Blood doping, it helps naughty athletes, could it help us?

[AdamS]

When the stakes are high some athletes break the rules to improve performance. I know this misuse is wrong/immoral in the context of competitive sport but given the nature of ME, I wondered if any of the treatments could help us in any way?

When I was reading from a great reliable source known as Wikipedia, I saw a few things I liked the look of:

• Potential to improve aerobic capacity (VO2 max) and endurance.
• HIF Stabilizers/manipulating the HIF pathway in general.

I didn't actually realise that the HIF pathway could be targeted therapeutically. I wonder what would happen if we did try to target it seeing as it has an influence on PDK1 ---> PDH ---> TCA cycle. There's also something called EPO that I don't know much about but sounded interesting.

HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia.
Kim JW1, Tchernyshyov I, Semenza GL, Dang CV.
Author information

Abstract
Activation of glycolytic genes by HIF-1 is considered critical for metabolic adaptation to hypoxia through increased conversion of glucose to pyruvate and subsequently to lactate. We found that HIF-1 also actively suppresses metabolism through the tricarboxylic acid cycle (TCA) by directly trans-activating the gene encoding pyruvate dehydrogenase kinase 1 (PDK1). PDK1 inactivates the TCA cycle enzyme, pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl-CoA. Forced PDK1 expression in hypoxic HIF-1alpha null cells increases ATP levels, attenuates hypoxic ROS generation, and rescues these cells from hypoxia-induced apoptosis. These studies reveal a hypoxia-induced metabolic switch that shunts glucose metabolites from the mitochondria to glycolysis to maintain ATP production and to prevent toxic ROS production.

I don't know if we'd want to inhibit or activate the HIF pathway...or to just leave it alone completely but there is some info on inhibitors here also there is some info on how HIF-1 Activation by Aerobic Glycolysis implicates the Warburg effect in cancer. One of the drugs is an ester version of Rapamycin, which has been discussed recently on PR.

Anyway, imagine this as a bit of pub talk about a few thoughts i've been having, feel free to add your own thoughts

 

[Mohawk1995]

Doesn't mean there might not be some value in exploring it, but my little knowledge of Performance Enhancing Drugs (PEDs) and of ME/CFS would have me believe that you are trying to stimulate something that is stuck in survival mode. Most likely would make it worse.

Initially we thought our son had Atypical Migraines. When we attempted to treat it with Abortive medications, he had a pretty severe adverse response with nausea, dizzyness and actually increased headache. ME/CFS is like a sleeping bear. You come along and poke it too hard and you will get far more than you bargained for coming right back at you.

I understand you are talking different pathways, but any clinical research needs to tread quietly and slowly into changing any biochemistry or other systemic issue related to ME/CFS.

 

[Mohawk1995]

In addition, Blood Doping/PEDs do not enhance performance without consequences. Whenever you attempt to short cut the natural process, there are usually consequences. Here is a link:

http://www.usada.org/substances/effects-of-performance-enhancing-drugs/

Pretty scary stuff even for someone who has lived bravely with ME/CFS.

 

[CCC]

Did you mean EPO? It kills people. There's a reason that one is banned and it's about more than 'unfair' advantage.

 

[eljefe19]

Saw someone on Reddit had great improvements using the nootropic Noopept which is positive on HIF-1;
https://www.ncbi.nlm.nih.gov/m/pubmed/27099787/

 

[Tunguska]

I didn't look into it as deep as others, because based on other threads it was unclear whether HIF-1 would be high or not in the disease and in what circumstances (on the other hand, it does get increased by LPS with or without JNK and FoxO). There were some good posts, if you search.

The EPO thing might not go far because it's activated by HIF-1 in response to hypoxia. It's just the body trying to increase O2 levels. But you could have HIF-1 activated by some signal that's not necessarily hypoxia in which case it shouldn't help that much.

I was temporarily interested in HIF-1 for different reason: I'm a poor thyroid responder and it's a possible cause for TH inactivation: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2230657/

The thing is that due to cancer research a lot of blame is put on Akt for contributing to HIF-1, but limiting Akt is definitely not the answer. So to exploit this you probably need a highly specific HIF-1 inhibitor, combined with Akt activator to feed the glucose and other reasons, and I imagine anti-oxidant to control the ROS (the ROS is too complicated, not going there).

But I don't know what would be a specific HIF-1 inhibitor in muscle and brain, and I didn't read your 2nd-3rd link there. So the closest is just to try to negate the effects of HIF-1, which is the PDK upregulation predominantly, and then it doesn't matter whether HIF-1 is involved or not. But people were already doing that with high-dose Thiamine. And one of the posters described good temporary success combining Thiamine and ALA (and something else?). I can't say because I don't respond to Thiamine, but that was the closest so far.

Maybe increasing HIF-1 would improve your response to exercise and help limit damage by exercise, relative to disease. But in normal circumstance (most of the time and in low-intensity activity) you'd want it off.

All this is merely entertaining the possibility that HIF-1 is the problem, with no justification.

 

[BurnA]

There's also something called EPO

It's Edgar to those in the know

 

[AdamS]

Did you mean EPO? It kills people. There's a reason that one is banned and it's about more than 'unfair' advantage.

Sounds horrendous.

 

[kangaSue]

There's also something called EPO that I don't know much about but sounded interesting.

EPO (erythropoietin) has been tried in ME/CFS. It helped to increase blood volume by increassing red blood cell mass but didn't make a difference to other symptoms.
http://phoenixrising.me/treating-cf...ome-mecfs-erythropoietin-and-low-blood-volume

 

[halcyon]

But you could have HIF-1 activated by some signal that's not necessarily hypoxia in which case it shouldn't help that much.

