Apelin dosage and evidence
Written by Aaron CuhaReviewed Sep 2026
The short answer
Apelin is a natural signal that widens arteries and makes the heart pump harder.
Evidence grade for Apelin: Limited. The rule: people have taken it in a published study, but fewer than 100 of them. The sum on this page: 3 completed trials, 68 people given it. A grade counts how much has been done to people, not whether it works.
- People given it
- 68
- Human studies
- 3
- Found nothing
- 0
Dose
No human dose established
Amounts that were given in studies sit in Human evidence on this page. None of them is a personal dose.
3 completed trials, 68 people given it
3 effects reported, 2 unwanted, 1 wanted, by people using it, not a trial
Goal pages: Fat loss and metabolism, Injury, healing and recovery, Heart and circulation, Immune system and inflammation, Gut health
In plain English
In plain English, from Aaron
This is how I would explain it to a friend. The evidence, with the numbers, is further down the page.
Apelin is a natural signal that widens arteries and helps the heart squeeze. It is made in blood vessels, the heart, fat and the brain. It wears off in minutes. There is no approved apelin drug.
What people take it for
- Stopping muscle loss with age.
- Heart health.
- Getting the good of exercise from a vial.
What studies in people showed
In people, the tests were short drips. In about 50 people, including 18 with heart failure, apelin widened arteries and helped the heart pump. Failing hearts still responded. A drug company tested a drug for apelin's receptor in 26 heart failure patients, but only for safety. Three other finished human studies never posted results. The muscle loss claim comes from mice. No study has given apelin to a person for muscle or ageing.
What people report
Reports, not study results
The good
- In the short drip studies, apelin widened arteries and helped the heart pump, even in failing hearts.
The bad
- There is no safety data for repeated doses of apelin in people.
- Three finished human studies never posted what they found.
Where these come from: No user reports. These come from the Edinburgh drip studies and the trial register records on this page.
My bottom line
The muscle claim is mouse work. If you want to keep muscle as you age, lift and eat enough protein. Do not bet on a mouse study in a vial.
An opinion, not a finding. I am a coach, not a doctor.
What it has been measured to do
Measured in people
Goals Apelin has been tested for in people, biggest studies first. We count only what the studies on this page say, so the real numbers may be higher.
- Heart attacks and strokes44 people · 2 studies
- Blood sugar and insulinno headcount stated · 1 study
Animal and lab work, not yet tested in people
Real results, but from animals or cells, not people. What works in a mouse often does not work the same way in a person. Nobody can patent this, so nobody would ever earn back the cost of a study in people. That is usually why there is none. The record on this one is set out below.
- Inflammation1 animal or lab study
33 of the 36 indexed goals have no study of any kind behind Apelin
No study in people, animals or cells on this page reports a result for these. That does not prove Apelin does nothing for them. It does mean anything you have heard about Apelin and one of these did not come from a study cited here.
Show full evidence
What is Apelin?
Apelin is a natural signal that widens arteries and makes the heart pump harder. That was shown with short drips in about 50 people, including 18 with heart failure. In failing hearts it still worked when a standard test drug did not. The claim that it reverses muscle loss with age comes from mice. Three finished human studies of apelin never posted their results.
Apelin is a family of small signals cut from one larger protein. The versions are apelin-36, apelin-31, apelin-28 and apelin-13. A form of apelin-13 is usually reported as the main one in the blood. All of them work through one receptor, called APJ. A second, unrelated signal called ELABELA uses the same receptor. Apelin is made in blood vessel linings, the heart, fat and the brain. The enzyme ACE2 breaks it down. That is the same enzyme that makes angiotensin-(1-7).
The human studies are short tests of the heart and blood vessels in small groups. They are careful work. The biggest set, from an Edinburgh group, compared apelin with a dummy drip. It included 18 people with moderate heart failure, 6 patients having heart scans and 26 healthy volunteers. Apelin widened arm blood vessels just as well in heart failure as in healthy people. A standard test drug, acetylcholine, had a weaker effect in heart failure. Apelin dripped into the heart arteries raised blood flow and how hard the heart squeezed. Apelin given into a vein raised how much blood the heart pumped and lowered blood pressure. In an earlier study of 24 healthy volunteers, apelin dripped into an arm artery widened it every time. It worked through nitric oxide and did nothing to veins. The fact that failing hearts still respond is the best reason to see apelin's receptor as a heart failure target.
