Oxidative Stress
Inflammation,
Elevated Cytokines
IL-1β, IL-6, IL-10, TNF-a
Inflammation,…
Hepcidin…
Low Iron
ssDNA Breakage, PARP ->
AP1, MAPK,
NF-kB ↑↑
ssDNA Breakage, PARP…
L-DOPA Decreased
Neurotransmitters, Blood Volume Impaired
Neurotransmitters, B…
Norepinephine, Epinephine Dysregulation
Norepinephine, Epine…
Fatty Acid Oxidation, Cori Cycle
Impaired
Fatty Acid Oxidation…
Postural Orthostatic Tachycardia Syndrome
Postural Orthostatic…
Histamine Increased
Backup Pathways to Succinyl-CoA, Succinate, Fumarate
Overused
Backup Pathways to S…
Mast Cell Activation Syndrome
Mast Cell Activation…
Hypovolemia,
Electrolyte Losses
Hypovolemia,…
Post-Exertion
(Lactic) Acidemia,
pH Shift Down
Post-Exertion…
Oxidized
Riboflavin Metabolite
Insufficiency
Oxidized…
Folate Metabolism, BH4 Impaired
Nitric Oxide ↓↓
Folate Metabolism, B…
Cholesterol Elevation,
BCAA Overuse,
Nitrogen Elevation
Cholesterol Elevatio…
Unproductive…
Complex II /
Succinate Dehydrogenase Impaired
Complex II /…
TCA Cycle Impairments
Acetyl-CoA…
Itaconate Pathway Activation
Itaconate Pathway Ac…
Pyruvate Dehydrogenase
Decreased
Pyruvate Dehydrogena…
Hypoxia Inducible Factors (HIF) Promoted
Hypoxia Inducible Fa…
Renal Function
Dysregulated
Renal Function…
LDH Increased, Lactic Acid
Increased
LDH Increased, Lacti…
Prolyl Hydroxylases
Decreased
Prolyl Hydroxylases…
Collagen Synthesis
Impaired
Collagen Synthesis…
Energy Deficiency
Intracellular
Pyridoxal-5′-Phosphate
Impaired
Intracellular…
Cell Membranes / Transporters Impaired, PEM,
Insulin Resistance
Cell Membranes / Tra…
Rouleaux, Thrombi,
Hypoxia, Metabolite Transport Impairment
Rouleaux, Thrombi,…
Low…
Thyroid Function
Decreased
Thyroid Function…
Low…
Low…
Excess Lead, Mercury, Uranium, Cadmium, Bismuth
Excess Lead, Mercury…
Glucose Metabolism
Impaired
Glucose Metabolism…
Low…
Low…
Muscle Weakness,
Gastroparesis
Muscle Weakness,…
Low…
Low…
Low…
Low…
Low…
Low…
Small Intestinal
Bowel Overgrowth, LPS
Small Intestinal…
Low…
Low…
Low…
Urea Cycle Dysregula…
Choline Increased, Acetylcholine Decreased
Choline Increased, A…
Cognitive…
Complex V Impaired,
ATP Decreased
Complex V Impaired,…
Low…
Figure 2.
Pathway Diagram: (High-Level) Hypothetical Disease Model for ME/CFS, Long COVID / Long Vaccine.
Pathway Diagram: (High-Level) Hypothetical Disease Model for ME/CFS, Long COVID / Long Vaccine.
