Malic acid supplement, sumac

[forestglip]

I would just be curious for the people that didn't report a noticeable effect from the malic acid: did you happen to track whether you still got PEM after activity that normally triggers it for you (if the activity was within a few hours of taking the malic acid/sumac)? @OrganicChilli @wingate @forestglip

Added: Only wondering if you happened to track it already--I would not want to push anyone else into PEM just to test my theory!

It seems like @MeSci may have had a similar experience of not much of an immediate effect, but a lack of negative effects after going shopping. Would you be able to confirm if you continued to see the same pattern?

I know that just asking the question might prime your responses, so I'll take any positive responses with a grain of salt regardless. And if you did still get PEM, that's still valuable information!

Unfortunately, I don't think it has any effect for me, preventing PEM or otherwise. I tried twice 30 minutes before activites I had to do. 2400 mg before a grocery trip and 800 mg before a dentist appointment. Still got a crash the next day both times. The day of the appointment, I had a wired feeling that kept me awake for an hour past when I normally fall asleep, which is pretty common for me after exertion.

 

[jnmaciuch]

Unfortunately, I don't think it has any effect for me, preventing PEM or otherwise. I tried twice 30 minutes before activites I had to do. 2400 mg before a grocery trip and 800 mg before a dentist appointment. Still got a crash the next day both times. The day of the appointment, I had a wired feeling that kept me awake for an hour past when I normally fall asleep, which is pretty common for me after exertion.

Thanks for letting me know! I think it sounds pretty definitive that it doesn’t change anything for you, sorry it didn’t end up giving you any relief.

Out of curiosity, did you happen to get any heartburn or the extra brain fogginess (difficulty reading/focusing eyes, focusing or staying on task in general) that I and others have mentioned?

 

[forestglip]

Out of curiosity, did you happen to get any heartburn or the extra brain fogginess (difficulty reading/focusing eyes, focusing or staying on task in general) that I and others have mentioned?

Nope, nothing at all that I noticed.

 

[jnmaciuch]

Nope, nothing at all that I noticed.

Interesting! Thanks for sharing that as well.

My mom said the same thing—she’s normally much more prone to heartburn as me and took a much higher dosage but was completely fine. Doesn’t have ME. It just made me rethink where some of these side effects might be coming from.

I think there could be a million reasons why malic acid does nothing for people, and the most obvious is just that if your cells have more than enough, there’s no reason to even absorb it. That would go for both completely healthy people, and pwME whose symptoms aren’t downstream of some lack of malate.

Even if it doesn’t alleviate ME symptoms, those side effects might just be an indicator of whether it’s being absorbed at all.

 

[Murph]

Can I ask a few questions about malate:

• Would it be used when a person is in ketosis?
• Does it have have a caloric value of its own or is it considered as a catalyst/co-factor for burning energy?
• Are there any substances that might be used disproportionately a) when relying on malic acid or b) when malate is in short supply?

 

[jnmaciuch]

Can I ask a few questions about malate:

• Would it be used when a person is in ketosis?
• Does it have have a caloric value of its own or is it considered as a catalyst/co-factor for burning energy?
• Are there any substances that might be used disproportionately a) when relying on malic acid or b) when malate is in short supply?

Sure! I’ll do my best to answer—as I’ve already stated, I’m not an expert on metabolism, I just have been doing quite a deep dive for a few months:

1) Malate is pretty much always being used, though there might be some shifts in various organ systems depending on factors such as nutrient availability. It will still play its role of transferring reducing agents to the mitochondria regardless.

From what I remember, malate is also involved in gluconeogenesis and it’s been suggested that it would be preferentially used for this in situations where fatty acid oxidation is increased (i.e. in carbohydrate deprivation).

However, this is something that would be happening only in the liver—it seems to be unknown how exactly malate might be affected more broadly in that situation.

2) The only time it ends up as a “fuel source” is when it is part of gluconeogenesis and eventually becomes a glucose molecule. Still, even in that scenario, it’s not malate itself that is being used.

Malate is really just one transient form of a molecule that’s constantly being changed as it goes through metabolic processes. (True for all molecules, obviously, but this is an example with a particularly high amount of constant flux and transformation). What’s special about the “malate form” is that this specific structure can cross the mitochondrial membrane.

That makes it an effective shuttle—once it crosses the barrier, one of the H atoms gets chopped off and passed off to NAD (becoming NADH) to be used in the electron transport chain. With one less H, the molecule-formerly-known-as-malate is now called oxaloacetate.

