Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, Paper Pub. 4/1/20 - Dr. Prusty

[sb4]

Good work on getting Prusty to answer your questions.

Or is it higher protein (lower carb) that is the most important aspect? AA or BCAAs supplements helping many (right @Mary, think I've seen you saying some place?). As Learner says, a common serum metabolite deficiency finding, there:

In my experience it is going lower carb that helps, not the higher protein.

Am I talking sense, here...? I *really* need to go find a very nice clear energy metabolism diagram that includes all the relevant metabolites and enzymes (without being too big). It confusing because "glycolysis" is used for both aerobic and anaerobic ATP metabolism, but with different end-points and inputs, I think...

I also find it confusing as differen't people use the term glycolysis in different ways. I think of it as glycolysis is the process that transforms glucose into pyruvate; from then on pyruvate can either go through PDH and become AcetylCoA (Aerobic glycolysis), or be converted into lactate (anerobic glycolysis).

Like @ShepherdK I am very interested in the PDH inhibition as I can see this leading to a decent health improvement in me as I am pretty sure I have this PDH inhibition.

 

[ZeroGravitas]

That's outside of the timeframe for my PEM.

It's interesting to think about. Of course, keep in mind that the comparison to PEM timing came from me grasping for insights that may well not be there.

It might be that it only explains the speed of initial disease state onset (then gives an underlying predisposition towards neuro/immune mechanisms, and whatever else). Or not even that.

PEM related crashes and fatigue is a complex physiological process and can involve many factors. We are in the process of understanding this complex phenomenon.

Virus reactivation and its consequential effects are slow process. It matches well with the slow onset process of the disease.

Even if reactivation related fatigue factor signalling does explain some aspect of PEM timing, these mechanisms obviously can't explain every aspect of everyone's disease.

Also, symptoms can be tricky to interpret - I react to my food intolerances within 30min of eating. But it's the food I ate 24h earlier that determines the reaction.

 

[ZeroGravitas]

Prusty answered pretty much straight back, again. So I've added the answers into the 2 question posts (above - question 13 onward).

Seems like I was wrong to question you, @ShepherdK, and feasibility of blood cells, etc (please excuse my nonsense blathering ):

(16) Do you think it could be possible to (quickly) confirm the finding of reduced PDH, SOD2, etc, activity directly in cells taken from patients?

(a) What cell type(s) might be suitable for this, if any? (Keeping in mind the lab methods required, too.)

Q16: Yes, it should be possible to test PDH and SOD2 levels in patients. Blood cells would be ideal as it will be difficult to get any other cells. But two factors are key to success. First, A simple western blot or mass spec would not tell you anything as it measures everything in the cells. One has to doSllK like experiments that we did where you measure the proteins as they are synthesized avoiding the proteins that have a longer half like and they are there in cell without much of changes. We plan to follow another very fascinating approach to check this in future. [Twitter]

 

[wigglethemouse]

@ZeroGravitas - can you correct 'doSllK' to 'pSILAC'in Q16 answer

 

[andyguitar]

In my experience it is going lower carb that helps, not the higher protein.

Like @ShepherdK I am very interested in the PDH inhibition as I can see this leading to a decent health improvement in me as I am pretty sure I have this PDH inhibition.

Both points might be connected to insulin levels.

 

[msf]

Just read the comments on s4me - awful and so negative. Especially from one person in particular. Talk about kicking you down 🙄 And when asked to explain, told that it would be impossible as we unscientific folk would never understand (paraphrased).... sigh and double sigh!!

The person I assume you are referring to always does that with any theory that does not agree with his own, and since his own is looking rather dubious these days, I'm surprised he is still taking an interest.

This paper seems very interesting anyway, it doesn't fit my own theory exactly but I shall nevertheless bravely make it to the end at some point.

 

[msf]

I made that comment about reading to the end before I read the last comment. Ironic really, but also quite predictable in this person's case.

 

[sb4]

Both points might be connected to insulin levels.

Whilst this is true for various reasons I don't think this is the case. For a while when I was doing high carb I took my BS and it was hit and miss how quickly it left the blood however often times it would be completely in normal range and I would still have symptoms.

Furthermore, at the time I was doing very high carb very low fat which if peters @hyperlipid is right about insulin / diabetes then I would be less likely to get symptoms with this approach however my symptoms where there as always.

