Health Research — Map of Content

Personal health research vault. Cross-referenced notes covering iron metabolism, neurodevelopment, mineral interactions, gut-brain axis, and clinical management.
Patient: Anthony G. | Age: 37 | Key conditions: AuDHD (ADHD-PI + Autism), Trichotillomania, HFE C282Y/H63D compound heterozygote

Lab Results

• Blood Results - December 2025 — comprehensive health assessment: ferritin 738, low folate, thyroid/HbA1c normal, RHR 88bpm, body composition
• Blood Results - March 2026 — iron studies + minerals: TSAT 60%, ferritin 380 (↓48%), low-normal copper/zinc, HFE confirmed

Genetics

• HFE Compound Heterozygosity — genotype analysis, penetrance data, emerging research
• HFE Compound Het - Disease Associations Beyond Iron — full disease association map: HCC (HR 5.25), colorectal cancer, arthritis, ALS, PCT, diabetes, QoL
• Genetic Architecture of AuDHD — shared genetics across ADHD, autism, TTM, iron; COMT, MTHFR, dopamine/serotonin genes, pharmacogenomics, GWAS overlap, pathway convergence

Iron Metabolism

• Transferrin Saturation - Clinical Significance — TSAT 60%, NTBI thresholds, guidelines
• Iron Overload and NTBI — non-transferrin bound iron, toxicity mechanisms
• Ceruloplasmin and Ferroxidase Activity — copper-iron export axis
• Tryptophan-Kynurenine Pathway — iron-driven inflammation → serotonin depletion → glutamate excitotoxicity
• research/Hepcidin and Brain Iron Regulation — astrocyte-derived hepcidin, BBB iron gating
• research/NTBI in the Brain — NTBI crossing BBB, CSF iron handling
• research/Ferroptosis and Neuronal Iron — iron-dependent cell death, GPX4/System Xc-
• research/Iron Chelation Therapy - Deferiprone — brain-penetrant chelator, neuroprotective studies

Neurodevelopment

• Iron-Dopamine-ADHD Axis — tyrosine hydroxylase, brain iron, HFE + ADHD intersection
• HFE Variants and Brain Iron — C282Y/H63D effects on CNS iron distribution
• Elvanse and Mineral Metabolism — lisdexamfetamine, appetite, mineral monitoring
• Late-Diagnosed Autism - Distinct Profile — biologically distinct subtype, AuDHD, masking, stimulant-mediated unmasking
• ADHD-PI and Internal Hyperactivity — predominantly inattentive ADHD with internal mental hyperactivity, CDS overlap
• Trichotillomania and Neurodevelopmental Links — BFRBs in AuDHD, dopamine-glutamate convergence, iron links, NAC evidence
• research/Iron and Myelination — oligodendrocyte iron dependency, white matter deficits
• research/Iron and Oxidative Stress in Autism — glutathione depletion, Nrf2 dysfunction
• research/Iron and GABAergic Function — GABA/glutamate E/I balance
• research/Iron Glutamate and Excitotoxicity — System Xc-, glutamate release, NAC mechanism
• research/Iron and OCD-Spectrum Repetitive Behaviours — basal ganglia iron in OCD, TTM links

Gut-Brain Axis

• Gut-Brain Axis and Neurodevelopment — microbiome in autism/ADHD, iron-gut dysbiosis, serotonin, vagus nerve, probiotics

Minerals

• Copper-Zinc-Iron Interactions — competitive absorption, DBH, the vicious cycle
• research/Copper-Iron-Dopamine Triangle — catecholamine cascade, TH/DBH/ceruloplasmin triad
• research/Zinc-Iron Brain Competition — ZIP/ZnT transporters, synaptic zinc, NMDA modulation

Sleep

• research/Iron and Circadian Rhythm — IRP1/IRP2, clock genes, sleep disruption
• research/Poor Sleep and AuDHD-HFE Interactions — sleep as central amplifier: ferroptosis, glymphatic failure, gut dysbiosis, executive dysfunction, sensory amplification, dopamine, TTM
• research/Sleep Intervention Protocols for AuDHD Adults — melatonin dosing, adapted CBT-I/ACT-i, chronotherapy, sensory environment, Elvanse timing, magnesium, staged protocol

Body Systems

• neurodevelopment/Interoception in AuDHD - Research Review — interoceptive accuracy, alexithymia, BFRB urge detection, emotional dysregulation, burnout, hunger/satiety under Elvanse, iron-insula link
• research/Autonomic Nervous System and Vagal Tone in AuDHD — HRV, polyvagal theory, vagus-gut-brain axis, sensory reactivity, HRV biofeedback, stimulant effects
• research/Endocrine Effects of HFE Iron Overload — hypogonadism, thyroid, insulin resistance, ferritin-testosterone correlation, phlebotomy recovery window

Exercise

• research/Exercise as Medicine for AuDHD-HFE — executive function, dopamine/BDNF, iron metabolism (hepcidin), sleep, gut microbiome, TTM, practical barriers and prescription

