Malic acid supplement, sumac

@EndME you bring up many great points, and it's largely the same thought process that I've been going through myself! I'll try to address each point individually:

I think to some extent there is a lot of individual variation, so things that are a fluke for 99% of pwME might be some random person's miraculous cure. In this case, even though not everyone gets an effect, I'm encouraged by the fact that several people who saw my story at random reported a similar boost.

So far, of the people that have tried it and reported to me (not counting this thread), 3 out of 4 claimed a huge boost, even describing similar duration and other effects when I did not share those details ahead of time.

Granted, that could still be placebo in some of their cases since they were not able to do similar blinding as me. But I think pwME have an intuition that even the strongest placebo is very unlikely to let a bedbound person get up and cook a full meal for the first time in months without PEM afterwards.

I don't think this is likely to be a treatment for all people with ME. At most, it might work for a subset. My hope in posting on here was to see if others would try it and confirm that it has a better efficacy rate than those random supplements or whatever psych treatment is in vogue.

 

I actually have done more extensive blinding since I first made this post, I just haven't written it up here yet.

I asked my family member to flip a coin to select between malic acid and my "placebo" six times. Then I asked them to put the selected pill in my morning pill box and write down which day was which. I spaced out the days so that there was little chance of residual effects or lingering PEM affecting the results.

On days when I was doing my test, I dumped all my morning pills into my hand without looking at them and took them all at once so I would be less likely to detect subtle differences in the gel capsules between malic acid and placebo. Since the other morning pills would be consistent, I figured they were unlikely to confound anything.

An hour later, I went for a walk as far as I could manage (or had time for). Afterwards, I guessed which one I had taken.

On some days I was able to walk nearly an hour (I didn't have time for longer with school obligations) without any pain or PEM, and other days I started getting muscle pain and weakness after 15 minutes. I guessed right about the supplement 6/6 times.

Obviously there could still be some lingering effect I'm not accounting for, but overall I feel like this is as thorough I could get on my own. I'm trying to see if I can arrange the same setup for other people that have reported a positive effect to me previously.

 

Apologies I may have been unclear in my original comment. My thought is that fructose might be negating the effects of the malic acid somehow. So apples or apple juice, which have both malic acid and high fructose, have no effect on me. Same would probably be true for other fruit juices with malic acid.

But sumac and the malic acid supplement both have high malic acid and no (or extremely little) fructose, which might be why they have an effect.

@EndME I hope I've addressed your questions/concerns! Thanks for engaging, it's always good to hear other people's thoughts on things like this.

 

Thanks for the responses!

I'll get to the other messages later, but wanted to clarify what I meant in this part of the message. My idea was that you thought the fructose was negating the effects of the malic acid somehow. So a pretty simple approach would be to take a fruit juice comparable to apple juice but without much malic acid and take your malic acid with that (if you were to take apple juice you'd be getting a double dose of malic acid and I don't know how that would fit your ideas). If you have no effects then you can maybe think it confirms your ideas, if you still think you feel the effects you might have to rethink your ideas about why apple juice wouldn't just work in the first place.

This experiment could be "blinded" fairly easily by taking different juices you aren't familiar with, some of which contain fructose whilst others could for example contain an artificial sweetener and others a combination etc.

 

Unfortunately I think there would be fructose present in any fruit juice that would make it impossible to do a test like this. No matter the malic acid content, the fructose is going to be much more abundant.

Taking enough malic acid to out-compete the fructose levels would probably just leave me with some extremely intense heartburn. As it stands, I think the fact that any fruit juice I’ve tried seems to make the malic acid supplement less effective for me is the closest I could get to testing this.

 

If the heartburn isn't placebo, then there's not really a way to blind yourself.

Does the fruit juice also prevent the heart burn?

 

I tried taking 2 tablespoons of sumac with water yesterday. I did not notice any difference in my symptoms either positively or negatively.

 

The heartburn doesn’t always happen, only at higher dosages than what I usually take. And when I have experienced it, it’s after other positive effects have already been noticeable

though that does give me the idea of using citric acid capsules as a potentially more equivalent placebo for others, thanks!

 

Thanks for letting me now! Sorry it did not work for you.

 

So as of now if I’m counting correctly including my PMs and this thread, we have:
4 people including me who report a definite boost
1 which didn’t report a big boost but lack of negative effects after some activity
3 with no effect

and then a bit of anecdotal evidence about a boost with malate formulations of other supplements

 

That's quite a good blinding technique, and a decent result! I'd like to see more data but it certainly appears as though Malic acid works for you. If hope the result continues and if there is a subset, I wonder how big it is!

