#1

What is Indolepropionamide?
IPAM is a tryptophan-derived indole that chemists describe as a “reverse melatonin.” The core indole ring is identical to melatonin’s, but instead of a 2-carbon N-acetyl side chain and a 5-methoxy group, IPAM carries a 3-carbon propionamide and no methoxy.

This gives it two key properties:

  1. High lipid permeability, so it crosses cell membranes and the blood–brain barrier with ease.

  2. Markedly longer tissue persistence (~6 h in rat brain versus <1 h for melatonin).

Main Mechanism:
IPAM lodges at mitochondrial Complex I, streamlines electron flow and prevents “leakage” that ordinarily forms superoxide and downstream reactive oxygen species (ROS). Because it can cycle between redox states without turning into a pro-oxidant, one IPAM molecule can neutralise many radicals—hence the label catalytic antioxidant.

It very likely does more we are not aware of.

What The Studies Say:
The only lifespan study published so far (rotifers, 2010) reported a staggering 200–300 % increase in mean life-span plus bigger body size and more offspring. No other compound has ever produced a comparable gain in that model. Crucially, the work has never been repeated and no whole-animal mammal lifespan data exist. This must change.

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Source for image: Indolepropionamide and its possible anti-ageing properties

Other Documented Benefits (all pre-clinical)

  • Aged-rat brain mitochondria regained youthful membrane potential and Complex I/IV activity after nanomolar IPAM exposure.
  • In old rats pre-treated with 0.5 mg ⁄ kg IPAM, mitochondrial collapse induced by rotenone or doxorubicin was completely prevented.
  • In vitro work with the closely related acid (IPA) shows potent protection against β-amyloid toxicity—suggesting IPAM may share anti-amyloid, neuro-protective potential.

Safety So Far:
Rotifers thrived at very high concentrations; rats showed no behavioural or biochemical toxicity after single 0.5 mg ⁄ kg injections. No data yet on chronic, reproductive or genotoxic safety.

Anecdotal Human Reports of IPAM (Reddit and Forums)
Based on user self-reports at doses between ~2 mg and 15 mg/day over several weeks.

Positive Effects

  • Increased energy and endurance, both subjectively and during exercise.

  • Potentiation of other substances (e.g., stronger effects from supplements taken alongside it).

  • Elevated libido and stronger erections reported by multiple users.

  • Significant stress reduction, possibly due to antioxidant or neurological effects.

  • Improved breathing – users described lungs feeling clearer and breathing easier.

  • Lower heart rate and easier cardiovascular output during physical exertion (e.g., sprinting, uphill movement).

  • Physical tasks feel less demanding, with reduced perception of effort.

  • Improved mood potentially tied to enhanced physical comfort or neurochemical modulation.

Neutral or Mixed Effects

  • No negative side effects reported by most users at these doses.

  • Sleep disruption vs. sedation – some users reported increased alertness or insomnia, while one noted sedation. This may indicate individual variability or dose/timing sensitivity.

Uncertain or Minimal Effects

  • One user reported no noticeable changes in sleep or performance, attributing any benefit to possible placebo.

Research Gaps:

  • Replication: the rotifer study must be reproduced.
  • Intermediate species: C. elegans, Drosophila, killifish lifespan tests should come before committing to multi-year mouse trials.
  • Mouse work: full health-span and lifespan studies plus 90-day toxicology are essential.
  • Human data: first-in-human phase-1 study to establish oral bioavailability, half-life, and tolerability.

Possible Downsides:

One potential downside of IPAM that immediately comes to mind is that its powerful, catalytic antioxidant activity could blunt the beneficial effects of physiological ROS, such as those produced during exercise or hormetic stress. Reactive oxygen species, while damaging in excess, also play essential signalling roles in mitochondrial biogenesis, adaptation to physical training, immune responses, and cellular repair processes.

Because of this I believe the timing of taking this substance would be key. Potentially at night before bed, far away from exercise and other sources of hormesis.

More studies need to be done:
IPAM is the most dramatic life-extension hit ever seen in a simple animal and an impressive mitochondrial protector in rodent tissue—but right now it is a one-paper wonder with zero data in larger species or humans.

C Elegans study with Ora Biomedical:

I’ve spoken with Ora Biomedical last night and inquired about the cost of them obtaining IPAM and running a test on C Elegans. It is about $400USD. This would likely leave some leftover IPAM to run combination tests in the future.

UPDATE: 4 people, including myself, have pledged to put $100US towards this study. This should cover the full cost of Ora obtaining the Indolepropionamide and running the study. This may leave some Indolepropionamide leftover for future tests as well. I have informed Ora Biomedical of this and ASAP once the fundraiser link is available I will publish it and notify all parties interested.

