Direct Causes of Fatigue (in CFS)

[sometexan84]

I'd like to put together a list of all the direct causes of fatigue, chronic/on-going fatigue. As this is a list benefiting my own research, I'd imagine many others could benefit from it as well.

I'm hoping others can help me build and modify this list as necessary so that it can become a solid resource.

This is a list for direct cause and effect fatigue. So things like a virus, or immune system, or genetics... they wouldn't be included here, as they are more correlative and indirect causes.

Please contribute by listing direct causes of chronic fatigue w/ link(s) to references for validation. And if possible, summarizing in a way that a layperson can understand.

Starting w/ the few I'm aware of (that I understand and can thus somewhat articulate -- pls correct me if I'm off on any of this) ....

Direct Causes of (Chronic) Fatigue (start of list...)
Please contribute by listing others w/ reference links and/or correcting what I have thus far

• Autonomic Nervous System Dysfunction - Unrefreshing sleep due to decreased parasympathetic activity. Sympathetic is part of the nervous system used to speed you up and get you going. Parasympathetic nervous system is for calming you down. So this would be fatigue caused by decreased or dysfunctional noctural parasympathetic activity (while you're sleeping). Resulting in getting unrefreshing sleep.
• Neuroinflammation - Brain inflammation causing a "sickness response". This sickness response can include extreme fatigue. It's very complicated, but the fatigue comes from chemicals called "inflammatory cytokines". These cytokines are being released in the brain because immune cells called "microglia" have become abnormally activated.
• Mitochondrial Fragmentation/Dysfunction (Cellular Bioenergetics Impairment) - Mitochondria are part of the cell responsible for producing energy for the body. More specifically, a chemical called ATP (adenosine triphosphate) makes the energy (whereas Mitochondria is the energy "factory" so to speak). Any disruption through mitochondria dysfunction or fragmentation (again, this makes energy) is going cause fatigue. As for the cause of this... it's due to a virus. So viral-mediated mitochondrial dysfunction.
• SITH-1 Protein (HHV-6B Reinfection) – This protein can cause depression-like symptoms, including fatigue. Some viruses (including HHV-6) can travel to your brain from your nose. Hitches a ride on your “olfactory nerves” located way at the top of your nasal passages, until it reaches the “olfactory bulb”, which is at the bottom of your brain, just behind where your eyes are. This “olfactory bulb” is an important reservoir for latent HHV-6. From here, SITH-1 is produced, messing with your brain cells and causing depression and fatigue symptoms.
  Fun Fact: Professor Kazuhiro Kondo, who discovered the SITH-1 Protein did in fact name it after the Dark Lord of the Sith from Star Wars.
• Overactive Immune System - This guy obviously has a recurring role in the melodramas of CFS. Maybe it triggers something else that causes lasting fatigue. But the studies I've seen show fatigue persists even after immune system normalizes. In and of itself, an overactive immune system (it appears) only has correlation and not causation for long-lasting fatigue. Let me know if you find otherwise.

Autonomic Nervous System Dysfunction

1. Autonomic Nervous System Functioning Related to Nocturnal Sleep in Patients With Chronic Fatigue Syndrome Compared to Tired Controls
2. Summary Review: The Dysfunctional Autonomic Nervous System in ME/CFS

Neuroinflammation

1. Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods
2. Jarred Younger, PhD | How Brain Inflammation Causes ME/CFS (YouTube)
3. MEA Summary Review: Whole-brain imaging study suggests brain inflammation in ME/CFS

Mitochondrial Fragmentation

1. Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
2. MEA Summary Review: The role of Mitochondria in ME/CFS

SITH-1 Protein

1. Can depression, psychiatric disorders and fatigue be triggered by a neurovirulent latent HHV-6B protein?
2. Researchers: Virus-derived protein triggers depression
3. Human Herpesvirus 6B Greatly Increases Risk of Depression by Activating Hypothalamic-Pituitary -Adrenal Axis during Latent Phase of Infection

 

[pattismith]

Interesting attempt of a synthesis in ME/CFS pathophysiology process.

The problem I notice is that only the autonomic nervous system failure has reach some consensus in the medical community, so I think research should focus on the ANS dysfunction in ME/CFS and the best way to test it.

