Supplements and Drugs That Reduce or Prevent PEM (Post-Exertional Malaise)

[Learner1]

NAD+ has one conversion to make ATP. NMN has two. NR has more, and some people cannot make use of it. Here is a diagram showing the relationship.

 

[livinglighter]

NAD+ has one conversion to make ATP. NMN has two. NR has more, and some people cannot make use of it. Here is a diagram showing the relationship.

View attachment 40488

Thank you for the explanation! I'll stick NAD+ and discontinue ribose.

 

[Pyrrhus]

NAD+ has one conversion to make ATP.

I'm curious. What conversion would that be? Maybe you meant "one conversion to make NADH".

Although NADH and ATP are both molecules that store energy, they are distinct molecules. In Oxidative Phosphorylation (also known as electron transport phosphorylation) the energy from NADH and other molecules is used to phosphorylate ADP to form ATP.

There are many forms of vitamin B3 which are ultimately converted to NADH, and as you say, Nicotinamide Riboside (NR) needs 3 steps to get to NADH, and Nicotinamide Mononcleotide (NMN) needs two steps to get to NADH. Nicotinamide, which is a form of B3 commonly found in B vitamin supplements, needs 4 steps and a Ribose molecule to get to NADH.

But this is all somewhat irrelevant to the main reason why people supplement with Ribose. The main reason why people supplement with Ribose is to boost the purine salvage pathway, which takes degraded ATP and restores it so that more ATP is available. [1][2] It is also interesting to note that purine salvage is a critical metabolic pathway in the brain, and it may become more important with injury to the nervous system. [3][4]

Hope this helps.

References:
[1] https://pubmed.ncbi.nlm.nih.gov/11568162/
[2] https://pubmed.ncbi.nlm.nih.gov/14660478/
[3] https://pubmed.ncbi.nlm.nih.gov/28836168/
[4] https://link.springer.com/chapter/10.1007/978-1-4757-0390-0_5

 

[bensmith]

@Learner1 not sure?

 

[Learner1]

@Learner1 not sure?

Sorry, of what?

 

[Learner1]

I'm curious. What conversion would that be? Maybe you meant "one conversion to make NADH".

References:
[1] https://pubmed.ncbi.nlm.nih.gov/11568162/
[2] https://pubmed.ncbi.nlm.nih.gov/14660478/
[3] https://pubmed.ncbi.nlm.nih.gov/28836168/
[4] https://link.springer.com/chapter/10.1007/978-1-4757-0390-0_5

Yes, I did.

The first paper concludes:

"Ribose supplementation did not affect subsequent muscle force production after 60 min of recovery."

The second paper says:

"The present study demonstrates that oral intake of ribose in humans after 1 wk of high-intensity training leads to an enhanced resynthesis of ATP,...

...Therefore, in humans ATP resynthesis probably occurs mainly via de novo synthesis...

...However, no significant resynthesis of ATP was observed at 24 h in Rib. This discrepancy may be explained by the fact that purine salvage constitutes an important pathway in rats (4) but apparently not in humans...

...Finally, the reduction in resting ATP observed after intense training does not appear to affect intense intermittent exercise performance."

In the third paper, the key part of the experiment was done on rats, which makes it not as useful AND the author has a significant conflict of interest.

In the fourth paper, rats were used as well.

It is extremely helpful not just you read abstracts, but to read the entire paper.


The conclusion is that most people will use de novo synthesis, that papers on high intensity athletes may not apply to PwME and that rat studies may not provide results that work in humans.

For those who are still interested, this paper describes how the various pathways are used and how they can be supported. One must realize that taking tryptophan can be counterproductive in that some of us have issues with the IDO2 metabolic trap HTrster has found.

https://neurohacker.com/how-is-nad-made-de-novo-synthesis

I've tested niacin, niacinamide, NADH, NAD+, NMN, d-ribose, and NR, each for a couple of months, and for me, only NADH, NAD+ and NMN have an effect. The NADH is too expensive yo get the dose I need, so I use either NAD+ or NMN daily, whichever is the best price. There is a lot of hype in the marketplace about NR by the makers of Niagen, but some of these claims they make have been disproven.

