what is the mechanism of fatigue?

Hi guys,

I didn't know where to post this and googling just confused me more so I'm wondering what are the mechanisms of fatigue???

so for example I know low-ATP can be a mechanism of fatigue.

Say your fatigue is hormonal or due to some medical condition does this mean you can cure it by increasing ATP levels??? Does all fatigue have the same mechanism or final underlying cause such as ATP or are there different mechanisms?? What are these mechanisms exactly??? Where can I do more reading about this???

I hope this post made sense sorry if I confused anyone :).

thanks for answering.

(sorry if this is in the wrong forum)


Senior Member
I'm not really sure what question you're asking, but one problem is there are clearly different kinds of fatigue.

Take a healthy person. Simply staying up all night is going to induce a very different kind of fatigue from running a marathon when you've just got up in the morning after a good sleep. The "fatigue" of ME/CFS is of a different flavour still, and I'm pretty sure I'm right in saying we don't yet really understand what is happening to cause it.


Southern California
@findinglife - there are so many different causes of fatigue: e.g., low B12, low folate, low B-6, hypothyroidism, weak adrenals, celiac disease or gluten intolerance, and so on. And you would have to do the appropriate thing to remedy each of these conditions, there is no one-size-fits-all solution.

So e.g., if your fatigue is hormonal as you suggested, then the solution I think would be to fix hormone levels.

there is something called "central fatigue", which I think may be related to CFS and post-exertional malaise. Here's an article which explains more: http://www.ncf-net.org/forum/Fword.htm
After reading this I started taking branched chain amino acids and glutamine and they have helped me recover more quickly when I crash, though I still do crash (post-exertional malaise, or PEM)

It sounds like you are having problems with fatigue but don't know the cause. A good doctor (which can be very hard to find!) or naturopath should be able to help you, at least somewhat. If you need help finding a doctor, it would be good to do a post about and hopefully someone on the board can help you with that.


Senior Member
what an interesting question!

I experience different fatigues, amongst them hormonal fatigue. When it's thyroid I'm sluggish, don't want to move my body and I'm cold (a coldness from within, from the bones).
When it's cortisol or progesteron deficiency I get a nervous kind of fatigue. Where I feel threatened but do not have the resources to deal with any stress that might come my way. This fatigue is fixed with hormonal replenishment. Fixing these two fixes thyroid fatigue in turn, together with a daily Kelp/Iodine supplement.

Then there's bodily fatigue. In me it's caused by low blood pressure (and subsequent inability of the nervous system to maintain homeostasis) and digestion. Digestion takes a mighty lot of energy! I've resorted to easily digested superfoods (egg yoke, gelatine) and this preserves my energy. I avoid all vegetables and raw foods.

For the homeostasis fatigue I know no other remedy than resting, reclining and pacing. Always the pacing.

Yes, I'll mention the cell processes fatigue. That'll be the ATP thing you mention, I guess. In my case I think my cells do not get all the amino acids and minerals they need to function properly. They also have some faulty enzymes which hinders the use of the building blocks they do get.

I make sure my cells get everything they need, I pamper them as if they lived in petri dishes. For this I take an amino acid supplement called Biotics Gland thingy. And lots of minerals. And rest (this aids the low blood pressure to deliver the stuffs to the cells).
Some tweaking occurs to aid my specific enzyme mutations. For example: I take extra vitD because I lack some receptors. I am verrry prudent with mB12 because it spurns the processes into overdrive. MAO A mutation asks I do not eat cheese, vanillin or MAO-inhibitors.

Also cell waste disposal, my cells need some help with this. Waste building up fatigues the system severely. I stretch and yawn, aiding the lymph system.

