0.1 mg to 10 mg per dose under the skin, two or three times a week up to daily
What was studied
No human dose I could find, by any route
The gap
No published human dose to compare against
How long it lasts
I could find no study of what an injected dose does over time, in any species, by any route. So no measured half life stands behind any of the injection schedules in circulation.
What it actually is
Humanin is a chain of 24 amino acids, the small building blocks that proteins are made from, and short chains like this are called peptides. What is unusual about it is where the instructions for building it are kept. They sit inside the small separate set of DNA carried by mitochondria, the compartments in a cell that turn food into usable energy, buried inside a gene called MT-RNR2 that is otherwise understood to build part of the machinery a mitochondrion uses to make proteins. Hashimoto and colleagues at Keio University found it in 2001, while screening for anything that kept nerve cells alive when the genes behind inherited Alzheimer's were switched on. A vial labelled humanin holds that 24 unit chain, and I could find no published study, and no registered one, giving it to a person by any route.
What it is supposed to do
Unlike its sibling MOTS-c, which has no published receptor that I could find, humanin has a worked out mechanism. It attaches to a receptor assembly on the outside of a cell built around gp130, the shared signalling stalk of the interleukin-6 family of immune messengers, and a second receptor has had its structure solved with a formylated humanin, a chemically altered form of the peptide rather than the plain one, sitting in it. It also binds IGFBP-3, the carrier protein for insulin like growth factor 1, the growth signal the liver puts out, and lowers circulating levels of that signal. None of that has been shown in a person who was given the peptide.
What people take it for
This entry does not survey what buyers say they are after. What it does trace is where each claim attached to humanin came from, and every one of them is an animal, a worm or a cell result. Longevity is the headline, and it traces to a paper titled a regulator of lifespan and healthspan whose own 100 mice showed no lifespan difference and whose lifespan result belongs to nematode worms that were genetically engineered rather than injected. Memory and thinking trace to a second paper from the same group using the same colony, analogue and dose, where the maze results everybody quotes come from subsets of 7 to 10 mice a group. Blood sugar and liver fat trace to rat and mouse work that mostly used modified versions of the peptide rather than humanin itself. The heart claim traces to seven treated minipigs against seven controls, and at that same dose the benefit was gone when the artery was blocked for 75 minutes instead of 60.
The dose question
What circulates
0.1 mg to 10 mg per dose under the skin, two or three times a week up to daily
What was studied
No human dose I could find, by any route
Every published dose is an animal dose. Yen 2020 gave 100 mice the analogue S14G at 4 mg per kg into the abdominal cavity
No studied dose to compare
There is nothing to compare against. I could find no published study, and no registered one, giving humanin or any version of it to a person by any route, so every schedule in circulation sits beside an animal number rather than a human one. Most of those animal numbers belong to S14G, the one letter mutant, while the vial holds the other molecule. Two of the three sites quoting doses say themselves that their figures are extrapolation from rodent work, and the spread between the three is a hundredfold for the same two molecules.
Reported because it is what people use. Nothing here recommends any amount.
How long it lasts
I could find no study of what an injected dose does over time, in any species, by any route. So no measured half life stands behind any of the injection schedules in circulation.
Route studied
Into the abdominal cavity in mice and into a vein in pigs, both with the S14G analogue. In one rat study native humanin was infused into the brain fluid spaces, where insulin action improved, and into a vein, where the same native peptide did not significantly alter insulin action. No human route that I could find.
Route used
Injected under the skin. All three sites quoting numbers describe that route.
How to check you have the right molecule
This entry publishes no molecular weight and no sequence to hold a laboratory report against, so the checks it gives are on the name and on the paperwork. The first is which of two molecules is being sold to you. A vial labelled humanin holds the 24 unit chain. S14G, usually written HNG, is that same chain with the serine at position 14 swapped for a glycine, and it carries most of the animal record, so a page quoting mouse or pig results under the word humanin is usually describing the other molecule. Read whether the studies a seller cites say humanin or S14G, and whether that matches what is in the vial. The second check is the citation. Go and run the searches yourself: ClinicalTrials.gov returns seven records for humanin and every one of them measures it in blood or tissue rather than giving it to anybody, and the European register matched nothing. One site also asserts that human safety and lowering of insulin like growth factor 1, the growth signal the liver puts out, have been demonstrated in human pharmacological studies, which is a study I could not find.
Paying for one molecule on the strength of another's results. The vial holds native humanin and most of the animal record belongs to S14G, the one letter mutant, reported as roughly a thousand times more potent. Follow that thousandfold figure and it thins out. The 2006 structure paper asserts it without measuring it, and the review most often cited for it hangs that sentence on entry 23 of its own bibliography, which is a 2001 paper about tau, the protein that clumps into the tangles seen in Alzheimer's brains, with no humanin in it anywhere. The laboratory that discovered the peptide put the gap at two to three orders of magnitude, 100 to 1000 fold, so the number everybody repeats is the top of a range. The second half of the same mistake is the dose. The three sites quoting figures run from 0.1 mg to 10 mg per dose, a hundredfold spread for the same two molecules, and two of the three say outright that their numbers are extrapolation rather than a finding.
What is known about harm
I could find no published human safety record for administered humanin or any analogue, and no approval anywhere I looked, so the empty record means untested rather than clean. Three things in the published record are worth knowing anyway. The cancer question was raised a year after the discovery, when Maximov and colleagues called humanin a potential oncopeptide and cautioned that treating Alzheimer's with it might raise cancer risk, in a hypothesis paper rather than an experiment, and twenty four years on serum humanin came back higher in 75 Egyptian women with breast cancer than in 70 matched controls, none of them given anything, though it separates the two groups poorly. The analogue suppresses platelets, the cells that start a clot, though in the mice tested bleeding time was not prolonged, and what it would do alongside a blood thinner is an open question. And in 94 people on dialysis, with the curve reproduced in 83 more by the same group, risk was raised at both ends of the blood level, worst below 450.7 and above 759.5 picograms per millilitre, so more is not obviously better.