Authors: Joshua Leisk, Aline Noçon ©2022, [DRAFT / INCOMPLETE – may contain errors]
Authors: Joshua Leisk, Aline Noçon ©2022, [DRAFT / INCOMPLETE – may contain errors]
ME/CFS: Correcting Chronic Mitochondrial Dysfunction
ME/CFS: Correcting Chronic Mitochondrial Dysfunction
cAMP,
Protein Kinase A
Impaired
cAMP,…
Borrelia, Bartonella
Infection, Opioids
Borrelia, Bartonella…
Vitamin D,
Vitamin A
Sufficiency
Vitamin D,…
(Pathogenic) GDH Elevation, as Direct Competition Against a-KGDH
(Pathogenic) GDH Ele…
v0.92
5-AR Inhibitors,
AR Antagonists
5-AR Inhibitors,…
Vitamin C…
Hyperoxaluria
Isocitrate Lyase Expressing Bacteria,
Glyoxylate Shunt
Isocitrate Lyase Exp…
D-Lactate Producing Bacteria
D-Lactate Producing…
Tyrosinase
Decreased, Tyramine Increased
Tyrosinase…
Dopamine Beta Hydroxylase
Insufficiency
Dopamine Beta Hydrox…
Clostridia1
Immune Deficiency,
T cell Exhaustion
Immune Deficiency,…
GABA…
Free Testosterone
Decreased
Free Testosterone…
Cortisol…
Peripheral Neuropathy
Estrogen…
Pathogenic &
Deficiency Based Pathway Promoters
Pathway Inhibitor
Pathogenic & Deficiency Base…
Lines intersecting at right
angles do not connect.
Lines intersecting at right…
Key:
ADP – Adenosine Diphosphate
AP-1 – Activator Protein-1
a-KGDH – alpha-Ketoglutarate Dehydrogenase
ATP – Adenosine Triphosphate
BH4 – Tetrahydrobiopterin
cAMP- Cyclic Adenosine Monophosphate
GABA – Gamma-Aminobutyric Acid
GDH – Glutamate Dehydrogenase
GI – Gastro-Intestinal
IDH – Isocitrate Dehydrogenase
HHV – Human Herpesviruses
HIV – Human Immunodeficiency virus
HYPDH – Hydroxyproline Dehydrogenase
LDH – Lactate Dehydrogenase
LPS – Lipopolysaccharides
MAPK – Mitogen Activated Protein Kinases
MDH – Malate Dehydrogenase
NF-kB – Nuclear Factor Kappa Beta
NO – Nitric Oxide
PARP – Poly (ADP-ribose) Polymerase
PEM – Post Exertion Malaise
PRODH – Proline Dehydrogenase
RR-MADD – Riboflavin-Responding Multiple Acyl-CoA Dehydrogenase Deficiency
ssDNA – Single Stranded DNA
TCA – TriCitric Acid
Th[#] – T Helper
Key:…
Intracellular Mineral Decrease, GI Absorption Blocked
Intracellular Minera…
Ferroportin, DMT-1 Decreased
Ferroportin, DMT-1 D…
1 Clostria Species – C. sporogenes, C.botulinum, C. caloritolerans, C. mangenoti, C. ghoni, C.bifermentans, C. difficile, C. sordellii
1 Clostria Species – C. sporogenes, C.botulinum, C. caloritolerans, C. mangenoti, C. ghoni, C.bifermentans, C. difficile,…
2 M.tuberculosis, C.albicans, P. indigofera, P. aeruginosa, A.calcoaceticus, S. Typhimurium, B. suis, Y. enterocolitica,
Y. pseudotuberculosis, Y. pestis, R. equi, E. coli., H. pylori strains P12, G27, 26, 695, Tx30a
2 M.tuberculosis, C.albicans, P. indigofera, P. aeruginosa, A.calcoaceticus, S. Typhimurium, B. suis, Y. enterocoli…
Complex III…
Complex I…
Complex IV…
ETF-QO…
NAD+ Redox…
FAD Redox…
Peroxynitrites ↑↑
BH4 Oxidation
Peroxynitrites ↑↑…
Low…
Acyl-CoA Dehydrogenases
Decreased, Mito Lipid Accumulation
Acyl-CoA Dehydrogena…
PRODH, HYPDH
Excess Activity
PRODH, HYPDH…
Innate Immune Respon…
Numerous
Pathogens –
eg. SARS-CoV-2,
Herpesviridae
Numerous…
Chronic Cranial Instability
Chronic Cranial Inst…
Lytic Reactivation
of Latent
HHV, HIV
Lytic Reactivation…
Riboflavin Kinase Decreased
Riboflavin Kinase De…
FAD Synthase Decreas…
Tinnitus, Myoclonus
Silicon…
SARS-CoV-2 Spike Protein, Fibrinogen
SARS-CoV-2 Spike Pro…
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