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Could the hydroxychloroquine + zinc coronavirus antiviral combo also work for enterovirus ME/CFS?

Hip

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A new study found evidence that hydroxychloroquine 400 mg plus zinc 50 mg daily has efficacy against COVID-19. This is in contrast to several other studies which found that hydroxychloroquine without zinc is not effective for COVID-19.

Hydroxychloroquine is a zinc ionophore, meaning that it binds to zinc ions and brings them inside cells. One inside the cell, these intracellular zinc ions have an antiviral effect against coronavirus. So it makes sense that giving COVID-19 patients a zinc supplement along with the hydroxychloroquine will be more effective than hydroxychloroquine alone.

Now intracellular zinc ions are not only antiviral for coronavirus, but also antiviral several other viruses, including coxsackievirus B, herpes simplex and hepatitis C virus. Ref: here.

Studies from 2007 and from 2009 found that zinc ionophores have antiviral efficacy against coxsackievirus B, a virus which is associated with many ME/CFS cases. In fact the 2009 study found zinc ionophores inhibit a range of picornaviruses (the family that enterovirus and coxsackievirus B belong to).

Now these 2007 and 2009 studies used zinc ionophores which are not generally available to the public (namely pyrrolidine dithiocarbamate, pyrithione and hinokitiol). However, we know that hydroxychloroquine is a zinc ionophore too, so we could use that instead.

Thus taking hydroxychloroquine plus zinc in the same doses used to treat coronavirus might well have some antiviral effect against the chronic enterovirus infections found in ME/CFS.



Unfortunately, at the moment hydroxychloroquine prices have shot up, because many people are buying this drug for coronavirus. Normally 100 x 200 mg tablets of hydroxychloroquine would cost $37, but prices are elevated above that now.

One possible substitute for hydroxychloroquine is ECGC (green tea extract), as this has been shown to function as a zinc ionophore. But I don't know how ECGC compares to hydroxychloroquine in terms of its zinc ionophore potency, and I am not sure what ECGC dose would be equivalent.

Other zinc ionophores include the drug PBT2, which is being trialed as an Alzheimer's treatment.

A list of zinc ionophores given here.
 

pattismith

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""zinc sulfate (220 mg capsule containing 50 mg elemental zinc twice daily
for five days)""

I suppose other zinc compounds can be given as well, do you think so?
 

Tammy

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A new study found evidence that hydroxychloroquine 400 mg plus zinc 50 mg daily has efficacy against COVID-19. This is in contrast to several other studies which found that hydroxychloroquine without zinc is not effective for COVID-19.
If hydroxychoroquine was not effective without zinc................why couldn't one come to the conclusion that it was the zinc itself that was effective and was in and of itself the thing that helped?
 
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Hip

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If hydroxychoroquine was not effective without zinc................why couldn't one come to the conclusion that it was the zinc itself that was effective and was in and of itself the thing that helped? Zinc is antiviral along with many other attributes that help the immune system.
In the studies mentioned above, it explains the antiviral action of zinc against the viruses listed occurs when zinc gets inside cells in a sufficient quantity. Hydroxychloroquine transports the zinc into cells. That's why the combination is effective.

There is one study looking to see if high dose intravenous zinc on its own might help COVID-19, but I don't think the results are in yet.

But I can tell you for sure that high dose oral zinc has not helped my ME/CFS at all, as I have tried this many times.

However, by adding hydroxychloroquine to the zinc I take, this will then transport the zinc into my cells, and this conceivably might fight my chronic enterovirus infection.

Remember that chronic enterovirus infections are intracellular infections: they are located inside cells. So by transporting the zinc into the cells using hydroxychloroquine, you may be able to target this intracellular infection.
 
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Tammy

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I have been successful at times (not every time) at warding off cold/ flu virus when I took high doses of zinc sulphate at first signs of symptoms.
 
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Hip

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I have been successful at times (not every time) at warding off cold/ flu virus at times when I took high dose zinc sulphate at first signs of symptoms.
Yes, zinc has been shown to reduce the risk of catching colds. Echinacea also.

But colds are a regular acute viral infection, whereas the enterovirus infections in ME/CFS are not, they are chronic intracellular infections, which is a different beast. You have to get inside the cell to tackle these intracellular infections. That's why I was thinking intracellular zinc might work, especially since the study I linked to above showed that intracellular zinc is antiviral for coxsackievirus B.

Taking some hydroxychloroquine with zinc gets the zinc inside the cell.
 

Tammy

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But colds are a regular acute viral infection, whereas the enterovirus infections in ME/CFS are not, they are chronic intracellular infections, which is a different beast. You have to get inside the cell to tackle these intracellular infections. That's why I was thinking intracellular zinc might work, especially since the study I linked to above showed that intracellular zinc is antiviral for coxsackievirus B.
When I first saw your post, I quickly glanced at the topic and my brain was focused on zinc and corona virus.

I do understand what you are doing and the reason behind it. Good luck with the experiment.

Just curious if there is any part of you that is uneasy with taking hydroxychloroquine and how long do you plan on taking it?
 