Possible new features coming to Ora Biomedical and the Million Molecule Challenge
I also discussed with Ora Biomedical about a new feature of their business and website of the ability for people like us to create fundraisers for such situations and they seemed interested in the idea and are looking to possibly implement it soonish.

It would function similarly to the Rapamycin Longevity Lab 601 mTOR inhibitor fundraiser, though I imagine they would not want clog up their main shop page with all of these smaller fundraisers, they may have a separate section listing all of these smaller fundraisers.

I imagine they will make an announcement in the next month or so in regards to this, and if this does eventuate I am going to create a small fundraiser to get this substance tested.

I could not personally afford to just drop $400 onto something like this right now, but I certainly could contribute and advocate for it.

If proven successful it would be something to try in combination with all of the current best longevity interventions we know of in further studies.

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Any experiences with Indolepropionamide?
#2

Normally I won’t fund C Elegans experiments because I don’t think they are much use, but on this occasion I will contribute 25%.

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#3

I’m very grateful for that John. Once Ora announces the fundraising capabilities I will create the campaign, contribute myself and I will reach out to you. I was also thinking of contributing 25%.

I think this idea with Ora Biomedical is really cool.

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#4

All we need to do is to find out a way of getting the funds to Ora. I am pretty certain on this forum we will manage to raise USD400, we are already half way there.

I asked another question of chatGPT

What enzyme creates Indolepropionamide?

Currently, there is no characterized enzyme in mammals or microbes that is known to biosynthetically convert any precursor into indolepropionamide (IPAM). All of the published work on IPAM to date describes its chemical synthesis and its detection in vivo, but does not identify an enzymatic pathway or enzyme responsible for its formation.

  • In the landmark study by Poeggeler et al., IPAM was synthesized chemically by converting indole-3-propionic acid first into its ethyl ester, then into the corresponding hydrazide, and finally into the amide via Raney-nickel–catalyzed hydrogenolysis—no biological enzyme was involved in this process (NCBI).
  • The Wikipedia article on indolepropionamide explicitly notes that while IPAM can be detected endogenously (its levels rise after L-tryptophan administration), no biosynthetic enzyme has been described to date (Wikipedia).

In short, indolepropionamide is produced chemically for experimental work, and although it appears naturally in animal tissues, the enzymatic machinery (if any) that might generate it has not yet been identified.

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#5

Given that this paper is 2010

It is surprising little has arisen from the molecule since.

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#6

As I said in the post I contacted Ora about setting up the ability of people to create small scale fundraisers similar to the Rapamycin Longevity Lab 601 mTOR inhibitor screening fundraiser, and they agreed it is a good idea and something they had thought of. I’m told next month it might be available, though I don’t want to make any promises.

If this shows promising data, I can see it being combined with the best molecules found in the 601 mTOR inhibitor screening.

That’s what makes this study so groundbreaking. The longevity scene is exploding right now, it is the perfect time for such a molecule to be rediscovered. Assuming it works.

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#7

Looking at pubmed there are, however, 24 citations. Hence it has not been ignored over time, but it appears no lifespan experiments have been done.

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#8

I’m only seeing 1 result for Indolepropionamide and 2 for Indole-3-propionamide.

#9

These are the citations:

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#10

I asked chatGPT to do a summary of the papers, it only looked at the first page which is only 10 papers, when it says there are 24 it is misleading people), however, and gave:
(I will try to get it to look at all of them).

Here’s an overview of the main findings reported in the 24 papers citing Poeggeler et al. (PMID 20421998). Broadly, these studies fall into several thematic areas:

