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IPT consists of an artificially generated pulse of hypoglycemia (low blood sugar) that apparently improves the effectiveness of drugs through several mechanisms. IPT makes cell membranes more permeable, and increases uptake of drugs into cells. It apparently makes tissues more permeable, too. It can help transport drugs across the blood-brain barrier. It may stimulate growth of blood vessels, and may stimulate and balance the immune system. In tumors, it apparently selectively delivers chemotherapy drugs to cancer cells, and makes the cells more susceptible to the drugs by modifying their metabolism and by stimulating them to begin dividing. IPT also may change the chemistry of the blood in a way that appears to improve health.

"If it ain't complicated it don't matter whether it works or not because if it ain't complicated up enough, it ain't right. So even if it works, don't believe it." --- William Faulkner, The Town

How does IPT work? While there are and have been a lot of theories and explanations, no one really knows for sure. IPT was developed empirically -- because it works. And it has been practiced for sixty years for that same reason.

Many things in science and medicine are only known empirically. There are many drugs and medical procedures whose effects are known and valued, but whose detailed mechanisms of action are still unknown. No one really knows what an electron is, but we use them every day using empirical methods and theories that work reliably. So we can ask, "How does IPT work?" And the Doctors Donato Perez Garcia will say, "Very, very well."

But there are certain advantages to at least having working theories about how IPT works. The greatest of these is that having working theories will make it easier for medical professionals to accept the reports of IPT's successes, and it will make it easier for them to feel justified in trying and using IPT. (Indeed, it is for lack of such understanding, or for having apparently contradictory working models, that some doctors have dismissed IPT in the past.)

A second advantage is that such theories provide doctors with a working model which they can use during the IPT procedure, to visualize what is happening, and to help them make their actions more responsive and effective.

And a third advantage is that such theories may enable researchers to think of new applications to try for IPT, and new ways to modify the method and the medications used, which may prove to have even greater effectiveness.

How does IPT work? If you want one simple answer in 25 words, you will be disappointed. My new favorite metaphor is to compare IPT to the holiday season. How does the holiday season work? Many things happen simultaneously, and there is a cyclic progression through time. There is a long build-up. Gifts are inventoried, displayed, shopped for, bought, wrapped, and delivered. Profits and banking happen. Publications and TV programs go out. People travel to distant cities. Meals are cooked. Houses are decorated. Finally the big event happens: eating, parties, exchanging and opening gifts. And then comes a shorter recovery, clean-up, and return to normal. Long build-up, therapeutic moment, and short recovery -- that's the IPT process in a nutshell.

Several of the IPT doctors have theorized about how IPT works. Dr. Perez Garcia 1 wrote in 1953. Dr. Perez Garcia y Bellon 2 wrote in 1978. Steven G. Ayre MD wrote in 1986 and since. And Jean-Claude MD wrote in 1995. But all are based mainly on observations and on research that was not specifically focused on the IPT protocol. Basic IPT lab research still needs to be done.

Here, then, are some theories of how IPT works. Some theories are based on detailed understanding of molecular biology and biochemistry. Others are based on years of observation, by doctors working with patients. Insulin has many actions in cells and in the body, and it has been studied more than any other hormone. It probably still has many mysteries to reveal. Until now, most of the research has focused, naturally, on insulin's roles in diabetes. And we have just begun to investigate its roles outside the diabetic realm. It could be that, in IPT, insulin is working in only some of the following ways. Or it could be working in all of them. And it could also be working in ways that we have not yet imagined.

This web page is only meant to give an overview. For more detailed understanding, please go to the Publications section of this website.

The IPT Process.
The patient shows up for treatment having fasted overnight. A tray of medications is prepared, based on the patient's illness, symptoms, and general condition. Doses are typically 1/2 to 1/20 of the dose normally given without IPT.

An intravenous (IV) drip is established. A small amount of IV insulin is given, about 0.1 to 0.4 units per kilogram of patient weight. Humalog ® (Lilly, fast-acting human-like insulin) is the current insulin of choice. Humulin ® (Lilly, regular human insulin) is also very effective. Any intramuscular and oral medications are given to the patient a few minutes later, so that they will have time to enter the bloodstream. The patient is always under close observation. In a rare case of insulin hypersensitivity, IV glucose can be immediately given to avoid any danger of shock.

