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New treatment for cancer targeting cell respiration and mitochondrial function has been published

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In September, a paper was published in the Journal of Orthomolecular Medicine which describes the scientific rationale for the hybrid orthomolecular protocol as well as providing detailed information on the protocol itself.

The hybrid orthomolecular protocol is a new strategy for treating cancer.  It involves the use of various supplements and dietary interventions, including vitamin D, zinc, ivermectin, benzimidazoles and DON, as well as a ketogenic diet and fasting.

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One of the authors of the September paper was Canadian physician Dr. William Makis; another was Dr. Paul Marik, author of the book ‘Cancer Care: The Role of Repurposed Drugs and Metabolic Interventions in Treating Cancer’.  Last week we published an introduction to Dr. Marik’s book, see HERE.

Announcing the paper for the new protocol for cancer had been published, Dr. William Makis tweeted the following:

The protocol for the prevention and treatment of cancer Dr. Makis was referring to was published in the Journal of Orthomolecular Medicine on 19 September 2024.  Below is a summary of this paper; you can read the paper titled ‘Targeting the Mitochondrial-Stem Cell Connection in Cancer Treatment: A Hybrid Orthomolecular ProtocolHERE.

Table of Contents

The Mitochondrial-Stem Cell Connection and Current Cancer Therapies

The concept of the mitochondrial-stem cell connection (“MSCC”) in cancer treatment combines the cancer stem cell theory and the metabolic theory, suggesting that cancer arises from impaired oxidative phosphorylation (OxPhos) in one or more stem cells, potentially leading to the formation of cancer stem cells (“CSCs”) and tumorigenesis, the gradual process by which normal cells acquire the ability to form tumours.

The MSCC theory aligns with the metabolic theory of cancer but specifically focuses on the crucial role of CSCs in every stage of the disease, differing from the CSCs theory, which typically presents cancer as a genetic disease.

Standard cancer therapies, based on the somatic mutation theory (“SMT”), target the DNA of cancer cells but do not restore OxPhos and sometimes even alter it, and only target bulk cells but cannot target CSCs, which have the strongest tumorigenic potential and are involved in metastasis.

The outcomes of new anti-cancer therapies have been limited, with an overall survival improvement of 2.4 months over the past fifteen years and 3.4 months over the past thirty years, which could be partially explained by the inability of these therapies to target the MSCC.

A hybrid orthomolecular protocol has been developed, which includes several orthomolecules, drugs and additional therapies that have demonstrated an ability to enhance OxPhos, reduce fermentable fuels, and target CSCs and metastasis, and is proposed as a new therapeutic strategy for cancer.

The key points that underpin the MSCC concept include: the alteration of OxPhos initiates tumorigenesis in one or more normal stem cells; the correlation between the degree of malignancy and significantly lower mitochondria and lower total respiratory capacity in tumour cells; and, cancer cells require glucose and glutamine as primary fuels to compensate for OxPhos insufficiency.

The tumour microenvironment, characterised by low pH, hypoxia, entropy, pressure and deformation, increased temperature, stroma, altered rotation of cytoplasmic water and damped bioelectricity or electromagnetic field, is a consequence of mitochondrial impairment.

Metastasis, the leading cause of cancer mortality, occurs due to fusion hybridisation between CSCs and macrophages, according to the MSCC.

The principles of the MSCC apply to all types of cancer, and the hybrid orthomolecular protocol has the potential to be a new therapeutic strategy for cancer treatment.

Vitamin C and Cancer Treatment

Vitamin C has been known for its anti-cancer properties for over 50 years, demonstrating cytotoxic effects on cancer cells both in vitro and in vivo.

Research has shown that vitamin C alone is more effective than chemotherapy in inducing apoptosis in colon cancer cells and reducing tumour weight and metastases in pancreatic cancer.

Vitamin C can directly infiltrate the tumour’s intracellular environment, reduce oxidative stress, target the mitochondria of cancer cells and induce cancer cell death, including metastases.

The alkaline intracellular environment of cancer cells can be compromised by vitamin C’s acidic pH, which can inhibit tumour progression and restore cellular respiration and apoptosis function.

Vitamin C can target and eradicate CSCs, protect against hypoxia and inflammation, and induce apoptosis in drug-resistant cancer cells.

High pharmacological intravenous doses of vitamin C have been shown to kill cancer cells but not normal cells, and can induce apoptotic cell death in tumour cell lines through a pro-oxidant mechanism.

Vitamin C can enter mitochondria in its oxidised form via glucose receptors and protect mitochondria from oxidative injury in normal cells.

Vitamin C has the ability to inhibit glycolysis and glutamate synthesis, specifically limiting glutamine synthesis by inhibiting glutamine synthetase (“GS”), leading to a decrease in the level of glutathione and an increase in reactive oxygen species (“ROS”) resulting in cell death.

