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

A Novel Approach to Cancer Treatment: Integrating the Mitochondrial-Stem Cell Connection Theory

On September 19, 2024, a groundbreaking protocol in integrative cancer treatment was peer-reviewed and published in a scientific journal, marking a significant advancement in the field. This innovative work was spearheaded by a team of researchers, including Dr. Makis, a prominent figure in oncology and metabolic research. Dr. Makis’s contributions have been pivotal in developing this protocol, which combines orthomolecular medicine with metabolic strategies to address cancer at its core. His insights and publications are widely disseminated on the “X” platform.

Understanding the Mitochondrial-Stem Cell Connection (MSCC) Theory

The MSCC theory posits that cancer arises from a deficiency in oxidative phosphorylation (OxPhos) within stem cells. This energy shortfall can lead to the development of cancer stem cells (CSCs), which are crucial for tumor growth, progression, and metastasis. Unlike traditional genetic theories of cancer, the MSCC emphasizes metabolic dysfunction as a primary factor in malignancy. By merging concepts from cancer stem cell theory and metabolic theory, this approach underscores the necessity for therapies that specifically target CSCs and their altered energy pathways.

Despite advancements in cancer therapies, conventional treatments often overlook the metabolic weaknesses of CSCs. These cells are resistant to standard therapies and significantly contribute to tumor recurrence and metastasis. Over recent decades, new treatments have only marginally improved survival rates, highlighting the urgent need for alternative strategies. In response, a hybrid orthomolecular protocol has been formulated, drawing from molecular biology, pharmacology, and clinical research. This protocol aims to enhance OxPhos, decrease cancer cell reliance on glucose and glutamine, and specifically target CSCs and metastatic processes.

Core Principles of the MSCC Theory

1. Impaired OxPhos: Dysfunctional energy production in stem cells can trigger the transformation into CSCs, which drive tumorigenesis (Martinez et al., 2024).
2. Energy Dependence: Cancer cells heavily depend on glucose and glutamine to compensate for OxPhos deficiencies, facilitating their survival and growth (Seyfried et al., 2020).
3. CSC Resistance: Conventional therapies often fail to eradicate CSCs, which possess strong tumorigenic potential and promote metastasis (Adams & Strasser, 2008).
4. Tumor Microenvironment: Mitochondrial dysfunction creates a hostile microenvironment characterized by acidity, hypoxia, and structural abnormalities, further supporting cancer growth (Martinez et al., 2024).
5. Universal Application: These principles apply to all cancer types, offering a cohesive framework for understanding malignancy.

Proposed Hybrid Orthomolecular Protocol

Based on a review of the scientific literature, the following protocol combining orthomolecules, drugs, and additional therapies for targeting the MSCC in cancer treatment is proposed:

• Intravenous Vitamin C:
  • Intermediate- and high-grade cancers: Dose of 1.5g/kg/day, 2-3 times per week (Fan et al., 2023). Established as a non-toxic dose for cancer patients (Wang et al., 2019).
• Oral Vitamin D:
  • All cancer grades: Dose of 50,000 IU/day for patients with a blood level ≤ 30ng/mL; 25,000 IU/day for levels 30-60ng/mL; and 5,000 IU/day for levels 60-80ng/mL. Established as a non-toxic dose (Cannon et al., 2016; Ghanaati et al., 2020; McCullough et al., 2019).
• Zinc:
  • All cancer grades: Dose of 1 mg/kg/day is established as a non-toxic dose for cancer patients (Hoppe et al., 2021; Lin et al., 2006).
• Ivermectin:
  • Low-grade cancers: Dose of 0.5 mg/kg, 3 times per week (Guzzo et al., 2002).
  • Intermediate-grade cancers: Dose of 1 mg/kg, 3 times per week (Guzzo et al., 2002).
  • High-grade cancers: Dose ranging from 1 mg/kg/day (de Castro et al., 2020) to 2 mg/kg/day (Guzzo et al., 2002).
• Benzimidazoles and DON (6-diazo-5-oxo-L-norleucine) :
  • Low-grade cancers: Mebendazole: Dose of 200 mg/day (Dobrosotskaya et al., 2011).
  • Intermediate-grade cancers: Mebendazole: Dose of 400 mg/day (Chai, et al., 2021).
  • High-grade cancers: Mebendazole dose of 1,500 mg/day (Son, et al., 2020) or Fenbendazole 1,000 mg 3x per week (Chiang, et al., 2021)
  • Benzimidazoles are much easier to obtain than DON (6-diazo-5-oxo-L-norleucine). However, for metastatic cancers, which rely heavily on glutamine (Seyfried, et al., 2020), a combination of DON and Benzimidazoles should be considered (Mukherjee, et al., 2023).
• Dietary Interventions:
  • All cancer grades: Ketogenic diet (low carbohydrate-high fat diet, 900 to 1500 kcal/day) (Weber et al., 2020). Ketone metabolic therapy consists of approximately 60-80% fat, 15-25% protein, and 5-10% fibrous carbohydrates. Adequate hydration and single-ingredient whole food ketogenic meals are necessary to achieve a glucose ketone index (GKI) score of 2.0 or below (Meidenbauer et al., 2015; Seyfried, Shivane et al., 2021). GKI should be measured 2–3 hours postprandial, twice a day if possible (Meidenbauer et al., 2015; Seyfried, Shivane et al., 2021).
  • Intermediate- and high-grade cancers: The ketogenic diet should be coupled with a water fast for 3 to 7 consecutive days in advanced cancers (Phillips et al., 2022; Arora et al., 2023). The water fast should be repeated several times (approximately every 3-4 weeks) throughout the treatment (Nencioni et al., 2018), but fasting needs to be undertaken cautiously in individuals using certain drugs and those with a BMI < 20, to prevent loss of lean body mass. For patients who cannot fast, the Fasting-Mimicking Diet (300 to 1,100 kcal/day of broths, soups, juices, nut bars, and herbal teas) can be used (Nencioni et al., 2018).
  • Additional Therapeutics:
    • All cancer grades: Moderate physical activity, 3 times per week. Increased heart and respiratory rate for a period of 45 to 75 minutes (Bull et al., 2020) with activities such as cycling, running, swimming, etc.
    • Press-Pulse therapy utilizes a two-axis approach for cancer treatment. The “Press” axis focuses on a ketogenic diet and stress management, while the “Pulse” axis combines 2-deoxyglucose (2-DG) to inhibit glycolysis, DON (6-diazo-5-oxo-L-norleucine) to block glutaminolysis, and hyperbaric oxygen therapy (HBOT) to reverse hypoxia. This metabolic strategy closely aligns with the proposed Mitochondrial-Stem Cell Connection (MSCC) theory.
    • Intermediate- and high-grade cancers or individuals who are unable to engage in physical activity: Hyperbaric oxygen therapy, 1.5 to 2.5 ATA for 45 to 60 minutes 2-3 times per week (Gonzalez et al., 2018; Poff et al., 2015).

Conclusion

The MSCC theory presents a compelling framework for re-evaluating cancer treatment by addressing the metabolic dysfunctions that underlie malignancy. The proposed hybrid protocol, supported by extensive research and clinical insights, offers a comprehensive strategy for enhancing OxPhos, targeting CSCs, and mitigating metastasis. Dr. Makis and his team stress the importance of further comparative studies to validate the effectiveness and safety of this approach in relation to standard therapies. This innovative strategy holds promise for improving outcomes across various cancer types, paving the way for more effective and personalized treatment options.