Pregnenolone As A Possible Treatment Of CFS/ME

[haidut]

I just posted yet another study showing that CFS/ME is a metabolic disorder that can be treated using various substances that activate PDH and Krebs cycle activity.
CFS/ME Once Again Confirmed As A Metabolic Disorder
This study took an alternative path and discovered that people with CFS/ME also have lower levels of the TRPM3 receptors compared to healthy controls. Given the TRPM3 importance and presence in so many organs, the downregulation likely explains the dysfunction experience by so many CFS/ME patients in organs like the brain, spine, digestion and even heart activity.

The science behind the Queensland Government’s CFS ‘breakthrough’ statement | Science Alert | 22 February 2017
"...But in several peer-reviewed papers published by the Griffith team last year, they showed that in CFS/ME patients, something seemed to be going wrong with TRPM3. In the latest study, the team looked at blood samples 15 CFS/ME patients and 25 healthy controls, and found that immune cells in chronic fatigue patients had far fewer functioning TRPM3 receptors than those of healthy participants. As a result, calcium ions weren’t making it inside the cell like they should be, meaning cell function was impaired. What makes matters worse is that TRPM3 isn’t just found in immune cells. The team tested its presence on immune cells as they’re easy to access in blood samples, but the receptor is found on every single cell in the body, which not only explains why CFS/ME has been so difficult to diagnose, but also why it’s so severe. “This is why it’s such a devastating illness, and why it’s been so difficult to understand,” one of the researchers, Don Staines, co-director of Griffith University’s National Centre for Neuroimmunology and Emerging Diseases, told ScienceAlert. “This dysfunction affects the brain, the spinal cord, the pancreas, which is why there are so many different manifestations of the illness – sometimes patients will suffer from cardiac symptoms, sometimes it will be symptoms in the gut.”

The good news is that there is an easy way to counter those lower TRPM3 levels by using pregnenolone, which has been shown to be a potent TRPM3 agonist.
Pregnenolone For Blood Sugar Control

And thyroid function is know to be crucial for the production of the TRPM3 receptor, so taking thyroid should have similar effect not to mention that it shows the intimate connection between metabolism and CFS/ME.

 

[Dante]

I just posted yet another study showing that CFS/ME is a metabolic disorder that can be treated using various substances that activate PDH and Krebs cycle activity.
CFS/ME Once Again Confirmed As A Metabolic Disorder
This study took an alternative path and discovered that people with CFS/ME also have lower levels of the TRPM3 receptors compared to healthy controls. Given the TRPM3 importance and presence in so many organs, the downregulation likely explains the dysfunction experience by so many CFS/ME patients in organs like the brain, spine, digestion and even heart activity.

The science behind the Queensland Government’s CFS ‘breakthrough’ statement | Science Alert | 22 February 2017
"...But in several peer-reviewed papers published by the Griffith team last year, they showed that in CFS/ME patients, something seemed to be going wrong with TRPM3. In the latest study, the team looked at blood samples 15 CFS/ME patients and 25 healthy controls, and found that immune cells in chronic fatigue patients had far fewer functioning TRPM3 receptors than those of healthy participants. As a result, calcium ions weren’t making it inside the cell like they should be, meaning cell function was impaired. What makes matters worse is that TRPM3 isn’t just found in immune cells. The team tested its presence on immune cells as they’re easy to access in blood samples, but the receptor is found on every single cell in the body, which not only explains why CFS/ME has been so difficult to diagnose, but also why it’s so severe. “This is why it’s such a devastating illness, and why it’s been so difficult to understand,” one of the researchers, Don Staines, co-director of Griffith University’s National Centre for Neuroimmunology and Emerging Diseases, told ScienceAlert. “This dysfunction affects the brain, the spinal cord, the pancreas, which is why there are so many different manifestations of the illness – sometimes patients will suffer from cardiac symptoms, sometimes it will be symptoms in the gut.”

The good news is that there is an easy way to counter those lower TRPM3 levels by using pregnenolone, which has been shown to be a potent TRPM3 agonist.
Pregnenolone For Blood Sugar Control

And thyroid function is know to be crucial for the production of the TRPM3 receptor, so taking thyroid should have similar effect not to mention that it shows the intimate connection between metabolism and CFS/ME.

