Malic acid supplement, sumac

Solaris said:
Is there any reason to suspect that malic acid would have a superior effect over NADH? Or (as I had read) is NADH incapable of entering the mitochondria directly? In which case, are NADH supplements completely pointless?
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Yes NADH isn’t supposed to cross the mitochondrial membrane. There’s a pool of NAD/NADH inside the mitochondria and one in the cytosol, and malate is the shuttle that moves “H” in between them.

I don’t know for sure that malate’s role in mitochondrial function is why malic acid helps me so much—it would make sense given the specific improvements I felt, but malate does several other things in the body. But if it is the mitochondrial aspect that’s relevant here, you’d be right that NADH supplements probably wouldn’t be doing much.
 
jnmaciuch said:
Hi all!

I'm a graduate student living with ME/CFS and currently studying ME/CFS and long COVID. I was recently reviewing literature on mitochondrial dysfunction and stumbled onto something very interesting which potentially explains several semi-consistent findings in the literature.

Specifically, I was struck by Lawson et al. (2016)'s findings of no mitochondrial dysfunction in ME/CFS and increased ATP production from glycolysis. Since there's been other evidence of mitochondrial dysfunction, this struck me as odd, so I dove a bit deeper into the referenced methods with the hunch that perhaps something that was in the cell media inadvertently "fixed" mitochondrial function.

Turns out something was added--malate and pyruvate. If my hunch is right, then the most significant effect of adding malate would be restarting the malate-aspartate shuttle--the main mechanism for supplying H+ to mitochondrial NAD+ and maintaining the pool of mitochondrial NADH.

And this explanation would actually explain some other consistent findings since mitochondrial NAD(P)H is a necessary substrate for other reactions, most notably steroid hormone synthesis (found to be decreased in ME/CFS and long COVID, full disclosure the second link is my paper currently in review) and bile acid synthesis (decreased in ME/CFS).

This may also result in reduced cytosolic NAD+, which would impair ethanol breakdown, potentially explaining alcohol intolerance common to ME/CFS (also my paper). Since mitochondrial NAD+/NADH levels also have a bidirectional relationship with circadian rhythm, this could also potentially explain sleep disturbances. It's also known that COVID can impair the oxidative arm of the TCA cycle, so I'm thinking similarities between long COVID and ME/CFS may be due to failure to recover the TCA cycle after infection.

Long story short, I'm currently trying to organize a study to formally test this. But while I'm waiting for logistics to sort themselves out, I figured I could use myself as a lab rat. Since malate in the form of malic acid is present in a lot of fruits (albeit at low concentrations) I tried to see what would happen if I consumed a lot all at once.

Turns out the highest concentration I had available in my kitchen was in the spice sumac, and ingesting ~2 tbsp with water led to my brain fog melting away almost immediately and out of nowhere I had the energy to get up and do some chores. I already take a stimulant which enables me to be in grad school, and this felt like taking double the stimulant without the racing heart or other negative side effects.
The effect lasted for about 2 hours.

Since it's possible that this was due to 1) placebo effect or 2) something else in the sumac, I found a malic acid supplement online to test out my theory further. The supplement happens to look almost identical to a serrapeptase supplement I already take (which has a very mild pain relief effect, but nothing close to what I experienced with the sumac), so I asked a family member to randomize which one they gave me. Huge boost from the malic acid, nothing from the 'placebo.'

I also had another friend with ME/CFS try the sumac and reported almost exactly the same effects and duration without me sharing those details in advance. I'm still trying to work out dosage (the full supplement seems to trigger some low blood sugar/headaches if I don't eat frequently) but I'm still amazed I saw this much of an effect.

In the mean time, if anyone else is willing to try this and report if it has any effect on you, I'd be extremely interested (especially if you're willing to do a placebo control!). Given the heterogeneity in this illness it's likely not everyone's symptoms are caused by the same cellular mechanism, so this may not work for everyone (I especially don't think it'll work if you don't experience PEM). But since it'll take a while to sort logistics for a formal study, I wanted to share on this community forum and see if others could provide some informal data.
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Interestingly, I found this old study (1992) that also discusses malic acid (and magnesium malate) for fatigue. https://magistralbr.caldic.com/storage/product-files/2060248082.pdf
 
MinIreland said:
Interestingly, I found this old study (1992) that also discusses malic acid (and magnesium malate) for fatigue. https://magistralbr.caldic.com/storage/product-files/2060248082.pdf
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Thanks! Yes, malic acid and other TCA cycle substrates been trialed in a couple different contexts as far as I remember. It seems to be quite hit and miss, usually no more than a few points of improvement across the treatment group in whatever primary outcome is being measured. I must admit that I’m not particularly swayed by the mechanistic theory in this FM article, even if the reported improvements in muscle pain are real.

My sense is that it may legitimately help for a small subset of people, but the factors that make it effective for that percentage are pretty much a black box at the moment.
 
I am sorry to ask this, but I can’t read the whole thread. Is 800mg malic acid the right amount? I’m planning to try this soon.
 
Verity said:
I am sorry to ask this, but I can’t read the whole thread. Is 800mg malic acid the right amount? I’m planning to try this soon.
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No problem, the thread definitely got extremely long.

800 mg is the size I purchased. Taking the full amount gives me heartburn unless I immediately do something physically active (I wish I knew why), so I will usually titrate according to activity. First thing in the morning if I’m not planning to do anything intensive that day, I will usually dump out most of the capsule to take ~200 mg
 
jnmaciuch said:
No problem, the thread definitely got extremely long.

800 mg is the size I purchased. Taking the full amount gives me heartburn unless I immediately do something physically active (I wish I knew why), so I will usually titrate according to activity. First thing in the morning if I’m not planning to do anything intensive that day, I will usually dump out most of the capsule to take ~200 mg
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Thank you! That’s helpful!
 
I have purchased malic acid and just took my first capsule (in combination with magnesium malate). I'll let you know if anything changes, although the timing is not great, given that I'm dealing with PEM at the moment (for me it seems that, the more rest I take, the more exhausted I start to feel. Perhaps a sign that I'm not very good at reading my body's signals yet and start increasing rest too late).

Update... I just realised that magnesium malate includes malic acid? So probably not necessary/wise to combine the two?
 
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Oxaloacetate is alive and well on Reddit. @jnmaciuch i remember you said its a waste of money and people might as well use malic acid (apparently some people tried it and only oxo helped, but I can't find the thread and it's anecdotal).

Now someone says this:

Probably worth doing the organic acids test to see if this is for you. It seems only some people with cfs have Krebs cycle issues so it would only be helpful to them
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I assume that's nonsense because we can't easily detect anything anywhere wrt to CFS?
 
OrganicChilli said:
I assume that's nonsense because we can't easily detect anything anywhere wrt to CFS?
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Yep. This test is used to detect pretty fundamental problems in metabolism that result in a substantial failure to produce certain metabolites.

If you’re not at that level of system failure, this test is just capturing a snapshot of a system that varies wildly person to person and hour to hour anyways. Way more likely to be artefact than anything useful
 
OrganicChilli said:
Oxaloacetate is alive and well on Reddit. @jnmaciuch i remember you said its a waste of money and people might as well use malic acid (apparently some people tried it and only oxo helped, but I can't find the thread and it's anecdotal).

Now someone says this:



I assume that's nonsense because we can't easily detect anything anywhere wrt to CFS?
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I tested below normal range for oxaloacetate and took the supplement years ago. It made no difference.
 
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