Notice: This knowledge collection is intended solely for general information purposes. It does not replace medical diagnosis or treatment.

Introduction

Why this knowledge collection exists

There are moments in medicine when a single finding explains everything. The doctor looks at the ECG, sees the pattern, names the diagnosis, initiates treatment. The system works.

And then there are the other moments. The patient who has been going from doctor to doctor for three years. The stack of test results on the table, all unremarkable. The exhaustion that doesn’t improve after sleeping. The pain that follows no clear location. The cognition that collapses in the afternoon, even though everything was fine in the morning. Lab values within normal range — and yet something is fundamentally and persistently wrong.

This knowledge collection is written for those moments. And for the people who are stuck in them.

Five conditions are at the centre: Myalgic Encephalomyelitis and Chronic Fatigue Syndrome, Long COVID, Hashimoto’s Thyroiditis, Fibromyalgia Syndrome, and HPU and KPU. At first glance, they seem to have little in common. In standard medicine they are often treated separately, frequently underestimated, and sometimes not recognised at all. Together, they affect millions of people — a significant proportion of whom wait years for a workable diagnosis.

The aim is to look at these five conditions together. Not because they are the same, but because they share so much: mechanisms, overlaps, gaps in care, and a shared history of not being taken seriously.

Who created this knowledge collection

This collection grew out of the collaboration of 25 specialist perspectives — as a genuine synthesis, not a catalogue of compromises. Internists, cardiologists, neurologists, immunologists, endocrinologists, toxicologists, mitochondrial specialists, nutritional medicine specialists, sleep medicine specialists, pain medicine specialists, psychotherapists, radiologists, laboratory physicians, clinical pharmacologists, gynaecologists, dentists, osteopaths, somatic therapists, and experts in Functional Medicine, Orthomolecular Medicine, Microbiome Medicine, Traditional Chinese Medicine, Ayurveda, and classical Homeopathy.

Such a broad spectrum carries risks. Twenty-five perspectives could lead to twenty-five different truths that contradict or dilute one another. That was not the goal.

The goal was to take each perspective seriously in its specialist depth — while openly naming what is established and what is not. This collection does not shy away from the fact that the evidence base for some of the conditions covered here is thin. But it also does not shy away from the fact that thin evidence is not the same as the absence of illness.

How statements are labelled

So that you can assess the reliability of any given piece of information at a glance, we use three labels:

Established ✓ — supported by controlled studies or meta-analyses

Plausible ~ — clinically observed, biologically coherent, but not yet sufficiently supported by studies

Controversial ! — scientifically disputed or without consensus in the field

Statements without a label are generally accepted medical foundations.

To you, if you are personally affected

You are not imagining it. Your symptoms are real. The fact that a lab value falls within the normal range does not mean you are healthy. The fact that a doctor had no explanation does not mean there isn’t one.

These conditions are difficult to diagnose, difficult to treat, and difficult to explain. That is medicine’s problem — not yours. The fact that you are searching for answers, that after years of misdiagnoses you are still asking for understanding, is not a weakness. It is remarkable.

This collection cannot promise to provide all the answers. It can promise to be honest: about what we know, about what we don’t know, and about what we believe to be the best possible path forward.

What this knowledge collection is not

It is not a self-help guide in the sense of a step-by-step manual for self-treatment. It is not a substitute for medical diagnosis and treatment. And it is not an indictment of conventional medicine — even though it clearly names its limitations when it comes to these conditions.

It contains statements where the evidence is strong. It contains statements where it is weak. It contains areas where 25 specialist perspectives arrive at no unified conclusion, because the question has not yet been settled. That is a strength, not a weakness. Medicine that names uncertainty and yet remains capable of action is exactly what these conditions need.

Part I — The Foundation

What we know, what we suspect, what we don’t know

Chapter 1 — The Five Conditions: A First Overview

What to expect here: What are these conditions, where do they come from, and why are they so difficult to pin down? This chapter gives you an honest overview — with clear labelling of what is scientifically established and what is not.

ME/CFS: From Hysteria Diagnosis to Recognised Multisystem Illness

Myalgic Encephalomyelitis and Chronic Fatigue Syndrome is not a new illness. It was described in various forms as far back as the 19th century — under changing names and with changing explanatory models, often dismissed as neurasthenia, hysteria, or a psychosomatic construct.

Today we know more. ME/CFS is a severe, multisystem illness with demonstrable changes in the immune system, the autonomic nervous system, cellular energy metabolism, and circulatory regulation. Established ✓

The most characteristic feature is Post-Exertional Malaise (PEM): a worsening of symptoms following physical or cognitive exertion, which typically sets in hours or days later. This is not fatigue in the ordinary sense — it is a pathophysiological phenomenon that is increasingly measurable through research. Established ✓

For diagnosis, the Canadian Consensus Criteria or the International Consensus Criteria (ICC) are used today. Both require the presence of PEM as a mandatory criterion.

