Alpha-ketobutyrate dosage and evidence
Written by Aaron CuhaReviewed Sep 2026
The short answer
One lifespan paper, in tiny worms. In people, a closely related body chemical, alpha-hydroxybutyrate, is not a sign of long life at all. It is an early warning sign of insulin resistance. It predicted worsening blood sugar in 3,841 people without diabetes across two long studies. No study of taking alpha-ketobutyrate
Evidence grade for Alpha-ketobutyrate: Preliminary. The rule: studied in people, but no published study has had people take it. The sum on this page: 2 human studies where nobody was given it. A grade counts how much has been done to people, not whether it works.
- People given it
- 0
- Human studies
- 0
- Found nothing
- 0
Dose
No human dose established
No published study on this page has given this compound to people and reported a result.
2 human studies where nobody was given it
3 effects reported, 2 unwanted, 1 wanted, by people using it, not a trial
Goal pages: Fat loss and metabolism, Ageing and longevity
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.
Alpha-ketobutyrate is a small molecule your body makes when it breaks down certain amino acids. It is sold in a few longevity supplements. Do not confuse it with alpha-ketoglutarate, or AKG, which is a different molecule.
What people take it for
- Living longer.
- Raising NAD+, an energy helper.
- Slowing cell ageing.
What studies in people showed
Nobody has given it to people in a study. What we do know about people points the wrong way. In 3,841 people without diabetes, higher levels of the chemical it turns into predicted who later got high blood sugar or diabetes. Now the worms. In one 2023 paper, it made tiny worms live longer. In a dish, skin cells aged more slowly. There is no mouse data.
What people report
Reports, not study results
The good
- In one careful worm study, it extended lifespan. That is the only good news on file.
The bad
- No person has taken it in a study, so there is no tested dose and no safety data.
- In people, the chemical it turns into rises in those heading toward diabetes.
- We have not collected user reports on this one yet.
Where these come from: The worm paper and the two human blood chemistry studies on this page. We have no forum reports on this one.
My bottom line
A worm result and a warning sign in human blood work. That is not a reason to take it. Wait for a human study.
An opinion, not a finding. I am a coach, not a doctor.
What it has been measured to do
Measured in people
Goals Alpha-ketobutyrate 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.
- Blood sugar and insulin1,261 people · 2 studies
- Living longerno 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.
- Cell energy and mitochondria1 animal or lab study
33 of the 36 indexed goals have no study of any kind behind Alpha-ketobutyrate
No study in people, animals or cells on this page reports a result for these. That does not prove Alpha-ketobutyrate does nothing for them. It does mean anything you have heard about Alpha-ketobutyrate and one of these did not come from a study cited here.
Show full evidence
What is Alpha-ketobutyrate?
One lifespan paper, in tiny worms. In people, a closely related body chemical, alpha-hydroxybutyrate, is not a sign of long life at all. It is an early warning sign of insulin resistance. It predicted worsening blood sugar in 3,841 people without diabetes across two long studies. No study of taking alpha-ketobutyrate as a supplement in people was found.
Alpha-ketobutyrate is sold because of one well-run worm paper. The human data on the same corner of body chemistry point in an awkward direction.
The worm paper is real, and it traced the chain of events in unusual detail. Adding alpha-ketobutyrate made normal worms live longer. It worked by raising NAD+, an energy helper, which switched on the worm's version of a sirtuin, a known ageing gene. That boosted peroxisomes, small cell parts that burn certain fats. Burning those fats made a little hydrogen peroxide, which acted as a signal. That switched on the worm's version of NRF2, which turned on the cell's recycling and cleanup genes. The same paper also found that skin cells in a dish aged more slowly, through a matching chain.
That is a worm and a dish. No mouse lifespan data for this compound could be found for this page. There is no study of people taking it, of any kind.
The human evidence comes at the same chemistry from the other side. The body makes alpha-ketobutyrate all the time, when it turns homocysteine into the amino acid cysteine. Then it turns alpha-ketobutyrate into alpha-hydroxybutyrate, using up NADH along the way. So alpha-hydroxybutyrate is a readout of how hard that pathway is running, and of the cell's energy balance. It has been studied a lot in people, because blood chemistry screening picked it out as an early sign of insulin resistance. In 1,261 people without diabetes in the RISC study, and 2,580 in the Botnia study, higher levels went with more insulin resistance. It also predicted who went on to develop high blood sugar within three years, and type 2 diabetes within 9.5 years, in both groups.
So the body chemistry the supplement is meant to create is, in people, a pattern that goes up in those heading toward diabetes. That does not prove taking it is harmful. It is a reason to want a human study before assuming it helps. There is not one.
How does Alpha-ketobutyrate work?
