Insulin Potentiation Therapy

Questions from the Clinic:

How effective is insulin potentiation therapy (IPT) in treating and preventing cancer? Is it a better alternative to standard chemotherapy? How exactly does it work?

Figure 1: Insulin potentiated therapy (IPT) entails the administration of insulin with chemotherapy drugs. Proponents of IPT theorize that insulin increases cell permeability to cancer fighting drugs, which means it can lower the doses of chemotherapy needed to fight cancer. Image courtesy of Memorial Sloan Kettering Cancer Center.

I. Overview

Insulin potentiation therapy, often stylized as IPT, is an alternative cancer therapy that uses insulin as an adjuvant to chemotherapy drugs. First developed by Dr. Donato Perez Garcia in the 1930s, IPT is believed by its proponents to minimize the negative side effects associated with chemotherapy drugs by using much lower doses in the 20% to 40% range, and augmenting with the insulin bolus, without reducing the efficacy of treatment.(1) Treatment strategies capable of improving the tolerability of cancer drugs are highly desirable, as many approved cytostatic drugs have relatively low tumor specificity and high toxicity. Alternative medications, like immune checkpoint inhibitors, can cause even more severe side effects than other conventional immunotherapies and require early recognition and intervention to safeguard patients.(2) Using lower doses to reduce common side effects while maintaining equal effectiveness by insulin potentiation sounds like a perfect scenario and thus fosters the curiosity around this option.(5)

II. Mechanism of Action

Substantial evidence indicates that the insulin receptor and its related signaling pathways are implicated in the development and progression of various cancers.(3,4) Relative to healthy cells, cancer cells express a greater number of insulin receptors. Proponents of IPT believe that this difference in insulin receptor density makes malignant cells more permeable to chemotherapy drugs in the presence of insulin. As a result, only a fraction of the normal dose of chemotherapy is required to achieve an antitumoral effect. By using lower doses of cancer drugs, clinicians can help limit side effects to healthy cells from therapy. In one breast cancer cell line (MCF-7), scientists have noted that insulin increases in vitro methotrexate uptake while simultaneously increasing its cytotoxicity. That said, it appears that the mechanism responsible for methotrexate’s increased cytotoxicity is more related to the increased synthesis of a substance called methotrexate polyglutamate and downregulation of ABCB1 – a methotrexate efflux transporter expressed by MCF-7 cells.(5) Furthermore, insulin treatment appears to act over a short-period time, however, there are distinct risks of augmenting insulin levels over extended periods of time.(6)

In the body, insulin is an anabolic hormone secreted by the pancreas that promotes the absorption of glucose from the blood into liver, fat, and skeletal muscle cells (Figure 2). Insufficient insulin results in diabetes, whereas excess insulin in the short term can cause a condition known as hypoglycemia.(7) In non-diabetics, the administration of insulin can cause blood sugar levels to fall drastically, as the hormone is already being produced normally in response to ingested food. If improperly addressed, hypoglycemia can trigger headaches and delirium, shock, coma, stroke, seizures, and even death.(8) Because of these risks, practitioners must weigh the possible benefits of IPT, utilize careful blood glucose monitory, and be attentive to these well-characterized treatment-related adverse events.

Figure 2: In addition to regulating the metabolism of carbohydrates, proteins, and lipids, the hormone insulin functions as a growth factor that stimulates cell mitosis and inhibits apoptosis – controlled cell death – through downstream activation of Ras and the mitogen activated protein kinase (MAPK) signaling pathway. Image courtesy of Rose et al. (2009)

III. Clinical Trial Data

To date, researchers have conducted a pair of clinical trials assessing IPT in patients with cancer.(5) In one trial, investigators evaluated quality of life in patients (n=16) with castration-resistant prostate tumors who all received chemotherapy via IPT and hormone therapy. Patients in Group A had been treated with epirubicin, vinblastine, and cyclophosphamide in combination with gosrelin, whereas patients in Group B received docetaxel and gosrelin. After 6 treatments with IPT, prostate specific antigen results showed that 50% of participants had a partial response, while stabilization was seen in 25% of patients. The remaining 25% of patients experienced progression. Median survival for all treated patients was 11.7 months. Although the study authors stated that recipients of IPT experienced no significant side effects, it is worthwhile to note that 5 of the 16 patients required blood transfusions before receiving treatment. Additionally, 5 out of the 16 participants in this trial experienced transient elevations in liver enzymes. Taken together, these findings warrant further investigation in larger trials to confirm if IPT is comparable to the standard of care.(9)

In an older clinical trial dating to 2004, investigators examined methotrexate response and toxicity in patients with metastatic breast cancer who had previously received hormonal therapy or chemotherapy (n=30). Participants enrolled in this trial were divided into 3 treatment groups of equal size. Patients in group 1 received 2, 21-day courses of insulin and methotrexate, patients in group 2 received 2, 21-day courses of methotrexate, and patients in group 3 received 2, 21-day courses of insulin. The trial’s primary endpoint was change in target tumor size after treatment. Notably, researchers observed that stable disease was more frequent in patients receiving combination therapy (methotrexate + insulin) than those receiving methotrexate or insulin alone. These findings lend credence to the theory that insulin enhances methotrexate’s antitumoral activity. Although these findings are compelling, the data offer no insights on long-term outcomes and require further corroboration through larger trials that enroll patients with other forms of cancer.(10)