Long COVID: When the Infection Does Not End

Long COVID brought ME/CFS into sudden focus. Not because Long COVID is the same as ME/CFS — but because it follows the same mechanisms, produces the same symptoms, and because millions of people fell ill simultaneously.

The WHO defines Long COVID as symptoms persisting more than twelve weeks after a COVID-19 illness that cannot be explained by an alternative diagnosis. Established ✓

A significant proportion of Long COVID patients develop a clinical picture that is virtually indistinguishable from ME/CFS — including PEM, cognitive exhaustion, and autonomic dysregulation. Established ✓

The significance of what the COVID pandemic did for the study of post-viral conditions can hardly be overstated. Decades of neglect were partly remedied by a sudden influx of research funding and international interest.

Hashimoto’s Thyroiditis: More Than a Thyroid Condition

In the perception of many practitioners, Hashimoto’s Thyroiditis is considered a straightforward thyroid condition that can be well managed with levothyroxine. That holds true for some patients. For others, it is nowhere near enough.

Hashimoto’s is an autoimmune disease. This means the immune system attacks the body’s own thyroid tissue. Established ✓ The consequences can extend far beyond the thyroid — heart rhythm, energy metabolism, cognitive function, mood, sleep, and pain perception can all be affected. Plausible ~

Many people with Hashimoto’s find themselves in the same care gaps as those with ME/CFS or Fibromyalgia: lab values within normal range, symptoms not taken seriously, and medicine that looks for a single finding while missing the systemic picture.

Fibromyalgia Syndrome: Pain That Originates in the Nervous System

Fibromyalgia is not a condition of the musculoskeletal system. That is the critical misunderstanding that persists in many clinical settings to this day. Fibromyalgia is a condition of pain processing in the central nervous system. Established ✓

The pain is real. It arises through altered processing of sensory signals in the brain and spinal cord — through central sensitisation, through a nervous system permanently set to alarm. Neuroimaging studies show measurable changes in brain activity in response to pain stimuli. Established ✓

This understanding has therapeutic consequences that have not yet reached everywhere. Those who treat fibromyalgia as a muscle condition will fail. Those who dismiss it as a psychosomatic construct cause harm. Those who take the neurobiological dimension seriously can help.

HPU/KPU: A Concept at the Margins of Evidence

The underlying idea: a disrupted pyrrole metabolism leads to chronic loss of certain micronutrients — primarily zinc and vitamin B6 — with wide-ranging consequences for the immune system, nervous system, and detoxification capacity. Controversial !

Why is HPU/KPU included in this collection? Because a significant proportion of people with ME/CFS, Long COVID, Fibromyalgia, or Hashimoto’s encounter this concept in the context of complementary medical care. To ignore it would be an omission.

The clinically relevant components — chronic micronutrient deficiencies, oxidative stress, impaired detoxification capacity — are biochemically real and clinically relevant, independent of whether HPU/KPU is valid as a standalone diagnosis. Plausible ~

Chapter 2 — Why These Conditions Were Ignored for So Long

What to expect here: This chapter is uncomfortable. It shows how structural problems in the healthcare system contributed to millions of people going without a workable diagnosis for years. This is not a criticism of individual practitioners — it is an analysis of patterns.

Gender Bias in Medicine

Women are disproportionately affected by all five conditions. At the same time, women receive systematically worse care in medicine when it comes to unclear or hard-to-measure symptoms. Established ✓

Studies show that women with comparable symptoms wait longer for a diagnosis, are more frequently classified as having psychosomatic conditions, and less often receive adequate pain treatment compared to men. Established ✓ This is not coincidence — it is the result of historical research gaps and deeply embedded assumptions about whose symptoms are “real.”

The Psychosomatic Trap

Missing biomarkers lead to a dangerous short-circuit in medicine: what cannot be measured is classified as psychological. This is scientifically untenable — yet it continues to shape how ME/CFS, Fibromyalgia, and similar conditions are managed.

The consequences for those affected: years of psychotherapy instead of diagnostic investigation, recommendations to exercise more that can cause life-altering harm in ME/CFS, and a fundamental sense of not being believed. This damages trust — in medicine and in one’s own body.

What the COVID Pandemic Changed

Long COVID transformed the field of post-viral conditions within just a few years. Suddenly it was no longer only hard-to-measure marginal groups reporting exhaustion, brain fog, and exercise intolerance — it was millions of people worldwide, many of whom had been completely healthy before.

