Skip to content

HBOT Protocol Optimization for Ketogenic Metabolic Therapy

Analysis Date: December 5, 2025
Purpose: Evaluate hyperbaric oxygen therapy (HBOT) integration with ketogenic diet and Seyfried metabolic approach
Status: Planning phase - pending safety clearance

πŸ”¬ Current Clinical Status (December 2025)

Latest Biomarkers (Dec 1-3, 2025)

Biomarker Value Reference Range Status Date
β-HCG 270 IU/L < 2 IU/L 🚨 Elevated Dec 1
CRP 1.9 mg/L 0-5.0 mg/L βœ… Normal Nov 17
Hemoglobin 10.3 g/dL 12.5-16.5 g/dL ⚠️ Low Dec 3
Platelets 61 Γ— 10⁹/L 140-420 Γ— 10⁹/L 🚨 Critical Dec 3

Ξ²-HCG Trend Analysis

Last 5 tests showing rapid acceleration:

2025-11-14:   24 IU/L
2025-11-17:   42 IU/L  (+75% in 3 days)
2025-11-22:  113 IU/L  (+169% in 5 days)
2025-11-27:  197 IU/L  (+74% in 5 days)
2025-12-01:  270 IU/L  (+37% in 4 days)

Interpretation: 11-fold increase over 17 days indicates aggressive disease progression despite EP chemotherapy (started Nov 24).

Recent Treatment Context

  • Nov 24-28, 2025: EP protocol #1 (Etoposide + Cisplatin), 5-day cycle
  • Nov 17, 2025: PET scan
  • Nov 14 & Nov 5: Hyperthermia + IV therapy sessions
  • Oct-Nov 2025: Regular hyperthermia sessions (8+ treatments)

⚠️ Safety Assessment for HBOT

Critical Contraindications Identified

1. Severe Thrombocytopenia (61 Γ— 10⁹/L)

Risk Level: 🚨 HIGH - Treatment contraindicated

  • Platelet count critically below safe threshold
  • Standard HBOT centers require platelets >50-75 Γ— 10⁹/L
  • Risk: Barotrauma-induced bleeding (ear, sinus, pulmonary)
  • Mechanism: Pressure changes during compression/decompression can rupture small vessels with inadequate platelet coverage

Action Required: - ❌ Do NOT proceed with HBOT at current platelet level - βœ… Wait for post-chemotherapy recovery (typically 14-21 days post-cycle) - βœ… Target platelet count >80-100 Γ— 10⁹/L before initiating HBOT - βœ… Oncology team clearance mandatory

2. Mild Anemia (Hemoglobin 10.3 g/dL)

Risk Level: ⚠️ MODERATE - Suboptimal but manageable

  • Reduced oxygen-carrying capacity diminishes HBOT effectiveness
  • Not a contraindication but impacts therapeutic benefit
  • Optimal: Hemoglobin >11.5-12.0 g/dL

Mitigation Strategies: - Consider iron supplementation (if iron deficiency confirmed) - Erythropoietin (EPO) support if appropriate - Nutritional optimization (B12, folate, protein) - Reassess after 2-3 weeks of support

3. Rapid Tumor Progression

Risk Level: ⚠️ CONTEXT-DEPENDENT

  • Ξ²-HCG doubling time: ~5-7 days (aggressive)
  • HBOT is adjuvant, not primary therapy
  • Must be combined with active systemic treatment

Clinical Implication: - HBOT alone will NOT control disease at this progression rate - Must run parallel to chemotherapy/immunotherapy - Primary goal: metabolic stress enhancement, not standalone cure

Other Contraindications to Screen

Before initiating HBOT, confirm absence of:

  • ❌ Untreated pneumothorax
  • ❌ Active upper respiratory infection
  • ❌ Ear/sinus pressure equalization problems
  • ❌ Severe COPD with air trapping
  • ❌ Seizure disorders (uncontrolled)
  • ❌ Claustrophobia (severe)
  • ❌ Recent bleomycin exposure (<3 months) - verify treatment history

🎯 Optimized HBOT Protocol Design

Overview: Phased Escalation Approach

Philosophy: Start conservative, escalate based on tolerance and response

Key Principles: 1. Maximize metabolic stress on cancer cells (keto + hypoxia-then-hyperoxia) 2. Minimize oxidative damage to normal tissues 3. Coordinate with chemotherapy cycles (avoid nadir periods) 4. Maintain therapeutic ketosis throughout

