Dr. Ronald W. Davis Answers Patient Questions: Q and A follow-up to 2/21/17 Research Update

[bertiedog]

I've seen Predisolone getting good reviews on here lately. I was under the impression that you wouldn't want to take this drug everyday however. Have you noticed any side effects?

I have been on 5-6mg Prednisolone since 2003, it was the only thing that helped the mild adrenal insufficiency I had developed. Over the years it is true that there is a tendency for one's blood sugars to be a bit insulin resistant so in view of this I have always monitored my blood sugars and have eaten a low carb diet. Eating in this way plus being quite active each day has kept my HbA1C well below pre diabetic ranges.

The other side effect I have is easy bruising but this is slightly confusing because I bruised easily before I was ever on it! I think my skin is probably a bit thinner than it should be but its not hugely noticeable and as I am 69 on Saturday it's difficult to know.

I did come off the steroid gradually in 2005 when my adrenals seemed to splatter into life but I ended up 2/3 months later with 2 crises, the last one was terrifying and I ended up passing out after uncontrollable diahorea and vomitting. My bp was so low that if I had been on my own I could have died. It was weird because when the vomiting started around 10 am something told me that I wasn't to be alone so I rang round for help which was just as well because by 12.30 I had passed out and couldn't come round properly or move at all there was just nothing in my body until I was given some hydrocortisone. Everything was black and it was the most frightening experience of my life and I knew then I would never be able to stop taking the steroid whatever the side effect.

On a positive note I had a DEXA scan 6 years ago and it showed that I had the bones of a 30 year old and bearing in mind I was 64 at the time they said that was rare. My GP could never understand this but I guess its cos I have a good diet, take loads of magnesium daily plus have stayed on low dose oestrogen and I walk every day with my dog unless I am sick with a virus/infection.

Pam

 

[keenly]

@keenly Interesting! I take all the agents I mentioned, and I've found it improves PEM probably 25%. Still my baseline activity level is like a 3 though.

Maybe you can convert uridine to thymidine which means you do not get a build up.

 

[eljefe19]

@Diwi9 Keep in mind, aerobic exercise inhibits mTORC1. I would suspect in PWME that any kind of over exertion inhibits mTOR and makes us crash.

 

[keenly]

Me too. Multiple and 2+ years of antibiotics for acne as a teen. Senior year, I had repeat problems with sinus infections and it took three rounds of antibiotics to wipe it out. I was an athlete (team captain) and pushed through illness. My coach reprimanded me in front of the team for missing practice when I was sick...

I wonder if the start of my ME/CFS was earlier than I've identified, but was just super mild.

I did Olympic weightlifting before I got sick. Teenage acne meds led to digestive issues, allergies etc, then things progressed after infection following surgery.

 

[keenly]

@Diwi9 Keep in mind, aerobic exercise inhibits mTORC1. I would suspect in PWME that any kind of over exertion inhibits mTOR and makes us crash.

Yes, I know this all too well. I was doing great till a month ago, then I crashed after jogging on treadmill, now I am fatigued just waling around block.

 

[Sasha]

Hopefully we can get a transcript. Will ask about that.

It's OMF and the CFSRC @ Stanford Genome Centre who are working the magic (aswell as many behind the scenes)


B

If anyone's going to transcribe I highly, highly, highly recommend using oTranscribe.com. It makes it looooooads easier.

 

[Diwi9]

@Diwi9 Keep in mind, aerobic exercise inhibits mTORC1. I would suspect in PWME that any kind of over exertion inhibits mTOR and makes us crash.

I'm excited that Dr. Davis responded to the question about mTOR. I know others have discussed it on PR, but I never studied biochemistry, so it's difficult to follow some threads. Of course my first instinct is to buckle down and "push" through the data

 

[eljefe19]

@Diwi9 Oh I totally understand. I barely used to be able to browse these forums let alone comment. That's how bad my brain fog and fatigue were. I studied Economics I'm no biochemist either. I'm just so goddamn bored, I am determined to cure myself.

What I didn't realize before was just how many supplements I was taking for other reasons that were inhibiting mTOR. However, around the same time I adjusted my supplements and medications, I also stopped doing any aerobic exercise at all. I used to force myself to do it, thinking that I would get stronger, but as everyone here knows the crash is inevitable.