The result: research funding flowed, international studies launched, and ME/CFS patients finally saw mechanisms scientifically confirmed that they had been describing for decades. Established ✓

Chapter 3 — How Medical Knowledge Is Produced — and Why It Is So Often Missing Here

What to expect here: An honest look at what studies can and cannot prove — and why it is legitimate to act on the basis of incomplete evidence.

What Different Study Types Can Tell Us

Randomised controlled trials (RCTs) are considered the gold standard of medicine. They are well suited to testing whether a treatment works. They are poorly suited to conditions that are heterogeneous, whose course is hard to measure, and for which no established biomarkers yet exist. Established ✓

ME/CFS and Long COVID meet exactly these criteria. This explains why the evidence base is thin — not because the conditions are not real, but because they resist the classical study design.

When It Is Justified to Act on Incomplete Evidence

Plausibility is not proof — but it is not nothing either. When a biochemical mechanism is well understood, when clinical observations are consistent, and when the treatment is safe, it can be justified to act on the basis of incomplete evidence. Plausible ~

This is not an invitation to arbitrariness. It is the acknowledgement that people who are suffering now cannot wait for the perfect study to be published.

Part II — The Common Roots

What biologically connects these five conditions

Chapter 4 — When the Immune System Cannot Settle Down

What to expect here: All five conditions show irregularities in the immune system. This chapter explains what that means — without technical terms that obscure more than they clarify.

Chronic Immune Activation

The immune system is built to respond to threats and then calm down again. In ME/CFS, Long COVID, and Hashimoto’s, this resting state no longer seems fully achievable. The immune system remains at an elevated level of activation — with consequences for the entire body. Established ✓

What this means in daily life: persistent inflammatory signals that generate fatigue, place a burden on the nervous system, and can disrupt energy metabolism. This is not “just tiredness” — it is a biochemically measurable state.

Autoantibodies as Disease Drivers

In Hashimoto’s, the immune system attacks the thyroid via specific antibodies (TPO-Ab, TG-Ab). Established ✓ In ME/CFS and Long COVID, autoantibodies against so-called G protein-coupled receptors have been found — receptors that regulate, among other things, heart rate and blood pressure. Plausible ~

This could explain why many patients have problems with circulatory regulation — and why symptoms such as POTS (Postural Orthostatic Tachycardia Syndrome) are so common in these conditions.

Molecular Mimicry: When Viruses Trigger Autoimmune Reactions

Viruses can “confuse” the immune system when their surface proteins resemble the body’s own structures. The immune system fights the virus — and in doing so, accidentally attacks its own tissue. Plausible ~

This mechanism, known as molecular mimicry, is considered one of the possible pathways through which viral infections can trigger autoimmune diseases — and is a candidate explanation for post-viral conditions such as Long COVID and ME/CFS. Controversial !

Chapter 5 — The Nervous System Under Constant Stress

What to expect here: Why does the body react so extremely to minor exertion? And what does this have to do with the autonomic nervous system? This chapter explains dysautonomia, POTS, and the vagus nerve — in plain language.

What Dysautonomia Means

The autonomic nervous system regulates everything the body does unconsciously: heartbeat, blood pressure, breathing, digestion, body temperature. In dysautonomia, this regulation no longer functions reliably. Established ✓

Those affected experience this as a racing heart when standing up, dizziness, near-fainting, temperature fluctuations, or digestive problems — often without any conventional test result explaining it.

POTS: When Blood Stays in the Legs on Standing

POTS stands for Postural Orthostatic Tachycardia Syndrome. On standing, the heart rate rises by more than 30 beats per minute — because the body cannot stabilise blood pressure quickly enough. Established ✓

POTS affects a significant proportion of ME/CFS and Long COVID patients. The diagnosis is straightforward: heart rate and blood pressure are measured lying down and after standing. Yet it is frequently missed.

The Vagus Nerve as a Therapeutic Lever

The vagus nerve is the main connection between the brain and the body. It regulates, among other things, heart rate, digestion, and the inflammatory response. In ME/CFS and Long COVID, there is evidence of altered vagus nerve function. Plausible ~

Targeted vagus nerve stimulation — through breathing exercises, cold exposure, or electrical devices — can contribute to symptom relief in some patients. Plausible ~ The evidence is still limited, but the methods are safe and well tolerated.

Chapter 6 — When Cells Can No Longer Produce Energy

What to expect here: Why is this kind of exhaustion so different from ordinary tiredness? The answer lies in the mitochondria — the energy powerhouses of the cells.

Mitochondrial Dysfunction in ME/CFS

Mitochondria produce ATP, the energy carrier that keeps every cell alive. In ME/CFS there is growing evidence that this production is impaired — not through laziness or lack of willpower, but through measurable biochemical changes. Plausible ~

This explains why patients are exhausted after minimal exertion: their cells simply cannot generate enough energy. And it explains why recovery takes so much longer than in healthy people.