Phase 1: Conservative Initiation (Weeks 1-2)

Prerequisites: - βœ… Platelets >80 Γ— 10⁹/L - βœ… Hemoglobin >11.0 g/dL - βœ… Oncology clearance - βœ… No active infections or contraindications

Protocol Parameters:

Parameter Specification Rationale
Pressure 1.5 ATA Low pressure minimizes barotrauma risk
Duration 45-60 minutes Short sessions assess tolerance
Frequency 2-3 sessions/week Mon/Wed/Fri schedule
Timing Late morning (10-11 AM) After overnight + morning fast
Fasting 6-8 hours pre-session Optimize ketosis, minimize glucose

Metabolic Targets (Pre-Session): - Blood glucose: <80 mg/dL (ideally 60-75 mg/dL) - Ξ²-hydroxybutyrate: 1.5-3.0 mmol/L - Glucose-Ketone Index (GKI): <3 (ideally <1)

Monitoring Requirements:

Daily: - Glucose/ketone measurements (fasting, pre-HBOT, post-HBOT) - GKI calculation - Symptom tracking (headaches, ear pressure, fatigue, nausea)

Weekly: - Blood tests: Ξ²-HCG, CRP, FBC (platelets, hemoglobin, WBC, neutrophils) - Weight and body composition - Ketone/glucose trend analysis

Decision Point (End of Week 2): - βœ… Escalate to Phase 2 if: Tolerating well, no adverse effects, Ξ²-HCG stable or declining - ⏸️ Continue Phase 1 if: Mild side effects, need more adaptation time - ❌ Stop HBOT if: Severe side effects, Ξ²-HCG rising, platelets dropping, oxygen toxicity signs

Phase 2: Therapeutic Escalation (Weeks 3-6)

Entry Criteria: - βœ… Phase 1 completed without significant adverse effects - βœ… Ξ²-HCG declining or stable (not rising) - βœ… Platelets stable >80 Γ— 10⁹/L - βœ… Good energy and tolerance

Protocol Parameters:

Parameter Specification Rationale
Pressure 1.8-2.0 ATA Increased metabolic stress
Duration 60-75 minutes Extended oxygen exposure
Frequency 4-5 sessions/week Intensive metabolic pressure
Timing Same fasting protocol Maintain ketosis
Schedule Pulse dosing: 5 days on, 2 days off Prevent burnout, allow recovery

Chemotherapy Coordination: - Avoid HBOT during platelet nadir (typically days 7-14 post-chemo) - Optimal timing: Days 1-6 post-chemo (before nadir) or days 15+ (after recovery) - Check CBC before each HBOT week

Enhanced Monitoring:

Twice Weekly: - Blood tests: Ξ²-HCG, CRP, FBC - Trend analysis and protocol adjustments

Daily: - Pre/post-HBOT glucose and ketones - Detailed symptom log - Watch for oxygen toxicity signs: - Visual disturbances (tunnel vision, light sensitivity) - Tinnitus or hearing changes - Muscle twitching or fasciculations - Seizures (rare but serious) - Nausea/vomiting

Decision Point (End of Week 6): - βœ… Advance to Phase 3 if: Ξ²-HCG declining consistently, excellent tolerance - ⏸️ Continue Phase 2 if: Partial response, need more time - ⬇️ De-escalate to Phase 1 if: Side effects emerging, fatigue - ❌ Stop HBOT if: Ξ²-HCG rising, safety concerns

Phase 3: Maintenance Protocol (Weeks 7+)

Entry Criteria: - βœ… Ξ²-HCG showing sustained decline (β‰₯50% reduction from baseline) - βœ… Excellent tolerance through Phase 2 - βœ… Stable blood counts

Protocol Parameters:

Parameter Specification Rationale
Pressure 2.0-2.2 ATA Maximum therapeutic pressure
Duration 75-90 minutes Full therapeutic window
Frequency 3-4 sessions/week Sustainable long-term
Cycling 4 weeks on, 2 weeks off Prevent oxygen toxicity accumulation

