Neuropeptide Y dosage and evidence
Written by Aaron CuhaReviewed Sep 2026
The short answer
The one big test in people was a year-long study of a pill that blocks one of its receptors, in 1,661 overweight and obese adults.
Evidence grade for Neuropeptide Y: 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, 20 people given it. A grade counts how much has been done to people, not whether it works.
- People given it
- 20
- Human studies
- 3
- Found nothing
- 1
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, 20 people given it
5 effects reported, 4 unwanted, 1 wanted, by people using it, not a trial
Goal pages: Fat loss and metabolism, Brain, memory and mood, Sleep
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.
This is a signal peptide your own brain makes. It is one of the most common ones in there. Nerves that run the fight or flight system release it too. In rodents, injected into the brain, it is the strongest hunger signal anyone has found.
What people take it for
- Weight, which runs the wrong way. This one drives hunger up.
- Anxiety and PTSD, off one small nose spray study.
- Living longer, which comes from one rodent paper.
What studies in people showed
The big test in people was of blocking it, not giving it. A pill that blocks one of its switches was given to 1,661 overweight and obese adults for 52 weeks, against a dummy pill. They did lose more weight. But the authors said it plainly in the title: not enough to matter. It added nothing on top of two other weight drugs either. The peptide itself has only been sprayed up the nose of 26 people with PTSD, as a first safety check. 24 finished. Even the top dose caused no trouble. One anxiety scale leaned its way. A second showed nothing. In 18 volunteers, dripped into an arm artery, it narrowed blood vessels. A diabetes drug made that narrowing stronger. That is a warning about the diabetes drug, not a treatment.
What people report
Reports, not study results
The good
- We have not collected user reports on this one yet.
- In the nose spray study, people tolerated every dose up to the highest.
The bad
- It narrows blood vessels when it reaches the body. That is a real reason for caution.
- It makes you hungrier, so the weight idea is backwards.
- Anything sold as this is unapproved, and nobody has checked what is in it.
- The longevity claim rests on one rodent paper whose own title ends in a question mark.
Where these come from: The nose spray and blood vessel findings come from the two small human studies on this page. There are no user reports.
My bottom line
Huge in a rodent brain, empty as a treatment, and the one real drug aimed at it failed. Nothing here for you.
An opinion, not a finding. I am a coach, not a doctor.
What it has been measured to do
Measured in people
Goals Neuropeptide Y 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.
- Mood and anxiety20 people · 1 study · 1 found nothing
- Losing weightno headcount stated · 1 study
- Blood sugar and insulinno headcount stated · 1 study
33 of the 36 indexed goals have no study of any kind behind Neuropeptide Y
No study in people, animals or cells on this page reports a result for these. That does not prove Neuropeptide Y does nothing for them. It does mean anything you have heard about Neuropeptide Y and one of these did not come from a study cited here.
Show full evidence
What is Neuropeptide Y?
The one big test in people was a year-long study of a pill that blocks one of its receptors, in 1,661 overweight and obese adults. They lost weight, but so little that the authors themselves called it not clinically meaningful. The only study that gave NPY itself to people sprayed it up the nose of 26 people with PTSD. In rodents, it is the strongest appetite booster known when injected into the brain.
Neuropeptide Y, or NPY, is one of the most common signal peptides in the brain. The nerves that run the fight-or-flight system also release it, along with noradrenaline. It is a chain of 36 amino acids. It belongs to one family with two gut hormones, peptide YY and pancreatic polypeptide. That is why the three are almost always discussed together.
In people, the big test was of blocking it, not giving it. Merck made a pill, MK-0557, that blocks one NPY receptor, called Y5. First they used brain scans to pick the dose, then ran a 12 week dose study. Then they ran a 52 week trial in 1,661 overweight and obese people, against a dummy pill. People on the drug did lose more weight. But the authors said it plainly in the paper's title: not clinically meaningful. Other trials found it added nothing on top of the weight loss drugs orlistat or sibutramine. It also did not stop weight coming back after a very low calorie diet.
