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THeMaCHinE
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GaryWary?
Is myo-inositol the same as inositol?
- Thread starter THeMaCHinE
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THeMaCHinE
New member
.
inositol is myo-inositol.
IP6 (inositol hex-phosphate) is the inositol we get in our food (veggies, pulses, and soy mainly). IP6 is the pre-cursor to inositol (myo-inositol). IP6 is converted into inositol in the gut by an enzyme. The enzyme is destroyed by ephedrine and caffeine (take note!).
IP6 is the most potent anti-cancer nutrient known. It is believed to be the priniple anti-cancer nutrient found in vegetables (i.e. the reason why people who munch plenty of veggies have lower risks of certain (most) cancers.
IP6 (inositol hex-phosphate) is the inositol we get in our food (veggies, pulses, and soy mainly). IP6 is the pre-cursor to inositol (myo-inositol). IP6 is converted into inositol in the gut by an enzyme. The enzyme is destroyed by ephedrine and caffeine (take note!).
IP6 is the most potent anti-cancer nutrient known. It is believed to be the priniple anti-cancer nutrient found in vegetables (i.e. the reason why people who munch plenty of veggies have lower risks of certain (most) cancers.
I take both inositol and IP6 (because I once had cancer - so I am just being safe).
For twelve years, Dr. AbulKalam Shamsuddin and his colleagues, sponsored in part by the American Institute for Cancer Research, have been performing ground-breaking experiments on the B vitamin inositol and its derivative, IP6, a natural component of grains such as rice, corn, and wheat, and legumes such as soybeans. After astounding laboratory results. IP6 is finaly available to the public as an anti-cancer nutrient.
This all-natural substance works to fight cancer, as well as to combat diabetes, heart disease and other serious disorders.
For twelve years, Dr. AbulKalam Shamsuddin and his colleagues, sponsored in part by the American Institute for Cancer Research, have been performing ground-breaking experiments on the B vitamin inositol and its derivative, IP6, a natural component of grains such as rice, corn, and wheat, and legumes such as soybeans. After astounding laboratory results. IP6 is finaly available to the public as an anti-cancer nutrient.
This all-natural substance works to fight cancer, as well as to combat diabetes, heart disease and other serious disorders.
This natural molecule, IP6, has reduced cancer growth in two dozen different animal studies.
"We have no studies like this with drugs or with other anti-cancer agents that are as remarkable as this one molecule," says medical journalist Bill Sardi.
As seen in this model, one key to IP6's power is six phosphate groups arrayed around a base of the B vitamin inositol. And remember that IP6 has other names: inositol hexaphosphoric acid and phytic acid.
Cancer researcher Abul Kalam Shamsuddin says that IP6 fights many kinds of cancer. "On cancer of the colon, prostate, breast, leukemias, lymphomas, fibrosarcomas, muscle tumors, and Dr. Sakomoto from Japan has tested on brain tumors."
Other aminal research shows action against liver cancer and lung tumors. Shamsuddin's financial interest needs to be noted: he has a paperback out on IP6 and rights to the only IP6 food supplement available.
But IP6 is not that easily dismissed; dozens of reputable scientists are looking into IP6, including many who spoke at the first world symposium on IP6 in June. One aspect that makes IP6 unique is that, unlike money, it actually grows on trees.
"And IP6 is in almost every species that's been tested. It's in the plants." Shamsuddin says the research warrants human studies on cancer prevention and treatment. "It's long overdue," he says. "We have had numerous other drugs that we know of, with much less scientific data."
CBN News asked the American Cancer Society about IP6. Officials there were not familiar with IP6, but were quite interested in learning more about this substance.
The National Cancer Institute has shown interest in IP6 by publishing an article in a 1992 cancer prevention volume and a 1995 article in the journal Cancer Research. But the NCI recently rejected Shamsuddin's proposal for testing IP6 against human cancer. It was decided that the agent would not be brought forward to the Decision Network. That means IP6 didn't make the finals for consideration of funding.
While funding for human research with IP6 is scarce, IP6, also called phytic acid, is plentiful in whole grains, beans, nuts, and seeds. The author of Phytic Acid: Chemistry and Applications, scientist Ernst Graf told CBN News that he personally eats lots of whole grains.
Shamsuddin adds that the most benefit comes from the IP6 concentrate used both in the laboratory and in the supplement he designed. And Ivana Vucenik, Shamsuddin's colleague at the University of Maryland, finds IP6 quite safe, especially compared to most cancer-fighting agents.
"The aminals did not show any kind of negative side effects, any kind of toxicity, they looked normal, and their body weight was normal," says Vucenik.
Vucenik is impressed with evidence of IP6's disease-fighting ability. "Anything that can boost our immune system is benefiting the patient's health," says Vucenik. "And so this is exactly what IP6 can do."
