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Does anyone else experience most of their fatigue in the afternoon?

MariaMagdalena

Senior Member
Messages
100
I am currently in a continuing PEM episode that started almost a month ago. I feel ok and need to put the bulk of activity between 9 am (if I am able to get up at 7) and 3 pm. I always need 2 hours in the morning to get over the high fatigue and fibro pain I wake up with. I have noticed that at about 3 pm I start tanking, but unlike many of you, the fatigue just builds and builds till it forces me into bed. If I wait till 9 to do my bedtime routine, I can hardly get through it. I have to do it in pieces starting 7:30 ish.
 

Rufous McKinney

Senior Member
Messages
13,249
I always need 2 hours in the morning to get over the high fatigue and fibro pain I wake up with. I have noticed that at about 3 pm I start tanking

This is pretty much what happens to me each day. A long long time to wake up, from the unrefreshing, a few hours of being sort of OK, then the symptoms creep in (or sweep in). Then they seem to win.

Sickness Behavior very strong here. The whole suite of symptoms- EATING is hard, for instance. I can hardly chew.
 

gbells

Improved ME from 2 to 6
Messages
1,491
Location
Alexandria, VA USA
One obvious reason symptoms are worse in the afternoon has to do with the circadian rhythm of the cortisol hormone. In the morning it is higher so inflammatory symptoms are lowered/suppressed. As it drops they increase. It indicates high inflammation is present.

Cortisol-High-Early-Morning.jpg
 

Wishful

Senior Member
Messages
5,684
Location
Alberta
One obvious reason symptoms are worse in the afternoon has to do with the circadian rhythm of the cortisol hormone.

That may be an obvious hypothesis, but it doesn't seem to fit my observations. My symptoms increase abruptly around 2:30PM and then taper off over the next hour or two. Your graph doesn't show any sort of abrupt change in the afternoon.

If it was because the immune system abruptly switched state when cortisol reached a certain low level, I'd expect to see a much wider variability of trigger time. Instead, at times in the past, I've felt abruptly worse, looked at the clock, and seen that it was 2:30 +/- maybe 15 minutes. I'm not sure what system in the body is involved in such precise timing, but cortisol level doesn't seem to fit.
 

Rufous McKinney

Senior Member
Messages
13,249
My symptoms increase abruptly around 2:30PM and then taper off over the next hour or two.

I can set my watch to 2:30 most days. The neck aching, the throat hoarse and painful., particularly if I spoke or chatted.... My symptoms don;t taper off, they continue to worsen.

Some of these timing issues are why I find the Yin Deficiency...to serve to explain the increased HEAT and INFLAMMATION which is generated later in the day. Yin is built up at nite, so our "unrefreshning sleep symptom" makes some sense as many body repairs occur in the nite. this Yin Deficiency here is likely my genetic predispostions, not the CAUSE of the ME.
 

Sidny

Senior Member
Messages
176
Oh and his colleagues have a different theory. Rather than stemming from a lack of sleep from the night before, they suggest that excessive daytime sleepiness is caused by direct degeneration of wake-promoting neurons.

Looking at brain tissue, the team found a significant tau buildup in three wakefulness-promoting brain centres, including the locus coeruleus (LC), the lateral hypothalamic area (LHA), and the tuberomammillary nucleus (TMN). Remarkably, this complex system had lost as many as 75 percent of its neurons.

Among the many fatalities was a type of neuron in the LHA that produces a neuropeptide called orexin. This neuron plays a crucial role in wakefulness; when it is deleted in mouse models, the animals show similar patterns to human narcolepsy - a chronic sleep disorder characterised by daytime drowsiness.

In the brains of patients with AD, UCSF researchers found orexin practically annihilated. In fact, the abundance of these orexin-producing neurons had decreased by more than 71 percent.

"To put this into another perspective, patients with narcolepsy .. have been reported to show 85-95 [percent] reduction in the number of orexinergic neurons, almost comparable to what we see in patients with AD," the authors write.

https://www.sciencealert.com/alzhei...he-neurons-that-keep-us-awake-study-shows/amp
Something similar might be happening to CFS sufferers who need naps during the day.

If indeed orexin is reduced in those patients and this can be proven clinically, then this is also quite a good argument for disability and proof that something is physically wrong.