  1. Gut microbiota–derived metabolites and the gut–brain axis
  • Ahmed et al. (2022) review how microbial transformation of dietary and host molecules produces metabolites (e.g., short-chain fatty acids, 4-ethylphenylsulfate, trimethylamine-N-oxide) that cross the gut barrier, modulate blood–brain barrier integrity, and engage immunological, neuronal, and endocrine routes to influence brain function and behavior (考研).
  • Edlund et al. (2017) used metabolomics to map peptidic small molecules secreted by the oral microbiome, revealing a vast “dark matter” of bioactive compounds whose physiological roles are largely unexplored (考研).
  1. Kynurenine pathway and indole derivatives in health and disease
  • Wang et al. (2025) present an updated review of the kynurenine pathway’s metabolites—such as kynurenic acid and quinolinic acid—highlighting their diverse roles in immune modulation, neuroprotection, and redox homeostasis, and discussing therapeutic implications for neurodegenerative and psychiatric disorders (考研).
  • Wei et al. (2019) demonstrate that an indole-derivative compound (NC001-8) activates the NRF2 antioxidant pathway in cellular Parkinson’s disease models, reducing oxidative damage and improving cell survival (考研).
  1. Antioxidant supplementation and lifespan extension
  • Snell et al. (2012) tested combinations of antioxidants in the rotifer Brachionus manjavacas, finding that certain pairings extended lifespan significantly, whereas others had no effect or were detrimental—underscoring the importance of specific redox interactions (考研).
  • Sadowska-Bartosz & Bartosz (2014) review human and animal trials of antioxidant supplements (e.g., vitamin E, coenzyme Q10), concluding that while biochemical markers of oxidative stress often improve, robust evidence for actual lifespan extension in humans remains lacking (考研).
  1. Comparative analyses of lifespan-extending compounds
  • Berkel & Cacan (2021) perform a meta-analysis across yeast, worms, flies, and mice to rank compounds (e.g., rapamycin, metformin, resveratrol) by their efficacy in extending lifespan, identifying species-specific responsiveness and potential translational candidates (考研).
  • Rukavina Mikusic et al. (2025) synthesize emerging data on how microbiota, mitochondrial function, and epigenetic modifications converge to regulate aging, proposing integrated therapeutic strategies targeting these interconnected pathways (考研).
  1. Metabolic and lipidomic profiling in disease contexts
  • Weerd et al. (2024) compare the serum metabolome and plasma lipidome of early-treated phenylketonuria patients to healthy controls, uncovering persistent alterations in amino acid pathways and phospholipid classes despite dietary management (考研).
  1. Neuroprotection via mitochondrial support
  • Collectively, these papers bolster the concept introduced by Poeggeler et al. that indole-based molecules can preserve mitochondrial integrity and promote organismal health and longevity—whether by modulating oxidative stress, engaging the NRF2 axis, or acting through the gut–brain axis to influence central nervous system resilience (考研).

Take-home message:
The citing literature expands on Poeggeler et al.’s finding that endogenous indoles protect mitochondria and extend lifespan by exploring:

  • How microbiota-derived metabolites communicate with the brain (Ahmed et al.)
  • The roles of kynurenine and other indole pathways in health and disease (Wang et al.; Wei et al.)
  • The (often nuanced) effects of antioxidant supplements on aging (Snell et al.; Sadowska-Bartosz & Bartosz)
  • Cross-species analyses of longevity compounds (Berkel & Cacan; Rukavina Mikusic et al.)
  • Metabolic dysregulation in genetic metabolic disorders (Weerd et al.)

Together, these studies underscore the multifaceted interplay between metabolism, microbiota, redox biology, and epigenetics in shaping mitochondrial health and organismal lifespan.

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#11

Good job.

The other ones might be referencing “Indole-3-Propionic Acid” which is a related compound, but not the same.

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#12

I made it do more work:

What the 24 papers that cite Poeggeler et al., 2010 (“Indole-3-propionamide protects mitochondria…” PMID 20421998) actually add to the story