And that has to do with boosting natural killer cells. These cells attack viral, bacterial, and fungal infections. Vucenik finds that IP6 is also active against heart and circulatory disease.
"IP6 can inhibit aggregation of human platelets," says Vucenik. "That is why it has great potential in preventing cardiovascular disorders."
This clumping of blood cells contributes to heart attacks and strokes. And because IP6 scavenges iron out of the body, tens of millions of older people could possibly benefit. Excess iron in their bodies speeds up aging and cell damage.
"If you take a dish of cells, and you have a salt shaker of iron, and you pour it on those cells, then they'll die quite readily," says Sardi. "A lot of wise cancer patients are moving ahead and starting to take IP6 on their own."
But the American Cancer Society and the National Cancer Institute advise caution until further research ends the controversy.
"We have no studies like this with drugs or with other anti-cancer agents that are as remarkable as this one molecule," says medical journalist Bill Sardi.
As seen in this model, one key to IP6's power is six phosphate groups arrayed around a base of the B vitamin inositol. And remember that IP6 has other names: inositol hexaphosphoric acid and phytic acid.
Cancer researcher Abul Kalam Shamsuddin says that IP6 fights many kinds of cancer. "On cancer of the colon, prostate, breast, leukemias, lymphomas, fibrosarcomas, muscle tumors, and Dr. Sakomoto from Japan has tested on brain tumors."
Other aminal research shows action against liver cancer and lung tumors. Shamsuddin's financial interest needs to be noted: he has a paperback out on IP6 and rights to the only IP6 food supplement available.
But IP6 is not that easily dismissed; dozens of reputable scientists are looking into IP6, including many who spoke at the first world symposium on IP6 in June. One aspect that makes IP6 unique is that, unlike money, it actually grows on trees.
"And IP6 is in almost every species that's been tested. It's in the plants." Shamsuddin says the research warrants human studies on cancer prevention and treatment. "It's long overdue," he says. "We have had numerous other drugs that we know of, with much less scientific data."
CBN News asked the American Cancer Society about IP6. Officials there were not familiar with IP6, but were quite interested in learning more about this substance.
The National Cancer Institute has shown interest in IP6 by publishing an article in a 1992 cancer prevention volume and a 1995 article in the journal Cancer Research. But the NCI recently rejected Shamsuddin's proposal for testing IP6 against human cancer. It was decided that the agent would not be brought forward to the Decision Network. That means IP6 didn't make the finals for consideration of funding.
While funding for human research with IP6 is scarce, IP6, also called phytic acid, is plentiful in whole grains, beans, nuts, and seeds. The author of Phytic Acid: Chemistry and Applications, scientist Ernst Graf told CBN News that he personally eats lots of whole grains.
Shamsuddin adds that the most benefit comes from the IP6 concentrate used both in the laboratory and in the supplement he designed. And Ivana Vucenik, Shamsuddin's colleague at the University of Maryland, finds IP6 quite safe, especially compared to most cancer-fighting agents.
"The aminals did not show any kind of negative side effects, any kind of toxicity, they looked normal, and their body weight was normal," says Vucenik.
Vucenik is impressed with evidence of IP6's disease-fighting ability. "Anything that can boost our immune system is benefiting the patient's health," says Vucenik. "And so this is exactly what IP6 can do."
And that has to do with boosting natural killer cells. These cells attack viral, bacterial, and fungal infections. Vucenik finds that IP6 is also active against heart and circulatory disease.
"IP6 can inhibit aggregation of human platelets," says Vucenik. "That is why it has great potential in preventing cardiovascular disorders."
This clumping of blood cells contributes to heart attacks and strokes. And because IP6 scavenges iron out of the body, tens of millions of older people could possibly benefit. Excess iron in their bodies speeds up aging and cell damage.
"If you take a dish of cells, and you have a salt shaker of iron, and you pour it on those cells, then they'll die quite readily," says Sardi. "A lot of wise cancer patients are moving ahead and starting to take IP6 on their own."
But the American Cancer Society and the National Cancer Institute advise caution until further research ends the controversy.
THeMaCHinE
New member
I'm unclear (still early) is inositol a derivative of IP6 or IP6 a derivative of inositol. Does taking say 6 - 8 grams/day of inositol cover the IP6 needs as well?
Thx for the info.
Thx for the info.
Add Some Rice To Your Life
Advances in Rice-Based Products with Potential Benefits to Health
By Raxit J. Jariwalla, Ph.D.
California Institute for Medical Research
San Jose, California 95128
The word '"fiber" comes to mind when we think of cereals, whole grains
and health. However, while fiber is important to our health, it is not
the sole ingredient endowed with medicinal value. Other constituents
locked within cereals and grains possess important physiologic and
pharmacologic properties which are being rapidly uncovered by medical
research. This is best exemplified in the case of rice and its
components, which was the focus of an international symposium held last
summer in Kyoto, Japan.
