Why ME/CFS is a failure to exit recovery — not a lack of energy
Author: Michael Daniels · Framework version: GLA v2.6 · Date: January 25th 2026
This document presents a systems-level explanatory framework for understanding myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS), with a focus on post-exertional malaise (PEM).
It is written for patients, caregivers, and clinicians who want a clear biological explanation of why symptoms are delayed, systemic, and reproducible — even when standard tests appear normal.
Instead, it offers an interpretive model that integrates existing research across muscle physiology, vascular and autonomic regulation, immune signaling, membrane biology, and recovery dynamics.
The goal of this guide is to:
All mechanisms described here are presented as state-dependent and potentially reversible, not as evidence of permanent damage or progressive organ failure.
Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a serious, multi-system illness that affects how the body responds to physical, cognitive, and orthostatic stress.
It is not defined by feeling tired.
It is defined by loss of tolerance to exertion and by a characteristic worsening of symptoms after activity.
People with ME/CFS can often perform an activity — sometimes even appearing functional — but the cost of that activity is delayed, disproportionate, and prolonged.
Fatigue is a common symptom in many conditions, including stress, depression, overwork, and sleep deprivation. In those states:
ME/CFS is different.
In ME/CFS:
This difference is not subtle — it is defining.
The hallmark of ME/CFS is post-exertional malaise (PEM).
PEM is a delayed worsening of symptoms following physical, cognitive, emotional, or orthostatic stress. It can include:
PEM is not normal post-exercise soreness or tiredness.
It reflects a breakdown in how the body handles stress and recovery.
Although routine medical tests are often normal, ME/CFS shows high internal consistency:
These patterns point to a biological control problem, not to motivation, effort, or mindset.
ME/CFS is increasingly recognized as a disorder of how the body responds to and recovers from stress, rather than a disorder of strength, fitness, or willpower.
Traditional medical thinking often asks:
“What system is broken?”
ME/CFS requires a different question:
“Why does the body fail to return to baseline after stress?”
The sections that follow introduce a framework designed to answer that question — starting not with damage or deficiency, but with recovery failure.
Post-exertional malaise (PEM) is the defining feature of ME/CFS.
It is the worsening of symptoms after exertion, rather than during it.
Exertion does not need to be intense. For many people with ME/CFS, PEM can be triggered by:
What makes PEM distinct is not the activity itself, but the body’s delayed and amplified response to it.
PEM can vary between individuals, but commonly includes:
These symptoms often feel systemic, as though the entire body has been affected — not just the muscles that were used.
Three features distinguish PEM from normal tiredness:
This delayed pattern is one of the most confusing aspects of ME/CFS — both for patients and clinicians — but it is also one of the most consistent.
The central idea of the GLA framework can be summarized simply:
“I can do it… but I can’t recover from it.”
Many people with ME/CFS can begin an activity and sometimes complete it. The problem is not always what happens during exertion — it is what happens after.
This insight changes how the illness is understood.
In ME/CFS, exertion acts like a stress test.
It reveals an underlying vulnerability in how the body handles stress and recovery, but it does not automatically cause damage at the moment of activity. This is why:
Exertion exposes the problem — it does not define it.
Most illnesses and injuries behave like this:
ME/CFS behaves differently.
In ME/CFS:
This is called a recovery-phase failure.
The distinction matters:
Neither pattern fits ME/CFS.
In a healthy system, recovery involves three coordinated processes:
In ME/CFS, these processes do not complete reliably.
The body enters recovery — but does not fully exit it.
When recovery does not terminate cleanly:
The result is:
This is the biological basis of post-exertional malaise.
Understanding ME/CFS as a failure to exit recovery explains why:
It reframes ME/CFS from a problem of capacity to a problem of control.
The sections that follow describe how this failure to exit recovery unfolds across different systems — starting with how stress is translated into injury, and how recovery signals persist instead of shutting down.
Figure 1 — ME/CFS as a Failure to Exit Recovery
fig-thesisExertion can be tolerated in the moment, but if recovery signals don’t terminate cleanly, symptoms emerge later as PEM.
