Your message made me very curious: Do you have findings from further investigations or a hypothesis as to how this strong difference in effect between different species comes about?
Regarding IPAM, we have not found any additional data on lifespan, except for one study in which the life-extending effect of IPA was investigated: Antioxidants can extend lifespan of Brachionus manjavacas (Rotifera), but only in a few combinations - PMC
This study was apparently later mistakenly cited in another paper as results relating to IPAM (even though IPA was used instead of IPAM), which caused some confusion during our research.
The most interesting thing is that he doesn’t have seem to have tested IPAM in c. elegans so he doesn’t have data. The test will create new information
When Burkhard Poeggeler notes that EUK‑8 ‘provides protection’, he likely refers to these ROS-scavenging, mitochondrial-targeted effects, which counteract IPA-induced toxicity in one species but not in another.
Thus, EUK‑8 might neutralize the oxidative damage IPA causes—but only in contexts where IPA actually triggers ROS overproduction.
The observed species-specific difference could result from inherent variations in:
Baseline ROS production,
Antioxidant defenses,
Cell-penetration and chemical uptake of EUK‑8,
Or differences in experimental dosing and timing.
Summary
EUK‑8 becomes protective under conditions of elevated oxidative stress, mimicking SOD and catalase within mitochondria and cytoplasm. This aligns well with Poeggeler’s hypothesis: EUK‑8 shields one species from IPA-induced ROS toxicity but may not protect another one where IPA doesn’t trigger ROS—or where ROS pathways differ due to species-specific physiology.
Yea I like him. Seems like a good guy that really does care about longevity and health from what I’ve read of his other work.
I’m making a number of changes to my routine based on a study he worked on “Nitric Oxide as a Determinant of Human Longevity and Health Span” as mentioned in that post I made today.
Wanted to expand a bit on my experience with IPAM (same one posted earlier). Additional (potential) side effects have emerged: mouth ulcers and constipation. The mouth ulcers are especially of interest, I can’t think of a reason besides IPAM for having them, but who know. When asking chatGPT for possible reasons, it responded with:
Mechanism
Description
Redox imbalance
Overactivation of mitochondrial ROS buffering could cause local oxidative damage.
Immune modulation
Immune overactivation or T-cell hypersensitivity response in mucosa.
As a potent antioxidant, it’s possible that IPAM creates rebound oxidative stress. The immune modulation reason has several potential mechanisms, which I don’t understand.
Mechanism
Explanation
T-cell hypersensitivity (Type IV)
IPAM may trigger CD4+/CD8+ mucosal response against epithelial tissue.
Neoantigen formation
IPAM or its metabolite binds to host proteins → modified self → immune attack.
Cytokine skewing (Th17/IL-17)
IPAM may promote mucosal inflammation by enhancing pro-inflammatory cytokines.
Aryl hydrocarbon receptor (AhR)
Indole core may activate AhR → immune imbalance, barrier disruption.
Microbiome-immune disruption
Alters immune tolerance via changes in microbiota → mucosal inflammation.
I’m not done with IPAM yet, but when these ulcers go away completely, I will start very low, probably 0.5mg, and see how it goes. This is just to bring awareness of other potential side effects, and to show that for some of us, this stuff have very potent impacts.
Our oldest son (now 45) was under the growth curve and diverging away from it. We noticed it around age 8. Started taking him to an endocrinologist to track his progress.
When he hit 11 he got in a hGH study and that really helped. Without that he would have topped out at 5’, he made it to 5’ 5" (about 5 years in) before bone growth stopped.
@Steve_Combi It takes so long now to loop in the endocrinologist that I just started giving the Ibutamoren hoping for the best. Probably a referral will materialize in a visit within a year. She’s gaining noticeably (though it’s still early days) however I can’t say her appetite is amazing now. I was expecting her to become a voracious beast but it’s only taken her appetite from horrid to merely meh. Part of me wonders if the stuff is 100% undiluted. It’s supposed to be a grehlin receptor agonist. Do you have a source you can absolutely trust for Ibutamoren that comes at the same price as UmbrellaLabs?
Ordered from everychem. I’ve chosen DPD courier (I’m in UK). Hoping to start 2-3mg (it’s a liquid dissolved in PEG-4 I think, so 0.3-0.5 ml per day). I will keep you all updated. Of course, if I fail to post anything ever again, that’ll mean something bad )
I’ll only be taking 0.3-0.5 ml, a dose far too low to elicit toxicity:
‘ PEG is used to improve pharmacokinetic properties of biologicals. Concern has been expressed about the toxicological effect and/or fate of the PEG. This paper reviews the available toxicity, metabolism and clearance data of PEG and PEGylated products in order to place such concerns in to appropriate context. The available data demonstrates that PEG itself only shows toxicity at high, parenteral doses and the usual target organ is the kidney as this is the route of excretion for unchanged PEG. A large therapeutic window (approximately 600-fold) exists between the maximum PEG burden from a current biological agent and the doses of PEG associated with human toxicity. Pathological changes which results in no functional deficit, PEG containing vacuoles in cells, have been observed with PEGylated biologicals. There is evidence that these PEG vesicle can resolve with time. In conclusion the doses used clinically for current and many future PEGylated biologicals are low and will result in exposures to PEG significantly lower than that required to elicit PEG toxicity. In all cases the routine regulatory toxicology studies would identify relevant pathology should it occur.’
, which I feel will be safe as it’s naturally produced by certain gut bacteria anyway