Sodium phenylbutyrate dosage and evidence
Written by Aaron CuhaReviewed Sep 2026
The short answer
In people, it is approved for a rare disease of ammonia build-up.
Evidence grade for Sodium phenylbutyrate: Moderate. The rule: at least one finished study in people, and at least 100 people who took it. The sum on this page: 2 completed trials, 148 people given it. A grade counts how much has been done to people, not whether it works.
- People given it
- 148
- Human studies
- 2
- Found nothing
- 0
Dose
Approved medicine. No human dose established for unlabelled uses
Labeled amounts sit on the prescribing information. This page records what trials measured, not a personal dose.
FDA-approved for urea cycle disorders, rare inherited conditions where ammonia builds up in the blood. It was also part of a combination drug approved for ALS (amyotrophic lateral sclerosis). That drug was later withdrawn after the study meant to confirm it failed. No ageing use.
4 effects reported, 3 unwanted, 1 wanted, by people using it, not a trial
Goal pages: Muscle and strength, 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.
Sodium phenylbutyrate is a prescription drug for rare diseases where ammonia builds up. It also helps misfolded proteins fold. A pill pairing it with a bile acid was approved for ALS, then pulled.
What people take it for
- Better protein care in ageing cells.
- ALS, as part of a two-drug pill that was later pulled.
What studies in people showed
In 137 people with ALS, a pill of this plus a bile acid slowed the loss of daily function a little over 24 weeks. Strength, breathing and survival did not change. A bigger trial then failed, and the pill was pulled. In 11 children with a rare ammonia disease, a newer form kept ammonia in check. Nobody has tested it for ageing. Now mice. It did not make either sex live longer.
What people report
Reports, not study results
The good
- It keeps ammonia down in rare urea cycle diseases, its approved use.
The bad
- Gut side effects in the ALS trial.
- It tastes bad and has to be taken often, in big amounts.
- A lot of sodium, which matters with high blood pressure or heart failure.
Where these come from: The side effects are from the trials and drug notes on this page. We have no user reports.
My bottom line
An early win in ALS did not hold up, and it did nothing for mouse lifespan. I would not take it for ageing.
An opinion, not a finding. I am a coach, not a doctor.
What it has been measured to do
Measured in people
Goals Sodium phenylbutyrate 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.
- Getting stronger137 people · 1 study
- Living longer137 people · 1 study
34 of the 36 indexed goals have no study of any kind behind Sodium phenylbutyrate
No study in people, animals or cells on this page reports a result for these. That does not prove Sodium phenylbutyrate does nothing for them. It does mean anything you have heard about Sodium phenylbutyrate and one of these did not come from a study cited here.
Show full evidence
What is Sodium phenylbutyrate?
In people, it is approved for a rare disease of ammonia build-up. A pill that paired it with a bile acid was approved for ALS and later pulled when a bigger trial failed. It targets two ageing processes at once: it helps misfolded proteins fold, and weakly changes how genes are switched. In mice, it did not extend lifespan in either sex.
This compound looked promising because it hits two items on the standard list of ageing hallmarks. One is the breakdown of protein quality control. 4-phenylbutyrate is a chemical chaperone, which helps misfolded proteins fold and eases stress in the cell's protein factory (the endoplasmic reticulum). Another is changes in how genes are switched on and off. It weakly blocks HDACs, enzymes that pack genes away.
It is also an approved drug, for urea cycle disorders, rare conditions where ammonia builds up. So its dosing and safety in people were already known. It has one more human record, as part of a two-drug pill for ALS (amyotrophic lateral sclerosis). That pill was later pulled from the market after its large final-stage trial failed.
In the mouse lifespan program's 2024 run, it did not make either sex live longer.
How does Sodium phenylbutyrate work?
It does two known things. As a chemical chaperone, it steadies half-folded proteins in a general way and calms the cell's alarm for misfolded proteins. That is why it is used where proteins misfold. As a weak HDAC blocker, it leaves genes less tightly packed and changes which genes are active. It also mops up extra nitrogen. It joins with glutamine to make a compound the kidneys pass out in urine. That is how it treats urea cycle disorders, and it has nothing to do with the ageing idea.
What have studies in people found about Sodium phenylbutyrate?
Approved for a rare metabolic disease, with a separate and telling history in ALS. Nothing on ageing.
- In 137 people with ALS (CENTAUR), a pill of sodium phenylbutyrate plus a bile acid, taurursodiol, slowed the loss of daily function a little over 24 weeks: 1.24 against 1.66 points a month. Strength, breathing and survival did not differ from the dummy pill. Side effects were mainly in the gut.
- That pill was approved for ALS on the strength of this small trial. It was pulled after a larger final-stage trial failed to confirm the benefit.
- In 11 children with a urea cycle disorder, switching to a newer form for a week kept ammonia about 25 percent lower. Side effects were mild. Everyone knew what they were taking.
- Approved for urea cycle disorders, where it works by mopping up nitrogen, not by helping proteins fold.
- The taste is a real problem for patients. It wears off fast, so it has to be taken often, in large amounts.
- At treatment doses it carries a lot of sodium, which matters for anyone with high blood pressure or heart failure.
- No human study has looked at lifespan, healthy years or anything else about ageing.
What this does not tell you: The urea cycle approval rests on mopping up nitrogen. It says nothing about the protein-folding idea. The ALS story is a warning, not support: an early good result did not hold up in a big enough trial. This site sees that pattern again and again. The mouse lifespan failure is the only direct test of the ageing idea, and it was a no.