Rice is an important staple cereal of a large fraction of the world's
population. It is primarily consumed after processing as polished
rice. The bran or germ which comprises 10% of whole rice is removed
during the polishing process. However, rice bran is an important source of
rice oil and other phytochemicals which possess antioxidative and
disease-fighting properties. Traditionally, rice-bran products have found
applications in agricultural, food and cosmetic industries. Now, medical
research has unraveled scientific evidence supporting a role for key
components of rice in health maintenance and disease prevention.
Rice-based products drawing much attention of biomedical researchers
include: myo-inositol (a B vitamin), its phosphate-derivative inositol
hexaphosphate (IP6 or phytate), rice-bran oil and polyphenols with
antioxidant function. IP6 is the major form of phosphorylated inositol
present in foods, constituting 1-5% by weight of most cereals, nuts,
oilseeds, legumes and grains. It occurs at 9.5-14.5% by weight in rice
bran. Antioxidative polyphenols in rice bran include ferulic acid, its
esterified derivatives (oryzanols), tocopherols and other phenolic
compounds.
The first international symposium on "Disease Prevention by IP6 and
Other Components of Rice" was held last June in Kyoto. About 520
people convened at this conference devoted to inositol, inositol
hexaphosphate and other components of rice. Some 20 speakers presented
papers on topics ranging from chemistry and mechanisms of action to
anti-cancer effects and other beneficial functions of IP6. About 10
studies were presented on ferulic acid, rice bran oil and other
components of rice. In addition, 65 other papers were presented in
poster sessions as reports of research which complemented above studies.
From the quality of the information presented, it can be said that
increased consumption of rice and its products would result in improved
health, with reduction in heart disease, renal stones and some forms of
cancer.
The symposium was sponsored by Tsuno Foods & Rice which, since 1947, has been
developing and improving ways of using rice bran for industrial manufacture
based on rice oil extraction and refinery. In fact, the symposium was held at
the occasion of the company's 50th anniversary. Its purpose was to foster
exchange of information and ideas about important developments that have
bearing on disease prevention by rice components with medicinal properties.
Back to Index
Beneficial Effects of IP6 and Inositol
The symposium started with a discussion of chemistry and usage of rice
components. S. Ogawa (Keio University) presented an impressive overview
of chemical structures and uses of myo-inositol and its related
compounds. T. Osawa (Nagoya University) discussed the protective role of rice
antioxidants in oxidative stress and Y. Watanabe (Ehime University, Matsuyama)
reviewed the synthesis of inositol triphosphate and phospholipids.
A large portion of the symposium was devoted to IP6 and its parent
molecule, inositol. It is difficult to summarize all the studies
presented at the conference. This article will touch upon major
findings of relevance to disease prevention and treatment.
Back to Index
Cancer
Let's consider the advances against cancer. A renowned epidemiologist
reviewed studies linking diet and life style to cancer (S.Sugano, Cancer
Institute, Tokyo). It's been known for sometime that consumption of whole
grains, vegetables and fruits is linked to reduced cancer risk. These foods
are rich in fiber which has been shown to protect against both colonic and
mammary cancer (reviewed by B.S. Reddy and L. A. Cohen, American Health
Foundation, New York). However, as it became apparent at the symposium, fiber
is not the sole anticarcinogen since other substances in fiber-containing
foods also exert protective influences on cancer. Thus, a multinational
epidemiologic study carried out in the mid 1980's had shown that foods rich in
phytate (IP6) but poor in fiber, such as cereals and grains, correlated better
with reduced risk of colon cancer than phytate-poor fiber foods such as fruits
and vegetables (Graf and Eaton, Cancer 1985; 56:717-718). IP6 is a strong
chelating agent and certain metals are known to promote cancer through
generationof reactive free radicals from oxidation of fats. IP6 also plays an
important role in regulating cell proliferation and differentiation.
In 1988, the first two studies were published, reporting inhibitory
effects of purified IP6 on tumor formation in experimental animals. One
study (Shamsuddin et al. Carcinogenesis 9:577-80) showed suppression of
cancer of the large bowel by IP6 and theother study (Jariwalla et al.
Nutr. Res. 8: 813-27) demonstrated reduction of the incidence and size
of soft-tissue tumors (fibrosarcomas) promoted by dietary factors.
Since then, a number of experimental studies have confirmed the
anti-cancer action of IP6 (reviewed by I. Vucenik and A.K.M. Shamsuddin, Univ.
of Maryland, Baltimore). The compound has been shown to inhibit various
rodent and human cancer cell lines in vitro and to protect against growth of
diverse cancers in vivo. Protective effects have been seen against cancers of
the breast, colon, pancreas, liver, skin and connective tissue. In vivo,IP6
not only prevents carcinogen-induced tumor development but it also interferes
with growth of pre-formed, transplanted tumors, suggesting that it may play a
role in both cancer prevention and treatment.
