Inositol

[Guest guest]

Elise,

How long has Josiah been off of the Depakote. I heard that most AEDs take

anywhere from 4 to 6 weeks sometimes longer to be totally out of your system.

If and when we finally decide to take off of all her meds, weI plan to

give about 2 months to be sure that it's not the meds or withdrawl seizures.

After two months, if she's still having seizures then we'll decide on where to

go from there. Either way it's not easy!

Grace

Elise Strong <elisestrong@...> wrote:

Hi, my son Josiah has been off medication for a little

over two weeks. No tonic clonics, which were his

norm, but now we are seeing the headbob seizures

(atonic?) which we had only seen previously when he

was ON medication. He was on depakote for about 3

months and it never controlled the t-c's. What is

going on? depakote still in his system? carnitine

deficiency? new morphed seizure disorder? Neurologist

has no clue (as per usual). Dr. braverman suggested I

give inositol- anyone else know about this stuff? I

couldn't find a whole lot on line. Thanks so much to

everyone. Elise

--- " M. " <mcpitza@...> wrote:

>

> From a UK Epilepsy website:

> http://www.epilepsy.org.uk/info/mozart.html

>

>

>

> The Mozart Effect

>

> The possible health benefits of the music of Mozart

> have been

> assessed in the April 2001 edition of the Journal of

> the Royal

> Society of Medicine.

>

> There has been controversy about the benefits ever

> since researchers

> claimed that listening to the K448 piano sonata

> improved spatial

> reasoning skills. Later research suggested that K448

> can reduce the

> number of seizures in people with epilepsy.

>

> Professor assesses international

> evidence on the effect

> of music on the brain, and calls for more work to be

> done to discover

> the key ingredient in the " Mozart Effect " .

>

> The original " Mozart effect " study in 1993 assessed

> volunteers'

> spatial reasoning after listening to sonata K448,

> relaxation tapes or

> silence. Results suggested that just 10 minutes of

> Mozart's music

> improved their performance of tasks such as

> paper-cutting and

> folding. Later studies found that rats negotiated a

> maze faster after

> hearing K448 than rats who were played white noise,

> silence, or

> minimalist music. Elsewhere, children taught a

> keyboard instrument

> for six months, learning simple melodies (including

> Mozart), did

> better on spatial-temporal tests than children who

> spent the time

> working with computers.

>

> Controversy arose when other researchers could not

> reproduce the

> positive results.

>

> Scans have shown that the human brain uses a wide

> distribution of

> areas to listen to music. Rhythm and pitch tend to

> be processed in

> the left side, timbre and melody on the right. Those

> parts of the

> brain which we use for spatial/temporal tasks

> actually overlap with

> the music processing parts. Professor

> suggests

> that " listening to music would prime the activation

> of those areas of

> the brain which are concerned with spatial

> reasoning " .

>

> More recent work with epilepsy patients has

> indicated what Professor

> calls " a more impressive indication of a

> Mozart effect " . Once

> again, sonata K448 was played to participants, most

> of whom showed a

> decrease in their epileptiform activity - the

> patterns in the brain

> that produce epileptic seizures.

>

> Computer analysis of pieces by various composers

> showed that the

> music of Mozart and Bach shared a common factor, a

> high degree

> of `long-term periodicity', in other words, wave

> forms repeated

> regularly, but not very close together, throughout

> the piece of

> music. By contrast, music which had no effect on

> either spatial

> reasoning or on epileptic seizures did not have this

> factor.

> Professor commented:

>

> " It is suggested that music with a high degree of

> long-term

> periodicity... would resonate within the brain to

> decrease seizure

> activity and to enhance spatial-temporal

> performance " .

>

> Professor concludes that any health benefits

> of listening to

> music are " not specific to Mozart's compositions " ,

> and calls for more

> research to be done on music other than K448, with

> longer listening

> times. For the benefits to be of real use, we need

> to discover

> exactly what musical criteria have to be present for

> the " Mozart

> effect " to take place.

>

> Apart from another Mozart Concerto, K488, only one

> other piece of

> music has been found to have a similar effect, a

> song by the Greek-

> American singer Yanni. Entitled 'Acroyali/Standing

> In Motion', it is

> featured on his album " Live At The Acropolis " . This

> composition was

> chosen by researchers because it was similar to

> Mozart's K448 in

> tempo, structure, melodic and harmonic consonance

> and predictability.

>

>

>

>

>

>

__________________________________________________

[Guest guest]

..... okay, following up... I see that inositol has been found to help

rebuild the myelin sheath around the nerves. This sheath is supposed to

act as an electrical insulator. Gamma Linoleic Acid (GLA) is supposed

to help with this as well, and I've already found that if I use a skin

lotion containing GLA (e.g, Borage Oil), the " burning face " symptoms

from computer use immediately go away.

Also interesting is that mercury is known to destroy this protective

sheath around the nerves, so there's a possible connection.

Also, an inositol deficiency can occur from prolonged use of

antibiotics, and I did have a prolonged use of antibiotics prior to

getting ES. Also caffeine use, but I think a lot of people consume

caffeine without getting ES...

Inositol is also good for panic attacks, which is something I often get

when trying to detox. So maybe this will help me detox without this

side effect.

Marc

[Guest guest]

I used to take a whole bunch of supplements. One of the best ones I

found was a product called " metal magnet " . By the way, have you ever

experimented with the spring life polarizer rods they sell that are 2

for 144 dollars. I'm thinking of attaching some to my pyramid.

Making a small pyramid out of them and making a small pyramid to

place in the tip or on top of my larger pyramid. I had good results

with the small pendent they sell but lost it somehow.