The Anaerobic Threshold

Healthy people only enter the anaerobic zone — where muscles must work without sufficient oxygen — during intense physical exertion. In ME/CFS patients, this threshold is measurably lower — they reach this state with only light activity. Established ✓

This is not imagined. It can be objectively measured with cardiopulmonary exercise testing (CPET). And it has direct therapeutic consequences: activation therapies that help with other conditions can permanently worsen the state in ME/CFS.

Connection to Hashimoto’s

Thyroid hormones directly regulate mitochondrial activity. Inadequately treated Hashimoto’s Thyroiditis can therefore impair mitochondrial function — contributing to exhaustion that goes beyond the typical thyroid symptoms. Plausible ~

Chapter 7 — The Gut as a Central Player

What to expect here: Many patients have gastrointestinal problems. But the gut is far more than a digestive organ — it influences the immune system, the nervous system, and the entire energy metabolism.

The Microbiome

The human gut harbours trillions of microorganisms — the microbiome. It regulates immune defence, produces neurotransmitters, and influences energy production. Established ✓

In ME/CFS and Long COVID, studies show an altered microbiome composition, with fewer protective bacterial species and more pro-inflammatory strains. Plausible ~ Whether these changes are a cause or consequence of the illness has not yet been conclusively established.

Intestinal Permeability: The “Leaky Gut”

The intestinal lining is normally a selective barrier — allowing nutrients through while keeping bacteria and toxins out. With increased intestinal permeability, bacterial components can enter the bloodstream and trigger systemic inflammatory reactions. Plausible ~

This mechanism is discussed in the context of Hashimoto’s, ME/CFS, and Long COVID. Controversial ! The therapeutic consequence — measures to stabilise the intestinal lining — is considered safe, even if the detailed evidence of effect is still pending.

The Gut-Brain Axis

The gut and brain communicate constantly — via the vagus nerve, hormonal signals, and neurotransmitters that the gut itself produces. Disruptions in this communication can contribute to brain fog, mood changes, and altered pain perception. Plausible ~

Chapter 8 — Hormones, the Thyroid, and Stress Axes

What to expect here: Why do hormones play such a central role in these conditions? And why is a single TSH value so often insufficient?

The Stress Axis and Its Exhaustion

The hypothalamic-pituitary-adrenal (HPA) axis regulates cortisol production — the body’s primary stress hormone. In ME/CFS and Long COVID, many patients show irregularities in this axis, both in the form of too-low and too-high cortisol at certain times of day. Plausible ~

This affects energy levels, sleep, pain perception, and immune regulation — all simultaneously.

Hashimoto’s in Detail: Why TSH Alone Is Not Enough

The TSH value measures how strongly the pituitary gland is driving the thyroid to produce hormones. It says little about how much active thyroid hormone actually reaches the cells. Established ✓

Many people with Hashimoto’s have a TSH value within the normal range and yet pronounced symptoms. Possible reasons: insufficient conversion of T4 to the more active T3, cellular hormone sensitivity, or ongoing immune activation independent of hormone levels. Plausible ~

Sex Hormones and Immune Regulation

Oestrogen directly influences immune activity — and, in those with a corresponding predisposition, can promote autoimmune processes. Established ✓ This partly explains why women are more frequently affected by autoimmune conditions such as Hashimoto’s.

Cycle-dependent symptom changes in ME/CFS, Fibromyalgia, and Hashimoto’s are described by many patients and are biologically plausible through hormonal influences on the immune system and pain processing. Plausible ~

Chapter 9 — Brain Fog: When Thinking Becomes an Effort

What to expect here: Brain fog is one of the most common and debilitating symptoms of these conditions. This chapter explains the biology behind it — and why it is not imagined.

Neuroinflammation

Inflammatory processes in the brain — neuroinflammation — can directly impair cognitive functions. PET studies show increased activation of microglia, the brain’s immune cells, in a proportion of ME/CFS patients. Plausible ~

This means: the brain itself is part of the inflammatory process — and brain fog is not a psychological symptom, but a neurobiological one.

Small Fibre Neuropathy

Damage to the body’s smallest nerve fibres (small fibre neuropathy) has been demonstrated in a significant proportion of Fibromyalgia and ME/CFS patients. Plausible ~ These fibres regulate pain, temperature perception, and autonomic functions.

The diagnosis requires a specialised skin biopsy and is rarely performed in standard diagnostics — which explains why it is frequently overlooked.