Alpha-ketobutyrate comes from a pathway the body uses to turn homocysteine into cysteine, an amino acid. It is the leftover piece. So the more that pathway runs, the more alpha-ketobutyrate is made. The body then either burns it for energy, or turns it into alpha-hydroxybutyrate. That second step is the claimed reason for the worm result. Turning alpha-ketobutyrate into alpha-hydroxybutyrate converts NADH into NAD+. That shifts the balance toward NAD+, which is the signal sirtuins respond to. In worms, this was shown to run through the worm sirtuin, then peroxisomes, then fat burning, then hydrogen peroxide as a signal, then the worm's NRF2 switch, and finally the cell's recycling genes. The same chemistry explains why alpha-hydroxybutyrate rises in people with insulin resistance. Stress on cells pushes the pathway harder, and a shifted energy balance pushes the second step forward. So the molecule is a gauge of the body's metabolic state. That makes it genuinely unclear what happens when you add it from outside.
What have studies in people found about Alpha-ketobutyrate?
No person has been given alpha-ketobutyrate in any published study that could be found. The human data only watch the body's own chemical, not a supplement. And they link this branch of body chemistry to worsening blood sugar, not to health or long life.
- No study of any kind has given alpha-ketobutyrate to people.
- In 1,261 adults without diabetes followed for 3 years and 2,580 followed for 9.5 years, alpha-hydroxybutyrate, which the body makes from alpha-ketobutyrate, predicted who developed high blood sugar and type 2 diabetes. That held after accounting for other risk factors.
- The same chemical goes up with insulin resistance, and down with how well the pancreas makes insulin, measured with a sugar drink test.
- No human study has measured lifespan, healthy ageing, NAD+ levels or any ageing measure in response to it.
- In pancreas cells in a dish, alpha-hydroxybutyrate blocked insulin release.
What this does not tell you: None of the human data involved giving anyone anything. So it cannot tell you what happens when you add the molecule from outside. A chemical that rises in a disease is not automatically a cause of it. Higher alpha-hydroxybutyrate in insulin resistance most likely reflects the pathway running harder and a shifted energy balance, not harm done by the molecule itself. But the logic cuts both ways. Nobody can tell you that pushing the same pathway harder is good for you either, because nobody has tried it in a person and measured anything.
The state of the research
Two things need saying at the top of any page about this compound.
First, alpha-ketobutyrate is not alpha-ketoglutarate. They are different molecules, with different chemistry and separate evidence. This site covers alpha-ketoglutarate separately, under calcium AKG. The short names AKB and AKG differ by one letter and get mixed up all the time, including in shop listings.
Second, the evidence here is one worm lifespan paper, with a carefully traced chain of events, plus cells in a dish. That is a fair reason for a researcher to be interested. It is not a reason for a person to take something. The gap between a worm and a person is the biggest gap on this page. A well-traced chain of events does not bridge it. It describes how the effect happened in the worm. It is not evidence that it happens in people.
The interesting twist is that this molecule is not new to the human body. The body makes it all the time, and it has been measured in thousands of people, because the chemical it turns into proved to be a good early warning sign for diabetes. That is the opposite of the usual story on this site, where a compound is sold with no human data at all. Here there is a lot of human data about the body's own molecule. It says this pathway runs higher in people whose blood sugar control is getting worse. Would taking the supplement copy that state, or relieve it? That is an open question. One simple study of blood levels and a sugar drink test would start to answer it. Nobody has published one.
This archive's position on supplements is simple. You take something because a number on your blood work is out of range. Then you retest, and you stop if the number does not move. That rule is awkward for this group. For most of them there is no shortage to fix, so no blood number tells you whether the bottle is doing anything. Where a compound here does move a number you can read, that number is a stand-in marker, not a shortage. Moving it is not the same as fixing something that was broken.
The evidence, in charts
Fig. 1a · how many people
1,261people, across 1 study in people cited here
| Study | People | Share |
|---|---|---|
| Diabetes 2013 | 1,261 | 100% |
The whole total is one study of 1,261. 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. 1 more study in people gives no headcount and is not counted here. Studies still signing people up are left out, and only studies cited on this page are counted.
Fig. 1b · evidence mix
2 of 3 sources here are studies in people. The rest is not.
- Study in people · done in people267%
- Animal study · done in animals133%
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 3 different years, 2010 to 2023, 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
- Supplement
- Molecule weight
- 102.1 Da for the free acid. A short-chain keto acid, not a peptide.
- Half-life
- Stated in words, not a numbersee the exact wording below
- Chain length
- None on file
Half-life as stated on file: Not characterised in humans. It is a fast-turnover intermediate of amino acid metabolism rather than a compound with a published supplemental pharmacokinetic profile.
No amino acid sequence is on file for Alpha-ketobutyrate, which is expected: a supplement is not built from amino acids.
The studies we cite
- Study in people2010alpha-hydroxybutyrate is an early biomarker of insulin resistance and glucose intolerance in a nondiabetic population.
In people, this chemical marks metabolic trouble rather than health. Researchers screened the blood chemistry of people without diabetes and found alpha-hydroxybutyrate, which the body makes from alpha-ketobutyrate, rising early in insulin resistance and poor glucose handling. Nobody was given anything here. This is the human setting the lifespan claim has to sit inside. In humans, this branch of metabolism runs high in the people heading toward metabolic disease, not in the ones staying well.
