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

By Editorial Team

Authors: 

Ilyes Baghli1, William Makis2, Paul E. Marik3, Michael J. Gonzalez4,5,6, William B. Grant7, Ron Hunninghake8, Thomas E. Levy8, Homer Lim9, Richard Z. Cheng10, Igor Bondarenko11, Paul Bousquet12, Roberto Ortiz13, Mignonne Mary14, Dominic P. D’Agostino15, Pierrick Martinez16

1 International Society for Orthomolecular Medicine, Toronto, ON, Canada
2 Alberta Health Services, Cross Cancer Institute, Edmonton, AB, Canada
3 Frontline COVID-19 Critical Care Alliance, Washington, DC, USA
4 University of Puerto Rico, Medical Sciences Campus, School of Public Health, San Juan, PR
5 Universidad Central del Caribe, School of Chiropractic, Bayamon, Puerto Rico
6 EDP University, Naturopathic Sciences Program, Hato Rey, Puerto Rico
7 Sunlight, Nutrition, and Health Research Center, San Francisco, CA, USA
8 Riordan Clinic, 3100 North Hillside, Wichita, KS, USA
9 Akesis Holistic Health, Manila, Philippines
10 Cheng Integrative Health Center, Doctor’s Weight Loss Center, Columbia SC, USA
11 Medical Institute for Nutrition Science and Technology, Riga, LV-1005, Latvia.
12 Association Internationale pour une Médecine Scientifique Indépendante et Bienveillante, Amiens, France
13 Mexican Association of Orthomolecular Nutrition, Mexico City, Mexico
14 Remedy Room Integrative Medicine, New Orleans LA, USA
15 Department of Molecular Pharmacology and Physiology, Laboratory of Metabolic Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
16 Association Cancer et Métabolisme, 30000 Nîmes, France.
Correspondence: pierrick.martinez@protonmail.com

Author(s): Baghli I, et al.
Date of Publication: 19 September 2024

Citation: Baghli I, et al. (2024) Targeting the Mitochondrial-Stem Cell Connection in Cancer Treatment: A Hybrid Orthomolecular Protocol. J Orthomol Med. 39.3

Abstract

The mitochondrial-stem cell connection (MSCC) theory suggests that cancer originates from chronic oxidative phosphorylation (OxPhos) insufficiency in stem cells. This OxPhos insufficiency leads to the formation of cancer stem cells (CSCs) and abnormal energy metabolism, ultimately resulting in malignancy. This concept integrates two well-established theories: the cancer stem cell theory and the metabolic theory. Drawing on insights from molecular biology, pharmacology, and clinical studies, this manuscript introduces a hybrid orthomolecular protocol targeting the MSCC. The protocol includes 7 therapeutic recommendations, consisting of orthomolecules, drugs, and additional therapies. The aim of this hybrid orthomolecular protocol is to achieve additive and synergistic effects to enhance OxPhos, inhibit the primary fuels of cancer cells (glucose and glutamine), target CSCs and metastasis. Thus, numerous experiments suggest that targeting MSCC could be a potential therapeutic approach for cancer treatment.
Keywords: cancer metabolism; mitochondria; oxidative phosphorylation; cancer stem cells; glucose; glutamine; orthomolecules; repurposed drugs; diet; lifestyle interventions

The Hybrid Orthomolecular Cancer Protocol: 7 therapeutic recommendations, consisting of orthomolecules, drugs, and additional therapies

1. Intravenous Vitamin C 

Intermediate- and high-grade cancers: Dose of 1.5g/kg/day, 2-3x per week (Fan, et al., 2023). Established as a non-toxic dose for cancer patients (Wang, F., et al., 2019). 

2. 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 5000 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). 

It is necessary to reach a blood level of 80 ng/mL of vitamin D (25-hydroxyvitamine D (25(OH) D) (Kennel, et al., 2010; Mohr, et al., 2014; Mohr, et al., 2015). This level is non-toxic (Holick, et al., 2011). Once this level is reached it must be maintained with a reduced daily dosage of ≈ 2000 IU/day (Ekwaru, et al., 2014). The vitamin D blood concentration should be measured every two weeks for high doses and monthly for lower doses. 

3. 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). The reference range for serum zinc concentration is 80 to 120 μg/dL (Mashhadi, et al., 2016; Yokokawa, et al., 2020). Once this level is reached it must be maintained with a reduced daily dosage of 5mg/day (Li, et al., 2022). The zinc blood concentration should be measured monthly.