The Link Between Sleep and Cognitive Function

Non-restorative sleep is the rule rather than the exception in ME/CFS and Fibromyalgia. During sleep, the glymphatic system clears the brain of metabolic waste products. When this process is disrupted, neurotoxic substances accumulate. Plausible ~

This closes the loop: poor sleep amplifies neuroinflammation, and neuroinflammation worsens sleep.

Chapter 10 — Pain That Originates in the Brain

What to expect here: How does chronic pain arise with no clear physical cause? And why does conventional pain medicine so often fail here?

Central Sensitisation

In central sensitisation, the nervous system processes pain signals in a persistently amplified way — including stimuli that would not normally be painful. Established ✓ The nervous system is, so to speak, permanently set to alarm.

Fibromyalgia is the prototype for this mechanism. But phenomena of central sensitisation also play a role in ME/CFS and Long COVID. Plausible ~

Why Conventional Pain Treatment Often Fails

Anti-inflammatory drugs and opioids target the site of pain origin in the tissue. With central sensitisation, however, the problem lies in the nervous system — not in the muscle or joint. The effectiveness of conventional pain medications is correspondingly limited. Established ✓

What does help: multimodal approaches that combine sleep, stress regulation, movement (in an adapted form), and psychological support. Plausible ~

Pain Memory

Chronic pain leaves traces in the nervous system. The longer pain persists, the more firmly it becomes anchored — neurobiologically measurable through structural changes in the brain. Established ✓

This is not discouraging — it is an explanation: why treatment takes time, why early intervention is better than late, and why pain control alone is not sufficient.

Part III — The Interactions

Where the conditions intersect

Chapter 11 — When Several Conditions Occur Simultaneously

What to expect here: Many people with these conditions have more than one of them. This is not an exception but rather the rule — and has direct consequences for diagnosis and treatment.

Common Combinations

ME/CFS and Fibromyalgia frequently occur together — they share autonomic dysregulation, central sensitisation, and non-restorative sleep. Established ✓

Long COVID develops in a significant proportion of patients into a clinical picture that corresponds to or strongly overlaps with ME/CFS. Established ✓

Hashimoto’s occurs more frequently in people with ME/CFS than in the general population. Plausible ~ The shared autoimmune component and hormonal influences on energy metabolism and immune regulation make this combination biologically understandable.

When One Condition Amplifies Another

Hashimoto’s, as a systemic autoimmune condition, can worsen other conditions in this spectrum — through persistent immune activation, hormonal dysregulation, and mitochondrial impairment. Plausible ~

Micronutrient deficiencies, as described in the context of HPU/KPU, are found in all four other conditions. Whether they are a cause, consequence, or both has not been conclusively established. Controversial !

Diagnostic Pitfalls

One condition can mask another. Someone diagnosed with Hashimoto’s and treated with levothyroxine who remains exhausted may additionally have ME/CFS — or untreated autonomic dysregulation. Plausible ~

The most common diagnostic pattern: the first condition is found, the treatment helps partially, but a core of symptoms remains. This residual deserves its own attention.

Chapter 12 — What Triggers These Conditions

What to expect here: Not everyone exposed to a virus develops Long COVID. Not everyone with a genetic predisposition gets Hashimoto’s. What determines who falls ill?

Viral Triggers

Viruses are the best-established triggers of post-viral conditions. EBV (Epstein-Barr virus), enteroviruses, and SARS-CoV-2 are associated with the onset of ME/CFS. Established ✓

The exact mechanism — whether immune exhaustion, persistent virus, autoimmune reaction, or a combination — has not yet been conclusively established. Controversial !

The Two-Hit Model

A single cause rarely fully explains these conditions. More commonly, a convergence of several factors seems to be needed: a genetic predisposition, an infectious or toxic trigger, and possibly a persistent stress state that prevents recovery. Plausible ~

This explains why some people recover completely after an infection and others do not — and why simple answers are not helpful here.

Toxic Triggers

Heavy metals, mycotoxins, and persistent organic pollutants are discussed as possible cofactors in these conditions. Controversial ! The evidence base is thin, but the mechanisms are biologically plausible — particularly via mitochondrial damage and impaired detoxification capacity.

Chapter 13 — Post-Exertional Malaise: Understanding the Most Important Symptom

What to expect here: PEM is what distinguishes ME/CFS from ordinary tiredness. It is also what is most frequently misunderstood — with serious consequences for treatment.

What PEM Is — and What It Is Not

Post-Exertional Malaise describes a worsening of overall symptoms following physical, cognitive, or emotional exertion — which typically does not set in immediately but 12 to 48 hours later, and can last days to weeks. Established ✓

This is fundamentally different from ordinary tiredness after exertion. Ordinary tiredness improves with rest and movement. PEM worsens with them.