That idea has only been tested for safety. Novartis tested a drug that switches on apelin's receptor, called CLR325. It finished a 26 patient study in stable heart failure in 2019. The study mainly counted side effects. Results were posted in 2020. Three other finished human studies have posted no results as of 11 September 2026. Two came from Toulouse, in 16 and 9 people, on apelin and how the body handles insulin. The third was a 14 person Edinburgh study of apelin as a shot under the skin and into a vein. A 15 person Basel study of apelin-13 in people made to hold on to too much water finished in 2025. Its results are not posted yet.
The claim that brings most people here is different. A 2018 paper was titled "The exerkine apelin reverses age-associated sarcopenia". Sarcopenia means muscle loss with age. The paper showed apelin output falls with age in people and in rodents. In older people, more apelin went with more benefit from exercise. Every treatment in that paper was in mice. That includes the mice missing apelin, the mice given it back, and their better muscle. PubMed labels that paper a large final-stage trial because of the human group inside it. It is not a study that gave anyone apelin. No study has given apelin or a drug like it to a person for muscle, ageing or performance. No apelin product is approved anywhere.
How does Apelin work?
In people, given by drip: apelin widens arteries through nitric oxide. Blocking nitric oxide weakens the effect, and aspirin does not. It has no effect on veins. It raises blood flow to the heart and how hard the heart squeezes. It raises how much blood the heart pumps while lowering blood pressure and the resistance in blood vessels. This happens in healthy people and in heart failure alike. In mice, working muscle makes apelin, and the amount falls with age. Mice missing apelin or its receptor lose a lot of muscle as they age. Giving it back improves their muscle. It does this through more cell power plants, better cell clean-up, less inflammation and muscle stem cells. Apelin is broken down by ACE2. Natural apelin wears off very fast in the blood. We could not confirm the exact time from a human study, so we do not give one. That fast wear-off is why drug makers moved to longer lasting apelins and to small molecules that hit the same receptor.
What have studies in people found about Apelin?
Short drip studies in about 50 people across two published Edinburgh papers. One drug company safety study of a receptor drug in 26 patients. Four small finished university studies of apelin itself, three of which never posted results. No human study has measured any health outcome. None has tested apelin for muscle, ageing or performance.
- Circulation 2010: 18 heart failure patients, 6 patients having heart scans and 26 healthy volunteers. Arm vessel widening still worked in heart failure. Apelin into the heart arteries raised blood flow and squeezing force. Apelin into a vein raised the heart's output and lowered blood pressure and vessel resistance.
- CLR325 (NCT02696967): a Novartis drug that switches on apelin's receptor, tested for safety in 26 heart failure patients. Finished 2019, results posted 2020.
- JACC 2008: 24 healthy volunteers. Apelin-36 and a form of apelin-13 widened arteries through nitric oxide. Veins did not widen.
- Apelin and insulin (NCT02033473, 16 healthy volunteers; NCT02724566, 9 people with type 2 diabetes): early Toulouse studies, finished 2014 and 2017. No results posted.
- Apelin-13 into a vein in people made to hold on to too much water (NCT06277336): 15 healthy volunteers, Basel, finished March 2025. Results not posted yet.
- Apelin as a shot under the skin and into a vein (NCT02259686): 14 healthy volunteers, Edinburgh, finished 2015. No results posted.
- Nature Medicine 2018, human part: apelin made by muscle falls with age and tracks the benefit of exercise in older people. This part only watched people. All the treatment was in mice.
