Talk about an oddball drug. Named after the earth smoke plant, dimethyl fumarate is an old compound used in industrial chemistry. Wikipedia reported that in 2012 you could get it for from $1 to $50 per metric ton (but you had to buy at least two tons of it). Technically, it’s a “methyl ester of fumaric acid” – an acid that has a fruit-like taste and has been used as a food additive. Our skin produces it when exposed to the sun. Plus, fumarate plays a key role in the citric acid cycle that produces ATP.
Fumaris officinalis – the earth smoke plant – produces fumaric acid.
Dimethyl fumarate was also used as a biocide in furniture or shoes to prevent growths of mold during storage or transport in humid climates. That resulted in cases of severe dermatitis and what came to be called the “poison chair” incident involving sofas coming from, you guessed it, China.
This is one strange substance.
Diimethyl fumarate is also an immunomodulatory drug with some pretty astonishing antioxidant properties. We know that increased levels of oxidative stress can tweak pain producing nerves – causing them to send pain signals to the brain. Researchers have long thought that antioxidants should be able to calm the fires, so to speak, in these nerves, but antioxidant trials have never really worked out.
It may be that the very complex antioxidant system simply doesn’t respond well to a few inputs. Maybe you need to turn the whole system on to get results – and that’s just what these University of Texas researchers tried to do. They decided to try to turn on a master antioxidant transcription factor (something which turns many genes on) called NFE2L2 – and dimethyl fumarate, it turned out, fit that bill.
Li J, Ma J, Lacagnina MJ, et al. Oral Dimethyl Fumarate Reduces Peripheral Neuropathic Pain in Rodents via NFE2L2 Antioxidant Signaling. Anesthesiology. 2020;132(2):343-356. doi:10.1097/ALN.0000000000003077
First, they induced neuropathic pain and allodynia in laboratory animals, and then treated them with dimethyl fumarate.
Not only did the animal’s pain behaviors decrease, but the drug increased levels of the master antioxidant in the body (glutathione) and reversed the damage caused by the oxidative stress. It also knocked down levels of a cytokine (IL-1B) implicated in pain production.
The researchers determined that dimethyl fumarate did this by activating NFE2L2 – that transcription factor which turns on over 200 antioxidant-related genes. Interestingly, dimethyl fumarate also restored mitochondrial activity in the dorsal root ganglia neurons. These neurons – which are found right outside the spinal cord – send pain signals to the spinal cord and then up to the brain. They’ve been proposed to play a role in both fibromyalgia and chronic fatigue syndrome (ME/CFS) and herpes viruses love to hang out in them. This study also suggested dimethyl fumarate might be helping to repair them.
The researchers had relieved pain in a novel way using non-opioid-based drugs.
Dimethyl fumarate has one big thing going for it in the U.S. and Europe; it’s already approved for use (Tecfidera/Skilarence) in multiple sclerosis. It’s apparently a pretty big deal in M.S. It’s Biogen’s biggest money maker ($4.4 billion/yr) and two major drug companies are butting heads over its patent protection. However that turns out, there’s no need, if the drug works, to spend tens or hundreds of millions of dollars developing a new drug. It’s already on pharmacy shelves.
A very different approach to pain…
Taking dimethyl fumarate, as one might suspect, though, isn’t exactly a walk in the park. Common adverse effects include flushing, abdominal pain, nausea, and diarrhea! The researchers suggested the drug may need to be improved by further refining “its fumaric acid esters”. (A sister drug, diroximel fumarate, that is under development, though, is much easier on the gut.)
The Pain Research Forum reported that the researchers hoped to start clinical trials in humans soon. While this study focused on neuropathic pain – just one type of pain found in FM – the authors believed dimethyl fumarate could work in other pain types, and they plan to investigate them as well.
We’ll see how it all turns out. This study suggests, though, that there’s no way to predict where an effective pain drug may come from. If an industrial chemical could possibly birth a new way of treating chronic pain, who knows where the next breakthrough will come from?
The other good news is that researchers are increasingly looking outside the traditional pathways of pain treatments and seeking to get at the core processes that are producing pain. Opioid drugs and altering neurotransmitters in the brain are out. Getting at the molecular roots of pain – in this case, getting at the source of the oxidative stress that makes nerves twitchy – is in.
Researchers are more and more tracking down the molecular processes that produce pain and coming up with different approaches to treating pain. That’s good news for all of us.
