#11 Malate / malic acid

cs3000

Info on
inflammation, restoring mitochondria, mitochondrial NADPH / glutathione & lifespan, a mechanism involved in glucose raising T3, cancer metastasis, chemo protection

L-malate has a good anti-inflammatory effect in arthritis https://www.nature.com/articles/s41392-024-02076-9.pdf
and in the small intestine

Giving aged rats 0.21g/kg L-malate orally restores their mitochondrial liver Complex I, III and IV enzyme activity to youth levels https://www.biomed.cas.cz/physiolres/pdf/60/60_329.pdf

malate stopped breast cancer metastasis well https://www.researchgate.net/publication/348261020_Mitochondrial_Malic_Enzyme_2_Promotes_Breast_Cancer_Metastasis_via_Stabilizing_HIF-1a_Under_Hypoxia

more / full writeup
https://cs3001.substack.com/p/11-supplementing-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.