What Do You Know About IP6/IP-6/inositol Hexaphosphate/phytate/phytic Acid?

[TreasureVibe]

So there exists a specific protein, indisputably a membrane pore large enough to admit calcium yet not specifically; this will allow passage of both larger and smaller ions:

'The IP₃ receptor, when activated, can conduct all four alkaline earth cations with conductances in the order of Ba²⁺ > Sr²⁺ > Ca²⁺ > Mg²⁺.' ―Yoshida​

While true that this particular membrane pore binds inositol triphosphate (KD ≈ 2–100·nM) it also binds ATP, calcineurin, FKBP12, and some variants will bind calmodulin.

'As shown in Fig. 1, the domain contains putative binding sites for various modulators of the channel such as ATP, Ca²⁺, calmodulin, FK506 binding protein 12 (FKBP 12)...' ―Yoshida​

'A specific binding site for ATP was detected in purified type 1 IP₃ receptor subunit (65), and two consensus sequences for ATP binding site were found in its amino acid sequence (24, 25), both located in the coupling domain of the receptor.' ―Yoshida​

Yutaka Yoshida isn't a physicist, and doesn't even attempt to describe how calcium actually enters the cell; review articles never prove anything, and its common for their authors to be overly-equitable and to not express strong beliefs (lest it turn into a theoretical article). Yet he does cite another review article in his section marked 'IV. Function of IP₃ receptor.'

Bezprozvanny, I. "The inositol 1,4,5-trisphosphate (InsP₃) receptor." The Journal of membrane biology (1995)

'The ability of Mg²⁺ ions to carry substantial currents through these channels is especially striking when the very high hydration energy and extremely slow substitution rate of water molecules in the inner hydration shell of Mg²⁺ ions (Hille, 1992) is taken into consideration. One possible explanation of this observation is that when Mg²⁺ ions pass through the selectivity filters of both intracellular Ca²⁺ channels they are able to keep the inner shell of water molecules. This suggestion implies that the narrowest portion of the channel pore should be at least 10·Å for both channels. An even larger estimate of the pore size (40·Å) was obtained for the RyR (Lindsay et al., 1991) based on the ability of large organic cations like Tris⁺ and TEA⁺ to permeate through these channels.' ―Bezprozvanny

'It could be concluded from the studies of InsP₃R (Bezprozvanny & Ehrlich, 1994) and RyR (Lindsay et al., 1991; Tinker & Williams, 1992) permeation that both channels are rather nonspecific cation selective channels, permeable to Ca²⁺ and monovalent cations.' ―Bezprozvanny
​

This is a nonspecific channel, and the author seems to doubt the existence of selective calcium channels:​

'As an aside, it follows from this discussion that if plasma membrane InsP₃-gated Ca²⁺-selective channels do exist (Kuno & Gardner, 1987; Fujimoto et al., 1992) they must be much more selective for divalent cations than intracellular InsP₃R.' ―Bezprozvanny
​

The author notes the affinity ATP has for this membrane pore, and also confirms the ionic series of permissivity:​

'These authors came to the conclusion that ATP was a necessary cofactor for the activation of what was then a hypothetical InsP₃R (Smith et al., 1985). The role of ATP as an allosteric activator of the InsP₃R was proposed later based on experiments with receptor that was purified and reconstituted into liposomes (Ferris et al., 1990). It was found that 10 gM ATP or nonhydrolyzable ATP analogues dramatically potentiated InsP₃-mediated Ca²⁺ flux into vesicles containing purified InsP₃R. The existence of a specific ATP-binding site on the InsP₃R was also demonstrated in the same report (Ferris et al., 1990).' ―Bezprozvanny​

'All four alkaline earth cations tested were able to pass through the InsP₃R with single channel conductances that fall in the sequence Ba > Sr > Ca > Mg. The same order of conductances was reported for the RyR (Tinker & Williams, 1992) although the absolute values of the single channel conductance are approximately twice as large for the RyR.' ―Bezprozvanny
​

Based on these considerations the inositol triphosphate receptor could just as easily be called the 'ATP barium pore,' the 'membrane FKBP12 receptor,' or the 'membrane nonselective ion channel.' Adenosine triphosphate (ATP) is known for it's propensity for complexing magnesium, which can also pass through the pore, yet will chelate calcium in its absence. The physical forces responsible for determining how much Ca²⁺ enters and exits through this pore had gone unexplained by both of these authors, and no mention of the fact that inositol phosphates chelate calcium. The closest thing to a physical explanation had been the mention of the luminal 'glutamate ring,' an amino acid often post-translationally modified to γ-carboxyglutamate—a calcium chelator and how vitamin K ultimately exerts its calcemic functions.