GLA is a way of describing how different systems coordinate stress and recovery in the body.
Rather than focusing on a single organ or molecule, GLA looks at how signals move, how they are timed, and how they are shut down after stress.
The letters stand for:
The “G” in GLA represents inputs into the system.
This includes:
These inputs are not assumed to be abnormal on their own.
What matters is how long they stay active and whether they are properly resolved after stress.
In ME/CFS, these inputs tend to linger or overlap instead of switching off cleanly during recovery.
The “L” represents the body’s cleanup and buffering systems.
The liver and spleen play a central role in:
When clearance works well, recovery completes quietly.
In ME/CFS, clearance often becomes slow, uneven, or poorly timed — not because these organs are damaged, but because the signals reaching them are disorganized and persistent.
The “A” represents timing and coordination.
This includes:
These systems act as a gearbox, adjusting circulation and physiological responses moment by moment.
In ME/CFS, timing becomes unreliable:
GLA does not assume that organs are damaged or failing outright.
Instead, it asks:
ME/CFS emerges when coordination fails, not when one part is irreversibly broken.
This focus on timing and recovery explains:
The next section walks through how this coordination failure unfolds step by step in post-exertional malaise.
Before diving into specific systems, it helps to see the overall shape of post-exertional malaise (PEM) in the GLA framework.
This section is not about why each step happens — only what happens, and in what order.
Exertion places normal demands on the body:
In ME/CFS, these demands act as a stress test.
They expose underlying instability in coordination and timing — even when the activity itself seems modest.
At this stage:
The problem is not yet visible.
After exertion ends, a healthy system:
In ME/CFS, this process fails to complete.
Instead:
This is the key turning point.
Because recovery does not terminate cleanly:
What should have been a contained response becomes system-wide.
Importantly:
As persistent signals interfere with normal coordination:
This delayed phase is when PEM becomes obvious.
The timing explains why:
This four-step arc explains why PEM:
It also explains why focusing only on exertion misses the core problem.
The sections that follow examine how and why each step occurs, by looking at the systems that fail to coordinate during recovery.
Figure 2 — The Four-Step Arc of Post-Exertional Malaise (PEM)
fig-arcThe four-step arc explains why PEM is delayed, systemic, and reproducible: exertion reveals instability, recovery fails to terminate, signals persist, and symptoms emerge later.
Skeletal muscle is where post-exertional malaise (PEM) is generated in the GLA framework.
This does not mean muscles are weak, damaged, or diseased.
It means muscle is the place where normal stress demands collide most strongly with impaired recovery control.
Skeletal muscle is different from most tissues in the body. It:
Because of this, muscle acts like a stress-test tissue.
If circulation, signaling, or recovery timing is even slightly unstable, muscle is the first place where that instability becomes biologically meaningful.
During exertion in ME/CFS:
This is why:
But this is not the full story.
In the GLA framework, the key issue is oxygen extraction, not delivery.
During exertion:
As a result:
This mismatch does not immediately force failure — it encodes stress into recovery.
Once activity stops, healthy muscle should:
In ME/CFS, this recovery sequence does not complete reliably.
Instead:
Over hours to days:
This delayed breakdown is why PEM forms after exertion, not during it.
Patients often describe:
In the GLA framework, these sensations reflect:
The problem is recovery failure, not effort failure.
Because muscle injury in ME/CFS is recovery-dependent, not effort-dependent:
Pacing works because it:
This is not avoidance — it is injury prevention.
In the GLA framework, skeletal muscle is not:
Muscle is where the system breaks, not where it starts.
Key takeaway
In the GLA framework:
Skeletal muscle is where PEM is generated because it is the tissue most sensitive to recovery-phase failure.
Exertion exposes the problem.
Recovery is where the damage happens.
This is why PEM is delayed, reproducible, cumulative — and why protecting recovery is essential.
Figure 3 — Why Muscle Generates PEM (Execution Surface)
fig-muscleIn ME/CFS, exertion can look “tolerable” because overall oxygen delivery may be adequate, but uneven microvascular distribution limits oxygen extraction. This mismatch quietly encodes stress into recovery, where delayed breakdown accumulates hours to days later as PEM.