> .... okay, following up... I see that inositol has been found to

help

> rebuild the myelin sheath around the nerves. This sheath is

supposed to

> act as an electrical insulator. Gamma Linoleic Acid (GLA) is

supposed

> to help with this as well, and I've already found that if I use a

skin

> lotion containing GLA (e.g, Borage Oil), the " burning face " symptoms

> from computer use immediately go away.

>

> Also interesting is that mercury is known to destroy this protective

> sheath around the nerves, so there's a possible connection.

>

> Also, an inositol deficiency can occur from prolonged use of

> antibiotics, and I did have a prolonged use of antibiotics prior to

> getting ES. Also caffeine use, but I think a lot of people consume

> caffeine without getting ES...

>

> Inositol is also good for panic attacks, which is something I often

get

> when trying to detox. So maybe this will help me detox without this

> side effect.

>

> Marc

[Guest guest]

> By the way, have you ever

> experimented with the spring life polarizer rods they sell that are 2

> for 144 dollars.

I own one of these rods, but so far I've found that the larger

Springlife

Polarizers are larger than I need to balance things out. And if I use

one that's too large, then I get adverse effects from that. Perhaps

if I get the right missing nutrient into my system, those adverse

symptoms will go away.

Since I was having so much trouble with my work badge, I also brought

in a bunch of my devices and my practitioner muscle tested me for

the amount that was " just right " . This doesn't change much (if at

all) from year to year, but today I brought in an Earthcalm Resonator

for the first time, so now her recommendations are:

at work: Quantum powerstrip plus Springlife Polarizer OM2

(aka " Pocket Rocket " ) pendant on top of computer

in car: Springlife Polarizer OM pendant

home computer: Springlife Polarizer Lifeforce pendant in between

monitor and keyboard

while sleeping: Earthcalm Resonator on nightstand

Basically the only thing that's change is while sleeping -- previously

she recommended that I use the Lifeforce pendant on nightstand.

Usually her recommendations are correct, but we'll see how it goes...

in the past, the cats didn't like the Earthcalm Resonator in the

house...

Marc

[Guest guest]

This is fascinating - and useful info. I once swallowed a mercury

filling - this was before I got very ill with Epstein Barr virus and

then ES. I did a lot of de-toxing with selenium during that time which

might have got rid of the mercury, but not the damage done to the

nerves.

re: Inositol

..... okay, following up... I see that inositol has been found to help

rebuild the myelin sheath around the nerves. This sheath is supposed to

act as an electrical insulator. Gamma Linoleic Acid (GLA) is supposed

to help with this as well, and I've already found that if I use a skin

lotion containing GLA (e.g, Borage Oil), the " burning face " symptoms

from computer use immediately go away.

Also interesting is that mercury is known to destroy this protective

sheath around the nerves, so there's a possible connection.

Also, an inositol deficiency can occur from prolonged use of

antibiotics, and I did have a prolonged use of antibiotics prior to

getting ES. Also caffeine use, but I think a lot of people consume

caffeine without getting ES...

Inositol is also good for panic attacks, which is something I often get

when trying to detox. So maybe this will help me detox without this

side effect.

Marc

[Guest guest]

> This is fascinating - and useful info. I once swallowed a mercury

> filling - this was before I got very ill with Epstein Barr virus and

> then ES. I did a lot of de-toxing with selenium during that time which

> might have got rid of the mercury, but not the damage done to the

> nerves.

I just found the following article that specifically links the

deterioration of the myelin sheath with hypersensitivity to

electricity:

http://www.aspartame.ca/page_oho3.htm

They say that it is diet related, and that eating fats/oils that

oxidize easily destroy the myelin sheath as well.

Yesterday, after my nutritionist found my need for inositol, she

was also concerned that I was getting enough fatty acids. She

noted that the Evening Primrose Oil was no longer testing that

great (probably because I'm already getting GLA in my Borage

Oil skin lotion). She EAV tested me strong on coconut oil, and

wanted me to take a tablespoon a day. It is interesting to note

that coconut oil does NOT oxidize at body temperature.

Marc

[Guest guest]

> > This is fascinating - and useful info. I once swallowed a mercury

> > filling - this was before I got very ill with Epstein Barr virus and

> > then ES. I did a lot of de-toxing with selenium during that time which

> > might have got rid of the mercury, but not the damage done to the

> > nerves.

.... and why just blame mercury, when it appears that the sheath can

be damaged by lots of things, including nutrasweet, MSG, red meat, etc.:

http://www.wnho.net/ms_and_aspartame.htm

I wonder how well the treatments for MS work for people who have

ES... I see a lot of information in the above article about what

to do and what not to do that I've already found to be true in

my own case.

Marc

[Guest guest]

Hope you use the organic, not hydrogenated. My favorite brand of

coconut is the Omega, but sometimes have to by Spectrum Naturals.

Don't care for the unfiltered myself, don't like everything to taste

of coconut.

Anyway, point getting to, coconut oil, couple tablespoons per day,

more or less, is also helpful for low thyroid.

~Snoshoe

She EAV tested me strong on coconut oil, and

> wanted me to take a tablespoon a day. It is interesting to note

> that coconut oil does NOT oxidize at body temperature.

>

> Marc

[Guest guest]

> If the inositol ends up keeping good for you in a few weeks, I might

> just give it a try too.