I would guess that this is simple a pore having no directionality, allowing ions either in or out just the same; it's complete nonspecificity towards both the 'activating' ligand and the ions permitted is freely admitted, and even a simple dialysis bag will allow unidirectional ion flow if a chelator is placed on one side (i.e. EDTA, ATP, IP₃). An experimental study I would like to see conducted would a comparison of Ca²⁺ flux after the addition of inositol triphosphate, adenosine triphosphate, ethylene diamine tetra-acetate, and simple pyrophosphate. I would think any membrane study that makes claims about the ability of a protein to actually cause unidirectional ion flow would need something akin to an 'EDTA dialysis model' serving as a control: Only then can you eliminate underlying dialysis forces from the equation, if they are not significant, or subtract them from the 'receptor-driven flux' if the are; that could prove its ontological status, but so far I have seen nothing to indicate that its anything more than merely an ion pore. ​

IP3 Receptors: Toward Understanding Their Activation
Colin W. Taylor and Stephen C. Tovey
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, United Kingdom
Correspondence:Email: ku.ca.mac@0001twc
2010

Abstract
Inositol 1,4,5-trisphosphate receptors (IP3R) and their relatives, ryanodine receptors, are the channels that most often mediate Ca2+ release from intracellular stores. Their regulation by Ca2+ allows them also to propagate cytosolic Ca2+ signals regeneratively. This brief review addresses the structural basis of IP3R activation by IP3 and Ca2+. IP3 initiates IP3R activation by promoting Ca2+ binding to a stimulatory Ca2+-binding site, the identity of which is unresolved. We suggest that interactions of critical phosphate groups in IP3 with opposite sides of the clam-like IP3-binding core cause it to close and propagate a conformational change toward the pore via the adjacent N-terminal suppressor domain. The pore, assembled from the last pair of transmembrane domains and the intervening pore loop from each of the four IP3R subunits, forms a structure in which a luminal selectivity filter and a gate at the cytosolic end of the pore control cation fluxes through the IP3R.


A BRIEF HISTORY OF IP3 RECEPTORS
Sidney Ringer, in his famous correction to an earlier paper, showed that Ca2+ entry can evoke a physiological response by demonstrating that beating of the frog heart requires extracellular Ca2+ (Ringer 1883). Almost a century passed before it became clear that this Ca2+ entry, via voltage-gated Ca2+channels, was not directly responsible for contraction, but instead provided the trigger for a much larger release of Ca2+ from stores within the sarcoplasmic reticulum (SR). The latter is mediated by type-2 ryanodine receptors (RyR) (Fabiato 1983; Cheng et al. 1993), which like many Ca2+ channels, are able both to transport Ca2+ through an open pore and respond to it. These observations highlight two general points. First, cells call upon two sources of Ca2+ to evoke increases in cytosolic Ca2+ concentration; second, interactions between these Ca2+ fluxes across the plasma membrane and the membranes of intracellular stores are important determinants of the physiological response. The same points apply to the Ca2+ signals evoked by receptors that stimulate phospholipase C (PLC) and, thereby, formation of inositol 1,4,5-trisphosphate (IP3).