The step at which IP6 acts during tumor development varies depending
upon the type of cancer studied. In colon carcinogenesis, IP6 was shown to
suppress bowel cancer when given before, during and even several months after
carcinogen administration (Shamsuddin and colleagues, Univ. of Maryland).In
a multi-organ rat carcinogenesis model, IP6 administered (as phytic acid)
during the promotion stage suppressed hepatic tumors but had no influence on
development of esophagal, colonic, pancreatic, renal and thyroid tumor lesions
(M. Hirose, National Institute of Health Sciences, Tokyo). In a
two-stage model of carcinogenesis in mouse skin, IP6 inhibited tumor
formation when given during the initiation stage but not during tumor
promotion, indicating differential sensitivity of skin cancer (T. Ishikawa,
Univ. of Tokyo). Clinical studies in humans against different tumor types
would be useful. Awaiting such studies,
what can be said presently is that naturally-occurring salt forms of IP6
appear to be safe in animal studies even when used at higher than
physiologic dosages.
The role of myo-inositol as a chemopreventive agent was also discussed.
It is another phytochemical with low toxicity and ability to inhibit
carcinogenesis in various organs which include mammary gland, colon and
lung. In studies evaluating its chemopreventive activity in lung
carcinogenesis (L. W. Wattenberg, Univ. of Minneapolis, Minnesota), it
was reported that myo-inositol has unusual properties, manifesting a
capacity to prevent lung cancer when given during separate phases of the
carcinogenic process as well as throughout the entire course of the process.
When administered throughout the carcinogenic process, it's effects were found
to be additive. Another study reported on suppression of liver cancer by oral
administration of myo-inositol, thus adding to the diverse spectrum of tumors
affected by this naturally-derived plant constituent (H. Nishino, Kyoto Prefectual
University of Medicine). Myo-inositol has also been reported to enhance the
anti-cancer action of IP6 in other animal studies.
Back to Index
Mechanism of Cancer Suppression
The mechanism by which IP6 or myo-inositol exert chemopreventive and
anti-cancer effects is not completely understood. IP6 is rapidly
absorbed by cells (in vitro and in vivo) and metabolized to lower
phosphates and inositol (reviewed by Shamsuddin). It has been suggested
that lower inositol phosphates may mediate cancer inhibition, although
direct evidence for this is lacking. Both IP6 and its lower phosphates have
metal chelating activity and may interfere with tumor formation by suppressing
metal catalyzed oxidation of fats. Alternatively, IP6 may block the activity
of key enzyme(s) affecting cell proliferation. One enzyme candidate is PI-3
kinase which plays a central role in signal transduction and cell
transformation triggered by growth factor or tumor promoter. IP6 has been
reported to inhibit PI-3 kinase activity in vitro (Z. Dong, Univ. of
Minnesota, Austin). While this enzyme inhibition may explain the
chemopreventive effect of IP6, it is not known whether it mediates IP6's
effect on pre-existing tumors or
established cancer cells. Other, as yet, unknown mechanism may be
involved in the anti-cancer effect of IP6.
Back to Index
Heart Disease
The ability of IP6 to reduce hyperlipidemia and protect against
cardiovascular disease (CVD) was also discussed. CVD is associated with high
mortality in Western and other industrialized countries. It is linked to
several risk factors among which is hyperlipidemia -- high levels of
cholesterol and triglycerides in blood.
It has been known that consumption of Bengal gram, a bean species rich
in IP6, is associated with reduced hypercholesterolemia. In one study,
which directly addressed the role of IP6 in hyperlipidemia, it was shown that
IP6-supplemented diet lowered total cholesterol and triglycerides levels in
serum of animals made hyperlipemic with a high cholesterol diet (reviewed by
R. J. Jariwalla, Calif. Institute for Medical Research, San Jose). The same
study demonstrated that dietary IP6 caused a lowering of the zinc/copper
ratio, a marker of hypercholesterolemia, without significantly affecting
levels of other minerals in serum. This lipid-lowering action of IP6 was seen
at dosages (upto 9% of the diet) that were free of adverse side effects in the
tested animals.
Another study reported on the hypolipidemic action of myo-inositol and
IP6 relevant to treatment of fatty liver (T. Katayama, Hiroshima Univ.). At
physiologic dosages (0.1 -0.5% of diet), these compounds inhibit rises in
hepatic total lipids andtriglycerides resulting from
administration of sucrose. The mechanism of this hypolipidemic effect in the
liver appears to be related to the inhibition of hepatic enzymes involved in
lipogenesis rather than inhibition of intestinal enzymes. Although
physiological levels of IP6 depress accumulation of lipids, they have little
effect on elevated serum lipids. Indeed, these dietary treatments (upto 2.5%
IP6) do not produce significant changes in hepatic cholesterol or serum total
lipid levels in sucrose-treated animals, consistent with findings from the
above study showing reduction of serum hyperlipidemia at higher supplementary
levels of dietary IP6.
