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Insulin Potentiation Therapy (IPT)

Dr.  Jonathan Stegall
Medically reviewed by Dr. Jonathan Stegall, MD — By Tom Escott on October 20, 2023

Insulin potentiation therapy (IPT) is an experimental treatment protocol that combines chemotherapy (or other medications) with insulin. It is claimed that the use of insulin increases the efficacy of chemotherapy drugs and targets cancer cells more selectively [1]. IPT enables a 75-95% reduction of conventional chemotherapy doses, and consequently, reduces toxic side effects [1]. However, there is currently minimal scientific research to determine purported efficacy against cancer.

Watch the video above for an in-depth conversation with Dr. Jonathan Stegall MD about Insulin Potentiation Therapy!

A basic principle of conventional chemotherapy is to give patients maximum tolerated doses with extended periods of time between treatments to allow for patient recovery [2]. Despite the development of new chemotherapy drugs and varied combinations, toxicity, chemoresistance, and insignificant prolongation of life expectancy are serious problems that remain unresolved [2] [3]. In light of the shortcomings of conventional chemotherapeutics, efforts to improve outcomes have led to a new treatment strategy known as “metronomic chemotherapy,”, which involves the use of lower doses of drugs at shorter time intervals [2]. Initial experimental and clinical results implementing metronomic chemotherapy are promising [2] [4] [5].

Similarly, Insulin Potentiation Therapy, also referred to as Insulin Potentiation Targeted Low Dose (IPTLD), uses fractionated doses of conventional chemotherapeutics at shorter time intervals, but departs from standard protocols by applying insulin to enhance the biological response [2]. This method is proposed to help target malignant cells and reduce collateral damage to healthy cells [2]. Proponents claim that insulin increases the ability of drugs to move into cancer cells and that IPT differentiates between cancerous and normal cells due to higher levels of insulin receptors on cancer cells [6].

Exploratory studies and early clinical research show some potential benefits of combining chemotherapy with insulin, but well-designed clinical research with large patient numbers is still lacking to determine safety and efficacy of the experimental treatment approach [7].

History of Insulin Potentiation Therapy

Dr. Donato Perez Garcia, a Mexican military physician, is credited with the invention of IPT based on experiments that began in 1926 [8]. Dr. Garcia suffered from serious digestive issues, which left him malnourished. He injected himself with insulin before meals in an attempt to stimulate his appetite and enhance nutrient uptake [8].

Based on his experimentations with self-administered insulin, he developed the theory that insulin helped to transport nutrients across the walls of the digestive system and deliver into tissues and cells. Based on this logic he also theorized that insulin could enhance the permeability of cells and absorption of drugs [8].

Dr. Garcia tested his hypothesis on dogs to determine if the use of insulin would enhance the uptake of syphilis medications into the central nervous system (CNS). The results of his experiment, based on autopsy investigations, revealed significantly higher levels of mercury and arsenic salts in the CNS of the dogs treated with insulin compared to the control group (not given insulin) [8].

While IPT was initially applied for the treatment of syphilis, Dr. Garcia later used IPT for other diseases including arthritis, asthma, colitis, ulcers, and polio [1] [8]. From 1947 onwards, Dr. Garcia also treated cancer patients with IPT and claimed to have positive results [1]. He continued to treat patients with IPT until his death in 1971 [8]. Dr. Garcia’s son and grandson continued to work with IPT and continued his legacy.

In 1975, Dr. Steven G Ayre, a Chicago based physician, reached out to the son of the founder of IPT, Dr. Donato Perez Garcia y Bellon. He was intrigued by the unique approach as he was looking for kinder and gentler ways to treat cancer [8]. In 1986, Dr. Ayre, Dr. Donato Perez Garcia y Bellon and Dr. Perez Garcia Jr, published a paper arguing that IPT can be used in the treatment of chronic diseases [9].

Dr. Ayre did not begin to use IPT in his own clinical practice until 1997, at which time he finally believed there was enough anecdotal evidence to support its use in patients. However, Dr. Ayre admitted that there was still a lack of rigorous scientific research and data to validate the efficacy of the treatment for cancer, but in his mind, anecdotal case reports collected over forty years were sufficient to indicate that the treatment could potentially be effective [8].

In 2000, Dr Ayre and his colleagues made a presentation to the Cancer Advisory Panel of the National Cancer Center for Cancer Complementary and Alternative Medicine at the National Institutes of Health [10]. This meeting initially resulted in collaborations with cancer researchers at the University of Wisconsin, as well as approval for clinical trials to study IPT [10]. However, the trials were shut down in 2001, because the FDA deemed they were being improperly run [11].