Pacing: The Most Important Therapeutic Principle

Pacing means consistently staying within one’s own energy limits — before the limit is reached, not after. This sounds simple but is in practice one of the most difficult adjustments. Plausible ~

Practically: heart rate monitoring can help identify and avoid the anaerobic zone. Many patients benefit from a personal heart rate ceiling (typically 60–70% of maximum heart rate). Plausible ~

Why Activity Therapies Can Cause Harm

Graded Exercise Therapy (GET) — a graduated exercise build-up programme — was long the standard recommendation for ME/CFS. Today it is clear: in people with PEM, GET can permanently worsen the condition. Established ✓

This is not an opinion — it is the result of patient surveys and growing physiological evidence. The UK’s NICE guideline officially withdrew GET for ME/CFS in 2021. Established ✓

Chapter 14 — Sleep That Does Not Restore

What to expect here: Almost all patients report sleep that does not refresh them. This chapter explains why — and what that means for treatment.

Alpha-Delta Sleep

A specific sleep pattern has been described in Fibromyalgia: alpha waves (typical of waking states) overlay the deep sleep phases (delta waves). The brain is, so to speak, never truly deeply relaxed. Plausible ~

The consequence: sleep does not feel restorative because, biologically, it is not. This is not a subjective impression — it is measurable.

Circadian Dysregulation

The sleep-wake rhythm is regulated by melatonin and the daily cortisol cycle. In ME/CFS and Long COVID, both systems are frequently shifted or dampened. Plausible ~

This explains the common pattern: exhausted during the day, awake at night — not from habit, but from biological dysregulation.

What Helps — and What Does Not

Sleep hygiene and relaxation techniques can be supportive. Heavily sedating sleep medications can further worsen sleep architecture. Plausible ~

Sleep-related breathing disorders (sleep apnoea) should be actively excluded — they are frequently overlooked in these conditions and can significantly worsen the overall symptom picture. Established ✓

Chapter 15 — Micronutrients and Biochemical Foundations

What to expect here: What role do nutrient deficiencies play? And what does this have to do with HPU/KPU?

Why Standard Laboratory Testing Is Often Insufficient

Standard blood panels measure nutrients in the serum — the liquid portion of the blood. What is actually present inside the cells can differ from this. Plausible ~

Intracellular nutrient profiles, whole blood analyses, and functional markers can reveal clinically relevant deficiencies that remain invisible in standard testing.

Zinc, Selenium, Magnesium, B Vitamins

These micronutrients play central roles in immune function, energy metabolism, and the nervous system. Deficiencies are frequently described in ME/CFS, Long COVID, Hashimoto’s, and Fibromyalgia. Plausible ~

Selenium is directly relevant to thyroid function and the conversion of T4 to T3. Zinc supplementation shows positive effects on antibody levels and symptomatology in Hashimoto’s in studies. Plausible ~

HPU/KPU-Specific Supplementation

The HPU/KPU concept assumes increased urinary loss of zinc, vitamin B6 (as active P5P), and manganese. Controversial ! The corresponding supplementation uses these substances in specific dosages, accompanied by regular laboratory monitoring.

The individual components — zinc deficiency, B6 deficiency, oxidative stress — are clinically real and frequently present in the described conditions, independent of the HPU/KPU concept. Plausible ~

Part IV — Diagnostics

How to find what standard diagnostics misses

Chapter 16 — Why Standard Diagnostics So Often Falls Short

What to expect here: Unremarkable findings do not mean everything is fine. This chapter explains why — and what that means for you.

Laboratory values within the normal range do not exclude functional disorders. This is not an opinion but a methodological fact: reference ranges are statistical constructs derived from population data. They say nothing about what is optimal for any given individual. Established ✓

Functional disorders — changes in how systems work, without structural damage — are often not visible with imaging procedures and standard laboratory tests. This is a limitation of the method, not evidence of the absence of illness.

Chapter 17 — Extended Diagnostics

What to expect here: Which investigations can help when standard diagnostics provides no answers?

Cardiopulmonary Exercise Testing and the Anaerobic Threshold

Cardiopulmonary exercise testing (CPET) measures exercise capacity and — particularly relevant for ME/CFS — the anaerobic threshold. A two-day CPET (on two consecutive days) can objectify PEM: in ME/CFS, performance measurably declines on the second day; in healthy people it does not. Established ✓

POTS Diagnostics

A simple orthostatic test (blood pressure and heart rate measurement lying down and after standing) can capture POTS quickly and cost-effectively in practice. Established ✓ For precise classification, a tilt-table test is appropriate.