The biochemical sequence linking these receptors to formation of IP3 emerged in the 1980s (Michell et al. 1989; Berridge 2005), but work in the decade before had established that many receptors regulate many different responses by increasing the cytosolic Ca2+ concentration (Rasmussen 1970; Berridge 1975). In his influential review, Bob Michell (Michell 1975), building on work showing that many of these receptors also stimulate phospholipid turnover (Hokin and Hokin 1953), had suggested a causal link between phosphoinositide hydrolysis and Ca2+ signals. Here, as in many studies, the emphasis was on Ca2+ entry, with a consensus only slowly emerging that Ca2+ fluxes across both the plasma membrane and the membranes of intracellular stores contribute to cytosolic Ca2+ signals (Rasmussen 1970; Berridge 1975; Williams 1980; Putney et al. 1981). In the years following Michell’s review, decisive evidence, much of it coming from Mike Berridge’s elegant studies of blowfly salivary gland, established that phosphoinositide hydrolysis is, as predicted by Michell, required for PLC-linked receptors to evoke Ca2+ signals (Berridge and Fain 1979). The same preparation was used to show that IP3 is the first water-soluble product of the signaling pathway (Berridge 1983). IP3, thus, emerged as a prime candidate for the cytosolic messenger linking events at the plasma membrane to release of Ca2+ from intracellular stores. Paradoxically, it was to be many years before the links between receptors that stimulate PLC and Ca2+ entry were resolved. These came with elaboration of the pathways linking empty Ca2+ stores to Ca2+ entry, the so-called store-operated Ca2+ entry pathway (Putney 1997; Park et al. 2009), and recognition that many trp channels are regulated by products of PLC activity (Nilius et al. 2007). IP3 receptors (IP3R) also contribute more directly to Ca2+ entry across the plasma membrane either because, at least in some cells, IP3R are functionally expressed in the plasma membrane (Dellis et al. 2006; Dellis et al. 2008), or perhaps through their direct interactions with other plasma membrane Ca2+ channels (Kiselyov et al. 1999). Here, we focus solely on Ca2+ release from the endoplasmic reticulum (ER) by IP3R. Some of the key steps in the evolution of our current understanding of IP3R are listed in Table 1.

IP3 Receptors: Toward Understanding Their Activation

 

[Travis]

Receptors Channels. 1994;2(1):9-22.
So what you're saying is Travis, it's basically one big international conspiracy to sell IP6?

Can you even read?

 

[TreasureVibe]

Can you even read?

It was just a joke. Yes I read how you argued that it is a non specific ion pore. The last article I posted even concludes something similar:

In summary, we suggest that IP3R activation is initiated when IP3 binds to the IBC, and perhaps thereby causes closure of its clam-like structure. That conformational change, which must also initiate the events that allow Ca2+ to bind to a stimulatory site, is passed to the rest of the IP3R entirely via the SD. The location of that Ca2+-binding site and, therefore, the structural links between it and the SD, are unresolved. We speculate that one face of the SD interacts directly with the IBC, and the opposite face interacts with the structure through which conformational changes pass to the pore. The pore is a relatively nonselective, large-conductance cation channel formed by the tetrameric assembly of the TMD5-6 regions of each subunit. Its structure is unresolved but likely to be broadly similar to K+ channels with a selectivity filter and gate at opposite ends of its membrane-spanning structure.

What is fascinating is the amount of literature written about IP3 and apoptosis calcium signaling, when there doesn't seem to be a real link proven (yet). Hence me joking that it is a conspiracy of some sort, frankly with the absolute goal of aiding Dr. Shamsuddin in selling his IP6, lol. It is bizarre that if it is a non specific pore in which IP3 doesn't do anything more special than other molecules, researchers have written so extensively about it.

 

[TreasureVibe]

What do you think of this?

Inositol hexaphosphate-induced enhancement of natural killer cell activity correlates with suppression of colon carcinogenesis in rats. - PubMed - NCBI
Inositol-phosphate-induced enhancement of natural killer cell activity correlates with tumor suppression. - PubMed - NCBI

 

[Travis]

It was just a joke. Yes I read how you argued that it is a non specific ion pore. The last article I posted even concludes something similar:

In summary, we suggest that IP3R activation is initiated when IP3 binds to the IBC, and perhaps thereby causes closure of its clam-like structure. That conformational change, which must also initiate the events that allow Ca2+ to bind to a stimulatory site, is passed to the rest of the IP3R entirely via the SD. The location of that Ca2+-binding site and, therefore, the structural links between it and the SD, are unresolved. We speculate that one face of the SD interacts directly with the IBC, and the opposite face interacts with the structure through which conformational changes pass to the pore. The pore is a relatively nonselective, large-conductance cation channel formed by the tetrameric assembly of the TMD5-6 regions of each subunit. Its structure is unresolved but likely to be broadly similar to K+ channels with a selectivity filter and gate at opposite ends of its membrane-spanning structure.