Long-Term Strategy: - Continue indefinitely as long as Ξ²-HCG remains suppressed - Reduce frequency if remission achieved (2 sessions/week maintenance) - Always coordinate with ongoing systemic therapy

πŸ₯‘ Ketogenic Diet Integration

Metabolic Rationale: Warburg Effect Targeting

Theory (Seyfried Metabolic Approach): 1. Cancer cells rely heavily on glucose fermentation (glycolysis) even in oxygen presence 2. Ketogenic diet reduces glucose availability 3. HBOT increases oxygen tension 4. Combined effect: Dual metabolic stress (low glucose + forced oxidative metabolism) 5. Normal cells adapt (can use ketones); cancer cells cannot (lack metabolic flexibility)

Pre-HBOT Fasting Protocol (6-8 hours)

Goal: Achieve deep ketosis before hyperbaric oxygen exposure

Protocol: - Last meal: 6-8 hours before HBOT session - Overnight fast + skip breakfast for morning sessions - Water: Allowed, encouraged (with electrolytes) - Electrolytes: Sodium, potassium, magnesium supplementation - Avoid: Coffee (can spike cortisol/glucose), supplements, medications (unless essential)

Target Metrics (Pre-HBOT): - Blood glucose: 60-80 mg/dL - Ξ²-Hydroxybutyrate: 2.0-3.5 mmol/L - GKI: <3 (ideally <1)

During HBOT Session

Nothing by mouth - maintain fasting state throughout treatment

Physiological State: - Deep ketosis + hyperbaric oxygen = maximum metabolic pressure - Cancer cells forced into energetically unfavorable state - Normal cells protected by ketone metabolism

Post-HBOT Nutrition (1-2 hours after)

Goal: Break fast while maintaining ketosis and avoiding metabolic spikes

Ideal Post-HBOT Meal:

High-Fat Base (70-80% of calories): - Avocado (whole) - MCT oil or coconut oil (1-2 tbsp) - Olive oil (generous) - Fatty fish (salmon, mackerel, sardines) - Grass-fed butter or ghee - Full-fat cheese (if tolerated) - Nuts/seeds (macadamia, walnuts, chia)

Moderate Protein (15-20% of calories): - Eggs (2-3 whole) - Fish/seafood - Grass-fed beef or lamb (modest portion, 4-6 oz) - Avoid: Large protein bolus (>40g) - can spike mTOR/insulin

Minimal Carbs (<5% of calories): - Leafy greens (spinach, kale, arugula) - Cruciferous vegetables (broccoli, cauliflower) - Avoid: All starchy foods, fruits (except small amount of berries if needed)

Electrolytes & Hydration: - Sea salt (1/2 tsp) - Potassium (200-400 mg) - Magnesium (200-400 mg) - Water (16-24 oz)

Antioxidants (Optional, Modest Doses): - Vitamin C: 500-1000 mg - Vitamin E: 200-400 IU - N-Acetyl Cysteine (NAC): 600 mg - Glutathione: 250-500 mg - Rationale: Modest support without blunting hormetic stress

Foods to Avoid Post-HBOT: - ❌ High carbohydrate foods (bread, rice, pasta, potatoes, fruit) - ❌ Excess protein (>40g in one meal) - ❌ Processed foods or seed oils - ❌ Alcohol

Daily Ketogenic Maintenance

Macronutrient Targets: - Fat: 75-80% of calories - Protein: 15-20% of calories (0.8-1.0 g/kg ideal body weight) - Carbohydrates: <5% of calories (<20-30g total carbs/day)

Caloric Strategy: - Mild restriction: 10-20% below maintenance calories - Goal: Maximize metabolic pressure while maintaining strength - GKI target: <3 consistently (ideally <1 on HBOT days)

Ketone Targets: - Ξ²-Hydroxybutyrate: 1.5-3.0 mmol/L (therapeutic range) - Higher is not always better (>5 mmol/L can indicate stress/dehydration) - Consistency more important than peaks

Glucose Targets: - Fasting: 70-85 mg/dL - Post-meal: <100 mg/dL - Press-pulse strategy: Keep glucose chronically low (press), HBOT as pulse

