Fumaric acid to activate NRF2 pathway

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Distinct Nrf2 Signaling Mechanisms of Fumaric Acid Esters and Their Role in Neuroprotection against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Experimental Parkinson's-Like Disease

pubmed.ncbi.nlm.nih.gov/272...

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Interesting. Here is the full text link: Distinct Nrf2 Signaling Mechanisms of Fumaric Acid Esters and Their Role in Neuroprotection against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Experimental Parkinson's-Like Disease 2016 ncbi.nlm.nih.gov/pmc/articl...

"Nrf2 activation by DMF but not MMF was associated with depletion of glutathione, decreased cell viability, and inhibition of mitochondrial oxygen consumption and glycolysis rates in a dose-dependent manner, whereas MMF increased these activities in vitro. However, both DMF and MMF upregulated mitochondrial biogenesis in vitro in an Nrf2-dependent manner. Despite the in vitro differences, both DMF and MMF exerted similar neuroprotective effects and blocked MPTP neurotoxicity in wild-type but not in Nrf2 null mice. Our data suggest that DMF and MMF exhibit neuroprotective effects against MPTP neurotoxicity because of their distinct Nrf2-mediated antioxidant, anti-inflammatory, and mitochondrial functional/biogenetic effects, but MMF does so without depleting glutathione and inhibiting mitochondrial and glycolytic functions. Given that oxidative damage, neuroinflammation, and mitochondrial dysfunction are all implicated in PD pathogenesis, our results provide preclinical evidence for the development of MMF rather than DMF as a novel PD therapeutic."

Fumaric acid is the sourest tasting acid in the world: sweet-factory.com/uae/sour-...

Fumaric acid IS sold as a supplement at a recommended dosage of 500 mg a day: amazon.com/Supersmart-MrSma...

Dietary Supplementation with Fumaric Acid Improves Growth Performance in Nile Tilapia Juveniles 2022 ncbi.nlm.nih.gov/pmc/articl...

"supplementation improved growth, feed efficiency, protein use, and intestinal villi morphometry. Additionally, the population of undesirable intestinal bacteria was reduced (Gram-negative) or eliminated after 28 days (Enterobacteriaceae) in fish fed fumaric acid diets. Therefore, this study supports the addition of fumaric acid to the diet as a reliable strategy to improve the production and intestinal microbiota health of Nile tilapia juveniles"

Dimethyl fumarate (DMF) vs. monoethyl fumarate (MEF) salts for the treatment of plaque psoriasis: a review of clinical data 2018 ncbi.nlm.nih.gov/pmc/articl...

So... Fumaric Acid looks promising. It seems the MMF (I have seen it called MEF) version may have the benefits without the negatives.

There is a prescription drug version of Fumaric Acid that is DMF and is called TECFIDERA

What are the possible side effects of TECFIDERA? tecfidera.com/content/dam/c...

TECFIDERA may cause serious side effects including:

x allergic reaction (such as welts, hives, swelling of the face, lips, mouth or tongue, or

difficulty breathing)

x PML a rare brain infection that usually leads to death or severe disability

x decreases in your white blood cell count Your doctor should do a blood test before

you start treatment with TECFIDERA and while on therapy.

x liver problems. Your doctor should do blood tests to check your liver function before you

start taking TECFIDERA and during treatment if needed. Tell your doctor right away if

you get any of these symptoms of a liver problem during treatment.

o severe tiredness

o loss of appetite

o pain on the right side of your stomach

o have dark or brown (tea color) urine

x yellowing of your skin or the white part of your eyes

• herpes zoster infections (shingles), including central nervous system infections

• other serious infections

The most common side effects of TECFIDERA include:

x flushing, redness, itching, or rash

x nausea, vomiting, diarrhea, stomach pain, or indigestion

x Flushing and stomach problems are the most common reactions, especially at the start

of therapy, and may decrease over time. Taking TECFIDERA with food may help reduce

flushing. Call your doctor if you have any of these symptoms and they bother you or do

not go away. Ask your doctor if taking aspirin before taking TECFIDERA may reduce

flushing.

These are not all the possible side effects of TECFIDERA. Call your doctor for medical

advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For

more information go to dailymed.nlm.nih.gov.