CONTENTS
Why we need to know.
The IPT
process.
Mechanisms proposed for how IPT
works.
1. Insulin
interacts with insulin receptors.
2.
More insulin receptors on tumor cells increase drug uptake.
3. Increased
uptake of medications into cells.
4. Increased
cell membrane permeability.
5. Increased
general permeability of tissues
6.
Increased transport of medications across the blood-brain barrier.
7.
Angiogenesis (formation of new blood vessels) increases.
8. Metabolic
changes in tumor cells.
9.
Tumor cell division stimulated: more susceptible to drugs.
10. Change of blood
chemistry and physics.
11. Osmosis of glucose into cells.
12. "Hunger" of cells.
13. Detoxification.
14. Immune system
stimulation and modulation.
15. Placebo effect and psychology.
16.
Lower doses of drugs work as well or better, with less or eliminated toxicity.
17.
Insulin stimulates proliferation and differentiation of stem cells and
fibroblasts.
18. The "Worm"
theory of IPT.
19. IPT
may not work
as easily in diabetic patients.
Why we need to know.
<Return to CONTENTS>
"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.
SGA
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. (See figure
below.) <Return to
CONTENTS>
- 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.
Click on this image for enlarged version. |
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. <Return
to CONTENTS>
1. Insulin interacts
with insulin receptors. Known.
<Return to
CONTENTS> 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. <Return to CONTENTS>
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. <Return to CONTENTS>
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.
<Return
to CONTENTS> Insulin alters
lipid synthesis in cells, apparently making cell membranes more fluid, and therefore more
permeable.
3. Increased
general permeability of tissues. Empirical.
<Return to CONTENTS>
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.
<Return to
CONTENTS> Dr. Perez Garcia 1 demonstrated this first in dogs, then in humans. Dr. S.G.SGA 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. <Return to CONTENTS>
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. <Return to CONTENTS>
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.
<Return to CONTENTS>
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.SGA
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. <Return to
CONTENTS> 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. <Return to CONTENTS>
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. <Return to CONTENTS>
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. <Return to CONTENTS>
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. <Return
to CONTENTS> 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. <Return to CONTENTS>
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. <Return to CONTENTS>
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) <Return to
CONTENTS> 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.
<Return to
CONTENTS> 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. <Return to CONTENTS>
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. More
"Zone" information can be found at http://www.ZonePerfect.com
<Return to CONTENTS>
