What is alpha-ketoglutarate (AKG)?

Alphaketoglutarate (AKG) is an important component of energy metabolism and is involved in many physiological functions and processes in our body. As AKG levels decrease with age and we cannot obtain this molecule from food, it has been investigated as a promising molecule in longevity research. In animal studies, alphaketoglutarate prolonged life by up to 50% and AKG also reduced biological age in humans by up to 8 years in one study. It also has a positive effect on bone metabolism and promotes muscle growth. You can find out exactly how AKG works in the body, what the current state of research is and what forms of the molecule there are here.

Alphaketoglutarate at a glance

Alpha-ketoglutarate is a small molecule consisting of five carbon atoms, six hydrogen atoms and five oxygen atoms. In our body, AKG is constantly being built up and broken down, as it plays an important role in energy metabolism, among other things. As the AKG level decreases over time, the molecule has become the focus of ageing researchers. They see good opportunities in using AKG to prevent age-related diseases such as diabetes, obesity and cardiovascular diseases .

Let's take a look at exactly how this can work.

Physiological function of alpha-ketoglutarate

Where is AKG actually found in the body? To find out, we need to take a closer look at the power plants of our cells. In the mitochondria the sugar from food is converted into energy in the form of ATP. This is precisely where alpha-ketoglutarate plays an essential role. In the so-called citrate cycle , the carbon skeleton of glucose is broken down. This occurs through the conversion of several molecules. One of these is alphaketoglutarate.

AKG is also important for nitrogen metabolism, i.e. for the utilization of proteins in the diet.

As a precursor of glutamate and glutamine, alpha-ketoglutarate also plays a key role in the energy metabolism of the digestive tract. There, AKG serves as a precursor of glutamine for the energy production of our intestinal cells.

As if that were not enough, alpha-ketoglutarate is also able to minimize the breakdown of the body's own proteins and increase protein synthesis. The molecule is involved in the formation of bone mass and skeletal muscle. According to the latest scientific findings, this effect provides a basis for clinical applications in the prevention of age-related diseases.

Hormones and immune system

Alphaketoglutarate (AKG) has a further influence on the endocrine system. Glutamine and glutamate are metabolized to ornithine and arginine. These two amino acids stimulate the release of growth hormones. It is assumed that AKG thus has a direct influence on bone metabolism. In addition, the longevity shooting star is involved in converting pro-collagen into collagen. Accordingly, the molecule is a supplier for collagen production in our body.

More on the topic collagen in the corresponding article in our magazine.

Interesting facts: Alpha-ketoglutarate is a stronger radical scavenger than ascorbic acid (vitamin C). The high antioxidant potential of AKG is another promising property of this molecule.

Healthy bones - important into old age

As we age, our bones become weaker. The large network of bone components becomes thinner and thinner, which leads to an ever-increasing likelihood of fractures. In 2010, 22 million women and 5.5 million men in Europe alone met the WHO's diagnostic criteria for osteoporosis, or bone loss. And the trend is rising.

According to estimates, osteoporosis is responsible for 80-90% of all fractures in old age and can therefore have a huge impact on quality of life. For this reason, healthy, strong bones are particularly important in old age.

So what can you do to minimize bone loss? The European guidelines recommend weight training, as this has been proven to increase bone density through the pull of the muscles on the bones. In addition, regular vitamin D supplementation is recommended, as this hormone also has an effect on calcium metabolism.

Alphaketoglutarate may be another supporter of healthy bones in old age. In a 6-month study, 73 post-menopausal women took either calcium alone or in the form of calcium alphaketoglutarate. Calcium alone did not bring any improvement - however, the regular intake of 1000 mg Ca-AKG increased bone density. Together with weight training, sufficient magnesium supply and vitamin DCa-AKG could therefore be a good precaution for healthy bones.

Milk makes for healthy bones? Myth or fact? This slogan has been used by the advertising industry for a very long time. The calcium in milk is supposed to ensure stronger bones. In this study, 96,000 older men and women were followed for 22 years. Interestingly, the men who consumed more milk in their youth had more fractures in old age. However, the effect is no longer significant once height is factored out.

Alphaketoglutarate and the skin: better wound healing and skin hydration

Collagen is one of the most important structural proteins of the skin, the concentration of which decreases with age. This is exactly where AKG can help by stimulating the conversion of pro-collagen to collagen.

Alphaketoglutarate was tested as a skin cream in humans and was able to significantly reduce wrinkles in this study, among other things. In addition, the administration of AKG increased the skin's moisture and improved its function. The antioxidant properties of alphaketoglutarate probably play a decisive role here.

The effect of AKG on wound healing, particularly in burn victims, has also been researched in humans. Alphaketoglutarate was able to contribute to faster wound healing and less scarring.

AKG a booster for the immune system

As a precursor of glutamine, alpha-ketoglutarate also has a hand in the immune system, as mentioned above. Glutamine is essential for the physiological function of lymphocytes, which include B cells, T cells and natural killer cells (NK cells). All these cells fight pathogens day in, day out with their various weapons.

