The Anti-Aging & Longevity Effects of Alpha-Ketoglutarate (2025)

What Is Calcium Alpha-Ketoglutarate?

Calcium alpha-ketoglutarate is a compound formed from calcium and alpha-ketoglutarate (AKG), a key intermediate in the Krebs cycle. The Krebs cycle, also known as the citric acid cycle, is essential for energy production in aerobic organisms. First discovered by Hans Adolf Krebs in 1937, this cycle generates energy by oxidizing nutrients. Ca-AKG combines the benefits of calcium, vital for bone health, with AKG, crucial for metabolic pathways.

How It Works in the Body

Ca-AKG performs several functions within the body, acting as a key player in various metabolic pathways. It participates in amino acid metabolism, energy production, and cellular signaling. This compound helps convert nutrients into energy via the Krebs cycle, contributing to cellular vitality and reducing the impact of aging.

It plays a crucial role in the cell energy, cell metabolism, bone mass, amino acid/protein synthesis, epigenetic regulation, stemness and differentiation, fertility and reproductive health

Clinical research shows that Ca-AKG may support muscle health by promoting muscle protein synthesis and reducing muscle breakdown, particularly after trauma or surgery. Studies indicate it might help maintain muscle mass and reduce muscle loss in aging individuals (R). Additionally, Ca-AKG has potential anti-inflammatory properties that could contribute to overall health and longevity.

By influencing DNA methylation, Ca-AKG may also play a role in regulating gene expression, further promoting healthy aging. This compound helps maintain cellular energy homeostasis, contributing to optimal function and vitality as we age.

The potential anti-aging benefits of Ca-AKG are promising, supporting the idea that maintaining optimal levels can combat age-related declines and promote well-being.

The role of alpha-ketoglutarate in aging and longevity

Alpha-ketoglutarate (AKG) is a small molecule naturally present in our body. During aging, levels of AKG decline.

AKG is used by the mitochondria, which convert this substance into energy, Besides, alpha-ketoglutarate has various other functions in the body.

Alpha-ketoglutarate and lifespan

A recent study in mice, conducted at the Buck Institute, one of the world-leading aging research institutes, found that alpha-ketoglutarate extended lifespan in old mice by approximately 12% to 16% (R).

Very interestingly, alpha-ketoglutarate extended healthspan by an impressive 40% to 52% : the mice didn’t only live longer, they stayed healthier and disease-free for considerably longer.

AKG also significantly reduced hair graying in elderly animals (R).

How alpha-ketoglutarate extends lifespan

AKG impacts and helps control aging in various ways.

First, AKG has epigenetic effects. The epigenome is the intricate molecular machinery surrounding the DNA that decides which genes are switched on or off. The older we get, the more the epigenome becomes dysregulated: some genes that should be silent are switched on, and some genes that should be active (like cancer protection genes) are switched off. This epigenetic dysregulation is one of the reasons why we age.

An important enzyme that regulates the epigenome is TET (ten-eleven translocation). This enzyme can reprogram the epigenome to a more youthful state. TET needs AKG to function properly and also requires vitamin C to carry out its work properly (R). That is why we added vitamin C (ascorbic acid) to the NOVOS formulation, together with calcium alpha-ketoglutarate, for added synergistic effects.

Amino Acid Metabolism

AKG is also at the nexus of carbohydrate and amino-acid metabolism. The older we get, the less flexible cells become at switching between carbohydrates and amino acids to produce energy. AKG, however, can help cells to maintain this metabolic flexibility for longer.

AKG also improves mitochondrial health, which makes sense, given this substance is also an energy source for the mitochondria.

AKG activates AMPK, an important metabolic and longevity switch (R).

Besides that, we see that alpha-ketoglutarate can help the body to detoxify: alpha-ketoglutarate helps the body to get rid of ammonia. Ammonia is a waste product from the protein metabolism that tends to accumulate in the body (the more protein you eat, the more ammonium you produce). As we get older, the body has more difficulty getting rid of the ammonia. Too much ammonia is toxic, and alpha-ketoglutarate helps to detoxify the body from ammonia.

Also, given that alpha-ketoglutarate serves as a fuel for the mitochondria, it could provide more energy and endurance. That is why athletes and bodybuilders have been taking alpha-ketoglutarate for decades. However, some studies show that alpha-ketoglutarate does not provide substantially extra energy (R). In these studies, however, the arginine-alpha-ketoglutarate form is taken, while ideally, the AKG form without arginine but with calcium should be taken, at least for longevity purposes.

AKG also plays a role in maintaining stem cell health (R), and in bone and gut metabolism (R).

