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Re: Do fumarates change into fumaric acid in vivo?

Posted: Wed Dec 13, 2017 5:01 am
by NHE
sam112233 wrote:Fumaric acid activates nrf2 itself.
Do you have a reference for this? Once the carboxylic acids are deprotonated on fumaric acid, the ability of the conjugated pi bond to participate in resonance with the carbonyl will be lost. The highly reactive carbocation will not be created and it won't oxidize thiols.
sam112233 wrote:Methanol just depletes glutathione making the person sicker.
Do you have a reference to support your implication that dimethyl fumarate releases methanol?
sam112233 wrote:If methanol was so good then alcoholics who drink methylated spirits would be in awesome health but instead they get sicker, and sometimes die after metho binges. It happened to one of my mums old tennants. Once he started on the metho there was no stopping him. He was found dead a few weeks later in the flat.
That's because the enzyme alcohol dehydrogenase normally takes ethanol and converts it to the aldehyde ethanal. When given methanol as a substrate, methanal is created instead. Note that methanal is also known by its common name formaldehyde.

Re: Do fumarates change into fumaric acid in vivo?

Posted: Wed Dec 13, 2017 5:09 am
by sam112233
The study was linked. And once in the organism the ester bonds breaking leaving methanol + fumarate. Yes methanol is toxic. Good observation. Pharma companies don't want someone taking fumaric acid because it is cheap, and effective. They wan't someone staying on their expensive, less effective, side effect causing patented compounds.

Re: Do fumarates change into fumaric acid in vivo?

Posted: Wed Dec 13, 2017 6:23 am
by NHE
sam112233 wrote:Naturally occurring molecules actually treat disease.
Tetrodotoxin is a "naturally occurring molecule." It only treats disease if you consider chronic heartbeat problematic. Indeed, there are plenty of nasty "naturally occurring molecules" that will do one in. Anatoxin-A will drop you dead in about 5 minutes. Domoic acid will destroy your short term memory. Aflatoxin from moldy peanuts causes cancer. And so on...

Re: Do fumarates change into fumaric acid in vivo?

Posted: Wed Dec 13, 2017 6:43 am
by NHE
sam112233 wrote:It is not the reactivity with thiols that makes di methyl fumarate good it is the fumarate. The methanol component is bad. Fumaric acid is better than methyl fumarate.

https://www.frontiersin.org/files/Artic ... 5-g001.jpg
https://www.frontiersin.org/articles/10 ... 00085/full
I'm not sure why you cited that article. It appears to argue that excessive levels of intracellular fumaric acid promote oncogenesis.
Loss of [fumarate hydratase] FH enzymatic activity results in accumulation of intracellular fumarate which has been proposed to act as a competitive inhibitor of 2-oxoglutarate-dependent oxygenases including the hypoxia-inducible factor (HIF) hydroxylases, thus activating oncogenic HIF pathways.

Re: Do fumarates change into fumaric acid in vivo?

Posted: Wed Dec 13, 2017 10:18 am
by sam112233
NHE wrote:
sam112233 wrote:Naturally occurring molecules actually treat disease.
Tetrodotoxin is a "naturally occurring molecule." It only treats disease if you consider chronic heartbeat problematic. Indeed, there are plenty of nasty "naturally occurring molecules" that will do one in. Anatoxin-A will drop you dead in about 5 minutes. Domoic acid will destroy your short term memory. Aflatoxin from moldy peanuts causes cancer. And so on...
How many supplement companies have them as an oral supplement? Shill. You must work for a pharma company. Fumarate is anti cancer.

Re: Do fumarates change into fumaric acid in vivo?

Posted: Fri Dec 15, 2017 7:02 am
by sam112233
Another treatment for MS is the amino acid threonine

Spot the double (or triple or quadruple) speak.

To determine whether the naturally occurring amino acid threonine, a potential precursor for glycine biosynthesis in the spinal cord, has an effect on spasticity in multiple sclerosis, 26 ambulatory patients were entered into a randomized crossover trial. Threonine administered at a total daily dose of 7.5 g reduced signs of spasticity on clinical examination, although no symptomatic improvement could be detected by the examining physician or the patient. In contrast to the side effects of sedation and increased motor weakness associated with antispasticity drugs commonly used for the treatment of multiple sclerosis, no side effects or toxic effects of threonine were identified

These data indicate that modest suppression of the clinical signs of spasticity in a population of patients with MS was achieved with oral administration of threonine. Despite this effect, no improvement in symptoms of spasticity or in global neurologic function was associated with therapy. While the clinical effects observed in this trial do not support the use of threonine in the treatment of MS, the clear reduction of spasticity scores in treated patients suggests that additional studies, employing higher daily dosages or combination therapies, may identify a therapeutic role for this amino acid in the treatment of this disease.

http://sci-hub.la/10.1001/archneur.1992.00530330045014