#11 Malate / malic acid

Mauritio

Great post !

The most interesting part was the part about GSH/GSSG.
In this methionine restriction study the GSH/GSSG ratio was through the roof. And until now I couldn't make sense of it. Why would a state of reductive stress increase life span by 43% ??
So maybe it's not the whole body that's supposed to be in an oxidized state. Although I don't know if they measured it the ratio in the mitochondria or outside of them .
https://bioenergetic.forum/post/19771

IL-10 is a good cytokines to raise. The strong increase in Testosterone by L. Reuteri is dependent on IL-10 increase (or it lowering IL-17). so malic acod should have some androgenic effects as well.
https://pmc.ncbi.nlm.nih.gov/articles/PMC3879365/

What's your experience with it like notice any benefits ?

dapose

Great stuff!
You ever seen any good reason to use Magnesium Malate?
I eat one Apple a day to keep my doctor away! Plus so OJ and cherries I think have some Malic acid too. Do you think supplementation to 600mgx2 in addition to the fruits amount would be too much?
Rock n Roll! Great post!
I think @DavidPS is a fan of malic acid but I might be wrong.
️

DavidPS

@dapose - It wasn't me. I get enough magnesium from my diet.

Do you think supplementation to 600mgx2 in addition to the fruits amount would be too much?

I have heard stories about people who take magnesium malate when they have constipation. If that is not the effect you desire, I would slowly increase the amount.

cs3000

@Mauritio updated some more on il-10 in the metastasis part. no noticeable effects at 1.2g so far
yeh impressive result gsh/gssg sounds especially important for mitochondria to be able to do their thing,
https://pubmed.ncbi.nlm.nih.gov/39214486/ right GSH/GSSG prevents tumor development/damage in the first place but GSH can protect cancered cells preventing theraputic effect / inhibiting it can slow proliferation , havent seen the results for how well it worked but surprisingly there adding GSH inhibited tumor proliferation (id like to see concentration used though, was it reasonable or overloaded, might not be relevant)

Mauritio

@cs3000 what do you think about the issue with malic , succinic and lipoic acid etc and heavy metals?
Peat warned against taking them (but was fine if they're endogenously produced)
because it might lead to re-depsositing heavy metals at even more vulnerable places like the brain.

cs3000

@Mauritio writing one about that, for aluminium malate can increase tissue deposits or can lower them. to minimize looks best taken away from contaminated food sources and after dietary aluminium in mucus moves lower through tract / in the morning. but even with increased deposit there's still a protective effect like with platinum. plants secrete malate to protect against aluminium
its hydrophilic but small molecular weight, theres a transporter for these dicarboxylate acids but i dont think expressed at the BBB, so only a small % gets through to the brain

big difference in tissue between https://doi.org/10.1177/096032718800700305
& https://doi.org/10.3109/15563658808995398
so giving it after instead of simultaneously either actively lowered brain concentration somehow? or prevented delayed distribution to brain

you seen anything that stands out for protecting against aluminium damage?
so far got rosmarinic acid / thyme, malate, silicic acid (some can get to the brain with its low molecular weight & BBB problems / or preventatively removing before brain deposit, peripheral could effect brain too indirectly), naringin (wary of high doses of these though), maybe selenium though its more for mercury. maybe thats enough. typically "low" concentrations in people vs these studies but doesnt take this much to cause dysfunction (chronic immune activation)

Mauritio

@cs3000 interesting so maybe taking it after food with heavy metals in them might be good. Or maybe the amount in chocolate or other foods isn't even high enough to matter.
But could be something worth taking after heavy metal exposure from MRI contrast.

I always thought the Peat's hypothesis on these acids was hard to prove. You'd have to kill the animal than look at every organ to confirm the Redeposition.

So malic acid seems at least safe enough to try for me.

For aluminum specifically not. MCP would be a general approach.

cs3000

@Mauritio malate / citrate increased aluminium in tissues when taken at the same time or close, so its protective (for overall survival at least) but with that timing its still facilitating absorption & tissue deposit like it can with nutritional metals, so idk about redeposits but can increase absorption (citric too & ray got a lot of it / some of both from drinking a lot of OJ) , in the 2nd one it lowered tissue amounts in the brain & liver a lot instead when given separate time periods (aluminium first for a while then the acids for a while)

(obviously doses acutely not relevant to humans for us is more of a slow burn, but brain amounts can hit that level)

Mauritio

@cs3000 Yeah I don't see why Ray was not against malic /citric acid from apple or orange juice but was against supplementing it...
For citric acid it might be its fungal origin(when from Supplements), but that still doesn't explain malic acid.

Mauritio

Malic Acid Improves Behavioral, Biochemical, and Molecular Disturbances in the Hypothalamus of Stressed Rats

https://pubmed.ncbi.nlm.nih.gov/37519180/

happyhanneke

@Mauritio
I soak my feet and hands in warm water with malic acid and it helps a lot for arthritis. I also add epsom salt.
I've never used it orally.

Mauritio

@happyhanneke interesting makes sense that it helps. I wouldn't be surprised if it helped even more if you added oral supplementation.

In the above study it basically reversed all signs (psychological and physical) of chronic mild stress, which is quite remarkable.
HED was ~3g, which is quite high.

Mauritio

Malic acid given to pregnant rats increased antioxidants and anti-inflammatories.
Again, most notably GSH.
It also increased fast twitch muscles in offsprings.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10519833/#sec3

Malic acid increases life span in C. Elegans . Is a mild mitochondrial uncoupler.
https://pubmed.ncbi.nlm.nih.gov/23472183/

Mauritio

Great thread on malate.

"Relatively small amounts of exogenous malate are required to increase mitochondrial oxidative phosphorylation and ATP production. Once an elevated mitochondrial malate concentration is attained, it may support an increased rate of substrate transport into the mitochondria without depleting its own matrix concentration, for malate is regenerated in the tricarboxylic acid cycle during the oxidation of the substrates with which it exchanges [49, 53]."
https://lowtoxinforum.com/threads/magnesium-malate-when-energy-fails.16611/

sunsunsun

isn't there zero reason to supplement malic acid if you eat a normal amount of apples? one apple has supplement level doses

Mauritio

@sunsunsun i get a bigger effect of malic acid than from eating an apple. I call this " the isolated compound paradox".