- Next Up – could an ingredient in Cannabis produce the next effective pain drug?
Sign me up for trials!
Finally potentially good fibro news, though years away, no doubt. Thanks for writeup.
Maybe we can grow a few of those plants for tea…
Steve,
Amazon sells it! I think they call it Common Fumitory Herb. Might be worth trying.
Yes, it will take time – although not as long as it might if the drug wasn’t already in use. It always takes a lot of time!
This makes sense to me. My maternal grandfather had MS and there is a lot of anxiety, ADHD in the wider family. All possibly indicating a predisposition to Fibro which i got after a severe infection. I personally felt there was a link between MS and FM for some years so it’s good to see it backed up with scientific research. One of the side effects of FM is IBS however so anything that by-passes the gut is preferable, sprays, liquids, even suppositories.
I think you’re not alone. My family has Sjogren’s Syndrome – a really bad case in it, and one ME/CFS patients did great on Copaxone an MS drug. If neuroinflammation is found in both diseases I imagine we will see more connections over time.
I have had painful Fibromyalgia for 19 yrs and recently developed Dysautonomia wh where the Central Nervous System does not function correctly such as body temperature regulation does not work normally and quite a number of other very uncomfortable problems. And nerve pain is increased 24/7. Does anyone know if this drug helps this condition? TU
I don’t know but you might want to check out Mestinon. Check out blogs on this website.
cort what do you know about PEA? its short for palmitoylethanolamide. fatty acid. remarkable effects on pain, energy, the whole thing. You can get good product many places. i take 3 a day and i am a new woman.
check it out!
Hi Vicky – Congratulations – we did a blog on PEA some time ago but I haven’t tried it. Thanks for the reminder.
https://www.healthrising.org/blog/2014/09/19/palmitoylethanolamide-pea-medical-food-fibromyalgia-chronic-fatigue-syndrome-mecfs/
I recognize that flower! It’s one of my favorite weeds around here. Grows everywhere, in I forget which season – winter, spring? Leaves remind of parsley. Not that it would be a good idea to go out and harvest it for infusions – who knows what adverse effects it may have and at what dose – just the fact that it grows EVERYWHERE.
No kidding. Definitely do not play with it – but wow – what a sharp eye you have.
I like every possible improvement. I do however feel a bit at unease with following information:
https://en.wikipedia.org/wiki/Dimethyl_fumarate
“In the treatment of psoriasis, the most common adverse events are gastrointestinal events, flushing and lymphopenia, which are usually mild. Other adverse events include progressive multifocal leukoencephalopathy (PML)”
The wiki site on PML states:
“Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal viral disease characterized by progressive damage (-pathy) or inflammation of the white matter (leuko-) of the brain (-encephalo-) at multiple locations (multifocal). It is caused by the JC virus, which is normally present and kept under control by the immune system. The JC virus is harmless except in cases of weakened immune systems.”
If I combine that with what Cort wrote:
“Interestingly, dimethyl fumarate also restored mitochondrial activity in the dorsal root ganglia neurons. These neurons – which are found right outside the spinal cord – send pain signals to the spinal cord and then up to the brain. They’ve been proposed to play a role in both fibromyalgia and chronic fatigue syndrome (ME/CFS) and herpes viruses love to hang out in them.”
Then I see the possibility that for some patients it might override a vital safety mechanism keeping viral activity in the brain under control.
I hope this isn’t the case, but I personally would prefer some high quality safety and efficiency studies before taking this drug.
Thanks for the good reporting once more Cort!
I agree! Too much unknown and the gut problems in particular are worrying in. Maybe there are other ways to get that master antioxidant regulator moving – maybe it will take a tweak to the drug. Time will tell.
I have been self-medicating with industrial grade dimethly fumarate since December 2012. I have maintained excellent control of a moderate to severe psoriasis, psoriatic arthropathy and ankylosing spondylitis. I have suffered no adverse effects and monitored by a medical practitioner. The drug works far better for me now than it did when I started taking it, allowing me to reduced the dosage from over four grams per week to less than a gram a week currently. My annual cost of medication is a little over one Australian dollar per year. I have also noted neuroprotective effects from the drug, so it is nice to see the research supporting the benefit. I used to talk a lot about my experience, but I have little interest in doing this these days after a number of confrontations with aggressive moderators on a prominent psoriasis forum.