I've had pretty bad allergies starting the day after beginning the

Inositol (sniffles/sneezing) -- could be some sort of cleansing

reaction, or a coincidence, or maybe I'm allergic to Inositol? :-)

Marc

[Guest guest]

---

That is interesting stuff about the coconut oil. I've been trying to

find a way to get more essential fatty acids myself. I don't like

taking them through the gut and have been applying them to the skin

that way. It is encouraging to read that you are using a skin cream

to get the GLS from borage oil and that it seems to be working. I

will have to try the coconut oil as well. Currently I am using extra

virgin olive oil and oil of cilantro. I notice that I get the same

kind of reactions to some extent rubbing the cilantro oil on my skin

as when I was juicing it before. When I was juicing it before I

noticed my body odor was taking on the smell of the cilantro. The

cilantro itself does not smell that bad. But the byproducts from the

juicing smell pretty bad after awhile if you dump them at the base of

a tree like I did. That was the smell my body was starting to take

on from juicing. When rubbing the cilantro on my skin I have notice

that if I pass gas it has the same aroma as the cilantro oil which I

have been rubbing on the back of my neck and jaw bone and all those

other places where the mercury is supposed to deposit itself.

> I just found the following article that specifically links the

> deterioration of the myelin sheath with hypersensitivity to

> electricity:

>

> http://www.aspartame.ca/page_oho3.htm

>

> They say that it is diet related, and that eating fats/oils that

> oxidize easily destroy the myelin sheath as well.

>

> Yesterday, after my nutritionist found my need for inositol, she

> was also concerned that I was getting enough fatty acids. She

> noted that the Evening Primrose Oil was no longer testing that

> great (probably because I'm already getting GLA in my Borage

> Oil skin lotion). She EAV tested me strong on coconut oil, and

> wanted me to take a tablespoon a day. It is interesting to note

> that coconut oil does NOT oxidize at body temperature.

>

> Marc

[Guest guest]

I initially had good results with inositol and hope yours continue.

:-) After a while I didn't notice a benefit and actually felt better

not taking it. I found out through kinesiology that I'd developed an

intolerance to it. My naturopath and I are pretty sure it wasn't an

additive since the Source Naturals package was labelled as pure

inositol powder. I'm hoping with time I'll be able to take it as a

rotational diet supplement.

Beau

> > http://www.space.com/scienceastronomy/050909_solar_flares.html

> >

> > FYI, since the EM environment might undergo strong variations and

> > affect those with ES.

>

> I've actually felt better than usual in the past couple days,

> so perhaps solar flares are good for me? :-)

>

> (or perhaps the continued intake of inositol is having some

> benefits)

>

> Marc

[Guest guest]

Dear ,

 

Just got your posting a while ago.

 

The fresh coconut sap is not  the alcoholic beverage " tuba " .  It is the freshly

gathered coconut sap, meaning, not allowed to ferment, direct to the

refrigerator after removing unwanted materials or pollutants.  Why refrigerate? 

Many prefer it served cool or chilled.

 

As to the vitamin inositol content of dwarf coconut varieties in the

Philippines, I'm not yet aware of such information. This should be done to

compare with the tall coconut variety ( likely the one used by Kosaki 1974). 

The statement that dwarf cocont varieties yields (per tree/month) more coconut

sap than tall varieties are claims by some.  This will be verified by the PCA

soon.

 

Cheers,

 

Sev Magat 

From: melly banagale <@...>

Subject: Inositol

Coconut Oil

Date: Friday, June 27, 2008, 12:17 AM

I am paging Sev Magat.

Hi Sev,

We shall be in San Pablo City in a few days. I have made arrangements for

coconut sap " tuba " to be obtained from the Laguna variety so that my husband and

I can take it. I understand that it helps maintain a healthy prostate and also

help control diabetic neuropathy.

I know you have said that the Mindanao dwarf propagated by PCA yield more

coconut sap. My question is, do they have the same quality of inositol in their

saps?

To all members,

Below is a very interesting paper by PUBMED on Inositol vs. cancer.

Thanks.

============ =========

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Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances

DB 1,2-DIMETHYLHYDRAZI NE CALCIUM PHYTATE

© 2003 The American Society for Nutritional Sciences J. Nutr. 133:3778S-3784S,

November 2003

------------ --------- --------- ---

Supplement: International Research Conference on Food, Nutrition, and Cancer

Cancer Inhibition by Inositol Hexaphosphate (IP6) and Inositol: From Laboratory

to Clinic1,2 Ivana Vucenik*,,3 and AbulKalam M. Shamsuddin

*Department of Medical and Research Technology and Department of Pathology,

University of land School of Medicine, Baltimore, MD 21201 3 To whom

correspondence should be addressed. E-mail: ivucenikumaryland (DOT) edu ' + u + '@'

+ d + ''//--> .

ABSTRACT TOP

ABSTRACT

LITERATURE CITED

Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated

carbohydrate that is present in substantial amounts in almost all plant and

mammalian cells. It was recently recognized to possess multiple biological

functions. A striking anticancer effect of IP6 was demonstrated in different

experimental models. Inositol is also a natural constituent possessing moderate

anticancer activity. The most consistent and best anticancer results were

obtained from the combination of IP6 plus inositol. In addition to reducing cell

proliferation, IP6 increases differentiation of malignant cells, often resulting

in a reversion to normal phenotype. Exogenously administered IP6 is rapidly

taken into the cells and dephosphorylated to lower-phosphate inositol

phosphates, which further interfere with signal transduction pathways and cell

cycle arrest. Enhanced immunity and antioxidant properties can also contribute

to tumor cell destruction. However, the

molecular mechanisms

underlying this anticancer action are not fully understood. Because it is

abundantly present in regular diet, efficiently absorbed from the

gastrointestinal tract, and safe, IP6 holds great promise in our strategies for

the prevention and treatment of cancer. IP6 plus inositol enhances the

anticancer effect of conventional chemotherapy, controls cancer metastases, and

improves the quality of life, as shown in a pilot clinical trial. The data

strongly argue for the use of IP6 plus inositol in our strategies for cancer

prevention and treatment. However, the effectiveness and safety of IP6 plus

inositol at therapeutic doses needs to be determined in phase I and phase II

clinical trials in humans.