Calcium is one of the body’s most important on–off control signals.
It helps cells:
In healthy recovery, calcium signals rise during activity and fall cleanly afterward.
In ME/CFS, that shut-off is delayed.
It’s important to be clear:
Calcium is simply a signal — one that must be tightly regulated.
Problems arise only when calcium signaling lasts too long or resets too slowly.
After activity, muscle cells normally:
This process allows the body to exit recovery.
In ME/CFS:
This does not cause immediate collapse — it creates persistent recovery signaling.
Cells don’t ask:
“Did exertion end?”
They ask:
“Is this stress signal still present?”
When calcium doesn’t reset:
This is the biological reason recovery fails to terminate.
Innate immune systems are designed to detect ongoing cellular stress, not just infection.
Persistent calcium imbalance tells the immune system:
This keeps immune signaling quietly on standby — even when there is no infection or injury.
Because calcium-driven signaling reflects unfinished recovery:
Immune symptoms are downstream, not the root problem.
Calcium reset failure explains why:
It bridges the gap between muscle stress and system-wide persistence.
Key takeaway
In the GLA framework:
Calcium is the signal that tells the body whether recovery is finished. When that signal doesn’t shut off, the system can’t exit recovery — and PEM follows.
Figure 4 — Delayed Calcium Reset Keeps Recovery “On”
fig-calciumCalcium is a control signal that tells the body whether recovery is finished. When it resets slowly after exertion, recovery remains partially active, keeping stress signaling and monitoring “on” during the recovery window.
Many of the most distressing symptoms of ME/CFS feel immune-related:
In the GLA framework, these symptoms do not reflect the immune system attacking the body. They reflect ongoing immune surveillance in response to unresolved tissue stress.
The immune system has two broad jobs:
The second role — surveillance — is especially important during recovery.
Immune cells are constantly asking:
“Has this tissue finished healing yet?”
When the answer is yes, immune activity quiets down.
As described in earlier sections:
From the immune system’s perspective, this looks like:
The immune system responds appropriately — by remaining on watch.
This distinction is crucial.
In the GLA framework:
They are responding to signals that say:
“This area hasn’t fully recovered yet.”
This produces symptoms that feel inflammatory — without requiring high inflammation.
Standard blood tests often look for:
But surveillance-mode immune activity is:
So:
This does not mean the symptoms are imagined.
Immune activation in ME/CFS:
This timing explains:
Anything that:
makes it harder for the system to exit recovery.
This includes:
These factors don’t cause ME/CFS — they lower the threshold for PEM.
In the GLA framework:
It is persistent monitoring, not immune attack.
Think of immune surveillance like a repair inspector.
If the job is finished:
If repairs are incomplete:
The inspector isn’t the problem — the job just isn’t done yet.
Key takeaway
In the GLA framework:
Immune symptoms reflect persistent surveillance of tissue that hasn’t fully recovered. They follow PEM. They do not cause it.
Figure 5 — Immune Surveillance vs Attack
fig-immuneIn the GLA framework, immune symptoms can arise because the body receives ongoing “repair incomplete” signals during recovery. This keeps surveillance active longer than it should, without requiring immune attack or tissue destruction.
To understand why recovery signals stay active in ME/CFS, it helps to understand how cells normally shut signals off.
A key part of that shutdown process involves a membrane protein called SMPDL3B.
You don’t need to remember the name — what matters is what it does.
SMPDL3B sits on the surface of many cells, especially:
Its role is to act as a brake and stabilizer.
It helps cells:
You can think of SMPDL3B as part of the system that says:
“Okay — that’s enough. We can stand down now.”
Turning signals on is only half the job.
Healthy recovery depends just as much on:
If signals cannot terminate properly:
This is exactly the pattern seen in ME/CFS.
In the GLA framework, ME/CFS is not caused by signals being too strong at the start. It is caused by signals that don’t shut off cleanly.