To date, scientific research on IPT is still lacking, with only a handful of small-scale

clinical trials and case studies in humans.

Research supporting Insulin Potentiation Therapy

Scientific research on IPT in humans is scarce, with only two small-scale clinical trials and a handful of case studies (observational reports) published in peer-reviewed journals [1]. Preliminary data indicates positive results against tumor growth, but effects on patient survival and long-term effects are yet to be evaluated [1].

In 2012, a small study on IPT was carried out involving 16 male patients with castration-resistant prostate tumors [12]. Treatment with insulin and low-dose chemotherapy resulted in a partial response (decrease in tumor size) in 50% of patients, stabilization in 25%, and progression in 25%. During the treatment, no significant side effects were observed. The researchers asserted that IPT provides a real opportunity for resolving the problem of toxicity associated with maximum tolerated doses of chemotherapy. They also stated that preliminary results are promising enough to hope for the future widespread clinical use of IPT [12].

A 2004 clinical trial on IPT with 30 breast cancer patients showed that disease stabilization was more frequently observed in patients treated with methotrexate (chemotherapy agent) and insulin compared to groups where the drugs were used separately [13]. Tumor size was also reduced more significantly with IPT treatment compared to other groups. Researchers stated that results of the study provide clinical evidence that insulin potentiates the effects of methotrexate. They concluded that in multi-drug resistant metastatic (widespread) breast cancer, the combination of methotrexate and insulin produced a significant antitumor response that was not observed when the drugs were applied separately [13].

A three- year study on IPT was carried out on 196 patients with a variety of different cancer types [2]. Of the test subjects, 188 had advanced metastatic disease, while 8 patients were treated adjuvantly after surgical removal of localized tumors. The results showed that patients tolerated IPT without difficulty or serious side effects. Lab tests indicated that the toxicity of chemotherapeutics could be largely mitigated when applied with insulin and in fractionated doses. Of the 196 patients, 106 (80%) reported a subjectively significant improvement in quality of life.

A 2009 study reports 3 cases of IPT treatment in patients with advanced metastatic cancer where prior conventional treatments had failed [3]. The study includes two women with breast cancer and one man with prostate cancer [1]. They were given an initial 4 to 6 courses of weekly IPT (insulin + different chemotherapy agent for each patient) followed by maintenance treatments at several-week intervals [1]. The treatment was well-tolerated without any significant side effects or toxicity reported. Remission was achieved in all patients [1]. Duration of remission ranged from 8 - 21 months at time of publication. [1].

Another study from 1990 documents the case of a woman with breast cancer treated with IPT twice weekly for 3 weeks and then weekly for 5 weeks [14]. At the end of her treatment regimen, the tumor was no longer palpable and after 3 months, no evidence could be detected on a mammogram [14].

In vivo (animal) studies have also indicated the potential role of insulin in enhancing the anticancer effects of chemotherapy agents. A study from 1987 conducted on tumor-bearing rats demonstrates that tumor sizes were more significantly reduced after treatment with chemotherapy and insulin compared to using chemotherapy drugs alone [15]. The enhanced anticancer effects of chemotherapeutics when combined with insulin has also been demonstrated in a variety of human cancer cell lines [16] [17] [18].

While IPT may be experimental in nature and lacking clinical data to validate safety and efficacy as a cancer treatment in humans, preliminary evidence suggests likely anticancer effects and indicates reduced toxic side effects compared to conventional chemotherapy.

Potential Applications of Insulin Potentiation Therapy

Even after several decades of scientific research into chemotherapy for the treatment and management of cancer, conventional chemotherapeutics are still plagued by numerous difficulties and problems [2]. The most significant of the potential complications are toxicity-related side effects and chemotherapy drug resistance [2]. In spite of the development of various novel chemotherapeutic agents and drug combination strategies, little progress has been made in terms of improving treatment outcomes, survival rates, and reducing adverse effects [2].

IPT as a treatment strategy is based on the theory that insulin and insulin-like growth factor (IGF) play a key role in the cell cycle (process of cellular division) [7]. IGF has been shown to affect cancer cell proliferation, adhesion, and migration, which are critical functions for cancer cell survival and metastases (spread of disease) [19]. In many forms of cancer, IGF receptors are found to be overexpressed, which means that cancer cells may be selectively more sensitive than normal cells to IGF [7].