However I worry sometimes about the reception for simple treatments. I try to be 100% intellectually open to a treatment that is near-free and makes healthy people say, "lol, you suffered for decades because you didn't eat enough _____?" But it's not appealling!

I suspect many of us want or subconsciously expect more symmetry between problem and solution - an utterly catastrophic disease seems like it should need a big, serious, heavy intervention. A surgery perhaps or a molecule that is expensive and very dangerous. That's a good rule of thumb for cancer- big cancer needs hard chemo. But scurvy kills even faster than cancer and the cure is simple. Same with oral rehydration therapy for cholera.

I think effective treatments could be lurking in plain sight and "if that worked we would know by know" might not always be true. Because the fine details matter (scurvy could be cured wth fresh oj but not with stored lime juice, oral rehydration therapy killed people til we got the osmotic gradient exactly right) and so effective treatments could be undermined even in a controlled experiment, let alone an uncontrolled one.

 

Thanks for your thoughts on this! I think it’s a really good perspective. I was surprised as anyone that sumac actually had an effect on me in higher dosages considering I was sprinkling it on food pretty frequently. I arrived to it with a “might as well try this silly thing, probably will just leave me with a bad taste in my mouth” mindset and ended up feeling such immediate relief that I started sobbing from joy.

I’m certainly hopeful that more people can get some relief from this. And hey, even if it is just me and the few others, that’s at least one more dedicated researcher in the field who now has more energy to keep going until we find things that work for everyone!

 

I agree with @Murph, as far as informally testing your idea this seems as good as anything you could do on your own. Of course wine also contains some larger amounts of malic acid without much fructose (some wines will give you upwards of 800mg per glas), which would maybe be rather paradoxical given that pwME seem to respond badly to it rather than the opposite.

I would say exactly the opposite since we already know exactly the opposite from numerous different studies. People can report recoveries and associate them to all sorts of different things (Rituximab, Ampligen, CBT, GET) without the treatments having any efficacy.

The arguments about subgroups, sometimes combined with some ridiculous post-hoc analysis, that then tend to come up tend to be meaningless and usually boil down to "even though the placebo-blinded study of this homeopathy failed, it must have worked for those that were responders". Of course it possible that misdiagnoses, different subgroups etc can potentially interfere with some results, but thusfar there is no evidence to suggest it and if someone really believes there are responders it would be fairly simple to design a study to show exactly that.

I suspect there's little you can do about not getting a biased sample set for your own malic-acid experiment (people only responding when they feel improvement, people that tend to experience improvements from supplements being more likely to participate etc), so I hope you can get to do some more fundamental biological research for your hypothesis at some point.

 

@jnmaciuch does malic acid do anything for you when you're in PEM? Or does it mostly prevent PEM? I still take it from time to time as I'm hoping for a placebo effect, but so far it's given me nothing but acid reflux. And have you ever tried taking it without a stimulant or other supplements?

FWIW my main PEM symptoms at the moment are a sore throat and a mega headache. I usually feel very tired shortly after exertion, but it's not necessarily part of PEM.

 

Interesting that you note wine--my first ME/CFS publication was actually about alcohol intolerance. Alcohol intolerance could actually be explained pretty easily by my malate hypothesis since cytosolic NAD+ is required for ethanol breakdown. If you have insufficient malate, then you're going to end up with much more NADH than NAD+ in the cytosol, so ethanol can't get broken down quickly.

Weirdly enough, a few weeks after I started the malic acid, I invited some friends over for dinner and we had some wine. Normally just half of a glass of wine is enough to make me feel almost immediately sloshed--something new that I noticed after I got ME/CFS. I'll only indulge once in a while if I have nothing to do the next day.

But that night on the malic acid, I didn't register that I was getting tipsy until I finished 2 whole glasses. I didn't even notice the difference in the moment--my friend was refilling our wine glasses (knowing that normally I switch to water on my own when the alcohol starts affecting me). She pointed it out to me after the 2nd full glass. And didn't have any of the normal next day effects of drinking alcohol.

You'd think that malic acid in the wine would be enough to give the same effect as the supplement, so it shouldn't make a difference if I took the supplement or not. I truly have no idea what's going on here. I suspect there are other complex sugars besides fructose from the wine fermentation that may also counteract malic acid absorption (or some other explanation I'm not thinking of). That night I also took my supplement 2 hours before dinner, so maybe it had already been absorbed into my cells by the time I was drinking wine.

