Targeting the Mitochondrial-Stem Cell Connection in Cancer Treatment: A Hybrid Orthomolecular Protocol - ISOM

A scientific and logical approach to treating cancer patients as a part of an integrative oncological management strategy.

Click below for the educational video on Cancer Stem Cells.

Click below to access the paper.

By targeting the Stem Cells of Cancer, you are targeting the source of the cancer cells.

Ian Brighthope

The paper proposes a hybrid orthomolecular protocol to target the mitochondrial-stem cell connection (MSCC) in cancer treatment. The MSCC theory posits that cancer stems from chronic oxidative phosphorylation (OxPhos) insufficiency in stem cells, which leads to the formation of cancer stem cells (CSCs) and abnormal energy metabolism, driving malignancy. The protocol aims to restore OxPhos, inhibit cancer cell fuel sources (glucose and glutamine), and specifically target CSCs and metastasis.

The protocol includes the following components:

1. Intravenous Vitamin C: Suggested for intermediate- and high-grade cancers at a dose of 1.5 g/kg/day, administered 2-3 times per week. Vitamin C enhances ATP production, reduces oxidative stress in cancer cells, and selectively targets CSCs. Vitamin C enters cancer cells via glucose receptors, generating hydrogen peroxide selectively toxic to cancer cells. High doses (1.5 g/kg/day) achieve pharmacologic concentrations that cancer cells cannot effectively metabolize, leading to oxidative stress and apoptosis. It inhibits glycolysis and glutaminolysis, the primary energy sources for cancer cells, and reduces tumor volume and metastasis.

2. Oral Vitamin D: Dose adjustments based on vitamin D levels in blood, with a maximum of 50,000 IU/day for deficient patients. A target level of 80 ng/mL is (200nmol/L) recommended to achieve anti-cancer effects and inhibit CSCs. High initial doses (up to 50,000 IU/day) correct deficiencies quickly, then maintenance doses (2,000 IU/day) are recommended. Serum levels are regularly monitored to ensure they reach and maintain therapeutic levels (80 ng/mL). Serum calcium and parathyroid hormone monitoring are necessary at these high doses. Vitamin D enhances OxPhos and reduces CSC viability. It has also been associated with lower cancer mortality rates and has shown preventive effects against cancer recurrence.

3. Zinc: Recommended at 1 mg/kg/day, shown to protect mitochondria, induce mitochondrial apoptosis in cancer cells, and enhance chemotherapy sensitivity in cancer cells. Zinc stabilizes mitochondrial membranes, minimizes oxidative damage, and reduces glycolytic activity in cancer cells. At 1 mg/kg/day, it also regulates cellular apoptosis mechanisms, notably reversing CSC-like properties in some cancer types. Studies support zinc’s role in suppressing tumour markers and reducing chemo-resistance in cancers such as breast and oral cancers.

4. Ivermectin: Proposed as an anti-cancer agent with varying doses for different cancer grades, up to 2 mg/kg/day for high-grade cancers. Ivermectin induces apoptosis and inhibits glycolysis and CSC growth. For low-grade cancers, 0.5 mg/kg three times per week is recommended, with doses increasing to 2 mg/kg/day for high-grade cancers. Ivermectin induces autophagy, interferes with the cancer cell glycolysis pathway, and disrupts CSC metabolism, showing superior outcomes over standard chemotherapies in some cases (e.g., breast cancer). Notably, it maintains a favourable safety profile even at high doses.

5. Benzimidazoles and DON (6-diazo-5-oxo-L-norleucine): Mebendazole and Fenbendazole are included for their anti-cancer effects. DON is suggested particularly for metastatic cancers reliant on glutamine. These drugs inhibit microtubule formation, induce cell cycle arrest, and reduce angiogenesis, which are essential for CSC survival. Mebendazole has shown comparable effects to conventional chemotherapy but with a safer profile.

DON (6-diazo-5-oxo-L-norleucine) is a potent inhibitor of glutamine metabolism, DON disrupts energy production in CSCs. Given glutamine’s central role in metastasis, DON is particularly effective in metastatic cancers. It can be administered alone or in combination with Benzimidazoles.

6. Dietary Interventions: A ketogenic diet and fasting are included to reduce cancer cell energy sources, primarily through inhibiting glycolysis and promoting OxPhos. Fasting-mimicking diets are advised for patients unable to fast. High-fat, low-carbohydrate diets (60–80% fat) are used to shift metabolism away from glucose dependency, targeting the Warburg effect seen in cancer cells. The diet is particularly effective when coupled with fasting or fasting-mimicking regimens to deprive cancer cells of glucose. Fasting promotes autophagy, reduces oxidative stress, and enhances the effectiveness of concurrent therapies. For patients unable to fast, a fasting-mimicking diet provides limited calories (300-1,100 kcal/day) in nutritionally dense liquids and foods.

Physical activity is recommended for all grades of cancer to improve mitochondrial respiration, while hyperbaric oxygen therapy (HBOT) is advised for advanced cancer patients or those unable to engage in physical activity. Regular moderate-intensity exercise (e.g., cycling, running) supports OxPhos, enhances mitochondrial health, and is associated with improved cancer survival rates. Exercise’s impact on glycolytic suppression and mitochondrial biogenesis may help inhibit cancer cell proliferation.

Cancer cells often thrive in hypoxic environments, and HBOT introduces high oxygen levels to induce oxidative stress, selectively harming cancer cells while supporting normal cell respiration. HBOT works synergistically with ketogenic diets, enhancing the protocol’s anti-tumour efficacy.

The protocol spans approximately 12 weeks, during which patients undergo regular monitoring and adjustments based on their response and treatment tolerance. Vitamin D and zinc levels are regularly checked, while glucose ketone index (GKI) is monitored to ensure metabolic ketosis.

Additional orthomolecules such as Vitamin K2, Coenzyme Q10, and magnesium may be considered by the treating physician to support mitochondrial function, depending on individual patient needs and availability of compounds. These supplements enhance OxPhos and cellular health in normal cells, while their pro-oxidant effects selectively target cancer cells.

The proposed protocol represents an innovative and integrative approach to cancer treatment, addressing both the metabolic and stem cell aspects of cancer. By enhancing OxPhos and targeting cancer’s metabolic vulnerabilities, it holds promise as an alternative or complementary therapy to standard cancer treatments. Further clinical studies are suggested to validate this approach's effectiveness and safety across different cancer types.

Summary provided by Ian Brighthope.

If you are a patient wishing to adopt the above protocol, you must seek the therapy from a qualified physician who is trained in integrative oncology.

The above is not intended to be medical advice as treatment must be tailored to the individual patient.