Supplement Support: - Electrolytes: Sodium (3-5g), potassium (2-4g), magnesium (400-600mg) - Omega-3 fatty acids: 2-3g EPA/DHA daily - Vitamin D: Maintain 50-80 ng/mL - B-complex vitamins - Trace minerals (zinc, selenium)

πŸ“Š Monitoring & Decision Framework

Weekly Blood Test Panel

Essential Biomarkers: - Ξ²-HCG (primary tumor marker) - CRP (inflammation marker) - Complete Blood Count: - Platelets (safety threshold >80) - Hemoglobin (oxygen-carrying capacity) - WBC and differential (immune function) - Neutrophils (infection risk if <1.0)

Optional/Periodic: - Comprehensive metabolic panel (electrolytes, kidney, liver) - LDH (tumor burden marker) - Other tumor markers (AFP, CEA, CA 19-9) - context-dependent

Daily Metabolic Tracking

Glucose/Ketone Monitoring: - Fasting (morning) - Pre-HBOT - Post-HBOT (1-2 hours after) - Before bed

Calculate GKI: 

GKI = Blood Glucose (mg/dL) Γ· 18 Γ· Blood Ketones (mmol/L)

Target: <3 (therapeutic)
Optimal: <1 (deep therapeutic)

Symptom Log: - Energy level (1-10 scale) - Headaches (frequency, severity) - Ear pressure or pain - Visual changes - Nausea or dizziness - Sleep quality - Cognitive function

Stop Criteria (Immediate Hold on HBOT)

Hard Stops (Safety): - 🚨 Platelets drop <50 Γ— 10⁹/L - 🚨 Visual disturbances or tinnitus (oxygen toxicity) - 🚨 Muscle twitching, seizure activity - 🚨 Severe ear barotrauma (persistent pain, hearing loss) - 🚨 Neutropenia <1.0 Γ— 10⁹/L (infection risk)

Soft Stops (Efficacy): - ⚠️ β-HCG rising consistently for 2+ weeks despite protocol - ⚠️ Severe fatigue interfering with quality of life - ⚠️ Weight loss >10% or muscle wasting - ⚠️ Patient preference/tolerance issues

Continue/Escalate Criteria

Positive Indicators: - βœ… Ξ²-HCG declining steadily (>20% reduction per cycle) - βœ… Platelets stable or improving (>80 Γ— 10⁹/L) - βœ… Hemoglobin stable or improving - βœ… CRP remains low (<5 mg/L) - βœ… Good energy and quality of life - βœ… No significant side effects - βœ… Consistent therapeutic ketosis (GKI <3)

When to Escalate: - Ξ²-HCG declining but slowly β†’ increase frequency or pressure - Excellent tolerance with no side effects β†’ advance to next phase - Plateauing response β†’ consider pulse dosing or protocol modifications

🚨 Current Recommendation (December 2025)

Immediate Status: NOT CLEARED FOR HBOT

Critical Safety Barriers:

  1. Thrombocytopenia (61 Γ— 10⁹/L)
  2. ❌ Below safe threshold
  3. βœ… Wait for recovery to >80 Γ— 10⁹/L

  4. Expected timeline: 14-21 days post-EP chemotherapy (next safe window: ~Dec 15-20)

  5. Mild Anemia (Hgb 10.3 g/dL)

  6. ⚠️ Suboptimal but not contraindication
  7. βœ… Work on improvement to >11.5 g/dL

  8. Strategies: Iron supplementation, EPO if appropriate, nutritional support

  9. Rapid Ξ²-HCG Rise

  10. ⚠️ Active disease progression
  11. βœ… Must prioritize systemic therapy (chemotherapy/immunotherapy)
  12. HBOT is adjuvant, not rescue therapy

Action Plan - Next 2-4 Weeks

Week 1 (Dec 5-11): - βœ… Continue EP chemotherapy cycle as scheduled - βœ… Monitor blood counts (CBC) twice weekly - βœ… Optimize ketogenic diet (achieve consistent GKI <3) - βœ… Begin glucose/ketone tracking practice - βœ… Iron/nutritional assessment and supplementation - ❌ No HBOT yet

Week 2-3 (Dec 12-25): - βœ… Recheck platelets and hemoglobin - βœ… Target: Platelets >80, Hemoglobin >11.5 - βœ… If blood counts recovered: Schedule oncology consultation for HBOT clearance - βœ… Identify local HBOT facility and schedule orientation - βœ… Continue optimizing keto protocol