 

[eljefe19]

@keenly Just FYI, while aerobic exercise inhibits mTOR in healthy people, anaerobic exercise activates mTOR. Personally I've found that I can do some weights without much PEM.

 

[Mary]

@Mary two years on Leucine, huh? Have you noticed any long term improvements? BCAA's upregulate mTOR but I imagine this takes some time to occur.

The main effect I've noticed is that my PEM recovery time is cut in half - from 2 days to 1 - so it's huge for me. And, this happened after 1 week of taking them.

When I first started crashing 18 years ago, a crash would last 3-4 days. Very slowly over the years my recovery time gradually improved, I don't know what exactly contributed to this (probably part of it was learning my limits better!), but by 2 years ago last November, I was recovering within about 2 days or a little more. And then one week after starting the BCAAs, I was stunned when my latest crash lifted by the end of the first day. And my recovery period has stayed at that, except for when I cut my dose of BCAAs, and the recovery period gradually lengthened into a day plus a bit more; when I finally realized what was going on, I went back to my original dose.

 

[lilpink]

@lilpink Anecdotally activating Akt/mTOR has been helpful for me, it smoothes out the push crash cycle. Doesn't do a whole lot for baseline energy, so far, however.

Thankyou I will investigate further

 

[keenly]

@Mary two years on Leucine, huh? Have you noticed any long term improvements? BCAA's upregulate mTOR but I imagine this takes some time to occur.

The main effect I've noticed is that my PEM recovery time is cut in half - from 2 days to 1 - so it's huge for me. And, this happened after 1 week of taking them.

When I first started crashing 18 years ago, a crash would last 3-4 days. Very slowly over the years my recovery time gradually improved, I don't know what exactly contributed to this (probably part of it was learning my limits better!), but by 2 years ago last November, I was recovering within about 2 days or a little more. And then one week after starting the BCAAs, I was stunned when my latest crash lifted by the end of the first day. And my recovery period has stayed at that, except for when I cut my dose of BCAAs, and the recovery period gradually lengthened into a day plus a bit more; when I finally realized what was going on, I went back to my original dose.[/QUOTE]
http://www.bodybuilding.com/fun/leucine-build-muscle-with-this-anabolic-amino-acid.html

Though researchers are not sure exactly how leucine activates mTOR, it has been shown that mTOR is sensitive to leucine concentrations and activation of mTOR is strongly associated with increased protein synthesis, which means more muscle growth.

 

[Christian Godbout]

The depth of mind and understanding of great scientists sometimes manifests itself through the simplest statements, I think the following (at 11:10) is a perfect example:

"Crashing re-initiates the disease over and over again"

 

[eljefe19]

One other thing about mTOR is that it has an inverse relationship with SIRT4, and SIRT4 was found to be overexpressed in PWME by Fluge and Mella. I think this is further evidence that we want to activate mTOR.

 

[Wolfiness]

Did I hear correctly that they've already tried "every FDA-approved drug" ?

 

[eljefe19]

Did I hear correctly that they've already tried "every FDA-approved drug" ?

I heard that too.

 

[A.B.]

Some antidepressants also activate mTOR. This would suggest that mTOR may not be important because antidepressants are commonly prescribed and don't actually seem to be working well in this illness.

 

[eljefe19]

@A.B. Which AD's have you found activate mTOR? I've found that Ketamine, Agmatine, Sarcosine and Creatine activate mTOR and also have AD effect, but as far as SSRI's go I haven't seen any references.

 

[eljefe19]

@A.B. You're right. Here is says that SSRI's as well as 5-HT2C antagonists activate mTOR. I'm thinking that SSRI's may not rule out mTOR because they also increase SIRT4, and this would be counterproductive in PWME. A 5-HT2C inhibitor may be helpful though, that reference says that these drugs also increase CREB and BDNF.

 

[Diwi9]

@eljefe19 - This discussion is winding me back to Dr. Jay Goldstein that discussed curing ME/CFS with a single dose of a drug. One of his favorite drugs was ketamine. It's interesting that Dr. Davis also talked about a single-dose cure.