Do fumarates change into fumaric acid in vivo?

Discuss Tecfidera (BG-12, dimethyl fumarate) as an oral treatment for multiple sclerosis.

Do fumarates change into fumaric acid in vivo?

Postby Anonymoose » Sat Jun 24, 2017 10:08 am

Need brainier folks than I for this one...

Dimethyl fumarate and clemastine fumarate are both alleged to have potential beneficial effects on some pwms for different reasons or unknown reasons. Dimethyl might reduce relapses. Clemastine might contribute to remyelination.

IF fumarates are changed into fumaric acids by our bodies, might it be fumaric acids that are helping?

Fumaric acid is produced in our skin when it is exposed to sunlight. Maybe vitamin d is just the obvious/only tested indicator of deficiency of compounds normally produced by the skin. Maybe it's a fumaric acid deficiency or a deficiency of something else normally produced when skin is exposed to sun that we are missing...

Help me brainiacs. Don't make me try to learn chemistry to quench my curiosity. I'd rather eat bugs!
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Re: Do fumarates change into fumaric acid in vivo?

Postby NHE » Sun Jun 25, 2017 2:09 am

Anonymoose wrote:Need brainier folks than I for this one...

Dimethyl fumarate and clemastine fumarate are both alleged to have potential beneficial effects on some pwms for different reasons or unknown reasons. Dimethyl might reduce relapses. Clemastine might contribute to remyelination.

IF fumarates are changed into fumaric acids by our bodies, might it be fumaric acids that are helping?

Fumaric acid is produced in our skin when it is exposed to sunlight. Maybe vitamin d is just the obvious/only tested indicator of deficiency of compounds normally produced by the skin. Maybe it's a fumaric acid deficiency or a deficiency of something else normally produced when skin is exposed to sun that we are missing...


Here is dimethylfumarate.

Image

It's the methyl ester of fumaric acid. It's a potent oxidizing agent that attacks thiol groups and is thought to act as an Nrf2 activator. There are many molecules in nature that do this. Here's a free review paper that discusses some of them.

Here is clemastine fumarate.

Image

As you can see, it's fumaric acid with a clemastine moiety. It's likely the clemastine that contributes to remyelination. However, I'm not familiar with clemastine. Apparently, it acts as an antihistamine.

https://www.ncbi.nlm.nih.gov/pubmed/8574128
https://www.ncbi.nlm.nih.gov/pubmed/9356796

Anonymoose wrote:Help me brainiacs. Don't make me try to learn chemistry to quench my curiosity. I'd rather eat bugs!


humor-f16/topic19944.html#p191837

Bugs are good. We eat bugs and bug parts all the time. It's nearly impossible for commercial food producers to eliminate all traces of them so there are federal regulations that limit the number of bug parts in food.
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Re: Do fumarates change into fumaric acid in vivo?

Postby Anonymoose » Sun Jun 25, 2017 5:40 am

Thanks, NHE. Why you always gotta use those dumb stick figures on me? ;oP
Does any of that mean fumarates change into or don't change into fumaric acid in our bodies?

I don't think it's certain that DF works via nrf2.
Dimethyl fumarate treatment induces adaptive and innate immune modulation independent of Nrf2
http://m.pnas.org/content/113/17/4777.short

Like everything else MS, I guess I'll just have to keep wondering about this too.
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Re: Do fumarates change into fumaric acid in vivo?

Postby NHE » Mon Jun 26, 2017 12:09 am

Anonymoose wrote:I don't think it's certain that DF works via nrf2.
Dimethyl fumarate treatment induces adaptive and innate immune modulation independent of Nrf2
http://m.pnas.org/content/113/17/4777.short


Schulze-Topphoffa et al. wrote:Significance: Dimethyl fumarate (DMF) (BG-12, Tecfidera), a fumaric acid ester (FAE), is a commonly prescribed oral therapy for multiple sclerosis (MS), a CNS autoimmune inflammatory demyelinating disease that may result in sustained neurologic damage. It is thought that the benefit of DMF in MS therapy is mediated through activation of the antioxidative transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, the role of Nrf2 in the antiinflammatory effects of DMF has not been fully elucidated. Here, we investigated the role of Nrf2 in DMF treatment of the MS model, experimental autoimmune encephalomyelitis (EAE), and demonstrated DMF can modulate T cells, B cells, and antigen-presenting cells, and reduce clinical and histologic EAE, independent of Nrf2.


Yes, We know that Tecfidera depletes and modulates immune cells. That's why patients need to be monitored for PML.

There have been speculations for years that the drug's efficacy in treating MS, as well as psoriasis, may just be due to simple immune suppression.

general-discussion-f1/topic21537.html#p203536
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Re: Do fumarates change into fumaric acid in vivo?

Postby Anonymoose » Mon Jun 26, 2017 11:23 am

The thing that excites me, being one strongly against using immunomodulation as a disease coverup rather than as a treatment for the cause of disease, is that just MAYBE it's the fumaric acid that's at least partially responsible for helping.

Unscientific, accidental study of one...After two extremely stressful, demanding years, my energy crashed again a few months ago. I had labs done and found my iron/ferritin in low end of normal range so I started taking iron and b complex and got some energy back but still wasn't great. My allergies started bugging me so I broke out my stash of clemastine fumarate and started taking one at night with my iron. For the first time in months I woke up with a clear head, ready to go. If I don't take both, I wake up foggy. Yesterday, I was googling fumaric acid some more and found a post on an autism board by a mom who saw improvements in son with succinate and fumarate supplements. Something to do with the Krebs cycle which I know very little about. Since I don't really like taking "medicine," I ordered supplements to test her idea out (ferritin fumarate and e tocopheral succinate). Then I looked at my current iron supplement, ultimate iron. It's form of iron is ferrous succinate. I was already unwittingly using the fumarate/succinate combo and it seems to work for energy and clarity of mind. Will keep playing and see what happens.

Anywho, I'm always thinking out of the box cuz the box that's out there doesn't work and no one, including big pharma or big doctor, has a complete grasp of anything having to do with a living body.

Thanks for helping me bounce things around. :)

Edit to add: I'm tan from taking dogs to dog park 6 hours a week...those trips made no difference in how I felt...'cept they were fun and made me happy. Maybe skin not making fumeric acid when exposed to sun? Too little info to even guess.
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Re: Do fumarates change into fumaric acid in vivo?

Postby Jimpsull » Tue Oct 03, 2017 7:58 pm

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Re: Do fumarates change into fumaric acid in vivo?

Postby Anonymoose » Tue Oct 10, 2017 8:43 am

Just a follow up on status of my goofy idea re: possible fumaric acid deficiency. After a washout, I had an organic acid panel run. My FA levels are perfectly normal...not even at the low end of range. Still low on vitamin d too (random factoid). Another one bites the dust.
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