ISOM Protocol: A Modern Metabolic Strategy Using Repurposed Drugs
The ISOM Hybrid Orthomolecular Protocol is a science-based cancer treatment framework developed by researchers affiliated with the International Society for Orthomolecular Medicine (ISOM) and practicing clinicians, including Dr. William Makis. Published in 2024, it represents one of the most advanced modern approaches to cancer built around mitochondrial medicine, cancer stem cell biology, metabolic therapy, and repurposed drugs.
Rather than viewing cancer primarily as a genetic disease, the ISOM protocol is based on the idea that cancer begins as a mitochondrial energy failure within stem cells. When oxidative phosphorylation becomes impaired, cells shift toward fermentation-based metabolism and evolve into cancer stem cells, which then drive tumor growth, resistance, and metastasis. The protocol aims to restore mitochondrial function in healthy cells while disrupting the metabolic pathways cancer cells depend on for survival.
The Science Behind the Protocol
The ISOM model integrates the metabolic theory of cancer and the cancer stem cell theory, proposing that genetic mutations are downstream effects rather than the root cause. Cancer cells survive through glucose- and glutamine-driven fermentation rather than oxygen-based energy production, and cancer stem cells exploit this metabolic advantage to persist after treatment. The ISOM protocol therefore targets mitochondrial respiration, metabolic fuels, and stem cell survival simultaneously.
Repurposed Drugs in the ISOM Protocol
Ivermectin, fenbendazole, and mebendazole are used as metabolic disruptors rather than cytotoxic drugs. They interfere with cancer cell energy production, disrupt microtubules, impair glucose and glutamine metabolism, and weaken cancer stem cell survival pathways. DON (6-diazo-5-oxo-L-norleucine) is included as a glutamine antagonist to suppress one of cancer’s primary metabolic fuels.
Rather than acting alone, these agents are layered to create sustained metabolic stress that cancer cells struggle to adapt to while normal cells remain resilient.
Orthomolecular and Metabolic Support
The protocol integrates high-dose vitamin C, vitamin D, and zinc to restore redox balance, immune function, and mitochondrial efficiency. A ketogenic diet, fasting strategies, exercise, and oxygen-based therapies are used to change the systemic metabolic environment, depriving cancer cells of glucose while strengthening oxidative metabolism in healthy tissue.
Dosage Directions (General ISOM Framework)
Important Note
These are educational reference ranges based on the published ISOM framework and clinical discussion by its authors. They are not medical advice and must only be used under physician supervision.
Repurposed Drugs
- Ivermectin: Typically used at 0.2–0.4 mg per kg body weight, taken 2–3 times per week, often on an empty stomach or with fasting days to enhance metabolic stress.
- Fenbendazole or Mebendazole: Commonly used at 222–444 mg daily, either continuously or 5 days on / 2 days off, depending on tolerance and protocol phase.
- DON (6-diazo-5-oxo-L-norleucine): Used at very low doses under medical supervision only, typically in intermittent cycles due to potency and limited safety margins.
Orthomolecular Support
- Vitamin C (oral): 2–4 grams daily in divided doses. Intravenous vitamin C is often used clinically at 25–75 grams per infusion, 1–3 times weekly.
- Vitamin D3: 5,000–10,000 IU daily, adjusted to maintain optimal blood levels (40–80 ng/mL).
- Zinc: 25–50 mg daily, typically with copper balance support if used long-term.
Metabolic Therapy
- Diet: Strict ketogenic or very low-carbohydrate diet, targeting blood glucose under ~90 mg/dL and nutritional ketosis.
- Fasting: 16–18 hour daily fasting windows or periodic 24–48 hour fasts, when medically appropriate.
- Exercise: At least 30 minutes daily, combining resistance training and aerobic movement.
- Oxygen Therapy (optional): Hyperbaric oxygen therapy (HBOT) sessions are commonly used 2–5 times weekly in clinical metabolic oncology settings.
Dr. William Makis and Clinical Translation
Dr. William Makis, a Canadian physician and co-author of the ISOM paper, has played a key role in translating repurposed drug oncology into real-world clinical practice. His work highlights real-world use of ivermectin, benzimidazoles, vitamin C, and metabolic therapies in advanced cancer settings, and he has described the ISOM framework as the most structured metabolic oncology protocol to date.
Why the ISOM Protocol Matters
The ISOM protocol addresses cancer at its metabolic core — targeting mitochondrial dysfunction, fermentation-based energy production, and cancer stem cell persistence. Rather than focusing solely on tumor genetics, it reshapes the entire metabolic environment, offering a complementary framework for patients seeking integrative, systems-based oncology strategies.
Protocol Stack (Quick Links)
Below are commonly referenced items mentioned in this article. Links are provided for convenience — always review the label and consult a professional before use.
Example: 222 mg capsule / 1 g granules equivalent
Example: 12 mg (as commonly referenced)