 

[Learner1]

Whilst this is true for various reasons I don't think this is the case. For a while when I was doing high carb I took my BS and it was hit and miss how quickly it left the blood however often times it would be completely in normal range and I would still have symptoms.

Furthermore, at the time I was doing very high carb very low fat which if peters @hyperlipid is right about insulin / diabetes then I would be less likely to get symptoms with this approach however my symptoms where there as always.

Have you seen pyruvate drop on low carb?

 

[sb4]

Have you seen pyruvate drop on low carb?

Not sure I understand. I had a urinary organic acids test whilst eating low carb:
Pyruvic Acid: 2.0 (0.28 - 6.7)
Lactic Acid: 8 (0.74 - 19)

 

[godlovesatrier]

Just to tag onto one reply. Branched chain aminos do help me a ton. I would take a lot more if it didn't cause so much swelling at the back of my head. But the fact it cancels a crash almost completely or causes a crash which is far else severe is pretty amazing. So like Mary that's been my experience. Maybe many metabolic issues based on sex, environment, lifestyle, food eaten, genetics and body makeup cause a blurry picture because every body is different.

 

[Learner1]

Not sure I understand. I had a urinary organic acids test whilst eating low carb:
Pyruvic Acid: 2.0 (0.28 - 6.7)
Lactic Acid: 8 (0.74 - 19)

I eat 50% fat, 20-25% protein and 25-30% carb. Pyruvate and lactate have gone below range on 2 different tests. I'm not convinced they're related, I think it's a mitochondrial issue, but the advice I was given was to eat more carbs.

 

[ShepherdK]

I eat 50% fat, 20-25% protein and 25-30% carb. Pyruvate and lactate have gone below range on 2 different tests. I'm not convinced they're related, I think it's a mitochondrial issue, but the advice I was given was to eat more carbs.

Based on the model I put together + my own anecdotal evidence - it looks like a diet of 40%-50% calories from fat is an optimal target. Severe ME/CFS cases may benefit from (temporary) clinical/traditional ketogenic diets (75%-80% fat), however I've seen the most improvement at the 40%-50% caloric fats range personally. That combined with antioxidant support + pulsed antivirals has put me on a solid road to recovery in 2020.

 

[wastwater]

I likely have inherited low PDP2
Red blood cell walls harden in pyruvate kinase deficiency
Is everyone thought to have inherited low PDP

 

[lateM98]

This is what I have to say about Prusty's findings:

Prusty's work seems like a very long shot. His work demonstrated that there is a transferable factor in ME/CFS plasma that results in a cellular hypometabolic state. But Dr. Ron Davis had already demonstrated that. Prusty's work also shows that HHV reactivation in a single cell causes nearby cell to go into a similar hypometabolic state. But that absolutely doesn't mean that HHV reactivation is what's causing ME/CFS cells to be like that. Did he test other viruses? It could that many other viruses causes nearby cells to go into hibernation, as a natural antiviral defense mechanics. We know that bacteria does a similar thing when confronted with antibiotics. We know that drugs that clog the internal workings of cells make it hard for viruses to replicate. So it's not hard to imagine that this is a natural and temporary cellular adaptation until the viral infection gets cleared. Did he demonstrate the area that this hypo-metabolic effect span? Where is the computational modeling to tell how many HHV cells need to be infected before the blood plasma start to cause every cell in the body to go hypo. So until Prusty demonstrate a clear link between HHV and ME/CFS, I don't think it's wise to start freaking out about HHV. If anything, Prusty demonstrated that most ME/CFS people don't have evidence of HHV reactivation and only a minority have partial HHV reactivation, which is nothing special.

 

[sb4]

@lateM98 I agree with what you say however I think it is exciting not because of HHV-6, but the idea that a partially activating virus can transmit a cell danger response to nearby cell is very interesting, as is the pathways by which the effected cells enter into this danger state. This thing makes a lot more sense to me and could lead to realistic treatments, more so than most theories about this disease.

 

[lateM98]

@lateM98 I agree with what you say however I think it is exciting not because of HHV-6, but the idea that a partially activating virus can transmit a cell danger response to nearby cell is very interesting, as is the pathways by which the effected cells enter into this danger state. This thing makes a lot more sense to me and could lead to realistic treatments, more so than most theories about this disease.

