Ca-AKG dosage: what the trial data actually supports

There is no established optimal Ca-AKG dosage for longevity. The dose most often seen in modern healthy-aging research is about 1,000 mg per day, but that number comes from the Rejuvant observational work and the ABLE trial design — not from a dose-ranging study proving that 1 g is best.

Human Ca-AKG studies have actually used a much wider range of exposures depending on the population and purpose. This guide separates those research doses from a personal dosing recommendation. For the wider evidence, see our Ca-AKG evidence guide and Ca-AKG Data Center.

Ca-AKG dosage: the short answer

If you are asking what dose has been used in modern longevity research, 1 g/day of sustained- or delayed-release Ca-AKG is the clearest answer.

If you are asking what dose has been proven to slow aging, extend lifespan or improve healthspan in humans, the answer is: none has been established.

If you are asking what doses humans have tolerated in published Ca-AKG studies, the range is broader than 1 g/day and depends heavily on the clinical context.

What doses have human Ca-AKG studies actually used?

Study	Population	Ca-AKG exposure	Duration	What the study can tell us
Cynober 1990	6 healthy men	3.6 g single oral dose	Acute	Shows oral Ca-AKG is metabolically active; not a longevity dose study.
Zimmermann 1996	14 haemodialysis patients	Mean 4.5 g/day	36 months	Long human exposure history in a very different clinical population.
Filip 2007	76 postmenopausal women with osteopenia	6 g/day	24 weeks	Randomized human efficacy and tolerability data for a bone endpoint.
Demidenko 2021	42 self-selected Rejuvant users	About 1 g/day sustained-release Ca-AKG	4–10 months, mean ~7	Observational biological-age signal; not dose-response evidence.
ABLE protocol	120 middle-aged adults	1 g/day sustained-release Ca-AKG	6 months + 3-month follow-up	Randomized trial dose; efficacy results are not yet published.

The acute healthy-volunteer study directly administered 3.6 g of Ca-AKG [1]. A small dialysis cohort later received a mean 4.5 g/day for 36 months [2]. The 2007 randomized osteopenia trial used 6 g/day, divided as two chewable tablets three times daily with meals [3].

Those older studies are useful for exposure and safety context, but they do not establish a longevity dose. Their populations, endpoints and formulations were different.

Why does 1,000 mg/day keep appearing in longevity supplements?

The number mainly comes from the modern delayed-release Ca-AKG lineage.

The 2021 Rejuvant retrospective involved a proprietary sustained-release product providing approximately 1 g/day of Ca-AKG plus vitamin A in the male formulation or vitamin D in the female formulation [4].

The ABLE randomized trial protocol then adopted 1 g/day of sustained-release Ca-AKG for six months [5]. A later recruitment publication confirmed that 120 participants were enrolled on that design, but it did not report efficacy or safety outcomes [6].

So 1 g/day is best described as a research-anchored modern longevity dose. It is not an RDA, an FDA-approved dose, or a dose proven to extend life.

Is 1,000 mg/day the optimal Ca-AKG dose?

We do not know.

No published dose-ranging longevity trial has compared, for example, 500 mg versus 1 g versus 2 g per day while holding formulation and population constant.

That means we cannot say whether:

• 500 mg would produce the same result as 1 g;
• 2 g would produce a larger effect;
• higher doses would add only calcium exposure and cost; or
• the formulation matters more than the milligram number.

The correct interpretation is therefore: 1 g/day is studied, not optimized.

Does delayed-release Ca-AKG change the dosage question?

Possibly, but the evidence does not justify converting the observational difference into a dose-equivalence formula.

In the 2026 cohort of 4,260 health-conscious adults, delayed-release AKG users had a lower DNA methylation Age Residual in cross-sectional analysis, while plain non-delayed AKG showed a smaller, statistically non-significant association [7].

That does not prove that delayed release is more potent milligram-for-milligram. The delayed-release product also contained vitamins, participants were not randomized, exposure details were incomplete, and the longitudinal delayed-release signal did not remain significant after fuller adjustment.

There is no validated conversion such as “1 g delayed-release equals 2 g standard Ca-AKG.” No head-to-head randomized dose study has established one.

What does the mouse dose translate to in humans?

It should not be used to set a human supplement dose.