Taking niacin or niacinamide alone can be problematic as they reverse methylation, do one may need significantly more folate, B12, B6 and other methylation nutrients if one takes them. Although, it's wise to be aware of one's status of them if one takes any of these supplements.

 

[livinglighter]

Unfortunately, I’m not well versed with the science behind all this, so I appreciate everyone explaining the mechanisms about the supplements we are using.

I can only add ribose used to work really well for me. However, after suffering a major relapse and sliding down the severity scale it stopped producing the same energy yielding results. Now NAD+ works for me
slightly better then ribose worked initially. So I would say perhaps start off on ribose as it seems cheaper and add or switch to NAD+ or the others @Learner1 is mentioning if it’s not promising. NMN seams slightly cheaper then NAD+, but it may just depend where you are in the world.

@Learner1 where do you source NAD+ if you don’t mind me asking? I’m buying the Tru Niagen label but I’m looking for cheaper sellers if it’s available.

Thanks.

 

[Learner1]

Tru Niagen is not NAD+. It's NR, nicotinamide riboside. Their website has a lot of hype, and some of their statements have been disproven.

LIAS Research sells NAD+. Alive by Nature sells both NAD+ and NMN. Enada sells NADH. All the other products I've seen, except for those from compounding pharmacies, are NR, niacin or niacinamide. I'd love to be proven wrong.

 

[Pyrrhus]

It is extremely helpful not just you read abstracts, but to read the entire paper.

I fully understand your cynicism- when I was in academia I saw far too many bad practices from reviewers of papers. But I can assure you that your cynicism is entirely misplaced here.

It's been a number of years since I studied the mechanism of action of Ribose to understand why so many ME patients report clear, consistent benefits from Ribose supplementation. I can assure you that I read full papers, and many more papers than the very few I chose to mention above.

But you raise some interesting points about the papers I mentioned. I will start a new thread to address those points as I don't want to take this thread off-topic.

 

[Learner1]

I fully understand your cynicism- when I was in academia I saw far too many bad practices from reviewers of papers. But I can assure you that your cynicism is entirely misplaced here.

It's been a number of years since I studied the mechanism of action of Ribose to understand why so many ME patients report clear, consistent benefits from Ribose supplementation. I can assure you that I read full papers, and many more papers than the very few I chose to mention above.

But you raise some interesting points about the papers I mentioned. I will start a new thread to address those points as I don't want to take this thread off-topic.

Great, thanks. You might also look into the effects of the NMRK1 and 2 gene variants.

 

[pattismith]

I had my exercice intolerance gone when taking yellow mustard seeds, (muscle pain/burning gone) three times a day.

Not sure I can keep it, because it seems my vasodilation + burning hands/feet is worsening...

 

[stefanosstef]

I had my exercice intolerance gone when taking yellow mustard seeds, (muscle pain/burning gone) three times a day.

Not sure I can keep it, because it seems my vasodilation + burning hands/feet is worsening...

Thanks.Dosage?

 

[pattismith]

Thanks.Dosage?

sinapis alba seeds, i took about 2.7 gr three times a day in my trial (about one week).

Dosage is not documented so I took what seemed a big dose to me, so that I couldn't miss the result on my body.
(Be careful, it's hot for the stomach, so maybe start with half the dose)
The good reputation yellow mustard has for muscle is not scientifically documented.
I was not aware of it in fact. I got the idea to take it because I use mustard powder on my scalp and face, so I was aware of it's anti-inflammatory virtues.
Doing some researches I found yellow Mustard seeds is useful for Psoriasis and blocks TLR7 activation.
I don't have Psoriasis but wanted to see if oral route may benefit to me the way it benefits locally.

 

[hapl808]

Does anyone have particular thoughts on what supplements or treatments would help for mental exertion PEM? When I have long phone calls or difficult mental work, I get the same PEM crash starting 12-36 hours after the exertion and lasting for 1-3 days.