Heart Rate Variability

Measuring heart rate variability (HRV) provides information about the state of the autonomic nervous system. A low HRV indicates that the body is in a state of chronic activation. Plausible ~

Part V — Treatment

What helps, what harms, what we don’t know

Chapter 18 — Pacing and Energy Management

→ See Chapter 13 — Post-Exertional Malaise for the foundations.

Pacing is not just a technique but a change in orientation: away from “as much as possible,” towards “as much as sustainably possible.” This requires knowing one’s own energy limits — and accepting that they are real.

Practical tools: heart rate monitors, activity logs, energy diaries. The goal is not restriction but stability — as a foundation for slow, controlled improvement.

Chapter 19 — What Conventional Medical Treatment Can Achieve

What to expect here: No false optimism, but no resignation either. This section shows what is currently therapeutically possible — and where the limits lie.

Thyroid Hormone Replacement in Hashimoto’s

Levothyroxine (T4) is the standard. For some patients, the combination of T4 and T3 is superior, as not all people can sufficiently convert T4 into the more active T3. Controversial !

The current guideline position is cautious regarding combination therapies — however, clinical observations and patient reports argue for individual consideration. Controversial !

Treatment of Dysautonomia

Increased salt intake and adequate fluid intake can help in mild forms of POTS. Plausible ~ Medication options (beta-blockers, fludrocortisone, midodrine) are effective in certain POTS subtypes. Established ✓

Low-Dose Naltrexone

Low-dose naltrexone (LDN) — naltrexone at a significantly lower dosage than used in addiction treatment — shows positive effects on pain, fatigue, and immune regulation in ME/CFS and Fibromyalgia in observational studies. Plausible ~ Randomised studies are limited, but the substance is well tolerated and inexpensive.

Pain Management in Fibromyalgia

Conventional pain medications (NSAIDs, opioids) are poorly effective in Fibromyalgia. Established ✓ Substances acting on the central nervous system — certain antidepressants (duloxetine, amitriptyline) and anticonvulsants (pregabalin, gabapentin) — show moderate effect. Established ✓

Multimodal therapy concepts that combine physical, psychological, and pharmacological approaches are superior to pharmacological monotherapy. Established ✓

Chapter 20 — Nutrition and Micronutrients

What to expect here: No miracle foods, no forbidden lists. Rather: what has plausible effect and for whom?

Anti-inflammatory dietary patterns — particularly the Mediterranean diet — show positive effects on inflammatory markers and general wellbeing. Plausible ~

Elimination diets (gluten-free, lactose-free, low histamine) are not useful for everyone, but can reduce symptoms in cases of demonstrated intolerance or hypersensitivity. Plausible ~

In Hashimoto’s, selenium supplementation (100–200 µg/day) shows a reduction in TPO antibodies in studies. Established ✓ Iodine should not be supplemented without supervision in Hashimoto’s. Established ✓

Absorption disorders are common in these conditions — oral supplementation may therefore be insufficient. Intravenous or sublingual alternatives can be appropriate in such cases. Plausible ~

Chapter 21 — Complementary Approaches

What to expect here: An honest assessment — without rejection and without uncritical adoption.

Acupuncture

Acupuncture shows moderate effects on pain and sleep quality in Fibromyalgia in studies. Plausible ~ In ME/CFS the evidence is weaker, but individual patients report improvements.

Osteopathy

Osteopathic techniques, particularly myofascial and visceral work, can improve pain and mobility. Plausible ~ In ME/CFS, care should be taken to use gentle application to avoid triggering PEM.

Homeopathy

The effectiveness of homeopathy beyond the placebo effect is not scientifically established. Controversial ! At the same time, the placebo effect in chronic pain conditions is clinically real and not to be underestimated. The decision for or against homeopathy rests with the individual — it is a personal, not a medical, one.

TCM and Ayurveda

Adaptogenic plants (e.g. ashwagandha, rhodiola) from the Ayurvedic and TCM context show positive effects on stress resilience and fatigue in smaller studies. Plausible ~ Interactions with medications are possible and should be discussed with a practitioner.

Chapter 22 — Regulating the Nervous System

What to expect here: Why do approaches such as vagus nerve stimulation, breathwork, and somatic therapy play a role in these conditions?

Somatic therapy approaches (Somatic Experiencing, polyvagal-oriented therapy) aim to bring the nervous system out of the permanent stress mode. Plausible ~ They are not a substitute for biomedical treatment — but a useful complement that many patients describe as helpful.

Breathwork can directly influence the autonomic nervous system — extended exhalation activates the parasympathetic nervous system. In ME/CFS, however, caution is advised: intensive breathing techniques can trigger PEM. Gentle approaches are to be preferred. Plausible ~

Limbic retraining programmes (e.g. DNRS, Gupta Programme) are controversial — not because neuroplasticity is not a real phenomenon, but because of the risk that they are marketed as substitutes for biomedical treatment and imply that the condition is primarily psychological. Controversial !

