Theories

Theories

Working hypotheses about what's driving this condition — what's suspected, the evidence for it, and the evidence against it. This is theories only; the active interventions built around them (and around simply managing symptoms) live on Current Strategies, and concluded trials live in Attempted Therapies.

Autoimmune

This condition is fundamentally autoimmune in nature — the immune system periodically over-activating or misfiring in a way that drives the digestive, hunger, and inflammatory symptoms. Histamine/MCAS (below) is treated as a specific sub-hypothesis under this umbrella rather than a separate theory, since the two overlap heavily.

Points in Favor

  • All three Moments of Remission (Berlin 2011, the Moderna shot in 2021, and the immune activation episode in 2026) coincided with periods of immune activation, and each produced days of dramatic improvement before symptoms returned.
  • Minor improvement in chronic skin infections during a parasitic intervention trial (parasites are known immunomodulators) — see Attempted Therapies.

Counterpoints

  • Low-Dose Naltrexone, tried specifically under this hypothesis, had to be discontinued due to severe nightmares even at tiny doses — before its efficacy could really be assessed either way.
  • The parasitic intervention itself triggered strong, classically allergic reactions as colony size increased, and had to be discontinued with an antiparasitic — muddying whether the modest skin improvement was a real signal or noise.

Sub-hypothesis: Histamine (MCAS)

A histamine/MCAS-like pathway ties into the hunger, wakefulness, and stress cycle.

Points in Favor

  • Some family history of histamine disorders.
  • Symptom pattern correlates with a lot of what MCAS sufferers describe in testimonials.
  • 24-hour urine histamine came back flagged high (see Labs & Trends).

Counterpoints

  • Sodium Cromolyn and DAO supplementation — both tried specifically for suspected histamine involvement — produced no real relief (see Attempted Therapies).
  • MCAS typically correlates with anaphylaxis and/or rashes (urticaria, flushing) — I present with neither.

Hereditary Alpha-Tryptasemia (HαT)

A genetic condition — extra copies of the alpha-tryptase gene (TPSAB1) — that produces MCAS-like symptoms through a different mechanism than autoimmune dysregulation or classic mast cell activation: the extra gene copies mean mast cells simply make more tryptase all the time, rather than periodically over-activating. It runs in an estimated 5–7% of the population, is easy to miss since it looks a lot like MCAS clinically, and is worth distinguishing from the histamine hypothesis above rather than lumping in with it.

Points in Favor

  • Joint hypermobility and connective tissue laxity are a well-documented HαT association, and I've had a lifelong predisposition to soft-tissue and tendon injuries.
  • Fallen arches, which I've had for as long as I can remember, are themselves a common downstream effect of that same connective tissue laxity.
  • Digestive dysmotility and an IBS-like symptom pattern (bloating, abdominal pain) are a documented feature of HαT.
  • The broader cluster of food/chemical sensitivity and MCAS-like symptoms fits the reported HαT symptom profile.

Counterpoints

  • HαT is generally defined by a persistently elevated baseline tryptase level (most commonly cited threshold ≥8 ng/mL, present all the time, not just during a reaction) — the extra gene copies constantly produce more tryptase, unlike the episodic spikes of classic MCAS. My tryptase came back at 3.9 ng/mL (see Labs & Trends), well within the normal range, which argues against this. (Caveat: a minority of confirmed HαT cases have been reported with normal serum tryptase despite carrying the TPSAB1 duplication, so this doesn't rule it out on its own — genetic testing, TPSAB1 copy number analysis, would be the definitive next step.)

Gastric Motility

Slowed digestive transit time — not just hormonal signaling — may be part of what determines whether I wake up hungry at night.

Points in Favor

  • While on painkillers after the 2024 nephrostomy, my digestion was slowed and I slept through the night much better, despite terrible energy otherwise (see In-depth History). Night hunger returned almost immediately after stopping them.
  • Increasing soluble fiber makes me feel a little more energetically stable.

Counterpoints

  • The added soluble fiber hasn't had much notable impact on waking up hungry, so slowing transit time alone doesn't reproduce the painkiller effect — something else about painkillers specifically (e.g. opioid receptor activity, not just motility) may be doing the work instead.

Hormonal Imbalance

Ghrelin spikes or another hormonal driver behind the hunger/waking pattern.

Points in Favor

  • Fits the acute, hunger-driven waking pattern.

Counterpoints

  • Testing has never conclusively pointed to any hormonal imbalance.

Next step: discuss with my doctor whether it's worth exploring Ozempic — not yet started, so not on Current Strategies.

Inflammation

Inflammation is a core part of the issue.

Points in Favor

  • Noticeable relief from NSAIDs.

Counterpoints

  • Turmeric-ginger supplementation and other herbal anti-inflammatories, tried against this theory specifically, have shown no strong results yet.