Gpld1 dosage and evidence
Written by Aaron CuhaReviewed Sep 2026
The short answer
Gpld1 is a liver enzyme released into the blood during exercise. In mice, it passed the brain benefits of running to old mice that had not run. It is higher in active older people, and has never been given to anyone.
Evidence grade for Gpld1: 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
4 effects reported, 4 unwanted, by people using it, not a trial
Goal pages: Brain, memory and mood
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 an enzyme your liver puts into the blood when you work out. In mice, it passed the brain gains of running to old mice that had not run.
What people take it for
- The brain benefits of exercise, without the exercise.
- Memory in later life.
What studies in people showed
Nobody has been given this. No trial that gives it to people is registered. The human record is 25 people measured once. Healthy adults aged 65 to 85 were sorted as inactive or very active. Movement trackers checked which. Levels were measured with thinking tests and brain scans, at one visit. In mice, plasma from old animals that had run was given to old animals that had not. It passed on the brain gains. Raising the enzyme with no running at all improved repair and memory. A 2026 paper named what it acts on. It sits on the blood vessels of the brain.
What people report
Reports, not study results
The good
- We have not collected user reports on this one yet.
The bad
- This enzyme has more than a hundred likely targets. Giving it would cut a lot besides the one that matters.
- Nobody has given it to a person, so there is no safety data.
- The one human study is 25 people measured at a single visit. It cannot show cause.
- Finding more of an exercise enzyme in people who exercise is close to saying the same thing twice.
Where these come from: The 25 person study and the mouse results come from the studies on this page. No user reports exist.
My bottom line
A good mouse story with a 25 person snapshot behind it. Until somebody aims it better, just do the workout.
An opinion, not a finding. I am a coach, not a doctor.
What it has been measured to do
Measured in people
Goals Gpld1 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.
- Memory and thinkingno headcount stated · 1 study
35 of the 36 indexed goals have no study of any kind behind Gpld1
No study in people, animals or cells on this page reports a result for these. That does not prove Gpld1 does nothing for them. It does mean anything you have heard about Gpld1 and one of these did not come from a study cited here.
Show full evidence
What is Gpld1?
Gpld1 is a liver enzyme released into the blood during exercise. In mice, it passed the brain benefits of running to old mice that had not run. It is higher in active older people, and has never been given to anyone.
Nobody has been given Gpld1. There is no registered trial that gives it to people.
The human evidence is measurement in small groups. The original 2020 Science paper reported more Gpld1 in the blood of active, healthy older people. A 2025 GeroScience study recruited healthy men and women aged 65 to 85, sorted as either inactive or highly active, and used movement trackers to confirm which. It measured GPLD1 in their blood, tested their thinking and scanned their brains, all at one visit. The registered study, NCT04645134, enrolled 25 people and watches rather than treats.
In 2020 a Science paper found that plasma from old mice that had exercised, given to old mice that had not, passed on the running benefits for new brain cell growth and memory. Screening that plasma turned up Gpld1, an enzyme made in the liver that cuts a kind of anchor holding proteins to cell surfaces. It rose after exercise and went with better memory in old mice. Raising Gpld1 in old mice, with no exercise at all, improved their ability to repair tissue and their memory. The authors describe a route from liver to brain.
A 2026 Cell paper from the same line of work went further in mice. It named the exact target that matters: an anchored enzyme sitting on the blood vessels of the brain. Copying the age-related rise in that enzyme harmed transport into the brain and harmed memory in young mice. Blocking it did what Gpld1 does in old mice, and improved things in a mouse model of Alzheimer disease.
How does Gpld1 work?
In mice, Gpld1 is a liver enzyme released into the blood after exercise. It cuts a kind of anchor that holds certain proteins onto cell surfaces, setting those proteins free. The 2026 Cell work names the one that carries the memory effect: an anchored enzyme on the blood vessel lining of the brain. Levels of it in brain vessels rise with age. Copying that rise harmed transport into the brain and harmed memory in young mice. Blocking it brought gene activity in the memory centre back to a young pattern and restored memory in old mice. Gpld1 has more than a hundred likely targets, which is why naming the right one mattered. None of this has been shown in a person.
