No melatonin. I’ve tried a few times but felt groggy the next morning. And I stopped trying to make it work because I have minor RLS, which can worsen with exogenous melatonin.
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I see. I thought if you were having trouble with sleeping on it, it might help.
Anyway keep up the reports on how you’re feeling on IPAM this is very interesting and useful information for us all.
To be fair the fact that it causes insomnia (hopefully temporarily) implies it is doing something to hype up the mitochondria. (or something else that causes sleep problems).
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I asked chatGPT about safety
IPAM is an endogenous molecule from what I have read. I’m curious the effects exogenous use will have on endogenous production.
It might be a metabolite of gut bacteria.
The 2023 study “Nitric Oxide as a Determinant of Human Longevity and Health Span” suggests that L-arginine supplementation can enhance human circulating IPAM levels.
A possible mechanism of endogenous IPAM production relating to L-arginine ingestion is L-arginine increasing nitric oxide production which inhibits the enzyme indoleamine-2,3-dioxygenase restoring a healthy L-tryptophan : L-kynurenine ratio.
This may leave more intact tryptophan to reach the gut microbiota to be metabolized into antioxidant indoles such as IPAM, IPA and more.
I’m unsure if that is the sole source of IPAM in the body or not.
It is endogenous AFAIK. However, there might be thresholds at which it causes harm.
I’ve seen evidence that at higher doses the benefits begin to fall off. I’ve not seen evidence of harm yet, but that doesn’t mean it isn’t there.
That’s why we decided on choosing 10um, 30um and 60um as the dose in the study instead of 10um, 20um and 30um. It gives us a broader picture of the effects.
There are likely to be limits as any increase in mitochondrial efficiency and there may be other effects. (are likely to be).
I’m thinking if we did intermittent mitophagy activators like urolithin A or something more powerful it could improve the response to IPAM in the long run.
You’re very interested in mitochondria, do you have any suggestions?
I am not really a fan of UA or C Elegans. Because of the paucity of results for IPAM I thought this would be interesting, but C Elegans is not that comparative to mammals.
Mitophagy is about improving mitochondria systematically and IPAM is about propping up dysfunctional mitochondria (and possibly improving well functioning ones, but I am not so sure about that). They are likely to be synergistic, but I would not test the synergy in C Elegans.
I was just asking in general. Do you have any particular mitophagy activators you are a fan of?
Rapamycin is I think the best. I don’t know what melatonin does in this aspect, it may help and it may not. Obviously exercise has a role as does HIF 1 alpha.
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Rapamycin does appear to be the best option and it fits with the overall goal of longevity.
There is a mediation called roxadustat that activates HIF 1 alpha but it likely has higher side effect profile than rapamycin. Can increase malignancy of tumors, best to avoid.
Apparently urolithin A and spermadine can also activate mitophagy through different pathways.
Hypoxic exercise can also activate HIF 1 alpha, without the risks of roxadustat.
So a potential strategy might be to utilize IPAM throughout the week and take a day off on rapamycin dosing day. Once every 2-4 weeks you could choose to do a higher dose pulse of urolithin A and/or spermadine for 2 days.
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I’m going to wait until most of my kids are in summer camp, a couple of weeks from now. I want less on my plate when I get started. It is absolutely a black box according to my own research and ChatGPT. Typically I don’t react much to pharmaceuticals but just in case….
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I found some interesting information in regards to IPAM recently as I’ve gone through more research. I posted about it here for anyone who is interested: The four best longevity interventions? - #179 by AustraliaLongevity
To summarize IPAM is an endogenous molecule and there are things we can do upstream from this to increase endogenous production.
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Very interesting! I’ve read recently that with a combo of arginin / citrullin and exercise, you can basically rejuvenate your heart.
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Seems we are finding a lot of really useful health information by looking deeper into indolepropionamide.
I have started taking citrulline daily in my electrolyte drink. I’m going to buy either L-arginine or L-arginine alpha-ketoglutarate.
Since IPAM is a gut metabolite I’m aiming to optimize gut health as well. I’ll be adding in inulin, resistant starch in addition to psyllium husk.
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When we know that citrullin / arginine raises IPAM and exercise further strengthens the effect, we can assume that directly supplementing IPAM with exercise would also be very powerful. It’s really exciting! 
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Poeggeler replied to an email I sent him! (translated with ChatGPT)
The different species occupy specific niches and can therefore also differ in their signaling and response.
Perhaps IPA triggers a toxic effect here that does not occur in the other species.
This is supported by the protection through EUK-8.
You have searched the literature very thoroughly.
In fact, I am also not aware of any further findings on this topic.
It remains exciting. Presumably, C. elegans will react differently, as there are specific adaptations here.
Wishing you much luck and success with your investigations. I am very curious about the outcome.
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Is he mixing up IPA with IPAM?
Good work getting a response.
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