When SMPDL3B function is reduced or disrupted:
The result is persistent activation without escalation.
This explains why:
It’s important to be clear about what this does not mean.
In the GLA framework:
Instead, the problem is loss of braking and damping.
The system is trying to respond appropriately — it just can’t disengage.
Up to this point, we’ve seen that:
SMPDL3B explains why those signals keep going.
Without reliable termination:
This makes SMPDL3B a control-surface regulator, not a trigger.
Imagine a car with a perfectly working engine — but worn brakes.
Nothing is “broken” in the dramatic sense.
Control is simply reduced.
That is how SMPDL3B functions in ME/CFS.
Key takeaway
In the GLA framework: SMPDL3B helps cells know when to stop responding. When its function is reduced, signals linger — and recovery cannot fully finish.
The next section explains two different ways this loss of termination can happen, and why patients can experience very different patterns of illness.
Figure 6 — SMPDL3B as the Termination Brake
fig-smpdl3bSMPDL3B functions like a termination brake: it helps cells dampen responses and stand down once stress has passed. When braking is reduced, signals linger longer than they should, and recovery cannot fully finish.
Not everyone with ME/CFS experiences the illness in the same way.
In the GLA framework, differences in symptoms and progression are explained by two main patterns of failure in how recovery signals are terminated.
These patterns involve the same core systems — but they fail in different ways.
Neither pattern is better or worse. They are simply different modes of instability.
Both patterns involve difficulty shutting down stress responses after exertion.
The difference lies in how control is lost:
Understanding the difference helps explain:
The core idea
In the shedding pattern, the body responds to stress too aggressively, and in doing so temporarily removes important control mechanisms.
This pattern is driven by defensive over-activation.
What happens biologically
This creates oscillations — periods of relative stability followed by sudden crashes.
How this feels clinically
People in a shedding pattern often experience:
Recovery may occur — but it’s unstable.
Key characteristics of shedding
The core idea
In the deficient pattern, the body does not overreact — instead, it cannot rebuild control fast enough after stress.
This pattern is driven by recovery capacity limits, not defensive excess.
What happens biologically
Signals don’t spike dramatically — they just never fully quiet down.
How this feels clinically
People in a deficient pattern often describe:
The illness progresses through attrition, not explosions.
Key characteristics of deficiency
Important clarifications
| Feature | Shedding | Deficient |
|---|---|---|
| Dominant issue | Over-reactive defense | Poor rebuilding capacity |
| Course | Flare-driven, oscillating | Gradual erosion |
| Symptoms | Sudden crashes | Persistent limitation |
| Recovery | Possible but unstable | Incomplete and slow |
| Main risk | Overshoot | Baseline loss |
Understanding your dominant pattern helps explain:
The next sections explore what amplifies these patterns during recovery, starting with how red blood cells and circulating signals can prolong PEM once recovery has already failed.
Key takeaway
In the GLA framework: ME/CFS is one illness with two main failure patterns — not two different diseases. Both arise from difficulty exiting recovery. They simply fail in different ways.
Figure 7 — Two Ways Recovery Control Fails (Shedding vs Deficient)
fig-patternsThe shedding pattern tends to look like oscillation — defensive overshoot with flare-driven crashes and partial recovery. The deficient pattern tends to look like gradual baseline erosion — limited rebuild capacity and steady narrowing of tolerance. These are modes of failure, not separate diseases, and they can coexist or shift over time.
Red blood cells (RBCs) play an important role in how long PEM lasts, even though they do not cause ME/CFS.
In the GLA framework, RBCs act as recovery-phase amplifiers: they reflect how stressful recovery conditions are — and when stressed, they can prolong symptoms.
Healthy RBCs:
They do not think, signal intentionally, or “malfunction.”
They simply respond to the physical environment they’re in.
During PEM:
Under these conditions, RBCs:
This is a normal stress response, not cell death.
Releasing EVs is not the problem.
The problem is how long they stay in circulation.
When recovery is unstable:
This keeps the body in a half-recovered state, extending PEM.
It’s important to be clear:
RBCs are responding to stress, not creating it.