Neuroprotection

• research/HFE and Long-Term Neurodegeneration Risk — Parkinson's/ALS/Alzheimer's meta-analyses, brain QSM imaging, neuroprotective strategy, deferiprone failure, intervention window
• research/NAC and Iron Metabolism — chelation properties, GSH restoration, NTBI reduction, ferroptosis protection, safety in iron overload, thalassemia RCT data

Symptoms

• Fatigue and Burnout — multifactorial drivers, autistic burnout, oxidative stress, endocrine disruption
• Arthropathy and Back Pain — HH arthropathy, lumbar involvement, imaging

Practical Management

• Dietary Management - Iron Overload — inhibitors, enhancers, meal strategy
• Diet and Supplement Strategy — current stack review, NAC, vitamin D, probiotics, inositol, treatment hierarchy
• Action Items and Monitoring Plan — GP script, phlebotomy, investigations, tracking
• research/UK Testing Guide - Pharmacogenomics and Endocrine — best-value UK tests: myDNA (£170), Body Fabulous methylation (£289), Medichecks endocrine (£249)

Research Meta

• research/Research Avenues Tracker — living tracker of promising research leads with evidence ratings

Key Findings from PubMed Verification (March 2026)

The following findings were verified against PubMed and OpenAlex on 2026-03-22, confirming their citations exist and conclusions are accurately represented:

1. Chang 2014 (HFE iron overload mice): Iron overload in HFE-model mice produces repetitive behaviour and dopamine disruption in the basal ganglia, providing direct mechanistic evidence that excess brain iron drives stereotyped behaviours relevant to trichotillomania
2. Grotzinger 2025 (cross-disorder GWAS): Mapping genetic architecture across 14 psychiatric disorders (n=1,056,201 cases) identified five genomic factors explaining ~66% of genetic variance and 238 pleiotropic loci — ADHD and autism load onto shared factors, with shared signal enriched in excitatory neurons. See Genetic Architecture of AuDHD
3. Iron overload causes gut dysbiosis AND cognitive impairment (PMID 39438708): Suparan et al. demonstrated that iron overload causes cognitive impairment via the gut-brain axis, with association between gut/blood microbiome alterations, cognition, and iron burden. See Gut-Brain Axis and Neurodevelopment
4. Jiang 2024 (System Xc- ferroptosis in autism models): Ferroptosis via the System Xc-/GPX4 pathway is implicated in autism models, linking iron-dependent cell death to glutamate dysregulation. See research/Ferroptosis and Neuronal Iron
5. Memantine RCT: 60.5% vs 8.3% for TTM (Grant 2023): Double-blind placebo-controlled study of memantine in 100 adults with TTM/skin-picking showed 60.5% improvement vs 8.3% placebo (NNT=1.9), providing strong confirmation of the glutamate hypothesis for BFRBs alongside the NAC evidence. See Trichotillomania and Neurodevelopmental Links
6. Brancati 2025 ("Hidden phenotype"): Found that 21.9% of adults with ADHD screened positive for ASD, with higher age at first clinical referral, greater emotional dysregulation, more mood/anxiety comorbidity, and evening chronotype — describing the "hidden phenotype" of autism in adults diagnosed with ADHD. See Late-Diagnosed Autism - Distinct Profile
7. No PubMed study exists on stimulant-mediated autism unmasking: Despite clinical recognition of this phenomenon, no peer-reviewed study has directly investigated stimulant medication unmasking autistic traits — this remains an evidence gap supported only by clinical observation and grey literature
8. East et al. (infant iron deficiency predicts SCT/CDS): Infant iron deficiency predicted SCT/CDS symptoms in childhood and adolescence, establishing an early developmental link between iron status and cognitive disengagement. See ADHD-PI and Internal Hyperactivity
9. Mitchell 2009 (H63D and glutamate): H63D HFE cells show directly increased glutamate release and reduced glutamate uptake capacity, demonstrating that Anthony's H63D variant may promote glutamate excitotoxicity — the same pathway implicated in trichotillomania and targeted by NAC. See Genetic Architecture of AuDHD

How to Use This Vault

1. Start here for an overview, then follow wikilinks into topics
2. Each note has a Cross-References section at the bottom linking to related notes
3. Use Obsidian's Graph View to visualise connections between topics
4. The Action Items and Monitoring Plan note contains practical next steps
5. The research/Research Avenues Tracker tracks research leads and their status
6. The Diet and Supplement Strategy note contains the supplement protocol
7. Update Blood Results - March 2026 with future test results to track progress

Key Themes Across Notes

1. Iron Overload Cascade

flowchart TD
    classDef gen fill:#d2b4de,stroke:#7d3c98,color:#1a0422
    classDef iron fill:#f1948a,stroke:#c0392b,color:#1a0505
    classDef out fill:#f7dc6f,stroke:#b7950b,color:#1a1400