------------ --------- --------- ---

KEY WORDS: • prevention • treatment • differentiation • phytic acid Cancer

remains a major health problem in the United States and in other developed

countries (1). In our continuing effort to reduce the public health burden of

cancer, there is a constant search for more effective cancer treatment, and

increased interest in the concept of prevention, as a promising approach to the

control of cancer (2). A novel anticancer function of inositol hexaphosphate

(IP6;4 also InsP6 and phytic acid) has been shown both in vivo and in vitro

(3–5). IP6 is a polyphosphorylated carbohydrate, contained in high

concentrations (0.4–6.4%) in cereals and legumes (6). Myo-inositol is a parent

compound of IP6. Only myo-inositol hexaphosphate has been found in plants; neo-,

chiro-, and scyllo-inositol hexaphosphates have been isolated from soil (7). The

phosphate grouping in positions 1, 2, and 3 (axial-equatorial- axial) is unique

for IP6, providing a specific

interaction with iron to

completely inhibit its ability to catalyze hydroxyl radical formation, making

IP6 a strong antioxidant, probably still the only role of IP6 that is widely

recognized and accepted. Almost all mammalian cells contain IP6 and much smaller

amounts of its forms with fewer phosphate groups (IP1-5), which are important

for regulating vital cellular functions. Inositol occurs ubiquitously in cell

membranes in conjugation with lipids, as phosphatidylinosito l. Recently,

inositol phospholipids in the plasma membrane have received much attention

because of their biological significance for signal transduction systems.

Phosphatidylinosito l 4,5-bisphosphate (PIP2), a phosphoinositide, is a

precursor for several informational molecules in signal transduction— inositol

1,4,5-P3 (IP3), 1,2-diacylglycerol, and phosphatidylinosito l

3,4,5-trisphosphate— linking receptor stimulation to Ca2+ mobilization (8). A

second messenger role in intracellular Ca2+ homeostasis

for IP4 was also shown. It

is now recognized that subsequent to PIP2 hydrolysis a cascade of inositol

phosphate metabolites are formed and that these multiple isomers show a complex

pattern of interconversion (8–10). Inositol phosphates are versatile molecules

with important roles in controlling diverse cellular activities (9,10). IP6 may

serve as a natural antioxidant (11) and possibly as a neurotransmitter (10).

Different binding proteins for inositol polyphosphates have been isolated,

indicating their importance for the cellular functions (12) such as effects on

ion channels and protein trafficking (13,14), endocytosis (15), exocytosis (16),

and efficient export of mRNA from the nucleus to the cell (17). How can

exogenously administered IP6 affect tumor growth? Pioneering experiments showing

this novel anticancer feature of IP6 were performed by Shamsuddin et al.

(18–20), who were intrigued by the epidemiologic data indicating that only diets

containing a high IP6 content

(cereals and legumes)

showed a negative correlation with colon cancer. Almost 15 y ago, Shamsuddin et

al. hypothesized that IP6 can be internalized by the cells and dephosphorylated

to IP1-5 and then can enter into the intracellular inositol phosphate pool and

inhibit tumor growth. It was also hypothesized that the addition of inositol, a

precursor of inositol phosphates and also a natural carbohydrate, to IP6 may

enhance the anticancer function of IP6 (18–20). Because inositol phosphates are

common molecules involved in signal transduction in most mammalian cell systems,

it was further hypothesized that the anticancer action of inositol phosphates

would be observed in different cells and tissue systems (18–20). All these

proposed hypotheses have been confirmed. Contrary to the dogma and skepticism at

that time, we showed that IP6 is taken up by malignant cells (21) and that

orally administered IP6 can reach target tumor tissue distant from the

gastrointestinal tract

(22). Because of the

highly charged nature of IP6, it was a common misconception that it could not be

transported into the cells. Analyzing absorption, intracellular distribution,

and metabolism of IP6 in HT-29 human colon carcinoma and cells of hematopoietic

lineage (K-562, human erythroleukemia and YAC-1, mouse lymphoma cells), we found

that IP6 is rapidly taken up by mechanisms probably involving pinocytosis or

receptor-mediated endocytosis, transported intracellularly, and dephosphorylated

into inositol phosphates with fewer phosphate groups (21). Similar data were

obtained when MCF-7 human breast cancer cells were incubated with [3H]-IP6 (SA

444 GBq/mmol, 370 Bq/106 cells): as early as 1 min after incubation, 3.1% of

IP6-associated radioactivity was taken up by MCF-7 cells, and 9.5% after 1 h. By

differential centrifugation 86% radioactivity was recovered from the cell

cytosol. Anion-exchange chromatography showed that 58% of the absorbed

radioactivity was in IP6 form.

When [3H]-IP6 was

administered intragastrically to rats, it was quickly absorbed from the stomach

and upper intestine and distributed to various organs as early as 1 h after

administration (22). Although the radioactivity isolated from gastric epithelium

at this time was associated with inositol and IP1-6, the radioactivity in the

plasma and urine was associated with inositol and IP1. These data indicate that

the intact molecule was transported inside the gastric epithelial cells, wherein

it was rapidly dephosphorylated, and that the metabolism of IP6 was very rapid.

