroquine and covid19 for the full walkthrough and research.
An initial study out of France combined this with azithromycin (also explained in the link above) for pretty powerful results which the NY study is now trying to replicate on a bigger scale.
So...is this just a quirk or hydroxychloroquine or do they know actual pathway it uses to raise the PH levels?
Hydroxychloroquine as a zinc ionophore
It turns out that hydroxychloroquine has a unique trip up its sleeve.
It's able to carry zinc across the cell's wall.
The technical explanation:
A substance which is able to transport particular ions across a lipid membrane in a cell
Studies found that chloroquine, a sister-molecule to hydroxychloroquine with the same effects were able to carry zinc across the cell membrane in such a fashion:
Chloroquine enhanced zinc uptake by A2780 cells in a concentration-dependent manner, as assayed using a fluorescent zinc probe.
They also showed that there was no effect on copper or iron. In fact, they used a technique to specify the effect on zinc.
One of the effects:
Chloroquine exerts a pleiotropic effect in eukaryotic cells, including an elevation of vacuolar pH when trapped in acidic organelles, such as lysosomes.
So, hydroxychloroquine is able to carry zinc specifically across the cellular gate.
Why does this matter for coronavirus?
Zinc PH effects and coronavirus
Different viruses actually focus on different segments of the assembly line.
As we mentioned above, the coronavirus (especially SARS group) really focuses on the low PH levels of the late endosome.
First, studies looked at boosting cellular zinc levels in cell cultures:
In this study, we demonstrate that the combination of Zn(2+) and PT at low concentrations (2 µM Zn(2+) and 2 µM PT) inhibits the replication of SARS-coronavirus (SARS-CoV) and equine arteritis virus (EAV) in cell culture.
It looks like zinc is the kryptonite to viral activity across the board:
Zn2+ ions inhibit viral entry, local replication, and spread to the organ during the viral pathogenesis process.
Again...only INSIDE the cell. Not just supplementation.
We need something to take the zinc across the cell membrane like hydroxychloroquine.
As we mentioned, hydroxychloroquine may be hard to come by for a bit during the surge of the pandemic.
So...are there other known zinc ionophores?
Remember...it's not just about taking zinc. It's about increasing its level in the endosome/lysosome of our cells.
Turns there are.
Quercetin and EGCG as zinc ionophore for coronavirus
In our CBD as antiviral for coronavirus, we also looked at supplements that have NIH documented antiviral effects.
Quercetin was on the list and now, maybe we know why.
EGCG is an extract from green tea and both are very safe.
We love quercetin separately because of its ability to support our toxin-removal pathway called Glutathione (see CBD and glutathione).
So...what do these two have in common with hydroxychloroquine?
Only the combinations of the chelators with zinc triggered a rapid increase of FluoZin™-3 fluorescence within liposomes, thus demonstrating, the ionophore action of quercetin, epigallocatechin-gallate, and clioquinol on lipid membrane systems
Let's translate the Klingon please.
Essentially, they showed that quercetin and EGCG were able to transport zinc across a lipid (fat which makes up cellular walls) barrier. An Ionophore for zinc!
This is the same special ability that hydroxychloroquine has.
Both of these substances belong to a class of chemicals called polyphenols.
Essentially, polyphenols are created by plants to deal with stress and remove ROS (reactive oxygen species).
Keep in mind that plants are also in an age-old battle against viruses as well.
Many of the substances that we derive benefit from in plants originate from this class (polyphenols) and flavones which act as protective barriers from bacteria and viruses.
Remember that different viruses have different approaches to breaking into our cells and even specialized niches where they thrive.
SARS (such as Covid19) need the low PH of the late endosome.
The ability to transfer zinc across the cellular barrier like hydroxychloroquine make EGCG and quercetin interesting workarounds.
Let's look at them separately.
Quercetin antiviral effects for coronavirus
We covered this partially in our CBD as an antiviral but let's dig deeper.
Aside from the zinc ionophore effect, quercetin is showing other effects directly on virus function.
One study on H5N1 flu found that quercetin would actually bind to a key receptor that viruses use to gain entry into our cell:
The study indicated that quercetin may exert its antiviral activity via interaction with viral HA protein and then inhibit virus entry into the cell.
