Naviaux et. al.: Metabolic features of chronic fatigue syndrome

[alex3619]

@alex3619 are they saying here that there is no mito suppression during torpor in the brain?

http://www.journals.uchicago.edu/doi/10.1086/668853

I only read the abstract, but basically, yes. However this was mammalian torpor, and less like what we are going though than in nematode worms, from what I currently surmise. Do keep in mind though that the methodology used is for essentially a tissue biopsy, though the animal was probably sacrificed. Most of the dynamic factors will be decreased. The salient point though is that most of the decline in energy production is for muscle etc., not the brain. However, consider this: if there is decreased circulation and lung oxygen perfusion then there would be a cap on what the brain can do, and this would not show up in this kind of testing.

 

[Bob]

https://twitter.com/i/web/status/773339100992663553

 

[Bob]

Just a reminder that we aren't necessarily in a dauer state; from what I understand, some of our physiological chemical signatures are fairly similar to those seen in a dauer state in invertebrates. But I think that's as far as it goes at the moment.

Also, even if our illness is very close to an adaptive dauer state seen in invertebrates, it doesn't mean that it is an adaptive state in humans. I'm convinced that it's a maladaptive state. In any case, it's clearly a disease state.

So, although I find it interesting, it might not always be helpful to compare aspects of ME/CFS in humans to a dauer state in invertebrates, and to expect them to be similar in nature.

 

[alex3619]

Dauer state is an analogous state, not the same state. Its a comparative model that can be used to springboard our understanding, but wont substitute for science into what is happening in us.

I have some concern that we may be misinterpreting the notion of conserved adaptive state. Such states and genetic changes are not about the individual, but the population. Its adaptive for the population, even if individuals die. How many live because they survive severe viral infections and other injury and the state switches off like its supposed to? Adaptations like that do not disappear from the gene pool, no matter how many individuals suffer or die.

 

[worldbackwards]

I didn't mean that dauer and dour might share an etymology, just that they are homophones.

That's a pretty serious accusation there.

 

[Cheesus]

That's a pretty serious accusation there.

 

[Seven7]

I think my issue is the burning stored fat for energy one. Any ideas how to address this one?

 

[EtherSpin]

I only read the abstract, but basically, yes. However this was mammalian torpor, and less like what we are going though than in nematode worms, from what I currently surmise. Do keep in mind though that the methodology used is for essentially a tissue biopsy, though the animal was probably sacrificed. Most of the dynamic factors will be decreased. The salient point though is that most of the decline in energy production is for muscle etc., not the brain. However, consider this: if there is decreased circulation and lung oxygen perfusion then there would be a cap on what the brain can do, and this would not show up in this kind of testing.

I wonder would a carefully selected regime of drugs and supps that enhance oxygen utilisation in the brain be of help in the short term. I did a couple of tilt tests when I was being diagnosed and I was on Piracetam to help me speak well during the appointments but on Piracetam I was on borderline of POTS threshold, off Piracetam Ive been consistently well into the POTS camp. https://examine.com/supplements/piracetam/#summary3-5

I wonder also if a separate long term thread would be feasible for non fogged up and very smart individuals to interpret results and identify beneficial supplements or drugs or even food items to make the most of the metabolic processes that are intact in our state.

 

[rosie26]

My temperature drops when I crash and I get body wracking chills

Same. The chills are a sign that I am deteriorating. The wracking chills are nauseating and I am always very sick when I get those.

 

[Seven7]

The chills are a sign that I am deteriorating.

try a vasso constriction tea next time see if it helps (not coffee).

 

[merylg]

I think my issue is the burning stored fat for energy one. Any ideas how to address this one?

HCG diet works for some... short term... interesting that it DOES work... but one can't keep daily plugging in HCG hormone as 1) it's expensive and 2) who knows the long term effects and 3) wonder if there is a rebound effect? How much fat is burned off & whether any is re-distributed in a harmful way... just thoughts!

 

[alex3619]

I think my issue is the burning stored fat for energy one. Any ideas how to address this one?

Is this issue that you want to burn more fat as fuel? Look at the biochemistry of extreme cold. People on higher fat diets, and I mean natural healthy fats, are more adapted to burning fat. This would fit with a high protein diet as well, given that high protein foods often contain higher fat. This is not a licence to just eat more fat though. Energy intake does need to be targeted. So arctic and antarctic explorers start eating a higher fat diet a few weeks before moving to extreme cold, though in their case they want to consume huge amounts of high energy food for those few weeks. When they get to the cold their body is already adapted to burning fat as fuel. Its unclear, however, how this will translate to ME or CFS or fibro patients. Its very likely a possible hypometabolic state will change things.

 

[IreneF]

It means that those who don't have it are more likely to die in the long run, which means that though it is harmful the benefits outweigh the harm on an evolutionary scale.

I thought it meant that its constituent DNA sequences had remained relatively unchanged over an evolutionary timescale, which would indicate that it's important to the organism's survival.

 

[alex3619]

I thought it meant that its constituent DNA sequences had remained relatively unchanged over an evolutionary timescale, which would indicate that it's important to the organism's survival.