What have studies in people found about Gpld1?
Watching only, and small. GPLD1 in the blood has been measured and found higher in physically active older adults, in a 25-person study measured at one moment and in the original 2020 report. Nobody has been given Gpld1.
- GeroScience 2025, "Associations between physical activity, brain health, cognitive function, and circulating GPLD1 in healthy older (65-85 years) individuals" (NCT04645134): 25 healthy adults aged 65 to 85, recruited as either inactive or highly active, with activity confirmed by movement trackers. GPLD1 in the blood, memory and thinking tests, and brain scans, all at one visit. It watches rather than treats, and everything was measured at one moment.
- Science 2020: more Gpld1 in the blood of active, healthy older people. That is a measurement inside a mouse paper, with no trial behind it.
- No trial that gives Gpld1 to people is registered, for anything.
What this does not tell you: 25 people measured at one visit cannot show which way cause runs, let alone prove an effect. Active older adults differ from inactive ones in many ways. And finding more of an exercise-released enzyme in people who exercise is close to saying the same thing twice. Nothing in the human record shows that raising Gpld1 would improve anything, and nobody has tried. Giving an enzyme with more than a hundred possible targets raises obvious questions about what else it would cut, and the mouse work is only now starting to answer them.
The state of the research
The human record here is 25 people measured once. That is worth stating plainly, because the Science paper's one human sentence, that Gpld1 is higher in active older people, gets repeated as if it were a trial result. It is a link found at one moment in time.
Gpld1 is one of the better worked out exercise factors, because the mouse work did the whole chain. Moving plasma across reproduced the effect. The factor was named. Giving that factor alone reproduced the effect without any exercise. And in 2026 the thing it acts on was named. Most exercise factors have far less.
The problem with moving this to people is specific, and worth saying rather than glossing over. Gpld1 is an enzyme with more than a hundred likely targets. Giving it to a person would cut a great deal besides the one target that carries the memory effect. The 2026 Cell paper points at a different and more workable plan: block the target instead of giving the enzyme. That version is more likely to become a drug than Gpld1 itself. It is also further away from anything a person can get today.
The evidence, in charts
Fig. 1a · how many people
25people, across 1 study in people cited here
| Study | People | Share |
|---|---|---|
| ClinicalTrials.gov 2021 | 25 | 100% |
The whole total is one study of 25. 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 4 sources here are studies in people. The rest are not.
- Study in people · done in people250%
- Animal study · done in animals250%
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, 2020 to 2026, 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
- Biologic
- Molecule weight
- Not on file
- Half-life
- None on file
- Chain length
- None on file
No amino acid sequence is on file for Gpld1, so none is drawn rather than guessed from a name.
The studies we cite
- Study in people2025Associations between physical activity, brain health, cognitive function, and circulating GPLD1 in healthy older (65-85 years) individuals
Nobody was given anything in this study, and it cannot show cause. Healthy men and women aged 65 to 85 were recruited as either inactive or highly active, with movement trackers used to confirm which. GPLD1 was measured once, from fasting blood, at a single visit. Thinking was tested and brains were scanned on the same day. Everything was captured at one moment in time. That design can show that two things travel together. It cannot show that one causes the other.
Healthy men and women aged 65 to 85 with body mass index 20 to 35, recruited as either inactive or highly active by a rapid activity assessment score and verified by accelerometry. Circulating GPLD1 was measured from fasting blood at a single clinical visit alongside Mini-Mental State Examination, the NIH Toolbox Cognition Battery, and brain MRI and functional MRI. Cross-sectional and observational: it measures association, not effect.
