Ferroptic Illnesses: Translating complex biology into bedside-ready diagnostics for ME/CFS, Long COVID, and related syndromes
A New Framework for Diagnosing Fatigue in Long COVID, ME/CFS, POTS, MCAS and endometriosis.
By Jessina Graham, NP
Endocrinology and Internal Medicine experience| Bedside Integration
Over the past few years, many of us in medicine have witnessed a surge of patients (often women) presenting with life-altering fatigue, autonomic dysfunction, chronic pain, and immune dysregulation. Their lab work frequently returns as "normal," leaving both provider and patient in diagnostic limbo. But what if "normal" isn’t normal enough?
I've spent years tracking these cases—quietly, longitudinally—across post-viral syndromes, connective tissue disease, and hormonal dysregulation. From my unique clinical lens, I’ve built a diagnostic framework that integrates:
Intracellular iron deficiency from sympathetic overdrive
Functional vitamin B6 (PLP) deficiency
Mitochondrial redox stress
Zinc/copper dysregulation secondary to mast cell activation
All converging to explain fatigue and systemic dysfunction in ME/CFS, POTS, MCAS, endometriosis and Long COVID through sublethal ferroptosis, an iron dependent type of cell death. Neurodegenerative diseases are likely in this grouping as well, including Parkinson’s and Alzheimer’s. I call this a ferroptic terrain. Ferroptosis is acute cell death, but this is complex chronic illness. No one has framed this yet, as specialties were all too siloed to put the big picture together across organ systems. But they were all seeing the same signs.
I just published the foundational model as a peer-accessible preprint, and released a pair of 2-page handouts. One for providers, one for patients to bring the theory directly to the bedside. More needs to be done, but we start here.
Key Points from the Paper
Sympathetic overdrive depletes intracellular iron, impairing heme synthesis
Functional B6 loss limits mitochondrial processing, even with normal serum B6
Elevated oxidative stress shifts energy production away from efficient ATP generation
This cascade is invisible on standard serum labs but measurable using targeted panels
Zenodo DOI (Full Paper):
https://doi.org/10.5281/zenodo.15676616
What You Can Do Now
Clinicians:
Order serum PLP (active B6), ferritin, transferrin saturation, RBC zinc/magnesium
Consider plasma lactate:pyruvate ratios to assess mitochondrial redox status
Use ICD-10 codes for fatigue (R53.82), micronutrient deficiency (E61.9), and malabsorption (K90.9) to justify testing
Patients:
Ask about intracellular micronutrient panels or mitochondrial markers
Track symptoms like temperature instability, orthostatic intolerance, or sudden exercise crashes
Consider therapy with provider guidance depending on lab results.
Downloadable Resources
Ferroptic Illnesses: Patient and Provider Handouts
These tools are meant to be used, not just read. They’re built to help clinicians at every level recognize patterns that have been missed for decades—and to validate patient experience with biological clarity.
This Is Just the Beginning
This isn’t theory. It’s a deployable, clinically translatable framework. And it’s just the first of several models. If you’ve been told your labs are fine and your symptoms don’t add up—this work is for you.
More is coming.
With resolve,
Jessina Graham, FNP, C-NP
B.S. Zoology
Graham Medical Consulting
Grahammedicalconsultingllc.com
This was really helpful in understanding what's been happening. I began liver supplements earlier this year, and they have been huge for reducing small fiber neuropathy, reducing fatigue, and lowering resting heart rate. I've also been taking an antihistamine to reduce inflammation more recently. I have POTS, hEDS, MCAS, long covid, celiac, Graves, ME. Everything worsened when I moved to 7200ft. I need to move to a lower altitude to get my system out of sympathetic and into rest mode.
Thank you.