• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To register, simply click the Register button at the top right.

Ethyl 3-Hydroxyhexanoate (EHX) Is Antiviral For Coxsackievirus B In Vivo

Hip

Senior Member
Messages
17,778
EHX acts as an enterovirus RNA-dependent RNA polymerase (RdRp) protein inhibitor.

EHX binds to some non-structural proteins of enterovirus, and in particular, it binds to enterovirus 3D protein, which is the enterovirus RdRp protein. RdRp is a critical protein in RNA virus replication. By binding to and deactivating this RdRp protein, EHX acts as an enterovirus replication inhibitor.



The mouse study linked to above administered 250 mg/kg of EHX twice daily for 5 days by intraperitoneal injection.

In the group of coxsackievirus B-infected mice not given EHX, 57% died; whereas in the group given EHX, 37% died. So that demonstrates in vivo efficacy of EHX against coxsackievirus B.

The mouse dose of 250 mg/kg twice daily would work out as a human dose of 20.3 mg/kg (diving 250 by the mouse-to-human conversion factor of 12.3). So for a 75 kg human, that is a dose of about 1500 mg twice daily. Whether that dose is safe in humans is not known.

This food ingredient safety paper (full text here) says the EHX no observed adverse effects level (NOAEL) is 13.47 mg/kg daily, but I am not sure if that figure is for rats or humans.



An interesting thing about the mouse study is that they tested EHX against some enterovirus replicons that the authors engineered. Replicons are very similar to non-cytolytic enterovirus found in ME/CFS patients.

They found EHX inhibits the enterovirus replicons too. This is good, as it suggests EHX could be effective against the non-cytolytic enterovirus infections that researchers like Dr Chia believe cause ME/CFS.



If you look at table 1 of the study, this shows the computer-calculated docking affinity of EHX to various viral proteins. You can see that it docks to the viral RdRp proteins of poliovirus and rhinovirus, which are both enteroviruses.

So EHX will likely have broad-spectrum antiviral effects against a wide range of enteroviruses.

Table 1 also shows that EHX binds to SARS coronavirus replicase 1a protein, so EHX may work for COVID infections too.

The half-life of plant-derived volatile compounds like EHX is short, but in the study, they found that EHX binds tightly to viral proteins, and it remains attached to these proteins up to 48 hours. So its antiviral action in the body lasts much longer that its short half life would suggest. So that's good.

EHX is a volatile organic compound (VOC) found in fruits, and such VOC compounds can usually cross biological membranes and the blood–brain barrier. So EHX should have antiviral effects within the brain too.



In the EU, ethyl 3-hydroxyhexanoate (EHX) can be bought from Laboratorium Discounter. 25 grams costs €65. 100 grams costs €176.

I've got some EHX on order, and will be trying this antiviral within weeks. It's one of the most interesting new enterovirus antiviral substances I have seen in a while.



EHX is a registered food additive and food fragrance (FEMA number 3545), with a fruity taste similar to grapes. EHX is a liquid at room temperature, with a density very similar to water (0.97 g/ml).

Given that the water solubility of EHX is reasonable (17 mg/ml), we can guess that oral bioavailability is going to be good. The food ingredient safety paper mentioned above says that oral bioavailability is assumed to be 100%, and dermal bioavailability (when EHX is placed on the skin) is also assumed to be 100%.

As with all substances tried experimentally, I am going to start with lower doses, and titrate up slowly, observing any side effects that may appear.
 
Last edited:

Hip

Senior Member
Messages
17,778
The only place we have found which sells EHX to individuals is Laboratorium Discounter in the Netherlands: they sell a 25 gram bottle of the EHX liquid, and a 100 gram bottle.

The brand of EHX Laboratorium Discounter sell is TCI (Tokyo Chemical Industry) EHX.

If you use a 1 drop per day dose, then the 25 gram bottle contains 1250 doses! Which is over 3 years supply.

It takes 1 week for the 100 gram bottle to be delivered in the EU, but 2 weeks for delivery of the 25 gram bottle (as they don't stock the 25 gram bottle, and have to order it from their supplier).

Those inside the EU can order EHX directly from Laboratorium Discounter: they will ship to any EU country. But unfortunately this seller does not ship outside the EU, so does not ship to the UK, US, Canada, Australia, etc.


But a way around this shipping restriction is to use a shopping forwarding service to re-ship your EHX purchase to your home address outside the EU.

A shopping forwarding company is one which gives you a personal address in a foreign country which you can use to receive shopping items bought in that country. On receiving your items, the forwarding company will re-ship them to your home address, usually with costs not much higher than standard international shipping prices.