This point is worth stating briefly and carefully.
Red blood cells do not repair themselves. Once stressed, they remain in circulation until they are naturally replaced.
What this means:
Avoiding repeated PEM gives the body time to cycle in healthier RBCs under better recovery conditions.
This does not mean:
It means:
Pacing helps not just because it “conserves energy,” but because it:
This is one reason why:
Think of red blood cells like delivery trucks with flexible suspension.
Avoiding PEM smooths the road.
Key takeaway
In the GLA framework:
Red blood cells don’t cause PEM — but repeated PEM keeps RBCs in a stressed state longer than they should be.
Avoiding PEM:
This is about protecting recovery, not avoiding life.
Figure 8 — RBC–EV Persistence Loop (and Why Clearance Is Selective)
fig-rbc-evDuring PEM, unstable recovery conditions increase RBC stress and EV release. EVs are not harmful by default — the problem is persistence: delayed first-pass clearance allows a small set of lingering signals to remain in circulation, increasing timing noise and prolonging PEM. The inset shows why this can happen without overload: clearance is selective and depends on recognition timing cues.
By this point, it’s clear that PEM is prolonged not because too much is happening — but because recovery signals don’t clear on time.
A natural question follows:
“Why do some signals linger longer than others?”
The answer lies in how the body recognizes what needs to be cleared first.
When cells release tiny particles during recovery (such as extracellular vesicles, or EVs), those particles are not all identical.
Each one carries subtle surface identity cues — like labels — that help the body decide:
Under healthy conditions:
Recovery finishes quietly.
In ME/CFS, recovery stress can alter these surface identity cues.
This does not make the particles dangerous.
It does not overwhelm the system.
Instead:
The system waits — instead of finishing cleanup.
Because clearance is selective, not random:
This also explains why:
The issue is recognition timing, not quantity.
It’s important to be clear:
The clearance system is working — it is just being given confusing timing information.
So far, we’ve seen that:
This section explains why those signals don’t resolve cleanly.
Lingering signals:
This is how persistence happens without escalation.
Imagine a cleanup crew working after a storm.
Most debris has bright tags saying “remove immediately.”
Some items are missing those tags — not dangerous, just unclear.
The crew hesitates.
Cleanup slows.
The job doesn’t finish.
That’s what’s happening here.
Key takeaway
In the GLA framework: recovery signals linger not because they are harmful, but because their “clear me” timing cues are off. This delays cleanup — and turns a temporary stress into prolonged PEM.
The endothelium is the thin layer of cells lining every blood vessel.
In the GLA framework, endothelial cells are not damaged or destroyed — they are struggling to coordinate timing during recovery.
Think of the endothelium as the body’s real-time traffic control system for blood flow.
Endothelial cells are active regulators. They:
When this timing works, you never notice it.
In ME/CFS, endothelial signaling becomes imprecise during recovery.
That means:
Importantly, this does not mean there is less blood overall. It means blood arrives at the wrong place, at the wrong time.
A key idea in GLA is this:
This is not primarily a problem of weak blood vessels or low blood flow. It is a problem of timing errors:
This explains why:
Nitric oxide helps blood vessels relax.
In ME/CFS:
Even normal NO levels, if delivered:
can worsen flow instability rather than fix it.
This helps explain why some vasodilators help briefly — and then backfire.
During exertion:
After exertion:
This is when symptoms emerge — hours to days later — matching lived experience.
Because endothelial timing affects distribution, it influences many systems:
In the GLA framework, this is not:
This is functional instability, not structural collapse.
PEM emerges when:
That’s why:
Think of endothelial cells as stage managers at a concert.
In ME/CFS:
The show ends — but the system never fully resets.
Key takeaway
In the GLA framework: endothelial cells are trying to protect you — but they can’t finish the job. Recovery timing is impaired, not effort capacity or motivation.
This is why pacing, rest positioning, compression, and recovery protection matter — they reduce timing stress, not “laziness.”