The 2020 Shahmirzadi study fed C57BL/6 mice chow containing 2% Ca-AKG from 18 months of age [8]. That exposure produced important preclinical findings, but the audited study record does not establish a validated human-equivalent Ca-AKG dose.

Simple body-weight or body-surface-area conversions can create a neat-looking number without accounting for species pharmacokinetics, continuous dietary exposure, absorption, salt chemistry or tissue concentrations. We therefore do not use the mouse dose to recommend a human dose.

Should Ca-AKG be taken once daily or split?

No trial has directly compared once-daily versus split dosing for a longevity outcome.

The study designs themselves show that both approaches have been used for different reasons. ABLE uses a 1 g/day sustained-release product, while the 2007 osteopenia trial divided 6 g/day across three meal-time doses [5] [3].

Those designs do not prove that one schedule is superior. If you are comparing morning versus evening, with food versus empty stomach, or medication spacing, see when to take Ca-AKG.

How long does Ca-AKG take to work?

There is no established “time to effect” for longevity because a clinical longevity benefit has not been demonstrated.

The available durations tell us when researchers measured outcomes, not how long a person should expect to wait for a benefit:

• The Rejuvant retrospective compared methylation age after 4–10 months of self-directed use, averaging about seven months [4].
• ABLE is designed around six months of supplementation and three months of follow-up [5].
• The randomized osteopenia trial assessed outcomes at 12 and 24 weeks [3].

These study durations should not be turned into promises such as “you will notice results after six months.”

What is the maximum safe Ca-AKG dose?

No formal tolerable upper intake level has been established for Ca-AKG itself.

Importantly, the human literature does include exposures above 2 g/day. A healthy-volunteer study used a single 3.6 g dose [1], one dialysis cohort averaged 4.5 g/day for three years [2], and the osteopenia RCT used 6 g/day for 24 weeks [3].

That does not make 4–6 g/day an appropriate self-directed longevity dose. Dialysis patients have very different calcium, phosphate and renal physiology, and the 6 g/day study was designed for bone metabolism rather than healthy aging.

The best conclusion is narrower: human exposure above 1 g/day exists, but there is no dose-ranging evidence defining an optimal benefit-risk range for healthy adults using Ca-AKG for longevity.

Calcium load matters

Ca-AKG is a calcium salt, so increasing the Ca-AKG dose also increases calcium intake.

The exact elemental-calcium amount depends on the salt's chemical form, hydration state and how the manufacturer declares the ingredient. Pure calcium alpha-ketoglutarate salts are roughly one-fifth to one-quarter calcium by mass. Check the product's Supplement Facts rather than assuming every 1 g Ca-AKG serving contains exactly the same amount.

This matters most if you already use calcium supplements, have significant kidney disease or have a history of calcium-containing kidney stones.

What about medication timing?

Ca-AKG-specific interaction trials are lacking. The practical interaction concern comes largely from its calcium component.

Calcium can reduce absorption of several medicines, including levothyroxine, tetracycline and quinolone antibiotics, oral bisphosphonates and iron. The exact spacing instructions depend on the medicine, so follow the medication label or pharmacist's advice rather than applying one universal four-hour rule.

For the broader safety evidence, see Ca-AKG side effects and safety.

What dose should you take?

This page can tell you what has been studied; it cannot determine a personal dose.

For a healthy adult considering Ca-AKG specifically for longevity, the most defensible research context is that 1 g/day is the common modern sustained-release study dose, while no effective or optimal longevity dose has been established.

Going higher is not automatically “more evidence-based.” Older studies used larger doses for different clinical indications, and there is no human dose-response trial showing that a higher longevity dose produces a better outcome.

Bottom line

Ca-AKG does not have an established recommended daily allowance or proven longevity dose.

1,000 mg/day is the most relevant modern longevity research dose because it is used in the Rejuvant observational work and the ABLE randomized design. But human Ca-AKG studies span much larger exposures, including 3.6 g acutely, about 4.5 g/day in a long-term dialysis cohort and 6 g/day in the osteopenia RCT.

Those studies show why “all human trials converge on 1 g” is incorrect. Dose, formulation, population and endpoint all matter. The evidence currently supports calling 1 g/day studied, not optimal.

For the full Ca-AKG evidence hierarchy, return to the Ca-AKG pillar.