GS inhibition can reverse the phenotype of M2 macrophages and promote the polarisation of M1 macrophages, reducing intracellular glutamine and eliminating metastases.

The use of intravenous vitamin C cancer treatment, pioneered by Cameron and Pauling, has been observed to improve survival times for many cancers, with survival times multiplied by 55 after 1 year in terminal cancer patients.

The research suggests that vitamin C can be a potential therapeutic agent for targeting the mitochondrial-stem cell connection in cancer treatment.

The use of intravenous vitamin C in cancer treatment has shown promise, with a study by Cameron and Pauling (1978) demonstrating its effectiveness when administered at 10 g/day for approximately 10 days, followed by oral supplementation.

However, a subsequent study by the Mayo Clinic failed to reproduce these results, likely due to the replacement of intravenous vitamin C with oral supplementation, which results in lower plasma concentrations and reduced effects.

But several case studies by the Riordan Clinic team and collaborators have reported tumour regression in patients receiving intravenous vitamin C.

It’s not only vitamin C, other anti-oxidant vitamins also have benefits concerning cancer.  Antioxidant vitamins – including vitamins A, C and E – have been shown to reduce cancer mortality when taken regularly but their anti-oxidant action is primarily beneficial for cancer prevention, as they can sometimes promote tumour growth.

Vitamin D and Cancer Treatment

Vitamin D has demonstrated anti-cancer effects in vitro and in vivo for almost all cancer types, targeting the mitochondria by improving metabolism and regulating mitochondrial respiration.

Vitamin D also targets CSCs and metastases, inhibiting glycolysis and glutaminolysis pathways.

Daily vitamin D supplementation has been shown to reduce total cancer mortality, but this effect is not observed with infrequent large bolus doses (single, high-dose administration of vitamin D, typically exceeding 200,000 international units (“IU”).)

It should be noted that cancer patients are often deficient in vitamin D and can benefit from effective therapy with minimal risk, including intravenous administration. 

The paper noted a case report which highlighted the potential benefits of vitamin D therapy in an elderly patient with advanced pancreatic cancer who was unable to undergo conventional treatments.  Instead, the patient received a daily dose of 50,000 IU of vitamin D3 for 9 months and experienced an unexpectedly prolonged period of disease-free progression, far exceeding what would have been expected with conventional chemotherapy.

And Chandler et al. showed a preventive effect of vitamin D supplementation in patients with a normal body mass index (“BMI”), demonstrating a 37% reduction in the incidence of metastatic cancer leading to a reduction in cancer mortality of 42%.

A randomised controlled trial found that vitamin D supplementation significantly reduced relapse or death in gastrointestinal cancer patients who were p53 immunoreactive, and meta-analyses reported inverse correlations between serum 25-hydroxyvitamin D levels and cancer incidence in at least 12 different cancer types.

Zinc and Cancer Treatment

Zinc supplementation has been recommended as a possible adjunctive treatment for cancer, as it protects mitochondria from damage by reactive oxygen species and induces mitochondrial pyruvate transport, oxidative phosphorylation and ATP production.

In various cancer cells – including ovarian, oral and breast cancer cells – zinc, especially if introduced together with zinc ionophores, has been shown to induce the degradation of mitochondria, restore apoptosis and suppress cancer stem cell-like properties.

Excess zinc can irreversibly block the energy production of cancer cells, cause NAD+ loss, and inhibit cellular glycolysis.  And as with vitamin D, zinc deficiency is implicated in many cancers, including oesophageal, liver, lung, breast and colon cancer.

There are 151 publications confirming the link between zinc deficiency and malignancy, and zinc shows toxicity toward cancer cells without harming healthy cells, with deficiency negatively correlating with survival rates.

Zinc may have a specific pro-oxidant effect on cancer cells, similar to vitamin C, and has been proposed as a potential adjunctive treatment for cancer.

Pharmaceutical Agents Targeting the MSCC

Several pharmaceutical agents have been identified as potential targets for the MSCC in cancer, including Vismodegib, Glasdegib, MK-0752, OMP-54F28, and Selinexor, which target genetic pathways associated with cancer stem cells.

Other agents, such as Metformin, Doxycycline, Tigecycline, and Bedaquiline, have been proposed to target mitochondria, but most of these agents do not restore mitochondrial homeostasis, instead altering or partly restoring dysfunction.

However, the paper warns that the alteration of mitochondrial function with pharmaceutical agents must be approached with caution, as it can be hazardous to healthy cells.

Ivermectin and Cancer Treatment

ivermectin, an anti-parasitic derived from Streptomyces avermitilis, has anti-cancer properties and induces autophagy and apoptosis of cancer cells through mitochondrial mediation.