Glutamine is also required for macrophages, which play an important role as scavenger cells in our body's defense against pathogens.

AKG can also directly increase the ability of phagocytosis. This means that the phagocytes (macrophages) are better able to "eat" (phagocytose) potential enemies. This is one of the possible ways in which AKG can boost the immune system.

Longevity findings on alpha ketoglutarate

The first studies have already been carried out as part of longevity research. These were carried out on nematodes, i.e. threadworms. Studies with the model organism Caenorhabditis elegans show that alphaketoglutarate can extend the lifespan of these organisms by around 50%. This mechanism is triggered by inhibition of ATP synthase and mTOR . In connection with autophagy, mTOR in particular has been the focus of longevity research for years and is also one of the four longevity pathways.

In addition, in another study with nematodes, administration of alpha-ketoglutarate delayed the onset of age-related phenotypes associated with a decline in worm coordination and motility.

Alpha-ketoglutarate (AKG) in human research

The world-renowned Buck Institute for Research on Aging - a leader in the field of longevity research for many years - published new research results from a mouse study in September 2020. They found that the mice given alphaketoglutarate were healthier and in some cases also had a longer lifespan. The administration of AKG also lowered inflammatory markers. Chronic inflammation has been associated with age-related diseases for years and is known as inflammaging a recognized hallmark of ageing.

A clinical study is planned at the National University of Singapore (NUS) to investigate the effect of alphaketoglutarate on people aged 45 to 65 years. The results of this study are of great importance for research and the rapid implementation of such studies shows that AKG is of great interest in the longevity community.

A study from 2021 was also able to show that the administration of alpha-ketoglutarate in a formulation with other substances (e.g. vitamins) was able to rejuvenate the biological age of 42 test subjects by a whole 8 years. The DNA methylation level was measured to determine the biological age. This confirmed the theory that alphaketoglutarate has a positive effect on epigenetics.

The duration of application of the alpha-ketoglutarate-based formulation was on average 7 months to achieve this effect.

Did you know? A 2012 study found that increased alpha ketoglutarate levels were detectable after physical activity. Exercise may be a good strategy to increase AKG levels. However, further studies are needed to confirm this effect.

Alphaketoglutarate and its effect on cells

AKG has an antioxidant effect and, according to studies, can therefore also increase fertility (at least in animals). To understand this in more detail, we need to take a brief look at the biochemistry behind it.

Oxygen radicals, known as ROS, are constantly being produced in our bodies. Too many of these highly active substances damage our cells, which is why there always needs to be a balance between the number of ROS molecules and ROS scavengers. One of the most important ROS scavengers in our body is glutathione. Put simply, the more oxygen radicals are produced, the more glutathione is consumed. AKG helps our body to keep glutathione levels at a healthy level.

And what is the connection with fertility? Oxygen radicals increase with age and this appears to be one of the factors why the egg cells in the ovaries are increasingly affected by damage. At least in animal studies, AKG was able to ensure that the egg cells remained healthy for longer.

Did you know? Glutathione is extremely important for our cells. In the liver, it helps us to break down harmful substances. However, glutathione levels decrease with age. The obvious idea of simply substituting glutathione is not always effective. Another molecule, GlyNACwas much more effective in the studies and was also able to positively influence various hallmarks of ageing in humans.

Ca-AKG, Na-AKG, O-AKG, A-AKG - what's behind the abbreviations

We have already had a few abbreviations for alpha-ketoglutarate. AKG, Ca-AKG, calcium-AKG or sometimes also in the English spelling as alpha-ketoglutarate. Depending on which molecule alpha-ketoglutarate is combined with, new abbreviations are created. Calcium and alpha-ketoglutarate become Ca-AKG. So that there is not too much confusion, we will show you what is behind the abbreviations:

• Na-AKG: Alphaketoglutarate together with sodium
• O-AKG: Stands for the combination of alpha-ketoglutarate with the amino acid L-ornithine
• A-AKG: The combination of the amino acid arginine and alphaketoglutarate produces A-AKG. Arginine as a precursor for NO synthesis has been shown in studies to widen blood vessels

Which forms of alpha-ketoglutarate are good for supplementation?

Alphaketoglutarate is produced in the body and is not found in food. However, studies show that fasting and exercise can increase the alphaketoglutarate level in the blood. Another way to absorb AKG is through dietary supplements.

A particularly suitable form for alpha ketoglutarate is calcium alpha ketoglutarate. The calcium combination ensures better bioavailability compared to the pure form. It is also known that AKG is better absorbed in the small intestine and at a low pH value and in the presence of iron and sulphur oxide ions.

In general, care should be taken to ensure that the calcium alpha-ketoglutarate is free from undesirable additives and fillers.

Conclusion on calcium alpha-ketoglutarate

Alphaketoglutarate is an exciting molecule in ageing research. In studies, it was not only able to reverse biological age, but also contributed to better bone density and stronger stem cells. Of particular interest is the fact that we do not naturally absorb alphaketoglutarate through our diet and levels fall with age. Supplementation in animals could lead to sometimes drastic leaps in lifespan. Whether this will also be the case for us remains to be seen.