Insulin potentiation therapy
Encyclopedia
Insulin potentiation therapy (IPT) is an alternative cancer treatment using insulin
and low-dose chemotherapy.
The therapeutic approach is said to take advantage of the endogenous molecular biology of cancer cells, specifically the secretion of insulin
and insulin-like growth factor, and the interaction of these biochemicals with their specific receptors. By using insulin in conjunction with chemotherapy drugs, significantly less drugs (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 claiming enhancing antineoplastic effects.
Insulin can serve to distinguish and differentiate cancer cells from healthy cells in several ways. Insulin is produced in the pancreas, one of whose many functions is the regulation of blood glucose levels. 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.
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.
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 affects normal tissues.
Something else to take into consideration is that ligand
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 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.
- promoter of cell division - for cancer growth.
The favorable effect in a treatment that is trying to kill cancer is 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.
However, 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 has to be used, causing healthy cells to be 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.
, making them more permeable.
Cell membranes are largely made up of triglycerides, which are built of fatty acids. The more saturated 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 °C. Stearic acid, once it has been de-saturated, becomes mono-unsaturated oleic acid
, which has a melting point of 5 °C. At physiologic temperatures (the temperature of the body, about 37.5 °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 °C. This cell membrane will be more permeable at physiologic temperatures. The chemotherapy 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.
A clinical trial of IPT for treating breast cancer was done in Uruguay
and concluded that "The group treated with insulin + methotrexate responded most frequently with stable disease" compared to being treated with methotrexate alone or insulin alone.
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. However CAPCAM have not in the time since undertaken any further research into IPT.
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
and low-dose chemotherapy.
The therapeutic approach is said to take advantage of the endogenous molecular biology of cancer cells, specifically the secretion of insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
and insulin-like growth factor, and the interaction of these biochemicals with their specific receptors. By using insulin in conjunction with chemotherapy drugs, significantly less drugs (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 claiming enhancing antineoplastic effects.
Controversy regarding effectiveness
Some physicians have labeled insulin potentiation therapy a form of quackery and have warned against its use.Claimed explanatory molecular biology
The proponents of IPT give the following explanation of the biology of cancer and its cells in order to understand the mechanisms of IPT, which relies upon insulin, the most integral component of IPT, having three significant actions upon cancer cells described below, as well as also dropping blood sugar levels and thus the energy source for cancer. Low blood glucose (below 60 mg/dl) also stimulates secretion of growth hormone, and growth hormone, it is presumed, helps to strengthen the immune system.Differentiation between cancer and normal cells
Insulin biologically differentiates cancer cells from normal cells based on insulin receptor concentration.Insulin can serve to distinguish and differentiate cancer cells from healthy cells in several ways. Insulin is produced in the pancreas, one of whose many functions is the regulation of blood glucose levels. 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.
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.
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 affects normal tissues.
Something else to take into consideration is that ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
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 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.
Modification of cancer cell metabolism
Not only does insulin provide cancer cells with the means to grow it has also been proven that IGFs are the most potent mitogenMitogen
A mitogen is a chemical substance that encourages a cell to commence cell division, triggering mitosis. A mitogen is usually some form of a protein.Mitogenesis is the induction of mitosis, typically via a mitogen....
- promoter of cell division - for cancer growth.
The favorable effect in a treatment that is trying to kill cancer is 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.
However, 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 has to be used, causing healthy cells to be 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.
Increase in cell membrane permeability
The third effect that insulin has on cancer cells is to activate enzyme activity in the cell membraneCell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
, making them more permeable.
Cell membranes are largely made up of triglycerides, which are built of fatty acids. The more saturated 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
Desaturase
A fatty acid desaturase is an enzyme that removes two hydrogen atoms from a fatty acid, creating a carbon/carbon double bond. These desaturases are classified as...
, 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
Stearic acid
Stearic acid is the saturated fatty acid with an 18 carbon chain and has the IUPAC name octadecanoic acid. It is a waxy solid, and its chemical formula is CH316CO2H. Its name comes from the Greek word στέαρ "stéatos", which means tallow. The salts and esters of stearic acid are called stearates...
– has a melting point of 65 °C. Stearic acid, once it has been de-saturated, becomes mono-unsaturated oleic acid
Oleic acid
Oleic acid is a monounsaturated omega-9 fatty acid found in various animal and vegetable fats. It has the formula CH37CH=CH7COOH. It is an odorless, colourless oil, although commercial samples may be yellowish. The trans isomer of oleic acid is called elaidic acid...
, which has a melting point of 5 °C. At physiologic temperatures (the temperature of the body, about 37.5 °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 °C. This cell membrane will be more permeable at physiologic temperatures. The chemotherapy 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.
Supportive research
In-vitro studies have shown how IPT works supporting the informal clinical work that has been conducted on hundreds of patients worldwide.A clinical trial of IPT for treating breast cancer was done in Uruguay
Uruguay
Uruguay ,officially the Oriental Republic of Uruguay,sometimes the Eastern Republic of Uruguay; ) is a country in the southeastern part of South America. It is home to some 3.5 million people, of whom 1.8 million live in the capital Montevideo and its metropolitan area...
and concluded that "The group treated with insulin + methotrexate responded most frequently with stable disease" compared to being treated with methotrexate alone or insulin alone.
In 2000, the National Cancer Institute
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
'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. However CAPCAM have not in the time since undertaken any further research into IPT.