Week 4+ (Late Dec onwards): - βœ… If cleared: Begin Phase 1 HBOT (1.5 ATA, 45-60 min, 2-3x/week) - βœ… Close monitoring of Ξ²-HCG trend with combined therapy - βœ… Coordinate HBOT timing with chemotherapy cycles

Expected Timeline

Optimistic Scenario: - Blood counts recover by Dec 20 - Oncology clearance obtained - HBOT initiation: Late December 2025

Realistic Scenario: - Blood count recovery delayed to early January - Second EP cycle may further delay (platelets drop again) - HBOT initiation: Mid-January 2026

Contingency: - If Ξ²-HCG continues rising despite EP protocol, may need treatment escalation - HBOT timing depends on primary therapy effectiveness - Reassess after 2-3 cycles of chemotherapy

πŸ“š Evidence Base & Rationale

HBOT Mechanisms in Cancer Context

Proposed Anti-Cancer Effects:

  1. Oxygen Radical Production
  2. Hyperoxic environment increases reactive oxygen species (ROS)
  3. Cancer cells have impaired antioxidant defenses (low catalase, SOD)

  4. Selective oxidative damage to malignant cells

  5. Metabolic Reprogramming

  6. High oxygen tension forces oxidative phosphorylation
  7. Cancer cells prefer glycolysis (Warburg effect)

  8. Metabolic stress from forced OXPHOS

  9. Angiogenesis Modulation

  10. Normalizes tumor vasculature
  11. Reduces hypoxic niches (hypoxia promotes metastasis)

  12. Improves chemotherapy penetration

  13. Immune System Support

  14. Enhanced neutrophil and macrophage function
  15. Improved tissue oxygenation supports immune cell activity
  16. May enhance checkpoint inhibitor effectiveness

Ketogenic Diet + HBOT Synergy

Seyfried "Press-Pulse" Hypothesis:

Press (Chronic Stress): - Ketogenic diet β†’ chronic glucose restriction - Forces metabolic adaptation - Cancer cells struggle to use ketones

Pulse (Acute Stress): - HBOT β†’ acute oxidative challenge - Chemotherapy β†’ DNA damage - Combined pulses overwhelm cancer cell defenses

Metabolic Vulnerability: - Cancer cells have mitochondrial dysfunction - Cannot efficiently produce ATP via OXPHOS - Ketosis + hyperoxia = energetic crisis for tumor - Normal cells adapt; cancer cells cannot

Limitations & Uncertainties

What We Know: - HBOT is safe when contraindications are screened - Some case series show benefit in refractory cancers - Metabolic therapy rationale is biochemically sound

What We Don't Know: - Optimal pressure, duration, frequency for cancer treatment - Which cancer types respond best - How to predict responders vs. non-responders - Long-term outcome data (most studies are small case series)

This Protocol's Approach: - Evidence-informed but individualized - Conservative escalation with close monitoring - Data-driven decision making (Ξ²-HCG as primary endpoint) - Patient safety prioritized above aggressive dosing

πŸ’¬ Discussion with Medical Team

Questions for Oncologist

  1. Safety Clearance:
  2. When are platelets expected to recover to >80 Γ— 10⁹/L?
  3. Any concerns about HBOT with current treatment regimen?

  4. Bleomycin exposure history? (contraindication for HBOT)

  5. Treatment Coordination:

  6. Optimal timing of HBOT relative to chemotherapy cycles?
  7. Should we avoid HBOT during specific windows (nadir, infusion days)?

  8. Any medications that interact negatively with HBOT?

  9. Monitoring Plan:

  10. Blood test frequency during HBOT?
  11. Additional biomarkers to track?

  12. Red flags to watch for?

  13. Efficacy Assessment:

  14. How will we define success? (Ξ²-HCG reduction targets)
  15. Timeline to assess whether HBOT is helping?
  16. When to discontinue if not effective?

