Insulin potentiation therapy

Insulin potentiation therapy (IPT) is an innovative pharmacologic strategy for the chemotherapy of cancer. This therapeutic approach takes advantage of the endogenous molecular biology of cancer cells, specifically insulin and insulin like growth factor secretion, and the interaction of these biochemicals with their specific receptors. By using insulin in conjuction with chemotherapy drugs, significantly less drug (about 10-15 % of a standard dose) can be targeted more specifically and more effectively to cancer cell populations, thus virtually eliminating dose-related side effects while enhancing antineoplastic effects.

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A Bit of Molecular Biology...

Here is a simplified explanation – not everyone has a PhD in biochemistry :) - of the biology of cancer and its cells in order to understand the mechanisms of IPT:

Insulin, the most integral component of IPT, has three significant actions upon cancer cells. 1. Insulin biologically differentiates cancer cells from normal cells based on insulin receptor concentration. 2. It modifies cancer cell metabolism which increases the S-Phase fraction, and 3. It increases cell membrane permeability. All of these actions serve to increase the efficacy of chemotherapy drugs.

Insulin can serve to distinguish and differentiate cancer cells from healthy cells in several ways. Produced in the pancreas, one of its many functions is the regulation of blood glucose levels. Chiefly, insulin activates a glucose transport protein within all cells – whether they be cancerous or healthy - which allows glucose, the energy source, to enter, thus lowering the blood glucose level.

Like anything else, cancer needs energy to grow. The growth of cancer is abnormally rapid, its sole purpose being to spread, therefore it has a voracious appetite compared to normal cells. Cancer cells have developed the ability to produce insulin and insulin-like growth factor (IGF) themselves; this way they can autonomously increase their glucose uptake.^{[1][2][3][4][5][6][7][8][9][10]}

Being able to produce its own insulin makes cancer different from normal cells, but there is a second abnormality that insulin highlights. Every cell in the body has insulin receptors on the outer surface of its membrane - from 100 -100,000 receptors per cell. But cancer cells have a much higher concentration of receptors. Breast cancer cells - for example - have six times more insulin receptors and ten times more IGF receptors per cell than normal cells. As an added boost, insulin is able to react with its own receptors and is also able to cross-react with and activate the IGF receptors on cancer cells. This means that insulin will affect cancer cells sixteen times as strongly as it effects normal tissues.^{[11][12][13][14][15][16][17][18][19][20][21][22]} Something else to take into consideration is thatligand effect is a function of receptor concentration. In a particular tissue, the more receptors there are for a certain ligand – such as insulin – the greater is going to be the effect of that ligand on that tissue.

By activating the insulin and IGF receptors on cancer cells through the administration of insulin during an IPT treatment, the biological differences of cancer cells can be highlighted – a vital consideration for the safety of cancer chemotherapy

2. Not only does insulin provide cancer cells with the means to grow, it has also been proven that IGFs are the most potent mitogen - promoter of cell division - for cancer growth.

Now why would growth be a favorable effect in a treatment, which is trying to kill cancer? The answer lies in the killing mechanism of chemotherapy medications. The standard pharmacologic treatment for cancer involves drugs, which are designed to attack cells that are dividing, cell division being the means by which tissue "grows." Cancer cells are rapidly dividing cells, and are constantly going through cell division. There are several phases to cell division, the one called the S-Phase being when cells replicate DNA. There are some chemotherapy agents that are "S-Phase dependent:" they attack cells that are in the S-phase of cell division, not cells in the resting phase.

Unfortunately hair cells, red and white blood cells and cells found in the digestive tract also fall into this category of rapidly dividing cells - the reason why the side effects related to standard chemotherapy are associated with these areas. In order to get a tumoral response in conventional chemotherapy, a high dose of drugs have to be used and unfortunately healthy cells are affected as well. The chemotherapy drugs by themselves cannot differentiate between rapidly dividing cancer cells and rapidly dividing healthy cells. By implementing insulin in conjunction with chemotherapy drugs, the cancer cells are highlighted as being different based on receptor concentration and are promoted to grow, which makes it likely that more of them will be in the S-phase cycle. These effects allow for the powerful chemo agents to target the cancer cells more specifically, sparing healthy cells and therefore chemo-related side-effects.

3. A third effect that insulin has on cancer cells is to activate enzyme activity in the cell membrane making them more permeable.

Cell membranes are largely made up of triglycerides, which are built of fatty acids. The more saturated that a fatty acid is, the higher the melting point (example: butter [a saturated fat with a higher melting point] is solid at room temperature, whereas olive oil [an unsaturated fat with a lower melting point] is a liquid). The enzyme that insulin activates is called delta-9 desaturase and the action of this enzyme is to de-saturate - to make a saturated fat into an unsaturated fat. Delta-9 desaturase - once it has been activated by insulin- de-saturates the fatty acids that make up the cell membrane of cancer cells. This fatty acid – saturated stearic acid – has a melting point of 65 degrees C. Stearic acid once it has been de-saturated, becomes mono-unsaturated oleic acid, which has a melting point of 5 degrees C. At physiologic temperatures (the temperature of the body, about 37.5 degrees C) tristearin – triglyceride with three stearic acids attached that composes the cancer cell membrane - is going to be more “waxy” than “oily” because of its higher melting point. This makes for a less permeable cell membrane. On the other hand, once the insulin has activated the enzyme delta-9 desaturase, the cell membrane of cancer cells is composed of triolein – the triglyceride with three oleic acids attached – with a melting point of 5 degrees C. This cell membrane will be more permeable at physiologic temperatures. The chemo drugs are thus able to enter the cancer cells more easily because of the increased cell membrane permeability, providing the required intracellular dose intensity to kill the cancer.