What this does not tell you: Every published human measurement is about blood flow and pressure, and lasts minutes to hours. Nothing shows apelin or a drug like it helps symptoms, exercise, hospital stays or survival in heart failure. The one drug company study in patients only checked safety in 26 people. The insulin question was asked twice in people, and the answers were never published. That could mean it did not work, the form given did not work, or a student thesis simply never got published. We cannot tell. There is no human data on apelin and muscle size, strength or ageing. The only human finding is that the body makes less of it with age. Nobody has studied repeated doses of natural apelin in people. The way research chemical buyers dose it has no basis in any published data.
The state of the research
Apelin looks like a good target that never became a drug. The Edinburgh studies from 2008 to 2010 are careful work in about 50 people, with a dummy drip for comparison. Failing hearts still respond to apelin when they no longer respond normally to acetylcholine. That is exactly the kind of result that gets a drug program started. The problem is that natural apelin is cleared from the blood within minutes. So the effort went into longer lasting apelins and small molecules like BMS-986224 and Novartis's CLR325. CLR325 got as far as a 26 patient safety study and, as far as the public record shows, no further. Bristol-Myers Squibb's drug is still at the animal stage in the papers we checked. A pill that switches on apelin's receptor is being tested for muscle, and it has its own page. None of this has produced a study in patients that tests whether it works.
The muscle loss claim rides on a different paper, and it needs a careful read. The 2018 Nature Medicine study is strong mouse biology with a group of people watched alongside it. PubMed labels it a large final-stage trial, which it is not in any way that matters for apelin. The human part shows that older people who make more apelin with exercise do better. The reversal of muscle loss is entirely in mice. Nothing in people supports apelin for body shape or performance. The three small studies that did ask a metabolism question in people finished years ago without reporting. Those are the Toulouse insulin studies and the Edinburgh dosing study.
The evidence, in charts
Fig. 1a · how many people
68people, across 3 studies in people cited here
| Study | People | Share |
|---|---|---|
| ClinicalTrials.gov 2016 | 26 | 38% |
| Journal of the American College of Cardiology 2008 | 24 | 35% |
| Circulation 2010 | 18 | 26% |
Counts are the number of people each study on this page says it signed up. That includes studies that only watched people and gave nobody the compound. 3 more studies in people give no headcount and are not counted here. Studies still signing people up are left out, and only studies cited on this page are counted.
Fig. 1b · evidence mix
6 of 10 sources here are studies in people. The rest are not.
- Study in people · done in people660%
- Animal study · done in animals330%
- Review of studies · sums up other studies110%
Counted from the list of sources on this page. It counts only what we cite, so there may be more studies out there. A review counts once, however many studies it sums up.
Fig. 2 · evidence over time
The studies cover 7 different years, 2008 to 2024, counted from the list of sources on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Not approved
AU
Not approved
CA
Not approved
Not approved in any of the four countries shown. This is what the law says, not a verdict on the science. See Legal status below for the full text and any notes.
Fig. 4 · how much does what
Nobody has tested different amounts in people
This chart would show how the effect changes as the amount goes up. For this compound, nobody has measured that in people. So we leave it empty. We will not borrow an animal chart and pretend it works the same in people.
Fig. 5 · what the molecule is
- Kind of compound
- Peptide
- Molecule weight
- 8,569 Da precursor (77 residues, UniProt Q9ULZ1); apelin-36 is residues 42 to 77 and apelin-13 residues 65 to 77
- Half-life
- None on file
- Chain length
- 13 amino acidscounted from the chain below
QRPRLSHKGPMPF
Stored as QRPRLSHKGPMPF (apelin-13; the circulating form carries an N-terminal pyroglutamate). The count above is of the amino acid letters only.
- Water-shy 7
- Water-loving 2
- Basic 4
One square per amino acid, left to right from the start of the chain, coloured by type. The type is a fact about the amino acid, not a finding about this compound.
The studies we cite
- Study in people2008Vascular effects of apelin in vivo in man
Apelin widens arteries in people, which is a measurement rather than a benefit. 24 healthy volunteers had two forms of apelin infused straight into an arm artery. Blood flow in the forearm rose reliably. Blocking nitric oxide blunted the effect and aspirin did not, which points to how it works. Neither form widened hand veins, where a standard drug did. Nobody's symptoms or survival were measured here. Public money paid for the work.