What is fascinating is the amount of literature written about IP3 and apoptosis calcium signaling, when there doesn't seem to be a real link proven (yet). Hence me joking that it is a conspiracy of some sort, frankly with the absolute goal of aiding Dr. Shamsuddin in selling his IP6, lol. It is bizarre that if it is a non specific pore in which IP3 doesn't do anything more special than other molecules, researchers have written so extensively about it.

I think it would still be named appropriately if it could actually open the pore, but I was thinking that perhaps even this hadn't been rigorously demonstrated. Imagine for once they had found a relatively-nonselective membrane pore that inositol triphosphate would also bind . . . and had just assumed that it was 'activating it.' Perhaps imagine further it doesn't actually bind the pore, per se, but binds the residual Ca²⁺ ions trapped in the pore's 'glutamate ring' (explaining the widely-variable dissociation constants of 2–100·nM). Even if it did open the pore or facilitate ion transport in some way that does not explain how calcium enters the cell. Of course the negative mitochondrial membrane potential (ψ ≈ −180·mV) would physically attract both these cations, but it is the Ca²⁺/Mg²⁺ ratio that really seems to matter and the pore is nonselective towards those. Perhaps what really happens is that the pore has enough resistance to flow that ions are held in the channel single file (i.e. Ca²⁺,Mg²⁺,Ca²⁺,Ca²⁺,Mg²⁺) until either ATP—which chelates magnesium—or inositol triphosphate presents itself to abstract the leading ion:

[1] Mg²⁺ . . . Ca²⁺, Mg²⁺, Ca²⁺, Ca²⁺, Mg²⁺ + ATP

[2] Mg²⁺, Ca²⁺, Mg²⁺, Ca²⁺, Ca²⁺ + Mg–ATP ​

...with the second-leading ion taking it's place in cue, and a new one being admitted into the channel from behind.

I am not exactly sure about the details and I'd have yet to read an experimental study (just the reviews), but I do know that the membrane pore Na⁺/K⁺-ATPase cannot possibly work as officially stated and is most likely the 'membrane aldosterone receptor.' There are many lines of evidence that lead towards this conclusion, one of which is that aldosterone-like molecules such as oubain and digitoxin bind to it—oubain is thē classic ligand—and these molecules are also diuretics. Also worth noting is that aldosterone & cortisol transcribe for Na⁺/K⁺-ATPase through the nuclear mineralocorticoid receptor, which does work as assumed, and that this enzyme's ATP-hydrolysis catalytic rates are pathetically low: This supposed 'sodium∶potassium pump'—literally powered by ATP's not-so-high in energy 'high-energy phosphate bond,' according to official lore—hydrolyzes ATP's phosphodiester at a rate of roughly once per second (carbonic anhydrase, for instance, has a turnover rate of between 10⁴ and 10⁶ reactions per second). 'Enzymes' this slow probably shouldn't even be considered enzymes, and it's absurd to think that a protein such as this could actually act like a 'pump'—supposedly by using energy derived from either ATP's bond energy, or its enthalpy of hydration.

 

[Travis]

What do you think of this?

Inositol hexaphosphate-induced enhancement of natural killer cell activity correlates with suppression of colon carcinogenesis in rats. - PubMed - NCBI
Inositol-phosphate-induced enhancement of natural killer cell activity correlates with tumor suppression. - PubMed - NCBI

I think it could be protecting against dimethylhydrazone by complexing with it directly; pyroxidal phosphate (B₆) is known to do this, and also has phosphate and hydroxyl groups.

Geake, C. "Vitamin B₆, and the toxicity of 1,1-dimethylhydrazine." Biochemical pharmacology (1966)
​

Since nobody seems to have shown an IP₃-induced increase in natural killer cell activity in the absence of both groups being poisoned with dimethylhydrazine, I am not convinced that this is a fundamental property of IP₃—which could simply be serving as an antidote.

 

[TreasureVibe]

I think it could be protecting against dimethylhydrazone by complexing with it directly; pyroxidal phosphate (B₆) is known to do this, and also has phosphate and hydroxyl groups.