4. Ivermectin 
  • Low-grade cancers: Dose of 0.5mg/kg, 3x per week (Guzzo, et al., 2002). 
  • Intermediate-grade cancers: Dose of 1mg/kg, 3x per week (Guzzo, et al., 2002). 
  • High-grade cancers: Dose from 1 mg/kg/day (de Castro, et al., 2020) to 2 mg/kg/day (Guzzo, et al., 2002). 
All these doses have been established as tolerable for humans (Guzzo, et al., 2002). 

5. Benzimidazoles and DON*
  • 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). 
All these doses have been established as tolerable for humans (Chai, et al., 2021; Chiang, et al., 2021; Son, et al., 2020). Benzimidazoles can be replaced or combined with DON, administered without toxicity; intravenously or intramuscularly: 0.2 to 0.6 mg/kg once daily; or orally: 0.2 to 1.1 mg/kg once daily (Lemberg, et al., 2018; Rais, et al., 2022). Benzimidazole are much easier to obtain than DON. 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). 

*DON (6-diazo-5-oxo-L-norleucine) is a glutamine-specific antagonist more potent than Benzimidazoles.

Read More: Fenbendazole cancer success stories (More than 130 case reposts)

6. 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 (≈ 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 < 20 BMI, to prevent loss of lean body mass. 

For patients who can not fast, the FastingMimicking Diet (300 to 1,100 kcal/day of broths, soups, juices, nut bars, and herbal teas) can be used (Nencioni, et al., 2018). 

7. Additional Therapeutics 

All cancer grades: Moderate physical activity, 3x 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.
 
Intermediate- and high-grade cancers or individuals who are unable to engage in physical activity: Hyperbaric oxygen therapy (HBOT), 1.5 to 2.5 ATA for 45 to 60 minutes 2-3x per week (Gonzalez, et al., 2018; Poff, et al., 2015).

The protocol should be followed for an average duration of 12 weeks, regardless of cancer type. The analysis of the interactions between each of the molecules revealed no contraindications to the combination of these substances (ANSM, 2023; CRAT, 2024; Lemberg, et al., 2018; Vidal, 2024). The treatment dosage and duration can be adjusted by the physician according to the individual patient, their ability to obtain the various molecules, and the treatment results. Adaptation of the protocol to include additional molecules to restore health, could be considered by the physician. These may include: vitamin K2 (Xv, et al., 2018), vitamin E (Abraham, et al., 2019), coenzyme Q10 (Liaghat, et al., 2024), methylene blue (da Veiga Moreira, et al., 2024), niacinamide (Yousef, et al., 2022), riboflavin (Suwannasom, et al., 2020), Artemisinin + 5-aminolevulinic acid (to cause porphyrin accumulation) (Adapa, et al., 2024), melatonin (Mocayar, et al., 2020), NADH (Medjdoub, et al., 2016), and magnesium (Ashique, et al., 2023), as examples. However, antioxidant dosages should be avoided.


Notes:

No single drug is a miracle cure for all cancers. Taking a particular drug or following a specific protocol as a standalone strategy cannot replace the critical importance of maintaining a healthy diet and lifestyle. Factors such as heavy smoking, excessive alcohol consumption, chronic stress, physical inactivity, overweight, and obesity are well-established cancer-promoting risks that must be addressed and removed to improve outcomes and reduce cancer risk.

The most effective way to fight cancer is by adopting a comprehensive, multi-faceted approach that includes maintaining good overall health. This means eating a nutritious, whole-food diet rich in fruits, vegetables, whole grains, and legumes while avoiding ultra-processed foods, excessive red and processed meats, and limiting alcohol intake. Regular physical activity, maintaining a healthy body weight, and avoiding tobacco use are equally important components of this strategy. Each of these lifestyle factors contributes incrementally to reducing cancer risk and can enhance the effectiveness of conventional treatments when used alongside them.

Research consistently shows that dietary and lifestyle patterns act synergistically to influence cancer risk. For example, the World Cancer Research Fund’s expert panel recommends a dietary pattern emphasizing fiber-rich foods, fruits, vegetables, and calcium-containing foods, combined with regular physical activity and smoking avoidance, to lower the risk of breast and colorectal cancers. Limiting alcohol and processed meat consumption is also advised, as these have been linked to increased cancer risk. These recommendations are supported by strong evidence demonstrating that adherence to healthy lifestyle guidelines can reduce cancer incidence by significant margins.

Everyone’s situation is unique, and cancer treatment must be personalized. It is vital to arm yourself with medical knowledge that complements what your oncologist provides. Being informed allows you to engage more effectively in your care, ask pertinent questions, and make decisions that align with your values and health goals.

Whether you are currently living with cancer or are a survivor, always consult your trusted healthcare provider to determine the best treatment plan tailored to your individual needs. Combining medical treatment with healthy lifestyle changes offers the best chance for improved outcomes and quality of life.

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