Insulin is used in IPT to enhance anticancer drug cytoxicity and safety, via 1) an effect of biological differentiation based on insulin receptor concentration, 2) an effect of metabolic modification to increase the S-phase fraction in cancer cells, enhancing their susceptibility to cell-cycle phase-specific agents, and 3) a membrane permeability effect to increase the intracellular dose intensity of the drugs. Significantly less drug can thus be targeted more specifically and more effectively to cancer cells, all this occurring with a virtual elimination of the dose-related side effects.^[23][24]

Insulin Potentiation Therapy - The Treatment at a Glance

This essay was written by Dr. Ayre to cover the essentials of IPT and was also used as part of the above text:

Insulin Potentiation Therapy (IPT) manipulates the mechanisms of malignancy to therapeutic advantage by employing insulin as a biologic response modifier of cancer cells' endogenous molecular biology. The autonomous proliferation of malignancy is supported by autocrine secretion of insulin for glucose/energy uptake by cancer cells, and a similar autocrine and/or paracrine elaboration of cellular factors to stimulate cancer growth. Amongst these, the insulin-like growth factors have been identified as the most potent mitogens for cancer cells (1-10). Of primary importance for IPT, cancer cell membranes also have six times more insulin receptors and ten times more IGF receptors, per cell, than the membranes of host normal tissues. Further, insulin can cross-react with and activate cancer cell IGF receptors. Thus, per cell, cancer has sixteen times more insulin-sensitive receptors than normal tissues (11-22). As ligand effect is a function of receptor concentration, these facts serve to differentiate cancer from normal cells - a vital consideration for the safety of cancer chemotherapy.

In light of these revelations, exogenous insulin acts to enhance anticancer drug cytotoxicity, and safety, via 1) a membrane permeability effect to increase the intracellular dose intensity of the drugs, 2) an effect of metabolic modification to increase the S-phase fraction in cancer cells, enhancing their susceptibility to cell-cycle phase-specific agents, and 3) an effect of biochemical differentiation based on insulin receptor concentration that focuses the first two insulin effects predominantly on cancer cells, sparing host normal tissues. Significantly less drug can thus be targeted more specifically and more effectively to cancer cell populations that are more susceptible to the chemotherapy drug effects (23-24), all this occurring with a virtual elimination of the dose-related side effects of these powerful drugs .

Because of this favorable side effect profile, cycles of low-dose chemotherapy with IPT may be done more frequently. There is good patient acceptance of the hypoglycemic side effect of insulin in this protocol, and the "rescue phenomenon" occasioned by the timely administration of hypertonic glucose actually serves to provide patients with an experiential metaphor for the rapid recovery of their well being. It is acknowledged that cancer treatment can often be debilitating for patients. In those undergoing treatment with IPT, an overall gentler experience promotes their concurrent use of other important elements in a program of Comprehensive Cancer Care, which includes nutrition for immune system support, and mind-body medicine to support a healing consciousness.

History

Insulin Potentiation Therapy was developed in the Mexico in the 1920's by Donato Perez Garcia, MD, Sr. (1896-1971). His research and work was followed and developed upon by his son Donato Perez Garcia y Bellon, MD (1930-2000). The current principal proponents of this treatment are Donato Perez Garcia, MD, Jr.- grandson and son, respectively, to the Drs. Garcia - and Steven G. Ayre, MD. Dr. Garcia practices in Tijuana, Mexico and claims that IPT is especially effective with breast cancer, but can also be effective with a number of other cancers, including small-cell lung cancer and prostate cancer. If a cancer can be affected by existing chemotherapy drugs, then insulin potentiation therapy can also be effective, but minus the major side effects. Dr. Ayre first became interested in IPT on the 1970's after talking with Dr. Garcia y Bellon. He opened the first clinic in the US providing IPT in November 1999 near Chicago, IL called Contemporary Medicine. He focuses on a comprehensive treatment for cancer involving nutritional and mind-body support in conjunction with low-dose chemotherapy.

IPT is currently practised throughout the world to treat cancer and other degenerative diseases.

Supportive Research

Several in-vitro studies have shown how IPT works supporting the informal clinical work that has been conducted on hundreds of patients worldwide.^[25][26]

The first clinical trial of IPT for treating breast cancer was done in Uruguay and published in 2003/04. Insulin combined with low-dose methotrexate resulted in greatly increased stable disease, and much reduced progressive disease, compared with insulin or low-dose methotrexate alone.^[27]

In 2000, the National Cancer Institute's Cancer Advisory Panel on Complementary and Alternative Medicine (CAPCAM) invited Drs. Perez Garcia and Ayre to present IPT to them as part of the National Cancer Institute's (NCI's) Best Case Series program.

The Elka Best Foundation, a non-profit organization set up by the daughter of an IPT patient, is working to support research and education in this area. The foundation also helps to develop communication between the certified practitioners and the public. Each year a conference is held in which IPT practitioners and other interested parties are invited to relate the continuing work that they have been producing.