Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and Purine Metabolism Deregulation in ME/CFS Cases, 2019, McGregor et al

Is it possible the confusion is arising because we’re assuming the high PEM patients are the, sicker, more severely affected patients?

That isn’t necessarily the case at all, the most ill patients may need to be much more vigilant about avoiding activity; whereas milder patients can push themselves into a right state of PEM, knowing they have the capacity to bounce back over next few days.

 

Exactly. I've hypothesised before, based on my own experience, that many 'mild' patients may be able to get away with a 'rolling PEM' state, on the basis that their PEM isn't so severe as to require avoidance - they are able to work through the effects of PEM whereas more severe patients get flattened so do all they can to avoid it.

 

Yes. But I overheat and get dehydrated too.

 

Yes, and my urine usually smells sweet. This only happens when I'm in a crash.

 

That sounds like diabetes.

 

I have never experienced 'mild' PEM in 28 years and don't consider myself severe. Are we experiencing different pathologies? When I experience delayed PEM it is what I would consider severe every time.

 

Insipidus Diabetes?

 

Well, what severity would you consider yourself? I spent many years slowly declining from mild through to, eventually, the severe end of moderate. When I was mild and still working full time, looking back, I would say that I was in a rolling PEM state which I would try to recover from at the weekend. But as I deteriorated then I became less and less able to carry on regardless - at my worst PEM would see me confined to my bed with crippling gut pain, but because I was no longer working I was typically able to keep those kind of experiences to once or twice a year.

 

@Andy tbh, I don't like using the severity chart. I'm housebound 80% of the time and only go out for short outings when I get a ride somewhere during the day. I feel better in the evenings. I'm not declining as far as I'm aware , and stay within my 'energy window' to avoid PEM. It's boring but I avoid PEM that way. I've been able to avoid it for a little over 3 years now. But my PEM is horrible, and when I am in PEM I am completely disabled, one time I almost called 911.

 

Could it have something to do with this bit from the paper, which seems to say our kidneys may behave similarly to those of people with diabetes insipidus (which causes excessive peeing)?

 

That's what I noticed too. It could be. It fits some of the symptoms, at least. Didn't acute renal failure lead to Sophia Mirza's death?

I wonder if this is a complication that occurs in severe cases, or if it is just something that happens to all of us, but to a lesser degree?

Obviously this is all just theory, and needs to be followed up, but this isn't the first time researchers have mentioned a diabetes-like presentation to ME patients.

 

I used to have extreme urination - looking back I think I was always prone to it for as long as I remember, and it landed me in hospital once with severely low blood sodium. I now take desmopressin - have done for many years - and it makes a huge difference. I have really had to fight for it at times, and even change doctors, and buy it online with my then-very-meagre income.

 

Right, diabetes could be one important cause to consider; but, it may just be dehydration.

Why does my urine smell sweet?

 

That could be possible too. Though I would've assumed dehydrated people's urine would smell more of urea, and that a proportion of those with dehydration may have high blood sugar anyway, since it's relatively common.

Glucose metabolism problems have been raised before in ME. The CFIDS Association has metabolic syndrome down as a common co-morbidity on their website, for instance.

 

When I need more desmopressin and am urinating a lot, it is almost colourless - almost pure water by the look of it (although it may contain some solutes, such as sodium).

 

I find the information hard to interpret too, as it requires an understanding of biochemistry that I lack entirely. But I think this sentence is important (my bolding):

Reductions in the purine metabolite, hypoxanthine, were also found in the serum metabolomes of the females in first morning fasted samples [2] and potentially indicated reductions in the ability to produce ATP.

It then goes on to say more about the potential implications of glycolytic dysregulation, including possibly linking it to immune system issues. It's all still at the theoretical stage, though!

I found this interesting, as supplementing with BCAAs appears to attenuate the symptoms of PEM quite noticeably for me:

Evidence also indicates a switch toward utilization of branched-chain amino acids as an energy source, especially during exhaustive events [17].

It's hard to prove an effect, of course, but as I stay within the suggested dose and only use them when I realise I've overdone it, they probably won't do me much harm.

 

I’m wondering if you would share what dose you take @Kitty ? I started on a small daily dose of BCAAs after having what seemed to be a positive affect from whey and then vegan protein.

I wonder if I have taken too much as I crashed about a month ago, and I’m currently weighing up whether to increase or reduce the BCAAs.

I feel worse than I have in years.

Always impossible to work out cause and effect but I can’t stop trying!

 

I had a custom BCAA formula made up for me based on the results from my OAT, fatty acids. oxidative stress, antioxidants etc results, and they made zero difference on how I felt.

 

Sorry you're feeling so crap – I hope it improves soon.

To be honest, I buy whatever's on sale at the time. My latest are from MyProtein, called Essential BCAA, and I take the dose suggested on the bottle.

They're not a cure for pushing too hard, but for me they reliably reduce the symptoms of PEM from overdoing things a bit. Normally, I'd wake up with a swollen throat and body-wide weakness, which would last a couple of days. If I start BCAAs as soon as I realise I've gone over my limit, this subsides within an hour or so of waking. I still need to rest just as much, but I don't feel really ill in the way I usually would.

They seem to work well for some folk, but I don't think it'd be a good strategy to use them as a way to exceed your envelope on a regular basis. I use them when I hit the wall by accident or unexpectedly, and it hasn't led to any crashes in the year or so since I started them.