Geake, C. "Vitamin B₆, and the toxicity of 1,1-dimethylhydrazine." Biochemical pharmacology (1966)
​

Since nobody seems to have shown an IP₃-induced increase in natural killer cell activity in the absence of both groups being poisoned with dimethylhydrazine, I am not convinced that this is a fundamental property of IP₃—which could simply be serving as an antidote.

A good question; would IP6 be able to chelate mercury in a safe way? There have been several anecdotal reports of people chelating heavy metals with it, as shown on their blood, urine and hair test. This is one of the few studies showing there is a possibility it could:

Speciation of phytate ion in aqueous solution. Sequestering ability toward mercury(II) cation in NaClaq at different ionic strengths. - PubMed - NCBI

Also, here's a study linking it to chelation of uranium:

Inositol hexaphosphate: a potential chelating agent for uranium. - PubMed - NCBI

What do you think of its chelating properties, seeing as it is a strong calcium and iron chelator? (i.e. IP3 is, its derivative)

 

[TreasureVibe]

I think it would still be named appropriately if it could actually open the pore, but I was thinking that perhaps even this hadn't been rigorously demonstrated. Imagine for once they had found a relatively-nonselective membrane pore that inositol triphosphate would also bind . . . and had just assumed that it was 'activating it.' Perhaps imagine further it doesn't actually bind the pore, per se, but binds the residual Ca²⁺ ions trapped in the pore's 'glutamate ring' (explaining the widely-variable dissociation constants of 2–100·nM). Even if it did open the pore or facilitate ion transport in some way that does not explain how calcium enters the cell. Of course the negative mitochondrial membrane potential (ψ ≈ −180·mV) would physically attract both these cations, but it is the Ca²⁺/Mg²⁺ ratio that really seems to matter and the pore is nonselective towards those. Perhaps what really happens is that the pore has enough resistance to flow that ions are held in the channel single file (i.e. Ca²⁺,Mg²⁺,Ca²⁺,Ca²⁺,Mg²⁺) until either ATP—which chelates magnesium—or inositol triphosphate presents itself to abstract the leading ion:

[1] Mg²⁺ . . . Ca²⁺, Mg²⁺, Ca²⁺, Ca²⁺, Mg²⁺ + ATP

[2] Mg²⁺, Ca²⁺, Mg²⁺, Ca²⁺, Ca²⁺ + Mg–ATP ​

...with the second-leading ion taking it's place in cue, and a new one being admitted into the channel from behind.

I am not exactly sure about the details and I'd have yet to read an experimental study (just the reviews), but I do know that the membrane pore Na⁺/K⁺-ATPase cannot possibly work as officially stated and is most likely the 'membrane aldosterone receptor.' There are many lines of evidence that lead towards this conclusion, one of which is that aldosterone-like molecules such as oubain and digitoxin bind to it—oubain is thē classic ligand—and these molecules are also diuretics. Also worth noting is that aldosterone & cortisol transcribe for Na⁺/K⁺-ATPase through the nuclear mineralocorticoid receptor, which does work as assumed, and that this enzyme's ATP-hydrolysis catalytic rates are pathetically low: This supposed 'sodium∶potassium pump'—literally powered by ATP's not-so-high in energy 'high-energy phosphate bond,' according to official lore—hydrolyzes ATP's phosphodiester at a rate of roughly once per second (carbonic anhydrase, for instance, has a turnover rate of between 10⁴ and 10⁶ reactions per second). 'Enzymes' this slow probably shouldn't even be considered enzymes, and it's absurd to think that a protein such as this could actually act like a 'pump'—supposedly by using energy derived from either ATP's bond energy, or its enthalpy of hydration.

Hmm, very fascinating Travis. What do you think of the proposed mechanism of apoptosome release, subsequent Caspase-3 activation and cell death that is proposed in the following illustration?

 

[Travis]

Hmm, very fascinating Travis. What do you think of the proposed mechanism of apoptosome release, subsequent Caspase-3 activation and cell death that is proposed in the following illustration?