NPY itself has only been given to people in small studies. 26 people with PTSD got NPY sprayed up the nose on one day and a dummy spray on another. Even the top dose caused no trouble. Higher doses did better on one anxiety scale and no better on the other. In a separate study, NPY was dripped into an arm artery in eighteen volunteers. It narrowed blood vessels, more so at higher doses. A diabetes drug of the DPP-4 kind made that narrowing stronger. That is a safety point about diabetes drugs, not a treatment.
In rodents, what it does is not subtle. Injected into the hypothalamus, the brain's hunger centre, it is the strongest appetite signal anyone has found. It rises when the animal fasts and falls after it eats. That result is thirty years old and it repeats. It is why drug companies spent a long time trying to block it.
The longevity claim you see in supplement writing comes from rodent work on the brain's cell clean-up process. Its own authors ended their title with a question mark.
How does Neuropeptide Y work?
NPY works through a family of receptors on cells. In people, four of them work: Y1, Y2, Y4 and Y5. Y1 and Y5 drive eating. Y2 sits on the NPY nerve cells themselves and turns them down. Peptide YY 3-36, a gut hormone from the same family, prefers Y2. That is why two peptides from one family push appetite in opposite directions. Outside the brain, Y1 also narrows blood vessels, where NPY is released with noradrenaline from fight-or-flight nerves. An enzyme called DPP-4 trims NPY into a shorter form, NPY 3-36. The shorter form prefers Y2 and lowers noradrenaline release. So blocking DPP-4 tips the balance back toward narrowing blood vessels. In rodents, NPY injected into the brain also boosts the cell clean-up process, called autophagy, in the hypothalamus, through Y1 and Y5. That is where the ageing claim comes from, and it is a rodent finding.
What have studies in people found about Neuropeptide Y?
One large year-long study of a pill that blocks an NPY receptor, which failed. One small first safety study of NPY itself in people with PTSD. And one blood vessel study in eighteen volunteers.
- MK-0557, a pill that blocks the Y5 receptor: 1,661 overweight and obese people for 52 weeks, against a dummy pill. They lost a little more weight, and the authors said the amount was not clinically meaningful.
- Other trials of the same pill found it added nothing to the weight loss from orlistat or sibutramine. It also did not stop weight coming back after a very low calorie diet.
- NPY sprayed up the nose in PTSD: 26 people started and 24 finished. Single doses went up to 9.6 mg and caused no trouble. Higher doses did better on one anxiety scale (the Beck Anxiety Inventory) and no better on another (the State-Trait Anxiety Inventory).
- NPY dripped into an arm artery in 18 volunteers narrowed blood vessels, more so at higher doses. The diabetes drug sitagliptin made the narrowing stronger.
- No study in people has given NPY for appetite, body weight, metabolic health or ageing.
What this does not tell you: The PTSD study was a single-dose safety check in 26 people. One anxiety scale moved and the other did not, and we found no follow-up study. Nothing shows that giving NPY changes any health outcome in any condition. The weight loss studies tested blocking the receptor, not the peptide, and the answer was no. The blood vessel data are a reason for caution about NPY reaching the body. They are not a reason to use it.
The state of the research
NPY is the clearest case on this site of a molecule whose biology is beyond doubt and whose treatment record is close to empty. The gap is worth understanding, because it keeps coming up.
Start with people. The Y5 program ran the full set of steps. Brain scans to check the drug reached its target, dose finding, a year-long trial in over sixteen hundred people, and add-on trials with two existing weight loss drugs. The result was a small effect you could detect but that made no real difference, and the authors said so in the title. The usual explanation is backup. Appetite is guarded by many overlapping signals, so removing one changes little.
Before that trial, the rodent evidence looked truly strong. NPY injected into the brain causes the biggest eating response of any known peptide. Anyone reading that research in the 1990s would have thought blocking NPY was a serious obesity plan, and the drug industry agreed.
What that means for you is specific. When you see NPY called the body's most powerful appetite hormone, that is true. It is also why a drug aimed at it failed. A strong effect from a brain injection in a rodent does not predict that a drug will work in a person.
The ageing claim deserves the same treatment. It rests on the cell clean-up process in the rodent hypothalamus, which its authors offered as an idea with a question mark. No lifespan study and no study in people supports it.