Questions for HBOT Facility

  1. Medical Screening:
  2. What are your platelet/hemoglobin thresholds?
  3. Do you treat cancer patients regularly?

  4. Physician medical director available for consultation?

  5. Protocol Flexibility:

  6. Can we customize pressure and duration?
  7. Availability for 2-5 sessions per week?

  8. Private chamber vs. multiplace chamber?

  9. Safety Protocols:

  10. Oxygen toxicity monitoring procedures?
  11. Emergency protocols if adverse event occurs?

  12. Barotrauma prevention and management?

  13. Logistics:

  14. Cost per session?
  15. Insurance coverage or self-pay?
  16. Scheduling flexibility for coordination with chemo?

πŸ“– References & Resources

Key Papers on HBOT + Cancer

  1. Seyfried TN, et al. "Press-Pulse: A Novel Therapeutic Strategy for the Metabolic Management of Cancer." Nutrition & Metabolism. 2017.

  2. Poff AM, et al. "The Ketogenic Diet and Hyperbaric Oxygen Therapy Prolong Survival in Mice with Systemic Metastatic Cancer." PLoS ONE. 2013.

  3. Stuhr LE, et al. "Hyperoxia Retards Growth and Induces Apoptosis and Loss of Glands and Blood Vessels in DMBA-Induced Rat Mammary Tumors." BMC Cancer. 2004.

  4. Moen I, Stuhr LE. "Hyperbaric Oxygen Therapy and Cancerβ€”A Review." Targeted Oncology. 2012.

Metabolic Therapy Resources

  1. Seyfried TN. Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer. Wiley, 2012.

  2. Schwartz K, et al. "Treatment of Glioma Patients with Ketogenic Diets: Report of Two Cases Treated with an IRB-Approved Energy-Restricted Ketogenic Diet Protocol and Review of the Literature." Cancer & Metabolism. 2015.

  3. Weber DD, et al. "Ketogenic Diet in Cancer Therapy." Aging. 2018.

Clinical Guidelines

  1. UHMS (Undersea and Hyperbaric Medical Society). "Indications for Hyperbaric Oxygen Therapy." 14th Edition, 2019.

  2. Jain KK. Textbook of Hyperbaric Medicine. 6th Edition, Springer, 2017.

πŸ“ Summary & Next Steps

Key Takeaways

  1. HBOT + Keto is a rational metabolic strategy based on Warburg effect targeting and Seyfried press-pulse hypothesis

  2. Current safety barriers prevent immediate start:

  3. Severe thrombocytopenia (61 platelets)
  4. Mild anemia (10.3 Hgb)

  5. Rapid tumor progression requiring primary therapy optimization

  6. Phased protocol designed for safety and efficacy:

  7. Start low (1.5 ATA, 45-60 min, 2-3x/week)
  8. Escalate based on tolerance and response

  9. Maintain therapeutic ketosis throughout

  10. Close monitoring is essential:

  11. Weekly blood tests (Ξ²-HCG, CRP, FBC)
  12. Daily glucose/ketone tracking

  13. Symptom surveillance for oxygen toxicity

  14. HBOT is adjuvant, not primary therapy:

  15. Must run parallel to effective systemic treatment
  16. Unlikely to control aggressive disease alone
  17. Best used as metabolic enhancement strategy

Immediate Action Items

  • [ ] Complete current EP chemotherapy cycle
  • [ ] Monitor blood counts twice weekly (target platelets >80, Hgb >11.5)
  • [ ] Optimize ketogenic diet (achieve GKI <3 consistently)
  • [ ] Begin daily glucose/ketone tracking
  • [ ] Iron/nutritional assessment and supplementation
  • [ ] Schedule oncology consultation to discuss HBOT integration
  • [ ] Research local HBOT facilities and costs
  • [ ] Recheck Ξ²-HCG trend after 2-3 weeks to assess EP response

Timeline

  • Now - Dec 15: Blood count recovery, keto optimization
  • Dec 15-20: Oncology clearance, HBOT facility selection
  • Late Dec/Early Jan: Initiate Phase 1 HBOT (if cleared)
  • Jan-Feb 2026: Escalate through phases based on response

Document Status: Living document - will update based on blood test results, treatment response, and clinical decisions.

Next Review Date: December 15, 2025 (after platelet recovery assessment)

This analysis represents a personalized treatment planning document based on current clinical data and published research. All decisions should be made in consultation with qualified medical professionals. HBOT is not FDA-approved for cancer treatment and should be considered experimental/adjuvant therapy.