My new tolerance to alcohol has continued with the supplement. I haven't tested yet if the intolerance comes back when I don't take it, but might be something to try in the future.

 

Have those placebo effects lasted long term, though? I've only heard of cases where there was a short term improvement but then it lapsed soon after. Although I normally don't care to look at studies about something I know to be useless, so maybe I'm missing some info.

Myself and the others I've spoken to are going on 1-2 months with consistency, though I suppose we'll have to see how long it lasts for us all.

I absolutely echo your frustration here for those fluke trials.

I'm specifically thinking of subsets in the context of molecular profiles--a colleague of mine recently wrapped up an interested analysis doing unsupervised clustering on multi-omic data of Long COVID patients. There were actually some interesting substantial differences between some of the subsets they identified, though of course it remains to be seen if that can be replicated in another study.

If I'm interpreting that optimistically, it means that there could be a couple different molecular mechanisms that all lead to a similar downstream effect which we're calling ME/CFS. Some effective treatments may only affect one of those possible mechanisms at a point father upstream, so it won't do anything to address downstream effects from a different starting point. Of course, it's hard to see anything like that in a simple supplement trial without in-depth molecular profiling data to go along with it.

If I ever end up being part of a malic acid clinical trial, I'm going to push for collecting metabolomic data from the participants pre- and post- trial to see if there is actually a consistent difference that predicts responders vs. non-responders.

But I'm more interested in doing a biological study to prove the mechanism first, so that's what I'll put my effort towards.

 

For me, it mainly prevents PEM in the first place. I've only experienced PEM once since I started the supplement, and that was when I had forgotten to take a second dose of the supplement during the day.

On a stimulant, my PEM tends to start only a few hours after activity with pretty noticeable fatigue and muscle pain. When I noticed and remembered to take the second supplement, it actually stopped the pain and fatigue from progressing. But I caught it pretty early, so not sure how it would affect me if I was already in full blown PEM.

I'm so sorry you're experiencing the acid reflux--I'd hate for you to continue getting only a negative effect from the supplement. Is there a lower dose that doesn't give you acid reflux? I'm able to get an effect from just half the pill.

I've tried it on its own without other supplements, so I don't believe the effect is dependent on them (if it does actually work for someone). I have not tried it without my stimulant since I would be unable to do school work without it and I can't really risk falling behind. I'll probably have to stop experimenting on myself soon and just go with what gives me the most energy for a while for the same reason.

However, at least 2 people who have PM'd me got an effect from the malic acid or sumac without a stimulant. They weren't able to go for a two-hour walk like me (probably a combination of malic acid + stimulants). But one described being able to get up and cook when they are normally bedbound. Another described being able to do several activities in a row at home when normally just a shower would wipe them out for the day.

I've personally never experienced a sore throat as part of PEM, mainly exhaustion, muscle pain or soreness, and brain fog. Headaches occasionally, but mostly if I haven't eaten recently. If there's any merit to my "subsets" theory, I wonder if different PEM symptoms are an indication. I know one of the responders I talked to has similar PEM experiences as me, but I haven't confirmed with the others.

Again, so sorry it does not work for you. I know how frustrating it can be to see something work well for someone else and not experience the same effect. I've been there myself so I really sympathize and hope you find something that works in the future.

It might be slow research-wise, but I will continue looking into the question of subsets to see if there are any hints for what might help the "non-responders." I don't plan on leaving anyone behind if I can help it!

 

Me too! Although people say that their symptoms fluctuate and some of them only appear after a few years of living with this illness.

 

Good point, that might be part of it. I got ME/CFS in 2018-2019. It was gradual so hard to point to when it started exactly.

 

Update!

I ended up making a silly mistake taking my stimulant before bed, so I had to skip taking it the next morning to avoid doubling up on dosage. Which means that yesterday was actually the first time that I took the malic acid during the day well after the stimulant would have worn off.

It seems like for me, the immediate difference in energy and brain fog is actually dependent on the stimulant. I didn't get any noticeable boost, and I seemed to go back to baseline levels of symptoms that are similar to what I remember pre-stimulant.

However, yesterday I still pushed myself to clean some rooms in the house, which is something that reliably triggered PEM for me pre-stimulant. It is 24 hours later and I still am not experiencing PEM.

Of course there are probably other confounding things, so I'm not sure how much can actually be interpreted from this experience alone. I didn't sleep much the night before, and it has been several years since I started the stimulant so my underlying condition may have changed. Additionally, I did take the stimulant this morning, so that might potentially have interrupted PEM as well.