24 healthy volunteers. Apelin-36 and (Pyr1)apelin-13 infused intrabrachially at 0.1 to 30 nmol/min caused reproducible forearm arterial vasodilatation (p < 0.0001), attenuated by a nitric oxide clamp (p 0.004) and unaffected by aspirin; neither peptide dilated dorsal hand veins where sodium nitroprusside did. Non-US government funded.
- Study in people2010Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure
In people with failing hearts, apelin still widened blood vessels and improved pumping while it was being infused. 18 patients with moderate heart failure, 6 more during heart imaging and 26 healthy volunteers took part. Arm vessel widening was preserved in heart failure, while the usual comparison drug had weakened. Apelin into the heart arteries raised blood flow and pumping force and lowered filling pressures. These are short infusions and machine readings, not months of feeling better. Public money paid for it.
18 patients with NYHA II to III heart failure, 6 at coronary angiography and 26 healthy volunteers in randomised double-blind placebo-controlled studies. Forearm vasodilatation to apelin was preserved in heart failure (p 0.3) while the acetylcholine response was attenuated (p 0.01); intracoronary apelin-36 increased coronary flow and left ventricular dP/dt max and lowered filling pressures; systemic (Pyr1)apelin-13 at 30 to 300 nmol/min raised cardiac index and lowered mean arterial pressure and vascular resistance in both groups, raising heart rate only in controls. Non-US government funded.
- Study in people2016A Study of CLR325 in Chronic Stable Heart Failure Patients
The only drug company trial of an apelin receptor activator in patients measured safety, not benefit. Novartis gave 26 people with stable heart failure either CLR325 or a dummy infusion. What it was built to count was side effects, serious side effects and deaths. It finished in January 2019 and posted results in March 2020, and those results are safety and blood level figures. Nothing posted says whether anybody's heart failure improved.
Novartis, phase 2, 26 enrolled, APJ receptor agonist CLR325 versus placebo in chronic stable heart failure, primary outcome adverse events, serious adverse events and death. Completed January 2019, results posted March 2020. The only industry trial of an APJ agonist in patients that has reported.
- Study in people2014Effect of Apelin on Insulin Sensitivity: Proof of Concept in Healthy Volunteers
This one finished and never said what it found. A hospital in Toulouse gave apelin or a dummy to 16 healthy volunteers and completed the study in October 2014. No results have been posted, and none had been as of September 2026. A companion study in 9 people with type 2 diabetes finished in April 2017 and is also silent. A completed trial that reports nothing is itself a finding, and not a reassuring one.
University Hospital Toulouse, phase 1, 16 healthy volunteers, apelin versus placebo, completed October 2014, no results posted as of 11 September 2026. A companion 9-person phase 1 in type 2 diabetes (NCT02724566) completed April 2017, also with no results posted. Completed and unreported is a finding.
- Study in people2014Cardiovascular Effects of Apelin In Healthy Volunteers
Another apelin study that finished and published nothing. The University of Edinburgh gave 14 healthy volunteers apelin as a shot under the skin or into a vein, at three different amounts. It completed in May 2015. No results had been posted as of September 2026. Ten years of silence on a fourteen-person study tells you how thin the human record for apelin really is.
University of Edinburgh, early phase 1, 14 healthy volunteers, apelin 1 mg subcutaneous, 1 mg intravenous or 5 mg subcutaneous. Completed May 2015, no results posted as of 11 September 2026.
- Study in people2024Effects of Intravenous [Pyr1]Apelin-13 on Healthy Volunteers With Artificially Induced SIAD
A newer apelin study has finished and has not reported. A hospital in Basel gave 15 healthy volunteers either a dummy or one of two amounts of apelin-13 into a vein, after deliberately inducing a state in which the body holds on to too much water. What it counted was how much urine people passed. It completed in March 2025 and the results are not yet posted.
University Hospital Basel, 15 healthy volunteers, placebo versus low and high dose intravenous apelin-13 in induced syndrome of inappropriate antidiuresis, primary outcome urinary excretion. Completed March 2025, results not yet posted.