In our preliminary studies, [3H]-IP6 was given via oral gavage to rats bearing

7,12-dimethylbenz[ a]anthracene- induced mammary tumors. A substantial amount of

radioactivity (19.7% of all radioactivity recovered in collected tissues) was

found in tumor tissue as early as 1 h after administration, providing at least

partial explanation for the antineoplastic activity of IP6 at sites distant from

the

gastrointestinal tract. In this

study only 50% of the radioactivity was excreted in urine within 72 h after

administration; in addition feces accounted for another 10% of radioactivity,

suggesting that at least 40% of the IP6-associated radioactivity was distributed

within the animal tissues. These data indicate that IP6 can reach and

concentrate at cellular targets. Chromatographic analysis of tumor tissue

revealed the presence of inositol and IP1, similar to plasma. Using a novel and

highly sensitive method combining gas chromatography– mass spectrometry analysis

and HPLC, Grases et al. (23,24) were able to identify IP6 in human urine and

plasma and detect IP6 and its less-phosphorylated forms (IP3-5) in mammalian

cells and in body fluids as they occur naturally. They also showed that the

levels of IP6 and its less phosphorylated forms fluctuate depending on the

intake of IP6. That the extracellularly applied IP6 enters the cell and that

this intracellular delivery is followed by a

dephosphorylation

of IP6 was recently confirmed by Ferry et al. (25). Anticancer action of IP6 As

hypothesized, it was demonstrated that IP6 is a broad-spectrum antineoplastic

agent, affecting different cells and tissue systems. In vitro studies with IP6

are summarized in Table 1.

View this table:

[in this window]

[in a new window]

TABLE 1 Antitumor effect of inositol hexaphosphate (IP6) in vitro

IP6 inhibited the growth of all tested cell lines in a dose- and time-dependent

manner. The growth of cells of hematopoietic lineage was inhibited: human

leukemic hematopoietic cell lines, such as K-562 (26,27) and human normal and

leukemic hematopoietic cells (27). The antiproliferative activity of IP6 was

further reported in human colon cancer HT-29 cells (28), estrogen

receptor–positive and estrogen receptor–negative human breast cancer cells (32),

cervical cancer (25), prostate cancer (15,33,34), and HepG2 hepatoma cell lines

(31). IP6 also inhibited the growth of mesenchymal tumors, murine fibrosarcoma

(39), and human rhabdomyosarcoma (38). However, cells from different origin have

different sensitivity to IP6 (the leukemic cell lines seem to be highly

susceptible to IP6), suggesting that IP6 may affect different cell types through

different mechanisms of action.

The potential of IP6 to induce differentiation and maturation of malignant

cells, often resulting in reversion to the normal phenotype, was first

demonstrated in K-562 hematopoietic cells (26). IP6 was further shown to

increase differentiation of human colon carcinoma HT-29 cells (28,29), prostate

cancer cells (33), breast cancer cells (32), and rhabdomyosarcoma cells (38).

The cancer preventive activity of IP6 in vitro was first tested in a

benzo[a]pyrene- induced transformation in the rat tracheal cell culture

transformation assay (30) and then was tested in a model using BALB/c mouse 3T3

fibroblasts (37) with modest efficacy. The observation that IP6 impaired the

transformation induced by epidermal growth factor or phorbol ester in JB6 (mouse

epidermal) cells (35) strongly suggested the potential role of IP6 as a cancer

preventive agent, because this model has been a well-characterized cell system

for studying the tumor promotion and molecular

mechanisms of antitumor

agents. Furthermore, IP6 reduced 12-O-tetradecanoylp horbol-13- acetate–induced

ornithine decarboxylase activity, an essential event in tumor promotion in

HEL-30 cells, a murine keratinocyte cell line (36). A summary of in vivo studies

using IP6 and inositol is shown in Table 2. Although experts in the field of

nutrition and cancer have been performing in vivo experiments by adding IP6 to

the diet, in all our cancer prevention studies, IP6 was given via drinking water

in concentrations ranging from 0.4% to 2.0%. We were able to obtain comparable

or even stronger tumor inhibition with much lower concentrations of IP6 when it

was given in drinking water. For example, much stronger tumor inhibition was

achieved with 0.4% IP6 in drinking water compared with the same amount given in

a 20% high fiber diet (52).

View this table:

[in this window]

[in a new window]

TABLE 2 Antitumor effect of IP6 and inositol in vivo

The effectiveness of IP6 as a cancer preventive agent was shown in colon cancer

induced in different species (rats and mice) with different carcinogens

(1,2-dimethylhydraz ine and azoxymethane) (18–20,40–46). IP6 was effective in a

dose-dependent manner given either before or after carcinogen administration.

The finding that IP6 was able to reduce the development of large intestinal

cancer 5 mo after carcinogen administration, when IP6-treated animals

demonstrated a significantly lower tumor number and size, has suggested its

potential use as a therapeutic agent (20). IP6 decreased the incidence of

aberrant crypts when they were used as an intermediate biomarker for colon

cancer (43,44). Studies using other experimental models showed that

antineoplastic properties of IP6 were not restricted to the colon. IP6

significantly reduced experimental mammary carcinoma in Sprague-Dawley rats

induced either by 7,12-dimethylbenz[ a]anthracene (51–54) or

N-methylnitrosourea (42). Using a

two-stage mouse skin carcinogenesis model, Ishikawa et al. (55) investigated the

effect of IP6 on skin cancer and found a reduction in skin papillomas when IP6

was given during the initiation stage but not when given during the promotion

stage (55).

