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Akg

Also known as: AKG, 2-oxoglutarate, alpha-ketoglutaric acid, 2-oxoglutaric acid, Alpha-ketoglutarate

Overview

Alpha-ketoglutarate (AKG) is a crucial endogenous metabolic intermediate, naturally synthesized within the mitochondria as a key component of the Krebs cycle (TCA cycle) during cellular respiration. It plays a vital role in energy metabolism and nitrogen balance within the body. As a dietary supplement, AKG is gaining attention for its potential benefits in areas such as healthy aging, muscle health, exercise performance, and recovery. Beyond its metabolic functions, AKG exhibits antioxidant properties and modulates immune and epigenetic pathways. While extensive preclinical research, particularly in animal models, highlights its diverse physiological roles, human clinical evidence is still emerging and somewhat limited. The current body of research, including systematic reviews, indicates a need for more high-quality randomized controlled trials to fully substantiate its efficacy and optimal usage in humans.

Benefits

AKG offers several potential benefits, primarily supported by preclinical and some preliminary human data. Its most prominent effect is on **longevity and healthspan**, where studies in mice have shown that AKG supplementation, particularly as calcium AKG (CaAKG), can extend lifespan and healthspan by reducing systemic inflammation and frailty. This is thought to involve the induction of anti-inflammatory cytokines like IL-10. For **muscle health**, AKG supports skeletal muscle regeneration by stimulating muscle satellite cells and promoting beneficial macrophage polarization. It enhances protein synthesis, inhibits muscle degradation, and reduces fibrosis, suggesting a role in preventing muscle atrophy in conditions like sarcopenia and cachexia. In the context of **exercise performance**, AKG supplementation has been linked to improved endurance, reduced fatigue, and faster post-exercise recovery in active individuals. A meta-analysis indicated a modest improvement in post-exercise fatigue recovery with nutritional supplements including AKG. Secondary benefits include its **antioxidant effects** and modulation of nitrogen/ammonia balance, contributing to overall metabolic health. Older adults may particularly benefit from improved muscle maintenance and reduced frailty, while athletes could experience enhanced recovery and performance. While animal studies show significant effects, human data are still preliminary, with modest effect sizes reported for exercise recovery.

How it works

Alpha-ketoglutarate (AKG) functions as a central metabolic hub, primarily through its role in the Krebs cycle, where it is essential for cellular energy production. Beyond this, AKG modulates immune responses by inducing the production of anti-inflammatory cytokines, such as Interleukin-10 (IL-10), which helps to suppress chronic inflammation. In muscle tissue, AKG supports regeneration by activating muscle satellite cells and influencing macrophage polarization, leading to enhanced protein synthesis and reduced muscle breakdown. It also plays a critical role in nitrogen metabolism by facilitating the removal of excess ammonia, thereby contributing to detoxification. AKG interacts with various body systems, including mitochondrial metabolism, the immune system, and muscle tissue repair mechanisms, by targeting key enzymes in the Krebs cycle, epigenetic regulators, and inflammatory pathways. Oral supplementation is generally well-absorbed, though specific bioavailability data for different forms are limited.

Side effects

Alpha-ketoglutarate (AKG) is generally considered safe at typical supplemental doses, with no major adverse effects reported in animal or limited human studies. There are no well-documented common side effects, though mild gastrointestinal discomfort is theoretically possible but rarely reported. Data on uncommon or rare side effects are insufficient, and no serious adverse events have been reported in the reviewed literature. Regarding drug interactions, no significant interactions have been documented, but caution is advised when combining AKG with other metabolic or immunomodulatory agents due to its broad physiological roles. There are no clearly established contraindications, but caution is recommended for individuals with pre-existing metabolic disorders until more comprehensive data are available. While studies have included older adults and athletes, the safety and efficacy of AKG in special populations such as pregnant or lactating women have not been adequately studied, and its use in these groups should be approached with caution.

Dosage

The minimum effective dose for Alpha-ketoglutarate (AKG) is not yet well-established, as human studies often vary widely in their dosing protocols. Common supplement doses typically range from 1000 to 2000 mg per day, often administered as arginine alpha-ketoglutarate (AAKG) or calcium alpha-ketoglutarate (CaAKG). However, specific dosing recommendations for AKG-only formulations lack a strong consensus. There is no established maximum safe dose, and safety data beyond typical supplement ranges are limited. Some evidence suggests that timing AKG supplementation around exercise may improve recovery, but more research is needed to confirm optimal timing. Calcium alpha-ketoglutarate (CaAKG) is a common form used in research, particularly for longevity studies, while arginine alpha-ketoglutarate (AAKG) is popular in sports nutrition. While co-administration with other nutrients might influence absorption, definitive data on this are lacking, and no specific cofactors are identified as necessary for AKG's efficacy.

FAQs

Is AKG safe?

Current evidence suggests AKG has a good safety profile at typical supplement doses, with no major adverse effects reported in studies.

Does AKG improve muscle growth?

Evidence supports AKG's role in muscle regeneration and preventing atrophy, but human clinical data specifically on muscle growth are limited and require further research.

Can AKG extend lifespan in humans?

Promising animal data suggest lifespan extension, but human evidence is currently lacking, and more research is needed to confirm this effect in people.

When should AKG be taken?

Some research indicates that taking AKG around exercise may be beneficial for recovery, but optimal timing for other benefits is not yet clear.

Is arginine alpha-ketoglutarate the same as AKG?

AAKG is a compound combining arginine and AKG. While it contains AKG, its effects may differ due to the additional presence and role of arginine.

Research Sources

https://pmc.ncbi.nlm.nih.gov/articles/PMC8508957/ – This animal study investigated the effects of calcium alpha-ketoglutarate (CaAKG) on lifespan and healthspan in mice. It found that CaAKG supplementation extended both lifespan and healthspan, reducing systemic inflammation and frailty, suggesting a potential role in anti-aging interventions.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11597751/ – This systematic review analyzed 112 peer-reviewed articles on AKG, concluding that it promotes muscle regeneration, prevents atrophy, and improves exercise performance. The review highlighted that while preclinical data are strong, more high-quality human randomized controlled trials are needed to confirm these benefits.
https://research.vu.nl/files/160079366/AlphaKetoglutarate_dietary_supplementation_to_improve_health_in_humans.pdf – This systematic review explored the potential antioxidant, metabolic, and immune benefits of AKG in both human and animal studies. It concluded that AKG shows promise in these areas but emphasized the sparsity of recent large-scale human clinical trials, highlighting significant research gaps.
https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1567438/full – This meta-analysis evaluated the impact of various nutritional supplements, including AKG, on post-exercise fatigue recovery. It found that these supplements collectively improved post-exercise fatigue recovery with a modest effect size, suggesting a potential benefit for athletes, though AKG-specific effects were not isolated.
https://vkm.no/download/18.645b840415d03a2fe8f26066/1502798687898/Risk+assessment+of+%22other+substances%22+-+L-arginine+and+arginine+alpha-ketoglutarate.pdf – This risk assessment report evaluated the safety of L-arginine and arginine alpha-ketoglutarate (AAKG) at typical supplement doses. It concluded that there were no safety concerns at doses of 1000-2000 mg/day, but noted that insufficient human safety data prevented a formal dose evaluation for higher intakes.