IP6 and its derivatives also manifest other benficial effects relevant
to CVD. In separate reports, IP6 was shown to inhibit platelet
aggregation (I. Vucenik, Univ. of Maryland, Baltimore) and to enhance
inflammatory responses of neutrophils in response to microbial stimuli
(P. Eggleton, Oxford Univ.). In earlier animal studies, lower inositol
phosphates have been shown to inhibit calcification in the aorta and
lipid peroxidation in ischemic kidneys, consistent with a role for
hydrolysates of IP6 in protecting against hardening of the arteries
(reviewed by R. J. Jariwalla).
Back to Index
Kidney Stones
Epidemiologic studies have shown that renal stones are more prevalent in
developed countries where populations consume diets based on refined
flour compared to those in developing nations consuming predominantly a
phytate-rich diet. IP6 is naturally present in human urine where normal
levels fluctuate between 0.5 to 5.0 mg/liter (F. Grases, Univ. of Balearic
Islands, Spain). Approximately 1-3% of oral doses are excreted in the urine
with an associated reduced risk of developing renal stones. Biochemical
studies have shown that phytate
can interfere with formation of calculi (crystals) of calcium oxalate
and phosphate (reviewed by F. Grases). This has been demonstrated in
vitro in a system that resembles calculi formation in the kidney as well as in
an animal model of nephrolithiasis where crystal/stone formation and
calcifications on renal papillary tissue are induced by ethylene glycol. In a
preliminary clinical study of 30 renal stone-formers, ingestion of 120mg/day
of IP6 was demonstrated to reduce the urinary risk of kidney stone
development.
Back to Index
Role in Transmission of Chemical Messages
A portion of the symposium was devoted to the role of IP6 and inositol
in signal transduction, the pathway for transmission of external
messages to the interior of cells. Inositol phopholipids present in
plasma membranes have drawn much attention because of their role as
intermediaries in transmission of signals elicited by growth factors and
mitogens acting at the cell surface. Since inositol occurs ubiquitously in
cell membranes in conjugation with lipids as phosphatidylinositol, it plays a
critical role in this process. Additionally, IP6 is the only known dietary
source of inositol phospholipids. During cell stimulation, these molecules
are converted by special enzymes (PI kinases and phospholipase C) to inositol
triphosphate (IP3) and diacylglycerol which act as second messengers inside
cells (reviewed by G. Weber, Univ. of Indiana, Indianapolis). IP3 also plays
a role in cell-to-cell communication and can be generated from IP6 via a
salvage pathway.
In one report (by G. Weber), the activity of signal-transduction enzymes and
concentration of IP3 were reported to be elevated in several types of tumors
above those in normal cells. Anti-tumor componds such as genistein and
quercetin act by inhibiting PI kinases and lowering IP3 concentration in tumor
cells leading to cellular differentiation and death. A nuclear
inositol-lipid pathway was also described with signal-transduction components
located and acting in the nucleus (L. Cocco, Univ. of Bologna, Italy). This
signalling pathway appears to be important in switching cell programming from
a proliferative to a differentiative state. Finally, it was
reported that IP6 is the dominant inositol phosphate in
insulin-secreting cells of the pancreas where it influences secretion of the
hormone by modulating activity of a calcium channel (P.O. Berggren,Karolinska
Institute, Stockholm).
Advances in Rice-Based Products with Potential Benefits to Health
By Raxit J. Jariwalla, Ph.D.
California Institute for Medical Research
San Jose, California 95128
The word '"fiber" comes to mind when we think of cereals, whole grains
and health. However, while fiber is important to our health, it is not
the sole ingredient endowed with medicinal value. Other constituents
locked within cereals and grains possess important physiologic and
pharmacologic properties which are being rapidly uncovered by medical
research. This is best exemplified in the case of rice and its
components, which was the focus of an international symposium held last
summer in Kyoto, Japan.
Rice is an important staple cereal of a large fraction of the world's
population. It is primarily consumed after processing as polished
rice. The bran or germ which comprises 10% of whole rice is removed
during the polishing process. However, rice bran is an important source of
rice oil and other phytochemicals which possess antioxidative and
disease-fighting properties. Traditionally, rice-bran products have found
applications in agricultural, food and cosmetic industries. Now, medical
research has unraveled scientific evidence supporting a role for key
components of rice in health maintenance and disease prevention.