Hip

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Just curious if there is any part of you that is uneasy with taking hydroxychloroquine and how long do you plan on taking it?
I've never had any significant physical medical side effects from any of the hundreds of drugs and supplements I've tried, but many have caused worsened mental health, which means I have to stop the drug and abandon the experiment. But I am prone to supplements and drugs causing adverse mental effects.

So that's my main concern, the possible mental health side effects; and hydroxychloroquine can cause depression and other mental symptoms. So if that happens, I would have to stop taking it.


I tend to approach taking any drug or supplement quite intuitively and consciously: I am on the lookout for any adverse effects, and if something does not feel right, I may just stop the med, or perhaps lower the dose. I am aways very cautious and aware.

In terms of hydroxychloroquine physical side effects that are of concern, long-term use or high doses can lead to retina damage, sometimes permanent. But the risks are mainly for people taking doses higher than 400 mg daily, or taking a total cumulative dose of more than 1000 grams (which equates to taking 400 mg daily for 7 years). Ref: here.

But for a short trial of hydroxychloroquine for a few weeks or maybe months, I think the risks will be reduced.

Hydroxychloroquine can also increase the QT interval, leading to heart arrhythmia. So you would not want to take it with other drugs that also increase QT (the hydroxychloroquine + azithromycin combo experimentally used to treat coronavirus is not the best of ideas in this respect, as azithromycin also increases QT).
 

Wolfcub

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This is very interesting Hip

It seems quite a simple strategy: a transporter to get the zinc inside the cells!
I'm glad you wrote this because I didn't know what was going on re: Hydroxycholoroquine....now I see more clearly.

It's an interesting concept and may be worth experimenting with?

Personally I suspect my ME/CFS was started by an enterovirus. Unfortunately I cannot quite pin it down because I can't fit my initial symptoms into any particular viral "profile" which makes me think I may have responded atypically in the first couple of weeks or so (back in early 2018)

I know I did try Echinacea (Angustifolia root tincture) in the beginning and raw garlic in pretty heroic doses. which usually busts anything and certainly helped with coronavirus.
Yet neither shifted whatever happened in 2018. They (and other herbals) helped relieve things slightly but never completely shifted it.
Every so often, I would repeat the regime for a week, with the same results; a little better but no victory.

Because they couldn't get INTO the cells ?!

Green Tea extract...? That is an alternative idea, so long as it suits whoever experiments.

Thanks for listing any possible side effects.

Are you maybe going to experiment?
 

Hip

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Are you maybe going to experiment?
I might wait to see if further trials can replicate the antiviral effect of hydroxychloroquine + zinc for coronavirus. If they can, then it suggests this combination really does have antiviral properties, which then might also work for chronic enterovirus infections.
 
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"I've just started taking hydroxychloroquine 200 mg + zinc 50 mg daily, in the hope that this might help my enterovirus ME/CFS. So it's interesting to see that you did well on hydroxychloroquine + HBOT. "
Hi Hip,
I have copied/pasted your reply from another thread.How long have you been taking these (H+Z) and have you noticed any improvement?How long do you hope to continue this treatment?You mentioned somewhere that the price of hydroxychloroquine had shot up.Which online chemist did you get it from?

Re zinc you mention intracellular zinc...Which one do you recommend?I have an enterovirus infection too, going back to 1980s(notified then)so this treatment may help me too.All treatments have some risks...What are the risks with this?
I'm getting on in years..feeling more crippled with bad brain(especially) & gut problems...walking is very difficult...balance badly affected too.Thanks.
 

Hip

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thread.How long have you been taking these (H+Z) and have you noticed any improvement?
Only a week, so probably too short a time to expect any results. According to this post from @used_to_race, when he started both hydroxychloroquine 400 mg daily (without zinc) and hyperbaric oxygen therapy (HBOT), it took two months before he saw substantial results (but it is not clear whether those results were due to hydroxychloroquine, HBOT, or a combination of both). He had EBV ME/CFS.



Re zinc you mention intracellular zinc...Which one do you recommend?I
Just any ordinary zinc supplement. It is the hydroxychloroquine which binds to the zinc and then pulls the zinc inside the cells. That's what makes the zinc accumulate intracellularly.



What are the risks with this?
Some of the risks are mentioned just above.
 

pamojja

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But I don't know how ECGC compares to hydroxychloroquine in terms of its zinc ionophore potency, and I am not sure what ECGC dose would be equivalent.
Has the zinc-ionophoric function really dose-dependend been tested via intracellular zinc?

In a roundabout way I actually did. For example my serum levels show I'm deficient in zinc, and had some excess in copper. Resulting in a devastating serum copper/zinc ratio.

However, interestingly at the same time zinc and copper tested in whole-blood - which is serum including all white and red blood cells and clotting factors intracellular content - both show even excessive high. Cu and Zn both improving recently in this respect.

Copper-Zinc.png


Though higher than normal whole blood zinc arose after 8 months on 70 mg/d elemental zinc intake only:

cu-zn.png


I did get the zinc-ionophores of 270 mg/d of EGCG and 200 mg/d of quercetin during that whole time, on empty stomach in the morning while zinc always with dinner only.