Calcium alpha-ketoglutarate is also involved in collagen production, can reduce fibrosis, and can thus play a role in maintaining healthy, youthful skin and delaying aging (R,R).

Promoting Longevity and Reducing Cellular Aging

Calcium Alpha-Ketoglutarate (Ca-AKG) plays a significant role in extending lifespan and promoting healthy aging. Research on aging mice has demonstrated that Ca-AKG administration can lead to notable improvements in longevity. These findings are corroborated by the TruAge DNA methylation test, which shows a decrease in biological age markers following AKG treatment (R).

The molecular mechanisms involved in AKG’s effects are complex, but vital for understanding its anti-aging properties. By influencing factors such as cellular metabolism, stem cell modulation, and DNA methylation, Ca-AKG demonstrates a multifaceted approach to promoting longevity. This metabolite’s ability to modulate environmental factors and the immune system further supports its role in combating age-related decline and chronic diseases.

Ongoing research aims to elucidate the full scope of AKG’s benefits, with a particular focus on its effects on neurodegenerative diseases and age-related decline. As clinical trials continue to explore the potential of this compound, Ca-AKG stands out as a promising candidate in the search for effective anti-aging interventions. Its comprehensive impact on molecular mechanisms and physiological functions underscores its significance in the realm of longevity research.

Enhancing Skin Health and Appearance

Ca-AKG positively impacts skin health. It supports collagen synthesis, essential for maintaining skin elasticity and firmness. The compound’s antioxidant properties help combat free radicals which contribute to skin aging. By reducing oxidative damage, Ca-AKG helps preserve a youthful appearance and improves overall skin health.

Supporting Bone Health

Bone health benefits from Ca-AKG as well. It aids in calcium absorption and bone mineralization, crucial for maintaining strong bones. Research by Riedel et al. (1996) found that Ca-AKG dietary supplement improved plasma arginine concentrations, which support bone metabolism (R). By enhancing bone density and skeletal muscle, and reducing bone resorption, Ca-AKG plays a vital role in sustaining skeletal strength as we age.

Additional Health Benefits

Calcium alpha-ketoglutarate (Ca-AKG) offers a variety of health benefits that go beyond longevity and cellular energy production.

Improving Metabolic Function

Ca-AKG improves metabolic function by playing a crucial role in the tricarboxylic acid (TCA) cycle. This cycle, also known as the Krebs cycle, is vital for cellular energy production. By enhancing the efficiency of this cycle, Ca-AKG helps in the production of ATP, the energy currency of cells. Increased ATP production supports overall metabolic health and ensures cells have the energy required for optimal function.

Anti-Inflammatory Effects

Ca-AKG has significant anti-inflammatory effects. Studies have shown that Ca-AKG reduces inflammation by modulating key signaling pathways involved in the inflammatory response. One mechanism involves inhibiting the activity of NF-κB, a protein complex that controls the transcription of DNA and is linked to inflammatory responses (R). By reducing inflammation, Ca-AKG helps mitigate symptoms of chronic inflammatory diseases and supports overall well-being.

Regular alpha-ketoglutarate versus calcium alpha-ketoglutarate

Most alpha-ketoglutarate supplements contain plain alpha-ketoglutarate.

However, scientists believe that the calcium form of alpha-ketoglutarate, namely calcium alpha-ketoglutarate (calcium AKG or CAKG), is significantly better than regular/plain alpha-ketoglutarate.

Calcium alpha-ketoglutarate can have additional beneficial effects compared to alpha-ketoglutarate. One reason for this is that calcium alpha-ketoglutarate is more slowly absorbed in the gut and released into the bloodstream, so it can work for longer in the body. This makes sense, given alpha-ketoglutarate is an important metabolite and ideally it should be present in our body at sufficiently high levels for as long as possible.

Most supplements on the market contain only plain alpha-ketoglutarate, not calcium alpha-ketoglutarate. Also, their dose of alpha-ketoglutarate is often too low. NOVOS contains a generous dose of calcium alpha-ketoglutarate.

Calcium alpha-ketoglutarate: an exemplary longevity supplement?

Calcium AKG ticks all the boxes of an ideal longevity molecule: there is substantial scientific evidence showing it extends lifespan in various model organisms (C. elegans, fruit flies and mice) (R).

Calcium AKG works beneficially on various biological aging mechanisms, such as epigenetic and mitochondrial dysfunction.

It is a natural substance that occurs in our body, but its levels decrease as we get older, causing age-related complications.

It has been taken by humans for many decades, with the only significant side effects seeming to be increased lifespan and healthspan.

For these reasons, calcium alpha-ketoglutarate (calcium AKG) is an important ingredient in our NOVOS Core formula.

NOVOS CORE & calcium alpha-ketoglutarate