Thanks for sharing that Bill. I forgot to mention that psoriasis is the other condition dimethyl fumarate is approved for in some countries.
How about that – a dollar a year! A cheap medication that helps is, of course, everybody’s dream
Thanks, Cort. Dimethyl fumarate has been used to treat moderate to severe plaque psoriasis in Germany since 1994, so parameters for minimising risk from things like PML are well established. I would point out that PML is a greater risk for patients taking methotrexate, but such drugs are taken because patients are generally at greater risk of harm from not treating a chronic illness. I am very careful with dimethy fumarate as it is a powerful drug, but I have experimented a lot with dosage (quantity and frequency) over the years, noting in my case that a larger dose has a greater therapeutic effect and allows less frequent dosing. Therapeutic guidelines are an essential starting point, but personal experience and observation are of greater importance in the long term.
Thanks for sharing your experiences.
It sure would be very nice if this was a one-size-fits-all drug.
Myself, I’ll stay at the sideline till it gets clearer if it is safe and beneficial for most of us to take it. I had a few too many things backfiring. But once more: thanks for sharing and keep being healthy and safe!
Thank you Jurgen. I think your cautious approach very sensible. I had an out of control disease: Covered in flaky skin, lots of arthritic pain and fusing vertebrae. I also had a fear of taking methotrexate, the only drug option available to me in Australia, so I was between a rock and a hard place.
One more observation about my self-treatment: expectation and experience have been at great variance, with many unanticipated treatment alterations, challenges and benefits. Consequently I am very skeptical when I read stories of alternative treatments where there is a seamless transition from theory to practice.
Cheers
Just an update. I had a shingles infection at the end of 2020 and unfortunately have a legacy of phn, albeit mild. Had I acted quickly when I realised what was happening I might have suffered no long term harm, but that is how it is. On the bright side I have maintained a lymphocyte count of around 1.5, so I think my risk of pml is about nothing. Again, dimethyl fumarate is a strong drug, so care, caution and regular monitoring are needed.
So encouraging to read. Oxidative stress makes so much sense to me from every thing I’ve read over the years. I hope focus remains in this area of research. As for the drug itself I trust none of us will be taking it without the typical years of trials etc which is the roadmap in the US.
Trust again, I will try anything to feel better, and with that mind set have found many things which didn’t go through your “years of trials” now I’ve returned to full time work. And if you research this drug is fda approved for multiple conditions and considered safe long term. Or maybe you’d like us all to lay in bed waiting years for your research.
Can you reach out to me? I have questions about self administering the medicine you were taking and if it continued to help you.
So can a doctor prescribe this off label now? Assuming it’s not covered by insurance, does anyone know the cost? Fibro pain and neuropathy are my biggest problems and if anyone has any ideas or suggestions other than opiates or low dose naltrexone, I am interested in hearing what is working for others. Thanks
I take this for my MS and if I had to pay for it would cost £30 per capsule or just under £22,000 a year.
Wow….
If this is Industrial grade can it be purchased online without a prescription?
Hi Lorre,
Dimethyl fumarate is a potent anti-fungal agent and I had no trouble importing it as such. I don’t advocate people doing what I did, and if you were capable of doing as I have done you would not need my help anyway. I have had great results and suffered no harm, which is as much as anyone could hope for.
Cheers
Alibaba, Pharma grade or industrial grade. No prescription required. Or IndiaMART. AFFORDABLE
Only use food grade sources from a reputable source. You just never know.
I am up for it, dont do flu vacc, or anti biotics for years, but with injury the game changes again. Osteoarthritis. How long is the study? Links
Thanks very tired lately.
Leesa,
The link to the study is the fifth paragraph from the top of the blog. Is that what you’re looking for? Sorry you’re feeling so tired…
Thank you for posting… I am in pain Evey joint of my body and burning tongue syndrome. Doctors don’t know why?? So it’s Fibromyalgia they say. I’m at my wit’s end. I wanna try this so bad. But am afraid too. Maybe if there is a recommendation of a product? I might consider.
Jenel, sorry to hear about your burning tongue. Our family member notices it seems to get worse in relation to chemical sensitivities sometimes and also stress. I think the thing that helped the most was gapapentin. Good luck.
There are a lot of substances which are not good for your health so one should be very careful while dealing with them. These updates are very nice and will help many people.
Dentist Longmont
Seems like carnitine fumarate might do the the same (provide fumarate/fumaric acid).