Malic acid supplement, sumac

Pharmacological and Antioxidant Activities of Rhus coriaria L. (Sumac), 2021
We show how accumulating evidence supports the antibacterial, antinociceptive, antidiabetic, cardioprotective, neuroprotective, and anticancer effects of this plant, especially that toxicity studies show that sumac is very safe to consume by humans and has little toxicity. Taken together, the findings we summarize here support the utilization of this plant as an attractive target for drug discovery.
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The review is very positive.
 
Nightsong said:
The supplement you referenced is 800mg/capsule. By contrast, various apple juices:

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Interesting, in the studies I looked at the only ones approaching that range were crab apples, which would make sense with the concentrated sour taste. More common apple species were in the 0-5 mg/g range iirc--I'll go back to my search history. I wonder if the effect is also dependent on whether it's ingested alongside a high sugar concentration or other organic compounds commonly found in fruits.
 
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Utsikt said:
@jnmaciuch would you be able to provide us with a specific dosage of malate? Tbs or tsp of something else isn’t really accurate..
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Unfortunately the dosage in sumac is going to be hard to gauge, esp since malic acid content varies wildly between subspecies and the grocery store brands I could find didn't list the source origin. the supplement I linked is 800mg, and I ended up adjusting to take half of it at a time every ~4 hours.
 
Utsikt said:
I know it might not be possible to answer, but do you have an estimated timeframe? And what about funding?
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At this point it's dependent on a lot of factors outside of my control--I likely would have funding through my lab, though the bigger issue is getting access to viable samples. There are two possible experiments I could do, one would provide much more detail but would involve IV infusion for several hours, which understandably would be extremely difficult to arrange for ME/CFS. Another method would be more indirect (measuring mitochondrial NAD/NADH) but would be easier to organize. I spoke to some other researcher who have used this assay and they normally do this on cancer cell lines. Not sure how well it would work on a PBMC blood sample since the cell count might be much lower, but I'm currently trying to test it out on my own samples just to see if it'll work.
 
Someone linked me to this clinical trial for oxaloacetate, which is the immediate upstream/downstream precursor to malate (though oxaloacetate would not be the form that is specifically crossing the mitochondrial membrane to deliver H+). Seems to have elicited some response with a subset of "superresponders", which (if it can be taken at face value) indicates that there's likely heterogeneity in exactly which part of cellular metabolism is pathobiological across ME/CFS.

https://www.healthrising.org/blog/2024/12/17/oxaloacetate-chronic-fatigue-syndrome-trial/
https://pubmed.ncbi.nlm.nih.gov/35764955/
 
jnmaciuch said:
Someone linked me to this clinical trial for oxaloacetate, which is the immediate upstream/downstream precursor to malate (though oxaloacetate would not be the form that is specifically crossing the mitochondrial membrane to deliver H+). Seems to have elicited some response with a subset of "superresponders", which (if it can be taken at face value) indicates that there's likely heterogeneity in exactly which part of cellular metabolism is pathobiological across ME/CFS.

https://www.healthrising.org/blog/2024/12/17/oxaloacetate-chronic-fatigue-syndrome-trial/
https://pubmed.ncbi.nlm.nih.gov/35764955/
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Thread on the trial here:
Oxaloacetate Treatment For Mental And Physical Fatigue In (ME/CFS) and Long-COVID fatigue patients, 2022, Cash and Kaufman
 
jnmaciuch said:
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
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I think you would just have to eat roughly one apple to get the equivalent of your 800mg capsule. Or, according to the table @Nightsong linked, about a half a glass of apple juice (one glass is around 250 mL).
Possibly I have stuffed up the calculations?
 
Hutan said:
Determination of Predominant Organic Acid Components in Malus Species: Correlation with Apple Domestication, 2018

FW is fresh weight. At 5 mg/g, and an average apple weight of 200 g, one apple would have 1000mg, or 1 g.
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Interesting! In that case, I think there is likely some effect of other organic compounds in apples, considering I eat apples pretty regularly (knowing they have malic acid) and didn't get the same effect. I'm particularly curious about the sugar compounds, since glucose concentrations are known to affect the balance of glycolysis/OxPhos. Or it could still be placebo despite my best attempts at mitigating that...
 
Utsikt said:
That’s great!

What do you mean by samples? From participants?

And do you intend to do a study of malate as a treatment, or is it just a study on cells/blood from patients to see how they respond to malate?
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Yes, likely blood samples from participants (if blood ends up working for the assays I'm interested in). The study I'm currently working on would not involve malate treatment, I would be mostly trying to identify whether there are TCA cycle abnormalities consistent with an impaired malate-aspartate shuttle. The NAD/NADH experiment would mostly be providing proof of concept so I have leverage to arrange a more complicated and expensive 13C experiment, which might be more likely to pinpoint where exactly in the TCA cycle there is an issue (if there is one at all).

A clinical trial with malate supplementation is also an option that I'm exploring, though I'm more interested in understanding the pathobiological mechanism since there might be a specific issue in an enzyme or transporter protein related to the malate-aspartate shuttle. If that can be pinpointed, it might open the door to more specific targeted therapies. If I'm right about this at all, supplementing malate would be more of a duct tape solution since the ability to produce endogenous malate in response to other environment triggers is vital.
 
MeSci said:
By the way, I used to use l-glutamine when I had to go shopping, and it worked well - I felt a distinct increase in energy. I can't remember why I stopped, but I've still got some. I refer to it here: https://www.s4me.info/threads/rando...l-syndrome-2018-verne-et-al.5494/#post-111183
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Thanks for sharing! That makes a lot of sense to me--several studies have pinpointed glutamine metabolism abnormalities, and my best guess is that it is part of a compensatory mechanism when TCA cycle/OxPhos is inhibited (a la the Warburg effect in cancer cells). Increasing glutamine would likely help prop up that compensatory mechanism even further
 
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Hutan said:
I think you would just have to eat roughly one apple to get the equivalent of your 800mg capsule. Or, according to the table @Nightsong linked, about a half a glass of apple juice (one glass is around 250 mL).
Possibly I have stuffed up the calculations?
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No I think you're probably right, my own calculations may have been incorrect initially. Interestingly, despite having cravings for sour fruits, I almost never have a craving for fruit juices and tend to crash after drinking them. I always attributed this to the sugar content without fiber to slow absorption, though obviously this might just be an individual quirk. Like I mentioned in previous comments, I think it would be worth exploring the interactions malic acid might be having with other compounds in e.g. apples vs in sumac
 
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I’v been trying out different otc supplements to support blood flow by increased NO. I found Citrulline Malate felt superior to other stuff I tried (l-arginine, concentrates of beetroot juice, bicarbonate etc.), but never really considered the role of malate. Interesting!

The citrulline malate powder comes at a 2:1 ratio, my dose has been in the range of 1-4 g of malate.
 
MeSci said:
One problem that I think pwME have when trying supplements is that they sometimes work well for, say, a couple of years, and then stop working.

Theory - that a new shortage/imbalance occurs.

I do hope that your work reveals something interesting and useful, @jnmaciuch.
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Yup, I think we're probably dealing with a very complex loop of feedback and compensatory mechanisms. It's entirely possible that a malate-aspartate shuttle impairment is caused by the cell trying to "protect" itself by shutting down mitochondrial function (though I can only make wild speculations on why that would occur). Or a million other things. That's largely why I'm more interested in understanding the biological mechanism.
 
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