IGF receptors can be activated by injecting exogenous insulin into the bloodstream. Insulin is also believed to increase the permeability of cell membranes, which means that insulin administration can be leveraged to increase intracellular concentrations of anticancer drugs and enhance toxic effects on cancer cells [6] [7]. Furthermore, based on the higher levels of insulin receptors on cancer cells compared to normal cells, IPT is believed to help target drugs directly to cancer cells.

Proponents of IPT claim that insulin works synergistically to enhance drug efficacy and selectivity for cancer cells, which means that reduced dosages of chemotherapeutics can be applied more frequently with similar anticancer effects [7] [20]. IPT can be administered with 10 times lower dosages and at much shorter time intervals compared to conventional chemotherapy [12]. This is an approach that has been implemented around the world in the integrative cancer treatment setting for decades with promising anecdotal results [20].

IPT is proposed to be a kinder and gentler way to administer chemotherapy with reduced toxicity, fewer chemotherapy-related side effects, and rates of efficacy purported to be similar to standard maximum tolerated dose chemotherapy protocols [12]. Some research suggests that IPT may also have a role to play in combating drug-resistant tumors given that insulin appears to potentiate the effects of chemotherapy and make cancer cells more susceptible to chemotherapeutic agents [13].

However, due to the lack of scientific research in humans and scarcity of reliable clinical data, claims of the efficacy of IPT can only be backed up with low certainty. Further research is still needed to determine if IPT warrants widespread clinical application.

Risks and Side Effects of Insulin Potentiation Therapy

The main risk involved in insulin potentiation therapy is hypoglycemia (low blood

glucose levels). Artificially introducing insulin by injection can result in rapid drops in blood sugar levels. If your blood sugar levels fall low enough it is possible to experience [21]:

  • Shock
  • Coma
  • Seizures
  • Stroke
  • Death

Because insulin is a hormone with the potential for significant effects on the body, it should only be administered by trained health professionals in conjunction with close monitoring of blood sugar levels at the time of treatment. Clinics which routinely use IPT feel that it is a very safe procedure with proper safeguards in place.

Concerns have also been raised that the reduced anticancer effects of lower doses of chemotherapy drugs may lead to increased drug resistance [1]. Other studies suggest the opposite, and indicate that IPT may provide a mechanism to combat drug-resistant cancers [13].

From the research that is available, IPT appears to be well-tolerated without serious adverse events reported. Small-scale studies show that toxicity levels in patients treated with chemotherapy and insulin were lower than groups where chemotherapy was given alone [1].

Due to the lack of reliable information published in peer-reviewed scientific journals it is impossible to judge with certainty the safety and efficacy of IPT [1].

The Center for Advanced Medicine

The Center for Advanced Medicine is a leading institution in the field of Integrative Oncology. It is led by Dr. Jonathan Stegall MD who is an Integrative oncologist in Atlanta, GA, and has seen firsthand what works and what doesn't when it comes to cancer treatment.

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Frequently asked questions about Insulin Potentiation Therapy (IPT)

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References of Insulin Potentiation Therapy (IPT)

References

[1] Geeraert, L., & CAM-Cancer Consortium. (2011). Insulin potentiation therapy. https://cam-cancer.org/en/insulin-potentiation-therapy

[2] Damyanov, C., Gherasimova, D. M., Avramov, L. A., & Masley, I. K. (2012). Insulin potentiation therapy in the treatment of malignant neoplastic diseases: a three year study. J Cancer Sci Ther, 4(4), 088-091. https://www.researchgate.net/profile/Latchezar-Avramov/publication/235788682_Insulin_potentiation_therapy_in_the_treatment_of_malignant_neoplastic_diseases_A_three_year_study/links/02e7e522de8afd91c0000000/Insulin-potentiation-therapy-in-the-treatment-of-malignant-neoplastic-diseases-A-three-year-study.pdf

[3] Damyanov, C., Radoslavova, M., Gavrilov, V., & Stoeva, D. (2009). Low dose chemotherapy in combination with insulin for the treatment of advanced metastatic tumors. Preliminary experience. J BUON, 14(4), 711-5. https://pubmed.ncbi.nlm.nih.gov/20148468/

[4] Fidler, I. J., & Ellis, L. M. (2000). Chemotherapeutic drugs—more really is not better. Nature medicine, 6(5), 500-502. https://www.nature.com/articles/nm0500_500

[5] Bocci, G., Tuccori, M., Emmenegger, U., Liguori, V., Falcone, A., Kerbel, R. S., & Del Tacca, M. (2005). Cyclophosphamide-methotrexate ‘metronomic’chemotherapy for the palliative treatment of metastatic breast cancer. A comparative pharmacoeconomic evaluation. Annals of oncology, 16(8), 1243-1252. https://pubmed.ncbi.nlm.nih.gov/15905308/