The metabolomic screen that identified alpha-hydroxybutyrate, the reduction product of alpha-ketobutyrate, as an early marker of insulin resistance and glucose intolerance in non-diabetic people. This is the human context that the lifespan claim sits inside: in people, this branch of metabolism is elevated in the direction of metabolic disease rather than health.
- Study in people2013Early metabolic markers of the development of dysglycemia and type 2 diabetes and their physiological significance.
Two long follow-up studies say the same thing, and it is not a longevity finding. 1,261 people without diabetes were followed for three years and 2,580 more for 9.5 years. Nobody was given anything; researchers watched and measured. Higher alpha-hydroxybutyrate went with more insulin resistance and predicted who would go on to develop high blood sugar or type 2 diabetes. That held after accounting for family history, sex, age, body size and fasting glucose. In pancreas cells in a dish, the same chemical blocked insulin release.
1,261 non-diabetic participants in the RISC study followed 3 years and 2,580 in the Botnia Prospective Study followed 9.5 years. Alpha-hydroxybutyrate was a positive correlate of insulin resistance and an independent predictor of incident dysglycaemia or type 2 diabetes, adjusted odds ratios 1.25 (95 percent CI 1.00 to 1.60) and 1.26 (1.07 to 1.48) per standard deviation, independent of familial diabetes, sex, age, BMI and fasting glucose. In INS-1e cells alpha-hydroxybutyrate inhibited glucose-induced insulin release.
- Animal study2023The metabolite alpha-ketobutyrate extends lifespan by promoting peroxisomal function in C. elegans.
In worms. Adding alpha-ketobutyrate made normal worms live longer. It worked through a long chain: more NAD+, the worm's sirtuin gene, more active peroxisomes that burn fats, hydrogen peroxide as a signal, and finally the worm's version of NRF2 turning on cleanup genes. In a dish, skin cells also aged more slowly. This paper has no data from mice or people.
Supplementing alpha-ketobutyrate extended lifespan in wild-type Caenorhabditis elegans. The mechanism traced through lactate dehydrogenase LDH-1 raising NAD+ production, SIR-2.1 mediating enhanced peroxisome function and biogenesis, raised acox-1.2 expression driving peroxisomal fatty acid beta-oxidation and hydrogen peroxide formation, and SKN-1 (the worm NRF2) driving autophagic and lysosomal gene expression. The paper also reports delayed cellular senescence in fibroblast cells through a SIRT1 to ACOX1 to hydrogen peroxide to NRF2 route. Worms and cells; no mammal lifespan data in this paper.
Common questions
Has Alpha-ketobutyrate been tested in people?
Not in a completed trial cited here. 2 human studies where nobody was given it. One lifespan paper, in tiny worms. In people, a closely related body chemical, alpha-hydroxybutyrate, is not a sign of long life at all. It is an early warning sign of insulin resistance. It predicted worsening blood sugar in 3,841 people without diabetes across two long studies. No study of taking alpha-ketobutyrate
What is the Alpha-ketobutyrate dosage?
No human dose established. No published study on this page has given this compound to people and reported a result. 2 human studies where nobody was given it
Is Alpha-ketobutyrate FDA-approved?
Not an approved drug. It is also not a standard supplement ingredient with a set daily amount. A few longevity supplements sell it, usually as a salt.
Is alpha-ketobutyrate the same as alpha-ketoglutarate?
No. They are different molecules with different jobs and separate research. Alpha-ketoglutarate is part of the cell's main energy cycle, and this site covers it separately. Alpha-ketobutyrate is a leftover piece from the pathway that turns homocysteine into cysteine. The short names AKB and AKG get mixed up all the time in product listings.
Does alpha-ketobutyrate extend lifespan?
In tiny worms, yes, in one 2023 paper. It traced a detailed chain through NAD+, the worm's sirtuin gene, peroxisomes and the worm's version of NRF2. No mouse lifespan data could be found for this compound, and there is no human data of any kind.
Does it raise NAD+ in people?
Nobody knows. The NAD+ effect is shown in worms. There, turning alpha-ketobutyrate into alpha-hydroxybutyrate converts NADH to NAD+ and shifts the balance toward NAD+. Nobody has measured NAD+ in a person given this compound.
Why is it linked to insulin resistance?
The chemical it turns into, alpha-hydroxybutyrate, was picked out by blood chemistry screening as an early sign of insulin resistance and poor blood sugar control. In two long studies with 3,841 people without diabetes in total, it predicted worsening blood sugar on its own. That most likely reflects the pathway running harder and a shifted energy balance, not harm from the molecule itself. But it does mean the human link with this pathway points toward metabolic disease, not away from it.
Is there a dose that has been tested in humans?
No. No study of people taking it as a supplement was found for this page. So there is no tested dose, no data on how the body handles it, and no safety data in people.