I've also heard of several people who were diagnosed with narcolepsy. Maybe the narcolepsy was caused by CFS?

Dying neurons? Sounds like a logical explanation to me. Since the onset of my illness after a viral brain infection, I’ve suffered from a significant diminishment in overall arousal and the Locus coeruleus plays a big role in that.

I’m not quite at the point of needing many naps or narcolepsy though. Obviously like with any neurodegenerative disease the damage doesn’t happen overnight but is long term and cumulative.

It’s amazing how the pathologies of so many differently labeled diseases all seem to overlap. The question is what can we do now to stop tau and b amyloid accumulation and prevent these neurons from dying?

Is the protein build up and subsequent neuron death due to pathogens and the immune response to them? Maybe an anti infective could help slow neurodegenerative progression, like how antivirals lowered the incidence of Alzheimer’s in the group who took them long term vs the group that didn’t.

As far as proving any of this clinically it seems like time and time again we find the “proof” in corpses but don’t have the technology to observe the physical change in living people besides obvious symptoms. (Ie enteroviruses in ME patients brains, herpes virus lesions in Sophia Mizras spine etc.)
 

Rufous McKinney

Senior Member
Messages
13,249
It’s amazing how the pathologies of so many differently labeled diseases all seem to overlap

I don't think thats particularly amazing...I see so many inter-connections between various versions of ME and other odd diseases....perhaps bodies have a repetoire of responses to a whole slew of things, which are in fact all variations of some theme. Just depends on what part of the brain is swollen up at any particular time..

So I have 10 Provigil I bought, a nooptropic which: is supposed to wake up the narcoleptic. I' ve yet to take one as apparently, I'm nervous about it, plus never feel good enough to care to: be MORE AWAKE. So if there is a permanent damage to key neurons, wonder how the nootropics like Provigil: work.
 

Rufous McKinney

Senior Member
Messages
13,249
Modafinil has helped a lot of people in this forum, but I dont balme you for being hesitant. It is a drug, and everyone reacts differently.

Its just pretty funny: my doctor gave me the scrip, to get thru the airport and I don't even try it.

the Notion of being: like fully AWAKE...seems to me to be counter-intuitive and therefore scary.

What I was GOING to do was figure out if I could actually get it here, for less money.

So I flunked that assignment. Instead I tried to get LDN, can't, and not only can't: I cannot even ask a friend to Fed Ex my own pills to me: they will stop it apparently. G-F.

I did ask in a thread: about experiences with Modafinil and received few responses. Later i seem to recall reading it might help strengthen veins...in which case maybe thats a GOOD THING.
 

Sidny

Senior Member
Messages
176
So if there is a permanent damage to key neurons, wonder how the nootropics like Provigil: work.
I don’t think Provigil working excludes that key neurons haven’t been damaged it just may improve the functioning of ones that haven’t been compromised.

https://en.m.wikipedia.org/w/index.php?title=Modafinil&action=edit§ion=11
As of 2017, the therapeutic mechanism of action of modafinil for narcolepsy and sleep-wake disorders remains unknown.[34][35] Modafinil acts as an atypical, selective, and weak dopamine reuptake inhibitor which indirectly activates the release of orexin neuropeptides and histamine from the lateral hypothalamus and tuberomammillary nucleus, respectively all of which may contribute to heightened arousal.[34][35][36]
https://en.m.wikipedia.org/wiki/Modafinil#cite_note-pmid22640618-36
 

grapes

Senior Member
Messages
362
My fatigue and brain fog is mostly in the afternoon, it starts around 11:30am and gets better around 5pm. The worst part of the day is 2-5pm for me.

I'm wondering if anyone else experiences the same? I searched around on the forum but couldn't find much about people having similar experiences of having a consistent tiredness window. Let me know if you have the same!

I'm wondering why I would just be tired for that period of time and feel (mostly) ok in the mornings and night? I wonder what changes in the body at that time. If this is common, has there been any research in this area?

