Inhaltsstoff-Glossar

Alpha-Ketoglutarate

What Is Alpha-Ketoglutarate?

Alpha-ketoglutarate is also referred to as alpha-ketoglutaric acid and is often written using the Greek prefix as α-ketoglutarate. In scientific literature, alpha-ketoglutarate is described as both a tumor-suppressor molecule and a longevity molecule that can be supplied externally. It is believed to have the potential to turn humanity's dream of a longer life and improved health into reality. Among its better-established functions are its versatile roles in energy metabolism, protein metabolism, and detoxification. Calcium and arginine salts of alpha-ketoglutarate are commercially available. Overall, alpha-ketoglutarate is considered safe and well tolerated.

Where Does Alpha-Ketoglutarate Naturally Occur?

Alpha-ketoglutarate is an endogenous substance. It is produced exclusively by the body and does not occur naturally in food. In principle, alpha-ketoglutarate is present in every cell of the body. Within the mitochondria, the body produces up to 2 kilograms of alpha-ketoglutarate each day, which is immediately utilized in the citric acid cycle. In general, cellular alpha-ketoglutarate levels increase after exercise and during fasting, while they decline with age.

Alpha-ketoglutarate and ammonium combine to form glutamate. Both this synthesis and the reverse reaction are catalyzed by the enzyme glutamate dehydrogenase. The body expresses the gene for this enzyme particularly in the brain, the retina of the eye, and the testes. Consequently, the alpha-ketoglutarate-dependent reaction plays an especially important role in these tissues.

What Is the Primary Function of Alpha-Ketoglutarate in the Body?

Its central role lies within the citric acid cycle. This cycle works together with the electron transport chain to generate adenosine triphosphate (ATP), the universal biological energy carrier. Alpha-ketoglutarate is an intermediate of energy metabolism, whose purpose is to generate ATP from fatty acids, glucose, or amino acids.

Within nitrogen metabolism, alpha-ketoglutarate serves as a building block for amino acids. Together with ammonium, it first forms glutamate, from which the body synthesizes additional non-essential amino acids such as glutamine. Glutamate also plays a crucial role in the synthesis of glutathione, one of the body's most important antioxidants, present in every cell. Alpha-ketoglutarate itself also acts as a free-radical scavenger and antioxidant, with antioxidant activity reported to be even stronger than that of vitamin C.

Particularly during illness and following injuries, the body's demand for glutamine exceeds its production capacity. Glutamine is not only essential for the division of white blood cells and the phagocytic activity of immune cells, but the body's requirements also increase significantly after surgery, trauma, and burns.

Alpha-ketoglutarate therefore functions as a regulator of nitrogen metabolism. This makes it one of the key molecules involved in the detoxification of ammonium. During amino acid breakdown, the body produces ammonium, which accumulates whenever amino acid metabolism is impaired. This is undesirable because ammonium is toxic to cells and places considerable stress on both the body and individual cells. Alpha-ketoglutarate regulates ammonium by binding and temporarily fixing it to form amino acids or releasing it when required. In the subsequent step, ammonium is transported to the liver and enters the urea cycle. Alpha-ketoglutarate therefore helps detoxify ammonium by converting it into urea, allowing the body to eliminate it safely through the urine.

What Are the Benefits of Alpha-Ketoglutarate Supplementation?

Alpha-ketoglutarate supplementation has demonstrated benefits in cases of injury, illness, and surgery. It contributes to ATP synthesis, supports oxygen supply, and helps control oxidative stress. Through its role in energy metabolism, it offers the potential to improve recovery. Studies have shown that it can accelerate healing after illness and surgical procedures. It also supports anti-catabolic metabolic pathways—particularly amino acid synthesis—when the body enters a strongly catabolic state. As an important precursor of glutamine, it is essential for proper immune function, including the production of cytokines.

Alpha-ketoglutarate is also being intensively studied for its potential role in cancer therapy. Many cancers alter the body's nitrogen metabolism. Since alpha-ketoglutarate is a central regulator of nitrogen metabolism, it may help compensate for disturbances in nitrogen balance. Researchers are particularly interested in alpha-ketoglutarate as an endogenous tumor-suppressor metabolite, not least because it inhibited the kinase "target of rapamycin" (TOR) in experiments involving nematodes.

In studies using nematodes and other animal models such as mice, researchers demonstrated life-extending effects of alpha-ketoglutarate. These studies found an association between fasting or calorie restriction, increased tissue levels of alpha-ketoglutarate, and prolonged lifespan. In mice, the calcium salt of alpha-ketoglutarate (Ca-AKG) improved both lifespan and healthspan, most likely because it reduced chronic inflammation and decreased frailty.

Alpha-ketoglutarate is commercially available as a dietary supplement in combination with either calcium or arginine. The calcium salt form (Ca-AKG) improves the molecule's chemical stability and solubility while also providing calcium, an important mineral for bone health. Similar principles apply to arginine alpha-ketoglutarate. Due to arginine's role in nitric oxide synthesis, this combination is believed to improve oxygen delivery to tissues and enhance physical performance. Ca-AKG has been used in several landmark studies investigating longevity and the reduction of chronic inflammation.