Malic acid supplement gave huge energy boost, reduced brain fog and muscle pain

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.

 

If anyone does try the sumac, fair warning that it's a bit unpleasant to ingest 2 tbsp all at once. I recommend softening with a bit of hot water and then mixing with yogurt and a tiny bit of honey for taste. I initially tried it with the water because I didn't want to risk any confounding factor from whatever I mixed it with, but I got the same effect mixed with water or yogurt.

 

Malic acid is the incredibly sour chemical, right? You didn't taste it at all on the capsules when doing the blinded test?

Edit: Also, was there any kind of physical response? Like flushing, heart racing, etc?

 

Hi @jnmaciuch

I'm interested to read your experience/ideas, but I'm afraid reading very long paragraphs of text without is impossible for me (& I know lots of other people with ME/CFS).

Not sure if it's possible with your posting method (i know it's tricky on some devices), but would it be possible to edit your post & break up the text into several short paragraphs please? I'm eager to read what you're saying.

Of course no problem if you're unable/dont want to, I'm just eager to read what you have to say & cant as it is.

Also I didnt recognise yr name so i checked yr profile saw this thread, which i missed The Epistemic Injustice of the Cognitive Behavioral Model of Chronic Fatigue Syndrome, 2023, Maciuch | Science for ME

Looks great! I'm too ill to read it at the moment but have bookmarked it & from the first quote that @ Hutan shared I certainly look forward to reading it!

 

Given the levels of malic acid in various fruit juices if it had any significant effect on ME/CFS I think we would know by now - IIRC it was first isolated from apple juice (mālum being Latin for apple).

 

well, why not?



Doesn't taste too bad. I'll let you know how i feel!

 

I'm pre-COVID ME/CFS. I tried 2 tablespoons of Ziyad brand Sumac a couple hours ago. No effect as far as I can tell.

Pleasantly surprised about the taste though. I was expecting to have to power through something gross, but the sourness was almost candy-like. I just mixed the spice with water and drank it.

 

It is pretty sour on its own (a little less sour than citric acid powder on some candies) but in the gel capsules you can't taste it at all. The only physiological effect I noticed was a very slight tightness around my heart (that's probably not the right word to describe it, it wasn't anything worrying enough to make me think I was having a heart attack. Closer to very mild heartburn, probably) and I noticed that I would get headaches if I didn't eat every few hours. But those issues went away if I dumped out half the supplement capsule to take a lower dosage.

 

The concentration in sumac is actually much higher than it would be for other fruits, and it took 2 tbsp before I felt an effect. The dosage in a capsule would also be much higher. I had experienced intermittent cravings for some fruits which I later learned to be higher in malic acid (cherries, apples, etc.) but I probably would have had to eat several dozen apples in one sitting to get the equivalent of one capsule worth of malic acid

 

Thanks for the note, I edited to include more breaks. Hope it is easier to read now

 

Thanks for the follow up! My friend and I both felt a noticeable effect within ~30 minutes, so you would probably have noticed a difference by now if it worked for you. Unfortunate that it did not give you a boost but negative data is still useful data!

 

Malate is also highly utilized by every cell in the body, so if you're trying to replace it through diet (since it can't be properly recycled by cells), you'd need to ingest quite a bit before OxPhos came back online and you noticed any effect. There's probably also an absorption/bioavailability issue--malic acid still needs to be converted to malate before it can be used for the shuttle

 

One hour update: I felt pretty cheerful over the last hour but I also realise I misread the post and took an amount measured in teaspoons (approx 7 or 8 grams) not 2 tablespoons (30-40g?).

Also I wonder if the absorption taken with yoghurt might be slower than with water.

Overall in retrospect I enjoyed the sour flavour. Perhaps I will repeat the experiment with a higher dose at some point.

Pure Malic acid seems to be very cheap and available in bulk. https://kegland.com.au/products/malic-acid-1kg

 

I know it might not be possible to answer, but do you have an estimated timeframe? And what about funding?

 

This might not be remotely equivalent but I recently switched my magnesium supplement from magnesium citrate to one containing magnesium malate and I have found it more helpful than the citrate, in terms of getting to sleep, not being constipated, and generally feeling slightly better than usual.

 

The supplement you referenced is 800mg/capsule. By contrast, various apple juices:

 

@jnmaciuch would you be able to provide us with a specific dosage of malate? Tbs or tsp of something else isn’t really accurate..

 

thanks @jnmaciuch

That looks interesting...

 

Both, hypometabolic and hypermetabolic states can be specified as mitochondrial dysfunction. There is often quite a bit of confusion about what is mito dysfunction.

​

 

Malic acid and magnesium was a supplement combo that was highly recommended back in the 90s when I first became ill. I took it during PVFS phase and felt almost recovered for 6 weeks. I started doing more activities after that but went back to previous levels soon after. I assumed it had been just a coincidence

I eat quite a bit of sumac with foods.