Alpha-Ketoglutarate (AKG)
Krebs-cycle metabolite that drops sharply with age; supplementation extended lifespan and healthspan in mice.
Summary
Alpha-ketoglutarate is made in cells, is used in the Krebs cycle for energy, and is a cofactor for DNA and histone demethylation enzymes; she cites a 10-fold decrease between ages 40 and 80. In mice, supplementation extended lifespan about 10% and compressed late-life frailty, with lower inflammatory cytokines, a reduced senescence inflammatory phenotype, fat browning and preserved ovarian function. Human data are limited: a manufacturer-run trial of AKG plus vitamins, athlete trials with modest effects, and an ongoing placebo-controlled trial (ABLE). A later post notes AKG activated autophagy to stimulate the hair-growth phase.
Takes a powdered arginine supplement that includes alpha-ketoglutarate, citing its 'many positive benefits for longevity.'From My Current Supplement Stack for Longevity
The evidence
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Human trial
A clinical trial of alpha-ketoglutarate plus vitamins in 42 people aged 41-79, run by the manufacturer (placebo design not described), reported an 8-year reduction in biological age after 7 months.
Read the study Discussed in Alpha-Ketoglutarate for Longevity -
Human trial
In male athletes aged 30-50, arginine alpha-ketoglutarate at 12 g/day gave some improvement in specific exercises such as bench press and was well tolerated.
Read the study Discussed in Alpha-Ketoglutarate for Longevity -
Animal
In mice, alpha-ketoglutarate extended lifespan by about 10% and significantly improved healthspan, reducing time spent frail or with diseases of aging.
Read the study Discussed in Alpha-Ketoglutarate for Longevity -
Animal
In the same mouse research, AKG prevented the age-associated rise in cytokines in females, increased anti-inflammatory IL-10 from T cells, and reduced senescent-cell inflammatory signaling.
Read the study Discussed in Alpha-Ketoglutarate for Longevity -
Animal
Dietary AKG increased browning ('beige-ing') of fat in mice.
Read the study Discussed in Alpha-Ketoglutarate for Longevity
Doses used in studies
Amounts reported in the research, not dosing recommendations.
| Dose | Context |
|---|---|
| 12 g/day arginine alpha-ketoglutarate, split into 3 doses | Male athletes aged 30-50 (exercise performance, safety) |
| 12 g/day arginine alpha-ketoglutarate | Male athletes; little effect on nitric oxide or blood flow |
Cautions
- The FDA considers alpha-ketoglutarate GRAS (generally regarded as safe); she also notes it has several anticancer properties.
- Arginine plus AKG products may lower blood pressure; check interactions with blood pressure medications, blood thinners, anticoagulants, erectile dysfunction drugs, nitrates and diabetes medications.
- The supplement level needed to increase healthspan in humans is unknown.