The following shopping forwarding companies provide a free address in Germany that can be used for buying items in the EU and getting them re-shipped internationally:

https://www.mailboxde.com <-- Ships to the US, UK and most of the world
https://www.forward2me.com/warehouses/germany <-- Ships to the US, UK and most of the world
https://www.europemailbox.com <-- Ships to the UK, but does not ship outside of Europe

You just have to register for a free account, and they will give you your own personal address in Germany.

When any shopping item arrives at this personal address, the forwarding company will send you an email, and may give several different re-shipping mailing options. You select the option you want and pay, and the item will be forwarded to your home address.



Note that shopping forwarding companies have restrictions on the goods they will forward, so it is worth reading their restrictions page. If the forwarding service receives your EHX and then says they cannot forward industrial chemicals, you can tell them the EHX is not an industrial chemical, but is a food additive fragrance (which it is, EHX has the food flavour FEMA number of 3545).

However, there is a chance that the shopping forwarding company will not forward the EHX, so you may then lose your purchase.

EDIT: I just emailed the German shopping forwarding company www.mailboxde.com to ask whether they can re-ship EHX, and they told me: "according to IATA, this chemical substance is allowed to be shipped with our service".

So www.mailboxde.com are able to forward EHX. Their total reshipping cost to the UK is about €20, and to the US is about €30.
 
Last edited:

godlovesatrier

Senior Member
Messages
2,488
Location
United Kingdom
Right so tricky to get in the UK. I misse that bit of info on discord. I'd love to try this but the side effects would no doubt prevent me from being able to.

On a side note now that imd have stopped doing testing it's become very difficult to even get a test. I know I've had opportunity to do this before but until very recently I didn't really have the spare money to do it.

So hopefully you've not answered this. Do we know if the ehx will cross the bbb or penetrate the CNS?
 

dylemmaz

Senior Member
Messages
136
EDIT: I just emailed the German shopping forwarding company www.mailboxde.com to ask whether they can reship EHX, and they told me they can. Their total reshipping cost to the UK is about €20, and to the US is about €30.
thanks for doing the hard work for us @Hip. i plan to order this and give it a trial.

@Pyrrhus i was wondering if this is something you will be trialing given your success with favipiravir? i remember reading (correct me if i’m wrong) that you had lots of success with favipiravir but stopped due to toxicity? do you have any thoughts on this? thank you so much
 

Hip

Senior Member
Messages
17,778
I attach the safety review study for EHX to this post.

Anyone considering trying EHX might like to read this safety assessment.

As you can see, the repeated dose NOAEL (no observed adverse effects level) for EHX is 13.47 mg/kg daily.

Though as with any new drug or substance being tested experimentally for ME/CFS, starting at a low dose and titrating the dose up over some days is a good idea.
 

Attachments

  • Ethyl 3-Hydroxyhexanoate Safety.pdf
    691.7 KB · Views: 30

sometexan84

Senior Member
Messages
1,229
Oh geez, they actually show a picture of the mice in the study... never seen that before :oh-dear:

I'd like to stay in the loop w/ EHX. Especially those considering taking it. Good stuff!
 

Dude

Senior Member
Messages
168
Just ordered that stuff, any experience so far? You Guys have a Discord channel running?
 

Hip

Senior Member
Messages
17,778
In the last week, I started experimenting with EHX.

I began with 1 drop of the EHX liquid daily, rubbed into to my skin (someone who took oral EHX found it upset their digestion, so transdermal application may be better).

On my pipette, 1 drop weighed 18 mg. So 18 mg of EHX was my daily dose.

After about 3 days of 1 drop daily, I noticed some improvements in energy, mood and brain fog. No side effects were observed at this dose level.



I then increased the dose to 2 drops transdermally each day, one drop in the morning, and another in the early evening. These drops I would place on the top of my thighs, and rub them into the skin. You can add a few drops of water too, to help spread the EHX across a wider area of skin.

No side effects were observed, so the next day, I further increased the dose to 4 drops daily.

But on the day after I took these 4 drops, I was hit with significant mental side effects: I developed an edgy and perturbed anxiety, which was very unpleasant.

So I stopped EHX, and now plan to go back to 1 drop per day, which seemed to be giving me benefits.
 
