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

[Jesse2233]

@Murph what brand / product do you get your leucine from?

 

[Jesse2233]

@Rose49 great video! How do we submit questions for the next one?

 

[Alvin2]

@Rose49 great video! How do we submit questions for the next one?

i was going to ask how were these questions submitted when i found this thread then forgot by the time i read it, so thanks for asking.

 

[TreePerson]

I have never heard of mTOR before. Upon quick research; The main activator of mTOR is a variety of amino acids, especially leucine and the hormone insulin.

Does this mean we should use Leucine?

Natural Inhibitors of mTOR

• Protein restriction (R, R2): Leucine restriction (R), Glutamine restriction? (R), Methionine restriction? (R), Lysine restriction? (R), Arginine restriction? (R), Threonine restriction (R), Isoleucine restriction (R),
• Glutamine? (R),
• Calorie restriction (R),
• Ketogenic Diets (R)
• Intermittent Calorie Restriction (R),
• Exercise (R, R2) – Inhibited in liver and fat cells. Activated in brain, muscle and heart….All good…
• Cortisol/Glucocorticoids (R)
• Metformin (R), (by enhancing PRAS40’s association with RAPTOR)
• NAC (R) (Clinical Trial: “profoundly reduced mTOR activity” in T cells)
• Resveratrol
  
  (R)(C1/C2), unique– increased the association between mTOR and its inhibitor, DEPTOR. (R)
• Aspirin (R) – colorectal cancer cells,
• Cod liver/ Omega-3 (R) (C1/C2),
• Extra Virgin Olive Oil (R)
• EGCG/Tea (R, R2) (C1/?) – ATP-competitive inhibitor of both PI3K and mTOR (R)
• Curcumin (R, R2) (C1/C2) ….unique mechanism – separates raptor from mTOR (R)
• R-Lipoic Acid (R) – also decreased p70S6 kinase (R)
• Caffeine (R, R2, R3)(C1/?),
• Fisetin
  
  (R) – fat cells,
• Apigenin
  
  (R) (AMPK+, Akt-)
• Quercetin (R), ( PI3K/Akt-, AMPK+, Hamartin+)
• Genistein (R),
• DIM (R),
• Ursolic acid (R),
• Alcohol (R) (C1/C2),
• Emodin (found in Fo-Ti, Resveratrol, Rhubarb, Aloe,) (R) (C2),
• Andrographis/Andrographolide (R), (PI3K/Akt-)
• Pomegranate/Ellagic acid (R),
• Reishi (R)
• Milk thistle/Silymarin
  
  (R),
• Oleanolic acid (R)(C1),
• Anthocyanins/Grape Seed Extract (R),
• Astragalus (R), (colon cancer)
• Rhodiola
  
  (R)
• Carnosine (R)
• Plumbagin(black walnut hull) (R), Glucagon (R), AICAR (R)
• Pathways: IGF(-)…PI3K(-)…Akt(-)… AMPK(+)…

I am confused and probably being very slow here. This is a list of things that inhibit mTOR? Wouldn't that mean they made matters worse? Or do some inhibit and some activate? So just to clarify- are ALL the things listed here potentially helpful or are some bad? What do the (R)s mean?
So sorry to be dense and apologies if someone has already asked and I've missed it.

 

[Janet Dafoe]

I think appealing to philanthropists is a very good approach as this disease is now at the stage where some very wealthy philanthropists would be attracted to support it. Philanthropists like a cause that has been ignored by governments without good reason. I would encourage OMF to pursue this. I would donate $20,000.00 to OMF for the purpose of soliciting philanthropists as I think it would pay huge dividends.

Wow! We'd love to talk with you about that! It would be wonderful. Can you pm me and I'll get you in touch with Ron and Linda Tannenbaum. Thank you!

 

[Janet Dafoe]

@Rose49 great video! How do we submit questions for the next one?

MECFSResearchQuestions@gmail.com

 

[Wolfiness]

So do the metabolic findings have any bearing on the issue of whether our fatigue is "central fatigue" or not?