Ivermectin has shown significant impacts on various cancer cell lines, inducing apoptosis in cancer cells in vivo and reducing tumour volume compared to controls.  It can target and regulate pyruvate kinase muscle isoforms, inhibit glycolysis, induce autophagy and have a selective pro-oxidant effect on cancer cells.

Ivermectin can also target CSCs, metastases and macrophages, and is more effective at inhibiting CSCs in breast cancer cells compared to chemotherapy.  In vivo, ivermectin alone is more effective than standard chemotherapy alone at reducing tumour weight and volume in pancreatic cancer.

Ivermectin is a very safe drug, with no serious adverse reactions found in healthy volunteers at high doses and no serious adverse effects in cancer patients taking high doses for extended periods.

Benzimidazoles and Cancer Treatment

Benzimidazoles, including fenbendazole and mebendazole, hold promising anti-cancer capabilities through microtubule polymerisation, induction of apoptosis, cell cycle arrest, anti-angiogenesis and blocking glucose and glutamine pathways.

Mebendazole and fenbendazole are structurally similar and generally just as effective in cancer, but only mebendazole is FDA-approved for use in humans.

Benzimidazoles induce apoptosis through mitochondrial injury and p53 expression, target CSCs and metastases, and are effective against chemo-resistant cancer cells.

Mebendazole is more potent against gastric cancer cell lines than other well-known chemotherapeutic drugs and leads to significantly prolonged survival compared to standard chemotherapy for glioblastoma multiforme.

Mebendazole is established as a safe drug, with long-term treatment demonstrated to be without significant side effects in paediatric patients and no severe adverse effects in patients with treatment-refractory gastrointestinal cancer.

Case reports have shown near-complete remission in patients with metastatic colon cancer and adrenocortical carcinoma after taking mebendazole, following the failure of chemotherapeutic agents.

A patient with metastatic cancer was treated with mebendazole 100mg twice daily, resulting in initial regression and subsequent stability of metastases for 19 months, with no significant adverse effects and satisfactory quality of life.

Similar results were observed with fenbendazole, where three patients with stage IV cancer experienced complete remission after treatment, despite previous progression of metastatic disease.

Diazo-5-oxo-L-norleucine (“DON”) and Cancer Treatment

DON is a glutamine-specific antagonist that has potent anti-tumour activity, specifically targeting glutamine and glucose uptake, and inducing apoptosis in CSCs.

Low daily doses of DON have been found to be non-toxic, making it a potential therapeutic option.

Fasting, Ketogenic Diet and Cancer Treatment

Fasting has been shown to improve mitochondrial activity, inhibit glycolysis and glutaminolysis, and induce autophagy, leading to the death of CSCs and enhanced anti-cancer effects when combined with other treatments.

A ketogenic diet and KMT have been found to inhibit CSC growth, restore apoptosis and increase cellular respiration, with therapeutic benefits enhanced when combined with DON and mebendazole.

The combination of a ketogenic diet and DON has been shown to reduce DON toxicity, and a case study reported the survival of a patient with grade IV glioblastoma for over 6 years after diagnosis, treated with a ketogenic diet and surgical reduction.

The goal of using a ketogenic diet and KMT is to restrict glycolysis and glutaminolysis pathways while transitioning the body into a state of ketosis to target cancer cells, with ketone supplementation studies demonstrating enhanced mitochondrial function and suppressed tumour growth.

Press-Pulse Therapy and Physical Activity

The proposed hybrid orthomolecular protocol for targeting the MSCC in cancer treatment combines various therapies, including diet, stress management, physical activity, and hyperbaric oxygen therapy (“HBOT”).

Additional therapeutic considerations include Press-Pulse therapy, which offers a two-axis therapy approach.

The “Press” axis involves a ketogenic diet and stress management, while the “Pulse” axis combines 2-deoxyglucose (2-DG), DON and HBOT to induce cancer-specific oxidative stress and reverse hypoxia.

Physical activity is beneficial in cancer treatment as it increases mitochondrial volume, improves mitochondrial respiration and decreases glycolytic activity, ultimately inhibiting cancer cell proliferation and inducing apoptosis.

HBOT has tumour-inhibitory effects, especially when combined with other therapies, and can target CSCs and metastases by increasing OxPhos.

The metabolic theory underlying the Press-Pulse therapy is closely related to the proposed MSCC theory, which aims to target the connection between mitochondria and stem cells in cancer treatment.

Hybrid Orthomolecular Protocol for Targeting the MSCC

At the end of the paper, the researchers describe in detail their proposed hybrid orthomolecular protocol for targeting the MSCC in cancer treatment, giving dosages and frequency for each of the drugs and vitamins. It involves the use of various supplements and dietary interventions, including vitamin D, zinc, ivermectin, benzimidazoles, and DON, as well as ketogenic diet and fasting.

It includes intravenous vitamin C at a dose of 1.5g/kg/day, 2-3 times per week, for intermediate- and high-grade cancers, and oral vitamin D at varying doses based on blood levels.