Almost the same thing. It remains unchanged because a change is counter to population survival. The key difference in my argument is the shift from organism to population of organisms. It used to be thought, and I don't know the current thinking, that with some variation the prevalence of a deleterious gene is a balance of its positive and negative effects. The more positive, the more common. The more negative, the less common. Those with both negative and positive effects will strike some kind of balance in the population.

Take sickle cell anemia. In malaria prevalent areas the gene that leads to this is very common. Those who have two copies often die young, from changes to the shape of their red blood cells. Those who have one copy have resistance to malaria. Those without it are more likely to die of malaria. So in some parts of the world this gene is fairly common, despite the negative effects.

 

[IreneF]

Almost the same thing. It remains unchanged because a change is counter to population survival. The key difference in my argument is the shift from organism to population of organisms. It used to be thought, and I don't know the current thinking, that with some variation the prevalence of a deleterious gene is a balance of its positive and negative effects. The more positive, the more common. The more negative, the less common. Those with both negative and positive effects will strike some kind of balance in the population.

Take sickle cell anemia. In malaria prevalent areas the gene that leads to this is very common. Those who have two copies often die young, from changes to the shape of their red blood cells. Those who have one copy have resistance to malaria. Those without it are more likely to die of malaria. So in some parts of the world this gene is fairly common, despite the negative effects.

It doesn't have to be harmful to be conserved, e.g. cytochrome c. A dauer-like state in humans may be (genetically) related to sickness behavior, for example, which is mediated by cytokines. The problem may not be the dauer-like state itself, but turning it off once it's outlived its usefulness.

Yes, I know about sickle cell and similar traits.

 

[alex3619]

It doesn't have to be harmful to be conserved

Most conserved genes are helpful and not harmful, and sometimes you can trace them, with variations, from modern animals back to very primitive organisms. My point is this is not always the case.
PS If the dauer state has a primary gene switch, that does not prove its one gene in us. I don't want to preempt the science and claim its all due to a single gene. It may be many genes, and other factors, acting in concert.

PPS There is also the issue of conserved gene structure, which is closely related to this. Some genes have remained almost unaltered in most species.

 

[Seven7]

@alex3619 tx! Is what I tried to do but ended up w high uric acid so Dr told me to lower the protein intake.

I would like a supplement do the enzyme he found low. I know this is my issue be cause I notice I have to eat constantly for energy. Is as of my body is unable to produce it from store fat. Also I keep gaining stored fat ( I am not that heavy to have 35% fat).

Is something I had figured by myself when I get into ketosis for example I could not move for the lack of energy. I do best on complex carbs ( I eat mostly roots). But it is as if I am lacking an enzyme or something to tell body use fat as energy.

 

[bertiedog]

I'm beginning to feel that prolonged ATP depletion is irreversible damage to the mito membrane and the cell dies. We can only protect the new mitos (that may not be as efficient) to prevent worsening.

When Acumen did a study of my mitochondria through Dr Myhill my cell membrane was described as normal.

Pam

 

[alex3619]

Is something I had figured by myself when I get into ketosis for example I could not move for the lack of energy. I do best on complex carbs

This suggests a problem with beta oxidation or fat mobilization, though it could be an issue that the switch to fat burning, which takes at least a few weeks, is slowed or limited. I am not sure who could do the necessary tests or who could best advise on this. It might be a good candidate for metabolomic testing. Many of us rely heavily on glycolysis. We might know more of the issues after a lot more of us have metabolomic testing, for now we are still guessing too much. I suspect we might find there are metabolic subgroups.

enzyme he found low.

Do you know the enzyme? You typically cannot supplement an enzyme directly, as it just gets digested if swallowed. IV would probably fail because it would be extracellular. You need someone who knows a lot about that metabolic pathway and associated pathways. Again, it seems this is the kind of puzzle that metabolomics was designed to investigate.

 

[Seven7]

This suggests a problem with beta oxidation or fat mobilization, though it could be an issue that the switch to fat burning, which takes at least a few weeks, is slowed or limited. I am not sure who could do the necessary tests or who could best advise on this. It might be a good candidate for metabolomic testing. Many of us rely heavily on glycolysis. We might know more of the issues after a lot more of us have metabolomic testing, for now we are still guessing too much. I suspect we might find there are metabolic subgroups.

Do you know the enzyme? You typically cannot supplement an enzyme directly, as it just gets digested if swallowed. IV would probably fail because it would be extracellular. You need someone who knows a lot about that metabolic pathway and associated pathways. Again, it seems this is the kind of puzzle that metabolomics was designed to investigate.

Great!! Thank you I think I was thinking of the graphs from the other lady: her slide reads as follow comparing thier results vs Naviaux.

Males low metabolites:
Serine/1-carbon MetBolism
SAM, SAH,Met
Very long Chain FAO
Propiogenic AA
Threonine

Both male and females
Sphingolipids, phospholipids, Glycosphingolipids, Purines, Microbiome, Cholesterol, B2(Riboflavin),
P5C, Arginine, Proline, Branch Chain AA

Females:
Fatty Acid oxidation ( how do I address this?)

Vit C/ collagen.
Bile Acids
Endocannabinoids
Vit b12
Amino sugars