The evidence, in charts
Fig. 1a · how many people
20people, across 1 study in people cited here
| Study | People | Share |
|---|---|---|
| International Journal of Neuropsychopharmacology 2018 | 20 | 100% |
The whole total is one study of 20. 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. 2 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
3 of 5 sources here are studies in people. The rest are not.
- Study in people · done in people360%
- Animal study · done in animals120%
- Review of studies · sums up other studies120%
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 4 different years, 2006 to 2018, counted from the list of sources on this page. The newest source on file is from 2018, more than five years ago. Research on it may have gone quiet.
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
- The precursor recorded in UniProt P01303 is 97 amino acids at 10,851 Da. The mature peptide is 36 amino acids and amidated at the C terminus; a mass for the mature chain is not asserted here.
- Half-life
- Stated in words, not a numbersee the exact wording below
- Chain length
- None on file
Half-life as stated on file: Very short. NPY is cleared from plasma within minutes, and dipeptidyl peptidase-4 cleaves it into a fragment with different receptor preferences rather than simply destroying it. No single agreed circulating figure is asserted here; the PTSD trial used an intranasal route specifically to get around the problem.
No amino acid sequence is on file for Neuropeptide Y, so none is drawn rather than guessed from a name.
The studies we cite
- Study in people2006Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight loss in overweight and obese adults
A drug built on the idea that blocking an appetite signal would make people lose weight was tested properly, and it did not work. Over sixteen hundred overweight and obese adults took the pill or a dummy one for a year, and nobody involved knew which. The weight loss was real but so small that the authors themselves called it not clinically meaningful. They concluded that blocking this one receptor is unlikely to ever work as a treatment. Merck ran the trial and Merck employees are among the authors.
The definitive human test of the NPY appetite hypothesis, and a negative one. After a positron emission tomography dosing study and a 12 week dose-ranging study identified 1 mg per day as the optimal dose, MK-0557 was taken into a 52 week, multicentre, randomised, double-blind, placebo-controlled trial in 1,661 overweight and obese patients. The weight loss was statistically significant at 52 weeks but the authors state plainly that its magnitude was not clinically meaningful, and conclude that targeting the Y5 receptor alone is unlikely to produce therapeutic efficacy. The trial was run by Merck, whose employees are among the authors.
- Study in people2018A Randomized Dose-Ranging Study of Neuropeptide Y in Patients with Posttraumatic Stress Disorder
The only time neuropeptide Y itself has been given to people was a first safety look, not an answer. Twenty six people with PTSD sprayed either the peptide or a dummy up the nose, then swapped a week later, and nobody involved knew the order. Twenty four finished both days. Even the highest dose caused no trouble. One anxiety questionnaire leaned in favour of the peptide after a distressing memory was read aloud. A second anxiety measure showed nothing. The authors ask for more study.
The only trial of NPY itself in people resolved here. Twenty six individuals with PTSD were randomised into one of five single ascending dose cohorts of intranasal NPY, from 1.4 mg to 9.6 mg, each dosed with NPY and with placebo a week apart under double-blind crossover conditions, with assessment after a trauma script provocation. Twenty four completed both days. NPY was tolerated to the highest dose. There was a significant treatment by dose interaction favouring NPY on the Beck Anxiety Inventory (F1,20 = 4.95, P = .038) and no significant interaction on the State-Trait Anxiety Inventory. The authors describe this as suggesting NPY may be associated with anxiolytic effects and call for future studies. Registered as NCT01533519, a phase 1 study, completed.
- Study in people2018DPP (Dipeptidyl Peptidase)-4 Inhibition Potentiates the Vasoconstrictor Response to NPY (Neuropeptide Y) in Humans During Renin-Angiotensin-Aldosterone System Inhibition
This is a small mechanism study about diabetes drugs, not a test of neuropeptide Y as a treatment. Eighteen non smokers, twelve healthy and six with type 2 diabetes, took sitagliptin or a dummy pill in turn, and nobody involved knew which. Neuropeptide Y was then infused into an arm artery and blood flow was measured. It narrowed blood vessels, and it narrowed them more when sitagliptin was on board. The authors think this may explain some heart effects of that drug class in people on blood pressure medicines.
