Taking hydrocortisone before activity to prevent PEM crashes---I think that's on target!!

[Hip]

@grapes, this might be something of interest:

The over-the-counter drug theophylline greatly potentiates the anti-inflammatory effects of corticosteroids. Ref: 1

So possibly taking theophylline with corticosteroids may allow you to get the same anti-PEM effects at a lower corticosteroid dose. In this study where they added theophylline to the corticosteroid regimen of asthma patients, they used a dose of 250 mg of theophylline daily.

Theophylline also has a vasoconstriction effect, and is thus useful for POTS, to reduce blood pooling in the legs on standing.

 

[grapes]

@grapes, this might be something of interest:

The over-the-counter drug theophylline greatly potentiates the anti-inflammatory effects of corticosteroids. Ref: 1

So possibly taking theophylline with corticosteroids may allow you to get the same anti-PEM effects at a lower corticosteroid dose. In this study where they added theophylline to the corticosteroid regimen of asthma patients, they used a dose of 250 mg of theophylline daily.

Theophylline also has a vasoconstriction effect, and is thus useful for POTS, to reduce blood pooling in the legs on standing.

Now that is interesting and I appreciate you telling me. I see it's a bronchodilator, too. It would be a good thing if it helped a weaker cortisol, but still effective, like Adrenal Cortex. Just did some reading, and there can be a problem with theophylline and thyroid levels. I'm hypothyroid on T3, and I'll have to dig deeper. I'm still very interested!

 

[grapes]

@grapes, this might be something of interest:

The over-the-counter drug theophylline greatly potentiates the anti-inflammatory effects of corticosteroids. Ref: 1

I'm not finding it over the counter anywhere....

 

[Hip]

I'm not finding it over the counter anywhere....

It's over-the-counter here in the UK, because I bought it OTC. But maybe it's prescription elsewhere?

 

[grapes]

It's over-the-counter here in the UK, because I bought it OTC. But maybe it's prescription elsewhere?

Sadly, looks like it's prescription here. Are you trying it with hydrocortisone?

 

[Hip]

Sadly, looks like it's prescription here. Are you trying it with hydrocortisone?

I don't really get much PEM from physical exertion, only get mild PEM from the mental exertion of socializing. So I am not the best candidate to test out these PEM busters that other have found effective. I tested prednisone 15 mg before socializing, but did not notice much anti-PEM benefit, but I should really test it some more.

 

[SlamDancin]

@Hip You should find this interesting. It doesn’t appear that the mitochondria “contain” a GR but rather different isoforms of GR have different effects on the mitochondria when they are activated and translocated to the mitochondria which requires a lot of mechanics to work.

Identification of GRγ as regulating nuclear genes encoding mitochondrial proteins, and interacting with mitochondrial proteins suggested a coherent biological programme for GRγ in regulating cellular energy metabolism. We analysed mitochondrial morphology, and discovered that both GR isoforms reduced mitochondrial circularity, a measure of mitochondrial fusion32.
GRγ expression resulted in a profound increase in mitochondrial mass, when compared to the GRα. Dynamic energy metabolism was investigated further, using Seahorse technology, which revealed GRγ dependent increase in ATP generation, and oxygen consumption. Interestingly, we saw these GRγ specific changes in the absence of added ligand. Therefore, our data supports the identity of complementary, but unique, GR isoform actions on mitochondrial energy expenditure. This also provides a mechanism for the transfer of time of day information to the mitochondria through the HPA axis33,34. In humans, serum cortisol concentrations are strongly circadian, peaking early morning, falling throughout the day to reach undetectable levels at night. Therefore, at night the ligand independent actions of GRγ on mitochondria would be dominant.

https://www.nature.com/articles/srep26419

GR shares this translocation machinery with other nuclear receptors too such as HIF-1alpha and the Aryl Hydrocarbon Receptor (AhR). Reduced GR translocation may be caused by lots of different factors but clearly for some pwME forcing this action through corticosteroids is extremely helpful. My own personal theory is it’s the AhR that we want to prioritize most as it’s the Kynurenine receptor. This is of course based on the preliminary results of Dr Phairs work. Then there’s the possibility that hypoxia could keep HIF-1alpha constantly hogging the translocation machinery and effectively antagonizing GR and AhR.

By the way does anyone understand the last sentence about non ligand activated effects? How does a receptor act without being ligand activated?

 

[Hip]

It doesn’t appear that the mitochondria “contain” a GR

I don't really understand that study you quoted (but I am brain foggy at the moment), it seems to be focused on the role of a particular subtype of the glucocorticoid receptor (GR).

But the studies I cited in the PEM busters thread do state that the GR is found on mitochondria. This study states:

With regard to mode of action, there is increasing evidence that mitochondria are controlled by the action of GCs, as GC receptors are found in mitochondria

 

[pogoman]

So late last night after my first full day of MISERABLE FATIGUE, I discovered I did have CoQ10 (ubiquinol) and creatine monohydrate. So this morning, feeling absolutely horrible with fatigue again, I took both over the next few hours: Over 2000 mg ubiquinol and 10,000 mg of creatine monohydrate. (I have ordered the creatine hydrochloride).

And by 2 pm today, I was feeling noticeably better!!

BUT....it all went south by late afternoon and evening. Felt horrible again.