Rice-based products drawing much attention of biomedical researchers
include: myo-inositol (a B vitamin), its phosphate-derivative inositol
hexaphosphate (IP6 or phytate), rice-bran oil and polyphenols with
antioxidant function. IP6 is the major form of phosphorylated inositol
present in foods, constituting 1-5% by weight of most cereals, nuts,
oilseeds, legumes and grains. It occurs at 9.5-14.5% by weight in rice
bran. Antioxidative polyphenols in rice bran include ferulic acid, its
esterified derivatives (oryzanols), tocopherols and other phenolic
compounds.
The first international symposium on "Disease Prevention by IP6 and
Other Components of Rice" was held last June in Kyoto. About 520
people convened at this conference devoted to inositol, inositol
hexaphosphate and other components of rice. Some 20 speakers presented
papers on topics ranging from chemistry and mechanisms of action to
anti-cancer effects and other beneficial functions of IP6. About 10
studies were presented on ferulic acid, rice bran oil and other
components of rice. In addition, 65 other papers were presented in
poster sessions as reports of research which complemented above studies.
From the quality of the information presented, it can be said that
increased consumption of rice and its products would result in improved
health, with reduction in heart disease, renal stones and some forms of
cancer.
The symposium was sponsored by Tsuno Foods & Rice which, since 1947, has been
developing and improving ways of using rice bran for industrial manufacture
based on rice oil extraction and refinery. In fact, the symposium was held at
the occasion of the company's 50th anniversary. Its purpose was to foster
exchange of information and ideas about important developments that have
bearing on disease prevention by rice components with medicinal properties.
Back to Index
Beneficial Effects of IP6 and Inositol
The symposium started with a discussion of chemistry and usage of rice
components. S. Ogawa (Keio University) presented an impressive overview
of chemical structures and uses of myo-inositol and its related
compounds. T. Osawa (Nagoya University) discussed the protective role of rice
antioxidants in oxidative stress and Y. Watanabe (Ehime University, Matsuyama)
reviewed the synthesis of inositol triphosphate and phospholipids.
A large portion of the symposium was devoted to IP6 and its parent
molecule, inositol. It is difficult to summarize all the studies
presented at the conference. This article will touch upon major
findings of relevance to disease prevention and treatment.
Back to Index
Cancer
Let's consider the advances against cancer. A renowned epidemiologist
reviewed studies linking diet and life style to cancer (S.Sugano, Cancer
Institute, Tokyo). It's been known for sometime that consumption of whole
grains, vegetables and fruits is linked to reduced cancer risk. These foods
are rich in fiber which has been shown to protect against both colonic and
mammary cancer (reviewed by B.S. Reddy and L. A. Cohen, American Health
Foundation, New York). However, as it became apparent at the symposium, fiber
is not the sole anticarcinogen since other substances in fiber-containing
foods also exert protective influences on cancer. Thus, a multinational
epidemiologic study carried out in the mid 1980's had shown that foods rich in
phytate (IP6) but poor in fiber, such as cereals and grains, correlated better
with reduced risk of colon cancer than phytate-poor fiber foods such as fruits
and vegetables (Graf and Eaton, Cancer 1985; 56:717-718). IP6 is a strong
chelating agent and certain metals are known to promote cancer through
generationof reactive free radicals from oxidation of fats. IP6 also plays an
important role in regulating cell proliferation and differentiation.
In 1988, the first two studies were published, reporting inhibitory
effects of purified IP6 on tumor formation in experimental animals. One
study (Shamsuddin et al. Carcinogenesis 9:577-80) showed suppression of
cancer of the large bowel by IP6 and theother study (Jariwalla et al.
Nutr. Res. 8: 813-27) demonstrated reduction of the incidence and size
of soft-tissue tumors (fibrosarcomas) promoted by dietary factors.
Since then, a number of experimental studies have confirmed the
anti-cancer action of IP6 (reviewed by I. Vucenik and A.K.M. Shamsuddin, Univ.
of Maryland, Baltimore). The compound has been shown to inhibit various
rodent and human cancer cell lines in vitro and to protect against growth of
diverse cancers in vivo. Protective effects have been seen against cancers of
the breast, colon, pancreas, liver, skin and connective tissue. In vivo,IP6
not only prevents carcinogen-induced tumor development but it also interferes
with growth of pre-formed, transplanted tumors, suggesting that it may play a
role in both cancer prevention and treatment.