Well I do know that p53 can release caspases through being electronically reduced. I see this as an 'emergency transcription factor' having an internal disulfide bridge which springs-open under reductive stress, which then binds its unique dNA response element encoding for such things as caspases (there is solid proof for this). Since thiols reliably become disulfides under oxidative stress (i.e. H₂O₂), and vice versa (i.e. Ȯ₂⁻), I find this mechanism of p53 activation entirely realistic. Nuclear factor-κB is also redox-active, and this is what encodes for iNOS and cyclooxygenase-2. There is even good indication that iNOS-inducing cytokines such as TNFα and IL-1β actually activate NF-κB through hydrogen peroxide, using it as a 'second messenger' by stimulating its production (perhaps a pathway coming later-on in evolution, only elaborating on the then-extant redox-active NF-κB system already in place).

 

[TreasureVibe]

Well I do know that p53 can release caspases through being electronically reduced. I see this as an 'emergency transcription factor' having an internal disulfide bridge which springs-open under reductive stress, which then binds its unique dNA response element encoding for such things as caspases (there is solid proof for this). Since thiols reliably become disulfides under oxidative stress (i.e. H₂O₂), and vice versa (i.e. Ȯ₂⁻), I find this mechanism of p53 activation entirely realistic. Nuclear factor-κB is also redox-active, and this is what encodes for iNOS and cyclooxygenase-2. There is even good indication that iNOS-inducing cytokines such as TNFα and IL-1β actually activate NF-κB through hydrogen peroxide, using it as a 'second messenger' by stimulating its production (perhaps a pathway coming later-on in evolution, only elaborating on the then-extant redox-active NF-κB system already in place).

Thanks Travis. Can it be neurotoxic, you think, judging from the studies using anesthetics which were neurotoxic through excess calcium mobilization?

And can it move mercury?

Refering to this study:

Prog Neuropsychopharmacol Biol Psychiatry. 2013 Dec 2;47:156-61. doi: 10.1016/j.pnpbp.2013.05.009. Epub 2013 May 28.
Dual effects of neuroprotection and neurotoxicity by general anesthetics: role of intracellular calcium homeostasis.
Wei H1, Inan S.
Author information
1
Department of Anesthesiology and Critical Care, University of Pennsylvania, 305 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104, USA. Electronic address: [email protected].
Abstract
Although general anesthetics have long been considered neuroprotective, there are growing concerns about neurotoxicity. Preclinical studies clearly demonstrated that commonly used general anesthetics are both neuroprotective and neurotoxic, with unclear mechanisms. Recent studies suggest that differential activation of inositol 1,4,5-trisphosphate receptors, a calcium release channel located on the membrane of endoplasmic reticulum (ER), play important role on determining the fate of neuroprotection or neurotoxicity by general anesthetics. General anesthetics at low concentrations for short duration are sublethal stress factors which induce endogenous neuroprotective mechanisms and provide neuroprotection via adequate activation of InsP3R and moderate calcium release from ER. On the other hand, general anesthetics at high concentrations for prolonged duration are lethal stress factors which induce neuronal damage by over activation of InsP3R and excessive and abnormal Ca(2+) release from ER. This review emphasizes the dual effects of both neuroprotection and neurotoxicity via differential regulation of intracellular Ca(2+) homeostasis by commonly used general anesthetics and recommends strategy to maximize neuroprotective but minimize neurotoxic effects of general anesthetics.

Source: Dual effects of neuroprotection and neurotoxicity by general anesthetics: role of intracellular calcium homeostasis. - PubMed - NCBI

 

[TreasureVibe]

Bump!

 

[TreasureVibe]

"Based on the studies of Dr. Pantellini, we are convinced that oxidative stress damages cell membrane structures, in particular the sodium-potassium ATPase (also known as the Na/K pump). This causes (an initially mild) depolarization and an increasingly greater alteration of the active transport mechanism of these two electrolytes, that have very different but fundamental functions in the cellular organization; potassium is the main regulator of intracellular metabolic processes through reversible salification of amino groups and imino of enzymes and proteins in a slightly acid environment; the other, sodium, is the main regulator of the alkaline reserve of the organism at extracellular level, with reversible salification of carboxylic groups of enzymes and proteins in a more or less basic environment.