3) the second part can be answered much more readily than the first. In an absence of malic acid, what you would expect is an upregulation of shuttling through the G3P shuttle as well as increased glycolysis as compensatory mechanisms. You’d also probably expect increased fatty acid oxidation as compensation for ATP that is not being made through OxPhos.

For the first part, I don’t know of any examples in the literature where cells are forced to use malate when they wouldn’t otherwise. Something to that effect could possibly be happening in some cells—it’s sort of what I suspect from my experiences of extra brain fog with the malic acid. But there’s just nothing I can specifically draw on from the literature to answer that definitively.

Thanks for your questions!

 

[MeSci]

Out of curiosity, did you happen to get any heartburn or the extra brain fogginess (difficulty reading/focusing eyes, focusing or staying on task in general) that I and others have mentioned?

I'm not the person you are asking, but I have noticed occasional heartburn, which I think has come after using sumac or l-glutamine. I'll try to note next time.

I also have difficulty focusing my eyes at times, but hadn't noticed an association with the supplements - again, I'll try to check next time.

Difficulty staying on task is quite common these days! I often feel that I'm swimming through a fog.

 

[jnmaciuch]

I'm not the person you are asking, but I have noticed occasional heartburn, which I think has come after using sumac or l-glutamine. I'll try to note next time.

I also have difficulty focusing my eyes at times, but hadn't noticed an association with the supplements - again, I'll try to check next time.

Difficulty staying on task is quite common these days! I often feel that I'm swimming through a fog.

Given that other people who got an effect from the sumac/malic acid reported the heartburn as well it’s probably that!

Since you also reported a bit of an energy boost on your trip to the store, I’m thinking that the negative side effects might also be an indicator that your body is absorbing it at all, since several others who got absolutely no effect also didn’t report any negative side effects even at much higher doses.

 

[poetinsf]

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

I obviously haven't been keeping up and missed this thread completely. But it sounds similar to cumin trial that I have been doing, so I thought I'd chime in.

Blinding is not possible when testing a herb off your kitchen shelf. You can control/randomize to some degree, however. I've been grouping similar activity days and then flipping coins to randomize. The problem is that it takes awful amount of time and some effort to carefully screen the candidate data. And then it still remains anecdote at the end regardless the amount of effort you spent.

The conclusion I drew from the experience is that it wasn't worth the time/effort to dress it up like some sort of trial, especially if your energy/brain power is limited by ME/CFS. Just take it and see if it has some effect on you, and then continue till you feel that it has no effect, in a Bayesian way. Even if it is purely placebo, it's still worth if it makes you feel better. We have nothing else after all.

 

[jnmaciuch]

I obviously haven't been keeping up and missed this thread completely. But it sounds similar to cumin trial that I have been doing, so I thought I'd chime in.

Blinding is not possible when testing a herb off your kitchen shelf. You can control/randomize to some degree, however. I've been grouping similar activity days and then flipping coins to randomize. The problem is that it takes awful amount of time and some effort to carefully screen the candidate data. And then it still remains anecdote at the end regardless the amount of effort you spent.

The conclusion I drew from the experience is that it wasn't worth the time/effort to dress it up like some sort of trial, especially if your energy/brain power is limited by ME/CFS. Just take it and see if it has some effect on you, and then continue till you feel that it has no effect, in a Bayesian way. Even if it is purely placebo, it's still worth if it makes you feel better. We have nothing else after all.

Thanks for your perspective. I’m fully aware of all the points you list as a junior researcher, there’s much more information later on in the thread.

I did not blind with the kitchen spice, but with a purified supplement form of malic acid. Blinding is possible with the help of another person, identical gel capsules, and additional precautions.

The effort of this protocol was absolutely worth it for me to confirm that it is malic acid itself as the causative factor, and that those effects were so pronounced and repeatable that it is unlikely to be misinterpretation of daily symptom fluctuations.

One person’s anecdote is an oddity, but the anecdotes of multiple people is grounds for further exploration. Which I’ve been doing in my capacity as a researcher, since it points to a mechanism which is very much in line with other findings in the field.

 

[jnmaciuch]

On that note, I’ve just completed 4 more “trial” days, using bulk-purchased empty capsules and citric acid as my placebo to account for any potential influence of heartburn. Both capsules were rinsed to remove any powder on the outside that could be detected as a taste difference. Still guessed correctly 10/10 times total.