The step at which IP6 acts during tumor development varies depending
upon the type of cancer studied. In colon carcinogenesis, IP6 was shown to
suppress bowel cancer when given before, during and even several months after
carcinogen administration (Shamsuddin and colleagues, Univ. of Maryland).In
a multi-organ rat carcinogenesis model, IP6 administered (as phytic acid)
during the promotion stage suppressed hepatic tumors but had no influence on
development of esophagal, colonic, pancreatic, renal and thyroid tumor lesions
(M. Hirose, National Institute of Health Sciences, Tokyo). In a
two-stage model of carcinogenesis in mouse skin, IP6 inhibited tumor
formation when given during the initiation stage but not during tumor
promotion, indicating differential sensitivity of skin cancer (T. Ishikawa,
Univ. of Tokyo). Clinical studies in humans against different tumor types
would be useful. Awaiting such studies,
what can be said presently is that naturally-occurring salt forms of IP6
appear to be safe in animal studies even when used at higher than
physiologic dosages.
The role of myo-inositol as a chemopreventive agent was also discussed.
It is another phytochemical with low toxicity and ability to inhibit
carcinogenesis in various organs which include mammary gland, colon and
lung. In studies evaluating its chemopreventive activity in lung
carcinogenesis (L. W. Wattenberg, Univ. of Minneapolis, Minnesota), it
was reported that myo-inositol has unusual properties, manifesting a
capacity to prevent lung cancer when given during separate phases of the
carcinogenic process as well as throughout the entire course of the process.
When administered throughout the carcinogenic process, it's effects were found
to be additive. Another study reported on suppression of liver cancer by oral
administration of myo-inositol, thus adding to the diverse spectrum of tumors
affected by this naturally-derived plant constituent (H. Nishino, Kyoto Prefectual
University of Medicine). Myo-inositol has also been reported to enhance the
anti-cancer action of IP6 in other animal studies.
Back to Index
Mechanism of Cancer Suppression
The mechanism by which IP6 or myo-inositol exert chemopreventive and
anti-cancer effects is not completely understood. IP6 is rapidly
absorbed by cells (in vitro and in vivo) and metabolized to lower
phosphates and inositol (reviewed by Shamsuddin). It has been suggested
that lower inositol phosphates may mediate cancer inhibition, although
direct evidence for this is lacking. Both IP6 and its lower phosphates have
metal chelating activity and may interfere with tumor formation by suppressing
metal catalyzed oxidation of fats. Alternatively, IP6 may block the activity
of key enzyme(s) affecting cell proliferation. One enzyme candidate is PI-3
kinase which plays a central role in signal transduction and cell
transformation triggered by growth factor or tumor promoter. IP6 has been
reported to inhibit PI-3 kinase activity in vitro (Z. Dong, Univ. of
Minnesota, Austin). While this enzyme inhibition may explain the
chemopreventive effect of IP6, it is not known whether it mediates IP6's
effect on pre-existing tumors or
established cancer cells. Other, as yet, unknown mechanism may be
involved in the anti-cancer effect of IP6.
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Heart Disease
The ability of IP6 to reduce hyperlipidemia and protect against
cardiovascular disease (CVD) was also discussed. CVD is associated with high
mortality in Western and other industrialized countries. It is linked to
several risk factors among which is hyperlipidemia -- high levels of
cholesterol and triglycerides in blood.
It has been known that consumption of Bengal gram, a bean species rich
in IP6, is associated with reduced hypercholesterolemia. In one study,
which directly addressed the role of IP6 in hyperlipidemia, it was shown that
IP6-supplemented diet lowered total cholesterol and triglycerides levels in
serum of animals made hyperlipemic with a high cholesterol diet (reviewed by
R. J. Jariwalla, Calif. Institute for Medical Research, San Jose). The same
study demonstrated that dietary IP6 caused a lowering of the zinc/copper
ratio, a marker of hypercholesterolemia, without significantly affecting
levels of other minerals in serum. This lipid-lowering action of IP6 was seen
at dosages (upto 9% of the diet) that were free of adverse side effects in the
tested animals.
Another study reported on the hypolipidemic action of myo-inositol and
IP6 relevant to treatment of fatty liver (T. Katayama, Hiroshima Univ.). At
physiologic dosages (0.1 -0.5% of diet), these compounds inhibit rises in
hepatic total lipids andtriglycerides resulting from
administration of sucrose. The mechanism of this hypolipidemic effect in the
liver appears to be related to the inhibition of hepatic enzymes involved in
lipogenesis rather than inhibition of intestinal enzymes. Although
physiological levels of IP6 depress accumulation of lipids, they have little
effect on elevated serum lipids. Indeed, these dietary treatments (upto 2.5%
IP6) do not produce significant changes in hepatic cholesterol or serum total
lipid levels in sucrose-treated animals, consistent with findings from the
above study showing reduction of serum hyperlipidemia at higher supplementary
levels of dietary IP6.