 

[suseq]

Every time I see, hear or read something from Dr Ron Davis I feel an inspiring awe and an impulse to give him a huge warm hug of thanks for what he, his family, his team and all associated with him are doing to find answers that will help us all. This illness has taken so much from his family and taught them more than anyone would want to know about it's devastating effects. That they have used this experience and their incredible expertise and compassion to seek and inspire help for us all is beyond thanks.

 

[Gingergrrl]

Very interesting to hear him confirm that mTOR may be central to this disease, and certainly you do not want to inhibit it.

Can someone explain in the most basic terms like you were talking to a five year old what mTOR means? And then the five year old can explain it to me LOL. I Googled it but still have no clue!

I am confused and probably being very slow here. This is a list of things that inhibit mTOR? Wouldn't that mean they made matters worse? Or do some inhibit and some activate? So just to clarify- are ALL the things listed here potentially helpful or are some bad? What do the (R)s mean?

@TreePerson You are not alone and I also did not understand if the things on the list were supposed to make things better or worse. When I view the list it is a mixed bag (for me) b/c I do very well with intermittent caloric restriction and Quercetin (as an example) but I am completely intolerant of aspirin and alcohol (as another example) and they are on the same list. So was just curious if the list was suggestions to avoid or to try?

I cannot help but like this man.

Agreed 100%

I've said all along that my ME/CFS didn't start until I was put on Penicillin 26 years ago.

The true beginning of my illness (trigger #1) was a neurotoxic reaction to Levaquin and am fascinated by how many people's illnesses began with a reaction to an antibiotic. I have not taken an ABX in almost 7 yrs and don't plan to ever take one again if I can avoid it.

Is there anything inconsistent with it being an autoantibody that is the thing in the serum?

I was wondering this, too, and it looked like the answer was no from @Rose49's reply.

I would donate $20,000.00 to OMF for the purpose of soliciting philanthropists as I think it would pay huge dividends.

Wow, that is amazing and God bless you for your generous donation opportunity and I would think it would bring in philanthropists! Truly awesome.

 

[Murph]

@Murph what brand / product do you get your leucine from?

The one the doc recommended is Dyamtize ISO 100. It's whey protein isolate with added flavour. Other brands probably substitute just fine but I haven't looked into that. I started off at one scoop a day. More recently I've been taking 3 scoops a day.

It's not cheap, (comes out at about $1.50 to $2 a scoop) but unlike most supps I take it is essentially food (albeit highly processed) so I can justify it by saying it helps makes other food costs lower!

 

[Alvin2]

Before i e-mail my question to Ron Davis what does PR members think of this question (has it already been answered)?
Considering the differing and sometimes unknown etiology among patients and very differing severity and reactions to medications/supplements do you think all ME/CFS patients have the same disease mechanism?

I think appealing to philanthropists is a very good approach as this disease is now at the stage where some very wealthy philanthropists would be attracted to support it. Philanthropists like a cause that has been ignored by governments without good reason. I would encourage OMF to pursue this. I would donate $20,000.00 to OMF for the purpose of soliciting philanthropists as I think it would pay huge dividends.

Why would they be attracted to support it, especially now?

 

[Gingergrrl]

Why would they be attracted to support it, especially now?

I think the difference (if I am understanding this correctly) is that @Louie is offering to donate $20K specifically to solicit philanthropists! So instead of OMF taking $20K from research studies, which they can barely afford as it stands now, they would have a separate donation that is specifically for this purpose and nothing would be taken away from the research money. That is how I read it and I think it is a phenomenal idea!

 

[Alvin2]

I think the difference (if I am understanding this correctly) is that @Louie is offering to donate $20K specifically to solicit philanthropists! So instead of OMF taking $20K from research studies, which they can barely afford as it stands now, they would have a separate donation that is specifically for this purpose and nothing would be taken away from the research money. That is how I read it and I think it is a phenomenal idea!

It is a great idea if it works, i am asking why they would be interested especially now, are they looking for a return, do they want their names associated with discoveries, are they looking to patent the research and monetize it at 10K a pill?
The Michael J Fox Foundation tried to take away a major discovery from its inventor (Nilotinib for Parkinsons) by offering him money to do more research with that condition attached, and when he refused they tried to go behind his back and convince the drug company to no longer provide him with the medication.
Always look a gift horse in the mouth.