This would be the best way to show to the medical community that ME/CFS is a real disease, with real neurological condition

 

[sometexan84]

Yea, for sure. Still lots of conjecture. Since I find myself steering more than my physicians (at this point), I'm trying my best to get a deeper understanding of it all. As much as I possibly can. It's helping me get better at choosing specialists to see, talk to them about tests I think I need, and it's really just helping me get more out of each doctor visit.

I feel like understanding more about the direct fatigue causes is a huge piece to the puzzle. And one that will have me better equipped to continue healing.

I also think this list would be helpful because I am of the opinion that we don't all have the same type/cause of fatigue.

 

[joshualevy]

Are you limiting it to physical disease? I think the most common direct cause of fatigue amoung teenagers is chronic lack of sleep. I can't tell you how many parents tell me "my kid is constantly tired, for months at a time" and I ask them "when does your kid go to sleep" and they say "I don't know. I was up late, and he/she was sitting in bed playing with their phone when I went to bed." Conversly, I've never heard a parent complain about how tired their kid is, if the kid went to bed before midnight.

 

[Wishful]

Add the Sith1 protein. See: https://forums.phoenixrising.me/thr...ics-the-classic-symptoms-of-depression.80435/

I'm not sure how specific it is to HHV6, but it does cause lethargy, which might fit the definition of 'fatigue'.

I'm fairly sure that my 'fatigue' is due to neuroinflammation. I don't have abnormal muscular fatigue, so my body's mitochondria seem to be working fine. Mito dysfunction only in brain cells is a possibility. My ME doesn't seem to be sensitive to changes in sleep pattern, so that doesn't seem like a likely cause either. It is--or at least was--sensitive to tryptophan levels in my brain, which indicates neuroinflammation was involved.

 

[Wishful]

If you're talking about muscular fatigue, this quote from wiki is important: "There are two main causes of muscle fatigue: the limitations of a nerve’s ability to generate a sustained signal (neural fatigue); and the reduced ability of the muscle fiber to contract (metabolic fatigue)."

Also: "The perception of mental fatigue is believed to be modulated by the brain's reticular activating system (RAS)." Thus there's real fatigue, and perceived fatigue, which might not be real fatigue.

I think toxins can cause fatigue too, but I'm too fatigued to look for good references.

 

[Booble]

It sounds like you want this list to be more technical than what I can offer but I will say what I think anyways.

- Low blood volume, indicated by the large overlap of POTS with CFS
- Allergic response on overdrive
- Overactive immune system
- Blood sugar disregulation
- Hormonal imbalances and or dysfunction

 

[Wishful]

Another useful quote from wiki:

"Chronic fatigue syndrome is a name for a group of diseases that are dominated by persistent fatigue. The fatigue is not due to exercise and is not relieved by rest.[28]
Through numerous studies, it has been shown that people with chronic fatigue syndrome have an integral central fatigue component.[1] In one study, the subjects' skeletal muscles were checked to ensure they had no defects that prevented their total use. It was found that the muscles functioned normally on a local level, but they failed to function to their full extent as a whole. The subjects were unable to consistently activate their muscles during sustained use, despite having normal muscle tissue.[29] In another study, the subjects experienced higher perceived effort in relation to heart rate as compared to the control during a graded exercise test.[30] The chronic fatigue subjects would stop before any sort of limit on the body was reached. Both studies proved that peripheral muscle fatigue was not causing the subjects with chronic fatigue syndrome to cease exercising. It is possible that the higher perception of effort required to use the muscles results in great difficulty in accomplishing consistent exercise.[1]
The main cause of fatigue in chronic fatigue syndrome most likely lies in the central nervous system. A defect in one of its components could cause a greater requirement of input to result in sustained force. It has been shown that with very high motivation, subjects with chronic fatigue can exert force effectively.[31] Further investigation into central nervous system fatigue may result in medical applications."

Also: "Central nervous system fatigue, or central fatigue, is a form of fatigue that is associated with changes in the synaptic concentration of neurotransmitters within the central nervous system (CNS; including the brain and spinal cord) which affects exercise performance and muscle function and cannot be explained by peripheral factors that affect muscle function"

I'm clearly suffering from central fatigue, rather than muscular.

Another paper ( https://www.sciencedirect.com/science/article/abs/pii/S000689931730389X?via=ihub ) is about tryptophan involvement in central fatigue.