[6] Benni, J. M., & Patil, P. A. (2016). Non-diabetic clinical applications of insulin. Journal of basic and clinical physiology and pharmacology, 27(5), 445-456. https://doi.org/10.1515/jbcpp-2015-0101

[7] Author unknown. (2021). Insulin Potentiation Therapy Purported Benefits, Side Effects & More. Memorial Sloan Kettering Cancer Center. [Online] https://www.mskcc.org/cancer-care/integrative-medicine/herbs/insulin-potentiation-therapy

[8] Jones, J. Insulin Potentiation Therapy: Reckless Human Experimentation or Bona Fide Medicine? https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=c5893687274059070a056e39b0f305a7d3700b6d

[9] Ayre, S. G., y Bellon, D. P. G., & Garcia Jr, D. P. (1986). Insulin potentiation therapy: a new concept in the management of chronic degenerative disease. Medical hypotheses, 20(2), 199-210. https://www.sciencedirect.com/science/article/abs/pii/030698778690126X

[10] Author unknown. Dr. Ayre. Contemporary Medicine. https://web.archive.org/web/20030817065503/www.contemporarymedicine.net/drayre/drayre.php

[11] Herbst, M. C. (2021). Fact Sheet and Position Statement On Insulin Potentiation Therapy. Cancer Association of South Africa (CANSA). https://cansa.org.za/files/2021/07/Fact-Sheet-and-Position-Statement-on-Insulin-Potentiation-Therapy-July-2021.pdf

[12] Damyanov, C., Gerasimova, D., Maslev, I., & Gavrilov, V. (2012). Low-dose chemotherapy with insulin (insulin potentiation therapy) in combination with hormone therapy for treatment of castration-resistant prostate cancer. International Scholarly Research Notices, 2012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357525/

[13] Lasalvia-Prisco, E., Cucchi, S., Vazquez, J., Lasalvia-Galante, E., Golomar, W., & Gordon, W. (2004). Insulin-induced enhancement of antitumoral response to methotrexate in breast cancer patients. Cancer chemotherapy and pharmacology, 53(3), 220-224. https://pubmed.ncbi.nlm.nih.gov/14655024/

[14] Ayre, S. G., y Bellon, D. P. G., & Garcia Jr, D. P. (1990). Neoadjuvant low-dose chemotherapy with insulin in breast carcinomas. European journal of cancer (Oxford, England: 1990), 26(11-12), 1262-1263. https://contemporarymedicine.net/neoadjuvant-low-dose-chemotherapy-with-insulin-in-breast-carcinomas/

[15] Peacock, J. L., Gorschboth, C. M., & Norton, J. A. (1987). Impact of insulin on doxorubicin-induced rat host toxicity and tumor regression. Cancer research, 47(16), 4318-4322. https://aacrjournals.org/cancerres/article/47/16/4318/491625/Impact-of-Insulin-on-Doxorubicin-induced-Rat-Host

[16] Oster, J. B., & Creasey, W. A. (1981). Enhancement of cellular uptake of ellipticine by insulin preincubation. European Journal of Cancer and Clinical Oncology, 17(10), 1097-1103. https://www.sciencedirect.com/science/article/abs/pii/0014296481902942

[17] Alabaster, O., Vonderhaar, B. K., & Shafie, S. M. (1981). Metabolic modification by insulin enhances methotrexate cytotoxicity in MCF-7 human breast cancer cells. European Journal of Cancer and Clinical Oncology, 17(11), 1223-1228. https://www.sciencedirect.com/science/article/abs/pii/S0277537981800272

[18] Zou, K., JU, J. H., & Xie, H. (2007). Pretreatment with insulin enhances anticancer functions of 5-fluorouracil in human esophageal and colonic cancer cells. Acta pharmacologica sinica, 28(5), 721-730. https://pubmed.ncbi.nlm.nih.gov/17439729/

[19] LeRoith, D., & Roberts Jr, C. T. (2003). The insulin-like growth factor system and cancer. Cancer letters, 195(2), 127-137. https://pubmed.ncbi.nlm.nih.gov/12767520/

[20] Ayre, S. G., y Bellon, D. G., & Garcia Jr, D. P. (2000). Insulin, chemotherapy, and the mechanisms of malignancy: the design and the demise of cancer. Medical hypotheses, 55(4), 330-334. https://doi.org/10.1054/mehy.2000.1063

​​[21]Healthline. https://www.healthline.com/health/insulin-potentiation-therapy#risks

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