What causes recurrent SIBO?

The Host Capacity Model identifies colonocyte bioenergetic failure as the upstream driver of recurrent SIBO. When colonocyte mitochondrial respiration fails, oxygen leaks into the lumen and reshapes the ecology toward facultative and sulfidogenic overgrowth—so antimicrobials clear the symptom but not the cause.

How is MCAS different from other mast cell conditions?

BiomeLogic stratifies MCAS into Pattern A/B/C/D activation phenotypes based on upstream drivers (barrier, neuroimmune, infectious, or connective-tissue mediated). Treatment differs by pattern, which is why generic mast-cell stabilizers fail in many patients.

Do you provide medical care or diagnoses?

No. BiomeLogic provides independent systems-biology consultation and mechanistic case analysis. It is not medical care, not a diagnosis, and does not replace your physician.

Can I 'cure' hEDS/POTS/MCAS with this protocol?

No, because the genetic component of hEDS is unchanged. But functional restoration is achievable: 40–60% reduction in hEDS pain/dysfunction, 50–70% improvement in POTS orthostatic tolerance, and 70–90% reduction in MCAS flare frequency. You're restoring function despite genetic constraints — not changing the genetics.

How long before I see improvement?

Energy improves weeks 2–3. POTS symptoms ease weeks 4–6. MCAS flares decrease ~60% by weeks 6–8. By weeks 8–12, hEDS pain and dysfunction show noticeable improvement. By week 16, most patients reach 50–70% functional improvement. A 4–6 month timeline to significant change is normal and doesn't indicate failure.

Do I need to stop my current medications?

No. Continue all current medications — antihistamines, beta-blockers, pain management — while implementing the protocol. As you improve, antihistamine needs may decrease, beta-blocker doses may be reduced, and pain medication needs often drop significantly. Do not discontinue without provider input.

What about exercise? I've been told exercise helps POTS.

Nuanced. Acute phase (weeks 1–8): avoid deconditioning but don't push exercise — recumbent activities only. Recovery phase (weeks 8–16): very gradual standing exercise, starting with 2–3 minutes tolerance and increasing 1–2 minutes per week. Maintenance phase (week 16+): graded exercise program, but remain cautious — overexertion can trigger MCAS flares.

Can dysbiosis cause hEDS/POTS/MCAS symptoms to worsen?

Absolutely. Dysbiosis perpetuates all three conditions. It worsens hEDS via barrier breakdown and endotoxemia, drives POTS flares via dysbiotic metabolites triggering autonomic instability, and directly triggers mast cells (especially via H₂S-producers). Dysbiosis treatment is non-negotiable in this overlap.

Is there a genetic test I should do?

Standard genetic testing for hEDS markers confirms diagnosis but doesn't change treatment. POTS-specific genetic testing has limited utility — POTS is mostly functional, not purely genetic. More useful: functional testing (NAD+, mitochondrial markers, dysbiosis assessment) that actually guides treatment.

What if I have hEDS but not POTS/MCAS?

Pure hEDS still benefits from NAD+ restoration — pain and dysfunction often improve 30–50%. Dysbiosis is still common because of inherent barrier vulnerability. The same protocol applies, but less intensive NAD+ dosing is usually sufficient.

Is it normal for symptoms to flare during recovery?

Yes, and it's usually not regression. Antimicrobials trigger bacterial die-off (Jarisch-Herxheimer reaction); endotoxin release temporarily activates mast cells. Expect 1–2 flares during weeks 4–8 — support with antihistamines, hydration, and salt intake. Flares typically become less frequent as dysbiosis resolves. If they worsen, alert your provider.

Condition framework

hEDS/POTS/MCAS Overlap: Treating the Shared Root Cause

Why hypermobility EDS, POTS, and MCAS co-occur — and how an integrated mitochondrial recovery protocol addresses all three at once.

The shared pathophysiology

hEDS, POTS, and MCAS patients share a specific vulnerability: their connective tissue and mast cells depend heavily on mitochondrial energy production. hEDS has a genetic component (often COL5A1, type V collagen deficiency), but symptom severity scales with energy availability for collagen cross-linking and matrix organization. POTS involves endothelial small fiber dysfunction and impaired baroreceptor reflex — both ATP-dependent. Severity scales with endothelial mitochondrial function. MCAS mast cells are energy-intensive; degranulation is ATP-dependent and regulation requires sustained NAD+. Mitochondrial dysfunction lowers the degranulation threshold.

The triggering event

Most hEDS/POTS/MCAS overlap cases are set off by an acute trigger: SARS-CoV-2 infection (most common), other viruses (EBV, Lyme), severe physical stress or trauma, severe infection, or environmental toxin exposure. The cascade is consistent: systemic insult damages endothelial and mast cell mitochondria → NAD+ depletion in endothelium causes vascular dysfunction (POTS worsens) → NAD+ depletion in mast cells lowers degranulation threshold (MCAS activates) → NAD+ depletion in fibroblasts and colonocytes worsens collagen disorder and barrier function → dysbiosis from barrier breakdown drives further endotoxemia → all three conditions activate simultaneously.