After 20 to 30 minutes, symptoms of mild hypoglycemia (low blood sugar) start to develop: hunger, thirst, drowsiness, mild sweat, increased body temperature, faster heartbeat (tachycardia) and palpitations. The doctor decides how long to wait, and how far these symptoms should progress. Deeper hypoglycemia seems to produce quicker and more profound medical results. Normal blood glucose ranges from 80 to 100 mg/dl. During IPT it falls to around 55 to 60 mg/dl. Using Humulin (human insulin of recombinant DNA origin, Lilly), the process takes roughly 29 to 42 minutes. Using Humalog (faster acting variant of Humulin), it takes only 18 to 21 minutes.

The "Therapeutic Moment" has arrived. The Drs. Donato say that at this time, "the doors are open", and medications can be most effectively absorbed. Intravenous medications are given, followed by IV hypertonic glucose. Symptoms of hypoglycemia rapidly disappear. And the patient is given a sweet beverage (Gatorade® or fruit juice) to complete the recovery of normal blood sugar levels. Total elapsed time for the IPT treatment (using Humalog) can be less than 90 minutes.

The patient is sent away with specific instructions on what light meals to eat, and sometimes with oral medications to take between treatments. Another treatment may be given in two days to two months, depending on the patient's condition and stage of treatment.

So basically, IPT works with a pulse of hypoglycemia, lasting about an hour. And somehow this simple pulse profoundly changes the functioning of the body, or greatly improves the functioning of the medications, or both.

The IPT Process --- a pulse of hypoglycemia

Looking at the suggested mechanisms that follow, perhaps we can describe IPT as a pulse of hyperinsulinemia, rather than hypoglycemia, as it is the extra insulin, not the hypoglycemia, that appears to drive most of the action. However it is much more difficult to measure insulin concentration in the blood, and degree of insulin binding to receptors, and to my knowledge this has never been done during the IPT protocol. So it is just easier to describe it as a pulse of hypoglycemia.

What is actually going on inside the body? What is there about this procedure that apparently makes it work so well? We will only know for sure after a lot more research is done. But here are some of the proposed mechanisms:

Mechanisms proposed for how IPT works.

1. Insulin interacts with insulin receptors. Known. These receptors are found in every cell, in every tissue in the body. They occur mainly on the cell membrane, but have also been found in the nucleus. Insulin receptors are found on the capillary lining (epithelium) of the blood-brain barrier (which vigilantly allows only desired substances into the brain). And they are very prevalent in cancer cells. All insulin does is interact with these receptors. But this simple action can play many roles in the function of many different cell and tissue types, from regulating absorption of glucose, to gene regulation, to tissue growth. All these actions are choreographed and coordinated with countless other hormones and mechanisms in the living mammalian body. Insulin is one of the most basic metabolic and control hormones. IPT probably triggers many of these actions temporarily, and may actually switch operating modes in the body, for longer lasting effects. Much more is known about insulin effects in diabetic people (for whom IPT may not work as easily) than in nondiabetic people.

7. More insulin receptors on tumor cells increase drug uptake. Proposed. Uncontrolled proliferation of cancer cells is stimulated by a number of growth factors, including insulin (which stimulates energy uptake) and insulin-like growth factors (IGF) I and II (which stimulate cell division and growth). There are many more receptors for these hormones on the cell membranes of cancer cells than there are in normal cells. And some cancer cells actually secrete these hormones themselves, resulting in still faster growth. More insulin receptors means more insulin effect, so more drug will enter cancer cells due to the various mechanisms already outlined. This allows the drug to be given in a smaller dose, far less toxic to normal cells, while building up lethally toxic concentrations in cancer cells. Thus the growth mechanism of the cancer cell is used against it in IPT.

4. Increased uptake of medications into cells. Known. Insulin has been shown to increase the concentration of drugs in cells. This could be due to increased cell membrane permeability. It could also be due to a phenomenon of receptor-mediated endocytosis, whereby the insulin receptor transports a drug across the cell membrane and into the cell, either attached or not to a molecule of insulin.

2. Increased cell membrane permeability. Proposed. Insulin alters lipid synthesis in cells, apparently making cell membranes more fluid, and therefore more permeable.

3. Increased general permeability of tissues. Empirical. Experience appears to demonstrate that IPT enables and increases penetration of medications into all compartments of body, even those which are difficult or impossible to penetrate by other means. These compartments include the central nervous system (CNS), through the blood-brain barrier, joints, solid tumors, and perhaps even the eyes. With IPT, Dr. Perez Garcia 1 was able to increase the concentration of toxic antimicrobial drugs in the CNS, and he believed that he was also able to remove them after they had performed their task. Dr. Perez Garcia 3's success with IPT treatment of arthritis may support the hypothesis that permeability of joint tissue is increased.