Just asking , do you follow some specific metabolic research based journals or just scan through all the prominent ones looking for papers based on your line of thinking?

 

[haidut]

Just asking , do you follow some specific metabolic research based journals or just scan through all the prominent ones looking for papers based on your line of thinking?

More of the latter. I also have a system that pulls related articles from various journals so if I like a certain article I usually get 10-15 more similar to it.

 

[Rad]

I have noticed bugger all effect on my cfs/M.E from pregnenolone.

Nor did B1 do anything noticeable.

I am an outlier I suppose, being a non-catabolic, normal temperature type with high cholesterol.

Davis is talking about Pyruvate Kinase but I am so fogged these days that I'm having some difficulty reading, let alone comprehending. This is different to the dehydrogenase that was mentioned in the earlier study.

I've tried thyroid and it does do something good but I haven't tried it for any length of time. 3 weeks max and felt appalling when I came off of it. 2 drops of thyromax.

B2 makes me sleep well although I already sleep well. Niacinamide was responsible for raising my temperatures but no other improvement on it.

 

[haidut]

I have noticed bugger all effect on my cfs/M.E from pregnenolone.

Nor did B1 do anything noticeable.

I am an outlier I suppose, being a non-catabolic, normal temperature type with high cholesterol.

Davis is talking about Pyruvate Kinase but I am so fogged these days that I'm having some difficulty reading, let alone comprehending. This is different to the dehydrogenase that was mentioned in the earlier study.

I've tried thyroid and it does do something good but I haven't tried it for any length of time. 3 weeks max and felt appalling when I came off of it. 2 drops of thyromax.

B2 makes me sleep well although I already sleep well. Niacinamide was responsible for raising my temperatures but no other improvement on it.

I don't think you want to increase pyruvate kinase. It's what suppresses pyruvate dehydrogenase. That reference to pyruvate kinase also threw me off. I suspect it is a typo in the popular press article and they probably meant PDH.

 

[Rad]

I went searching for the mention of Kinase but only found it at the start of the article on Healthrising in the second paragraph.

So I went through the transcript of the first video with Dr.Davis but there's nothing there. Just watched second and didn't hear anything.

I found this quote on meaction.net from Dr.Davis himself

“We have not investigated that, but it is consistent with glycolysis being shut down,” Davis said. “We also think that pyruvate kinase might be shut down. Those are not inconsistent and it is possible there are blocks in both of them.”

Member nandixon on phoenixrising had a stab at an answer:

"What may be happening with the addition of pyruvate inhibiting the increase in impedance in Dr Davis' device when tested with ME/CFS serum, is that the pyruvate is freeing the pyruvate dehydrogenase (PDH) complex from excess inhibition (i.e., phosphorylation) by the pyruvate dehydrogenase kinases (PDKs). This is because pyruvate is a potent inhibitor of the PDKs.

If true, this would appear very consistent with the recent Fluge & Mella study, which indicated the PDH complex to be inhibited and which also found increased mRNA expression for most of the PDKs (PDK1, 2 & 4).

I wonder if Dr Davis has tried adding insulin to one of his test runs with ME/CFS serum? If the insulin also prevents the increase in impedance, that may narrow things down to indicate that the unknown substance in the blood is having an effect somewhere in this pathway:

Insulin--> PI3K/Akt/mTOR(mTORC1)--> PDH

(This is a simplified depiction of the pathway.)"

Further in to the thread was interesting as many people were reporting that cognitive tiredness is there predominant problem over the physical side. That's always been my problem as I am careful with the physical because every time I overdo it, the backlash is worse. I was using intranasal insulin to control the cognitive tiredness as it got so bad that a minute of conversation would ruin me. If I tried to come off of it, the tiredness immediately returned but I managed to get off it using tyromax orally, 2 drops - ONE IN THE AM AND ONE IN THE PM. On the wrists it did nothing for the tiredness but on the pate was slightly more energizing but tiredness was still there. Mentions of oral use working differently made me try it and I'm glad I did. I can talk and write for longer now but still am aware of a limitation.

 

[haidut]

I went searching for the mention of Kinase but only found it at the start of the article on Healthrising in the second paragraph.

So I went through the transcript of the first video with Dr.Davis but there's nothing there. Just watched second and didn't hear anything.