A few things I've already checked
  • I've gotten blood sugar checked, wearing a "patch" to monitor it for 2 weeks, that came back normal.
  • My adrenals are mostly ok, they are slightly off, but not drastically so. I respond really well to an "Adrenal complex" supplement with licorice root, which I take daily. I also do well with electrolyte/sea salt drinks.
  • As far as food, I've tried everything, paleo, keto, elimination, etc... nothing will change my fatigue window. I really don't think my fatigue is diet related, even though that theory is an easy go-to when you are talking about "afternoon fatigue".
Cortisol dips do that to me. I think that's what is going for me at 4 pm because my cortisol is high during the night, waking me up a lot. This it dips in late afternoon.
 

grapes

Senior Member
Messages
362
One obvious reason symptoms are worse in the afternoon has to do with the circadian rhythm of the cortisol hormone. In the morning it is higher so inflammatory symptoms are lowered/suppressed. As it drops they increase. It indicates high inflammation is present.

Cortisol-High-Early-Morning.jpg
That is actually a possibility. When I experience a PEM crash, it seems to mess up my adrenals with high cortisol at night waking me up and low by 4 pm or so with major fatigue and sleepiness for a couple of hours.
 

Wishful

Senior Member
Messages
5,684
Location
Alberta
The cortisol crash is pretty, but it doesn't explain why my ME symptoms abruptly get worse at 2:30 PM and then drop back over a few more hours. Definitely not as simple as cortisol level, at least for me.
 

grapes

Senior Member
Messages
362
Well, it could explain your situation (though I know it could be something else for you). With the normal circadian rhythm of cortisol, it's the highest in the mornings which wakes us up, still higher the rest of the morning, then decreases a lot in the afternoon, and is the lowest in the evening to help us fall asleep.

But stress can mess that up. In an adrenal group I belong to, some people whose adrenals are stressed can have a one time result on a cortisol saliva test where it falls super low. I saw one girl who just had a super low noon only when it should have been higher. It reminds me of a possibility for you.

I also saw one woman who had high cortisol in the morning and noon, then low in the late afternoon. And that seems to fit me, too.
 

Wishful

Senior Member
Messages
5,684
Location
Alberta
The width of my 2:30 PM worsening seems a lot narrower than the graph suggests. That doesn't rule cortisol out as a possibility, but I don't feel that it's a strong possibility either.
 

grapes

Senior Member
Messages
362
The width of my 2:30 PM worsening seems a lot narrower than the graph suggests. That doesn't rule cortisol out as a possibility, but I don't feel that it's a strong possibility either.

No, don't go by that graph. There are many versions of having low cortisol that the graphic doesn't represent!! I've seen all sorts of adrenal saliva cortisol tests and they are very varied as to how someone has low cortisol. And by the way, today is the FIRST day this week that I didn't crash at 4 pm, all because I raised the cortisol I'm on!! With all I've seen, I just knew that it's what was going on for me.

I hope this is good food for thought, at least.
 
Messages
34
umm. so thats interesting, as Dr. Phair also thinks our dopamine pathways are metabolically trapped..but has yet to study that one....
This is possible. Dopamine/catecholamines requires b6, magnesium, vitamin C, and copper enzymes. For those with COMT then it requires Sam-E. Lots of possible pitfalls.
 

pattismith

Senior Member
Messages
3,931
Circadian rhythm doesn't impact cortisol level only,

between 11AM and 2 PM Orexin decreases in the brain, Melatonin raises in the brain, Blood Pressure decreases, Histamine and Dopamine raise in the brain.

My brain fog is related to a sleepy state, and it clearly picks very quickly after 11 AM.

Low Dopamine is associated with restless legs, headache, hyperalgesia/allodynia, which I have all so I know it's a problem for me.

If I take Methylphenidate in the morning, my pain drops immediately and I can be awake for 3 hours.
But after 11 AM, I need twice the morning dose to stay awake and fight the sleepiness/brain fog/headache/pain state.


1609569151049.png


1609569379648.png


Frontiers | Plasma Orexin-A Levels Do Not Undergo Circadian Rhythm in Young Healthy Male Subjects | Endocrinology (frontiersin.org)

1609572297658.png


this graph is from a schizophrenia study, but I took it to show the lowest Dopamine at 12 AM

Schizophrenia: the role of sleep and circadian rhythms in regulating dopamine and psychosis in: Reviews in the Neurosciences Volume 27 Issue 7 (2016) (degruyter.com)