Thematic thread (≈ number of papers) Consistent take-home message Representative examples
1. Microbiota → mitochondria → brain & ageing (7 papers) Gut (and oral) microbes make small tryptophan/indole-derived or SCFA metabolites that fine-tune mitochondrial biogenesis, redox balance and epigenetics in host cells; dysbiosis therefore accelerates metabolic syndrome, neuroinflammation and cognitive decline, whereas pre-/post-biotics may slow it. Systematic review on the “microbiota-mitochondria-epigenome triad” (考研); “gut–brain axis & kynurenines” review (考研); microbiome & cognitive ageing (考研); prebiotics in Alzheimer’s (考研); gut microbial metabolism in AD 2024 (考研); oral-microbiome peptidomics gap (考研); carrageenan oligosaccharides extend Drosophila lifespan via gut flora (考研).
2. Tryptophan–kynurenine/indole chemistry (6) Multiple groups zoom in on downstream metabolites of tryptophan (kynurenic acid, indole-3-propionic acid, novel ester/amide derivatives) as mitochondria-centric antioxidants, neuromodulators and even cholinesterase inhibitors, echoing Poeggeler’s concept that certain indoles are “endogenous melatonins”. 2025 kynurenine-pathway mega-review (考研); esterified indole-3-propionic acid as dual AChE/BuChE blocker (考研); kynurenic acid & analogues improve stress resistance and survival in bdelloid rotifers (考研); Parkinson’s cell study with synthetic indole NC001-8 activating NRF2 (考研).
3. Classic and “mito-targeted” antioxidants (7) Meta-analyses and rotifer screens confirm that only a subset or specific combinations of antioxidants (e.g., aspirin, minocycline, lipophilic algal lipids) extend lifespan—probably because they reach and protect mitochondria efficiently. DrugAge-wide comparison of lifespan-extending molecules (aspirin #1) (考研); antioxidants work in rotifers but only in a few cocktails (考研); red-algal extracts add 9–14 % to rotifer life span (考研); comprehensive antioxidant-supplementation review (考研).
4. Melatonin & friends at mitochondria (4) Building on Poeggeler’s earlier melatonin work, authors show that melatonin (i) re-programs cancer-cell metabolism towards OXPHOS, (ii) shares a “common mitochondrial-respiratory target” with other bioactives, and (iii) speeds β-amyloid clearance via meningeal lymphatics. Melatonin-mitochondria-cancer review (考研); melatonin/respiration review (考研); melatonin promotes Aβ lymphatic drainage in APP mice (考研).
5. Gas & hormone signalling to mitochondria (3) Endogenous gases/hormones match indoles in safeguarding mitochondrial fitness: (a) nitric-oxide tone predicts human longevity, (b) thyroid hormones trigger follicular mitochondrial biogenesis, (c) amino-acid supplementation rescues energy failure in α-synuclein-stressed neurons. NO–longevity review (考研); T3/T4 up-regulate mitochondrial mass in human hair follicles (考研); amino-acids drop ROS in PD cell model (考研).
6. Methodology & model-organism papers (3) Rotifers are promoted as rapid, vertebrate-relevant ageing models; life-table and omics tools make them ideal for testing mitochondrial protectants such as indole derivatives, antioxidants and algal lipids. Rotifers as ageing models review (考研) plus lifespan/antioxidant screens above.

Big picture synthesis

  • Convergence on mitochondria — Whether the intervention is a microbial metabolite, melatonin analogue, hormone, gas transmitter or antioxidant mix, the beneficial phenotype almost always tracks back to improved mitochondrial redox coupling, biogenesis or signalling—precisely what Poeggeler et al. proposed for indole-3-propionamide.

  • Microbiome moves centre-stage — Several post-2020 papers re-frame indole/kynurenine chemistry as host–microbe co-metabolism, suggesting that nurturing the right microbes (or delivering their metabolites) could be a practical route to the mitochondrial protection Poeggeler demonstrated in rodents and rotifers.

  • Therapeutic scouting is widening — High-throughput drug-age mining, lipidomics, cholinesterase docking and rotifer combinatorial screens all extend Poeggeler’s single-compound insight toward pipelines for next-generation mito-protectants.

  • Translational hints — Melatonin and NO reviews argue for repurposing cheap, well-tolerated agents, while cholinesterase-blocking indole-3-propionate esters and microbiota-targeted prebiotics point to disease-specific tailoring (Alzheimer’s, Parkinson’s, metabolic syndrome).

In short: The citing literature corroborates and broadens Poeggeler’s central thesis—small, naturally occurring molecules that reach and stabilise mitochondria can slow functional decline across taxa—and now links it to gut microbiota, gasotransmitters, endocrine loops and combinatorial antioxidant strategies.

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#13

Available as supplements online at many sites.

Been around since 2018, yes 2018

Review

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#14

That page isn’t selling it, it’s just a writeup of some information. You can purchase it on a number of different research chemical websites, but we don’t have enough human data for that to be advisable.

I’d rather put the money I’d take spending on getting this towards a new lifespan study and get more data. This is what I am organizing here. Hopefully the fundraiser is up soon.

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#15

There are places it can be bought. However, as it stands we don’t know much about it. It might be useful and it might not.

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#16

As I have posted countless times…

“If you wait until you are ready, it is almost certainly too late.”
~ Seth Godin

“I am not the waiting type.”
~Joseph

You can wait.

I purposely did not post a site selling this compound.

It was a article by “Marion Tible PhD a researcher in cellular biology and physiopathology. Formerly a researcher in thematics varying from cardiology to neurodegenerative diseases.”

It is not difficult to locate and purchase this compound

Simple search

FWIW…

2004 patent…

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#17

If you do use it please give as much information as you can on your experience. I am interested to hear it from the perspective of someone interested in longevity.

#18

Also discussed on this thread…
…

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#19

I’d love to see lifespan studies on this component too! Any chance this could be done via crowdfunding? A +260% median lifespan extension might be highly unlikely in mammals, but it’s really intriguing. Running a small study could be worthwhile, and the worm bot might be a great place to start.

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#20

So are you willing to put up some cash towards the wormbot. It costs USD400 and USD200 have been promised so far?

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