In this way we obtain an increasingly bigger modification of the acid-based environment and redox-reactions between cytoplasmic molecules.

We are convinced that this fact constitutes the activating mechanism (trigger) for mutation into a cancerogene cell. In fact, research relating to the sarcoma (malignant tumor) of Rous that was already published in the 30′s (Moraveck and Kishi) proved that the neoplastic cell is lacking potassium and rich of sodium, with an increasingly greater imbalance along with the development of cell degeneration.

This seems to be the common denominator in all neoplastic diseases and is also verifiable through a careful evaluation of the four hematic electrolytes (sodium, calcium, potassium, magnesium) in the blood.

The described mechanism turns out to be very dangerous for the cell when:

• it activates a rapid transfer of calcium from intracellular deposits (mitochondria), that could be responsible for mitogenic activation (i.e. cell duplication);

• it allows a considerable transport of glucose into the cytoplasm (together with sodium, SGLUT symport) with a speed that increases along with the increasingly greater alteration of the sodium/potassium pump (which is the only active control element of the two electrolytes).

These processes lead to a modification in cell respiration, with a decrease of oxidative phosphorylation and a substantial increase of glycolysis. The production of lactic acids, formed by pyruvate reduction, is also increased. Moreover, this pyruvate reduction prevents the start of the S-phase of the mitosis and its steady decrease in the cytoplasm (for the conversion into lactic acid) takes this block on mitosis away, pushing the cell towards uncontrolled proliferation."

From: Potassium Ascorbate || Information - Fondazione Valsè Pantellini


Does the highlighted sentence mean that IP6+inositol/IP3 is carcinogenic, or dangerous at the least, @Travis?

I hope anyone else with knowledge can react to this!

Thanks

Also made a separate topic for this here: Potassium Ascorbate With Ribose For Cancer (With Cell Level Explanation Inside) Possible Treatment

 

[Obi-wan]

Still staring at my bottle of IP-6 & Inositol...

 

[Lurker]

I went through a bottle 3 per day before breakfast for a couple months to lower my ferritin to no effect. Blood donation has been very effectively ective though. Maybe it was too little or not the correct protocol. For “colon health” aka cancer I think the bottle said to take with food.

 

[TreasureVibe]

I've sent a message to IP-6.net with a question and received an e-mail personally answered by Dr. Shamsuddin. I asked if the cellular calcium chelating actions of IP3 were safe for heart health and such, and if there was no possibility for "switching the wrong buttons" or so to speak. I mentioned the Lindane study and rat myocardial cell IP3 study. I mentioned I asked this partially because I was thinking of giving it to a relative with a past of hypertension.

Here is his reply:

Thank you for your message; it is a very interesting academic question; the answer of which I don't know for sure. First it's not known how efficiently IP3 can chelate Ca in vivo. Secondly, IP6 from IP6+inositol provides Ca as the former is sold as Ca Mg salt, at least by www.SeymourBiotech.com. Thus, I do not think that the BP would be adversely affected; on the contrary, a clinical study has shown that Inositol in large doses lowers BP (please see attached)!

My best,

A. K. M. Shamsuddin, MD, PhD.

He uploaded a PDF file with a clinical trial phase 1 study on Inositol, which I have added to this post.

 

[GorillaHead]

Wish travis was here. So close to finding out more


So too much intercellular calcium is caused by oxidative stress?

 

[Recoen]

Wish travis was here. So close to finding out more


So too much intercellular calcium is caused by oxidative stress?

Yes, CO2 carries it out along with ATP structuring the cytoplasm restoring intracellular and extracellular concentrations. Ling’s work is definitely worth reading- his book “In Search of the Physical Basis of Life” is a great synopsis.

 

[Geronimo]

Sooo....ip6 leads to more ip3 which leads to inhibition of the ip3 receptor, which is....good?

 

[Geronimo]

Bump

 

[Locutus]

I've been taking Cell Forte IP-6 & Inositol since Aug 2019. I take 10 pills a day at night, lately for a few months now.
I stumbled upon it when I had TERRIBLE insomnia...
I keep taking it.
Any issue? Its not a miracle cure for insomnia but it I think it helps...
I was re-evaluating my supps and I did not really find a Peat reason to stop this...