Currently, there are no clinical trials assessing IPT in patients with cancer at ClinicalTrials.gov to offer future insights. More rigorous investigations of IPT protocols are needed, as the remaining evidence supporting the use of IPT comes from individual case reports.(11)

IV. Cost and Accessibility

According to the Complementary and Alternative Medicine for Cancer website, IPT costs around $1,800 to $2,000 per session. More intensive regimens, which lasts up to 4 weeks, costs between $15,500 and $17,500.(12) Certain integrative cancer care providers like the Arizona Center for Advanced Medicine (ACAM) quote $50,000 for the first 2 months of IPT treatment, along with associated evaluations, lab tests, and group discussions. Notably, this figure excludes the expense associated with chemotherapy drugs administered in conjunction with IPT. According to ACAM, the frequency of treatment drops to once a month during the first year and occurs at progressively longer intervals for a total of 5 years.(13) In the view of insurance agencies, IPT is an investigational procedure that is considered not medically necessary for the treatment of cancer. Consequently, the expenses associated with IPT are not covered by insurance policies and must be paid out-of-pocket.(11) Worldwide, there are approximately 65 practitioners of IPT according to the Academy of IPT, which licenses two practitioner associations in Germany and Russia.(5) Patients seeking IPT in the United States may find some options in various states such as the Ayre Clinic for Contemporary Medicine, located in Burr Ridge, IL.(14)

V. Conclusions

To date, scant scientific research on IPT supports its integration into the standard of care for patients with cancer. Although positive findings from case reports and a couple clinical trials exist, and a compelling mechanism of action, scientists have not corroborated this data repeatedly in well-designed, adequately powered, large clinical trials. IPT perhaps warrants further consideration in some specific contexts like breast and prostate cancers, but it is not an approach that patients should independently pursue during their treatment, especially to replace known effective standard of care options. High costs, unclear efficacy, and uncharacterized long-term outcomes rule heavily against its use. While improvements to the standard of care are welcome, care providers should not rush to embrace alternatives that have not undergone reasonable testing and validation.

Stay strong and curious,

- Chuck

Charles J. Meakin MD, MHA, MS

Disclaimer: This information is not meant as direct medical advice. Readers should always review options with their local medical team. This is the sole opinion of Dr. Meakin based on a literature review at the time of the blog and may change as new evidence evolves.

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1 Insulin potentiation therapy. Memorial Sloan Kettering Cancer Center. https://www.mskcc.org/cancer-care/integrative-medicine/herbs/insulin-potentiation-therapy#msk_professional/. Updated February 25, 2021. Accessed February 18, 2022.

2 Schirrmacher V. From chemotherapy to biological therapy: a review of novel concepts to reduce the side effects of systemic cancer treatment (review). Int J Oncol. 2019;54(2):407-419.

3 Malaguarnera R, Belfiore A. The insulin receptor: a new target for cancer therapy. Fron Endocrinol (Lausanne). 2011;2:93.

4 Vella V, Milluzzo A, Scalisi NM, et al. Insulin receptor isoforms in cancer. Int J Mol Sci. 2018;19(11):3615.

5 Sisung TM, Schmidt KT, Figg WD. Quackery: insulin potentiation therapy for cancer? Lancet Oncol. 2019;20(2):191-192.

6 Maryniuk M. The dangers of taking insulin when you don’t need it. Heathfully. https://healthfully.com/the-dangers-of-taking-insulin-when-you-dont-need-it-6999849.html/. Updated October 21, 2019. Accessed February 18, 2022.

7 Mathieu C, Martens P-J, Vangoitsenhoven R. One hundred years of insulin therapy. Nat Rev Endocrinol. 2021;17(12):715-725.

8 Snyder A, Falck S. Insulin potentiation therapy and cancer. Heathline. https://www.healthline.com/health/insulin-potentiation-therapy/. Published November 14, 2017. Accessed February 18, 2022.

9 Damyanov C, Gerasimova D, Maslev I, et al. Low-dose chemotherapy with insulin (insulin potentiation therapy) in combination with hormone therapy for treatment of castration-resistant prostate cancer. ISRN Urol. 2012;2012:140192

10 Lasalvia-Prisco E, Cucchi S, Vazquez J, et al. Insulin-induced enhancement of antitumoral response to methotrexate in breast cancer patients. Cancer Chemother Pharmacol. 2004;53(3):220-224.

11 Amerigroup Corporation. MED.00128: Insulin Potentiation Therapy Medical Policy. https://provider.healthybluenc.com/dam/medpolicies/healthybluenc/active/policies/mp_pw_a050300.html. Published December 29, 2021. Accessed February 18, 2022.

12 Geeraert L. Insulin potentiation therapy. Complementary and Alternative Medicine for Cancer. [link]. Published February 5, 2013. Accessed February 18, 2022.

13 Arizona Center for Advanced Medicine: Integrative Medical Center. Frequently asked questions about IPT-LD. https://www.arizonaadvancedmedicine.com/articles/2018/june/frequently-asked-questions-about-ipt-ld/. Published June 25, 2018. Accessed February 18, 2022.

14 Ayre Clinic for Contemporary Medicine. https://contemporarymedicine.net/. Accessed February 18, 2022.