IP6 and its derivatives also manifest other benficial effects relevant
to CVD. In separate reports, IP6 was shown to inhibit platelet
aggregation (I. Vucenik, Univ. of Maryland, Baltimore) and to enhance
inflammatory responses of neutrophils in response to microbial stimuli
(P. Eggleton, Oxford Univ.). In earlier animal studies, lower inositol
phosphates have been shown to inhibit calcification in the aorta and
lipid peroxidation in ischemic kidneys, consistent with a role for
hydrolysates of IP6 in protecting against hardening of the arteries
(reviewed by R. J. Jariwalla).
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Kidney Stones
Epidemiologic studies have shown that renal stones are more prevalent in
developed countries where populations consume diets based on refined
flour compared to those in developing nations consuming predominantly a
phytate-rich diet. IP6 is naturally present in human urine where normal
levels fluctuate between 0.5 to 5.0 mg/liter (F. Grases, Univ. of Balearic
Islands, Spain). Approximately 1-3% of oral doses are excreted in the urine
with an associated reduced risk of developing renal stones. Biochemical
studies have shown that phytate
can interfere with formation of calculi (crystals) of calcium oxalate
and phosphate (reviewed by F. Grases). This has been demonstrated in
vitro in a system that resembles calculi formation in the kidney as well as in
an animal model of nephrolithiasis where crystal/stone formation and
calcifications on renal papillary tissue are induced by ethylene glycol. In a
preliminary clinical study of 30 renal stone-formers, ingestion of 120mg/day
of IP6 was demonstrated to reduce the urinary risk of kidney stone
development.
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Role in Transmission of Chemical Messages
A portion of the symposium was devoted to the role of IP6 and inositol
in signal transduction, the pathway for transmission of external
messages to the interior of cells. Inositol phopholipids present in
plasma membranes have drawn much attention because of their role as
intermediaries in transmission of signals elicited by growth factors and
mitogens acting at the cell surface. Since inositol occurs ubiquitously in
cell membranes in conjugation with lipids as phosphatidylinositol, it plays a
critical role in this process. Additionally, IP6 is the only known dietary
source of inositol phospholipids. During cell stimulation, these molecules
are converted by special enzymes (PI kinases and phospholipase C) to inositol
triphosphate (IP3) and diacylglycerol which act as second messengers inside
cells (reviewed by G. Weber, Univ. of Indiana, Indianapolis). IP3 also plays
a role in cell-to-cell communication and can be generated from IP6 via a
salvage pathway.
In one report (by G. Weber), the activity of signal-transduction enzymes and
concentration of IP3 were reported to be elevated in several types of tumors
above those in normal cells. Anti-tumor componds such as genistein and
quercetin act by inhibiting PI kinases and lowering IP3 concentration in tumor
cells leading to cellular differentiation and death. A nuclear
inositol-lipid pathway was also described with signal-transduction components
located and acting in the nucleus (L. Cocco, Univ. of Bologna, Italy). This
signalling pathway appears to be important in switching cell programming from
a proliferative to a differentiative state. Finally, it was
reported that IP6 is the dominant inositol phosphate in
insulin-secreting cells of the pancreas where it influences secretion of the
hormone by modulating activity of a calcium channel (P.O. Berggren,Karolinska
Institute, Stockholm).
THeMaCHinE
New member
Zyglamail said:
Zyg -- from what I've been able to tell (and it depends on the application), but low dose seems to run in the 3 gram range, high dose runs up in the 9 gram range. I take 6 - 8 daily to combat depression-type issues and it seems to do the trick for me. I use the powder, mixed up with grapefruit juice over 3 doses/day. Runs about a $1/day cost.
inositol for anxiety and depression. between 4g and 50g (these are the extremes).
IP6 for anti-cancer and anxiety and depression. 1g a day is plenty. 1g a day is believed to be the optimium amount required by humans. It is believed that westerners do not get always get 1g. Rice is the main source of IP6. Japan has the lowest cancer rates in the world.
IP6 is coverted into inositol (myo-inositol). Therefore, in the same way that it makes sense to take 5HTP instead of tryptophan (not that you can buy tryptophan anymore)... it makes sense to take inositol instead of IP6. Why? Because it doesn't need to be converted in the gut - just absorbed by the gut and into the bloodstream it goes. No limitation to absorbtion.
IP6 is expensive - usually 2 x inositol cost.
IP6 for anti-cancer and anxiety and depression. 1g a day is plenty. 1g a day is believed to be the optimium amount required by humans. It is believed that westerners do not get always get 1g. Rice is the main source of IP6. Japan has the lowest cancer rates in the world.
IP6 is coverted into inositol (myo-inositol). Therefore, in the same way that it makes sense to take 5HTP instead of tryptophan (not that you can buy tryptophan anymore)... it makes sense to take inositol instead of IP6. Why? Because it doesn't need to be converted in the gut - just absorbed by the gut and into the bloodstream it goes. No limitation to absorbtion.
IP6 is expensive - usually 2 x inositol cost.