The state of the research
Two separate failures for the same compound in the same few years is worth noting. Its mouse lifespan test found nothing. Its best-known human use, in ALS, was approved on a small trial and then pulled when the large final-stage trial did not hold up.
The protein-folding idea itself is not hurt much by this. 4-phenylbutyrate is a weak, blunt chaperone, and a failure with a blunt tool says more about the tool than the idea. But it is the only lifespan test the idea has had.
The National Institute on Aging runs the Interventions Testing Program at three separate labs: The Jackson Laboratory, the University of Michigan and the University of Texas Health Science Center at San Antonio. It uses UM-HET3 mice, a mixed breed made by crossing four strains, so a result cannot be a quirk of one strain. Compounds go in the food. Both sexes are tested. Each group is big enough to spot about a 10 percent change in lifespan. Results are checked with one test for typical lifespan and another for the longest-lived mice. The failures are published next to the wins. No other ageing research has all of that together. That is why a no from this program means much more than a no from one lab.
The evidence, in charts
Fig. 1a · how many people
148people, across 2 studies in people cited here
| Study | People | Share |
|---|---|---|
| CENTAUR, The New England Journal of Medicine 2020 | 137 | 93% |
| Molecular Genetics and Metabolism 2011 | 11 | 7% |
One study holds 93% of these people, so the total rests more on one study than its size suggests. 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. 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, 2011 to 2024, counted from the list of sources on this page.
Fig. 3 · legal status at a glance
US
Approved
UK
Approved
AU
Approved
CA
Approved
Approved in all 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. 5 · what the molecule is
- Kind of compound
- Small molecule
- Molecule weight
- 186.2 Da for the sodium salt. A small molecule, not a peptide.
- Half-life
- About 48 minutesUltra-short, minutes
- Chain length
- None on file
Half-life as stated on file: Roughly 0.8 hours for the parent compound, which is rapidly converted to phenylacetate and then conjugated, requiring multiple daily doses clinically.
No amino acid sequence is on file for Sodium phenylbutyrate, which is expected: a small molecule is not built from amino acids.
The studies we cite
- Study in people2020Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis.
In ALS, a pill combining sodium phenylbutyrate with a bile acid slowed the loss of daily function a little over six months, compared with a dummy pill. 137 people took part. The other measures of strength, breathing and survival did not differ. This small trial led to an approval that was pulled after a larger trial failed.
137 people with definite ALS randomised 2:1 double-blind to sodium phenylbutyrate 3 g plus taurursodiol 1 g, or placebo, for 24 weeks (CENTAUR). ALSFRS-R declined 1.24 versus 1.66 points per month (difference 0.42, 95% CI 0.03 to 0.81, p=0.03). The secondary outcomes (muscle strength, neurofilament, slow vital capacity, survival composites) did not separate from placebo. Adverse events were mainly gastrointestinal.
- Study in people2011Ammonia control in children with urea cycle disorders (UCDs); phase 2 comparison of sodium phenylbutyrate and glycerol phenylbutyrate.
Eleven children with a urea cycle disorder, already on sodium phenylbutyrate, were switched to a newer form for a week. Ammonia ran about 25% lower on the newer form. Side effects were mild on both. Eleven children, one week on each, no dummy pill.
11 subjects with urea cycle disorders on maintenance sodium phenylbutyrate (mean 12.4 g daily, 322 mg/kg/day) were switched open-label to an equimolar dose of glycerol phenylbutyrate, 7 days on each with 24-hour ammonia profiles. Ammonia was about 25% lower on glycerol phenylbutyrate, within the non-inferiority margin. Possibly related adverse events in 2 subjects on sodium phenylbutyrate and 4 on glycerol phenylbutyrate, all mild except one.
- Animal study2024Astaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002, dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not
In mice. In the NIA mouse lifespan program, 4-phenylbutyrate did not clearly make either sex live longer at the dose and method used.
Interventions Testing Program. 4-phenylbutyrate did not increase lifespan significantly at the dose and method of administration tested, in either sex.
Common questions
Has Sodium phenylbutyrate been tested in people?
Yes. 148 people given it across 2 completed trials cited here, 0 of which found nothing. In people, it is approved for a rare disease of ammonia build-up.
What is the Sodium phenylbutyrate dosage?
Approved medicine. No human dose established for unlabelled uses. Labeled amounts sit on the prescribing information. This page records what trials measured, not a personal dose. FDA-approved for urea cycle disorders, rare inherited conditions where ammonia builds up in the blood. It was also part of a combination drug approved for ALS (amyotrophic lateral sclerosis). That drug was later withdrawn after the study meant to confirm it failed. No ageing use.
Is Sodium phenylbutyrate FDA-approved?
FDA-approved for urea cycle disorders, rare inherited conditions where ammonia builds up in the blood. It was also part of a combination drug approved for ALS (amyotrophic lateral sclerosis). That drug was later withdrawn after the study meant to confirm it failed. No ageing use.
Does relieving endoplasmic reticulum stress extend lifespan?
The one lifespan test using a chemical chaperone found nothing in either sex. The compound is weak and blunt, so it is fairer to say the idea has been poorly tested than proven wrong. There is no good evidence in mammals that it extends lifespan.
What happened with the ALS drug?
A two-drug pill containing 4-phenylbutyrate was approved for ALS based on a small trial. It was pulled from the market after a larger final-stage trial failed to confirm the benefit. It is a textbook case of an early good result not holding up under proper testing.
Is it worth taking?
Nothing supports it for ageing. It also wears off fast, so it must be taken often. It carries a lot of sodium and famously tastes bad.