I've tried Q10, magnesium, BCAA, D-Ribose, NMN, Chinese skullcap, etc. Maybe magnesium helps reduce recovery time, ibuprofen seems to help as a shielder but not reliever, maybe BCAA helps but it's negligible, etc.

Curious if people have suggestions for supplements that could specifically work as mental exertion PEM shielders or relievers.

 

[Hip]

Does anyone have particular thoughts on what supplements or treatments would help for mental exertion PEM?

A while ago I went through my supplements and drugs journal, looking for reports of when I exerted myself mentally but did not get the usual mental PEM.

In my case, I visit certain friends every week for several hours of light socializing. I invariably find that I get mental PEM the next day after this social outing, as regular as clockwork. But on a several occasions, I noted in my journal that my post-socializing mental PEM was much reduced.

On these occasions, this is what I took a few hours before going out socializing:

Occassion 1: Tagamet (cimetidine) 50 mg + Peak ATP (adenosine 5'-triphosphate disodium) 125 mg

Occassion 2: trimetazidine 35 mg + amiloride 10 mg + niacinamide 1000 mg

Occassion 3: creatine monohydrate 2 grams + hyaluronic acid 400 mg

Occassion 4: allicin 180 mg x 6 + breathing oxygen for 2 hours immediately after socializing

Occassion 5: vinpocetine 40 mg + progesterone cream 600 mg + CJC-1295 growth hormone stimulant

Occasion 6: rifaximin 200 mg

So these items may work to reduce mental PEM. My plan was to retest all of these, but of course once the coronavirus pandemic hit, it curtailed all my social activity, so I have not yet had the opportunity to retest.

 

[livinglighter]

Does anyone have particular thoughts on what supplements or treatments would help for mental exertion PEM?

chromium picolinate 1000 - 2000 mcg

Tru Niagen which is NR

I believe they act as relievers.

 

[Hip]

chromium picolinate 1000 - 2000 mcg

Tru Niagen which is NR

I believe they act as relievers.

Have you observed yourself that these supplements help dissipate or reduce mental PEM?

 

[livinglighter]

Have you observed yourself that these supplements help dissipate or reduce mental PEM?

I had a severe relapse and tried Tru Niagen/NR because ribose wasn’t working anymore. Although it didn’t do anything or much for my physical PEM, it immediately reduced/dissipated my mental PEM. So I continued to use it for that until I tried NAD+.

Chromium Picolinate - I took to reduce/cut my carb cravings to try and aid weight loss. I’m unfortunate in suffering from metabolic symptoms such as rapid weight gain, inability to lose weight, crashing after meals, hypo-like symptoms, etc. Not only has it reduced carb/sugar cravings and crashing immensely, it acts as a PEM reliever. I notice I wake up with far less brain fog because of it. I take 2000 mcg as soon as I wake up, but most advice states to take it at intervals throughout the day.

 

[Hip]

Although it didn’t do anything or much for my physical PEM, it immediately reduced/dissipated my mental PEM.

Just so we are clear: mental PEM is where you get PEM symptoms (such as increased fatigue, increased brain fog, etc) after a bout of mental exertion (like social chat with friends, talking to someone on the phone for some time, reading, concentrating on a difficult mental task, etc). Typically the PEM will hit the next day, after a bout of mental exertion.

 

[hapl808]

Yes, thanks for the clarification @Hip - that's how I meant to use it. The PEM crash from mental exertion feels almost the same for me as the PEM crash from physical exertion. Since it starts 12-36 hours later for me, I think it took me a number of years to make the connection. Like you, I try to keep a careful journal so I can make connections later.

I should try allicin again - in the past I noticed it improved a lot of my symptoms, but never trialed it specifically for PEM. Was there a reason for the other combos, or just what you noticed you took? I've also never tried ATP supplements, so I'll have to look into that as well.

Was any one of those four combos particularly more effective than the others? Thanks again for all the info!