Introduction

Ivermectin is one of the repurposed pharmaceutical agents included in the Mitochondrial Stem Cell Connection (MSCC) Protocol as proposed by Baghli et al. in the Journal of Orthomolecular Medicine (Vol. 39, No. 3, 2024). It is presented as part of a broader integrative strategy to target the metabolic and mitochondrial vulnerabilities of cancer cells—specifically cancer stem cells (CSCs), which are known for their resistance to conventional therapies and their role in metastasis.

Within the MSCC framework, ivermectin is not used for its antiparasitic properties, but rather for its emerging anticancer effects that include inducing mitochondrial dysfunction, promoting apoptosis, and interfering with glucose metabolism. It is positioned alongside other metabolic and orthomolecular therapies to support the overarching aim of enhancing oxidative phosphorylation (OxPhos), inhibiting fermentable fuel pathways, and disrupting cancer cell survival mechanisms. Its low toxicity, broad availability, and multimodal effects make it a compelling candidate in this educational model.

History

Discovered in the late 1970s, ivermectin was derived from a soil bacterium (Streptomyces avermitilis) and initially developed as an antiparasitic agent. It gained widespread recognition for its efficacy in treating parasitic infections such as onchocerciasis (river blindness) and lymphatic filariasis. Ivermectin’s global health impact was so profound that its discoverers, Satoshi Ōmura and William C. Campbell, were awarded the Nobel Prize in Physiology or Medicine in 2015.

Ivermectin has since been prescribed in billions of doses worldwide and is included on the World Health Organization’s list of essential medicines. It is used extensively in both human and veterinary medicine, with a well-documented safety profile. This long history of use, combined with affordability and accessibility, has led researchers to explore its potential in off-label contexts such as cancer treatment.

Mechanism of Action in the MSCC Protocol

In the MSCC Protocol, ivermectin is primarily recognized for its ability to disrupt mitochondrial function in cancer cells, a key mechanism aligned with the protocol’s emphasis on restoring healthy OxPhos and targeting metabolic vulnerabilities. Specifically, ivermectin induces mitochondrial-mediated apoptosis and can selectively generate oxidative stress in cancerous, but not normal, cells (Juarez et al., 2018; Tang et al., 2021).

Ivermectin also affects cancer cell metabolism by inhibiting glycolysis, the energy-generating process that cancer cells rely on in the absence of functional mitochondria. It can interfere with glucose uptake and utilization by modulating enzymes like pyruvate kinase M2 (Li et al., 2020), thereby depriving cancer cells of a critical fuel source and enhancing metabolic stress (Feng et al., 2022).

Importantly, the protocol highlights ivermectin’s ability to target CSCs and tumor-associated macrophages—two key drivers of metastasis and therapy resistance. Studies cited in the protocol show that ivermectin inhibits CSCs more effectively than chemotherapy in vitro and reduces tumor volume in vivo in pancreatic cancer models (Dominguez-Gomez et al., 2018; Lee et al., 2022). Its influence on immune modulation, including macrophage polarization, further supports its inclusion as a multipurpose agent in the MSCC strategy.

Scientific Evidence

The MSCC Protocol references multiple studies to support ivermectin’s anticancer properties. In vitro studies have shown that ivermectin can induce apoptosis in various cancer cell lines, including breast and glioma cells, by triggering mitochondrial dysfunction and inhibiting key metabolic pathways (Liu et al., 2020; Sharmeen et al., 2010). Juarez et al. (2020) demonstrated that ivermectin significantly reduced tumor size in animal models, performing better than standard chemotherapy in some cases.

The protocol also highlights ivermectin’s selective toxicity toward cancer cells. Unlike chemotherapy agents that damage both healthy and malignant cells, ivermectin appears to exert a pro-oxidant effect selectively in cancerous tissues, sparing normal ones (Wang et al., 2018). In one comparative study, it was more effective than paclitaxel in suppressing breast cancer CSCs (Dominguez-Gomez et al., 2018).

Despite these promising results, the authors emphasize that the evidence remains early-stage, with most findings derived from preclinical models. They acknowledge that further human trials are needed to validate ivermectin’s safety and efficacy in oncologic settings. Nevertheless, the protocol includes ivermectin due to its multi-targeted effects, favorable safety data, and the urgent need for CSC-directed strategies.

Dosing

The MSCC Protocol proposes the following educational dosing model for oral ivermectin:

• Low-grade cancers: 0.5 mg/kg, 3x per week

• Intermediate-grade cancers: 1 mg/kg, 3x per week

• High-grade cancers: 1–2 mg/kg daily

These doses are derived from clinical safety data showing no significant adverse events at these levels (Guzzo et al., 2002; de Castro et al., 2020). However, the protocol clearly states that these are educational guidelines and not treatment recommendations.

Clinical & Safety Considerations

Ivermectin is considered a safe drug at approved doses, with decades of human and veterinary use supporting its tolerability. Clinical studies have used doses up to 2 mg/kg in healthy individuals without significant toxicity. Nonetheless, it is critical to recognize that its use in cancer is off-label and has not been approved by regulatory agencies for this purpose.

Potential safety concerns include interactions with drugs that affect the GABAergic system, particularly in patients with neurologic conditions or impaired liver function. There is also concern over improper self-administration, especially when used without clinical oversight. While interest in ivermectin has grown in integrative oncology, it remains a controversial compound outside its established use due to ongoing debates around repurposing and regulatory approval.

Summary

Ivermectin plays a unique role in the MSCC Protocol as a repurposed drug with documented effects on cancer metabolism, mitochondrial function, and cancer stem cells. Its inclusion reflects the protocol’s strategy of using well-characterized compounds with multifaceted mechanisms to disrupt tumor survival and promote oxidative balance. When used in conjunction with metabolic therapies such as fasting and ketogenic diets, ivermectin’s effects may be potentiated, offering a synergistic approach to targeting CSCs and tumor microenvironments.

Although the evidence supporting ivermectin in cancer remains largely preclinical, its low cost, global availability, and established safety record make it a compelling candidate for continued research. The MSCC Protocol leverages these strengths as part of a broader educational model designed to explore new frontiers in cancer metabolism.

Educational Framing

This section is provided solely for educational and informational purposes, based on the cited literature within the MSCC Protocol. It does not constitute a treatment guideline or medical recommendation. Readers are encouraged to consult qualified medical professionals before considering any interventions or off-label therapies.

References

• Guzzo et al., 2002

• Liu et al., 2020

• Juarez et al., 2018; 2020

• Dominguez-Gomez et al., 2018

• Lee et al., 2022

• de Castro et al., 2020

• Feng et al., 2022

• Tang et al., 2021

• Li et al., 2020

• Sharmeen et al., 2010

• Wang et al., 2018

(All references are from Targeting the Mitochondrial Stem Cell Connection in Cancer Treatment, JOM 2024)

Disclaimer

This section is for educational purposes only and does not constitute medical advice. Always consult a licensed healthcare provider before starting any treatment.