Eighteen non-smokers, twelve healthy controls and six with type 2 diabetes, in randomised double-blind placebo-controlled crossover studies of sitagliptin against placebo, with NPY infused into the brachial artery and forearm blood flow measured by plethysmography. NPY caused dose-dependent vasoconstriction, and sitagliptin significantly potentiated it during enalaprilat and during valsartan. The authors suggest this could contribute to the cardiovascular effects of DPP-4 inhibitors in patients taking an ACE inhibitor or an angiotensin receptor blocker. This is a mechanistic safety finding about diabetes drugs, not a therapeutic result for NPY.
- Review of studies2012Neuropeptide Y, peptide YY and pancreatic polypeptide in the gut-brain axis
A standard review of NPY and its two gut hormone cousins, peptide YY and pancreatic polypeptide. It explains why this page should be read next to the PYY page. The same receptor family carries opposite appetite signals, depending on which peptide lands on which receptor.
The standard review placing NPY in its family with peptide YY and pancreatic polypeptide, and the reason this page cannot be read in isolation from the PYY page. The same receptor family carries opposite appetite signals depending on which member binds which receptor.
- Animal study2015NPY/neuropeptide Y enhances autophagy in the hypothalamus: a mechanism to delay aging?
In rodents, this paper is where the NPY longevity claim comes from. The authors found NPY boosts the cell clean-up process in the hypothalamus, and helps drive the same boost from eating less. They offered longer life as an idea, with a question mark in the title. There was no lifespan test and no work in people.
The source of the NPY longevity claim, and the authors put the question mark in their own title. They report that NPY stimulates autophagy in rodent hypothalamus, mediates caloric restriction induced autophagy in hypothalamic neurons, and acts through Y1 or Y5 receptors. Their proposal that modulating NPY could extend longevity is stated as a hypothesis. There is no lifespan experiment here and no human work.
Where to buy Neuropeptide Y
No seller we track lists Neuropeptide Y 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 Neuropeptide Y been tested in people?
Yes. 20 people given it across 3 completed trials cited here, 1 of which found nothing. The one big test in people was a year-long study of a pill that blocks one of its receptors, in 1,661 overweight and obese adults.
What is the Neuropeptide Y 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, 20 people given it
Is Neuropeptide Y FDA-approved?
NPY is a brain chemical your own body makes. It is not a drug, and there is no approved product containing it. No drug acting on any NPY receptor is approved for obesity or for any other use. An NPY nasal spray has been tested in people with PTSD in one early safety study.
Can you take neuropeptide Y for appetite or weight?
No, and the idea runs the wrong way. NPY makes you hungrier. The treatment idea was to block it, and that was tested. A pill that blocks the Y5 receptor was given to 1,661 people for 52 weeks. The weight loss was so small the researchers themselves said it was not clinically meaningful. No drug that works on any NPY receptor is approved.
Does NPY slow ageing?
There is no evidence that it does in any species. The claim comes from work showing NPY boosts the cell clean-up process in the rodent hypothalamus. The paper's title ends in a question mark, and the authors offered the longevity link as an idea. No lifespan experiment and no study in people supports it.
Has NPY been given to humans at all?
Yes, twice in the studies we found. It was sprayed up the nose of 26 people with PTSD, in a first safety study with single doses. It caused no trouble up to 9.6 mg, and higher doses did better on one anxiety scale but not the other. It was also dripped into an arm artery in 18 volunteers, where it narrowed blood vessels. That was a test of how the body works, not a treatment.
How is NPY different from PYY?
They are close cousins in the same family, and they push in opposite directions. NPY works on Y1 and Y5 to drive eating. PYY gets trimmed by the enzyme DPP-4 into PYY 3-36. That form prefers the Y2 receptor, which turns NPY nerve cells down and cuts how much you eat. Same receptor family, opposite effect. That is why the two pages belong next to each other.
Is it legal to buy?
NPY is a peptide your own body makes, not an approved product anywhere. Unlike most hormones in this group, there is no approved medicine that works on its receptors. Anything sold as NPY is unapproved, and nobody has checked what is really in it. The only dosing in people is one small first safety study.