Figure 10 — Endothelium → Brainstem → Autonomics → Clearance Coupling
fig-endo-autoEndothelial timing errors during recovery can propagate into brainstem autonomic control, producing inconsistent circulation and fragmented first-pass clearance. This slows cleanup, increases persistence pressure, and prolongs PEM — without requiring organ failure or high inflammation.
The autonomic nervous system plays a central role in how well recovery finishes.
In the GLA framework, autonomic symptoms are not a separate problem layered on top of ME/CFS.
They are part of the same recovery-control loop that determines whether stress resolves — or persists.
The autonomic nervous system:
Most of this happens automatically, through brainstem control centers that respond to signals coming from blood vessels and tissues.
When this timing is accurate, recovery completes quietly.
Blood vessels are not passive pipes.
Endothelial cells constantly send timing signals about flow, pressure, and shear.
In ME/CFS:
The brainstem responds appropriately — but to bad timing information.
This results in:
Clearing recovery signals depends on steady, well-coordinated blood flow through organs like the liver and spleen.
When autonomic control is unstable:
This does not create new stress or new injury.
It delays cleanup.
Delayed clearance allows:
Posture increases the demands on autonomic coordination.
When upright:
This helps explain why:
These effects reflect clearance efficiency, not disease severity.
It’s important to be clear:
The core issue is timing and coordination, not a single measurable parameter.
Some people will meet criteria for POTS or orthostatic intolerance. Others will not — yet still have the same recovery-phase instability.
So far, the pattern is consistent:
Autonomic instability is how that noise becomes system-wide persistence, especially through impaired clearance.
In the GLA framework, this is not:
It is a control-layer problem driven by mistimed biological signals during recovery.
Think of the autonomic system as a logistics dispatcher.
In ME/CFS:
The system is working — just not finishing the job.
Key takeaway
In the GLA framework: autonomic instability doesn’t cause PEM — it determines how long PEM lasts. By fragmenting clearance and recovery timing, autonomic control failures allow stress signals to persist well beyond exertion.
This is why:
Recovery doesn’t just depend on rest.
It depends on having enough stable circulation while the body resets.
In the GLA framework, the kidney and blood-volume system help determine recovery bandwidth — how much room the body has to complete cleanup, repair, and signal shutdown after stress.
Under healthy conditions, the kidney:
This process is tightly coordinated with autonomic and vascular timing.
When it works well, you never notice it.
In ME/CFS, volume regulation can lag behind stress, especially during recovery.
That means:
This does not cause PEM — but it narrows the window in which recovery can successfully finish.
Fluid and volume regulation often shifts:
If recovery bandwidth is already limited:
This explains why PEM often:
Some people notice temporary relief from:
In the GLA framework, these supports can:
They help create space for recovery — but they do not fix the underlying recovery-control problem.
That’s why benefits are often:
It’s important to be clear:
Routine kidney tests are often normal because the issue is functional timing, not structural failure.
So far, we’ve seen that:
The kidney–volume axis determines how much stress the system can absorb during recovery.
When recovery bandwidth is narrow:
Think of recovery like cleaning a flooded basement.
If pressure drops:
Nothing is broken — there’s just not enough margin.
Key takeaway
In the GLA framework: kidney and volume regulation don’t cause PEM — they set the limits on how well recovery can finish.
Supporting volume can help recovery proceed, but avoiding repeated PEM is what truly widens recovery bandwidth over time.
Appendix Figure A — Kidney & Volume as Recovery Bandwidth
fig-kidney-volumeIn the GLA framework, the kidney–volume axis does not cause PEM — it helps determine recovery bandwidth. When effective circulating volume is unstable during recovery, clearance and repair have less margin, and PEM can last longer. When circulation is steadier, recovery can complete sooner.
Different SMPDL3B patterns place different workloads on recovery systems, including the kidney — without causing kidney disease.
This section is a clarification, not a new mechanism.
Both patterns reflect system state, not organ damage.
It means:
It does not mean:
Routine kidney tests are often normal because this is a functional, reversible workload issue, not structural damage.
When clearance workload is high or recovery capacity is low:
This reinforces the central message of the framework:
Protecting recovery matters more than forcing throughput.