The therapeutic properties of IP6 were demonstrated in the FSA-1 mouse model of

transplantable and metastatic fibrosarcoma (39). After subcutaneous inoculation

of mouse fibrosarcoma FSA-1 cells, mice were treated with intraperitoneal

injections of IP6 and a significant inhibition of tumor size and survival over

untreated controls was observed. In this model experimental lung metastases are

developed after intravenous injections of FSA-1 cells; intraperitoneal

injections of IP6 resulted in a significant reduction of metastatic lung

colonies (39). A strong anticancer activity of IP6 was also demonstrated against

human rhabdomyosarcoma RD cells transplanted in nude mice (38), where the

efficacy of IP6 was tested on the tumor-forming capacity of RD cells.

Peritumoral treatment with IP6 (40 mg/kg) initiated 2 d after subcutaneous

injection of rhabdomyosarcoma cells suppressed the tumor growth by 25–49-fold

(38). IP6 was also potent in inhibiting

experimental hepatoma (31,48).

We tested the effect of IP6 on tumorigenicity and tumor regression in this

model. A single treatment of HepG2 cells in vitro by IP6 resulted in the

complete loss of the ability of these cells to form tumors when inoculated

subcutaneously in nude mice (48). Additionally, the preexisting liver cancers

regressed when they were treated directly with IP6 (48). Myo-inositol itself was

also demonstrated to have anticancer function, albeit modest. It inhibited

pulmonary adenoma formation in mice (49,50). We found that inositol alone or in

combination with IP6 can prevent the formation and incidence of several cancers

in experimental animals: in soft tissue, colon, metastatic lung, and mammary

cancers. Additionally, we showed that inositol potentiates both the

antiproliferative and antineoplastic effects of IP6 in vivo (3–5,19,39,51, 52).

Synergistic cancer inhibition by IP6 when combined with inositol was observed in

colon cancer (Table 3) (19) and mammary

cancer studies (Table

4) (51,52). Similar results were seen in the metastatic lung cancer model (39).

Thus, the combination of IP6 and inositol was significantly better in different

cancers than was either one alone.

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TABLE 3 Synergistic cancer inhibition by IP6 when combined with inositol (Ins)

1,2-dimethylhydrazi ne (DMH)- induced colon carcinoma in mice

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TABLE 4 7,12-Dimethylbenz[ a]nthracene (DMBA)-induced mammary carcinoma in rats

Mechanisms of action of IP6

The mechanisms involved in the anticancer activity of inositol compounds are not

fully understood. It is known that virtually all animal cells contain inositol

phosphates and that the inositol phosphates with fewer phosphate groups,

especially IP3 and IP4, have an important role in cellular signal transduction,

regulation of cell function, growth, and differentiation (8,9). We hypothesized

that one of the several ways by which IP6 plus inositol exerts its action is via

lower-phosphate inositol phosphates. Measurement of intracellular inositol

phosphates after IP6 treatment showed an increased level of lower-phosphate

inositol phosphates (IP1-3) (21,24–26); their involvement in signal transduction

pathways can affect cell cycle regulation, growth, and differentiation of

malignant cells (3–5). Derivatives of phosphatidylinosito l transmit cellular

signals in response to extracellular stimuli, and enzymes responsible for the

phosphorylation and

hydrolysis of these signaling

lipids play an important role in a broad range of biological effects. A central

molecule is a phosphatidylinosito l-3 kinase, which primarily phosphorylates the

lipid phosphatidylinosito l on the 3 position of the D-myo-inositol ring,

yielding phosphatidylinosito l-3-phosphate, but also can use phosphorylated

forms of phosphatidylinosito l as substrates. IP6 inhibits phosphatidylinosito

l-3 kinase (35). This action is related to the IP6 structure that is similar to

D-3-deoxy-3- fluoro-PtdIns, an inhibitor of phosphatidylinosito l-3 kinase (35).

In addition to the blocking of phosphatidylinosito l-3 kinase and activating

protein-1 by IP6 (35), protein kinase C (16,57) and mitogen-activated protein

kinases (15,35) are involved in IP6-mediated anticancer activity. The role of

IP6 among these multiple signaling pathways and their cross-talk in regulation

of cell functions needs to be addressed in the future. IP6 can also modulate

cellular response at the

level of receptor binding.

IP6, after sterically blocking the heparin-binding domain of basic fibroblast

growth factor, disrupted further receptor interactions (58). This modulation in

binding and the activity of basic fibroblast growth factor is thought to be due

to the chair conformation of IP6 mimicking that of the pyranose ring structure

in heparin (58). The observed anticancer effect of inositol compounds could be

mediated through several other mechanisms. The antioxidant role of IP6 is known

and widely accepted; this function of IP6 occurs by chelation of Fe3+ and

suppression of ·OH formation (11). Therefore, IP6 can reduce carcinogenesis

mediated by active oxygen species and cell injury via its antioxidative

function. This activity seems to be closely related to its unique structure. The

phosphate grouping in positions 1,2,3 (axial-equatorial- axial) is unique to

IP6, specifically interacting with iron to completely inhibit its ability to

catalyze hydroxyl radical

formation, making IP6 a

strong antioxidant. This anticancer action of IP6 may be further related to

mineral binding ability; IP6 by binding with Zn2+ can affect thymidine kinase

activity, an enzyme essential for DNA synthesis, or remove iron, which may

augment colorectal cancer (3–5,41,46). Besides affecting tumor cells, IP6 can

act on a host by restoring its immune system. IP6 augments natural killer cell

activity in vitro and normalizes the carcinogen-induced depression of natural

killer cell activity in vivo (59). Value of IP6 as a therapeutic and preventive

agent for cancer Safety. IP6 is a natural compound and an important dietary

component. Some concerns have been expressed regarding the mineral deficiency

that results from an intake of foods high in IP6 that might reduce the

bioavailability of dietary minerals. However, recent studies demonstrate that

this antinutrient effect of IP6 can be manifested only when large quantities of

IP6 are consumed in combination with a

diet poor

in oligoelements (60–63). A long-term intake of IP6 in food (60,61) or in a pure

form (64) did not cause such a deficiency in humans. Studies in experimental

animals showed no significant toxic effects on body weight, serum, or bone

minerals (Table 5) or any pathological changes in either male F344 or female

Sprague-Dawley rats for 40 wk (40,51,52). Grases et al. (65) confirmed our

findings and also reported that abnormal calcification was prevented in rats

given IP6.