UPDATE: continued the high CoQ10 the next day, today, and felt significantly less tired.

I will say this: several years ago, when I had monster fatigue while detoxing heavy metals, I discovered that high dose CoQ10 did help a lot to counter that fatigue. I was close to 3000 mg ubiquinol.

I discovered several years ago that B2, coq10 and l-carnitine helped my myopathy and neuro symptoms, then later found out that those were the core ingredients for the "mito cocktail".
If I stop any of them I get pain and weakness.

With PEM its always heat related for me, I've had two occurrences of dark brown urine I suspect was rhab earlier this summer when I was doing outside physical labor in the heat.

I've tried creatine numerous time to see if it helped but it never did, I must be of the small minority of people not responsive to it.

 

[hamsterman]

I discovered several years ago that B2, coq10 and l-carnitine helped my myopathy and neuro symptoms, then later found out that those were the core ingredients for the "mito cocktail".
If I stop any of them I get pain and weakness.

With PEM its always heat related for me, I've had two occurrences of dark brown urine I suspect was rhab earlier this summer when I was doing outside physical labor in the heat.

I've tried creatine numerous time to see if it helped but it never did, I must be of the small minority of people not responsive to it.

Yeah, heat is a huge factor. When I monitored my HR, I noticed that my HR went up when I wasn't doing anything at all, but the temperature was rising.

As far as creatine, for me, it doesn't necessarily make me feel better, or reverse PEM, or anything like that. What it does is it allows my muscles to do a little bit more than they normally would, with the same apparent exertion. Also, it'll give you a slight increase in mental power... but it doesn't in anyway help with motivation, energy, or well-being, or anything like that. It just allows you to do a tad bit more... so if you normally have problems with doing any sorta multi-step mental task, this might help a bit. But if I'm PEMing, it doesnt seem to help at all.

 

[olegsel]

It doesn’t appear that the mitochondria “contain” a GR but rather different isoforms of GR have different effects on the mitochondria when they are activated and translocated to the mitochondria which requires a lot of mechanics to work

That is why sleep does not provide recovery.

 

[SlamDancin]

That is why sleep does not provide recovery.

Do you mind explaining what you meant by this exactly? Sounds interesting.

 

[SWAlexander]

Note that it is normal doses of corticosteroids (eg, prednisolone 20 mg, or hydrocortisone 80 mg) that can prevent PEM, not the low doses (eg, prednisolone 5 mg, or hydrocortisone 20 mg) that some ME/CFS patients take daily.

I´m taking hydrocortisone instead cortisol. I have adrenal insufficiency.
PEM can cause Addison´s crisis.
In a lecture on Addison´s crisis, I learned that hydrocortisone supports the little cortisol that is left, while prednisone replaces our own cortisol production and puts your adrenal gland to sleep.
Also TSH, especially T3 and T4 should get closer attention and should be frequently checked.

 

[Gingergrrl]

@Alvin2 I'm tagging you in case anything in this thread is helpful for you (and I haven't read the entire thread yet myself).

 

[Alvin2]

@Alvin2 I'm tagging you in case anything in this thread is helpful for you (and I haven't read the entire thread yet myself).

Thanks
I would never have thought to use Hydrocortisone as a PEM shield

 

[Wayne]

The following thread contains information on combining coritsol with Vitamin C for enhanced results.

Dr. Thomas Levy -- How COVID Helped Me Regain Good Health

 

[SWAlexander]

coritsol with Vitamin C

Vit C is not my problem.
I, like most people with low cortisol, have permanent low Vit D.
It is a pain in the ... to convince doctors to test or prescribe higher (10 000 i.u.) dose V 3.

 

[Gingergrrl]

Thanks I would never have thought to use Hydrocortisone as a PEM shield

I hadn't thought of it either since my reason for initially starting hydrocortisone (and my current reason for continuing it) both have nothing to do with PEM.

I, like most people with low cortisol, have permanent low Vit D.

Why do people with low cortisol have permanent low Vit D?

It is a pain in the ... to convince doctors to test or prescribe higher (10 000 i.u.) dose V 3.

Can you buy Vit D 10,000 IU's over the counter or on Amazon or is it prescription only where you live? If it's prescription, can you buy the 5,000 IU's and take two pills at a time?

 

[SWAlexander]

Vit D 10,000

There are no 10,000 I. U. Vit. D. in Germany. So I take over the counter 2x 5500 I. U. Vit. D. daily and still remain close to low. But that is manageable.

 

[gm286]

Chiming in. I too have probably developed adrenal insufficiency from about 3 years of prednisone use (10mg). Doctors want me off it, still trying to taper, but there is little hope I will manage that.

It was suggested to me by a young doctor in France years ago. It instantly helped, this was following over a decade of fatigue, brain fog, sickness in the morning.

The info on here is useful. See also this thread (hugely predictive factor in ME/CFS + Long Covid = low cortisol).

I now believe that, from my earliest years (adolescence), every time I caused serious shake ups in energy metabolism / adrenal function / stress / strong illness (obviously without realizing it) that my cortisol continued to drop without recovering. For me, this is perhaps the centrefold / foundation of ME/CFS.

Maybe one day I will be able to get to 5mg prednisone, maybe use hydrocortisone as someone mentions above that it is more supportive, less repressive than prednisone.