Therefore my specific question would rather be, are there any substances with the reversing effect of zinc-ionophores? Shuffling zinc back out of cells into serum again?
 
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Hip

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Has the zinc-ionophoric function really dose-dependend been tested via intracellular zinc?
Yes in this paper they show that the drug chloroquine enhanced zinc uptake in cells, which they say means this drug is an ionophore of zinc. I read that the closely-related hydroxychloroquine is also a zinc ionophore.

An ionophore is "a substance which is able to transport particular ions across a lipid membrane in a cell".


There is a good Wikipedia article on ionophores, which also includes a large list of zinc ionophore substances. But the only non-toxic and available zinc ionophores on that list are:
  • Chloroquine
  • Hinokitiol
  • EGCG
  • Quercetin
In Japan they are suggesting that hinokitiol + zinc could be used to treat coronavirus, instead of hydroxychloroquine + zinc, as the food additive hinokitiol has lower toxicity compared to hydroxychloroquine. But hinokitiol (also called beta-thujaplicin) is hard to obtain.


Actually, it was over 10 years ago that I read and saved on my computer this study showing that zinc ionophores are antiviral for picornaviruses (a virus family which includes enterovirus, coxsackievirus B and echovirus). But at the time I did not know of any viable zinc ionophores to use. It was only when reading about hydroxychloroquine as a potential coronavirus treatment did I realize that this drug is a useful zinc ionophore.



zinc and copper tested in whole-blood - which is serum including all white and red blood cells and clotting factors intracellular content
I understand that in theory this approach might be used to measure intracellular zinc levels, but I am not sure if it would work in practice, as this 1986 paper states that "there are no reliable methods to assess cellular zinc status".

Things may have changed since 1986, but I don't think there are any simple ways to accurately measure intracellular zinc, as this 2016 paper discussing techniques for testing intracellular zinc talks about using fluorescent zinc ion sensors.

Though I came across this page which claims their test measuring zinc levels in red blood cells reflects intracellular levels: "RBC testing provides a measurement equivocal to intracellular levels." (I think they meant to say "equivalent" rather than "equivocal"). But I could not find much online to validate their claim.



Therefore my specific question would rather be, are there any substances with the reversing effect of zinc-ionophores? Shuffling zinc back out of cells into serum again?
Not that I know of.
 
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Hip

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One thing I have noticed with the hydroxychloroquine 200 mg + zinc 50 mg combo I have been taking daily is that it makes me quite a bit more tired. Fatigue is a listed side effect of hydroxychloroquine.

But interestingly, when I was experimenting with EGCG 1000 mg + zinc 50 mg for a few weeks, this seemed to energize me, in a stimulant sort of way. This high-dose of EGCG boosted mood, motivation and mental focus, I found.

This may be because EGCG is known to activate the dopamine reward pathways (mesolimbic system). Ref: 1 2

Although when I stopped taking high-dose EGCG, it had a significant comedown, where you feel mentally flat with ennui for several days. So probably best to taper off high-dose EGCG slowly.



What I may do is take both hydroxychloroquine and EGCG at the same time with zinc. Possibly this may slightly further increase intracellular zinc, and the energizing effects of the EGCG possibly may counterbalance the fatiguing effects of hydroxychloroquine.

Note that it may be worth taking some folinic acid with the EGCG, as EGCG has an anti-folate action: it inhibits the enzyme dihydrofolate reductase (DHFR). Folinic acid is used to correct for DHFR deficiency.



I am not sure if EGCG will have any major impact on intracellular zinc though, because in the in vitro study which examined the zinc ionophore potency of various polyphenol supplements, they used concentrations of 50 μM of these supplements in the cell line.

Whereas by my pharmacokinetic calculations, even a high oral dose of 1000 mg of EGCG will only result in a free concentration of 1 μM of EGCG in the blood. So that's 50 times less the concentration in the study.

From the study, here are the relative zinc ionophore potencies of the various substances tested in the study:

Zinc Ionophore Potency (increment in fluorescence ∆)

clioquinol . . . . . . . . . . . . . . . . . . 57-fold
pyrithione . . . . . . . . . . . . . . . . . 54-fold

epigallocatechin-3-gallate . . .36-fold
quercetin . . . . . . . . . . . . . . . . . .18-fold
luteolin . . . . . . . . . . . . . . . . . . . .12-fold
tannic acid . . . . . . . . . . . . . . . . 12-fold
gallic acid . . . . . . . . . . . . . . . . . . 8-fold

rutin . . . . . . . . . . . . . . . . . . . . . . . 4-fold
dihydroquercetin (taxifolin) . . .4-fold
caffeic acid . . . . . . . . . . . . . . . . . 3-fold
catechin hydrate . . . . . . . . . . . . 2-fold
catechol . . . . . . . . . . . . . . . . . . . .2-fold
genistein . . . . . . . . . . . . . . . . . . . 2-fold

Substance concentration used: 50 μM (plus 10 μM zinc chloride)
 

Abrin

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I saw Fauci the other day talking about this study and saying that this study was highly flawed?

I was just wondering if anyone had any more information about that? With my brain fog I absorb the written word more than hearing people's voices.