I found this quote on meaction.net from Dr.Davis himself

“We have not investigated that, but it is consistent with glycolysis being shut down,” Davis said. “We also think that pyruvate kinase might be shut down. Those are not inconsistent and it is possible there are blocks in both of them.”

Member nandixon on phoenixrising had a stab at an answer:

"What may be happening with the addition of pyruvate inhibiting the increase in impedance in Dr Davis' device when tested with ME/CFS serum, is that the pyruvate is freeing the pyruvate dehydrogenase (PDH) complex from excess inhibition (i.e., phosphorylation) by the pyruvate dehydrogenase kinases (PDKs). This is because pyruvate is a potent inhibitor of the PDKs.

If true, this would appear very consistent with the recent Fluge & Mella study, which indicated the PDH complex to be inhibited and which also found increased mRNA expression for most of the PDKs (PDK1, 2 & 4).

I wonder if Dr Davis has tried adding insulin to one of his test runs with ME/CFS serum? If the insulin also prevents the increase in impedance, that may narrow things down to indicate that the unknown substance in the blood is having an effect somewhere in this pathway:

Insulin--> PI3K/Akt/mTOR(mTORC1)--> PDH

(This is a simplified depiction of the pathway.)"

Further in to the thread was interesting as many people were reporting that cognitive tiredness is there predominant problem over the physical side. That's always been my problem as I am careful with the physical because every time I overdo it, the backlash is worse. I was using intranasal insulin to control the cognitive tiredness as it got so bad that a minute of conversation would ruin me. If I tried to come off of it, the tiredness immediately returned but I managed to get off it using tyromax orally, 2 drops - ONE IN THE AM AND ONE IN THE PM. On the wrists it did nothing for the tiredness but on the pate was slightly more energizing but tiredness was still there. Mentions of oral use working differently made me try it and I'm glad I did. I can talk and write for longer now but still am aware of a limitation.

Thanks. I think the quote you found suggests that the "pyruvate kinase" (PDK) being shut down reference was a typo. PDK is what inhibits PDH. So, in CFS/ME PDK is probably high and this is what keeps PDH down.

 

[Deleted member 5487]

Thanks. I think the quote you found suggests that the "pyruvate kinase" (PDK) being shut down reference was a typo. PDK is what inhibits PDH. So, in CFS/ME PDK is probably high and this is what keeps PDH down.

haidut, I could use your help

I am curious of oral Pregnenolone is safe for a 21 one year old male. I constantly fatigued despite consuming 3k+ calories adequate sugar/protein?

Whenever I workout the entire next day is a fog of fatigue. Pregnenolone seems to brighten up everything and give me alot more energy, However I tend to get gyno like symptoms of sensitivity when I take it for a few days. Any Idea whats going on?

In highschool I was capable of working out 3-4 hours a day in football and have energy to spare, now it's if I am progressively aging and my CNS is taxed out.

I am addicted to nicotine and caffeine which probably furthers my fatigue and pregnenolone steal.

 

[haidut]

haidut, I could use your help

I am curious of oral Pregnenolone is safe for a 21 one year old male. I constantly fatigued despite consuming 3k+ calories adequate sugar/protein?

Whenever I workout the entire next day is a fog of fatigue. Pregnenolone seems to brighten up everything and give me alot more energy, However I tend to get gyno like symptoms of sensitivity when I take it for a few days. Any Idea whats going on?

In highschool I was capable of working out 3-4 hours a day in football and have energy to spare, now it's if I am progressively aging and my CNS is taxed out.

I am addicted to nicotine and caffeine which probably furthers my fatigue and pregnenolone steal.

Ray says it is one of the safest supplements. I think the optimal dose for younger people is probably under 50mg daily, possibly no more than 30mg daily. So, you can try varying the dose and if a lower dose works for you this way there is less risk of it messing up your natural hormone levels.

 

[Deleted member 5487]

Ray says it is one of the safest supplements. I think the optimal dose for younger people is probably under 50mg daily, possibly no more than 30mg daily. So, you can try varying the dose and if a lower dose works for you this way there is less risk of it messing up your natural hormone levels.

Appreciate the help, Will continue to listen to Danny Roddy podcasts with you.