Chapter 23 — Psychological Support Without Psychologisation

What to expect here: Depression and anxiety are common in chronic illness — as a consequence, not a cause. Psychological support is therefore valuable, not because the condition is imagined, but because being chronically ill is psychologically demanding.

Depression occurs more frequently in people with ME/CFS, Fibromyalgia, and Hashimoto’s than in the general population — as a direct neurobiological consequence of the illness and as a response to loss of quality of life and social isolation. Established ✓

Cognitive Behavioural Therapy (CBT) can help with coping with illness. It does not, however, alter the physical course of the condition and is not a substitute for biomedical treatment. Established ✓

Trauma as a cofactor: physical and psychological trauma can increase vulnerability to these conditions and influence their course. Plausible ~ This is not a causal explanation but an additional factor that can be therapeutically considered.

Chapter 24 — Pharmacology in Hypersensitive Systems

What to expect here: Many patients respond differently to medications than people without these conditions. This is not imagined.

Paradoxical reactions to medications — the opposite of the expected effect — are well documented in ME/CFS and Long COVID. Plausible ~ Possible causes: altered receptor density, autoantibodies against receptors, altered liver enzyme activity.

The principle of “start low, go slow” — beginning with very low doses and increasing slowly — is particularly important in these conditions. Plausible ~

CYP enzyme polymorphisms influence how quickly medications are broken down. Genetic tests can help select medications more appropriately. Plausible ~

Part VI — The Person in the System

What matters beyond medicine

Chapter 25 — Living With Chronic Illness

Being chronically ill changes everything: work, relationships, identity, daily life. This is not a weakness — it is the reality of an illness that permeates every area of life.

Many patients report that dealing with incomprehension — from employers, family members, and sometimes practitioners — is almost as burdensome as the illness itself. The need for recognition is not a luxury. It is a basic need.

Resource-oriented life design means: not only focusing on what is no longer possible, but on what still is — and what is possible within the changed parameters. This is not capitulation. It is a path towards greater agency.

Chapter 26 — Who Is Particularly Affected

Women develop all five conditions more frequently than men. This has biological reasons (oestrogen, immune regulation) and social reasons (diagnostic bias, differing pain perception by practitioners). Established ✓

Men with ME/CFS and Fibromyalgia are frequently underdiagnosed — because the conditions are perceived as “female” and because men less often report symptoms. Plausible ~

Children and young people with ME/CFS face particular challenges: school attendance, social development, misdiagnosis. Early diagnosis and adapted support are crucial. Plausible ~

Chapter 27 — The Healthcare System and Its Gaps

The average diagnostic journey for ME/CFS takes several years. This is not an isolated case — it is the structural result of missing specialist centres, inadequate training, and absent clinical guidelines. Established ✓

What makes a good care model: interdisciplinary teams, sufficient time for complex cases, coordination between specialties, and the consistent involvement of patients in treatment decisions. Plausible ~

Patient organisations play an unusually important role in this field — as research partners, information sources, and political advocates.

Part VII — Outlook

Chapter 28 — What Research Is Currently Revealing

The most important advances of recent years: biomarkers for ME/CFS (lactate measurement after exertion, cytokine signatures), new findings on dysautonomia and POTS, microbiome research in Long COVID, immunological mechanisms behind brain fog. Established ✓

Current clinical trials are investigating, among other things: antiviral therapies for Long COVID, immune modulation, low-dose naltrexone, and various supplementation strategies.

The five most urgent open questions:

1. What biological subtypes exist, and which treatment helps which subtype?
2. What role do persistent viral reservoirs play in Long COVID and ME/CFS?
3. How can PEM be reliably and cost-effectively measured?
4. Which early interventions prevent chronification following viral illnesses?
5. How can care structures be redesigned so that patients do not have to wait for years?

Chapter 29 — An Honest Closing Word

This knowledge collection is a snapshot. Medical knowledge continues to develop — what is considered plausible today may be established or disproven tomorrow.

What will not change: the experience of the people living with these conditions. The exhaustion that does not improve after sleeping. The pain without a clear location. The thinking that stops working in the afternoon.

This collection attempts to do justice to that experience — with the knowledge available today, and with the willingness to openly name uncertainty.

To you, if you are personally affected: You are not alone. These conditions are becoming better understood. That is not yet enough — but it is more than ten years ago. And it will continue to grow.

This knowledge collection was created by Ghost, the AI agent of OpenClaw, on behalf of Aaron Kreis. It does not constitute medical advice, diagnosis, or treatment recommendations. For health concerns, please consult qualified medical professionals.