 

[Booble]

Is it just "perceived" when the fatigue causes you to become dizzy or faint?

 

[andyguitar]

Looking at symptoms other than fatigue might be usefull @sometexan84 as other things that cause fatigue dont always have symptoms like cfs.

 

[Rufous McKinney]

subjects with chronic fatigue can exert force effectively.[31]

That research is from 1988...do you think it still pertains?

 

[Wishful]

That research is from 1988...do you think it still pertains?

I'm not sure of the validity of that research, but I do have chronic fatigue and my physical performance is as high as pre-ME, so yes the claim is valid.

 

[sometexan84]

Add the Sith1 protein. See: https://forums.phoenixrising.me/thr...ics-the-classic-symptoms-of-depression.80435/

Added to OP

 

[sometexan84]

Looking at symptoms other than fatigue might be usefull @sometexan84 as other things that cause fatigue dont always have symptoms like cfs.

You aren't wrong! I'll admit that I'm a bit biased since chronic fatigue is my only symptom (aside from hair loss and weight gain).

Besides, I've seen lots of resources for CFS like symptoms, treatments, initial triggers/causes. But whenever I went looking for a resource regarding direct biological causes of fatigue, all I had were my own notes.

 

[sometexan84]

Are you limiting it to physical disease? I think the most common direct cause of fatigue amoung teenagers is chronic lack of sleep. I can't tell you how many parents tell me "my kid is constantly tired, for months at a time" and I ask them "when does your kid go to sleep" and they say "I don't know. I was up late, and he/she was sitting in bed playing with their phone when I went to bed." Conversly, I've never heard a parent complain about how tired their kid is, if the kid went to bed before midnight.

Fair enough. Made a couple of edits to make it clear we're talking about CFS.

 

[Wishful]

chronic fatigue is my only symptom (aside from hair loss and weight gain).

Darn that ME! It's giving me those symptoms too!

As for fatigue, everyone thinks they know what that is, but when you want actual details, no one knows. I expect it will turn out to be a lot more complex than 'not enough ATP' or 'a buildup of <whatever>'.

 

[Booble]

The fascinating thing is the differences in symptoms. Which makes one wonder if what we are really dealing with is multiple different conditions that have all been lumped together in one big "chronically feel like shit" bucket. I wonder if we'd get more answers if things were subsetted such that there could be more focus. Studies could then be done on people grouped together with the same "sub-type" of ME/CFS. Or maybe this is already the case?

 

[Wishful]

I still think it's one core dysfunction, with upstream sensitivities and downstream symptoms and further disorders that depend on individual variations. Even small changes in neural function in some parts of the brain can have major effects on other parts of the body, giving one person serious gut issues, and another person severe muscle impairment. Since there's limited funding available, I'd rather have it go to finding/treating/curing the core dysfunction--which should treat/cure all the related symptoms--rather than have it go towards treating a bunch of individual symptoms that we don't all share, and leaving all of us with other remaining symptoms.

I've managed to treat or even cure some of my symptoms, but I'm still suffering from mental lethargy (chronic central fatigue?), so treatments for muscle fatigue or pain or POTS or any of the other symptoms that other PWME have wouldn't do anything for me. If we knew in advance that finding a treatment for ME-induced POTS (or whichever specific symptoms a subgroup has) would require only $200k and three months, and would help 3 million people, then sure, we should spend that. However, it could take 50 years and billions of dollars. Finding the core cause of ME might be cheaper and easier, and should help all subgroups of ME.

 

[andyguitar]

Ok, here's a question for you all...... Is the fatigue you suffer from now not just much,much worse than what you would have experienced from lack of sleep/ over activity/ a night on the tiles in the days when you were healthy but also in someway different? I thought i'd throw that question in as the "fatigue" in cfs might not be fatigue at all.

 

[Rufous McKinney]

Is the fatigue you suffer from now not just much,much worse than what you would have experienced from lack of sleep/ over activity/ a night on the tiles in the days

Its very different from any form of sleepy, tired from being out late, over doing..its none of that.

Malaise overshadows the fatigue most of the time.

We use a limited vocabulary which rarely is really describing what this feels like. And then since nobody asks.....

I recall staying up late to hear a friends band (about 10 years ago, now). Got home at 1 am. It took me like a week to recover from this one event. I didnt know about PEM then. It was just This Is Ridiculous.