5. Increased transport of medications across the blood-brain barrier. Dr. Perez Garcia 1 demonstrated this first in dogs, then in humans. Dr. S.G.Ayre demonstrated this with AZT in rats. Pardridge at UCLA has investigated and verified some of the mechanisms involved. This is highly significant for treatment of CNS conditions, and for elimination of chronic infections which may be harbored in the CNS.

6. Angiogenesis (formation of new blood vessels) increases. Empirical and Proposed. The literature shows that insulin can act as a stimulator of angiogenesis in vitro. There are also reports of insulin speeding up healing of wounds. The Doctors Donato have found IPT to help clear up vascular problems. It could be that IPT, by stimulating angiogenesis, will help bypass blocked or injured blood vessels. Some cancer researchers are trying to inhibit angiogenesis as a way of cutting off circulation to tumors. IPT would appear to go against this direction, but it has other, quicker ways to kill tumors, as will be seen next.

8. Metabolic changes in tumor cells. Proposed. Some researchers propose that insulin may change metabolism of cancer cells in such a way that they become more sensitive to certain chemotherapy drugs. For instance, it was reported that insulin increased toxicity of methotrexate (a common chemotherapy drug) by a factor of 10,000 in breast cancer cells in vitro.

9. Tumor cell division stimulated: more susceptible to drugs. Proposed. It is known that insulin will also stimulate (or cross-react with) the receptors for IGF I and II. Thus insulin alone can simultaneously stimulate cell metabolism through reacting with its own receptor, and also stimulate cell division through cross-reacting with IGF receptors. Since IPT involves a pulse of insulin, it has been proposed by S.G.Ayre that this pulse may stimulate a large fraction of tumor cells to enter the S-phase of cell division simultaneously. And cells in S-phase are much more susceptible to the killing effects of some chemotherapy drugs. In treatment of diseases other than cancer, stimulated cell division may actually be a desired effect for the cells, helping diseased tissues regenerate and heal.

10. Change of blood chemistry and physics. Known and Proposed. It is well known that insulin and glucose levels in the blood bring profound changes in blood chemistry and physical properties. Drs. Perez Garcia 1 and 2 studied this effect during IPT treatments. They suggested that a major part of IPT's effectiveness could be due to these changes in the biophysicochemical properties of the blood. Their understanding was that these changes were not just temporary, occurring only during the treatment, but that they persisted long after the treatment was over. Sometimes they spoke of changes in the "biological terrane" of the body so that it is less hospitable to disease, and more supportive of health. In the BioPulse process, other doctors use hour-long controlled hypoglycemia sleep periods to increase oxygen and pH and lower sugar in the blood, producing an environment that is adverse to tumors. No doubt this also occurs during the shorter hypoglycemic pulse of IPT.

11. Osmosis of glucose into cells. Proposed. This was an early explanation proposed by Dr. Perez Garcia 1. His idea was that insulin would cause all the glucose to leave the blood and enter the cells. This would result in an osmotic gradient, which could speed the passage of medications across the cell membrane.

12. "Hunger" of cells. Proposed. Also proposed as a working hypothesis in the early days of IPT by Dr. Perez Garcia 1. Through fasting, and then administration of insulin, the blood would be cleared of glucose, and the cells would be starved (as indeed the brain is during hypoglycemia). Hungry cells would then be more likely to take in medications along with the glucose that is suddenly added at the Therapeutic Moment.

13. Detoxification. Empirical. Based on his experience with treating syphilis using toxic heavy metal drugs, Dr. Perez Garcia 1 postulated that IPT could also detoxify the cells, tissues, and whole body. It makes sense to me. If cell membranes and tissues are more permeable, then toxins will be more free to be mobilized and set up for elimination. This was also apparently part of the reasoning behind the former practice of giving a patient an enema before each IPT treatment. The thought was that this would eliminate toxins from the body that might otherwise be absorbed through a more permeable intestinal wall. Dr. Perez Garcia 3 has observed that patients with weak livers (low detoxification capability) usually do not do very well with IPT for cancer treatment. This indicates that while IPT may kill tumor cells, and may flush toxins into the circulation, the organs of elimination must still be in good working order. Another application of the detoxification obtained through IPT is in the treatment of alcoholism, drug addiction, and smoking reported by Dr. Paquette. Note that both the Drs. Perez Garcia and Dr. Paquette have focused as much attention on detoxifying the body as they have on treating the presenting disease. Their typical IPT treatments have included small amounts of drugs to stimulate and detoxify the liver.