    A[HFE C282Y / H63D]:::gen --> B[Iron Overload]:::iron
    B --> C[NTBI + Oxidative Stress]:::iron
    B --> I[Brain Iron]:::iron
    B --> N[Gut Dysbiosis]:::iron

    C --> E[Fatigue + Joint Damage]:::out
    C --> GSH[GSH Depletion]:::iron
    GSH --> FPT[Ferroptosis]:::out
    GSH --> GLU[Glutamate Excess]:::out

    I --> ADHD[ADHD Symptoms]:::out
    I --> TTM[Trichotillomania]:::out
    I --> ASD[Autism Symptoms]:::out

    N --> KYN[Kynurenine Shunt]:::iron
    KYN --> TTM
    KYN --> SLP[Poor Sleep]:::out

    B --> TEST[Low Testosterone]:::out

2. Sleep as Central Amplifier

flowchart TD
    classDef sleep fill:#85c1e9,stroke:#2471a3,color:#0a1929
    classDef out fill:#f7dc6f,stroke:#b7950b,color:#1a1400
    classDef feed fill:#f1948a,stroke:#c0392b,color:#1a0505

    R[Poor Sleep]:::sleep

    R --> AH[Low Glymphatic Clearance]:::sleep
    R --> AI[Gut Dysbiosis]:::sleep
    R --> AJ[Low Executive Function]:::sleep
    R --> AK[DA Downregulation]:::sleep
    R --> AL[Sensory Amplification]:::sleep
    R --> AM[High Cortisol]:::sleep
    R --> FPT[Ferroptosis Acceleration]:::sleep

    AH --> BI[Brain Iron]:::feed
    AI --> IDO[IDO Activation]:::feed
    AM --> IDO
    AJ --> ADHD[ADHD Symptoms]:::out
    AJ --> TTM[Trichotillomania]:::out
    AK --> ADHD
    AL --> ASD[Autism Symptoms]:::out

    ADHD --> R
    ASD --> R
    MASK[Masking Cost]:::out --> R
    HYP[Internal Hyperactivity]:::out --> R
    ELV[Elvanse]:::out --> R
    AL -.-> R

3. Interventions and Targets

flowchart LR
    classDef protect fill:#58d68d,stroke:#1e8449,color:#0a1f12
    classDef med fill:#f0b27a,stroke:#ca6f1e,color:#1a1000
    classDef target fill:#f1948a,stroke:#c0392b,color:#1a0505

    subgraph TREAT ["Treatment"]
        M[Phlebotomy]:::protect
        L[Diet Changes]:::protect
        BA[Exercise]:::protect
        BB[NAC]:::protect
        AN[Melatonin]:::protect
        AO[Chronotherapy]:::protect
        AP[Sensory Optimisation]:::protect
    end

    subgraph MEDS ["Medication"]
        J[Elvanse 70mg]:::med
    end

    %% Phlebotomy targets
    M -.-> IO[Iron Overload]:::target
    M -.-> PIT[Pituitary Iron]:::target
    M -.-> TEST[Low Testosterone]:::target

    %% Diet targets
    L -.-> IO

    %% Exercise targets
    BA -.-> BI[Brain Iron]:::target
    BA -.-> DA[DA Downregulation]:::target
    BA -.-> SLP[Poor Sleep]:::target
    BA -.-> GUT[Gut Dysbiosis]:::target

    %% NAC targets
    BB -.-> GSH[GSH Depletion]:::target
    BB -.-> FPT[Ferroptosis]:::target
    BB -.-> GLU[Glutamate Excess]:::target
    BB -.-> TTM[Trichotillomania]:::target

    %% Sleep interventions
    AN -.-> SLP
    AO -.-> SLP
    AP -.-> SENS[Sensory Reactivity]:::target

    %% Elvanse effects
    J --> APP[Appetite Suppression]:::med
    APP -.-> CUZN[Cu / Zn Depletion]:::target
    J --> UNMASK[Autistic Unmasking]:::med

Citation Summary

All notes contain inline citations. Key journals referenced:

• Nature, Nature Genetics (autism subtypes, GWAS)
• Blood, Hepatology, J Hepatol (haematology/hepatology)
• Arch Gen Psychiatry, JAMA Psychiatry (NAC for trichotillomania)
• Radiology, Eur Radiol (brain iron imaging)
• PLoS One, Sci Rep, BMC Genomics (general science)
• Molecules, Nutrients, Biol Trace Elem Res (mineral metabolism)
• Front Psychiatry, Front Microbiol, Dev Cogn Neurosci, Int J Mol Sci (neuropsychiatry, gut-brain)
• Gut Microbes, BMC Microbiol (microbiome)
• Mol Autism, Autism Research (autism-specific)
• J R Coll Physicians Edinb, JBMR Plus (musculoskeletal)
• EASL Guidelines, BJH Guidelines, GeneReviews (clinical guidelines)

Disclaimer: This research vault is for personal information-tracking purposes. It does not constitute medical advice. All clinical decisions should be made with qualified healthcare professionals.