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TABLE 5 Effect of inositol compounds on bone minerals

IP6 does not affect normal cells. The most important expectation of a good

anticancer agent is for it to only affect malignant cells and not affect normal

cells and tissues. That property was recently shown for IP6. When the fresh

CD34+ cells from bone marrow was treated with different doses of IP6, a toxic

effect (inhibition of the clonogenic growth or as cytotoxicity on liquid

cultures) was observed that was specific to leukemic progenitors from chronic

myelogenous leukemia patients but no cytotoxic or cytostatic effect was observed

on normal bone marrow progenitor cells under the same conditions (27). Recently,

we (66) showed that IP6 inhibited the colony formation of Kaposi's sarcoma (KS)

cell lines, KS Y-1 (AIDS-related KS) and KS SLK (Iatrogenic KS), and CCRF-CEM

(human adult T lymphoma) cells in a dose-dependent manner (66). However, in

striking contrast to taxol, used as a control, IP6 did not affect the ability of

normal cells (peripheral blood

mononuclear

cells and T-cell colony-forming cells) to form colonies in a semisolid

methylcellulose medium. Malignant and normal cells are known to have a different

metabolism, growth rate, expression of receptors, etc., but the mechanism for

this different selectivity of IP6 for normal and malignant cells needs to be

further investigated.

IP6 acts synergistically with standard chemotherapeutics. Current cancer

treatment recognizes the importance of using combination therapy to increase

efficacy and decrease side effects of conventional chemotherapy. Another

important aspect of cancer treatment is overcoming acquired drug resistance. Our

recent data demonstrate that IP6 acts synergistically with doxorubicin and

tamoxifen, being particularly effective against estrogen receptor–negative and

doxorubicin- resistant cell lines, both conditions that are challenging to treat

(67). These data are particularly important because tamoxifen is usually given

as a chemopreventive agent in the posttreatment period and doxorubicin has

enormous cardiotoxicity and its use is associated with doxorubicin resistance.

IP6 affects principal pathways of malignancy. Our goal is to identify agents

that can target tumors at vulnerable sites and interrupt specific pathways of

carcinogenesis. From the behavior and

characteristics of malignant cells, several principal pathways of malignancy

have been established, such as proliferation, cell cycle progression, metastases

and invasion, angiogenesis, and apoptosis; interestingly, IP6 targets and acts

on all of them. Uncontrolled proliferation is a hallmark of malignant cells, and

IP6 can reduce the cell proliferation rate of many different cell lines of

different lineage and of both human and rodent origin (3–5,26,28,31– 33,38).

Although normal cells divide at a controlled and limited rate, malignant cells

escape from the control mechanisms that regulate the frequency of cell

multiplication and usually have lost the checkpoint controls that prevent

replication of defective cells. IP6 can regulate the cell cycle to block

uncontrolled cell division and force malignant cells either to differentiate or

go into apoptosis. IP6 induces G1 phase arrest and a significant decrease of the

S phase of human breast (68,69),

colon (69), and prostate

(34) cancer cell lines. However, IP6 causes the accumulation of human leukemia

cells in the G2M phase of the cell cycle; a cDNA microarray analysis showed a

down-modulation of multiple genes involved in transcription and cell-cycle

regulation by IP6 (27). One important characteristic of malignancy is the

ability of tumor cells to metastasize and infiltrate normal tissue. A

significant reduction in the number of lung metastatic colonies by IP6 was

observed in a mouse metastatic tumor model using FSA-1 cells (39). Using highly

invasive MDA-MB 231 human breast cancer cells, we demonstrated that IP6 inhibits

metastasis in vitro through effects on cancer cell adhesion, migration, and

invasion (70,71). Tumor cells emit substances known as matrix metalloproteinases

that allow metastatic cells to pass into the blood vessels; IP6 significantly

inhibited secretion of MMP-9 from MDA-MB 231 cells (70). Tumors depend on the

formation of new blood vessels to support

their growth and

metastasis. Many tumors produce large amounts of vascular endothelial growth

factor, a cytokine that signals normal blood vessels to grow. IP6 inhibited the

growth and differentiation of endothelial cells (66,72) and inhibited the

secretion of vascular endothelial growth factor from malignant cells (27,66,72).

IP6 can also adversely affect angiogenesis as antagonist of fibroblast growth

factor (58). Apoptosis is a hallmark of action of many anticancer drugs. It has

been reported that IP6 induces apoptosis in vivo (45) and in vitro in prostate

(34) and cervical cancer (25) cell lines, involving cleavage of caspase 3,

caspase 9, and poly ADP-ribose polymerase, an apoptotic substrate, in a time-

and dose-dependent manner. Effectiveness of IP6 as a cancer preventive agent.

Possible mechanisms of the cancer preventive action of IP6 include carcinogen

blocking activities, antioxidant activities, and antiproliferation and

antiprogression activities (73).

