The more I think about it and read and reread Shamsuddin’s book, the more excited I am about this as a safe and effective synergy with rapamycin.
Other synergies have mTOR inhibition as part of their effect or are limited by side effects. This is now known to safe and no evidence of any rapamycin overlap.
It’s a shame that he has no interest in longevity and never tested it for that indication, but anything that can prevent CAD, cancer , and AD, will probably give longevity. I’m all in.
He also developed IP6c* Pages 230 to 233, received several patent for IP6c.
On his web site ip-6.net under “What’s New?”
From the abstract of the above paper: “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.”
Were human trials ever done to prove that IP6 plus inositol is indeed safe at these doses?
That paper is almost 20 years old. I wonder what if anything has happened with IP6 since then?
Yes - Pubmed here… but I haven’t had a chance to review the papers yet:
He was also an author in book titled; “Inositol & its Phosphates: Basic Science to Practical Applications” A.K.M. Shamsuddin, Guang-Yu Yang
Bentham Science Publishers, Mar 4, 2015
This is a fairly recent and comprehensive overview
And to get an idea of safety, those cultures with predominance of corn in their diet are consuming the equivalent of 20-40 IP 6 capsules per day.
I’ve been looking for foods high in both IP6 and inositol.
Interestingly they are considered anti-nutrients because they block the absorption of many minerals.
Given that, this should be eaten well after or long before any other meal where you hope to be absorbing minerals.
Anyway, a dish I appear to consume 4 or 5 days a week does happen to have many of the foods high in both i.e. my porridge oats dish. Specifically, when I cook this I add in some wheat bran, sunflower seeds and linseeds and a very generous sprinkling of cinnamon (significantly damps down any blood glucose increase - no spikes as per my CGM). Once cooked, on top I’ll add a mixture of Almonds, Walnuts, Hazelnuts, Macadamia and Pistachios and a chopped banana with either goji berries or chopped prunes.
Having looked at all this, adding Brazil nuts in place of the Macadamia and Pistachios would enhance the amounts, as with also adding cocoa powder into the mix.
I also noticed that apparently grapefruit juice is also very high in inositol.
The absorption issue has been studied ad nauseum and there’s no evidence for it having any clinical relevance, though I’m aware that they keep saying it. A shame.
Thanks for the reply and good to know that no evidence exists on that absorption issue.
Either way, for those who don’t want to add ever more supplements but are interested in those particular protective effects, that is a dish high in the IP6/Inositol combination.
Alzheimer’s disease involves the progressive degeneration of the brain, severely impacting mental faculties. Since the Ca2+ hypothesis of Alzheimer’s was proposed in 1994, several studies have shown that disruptions in Ca2+ signaling are the primary cause of Alzheimer’s disease. Familial Alzheimer’s disease has been strongly linked to mutations in the presenilin 1 (PS1), presenilin 2 (PS2), and amyloid precursor protein (APP) genes. All of the mutated forms of these genes observed to date have been found to cause abnormal Ca2+ signaling in the ER. Mutations in PS1 have been shown to increase IP3-mediated Ca2+ release from the ER in several animal models. Calcium channel blockers have been used to treat Alzheimer’s disease with some success, and the use of lithium to decrease IP3 turnover has also been suggested as a possible method of treatment.
Once active, VPS34 phosphorylates the lipid phosphatidylinositol to generate phosphatidylinositol 3-phosphate (PtdIns(3)P) on the surface of the phagophore. The generated PtdIns(3)P is used as a docking point for proteins harboring a PtdIns(3)P binding motif. WIPI2, a PtdIns(3)P binding protein of the WIPI (WD-repeat protein interacting with phosphoinositides) protein family, was recently shown to physically bind Atg16L1. Atg16L1 is a member of an E3-like protein complex involved in one of two ubiquitin-like conjugation systems essential for autophagosome formation. The FIP200 cis-Golgi-derived membranes fuse with ATG16L1-positive endosomal membranes to form the prophagophore termed HyPAS (hybrid pre-autophagosomal structure). ATG16L1 binding to WIPI2 mediates ATG16L1’s activity. This leads to downstream conversion of prophagophore into ATG8-positive phagophore via a ubiquitin-like conjugation system.
Okay, IP3 is common (and used in intracellular pathways). IP6 doesn’t seem to be common. It’s the number of phosphate groups attached
PTEN acts as a tumor suppressor gene through the action of its phosphatase protein product. This phosphatase is involved in the regulation of the cell cycle, preventing cells from growing and dividing too rapidly. It is a target of many anticancer drugs.
The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin-like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating the Akt/PKB signaling pathway.
It’s unclear if inositol cleaves into PIP3 or inorganic phosphate, but it could happen, so I’d be careful
Thanks. It’s complicated but worth considering.