- Review of studies2010Apelin and ACE2 in cardiovascular disease
A review of apelin, its receptor, and how the enzyme ACE2 breaks it down. That is the link between apelin and angiotensin-(1-7).
Review of the apelin-APJ system and its degradation by ACE2, the link between apelin and the angiotensin-(1-7) axis.
- Animal study2018The exerkine apelin reverses age-associated sarcopenia
Mostly in mice. Mice missing apelin or its receptor lost a lot of muscle with age. Giving apelin signals back improved their muscle. A human part only watched people. In older people, muscle made less apelin with age, and more apelin went with more benefit from exercise. Nobody was given apelin. Public money paid for the work.
Apelin production by contracting muscle falls with age in humans and rodents and associates with exercise benefit in older people (observational). Mice lacking apelin or its receptor showed marked age-related muscle deterioration, and restoring apelin signalling improved muscle function via mitochondrial biogenesis, autophagy, anti-inflammatory pathways and muscle stem cells. The interventions are all in mice; PubMed's phase 3 trial label refers to the embedded human cohort, not to apelin administration. Non-US government funded.
- Animal study2024Apelin regulates skeletal muscle adaptation to exercise in a high-intensity interval training model
In animals doing hard interval training. Apelin signals shaped how their muscle adapted. This builds on the 2018 mouse work. No people were involved.
Animal model of high-intensity interval training in which apelin signalling shaped muscle adaptation. Extends the 2018 mouse work; no human component.
- Animal study2021In Vitro and In Vivo Evaluation of a Small-Molecule APJ (Apelin Receptor) Agonist, BMS-986224, as a Potential Treatment for Heart Failure
In rats and mice. This tested a small pill-type drug that switches on apelin's receptor. It was built to get around how fast natural apelin wears off. Animal work only.
Rodent pharmacology of an orally available small-molecule APJ agonist developed to overcome the short half-life of native apelin. Preclinical.
Where to buy Apelin
No seller we track lists Apelin yet. We read sellers’ public product lists every week, and this section fills in as soon as one does. Every seller, graded
Common questions
Has Apelin been tested in people?
Yes. 68 people given it across 3 completed trials cited here, 0 of which found nothing. Apelin is a natural signal that widens arteries and makes the heart pump harder.
What is the Apelin dosage?
No human dose established. Amounts that were given in studies sit in Human evidence on this page. None of them is a personal dose. 3 completed trials, 68 people given it
Is Apelin FDA-approved?
Not FDA-approved. No apelin peptide, and no drug that switches on its receptor (APJ), is approved anywhere. CLR325, a Novartis drug that switches on APJ, finished a mid-stage safety study in 26 patients with heart failure in 2019. Natural apelin has only been given to people in short, one-off studies of how the body works.
Does apelin reverse sarcopenia?
In mice. The 2018 paper with that title showed that giving back apelin signals improved muscle in ageing mice. Its human part only watched people. It found apelin output falls with age and tracks the benefits of exercise in older people. No study has given apelin or a drug like it to a person for muscle. PubMed labels that paper a large final-stage trial because of the human group inside it. It is not an apelin trial.
What does apelin do in humans?
Given by drip to about 50 people, it widens arteries through nitric oxide. It does not widen veins. It raises blood flow to the heart and how hard the heart squeezes. It raises how much blood the heart pumps while lowering blood pressure. In 18 heart failure patients, the artery widening still worked while a standard test drug, acetylcholine, worked less well. All of this was measured over minutes to hours. None of it is about health outcomes.
Is there an apelin drug?
No. Novartis's drug CLR325, which switches on apelin's receptor, finished a 26 patient safety study in heart failure in 2019. No study of whether it works followed. Natural apelin wears off within minutes, which is why drug makers moved to longer lasting versions and small molecules. No apelin product is approved anywhere.
Does apelin improve insulin sensitivity?
In rats and mice, yes. In people, two early studies from Toulouse asked exactly that. They were in 16 healthy volunteers and 9 people with type 2 diabetes, and finished in 2014 and 2017. Neither has posted results. The human answer is unpublished.