14. Immune system stimulation and modulation. Empirical and Known. Rapid healing of infections and wounds, and improved health for people with immune system over-reactivity (arthritis and allergies) seems to indicate that IPT can stimulate the immune system and perhaps switch it into a less reactive mode. There are certainly insulin and IGF-I receptors on immune cells. And a quick look at Medline shows me that insulin is present in mother's milk and may help stimulate development of the digestive and immune system, and that IGF-I may assist in the development of the immune system in children. This is a whole field to investigate.

15. Placebo effect and psychology. Empirical and Known. I have speculated jokingly from time to time that it might be the Drs. Donato themselves, and not IPT, who have produced all the good results. It is well documented that the doctor-patient relationship is indeed important in the healing process. And the placebo effect is also well known. I have heard that some doctors who have tried IPT without much training from the Drs. Perez Garcia, may have had only mixed success. Could this be due to a lower level of knowledge and experience, or could it be due to some lack of confidence, or lack of personal contact with the Drs. Perez Garcia? Even Dr. Perez Garcia 3 has told me that IPT seems to work much better for patients who have a positive attitude. Because of this, he is often reluctant to treat patients who do not have a positive attitude. Only double blind placebo-controlled testing could eliminate these variables for sure.

16. Lower doses of drugs work as well or better, with less or eliminated toxicity. Empirical. This is the essential observation of the doctors who have used IPT. In the early days of IPT, Dr. Perez Garcia 1 even used larger doses of toxic heavy metal drugs, with better results and less toxicity. Because of the lower doses typically needed with IPT to achieve the drug effect, there may be less interaction between drugs, allowing a single IPT treatment to deliver a custom-tailored cocktail of multiple drugs and nutrients.

17. Insulin stimulates proliferation and differentiation of stem cells and fibroblasts. Known and proposed. (3/4/00) A quick search of Medline shows me that insulin and IGF-1 are potent growth factors that stimulate proliferation and differentiation of adult stem cells in brain (J Neurosci Res 59(3):332-341), and I suspect that this may be true in other tissues as well. Insulin and IGF-1, particularly in combination with zinc, stimulates DNA synthesis (cell growth) in skin fibroblasts (Eur J Biochem 266(3):943-51), and I suspect that this may be true in other tissues as well. So insulin, and IGF-1, with which it cross-reacts, are apparently directly involved in many cell growth, proliferation, and differentiation processes. IPT is probably not just stimulating the immune system, but is stimulating the body's regeneration system.

18. The "Worm" theory of IPT. Proposed. This is my own hypothesis (7Sept99). Insulin-like molecules and their receptors go way back in evolution. Even nematodes (a type of small worm) have them. In these worms, the insulin-like molecules have key roles in reproduction, metabolism, and longevity. It could be that IPT triggers one or more ancient biological mechanisms that were crucial to the life processes and life cycles of our earliest ancestors. This may happen through the expression of some normally inactive genes. Careful observation of nematodes in different environments and through the stages of their life cycle may give us some deeper insights into how IPT works.

19. IPT may not work as easily in diabetic patients.. Empirical. All three of the Doctors Donato have agreed to this observation. Diabetic patients need special attention and care. They can be treated with IPT using lower doses of insulin, but more experience is needed to treat them. (A brief description of how Drs. Perez Garcia 1 and 2 treated them in the late 1970s.) One explanation could be that frequent rises and falls of insulin and glucose concentrations in the blood may alter the numbers and the behavior of insulin receptors on cell membranes, or otherwise alter the whole insulin-regulated system of cells.

However, note that we have several case histories where IPT brought good results to diabetic patients.

Doctors new to the idea of IPT seem to always bring up this diabetes question: If IPT works so well, why don't we notice drug potentiation among diabetic people, who are taking extra insulin all the time? I talked once to someone who had just become diabetic, and he told me that he had indeed noticed a drug potentiating effect at the beginning. Also, I believe it is well known that diabetics are much more susceptible to the effects of alcohol.

In July of 1998 I met best-selling author Dr. Barry Sears, writer of The Zone and The Anti-Aging Zone, and other "Zone" books. When I told him about IPT, he was not surprised in the least, much to my own surprise. To him, IPT made perfect sense. Citing a recent article (Markovic et al. Diabetes Care 21: 695-700) he hypothesized that the 40-30-30 diet (40% of dietary calories from carbohydrates, 30% from protein, 30% from fat) that he espouses could help diabetic people reform their insulin receptors to the point that IPT would work well for them. This hypothesis has yet to be tested.

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