Why standard treatment fails

Each specialty treats its condition independently. hEDS specialists focus on physical therapy and pain management. POTS specialists focus on volume expansion and salt. MCAS specialists focus on antihistamines and low-histamine diet. None address the shared candidate upstream mechanism: mitochondrial NAD+ depletion. Patients cycle through flares despite maximal specialist care.

Phase 1: Integrated bioenergetic assessment (weeks 1–2)

Core panel: intracellular NAD+ panel (target >500 μM for POTS/MCAS; >600 μM for hEDS functional recovery); Organic Acid Test; mitochondrial damage markers (lactate, carnitine, CoQ10 — often low in hEDS/POTS overlap). Endothelial/POTS markers: blood pressure response to standing (HR ↑ 30+ bpm confirms POTS), heart rate variability, plasma volume status, small fiber density testing if available. Mast cell markers: baseline tryptase, histamine, calprotectin. Dysbiosis assessment is almost always needed — barrier breakdown is severe in this population because hEDS patients have inherent connective-tissue vulnerability.

Phase 2: Integrated dysbiosis & vascular dysfunction mapping (weeks 2–4)

Full dysbiosis profile, barrier integrity (zonulin and calprotectin often significantly elevated), small fiber dysfunction assessment if POTS is prominent, autonomic tone assessment via heart rate and blood pressure variability. In overlap cases, dysbiosis is typically more severe than in non-hEDS dysbiosis — barrier breakdown is catastrophic when connective tissue is already vulnerable.

Phase 3: Integrated recovery protocol (weeks 4–16+)

Intensive NAD+ restoration (primary). IV NAD+ 500 mg weekly for 12–16 weeks (most effective; longer duration than dysbiosis-only because tissue remodeling is required); or high-dose oral NMN 1,000–2,000 mg daily for 16–24 weeks; or combination (IV weeks 1–8, oral 1,000 mg weeks 8–24+). Target NAD+ >550 μM. POTS symptoms often improve weeks 4–6; MCAS flares decrease weeks 6–8; hEDS pain and dysfunction improve weeks 8–12.

Dysbiosis protocol concurrent. Antimicrobial phase weeks 4–10; dietary phase weeks 4–16 with low-FODMAP restriction transitioning to reintroduction; sodium butyrate 1–2 g daily extended duration; L-glutamine, zinc carnosine, bone broth; probiotics from week 8.

POTS-specific support. Volume expansion: salt 9–12 g daily, fluids 2.5–3 L daily, 30–40 mmHg compression stockings. Pyridostigmine 30–60 mg three times daily if severe (cholinergic bridge while NAD+ recovers). Do not push exercise during weeks 1–8; recumbent cycling and lying leg raises weeks 8–12; gradual standing progression weeks 12+. Track orthostatic vitals weekly — POTS improvement usually visible by week 8–10, with 30–40% improvement by week 16.

MCAS-specific support. Continuous H1 blocker (cetirizine or fexofenadine) rather than as-needed; H2 blocker (famotidine twice daily); cromolyn sodium 20 mg before meals or triggers. As dysbiosis resolves, MCAS flares typically drop 60–80% by week 12 and 80% by week 16. Add molybdenum cofactor, zinc carnosine, and reduced glutathione if H₂S SIBO is present.

hEDS-specific support. The genetic component is unchangeable, but symptom severity depends on energy. Avoid aggressive PT during weeks 1–8; gentle stretching and posture optimization weeks 8–12; very gradual strengthening weeks 12+. Connective tissue cofactors: vitamin C 500–1,000 mg, copper 2–4 mg, zinc 15–30 mg, bone broth 12–16 oz, collagen hydrolysate 10–15 g daily. Pain management: avoid NSAIDs (worsen gut barrier); consider topical capsaicin or topical NSAIDs; low-dose naltrexone 4.5–5 mg nightly (helpful in this overlap for both pain and immune modulation). hEDS pain and dysfunction typically improve 30–50% by week 12 with continued improvement through week 24+.

Phase 4: Long-term integration & prevention (weeks 16+)

Retest at week 16: NAD+ >550 μM, metagenomics showing dysbiosis resolution, POTS orthostatics improved, MCAS flares 70–80% reduced, hEDS pain/function 30–50% improved. NAD+ support is lifelong — daily high-dose NMN or quarterly IV boosts. Continue resistant starch, polyphenol-rich foods, probiotics, salt and fluid intake per POTS protocol, connective tissue support, and compression garments if needed. Weekly stress management and gentle movement. Monthly POTS vital monitoring, MCAS flare tracking, and hEDS pain/function assessment. Quarterly IV NAD+ boost if symptoms relapse — this often prevents acute decompensations.

Frequently asked questions

Bring a case for mechanistic review.

Request a Consultation