Then there's the fatigue caused by organs. My liver seems to have a hard time with things. It flops out of commission whenever I experience stress. I aid it with the aforementioned Biotics supplement. And by taking HCL with every meal. And by laying down when my food passes the duodenum. And by not eating things that upset my liver (empty calories, alcohol, BBQ)

So to me the fatigue comes from different levels that intercept and influence each other. I can now identify some of them.
There's also the Central Nervous System. Mine gets overworked all the time. I'm "a stress-chicken", that's a Dutch expression. Always alert, always running around, always assuming worst case scenarios. This is very taxing to the body and needs daily doses of zen to neutralize effects. If I don't crippling fatigue will set in.

Whenever the CNS is legitimately stressed out (caused by a life event) I'll need 3 months (or 13 months) to recuperate. This is a normal reaction to stress (see dr. Selye) only in our era we are not used to taking so much time licking our wounds. I try to see this type of fatigue not as part of the illness but as a natural occurence. It does add to the other types I mention above though.

To answer your specific questions, in my opinion and I'm no expert:
1. Say your fatigue is hormonal or due to some medical condition does this mean you can cure it by increasing ATP levels???

nope. Not for the hormonal part anyway. Fatigue from hormones means you lack the effects of those hormones. ATP won't fix that, you need the hormones themselves. Hormones are not scary, you just have to act responsible. Just like when driving a motor bike or feeding a shark/a baby.

2. Does all fatigue have the same mechanism or final underlying cause such as ATP or are there different mechanisms??

I don't know.
I myself look at this problem through the different scales it addresses (whole body, the two vessel structures (blood; lymph), organs, intercellular fluids, cells, cell membranes, enzymes, DNA). Your opinion should probably differ from mine.

3. What are these mechanisms exactly???

I have studied the various levels I mention above because that's my working theory for fatigue. I have not healed however. My energy level has improved from a 15% to 50%. Not tasking the digestion system has been the major contributor to that one.
HRT and full amino acids and minerals have mainly improved mood and have reduced bodily stress levels.

4. Where can I do more reading about this???

hormones: "What your dr. didn't tell you about perimenopause" by dr. Lee; some book by dr. Thiery Hertoghe; website Stop the Thyroid Madness; website of a woman who has addison's and runs marathons. I do not have links for you.... sorry. Do you want them?
cortisol: the wikipedia page.
stress and the havoc it wrecks on the body: work by dr. Selye
sleep: some India dr. who does research on sleep phases. I've got his website somewhere...
cells and membranes: a book for students: "The Cell, a molucular approach"
the body and digestive system: basic biology books and websites. Aimed at students. It's a fascination subject!

As far as I know there is not a coherent field where scientists think about fatigue. You've got to cobble together your own theory, based on your experiences with your own body.
Hospitals where scientist specialize in fatigue, such as Radboud in Nijmegen or some CFS centre, they usually think it's all in the head and the patient just has a poor attitude. They often promote gradual increasing exercise. Run/wheel away from those places.

PS. I think there're other forms of fatigue I have not identified yet. One might very well be The ME Fatigue, the one, the special one.
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Senior Member
what is the mechanism of fatigue?
You might find Michael VanElzakker's vagus nerve infection hypothesis of ME/CFS of interest.

VanElzakker points out that the sickness behavior response has very similar symptoms to those of ME/CFS. The sickness behavior response is a bit like an in-built reflex response that triggers fatigue, brain fog, and several other symptoms.

When you come down with a significant infection like the flu, and feel very tired and mentally fogged, and down in your mood, you are experiencing the sickness behavior response.

Sickness behavior can be switched on by nerve signals sent to the brain via the vagus or trigeminal nerves, when either of these nerves sense an infection and inflammatory cytokines in the body. VanElzakker hypothesizes that a chronic infection of the vagus nerve itself would result in the vagus nerve constantly sending inflammatory signals to the brain, thereby permanently switching on sickness behavior, and thus constantly causing the symptoms of ME/CFS, including the symptom of fatigue.

If it turns out that ME/CFS is caused by the chronic activation of the sickness behavior response (and at the moment this is just a hypothesis), then sickness behavior would be the mechanism behind the fatigue in ME/CFS.