Therefore, the

strategy of chemoprevention is to use agents that will inhibit mutagenesis,

induce apoptosis, induce maturation and differentiation, and inhibit

proliferation (74). The antioxidant activity of IP6 is widely accepted and

indisputable (11), and IP6 possesses antiproliferative and antiprogression

activities. Its induction of terminal differentiation (26,28,29,32, 33,38),

restoration of immune response (59), modulation of growth factors (58),

modulation of signal transduction pathways (15,16,35,57) , induction of

apoptosis (25,34,45), and possibly inhibition of oncogene activity and

restoration of tumor suppressor function are well documented. IP6 not only

inhibits the activities of some liver enzymes (75,76) but also significantly

increases the hepatic levels of glutathione S-transferase (44,77), both of which

indicate its possible role in carcinogen-blocking activities and cancer

protection. Although IP6 may belong to almost all previously mentioned

categories of cancer

preventive drugs, affecting almost all phases of cancer prevention, it still

appears that IP6 is not a direct antagonist to the carcinogen because of its

moderate efficacy in vitro when tested and compared with other chemopreventive

agents (30) and a lack of dramatic decrease in cancer incidence when tested in

vivo. However, because cancer prevention is a long process, a long

administration of cancer preventive agent is generally needed, requiring usually

10–40 y of continuous treatment (2,73), and, therefore, it is very important

that cancer preventive agents have low or almost no toxicity. IP6, a natural

compound with virtually no toxicity, can satisfy this special and very important

requirement for cancer prevention. IP6 plus inositol and patients An enhanced

antitumor activity without compromising the patient's quality of life was

demonstrated in a pilot clinical trial involving six patients with advanced

colorectal cancer (Dukes C and D) with

multiple liver and

lung metastasis (78). IP6 plus inositol was given as an adjuvant to chemotherapy

according to Mayo protocol. One patient with liver metastasis refused

chemotherapy after the first treatment, and she was treated only with IP6 plus

inositol; her control ultrasound and abdominal computed tomography scan 14 mo

after surgery showed a significantly reduced growth rate. A reduced tumor growth

rate was noticed overall and in some cases a regression of lesions was noted.

Additionally, when IP6 plus inositol was given in combination with chemotherapy,

side effects of chemotherapy (drop in leukocyte and platelet counts, nausea,

vomiting, alopecia) were diminished and patients were able to perform their

daily activities (78). Further controlled randomized clinical trials are

necessary to confirm these observations. Other biological effects of IP6 In

humans, IP6 not only has almost no toxic effects, but it has many other

beneficial health effects such as inhibition

of kidney stone

formation and reduction in risk of developing cardiovascular disease. IP6 was

administered orally either as the pure sodium salt or in a diet to reduce

hypercalciuria and to prevent formation of kidney stones, and no evidence of

toxicity was reported (64,65,79,80) . A potential hypocholesterolemic effect of

IP6 may be very significant in the clinical management of hyperlipidemia and

diabetes (75,76,81). IP6 inhibits agonist-induced platelet aggregation (82) and

efficiently protects myocardium from ischemic damage and reperfusion injury

(83), both of which are important for the management of cardiovascular diseases.

Many potential beneficial actions of IP6 have been described. The inclusion of

IP6 plus inositol in our strategies for prevention and treatment of cancer as

well as other chronic diseases is warranted. However, the effectiveness and

safety of IP6 plus inositol need to be determined in Phase I and Phase II

clinical trials in humans.

FOOTNOTES

1 Presented as part of a symposium, " International Research Conference on Food,

Nutrition, and Cancer, " given by the American Institute for Cancer Research and

the World Cancer Research Fund International in Washington, D.C., July 17–18,

2003. This conference was supported by Balchem Corporation; BASF

Aktiengesellschaft; California Dried Plum Board; The Soup Company;

Danisco USA, Inc.; Hill's Pet Nutrition, Inc.; IP-6 International, Inc.; Mead

Nutritionals; Roche Vitamins, Inc.; Ross Products Division; Abbot

Laboratories; and The Solae Company. Guest editors for this symposium were Helen

A. Norman and Ritva R. Butrum. 2 Studies from the authors' laboratories were

supported by the American Institute for Cancer Research, the Komen Breast

Cancer Foundation, the University of land Designated Research Initiative

Fund, and the University of land Women Health Research Foundation. 4

Abbreviations used: Ins, inositol; IP6,

inositol hexaphosphate;

IP3, inositol 1,4,5-P3; KS, Kaposi's sarcoma; PIP2, phosphatidylinosito l

4,5-bisphosphate.

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[Guest guest]

has anyone ever used this to get there child to sleep?

[Guest guest]

what is pcos?

On Sep 25, 2008, at 6:14 PM, Gray wrote:

> nope, but I have PCOS, and insitol plays a role in that. Wonder if

> there could be a connection with that and my child's asd?

>

>

>

> > From: Arias <thinkingheads@...>

> > Subject: [ ] Inositol

> >

> > Date: Thursday, September 25, 2008, 5:22 PM

> > has anyone ever used this to get there child to sleep?

>

>

[Guest guest]

How does Inositol play a role in PCOS?

From: [mailto: ]

On Behalf Of Gray

Sent: Thursday, September 25, 2008 7:15 PM

Subject: Re: [ ] Inositol

nope, but I have PCOS, and insitol plays a role in that. Wonder if there

could be a connection with that and my child's asd?

> From: Arias <thinkingheads@...

<mailto:thinkingheads%40sbcglobal.net> >

> Subject: [ ] Inositol

>

<mailto: %40>

> Date: Thursday, September 25, 2008, 5:22 PM

> has anyone ever used this to get there child to sleep?