What's that HA mentioned there? Its hemagglutinin.
The viral envelop protein hemagglutinin plays a critical role in virus entry.
That's H5N1 and every virus has its own special way of working.
What about SARS which Covid19 belongs to.
Assays with the HIV-luc/SARS pseudotyped virus showed that quercetin also had antiviral activity against HIV-luc/SARS, with an EC50 of 83.4 μM (Fig. 3).
The chart showed a drop in viral activity from 100 to 25 with increasing quercetin levels (still well within a healthy range).
What about EGCG?
EGCG antiviral effects for coronavirus
So in addition to the zinc effect (or maybe because of it???), EGCG is also showing interesting antiviral effects.
Again, let's zero down to SARS so it's specific to the coronavirus or covid19 class.
There's a key pathway that coronaviruses like covid19 use called 3CLpro.
This is an enzyme used by the virus to do its work.
The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is vital for SARS-CoV replication and is a promising drug target.
Okay...before your eyes glaze over, why does this matter for EGCG?
Quercetin, epigallocatechin gallate and gallocatechin gallate (GCG) displayed good inhibition toward 3CL(pro) with IC(50) values of 73, 73 and 47 μM, respectively.
Okay….there's quercetin and EGCG (the epigallocatechin) leading the back in blocking this key virus pathway.
That's going deep into the weeds but the net effect for EGCG:
EGCG appears most likely to inhibits the early stage of infections, such as attachment, entry, and membrane fusion, by interfering with viral membrane proteins.
What about safety of these two substances?
After all, there are side effects for hydroxychloroquine?
Safety of EGCG and Quercetin for Covid19
This is probably our favorite part and it really leads into the next section as to whether one is better than the other.
Both of these substances had validity long before we were sheltering in place.
Anti-cancer effects (via the same zinc pathway) and toxin removal were front and center.
As a widespread flavonoid, quercetin is a safe and dietary supplement based on its broad range of biological effects in animals.
Quercetin has been safely used in amounts up to 500 mg twice daily for 12 weeks.
Make sure to work with your naturopath or doctor with any supplement.
Initial animal studies pointed the way:
From these studies, a no-observed adverse effect level of 500 mg EGCG preparation/kg/day was established.
There is a difference between the two when looking at two in terms of safety.
What is the best supplement to mirror the PH effects of hydroxychloroquine
Both work as zinc ionophores like hydrochloroquine.
The viral protein effect was the same in the above study (73 and 73).
The safety profile, however, for quercetin is much better for a broader range of people.
If you read the safely research for quercetin, it's really strong.
EGCG can have issues with specific medications and and other health issues.
It's really a question of kidney and liver function for people with impaired function there.
Studies are showing that Quercetin is about 35% as potent as hydrolchloroquine for the zinc transport function.
Based on our hydroxychloroquine and coronavirus review, they were using 400 mg to start and 200 for follow up days.
That would put the quercetin dosage just over 1000 mg per day which fits with the safelty test above (500 mg x 2 for 12 weeks).
Of course, the quercetin could be used when sick or even preventatively.
We've personally taken quercetin for years now having nothing to do with its antiviral effects.
It's a huge promoter of our detox system (see CBD and glutathione) with positive effects on cancer, longevity, and metabolism.
We even did a full review of its cousin, fisetin, for antiaging effects which quercetin has has (just not as strong).
That's a deep dive into how these molecules work and the longevity studies are pretty amazing.
We personally take a concentrated form of quercetin which studies show has a 50x increase in bioavailability from Life Extension (see here) It's only $9...again, this stuff is cheap.
The safety profile of EGCG as an extract is not as strong as Quercetin.
Since they both showed effects on the zinc transport effect of hydroxychloroquine and viral cell entry (the 73 and 73 above), quercetin would be the safer option between the two.
Of course, drinking green tea has its own benefits!
A final note...we don't sell quercetin, EGCG, or other supplements as our main focus is CBD.
Why spend all this time reviewing it then?
If we come across research that can help people (like with fisetin, berberine, metformin, low dose naltrexone, psilocybin, hydroxychloroquine, siberian rhubarb, etc), we're going to do deep dives so people can understand what's available.
We've been there and so our goal is to help people take control of their health.
SelfCare based on Research. Be well and take care of each other.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.