I think at this point I’m very satisfied that it’s not placebo effect in my case.

 

[poetinsf]

One person’s anecdote is an oddity, but the anecdotes of multiple people is grounds for further exploration.

I agree. The point was that, no matter how rigorous you are with n=1 trial, it's still an anecdote. You may be able to blind to some extent with extracts, but that's mostly for your own satisfaction and not much more.

 

[jnmaciuch]

I agree. The point was that, no matter how rigorous you are with n=1 trial, it's still an anecdote. You may be able to blind to some extent with extracts, but that's mostly for your own satisfaction and not much more.

I don’t think anyone, definitely not myself, was under the impression that this would ever be a publishable clinical result.

I never claimed it would be anything other than anecdotal, just that I was looking for more anecdotes from other people that might justify looking into it further with actual research. I thought that was fairly obvious? This is a science forum after all.

 

[Murph]

I agree. The point was that, no matter how rigorous you are with n=1 trial, it's still an anecdote. You may be able to blind to some extent with extracts, but that's mostly for your own satisfaction and not much more.

Anecdote is a funny word. It simply describes a person saying what happened. But is loaded - it conveys an absence of rigour, often suggests the story comes from an uncontrolled situation, and is possibly second hand.

An n=1 self trial will lack sample size and institutional oversight. It may not feature rigorous record keeping and will often not generalise. If these are the concerns i think stating them explicitly is probably helpful.

 

[poetinsf]

I never claimed it would be anything other than anecdotal,

I was speaking in general, and not about your project specifically. I chimed in only because n=1 trial was something I had opportunity to think about recently.

just that I was looking for more anecdotes from other people that might justify looking into it further with actual research. I thought that was fairly obvious?

Yes it was, but that wasn't what I was getting at. This just occurred to me though: a researcher actively driving the anecdotal basis for further research could bias the population and promote placebo effect. Unless people apply similar rigor, which I wouldn't for the reasons I pointed out. It then could become a self-fulfilling prophesy. Just a thought that popped into my head.

 

[poetinsf]

An n=1 self trial will lack sample size

The problem with n=1 is that, no matter how rigorous, it only applies to that subject. As you pointed out previously, it could be actually working for that subject. Or it could be a true anecdote as you defined. Since we don't know which for sure, it's probably safer, and reasonable, to just call it an anecdote from the third person point of view.

 

[Utsikt]

The problem with n=1 is that, no matter how rigorous, it only applies to that subject. As you pointed out previously, it could be actually working for that subject. Or it could be a true anecdote as you defined. Since we don't know which for sure, it's probably safer, and reasonable, to just call it an anecdote from the third person point of view.

I think people here generally understand the limitations of any n=1 observation, regardless of what you call it.

 

[jnmaciuch]

I was speaking in general, and not about your project specifically. I chimed in only because n=1 trial was something I had opportunity to think about recently.


Yes it was, but that wasn't what I was getting at. This just occurred to me though: a researcher actively driving the anecdotal basis for further research could bias the population and promote placebo effect. Unless people apply similar rigor, which I wouldn't for the reasons I pointed out. It then could become a self-fulfilling prophesy. Just a thought that popped into my head.

Sure, theoretically. My research interest is in biological mechanism though, which wouldn’t involve any administration of malic acid unless it was directly to sampled cells.

 

[jnmaciuch]

Just an interesting tidbit:

went for a long walk today, and took just enough malic acid that the “immediate PEM” muscle pain and stiffness only started ramping up right as I was getting home. Took 3 full tablets (2400mg) once I got home to see if it would prevent things from ramping up further if I caught it early.

So far seems successful—I can still feel it, but it’s very dulled. But the interesting part is that despite taking such a high dosage, I didn’t get the extra brain fog or heartburn.

In the mornings when I haven’t done any activity yet, I can’t take more than 400mg or my brain will feel way too soupy.

Which tells me that whatever effect it has on my brain, it might be dependent on how much actually gets to my brain vs. getting taken up by muscle or other tissue. And physical activity seems to increase how much other cells are taking up, possibly because they’re just using more and might end up more “deficient.”

[Edit: @MeSci perhaps this will be helpful for you—maybe the trick to avoiding the brain fog side effect is taking sumac right before you’re going to be on your feet/physically active]

 

[petrichor]

Just reporting that I've tried taking malic acid some more times and haven't noticed any difference either in terms of immediate effects or in preventing PEM