From the study text : Partial iHHV-6 reactivation was characterized by the production of noncoding RNA without active viral replication.
The stress danger response is probably mediated by a Toll-Like Receptor, TLR8 for instance detects RNA. There is still the question of how much viral RNA you need before you have ME/CFS. Also you can't practically block TLR8 or any TLR for that matter. That been said, most TLRs signals converges at few nodes, and we can block many of them. I guess I can cook up an experiment for that one

 

[Marylib]

Just to tag onto one reply. Branched chain aminos do help me a ton. I would take a lot more if it didn't cause so much swelling at the back of my head. But the fact it cancels a crash almost completely or causes a crash which is far else severe is pretty amazing. So like Mary that's been my experience. Maybe many metabolic issues based on sex, environment, lifestyle, food eaten, genetics and body makeup cause a blurry picture because every body is different.

If I get them IV, it helps. Otherwise, in my case, no change. Glad they help you!

 

[raghav]

I dont know whether this is OT or not.
https://www.sciencedirect.com/science/article/pii/S075333222030024X
The protective effect of cordyceps sinensis extract on cerebral ischemic injury via modulating the mitochondrial respiratory chain and inhibiting the mitochondrial apoptotic pathway
Abstract
Cerebral ischemia is a common refractory brain disease, resulting from a reduction in the blood flow to the brain. Mitochondrial dysfunction leads to ischemic stroke and brain injury. Cordyceps sinensis (CS) is an important traditional Chinese medicine, which has been linked to neuroprotection in recent studies. In this study, we investigated the role of the mitochondrial respiratory chain and the mitochondrial apoptotic pathway on the protective effect of Cordyceps sinensis extract (CSE) against cerebral ischemia injury both in vivo and in vitro. In a murine middle cerebral artery occlusion (MCAO) model, administration of CSE relieved neuronal morphological damage and attenuated the neuronal apoptosis. CSE also reduced neurobehavioral scores and oxygen free radical (OFR), while improving the levels of ATP, cytochrome c oxidase (COX), and mitochondrial complexes I-IV. Furthermore, the mRNA expression of Bax, cytochrome c (Cyt c) and caspase-3 were down-regulated. In brain microvascular endothelial cells (BMECs) exposed to oxygen and glucose deprivation (OGD), CSE prevented OGD-induced cellular apoptosis, and recovered the reduction of mitochondrial membrane potential (MMP). Moreover, CSE treatment induced an increase of Bcl-2 protein expression and a decrease of Bax, Cyt c and caspase-3 protein expression. Meanwhile, the caspase-3, -8, and -9 activities were also inhibited. The results indicate that CSE can relieve cerebral ischemia injury and exhibit protective effects via modulating the mitochondrial respiratory chain and inhibiting the mitochondrial apoptotic pathway.

I had to go off cordyceps sinensis for the past 45 days due to lockdown. But I received it a week ago and I started taking one capsule initially (Now Foods Cordyceps 750 mg) and then increased it to the recommended 2 capsules and withing 2 hours my energy levels went from 10 % to 50 % both physical and mental. I have been taking cordyceps sinensis for the past 6 years and it has been a great help. From bedbound it has made me home bound with some outside activity. My HUA (Hours upright active) also has gone up from 2 to almost 8 hrs. I prefer Planetary Herbals Cordyceps 450 Full spectrum. But since I could not get it I tried Now Foods and it is also good. Planetary Herbals form has calcium 50 mg which some might not prefer.

It reduces brain fog by 90 % in me. It also has completely eliminated joint pains due to food allergies.

 

[Murph]

@lateM98 I agree with what you say however I think it is exciting not because of HHV-6, but the idea that a partially activating virus can transmit a cell danger response to nearby cell is very interesting, as is the pathways by which the effected cells enter into this danger state. This thing makes a lot more sense to me and could lead to realistic treatments, more so than most theories about this disease.

agreed. I think the idea is that a biological particle - perhaps small non coding rna - is causing the problem. In some people this will be because of HHV6, but I don't think Prusty is hung up on that - he knows that hhv6 is only one of th e causes of the biological particle.