You might then ask: OK, if the fatigue in ME/CFS comes from sickness behavior, what then is the mechanism that causes fatigue to appear within sickness behavior? Well, the answer to that is not yet known, but Rönnbäck and Hansson have theorized that the fatigue in sickness behavior may be due to raised levels of extracellular glutamate in the brain.

@Marco wrote a great article on how raised levels of glutamate might be driving many ME/CFS symptoms: Glutamate - One More Piece in the Chronic Fatigue Syndrome (ME/CFS) Puzzle?

Some people on this forum experience a major improvement in their ME/CFS after taking a drug (Rocpehin) that clears extracellular glutamate from the brain (see this thread).
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Senior Member
Coincidentally, Ceftriaxone, or Rocephin, is the drug recommended by the IDSA for cases of neuroborreliosis.


Senior Member
Coincidentally, Ceftriaxone, or Rocephin, is the drug recommended by the IDSA for cases of neuroborreliosis.
Yes, and it did occur to me that Rocephin might be helping Lyme disease in more than one way: (a) from its potent antibacterial action, but also (b), from its ability to significantly increase glutamate clearance from the brain. On the assumption that the fatigue and brain fog in ME/CFS and Lyme might involve elevated glutamate, then Rocephin may be helpful because it dramatically ramps up glutamate clearance by 3-fold.

@lizw118, who has ME/CFS and Lyme, reported on the Rocephin thread becoming "almost totally well" within two days of taking a Rocephin injection. That seems too fast to be due to Rocephin's antibacterial action, which takes weeks to work, so my assumption is that this was due to the glutamate clearance produced by Rocephin, which occurs on a timeframe of around 2 days according to one study I read.


Senior Member
There's a tonne of theories on this but with some very profound results coming from the Norwegian Rituximab studies the mechanism causing the extreme relapsing fatigue could be autoimmune in origin.

Just for a bit of background, Rituximab is a B cell depleting drug - essentially it used to wipe out a part of the bodies immune system that produces antibodies. This particular drug is used for certain autoimmune diseases where the body's own immune cells attack itself. So far it looks like 2/3 of people with CFS/ME will respond very well to Rituximab - many achieving a high degree of remission so a suspected mechanism is that fatigue is caused by an autoimmune process that is alleviated if the human bodies B cell population is depleted.

I've posted a section from an article by Cort Johnson about 2 doctors; Fluge and Mella and the link at the end.

We have written a manuscript on our thoughts and hypotheses including the relation between immune response, endothelial function, and the possible effector system for symptom maintenance in ME/CFS. However, we still believe that we need more data to underpin out thoughts and have therefore not submitted the paper yet.

[Dysfunction of the endothelial cells lining the blood vessels in the circulatory system has been a subject of interest in ME/CFS since MERUK’s pioneering efforts in the early 2,000’s. These cells – present everywhere from largest arteries to the small capillaries – control how dilated or narrowed the blood vessels are, affect inflammation, control blood clotting and more. Each of these factors have been implicated in ME/CFS at one time or the other. In 2012 Newton et al. reported both small and large blood vessel dysfunction was present in ME/CFS.

The finding last year that autoantibodies to the adrenergic receptors found on endothelial cells are present in postural orthostatic tachycardia syndrome (POTS) suggested an autoimmune process was knocking out one group of POTS patients. Now Fluge/Mella appear to be proposing that a similar autoimmune process is messing up the blood vessels and producing the sympathetic nervous system activation in ME/CFS. If that’s so Rituximab’s efficacy could lie in its ability to restore proper blood flows (and presumably blood volume) to ME/CFS patients allowing them to exercise, think, digest, etc. as healthy people do. This is a hypothesis that is pregnant with possibilities.

Fibromyalgia patients should note that Rice has found evidence of small blood vessel dysfunction in the hands that may also be impeding normal blood flows throughout the body. – Cort. ]

- See more at: http://simmaronresearch.com/2015/01...e-rituximab-fluge-mella/#sthash.CBwZWm5y.dpuf