The Headline Number
Eight years. That is how much younger a group of supplement users appeared on a DNA methylation test after an average of seven months on Rejuvant, an alpha-ketoglutarate (AKG) formulation with vitamins. The finding appeared in Aging (Albany NY) in November 2021, with a p-value of 6.538×10⁻¹². It is the kind of figure that goes viral.
It is also the kind of figure that needs a closer look. The study had no placebo group.
What the Researchers Actually Did
The paper is a retrospective analysis, not a randomized trial. Here is the design as reported:
- Participants: 42 individuals taking Rejuvant, an alpha-ketoglutarate-based formulation that also contains vitamins.
- Duration: an average of about 7 months, with a range of 4 to 10 months.
- Measurement: DNA methylation (DNAm) age using the TruAge test, taken at baseline and again at the end of supplementation.
- Result: an average decrease in biological age of roughly 8 years.
- Consistency: a large majority of participants showed a decrease.
- Subgroup signal: people who were chronologically and biologically older appeared to benefit more.
The authors call the result "noteworthy" and describe the product as "an intriguing candidate to affect human aging." They also state that continued testing, "particularly in a placebo-controlled design, is required."
Why DNA Methylation Clocks Are Used
Human lifespan is too long to run survival studies on every promising compound. Researchers therefore use biomarkers such as DNAm clocks, which read patterns of methylation across the genome and convert them into an estimated biological age. Many interventions extend lifespan in animal models, but few have been validated in people. Clocks are an attractive shortcut for that reason.
AKG has a reasonable background story. It is a metabolite in the Krebs cycle, and preclinical work in animals has linked it to longer healthspan. That is the context in which this human data was generated. But a clock is still a proxy. A drop on a clock is not the same as living longer or staying healthier.
Why the Number Needs a Placebo Trial
The p-value looks overwhelming, but a tiny p-value only says the change is unlikely to be random noise within this dataset. It does not say the supplement caused the change. Several issues stand in the way of that conclusion.
1. No control group. Without a comparison group taking placebo or nothing, there is no way to tell how much of the shift came from Rejuvant and how much from everything else. That includes lifestyle changes, seasonal effects, and test variability.
2. Retrospective, self-selected users. These were customers who chose to buy the product and then had their data analyzed afterward. People who start a longevity regimen often change other habits at the same time, such as diet, sleep, and exercise.
3. Possible regression to the mean. People whose first reading is unusually high tend to score lower on a retest, even with no intervention. The reported larger benefit in older and biologically older participants is exactly the pattern regression to the mean can produce, though the data cannot separate that from a real effect.
4. Measurement noise. An eight-year swing in under a year is far larger than the change you would expect from natural aging. Large shifts like that should make a reader ask how reproducible the test is, and whether the result reflects durable biology or fluctuation.
5. Conflicts of interest. The paper discloses that TruMe, the testing company, entered a customer service agreement in July 2019 to test Ponce de Leon Health customers taking Rejuvant. The paper states that neither company has cross-ownership or other financial interests to report. B.K. Kennedy, a coauthor, is a scientific consultant and board member for Ponce de Leon Health, and other coauthors are affiliated with the companies involved. That does not invalidate the data, but it is a reason to want independent replication.
What This Means for You
What the paper says about dose: The abstract does not give a dose. If you are evaluating this seriously, read the full text (PMC8660611) and the product label rather than relying on headlines. Calcium alpha-ketoglutarate (Ca-AKG) products in the wider market vary in serving size, so do not assume a figure from another brand matches what was used here.
Timing: The participants used the product for 4 to 10 months, averaging about 7. That is the only duration the data cover. There is no evidence here about long-term use, or about what happens to the clock reading after stopping.
- Healthy adults who are interested in longevity and comfortable treating this as an experiment, not a proven therapy.
- People who already track biomarkers and would want a control period, such as repeat baseline tests, to understand their own test variability.
Who should skip it or talk to a clinician first:
- Anyone who is pregnant or nursing.
- People with kidney disease, or those with conditions affecting calcium handling.
- Anyone taking prescription medication, since interactions have not been addressed in this paper.
- Anyone hoping a supplement can substitute for exercise, sleep, or medical care.
Why to stay skeptical:
- An 8-year "reversal" with no control group is a hypothesis, not a result.
- Clock changes are not clinical outcomes. The paper shows no data on disease risk, function, or survival.
- Wait for a randomized, placebo-controlled trial before treating the number as real.
The Bottom Line
This study is best read as a starting signal. A consistent drop across 42 users is interesting enough to justify a proper trial, and the authors say as much. As evidence that a supplement turns back the clock by eight years, it falls short. Until a placebo-controlled study replicates it, the headline number is a reason to run the experiment, not a reason to buy the product.
This article is for informational purposes and is not medical advice.