It's activated by inflammatory cytokines as well, such as TNF-a and IL-1 which are abnormal in this disease. But didn't the recent Fluge and Mella paper find HIF-1 expression was normal in the patients?

 

[heapsreal]

Did you mean EPO? It kills people. There's a reason that one is banned and it's about more than 'unfair' advantage.

Yet its given to dialysis patients.

 

[heapsreal]

The dangers of many of these substances is way over rated or else they wouldnt have been approved in a medical setting in the first place. We arent seeing huge numbers of athletes dropping dead everywhere either, theres the odd athlete but usually from a coexisting condition and because they arent being monitored by a knowledgeable doctor.

This biggest mistake many governments did was categorize them in the same class as heroin etc and severly restrict drs prescribing them where people could be monitored properly and guided medically by their doctors. Instead its driven this class of drugs underground and the quality of the drugs are substandard as most are made in underground labs, so people who use these substances dont even know what they are really getting and they generally dont have access to a doctor to monitor them because of government regulation.

The general public dont realise that the majority of professional athletes use performance enhancers. Testing of athletes is easily beaten and its said that drug testing only catches the dum athletes. Lance Armstrong never tested positive for illegal substances and beat the tests consistently. Do you ever wonder why all these sports teams and even individual sportsman have their own doctors, its not to strap ankles thats for sure.

I personally think that under the guidance of an appropriate trained dr (most dont have a clue) the drugs could have great benefits to so many people. The problem might be they are too effective and this cuts into the profits of drugs that just treat symptoms.

Theres mega more deaths related to alcohol, smoking and even many otc drugs then alot of PEDS, why isnt alcohol or smoking band? Because govts love the revenue they raise. They pretend to care by raising taxes on alcohol/smoking but not too much as they dont want to stop people using these substances as they dont want to lose the money they get from them.

In this age of fake news, the wool has been pulled over most peoples eyes consistenly to support an agenda of a few.

 

[lansbergen]

In this age of fake news, the wool has been pulled over most peoples eyes consistenly to support an agenda of a few.

yep

 

[CCC]

The dangers of many of these substances is way over rated or else they wouldnt have been approved in a medical setting in the first place. We arent seeing huge numbers of athletes dropping dead everywhere either, theres the odd athlete but usually from a coexisting condition and because they arent being monitored by a knowledgeable doctor.

Actually, when EPO was first used, we did see athletes dropping dead everywhere in one group of athletes in one particular sport (early adopters or human guinea pigs?). It was a long, long time ago, and it was initially a mystery illness that no one in the country concerned could explain. The stupidist thing is that it wasn't for a sport likely to lead to loads of fame, glory or money.

So use it, but get proper medical supervision (and maybe put you career as an elite athlete on hold).

 

[Snow Leopard]

ME is not due to a lack of oxygen carrying capacity in the blood, so I'm not sure whether this would work at all. It is certainly not a viable treatment (you have to donate blood to yourself!) but it might be interesting to know the effect.

 

[Mohawk1995]

I personally think that under the guidance of an appropriate trained dr (most dont have a clue) the drugs could have great benefits to so many people. The problem might be they are too effective and this cuts into the profits of drugs that just treat symptoms.

Could be true for some people, but based on what has been explored with ME it seems more likely to cause harm than good or at best not help while subjecting ones body to substances that clearly carry some risk.

As for athletes using PEDs, the jury is still out on the long term effects. Yes they are "being managed" better, but being a Collegiate athlete and being around some Olympians who I know did not use PEDs I think the thought that most high end athletes "cheat" may be overstating it. It will be interesting to see if there is a link between PEDs and CTE down the road. I happen to believe there will be one identified.

Every substance one puts in their body has risks. For years the number one medication that caused death was aspirin. Of course now it appears to be opioids. The issues as I see them, usually arise from wanting a quick change. Can't blame a person for wanting it, but can blame the medical provider who does not practice Evidence Based Medicine in so doing.

 

[AdamS]

But didn't the recent Fluge and Mella paper find HIF-1 expression was normal in the patients?

You could be right actually..

There were no differences for PPARα (PPARA) (Figure 3E), the PPAR transcriptional target and peroxisomal fatty acid β-oxidation enzyme, acyl-coenzyme A oxidase 1 (ACOX1), or the transcription factor HIF1α (HIF1A)

However they they go on to say...

Likewise, autoantibodies in ME/CFS may interfere with key metabolic signaling pathways involving factors such as HIF1 (24) and PPARs, as well as AMPK, which was abnormally activated in skeletal muscle cells of ME/CFS patients (46). These factors are associated with PDK (22) and SIRT4 (47) in the regulation of oxidative metabolism.

Who knows

 

[Tunguska]

It's activated by inflammatory cytokines as well, such as TNF-a and IL-1 which are abnormal in this disease. But didn't the recent Fluge and Mella paper find HIF-1 expression was normal in the patients?

Yeah and nandixon didn't think it was relevant either. [AdamS just beat me to it] I only wonder about context (activity) and the different subgroups problem...
Causes under non-hypoxia are listed in http://onlinelibrary.wiley.com/doi/...ionid=465D8121A30B202D8C7CD668528E5865.f04t01

 

[adreno]

I was considering trying Noopept. But now I'm wondering whether it's worth messing around with HIF-1.

 

[Tunguska]

I was considering trying Noopept. But now I'm wondering whether it's worth messing around with HIF-1.

I tried noopept and mostly felt sedated. But, I didn't try combining it.