- Study in people2021Physical Activity and Cognitive Function in Older Adults: A Novel Role for GPLD1
This is the registration for the human GPLD1 work, and it is small. Pennington Biomedical Research Center enrolled 25 people, starting in April 2021, and listed it as completed. It is an observational study, measured at a single point in time. Nobody was given GPLD1 or anything else. The mouse claims about this protein rest on mouse work, not on this.
Registry record for the human GPLD1 work. Sponsor Pennington Biomedical Research Center, observational cohort with a cross-sectional time perspective, 25 participants enrolled, start 1 April 2021, listed as completed. An observational study of 25 people, not an intervention.
- Animal study2020Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain
In mice, with one human measurement inside it. Plasma from old mice that had exercised, given to old mice that had not, passed on the running benefits for new brain cell growth and memory. The enzyme Gpld1, made in the liver, rose after exercise and went with better memory. Raising it in old mice, with no exercise, improved tissue repair and memory. The paper also reports more Gpld1 in the blood of active, healthy older people. Funded by the US National Institutes of Health.
Mouse, with a human measurement component. Plasma from exercised aged mice transferred the effects of exercise on adult neurogenesis and cognition to sedentary aged mice. Plasma Gpld1, a liver-derived GPI-degrading enzyme, rose after exercise and correlated with improved cognition; increasing systemic Gpld1 in aged mice improved age-related regenerative and cognitive impairments without exercise. Gpld1 concentrations in blood were also increased in active, healthy elderly humans. NIH funded.
- Animal study2026Liver exerkine reverses aging- and Alzheimer's-related memory loss via vasculature
In mice, the researchers found what Gpld1 acts on to help memory: an anchored enzyme sitting on the blood vessels of the brain. Copying the age-related rise in that enzyme harmed transport into the brain and harmed memory in young mice, and blunted what Gpld1 could do in old ones. Blocking it brought gene activity in the memory centre back to a young pattern and restored memory. In a mouse model of Alzheimer disease, either raising Gpld1 or blocking that enzyme cut the sticky plaque build-up and improved memory.
Mouse. GPI-anchored tissue-nonspecific alkaline phosphatase on the brain vasculature was identified as the Gpld1 substrate mediating cognitive rejuvenation. Mimicking age-related increases in cerebrovascular levels of that enzyme impaired blood-brain transport and cognition in young mice and blunted Gpld1's benefit in aged mice, while inhibiting it restored youthful hippocampal transcriptional signatures and rescued cognition. In an Alzheimer disease model, raising Gpld1 or inhibiting the enzyme reduced amyloid beta pathology and improved cognition.
Common questions
Has Gpld1 been tested in people?
Not in a completed trial cited here. 2 human studies where nobody was given it. Gpld1 is a liver enzyme released into the blood during exercise. In mice, it passed the brain benefits of running to old mice that had not run. It is higher in active older people, and has never been given to anyone.
What is the Gpld1 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 Gpld1 FDA-approved?
Not approved, and never given to a person. No study that gives Gpld1 to people is registered for any use. The only registered human study just measures it and does not give it.
Can Gpld1 give you the benefits of exercise?
In old mice, raising Gpld1 with no exercise at all improved their ability to repair tissue and their memory. That is the finding that caused the interest. Nobody has been given it, so the question is open in people. And the higher Gpld1 in active older adults is a link measured at one moment, in 25 people.
Is there a human trial?
Only one that watches rather than treats. NCT04645134 at Pennington Biomedical Research Center enrolled 25 healthy adults aged 65 to 85. It measured GPLD1 in the blood alongside thinking tests and brain scans, at one visit. No trial that gives Gpld1 to people is registered anywhere.
What does Gpld1 actually do?
It is a liver enzyme that cuts a kind of anchor holding proteins onto cell surfaces, setting those proteins free. A 2026 Cell paper named the target that matters: an anchored enzyme on the blood vessels of the brain. Blocking that enzyme did what Gpld1 does in old mice. All of that is in mice only.