Last edited:

Hip

Senior Member
Messages
17,778
Note that with EHX there is the possibility of psychiatric side effects. EHX is a volatile organic compound (VOC) from fruit. All such compounds can cross the blood-brain barrier, and may cause psychiatric symptoms:
Due to the high lipophilicity of VOCs, they can cross biological membranes and the blood–brain barrier (BBB) and thus resulting in numerous neuropsychiatric disorders, comprising of diminished impulsive control, changes in the motor and cognitive functions, hallucinations, headache, dizziness, and dementia.
Source: here


My recent experiment with EHX detailed in my last post showed that though it is a natural substance from fruit, it can cause psychiatric side effects.

And a test of EHX I made last year had similar results: when I took a transdermal dose of 100 mg daily for two days in a row, I developed some perturbing stress sensitivity/emotional sensitivity symptoms. Those side effects took about 3 days to clear (which matches the 48 hour half life by which EHX binds to viral proteins).

I definitely felt the diminished impulse control mentioned in the quote above, as when I took higher doses of EHX, when small things around me annoyed me, I got strong angry feelings, and it felt like the flare up of this anger is a bit out of control. So EHX can reduce impulse control.


Nevertheless, I found that with just 1 drop (18 mg) per day, my mood and mental health seemed improved, as did my energy and brain fog. So 1 drop a day seems to work well for me. But anything above that causes psychiatric side effects.
 
Last edited:

Hip

Senior Member
Messages
17,778
Just to sum up my results with EHX so far:

I got noticeable improvements in energy, brain fog and mood after just 3 days of taking 1 drop of EHX transdermally. The benefits appeared pretty fast.

Unfortunately I then increased my dose to 4 drops daily, and got some mental health side effects, so had to stop. The mental side effects took about 5 days to clear after stopping EHX. The mental side effects were related to emotional sensitivity and impulse control.

I think EHX reduces emotional impulse control, so that emotions can flare up in an over-reactive way. If anyone were prone to anger or losing their temper easily, then they might want to be cautious with EHX. It may be that at higher doses, this VOC can cause toxic effects on the brain.


But the 1 drop dose may be effective for treating ME/CFS, and may not cause any side effects. I will return to this dosage shortly.

If 1 transdermal drop per day is sufficient to get some benefits, this would make EHX a very economical ME/CFS treatment, since 1 drop costs about $0.02.
 

Hip

Senior Member
Messages
17,778
@Rim1 reports that he has taken 4 drops of EHX (which totals to about 80 mg) transdermally each day for over 2 weeks, and has not had any side effects whatsoever.

He initially noticed some improvements in brain fog and energy, but these faded after about 4 days. Though he does not know whether he is an enterovirus ME/CFS patient or not, as he has not been tested for enterovirus.

So 4 drops daily taken transdermally would appear to be a tolerated dose.
 
Last edited:

Dude

Senior Member
Messages
168
Short update.. About a week ago I finished trying ethyl 3-hydroxyhexanoate. I applied 2x 20ml to the skin daily for 4 weeks. Unfortunately I had no reaction, neither positive nor negative.
 

Hip

Senior Member
Messages
17,778
Short update.. About a week ago I finished trying ethyl 3-hydroxyhexanoate. I applied 2x 20ml to the skin daily for 4 weeks. Unfortunately I had no reaction, neither positive nor negative.

Thanks for that report.

Would you know if you are an enterovirus ME/CFS patient? Have you been tested for enterovirus using antibody tests based on the sensitive neutralisation method?
 

Dude

Senior Member
Messages
168
I have not been tested for enterovirus. I just tried it out of curiosity, so don't let me discourage you. My trigger was a norovirus disease, although I am not sure whether it was the virus or the dehydration. I recently read a story from a board member who developed mecfs after a bike race due to dehydration. Could be the trigger for me as well. But I still have good news, I'll write it in another thread.
 

Hip

Senior Member
Messages
17,778
My trigger was a norovirus disease, although I am not sure whether it was the virus or the dehydration.

Was your infection diagnosed as norovirus via a blood test? Because enterovirus infection can produce very similar gastrointestinal symptoms (vomiting and diarrhoea) to norovirus.
 

Dude

Senior Member
Messages
168
Was your infection diagnosed as norovirus via a blood test? Because enterovirus infection can produce very similar gastrointestinal symptoms (vomiting and diarrhoea) to norovirus.
I didn't get tested at the time. My wife got it the day before and 24 hours later everything was fine again. Which almost certainly points to Noro. We had tried to disinfect everything because the virus is considered highly contagious, but the next day it started for me too. I had extreme cramps due to the high levels of minerals and fluid loss and was unable to move for a while. Shit was scary.