 

[Murph]

IN the video, at the 2.20 mark, Ron talks about using a filter on serum to see if filtered serum still produces the impedance effect that characterises mecfs. He says most of the effect disappears from using the filter. That suggests the target molecule, hypothesiesd to be causing the trouble, is a big one that has been caught in the filter. "probably a protein." and not likely to be a metabolite. (I'm catching the inference here that metabolites are smaller.)

(let me know If I'm getting this right.)

A question: Do amino acids (in this context) count as "big like a protein"?

 

[Janet Dafoe]

IN the video, at the 2.20 mark, Ron talks about using a filter on serum to see if filtered serum still produces the impedance effect that characterises mecfs. He says most of the effect disappears from using the filter. That suggests the target molecule, hypothesiesd to be causing the trouble, is a big one that has been caught in the filter. "probably a protein." and not likely to be a metabolite. (I'm catching the inference here that metabolites are smaller.)

(let me know If I'm getting this right.)

A question: Do amino acids (in this context) count as "big like a protein"?

Yes you are.
Big = larger than 10,000 molecular weight. Proteins, protein groups or antibodies (including autoantibodies). Amino acids are smaller, around 300 molecular weight.

 

[Gingergrrl]

It is a great idea if it works, i am asking why they would be interested especially now, are they looking for a return, do they want their names associated with discoveries, are they looking to patent the research and monetize it at 10K a pill?

These are great questions and I have no idea re: the answer but assume that OMF would properly vet the donor and the potential philanthropists and have protections in place.

 

[Alvin2]

These are great questions and I have no idea re: the answer but assume that OMF would properly vet the donor and the potential philanthropists and have protections in place.

I'm sure they would, i ask so as to get an understanding of the workings of this type of funding

 

[A.B.]

Can someone explain in the most basic terms like you were talking to a five year old what mTOR means? And then the five year old can explain it to me LOL. I Googled it but still have no clue!

Introduction
Most organisms have evolved mechanisms for efficiently transitioning between anabolic and catabolic states, allowing them to survive and grow in environments in which nutrient availability is variable. In mammals, an example of such a mechanism is the signaling network anchored by the protein kinase mTOR (originally ‘mammalian TOR’, but now officially ‘mechanistic TOR’). This pathway, which responds to diverse environmental cues, controls many processes that generate or use large amounts of energy and nutrients. It is increasingly apparent that mTOR signaling impacts most major cellular functions, giving it an outsized role in regulating basic cell behaviors like growth (mass accumulation) and proliferation. Because mTOR deregulation occurs in human disease, including cancer, obesity, type 2 diabetes, and neurodegeneration, there are significant ongoing efforts to pharmacologically target the pathway. Here, we review our current understanding of the mTOR pathway and its role in health and disease, as well as discuss pharmacological approaches for modulating mTOR activity.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3331679/

Having a chronically downregulated mTOR sounds a lot like being in a Dauer state, or starvation. mTOR also controls how the cell produces energy, inhibition of mTOR seems to lead to increased reliance on glycolysis and decreased utilisation of pyruvate.

Or very simplified. mTOR looks at the environment and controls fundamental processes in the cell:

mTORC1 is the better characterized of the two mTOR complexes and a remarkable feature of this branch of the pathway is the number and diversity of upstream signals it senses. The mTORC1 pathway integrates inputs from at least five major intracellular and extracellular cues--growth factors, stress, energy status, oxygen, and amino acids--to control many major processes, including protein and lipid synthesis and autophagy.

 

[Aroa]

Thank you so much Ron and @Rose49 for taking the time to answer our questions, I know you will be more than busy. These updates always inspire us hope and joy.

I feel this research is a sort of revolution where many parts of cutting-edge science converge for a real and quick benefit of Patients. I am afraid this is not very usual.

I think this is a major reason why NIH and Philanthropists should consider funding this research

 

[Murph]

Yes you are.
Big = larger than 10,000 molecular weight. Proteins, protein groups or antibodies (including autoantibodies). Amino acids are smaller, around 300 molecular weight.

Thanks!

Next question is an attempt to build a bridge from california to Norway: we know they can make antibodies... what other types of protein and protein groups can B-cells make?