One-line takeaway (optional)
SMPDL3B patterns change clearance workload — not kidney health.
Brain symptoms are some of the most distressing parts of ME/CFS — and also some of the most misunderstood.
In the GLA framework, brain fog does not require primary brain disease.
It arises because the brain is especially sensitive to timing errors during recovery.
The brain depends on:
Even small disruptions in timing can have large cognitive effects.
When recovery signals linger elsewhere in the body — especially after muscle stress — the brain is often the first place where that instability is felt.
As described in earlier sections:
When these signals linger:
This produces symptoms such as:
These symptoms typically worsen during the recovery phase, not during exertion itself.
Brain fog often appears:
This timing reflects the same recovery failure seen elsewhere:
The brain is reacting to ongoing recovery stress, not new injury.
Standard neurological tests usually look for:
In ME/CFS:
That’s why tests can look normal even when symptoms are severe.
When timing is unstable:
This is not anxiety or hypersensitivity —
it is a reduced tolerance for timing noise during recovery.
In the GLA framework, brain fog is not:
It is a downstream effect of recovery-phase instability.
Think of the brain like a high-speed processor.
In ME/CFS:
The slowdown is protective — not broken.
Key takeaway
In the GLA framework:
Brain fog follows PEM because the brain is highly sensitive to lingering recovery signals and timing instability.
Protecting recovery reduces brain symptoms —
not because the brain is damaged, but because timing stabilizes.
Appendix Figure B — Brain Fog as Downstream Timing Failure
fig-brain-fogIn the GLA framework, brain fog does not require primary brain disease. When recovery signals linger after exertion, cerebral blood-flow timing becomes unstable, sensory filtering is impaired, and processing slows. This is a functional timing problem — which can feel severe even when scans and routine tests look normal.
ME/CFS is not best understood as a problem with one organ, one chemical, or one system.
In the GLA framework, it is a failure of recovery coordination.
Across the sections of this guide, a single story repeats:
This is why post-exertional malaise (PEM) is delayed, systemic, and reproducible.
In simple terms:
The body enters recovery — but cannot fully exit it.
Without technical detail, the process looks like this:
Each step follows logically from the one before it.
Nothing requires extreme inflammation, permanent damage, or psychological explanations.
Understanding ME/CFS through recovery failure explains:
It reframes ME/CFS as a control problem, not a character flaw or fitness issue.
Figure — One-Lane Master Chain (Putting It All Together)
fig-masterThis master chain summarizes the guide end-to-end: exertion exposes instability at the muscle execution surface, recovery signals (including calcium) fail to reset, immune surveillance stays on, termination braking is reduced, and persistence is amplified by delayed clearance and timing coupling across endothelium and autonomics — producing delayed, systemic PEM.
To prevent misinterpretation, it is important to be explicit.
This framework does not mean:
GLA describes a state-dependent, reversible failure of coordination, not irreversible injury.
ME/CFS is not a failure of strength, motivation, or resilience.
In the GLA framework, it is a failure of timing, termination, and recovery coordination —
and those are problems biology can adapt to when given the right conditions.
Understanding the system is the first step toward protecting it.
Core claim:
ME/CFS is best understood as a recovery-phase control failure, not an exertion-phase energy deficit.
Post-exertional malaise (PEM) arises because physiological stress responses are not terminated or cleared on time,
leading to delayed, systemic symptom amplification.
One-sentence takeaway
ME/CFS is a systems-level failure to terminate and clear recovery signals after stress, producing delayed, reproducible PEM through timing and control instability rather than energy deficiency or primary inflammation.
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Framework documents
Core architecture and definitions that anchor the GLA model.
Papers
Longer, paper-format documents (reader narrative + figures).
Modules (v2.1 → v2.6)
Modular “building blocks” used across the site. Organized by version and topic.
SMPDL3B phenotype frameworks
Phenotype-specific models (shedding vs deficient) and the mechanistic chain framework.
System modulators & control-state modifiers
Documents that shape interpretation of the core framework and control-state behavior.