 

[energyandstruct]

I don't think you want to increase pyruvate kinase. It's what suppresses pyruvate dehydrogenase. That reference to pyruvate kinase also threw me off. I suspect it is a typo in the popular press article and they probably meant PDH.

i think davis and fluge, mella, all talked about PDH being impaired. But CFS is not pyruvate dehydrogenase complex deficiency, which results in severe brain damage from lactate, etc... and severe mortality. It may only be partially impaired. when i saw those articles i thought "great i can just supplement some cofactors for the kreb's cycle", but now I'm thinking that there is something causing the impaired metabolism that is more complex. for example, ron davis has found a big molecule in the blood in CFS patients that seems to be causing the fatigue. when he put CFS cells in healthy controls blood, they had better impedance.

 

[haidut]

i think davis and fluge, mella, all talked about PDH being impaired. But CFS is not pyruvate dehydrogenase complex deficiency, which results in severe brain damage from lactate, etc... and severe mortality. It may only be partially impaired. when i saw those articles i thought "great i can just supplement some cofactors for the kreb's cycle", but now I'm thinking that there is something causing the impaired metabolism that is more complex. for example, ron davis has found a big molecule in the blood in CFS patients that seems to be causing the fatigue. when he put CFS cells in healthy controls blood, they had better impedance.

What is that big molecule he found?

 

[Rad]

What is that big molecule he found?

All I've read I'd quite old but he was saying that it was a large molecule, possibly a protein or an antibody or something attached to an antibody.

I haven't seen any further explanation in the superficial literature. He was using fancy techniques to discover it's size and shake as I remember.

 

[energyandstruct]

What is that big molecule he found?

he hadn't identified it yet, just noted that it didn't pass through a certain size filter:

he noted that when cfs cells were put in healthy control's blood, their impedance was like the healthy controls.

People have speculated that the molecule is an anti-CD39 antibody, based on naviaux's work:
Ponderings and speculations about purinergic signaling, in pursuit of a unified ME/CFS theory



here's the interesting thing about pregnenolone, and why i will try it: Naviaux's landmark CFS study suggests that CFS is a hypometabolic state akin to dauer in worms. dauer is entered into b/c of environmental stress of some kind. Dauer exit has been prompted by NAD+ (which i'd love to try high dose IVs of), and something called dafachronic acid. When I look at dafachronic acid, it seems like a specific steroid to c. elegans, the worm species. But as for analogies in humans--well its a steroid and it acts on nuclear receptors. Just like hormones such as testosterone, estrogen, etc...

could the answer to CFS be as simple as a hormone? part of me doubts it, there are many people who've tried these hormones. But worth a try, eh?

and the NAD+ is particularly interesting

 

[energyandstruct]

I will let u guys know how it goes. planning on starting with small doses, have a semi-accurate scale. What doses and method of administration would u all recommend?

 

[SB4]

I will let u guys know how it goes. planning on starting with small doses, have a semi-accurate scale. What doses and method of administration would u all recommend?

I'd start really slow and work up. As with this disease people can be very sensitive to changes. Maybe 1mg and build from there?

 

[energyandstruct]

I'd start really slow and work up. As with this disease people can be very sensitive to changes. Maybe 1mg and build from there?

There’s no way I could accurately measure out 1 mg. Was gonna start with ten mg for that reason

 

[SB4]

There’s no way I could accurately measure out 1 mg. Was gonna start with ten mg for that reason

Yeah it's difficult. Give 10 a try but for me it was a bit too much.

 

[Suikerbuik]

There’s no way I could accurately measure out 1 mg. Was gonna start with ten mg for that reason

Do 10mg pregnenolone in 10g dextrose, or something else you can easily meassure (in 1g dextrose 1mg would equal ~100mg), and mix well. The issue of unequal distribution can be overcome by making a solution in for example MCT.

 

[energyandstruct]

Update, I had bad effects from my pregnenolone trial. Ray suggests it could be impurities (I was using Health Natura's). This is the second brand i've tried. Similar effects both times--agitation, mood swings and random weepiness, followed by really intense irritation. Like i'm normally a little irritable because I'm sick and feel like ***t all the time but this was another level. i felt compelled to get into arguments at the drop of the hat. Tried two separate doses. Considering trying stressnon, may be easier to dilute as it's already in liquid form?