Vitamin D is recommended at a dose of 2000 IU/day to reach a blood level of 80 ng/ml, which is considered non-toxic and should be maintained with regular measurements every two weeks for high doses and monthly for lower doses.

Zinc is recommended at a dose of 1 mg/kg/day for cancer patients, with a reference range for serum zinc concentration of 80 to 120 μg/dl, and should be maintained with a reduced daily dosage of 5mg/day, with monthly measurements.

Ivermectin is recommended at different doses depending on the grade of cancer: 0.5mg/kg, 3x per week for low-grade cancers, 1mg/kg, 3x per week for intermediate-grade cancers and 1-2 mg/kg/day for high-grade cancers.

Benzimidazoles, such as mebendazole and fenbendazole, are recommended at different doses depending on the grade of cancer: 200 mg/day for low-grade cancers, 400 mg/day for intermediate-grade cancers and 1500 mg/day or 1000 mg 3x per week for high-grade cancers.

DON can be used as an alternative or in combination with benzimidazoles, administered intravenously or intramuscularly at 0.2 to 0.6 mg/kg once daily, or orally at 0.2 to 1.1 mg/kg once daily.

A ketogenic diet, consisting of approximately 60-80% fat, 15-25% protein, and 5-10% fibrous carbohydrates, is recommended for all cancer grades, with the goal of achieving a glucose ketone index (“GKI”) score of 2.0 or below.

Intermediate and high-grade cancers should be treated with a combination of the ketogenic diet and a water fast for 3 to 7 consecutive days, repeated every 3-4 weeks, or a Fasting-Mimicking Diet for patients who cannot fast.

Additional therapeutics, such as moderate physical activity and hyperbaric oxygen therapy, are recommended for intermediate and high-grade cancers or people who are unable to engage in physical activity.

The protocol should be followed for an average duration of 12 weeks, regardless of cancer type.

The proposed hybrid orthomolecular protocol for cancer treatment involves a combination of substances that target the MSCC without any contraindications.

The treatment dosage and duration can be adjusted by the physician according to individual patient needs, and additional molecules can be included to restore health, such as vitamin K2, vitamin E, coenzyme Q10 and melatonin.  However, anti-oxidant dosages should be avoided.  

The protocol aims to induce a pro-oxidant effect in cancer cells, leading to apoptosis, while protecting healthy cells by increasing OxPhos activity.  It specifically targets fermentable fuels, CSCs and macrophages, thereby addressing metastases created by fusion hybridisation between CSCs and macrophages.

The MSCC is a key element in the therapeutic approach to cancer, and targeting it can help in both the prevention and treatment of cancer.  Numerous experiments in cells, animals, and humans support the role of targeting the MSCC in both the prevention and treatment of cancer, the paper’s authors wrote.

However, comparative studies in animals and humans are needed to evaluate the effectiveness and safety of this hybrid protocol against standard therapies, they said.

You can read the paper online HERE. Although it is a little technical in parts, it is a relatively easy read.  We have attached a copy of the study below should it be removed from public view.

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author avatar
Rhoda Wilson
While previously it was a hobby culminating in writing articles for Wikipedia (until things made a drastic and undeniable turn in 2020) and a few books for private consumption, since March 2020 I have become a full-time researcher and writer in reaction to the global takeover that came into full view with the introduction of covid-19. For most of my life, I have tried to raise awareness that a small group of people planned to take over the world for their own benefit. There was no way I was going to sit back quietly and simply let them do it once they made their final move.

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A Person
A Person
9 months ago

The fasting part is interesting:

“…Prolonged fasting – this is 72 hour, 3 day, 5 day or 7 day water fast…72 hours is when the body’s process of autophagy kicks in and starts clearing those pre-cancerous cells, cancerous cells…You can take black coffee or plain tea with it to stimulate this process of autophagy – this body’s process of recycling damaged pre-cancerous or cancerous cells. I actually had a prostate cancer patient who did a 7 day water fast and dropped his PSA by more than a hundred points. I mean, that is basically evidence that cancer cells are being killed off by the body in this process…” (1:22:36), William Makis

From Replicon Vaccines: The Next Crime of the Century. Drs. Bridle, Makis, Karrow, and Trozzi with Iron Willvideo

Wayne Lusvardi
Wayne Lusvardi
9 months ago

Why would anyone prescribe antioxidants like Vitamin C when Otto Warburg accurately described cancer as a shift from oxygen to sugar?
Why wouldn’t we try oxidation therapy? And DON is a Glutamine antagonist but Glutamine is needed to close up small intestine gaps that can be a root cause of cancer.Moreover, Vit. D is a synthetic hormone or steroid not a vitamin at all. Sunlight + cholesterol make natural Vitamin D. So, are we supposed to follow the low cholesterol propaganda too?