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 in humans AKG also reduced biological age 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.
Alpha-ketoglutarate 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 attention for researchers into ageing. They see good opportunities for using AKG to prevent age-related diseases such as diabetes, obesity and cardiovascular disease.
We will now take a look at exactly how this can work.
Physiological function of alpha-ketoglutarate
Where does AKG actually occur 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 alphaketoglutarate 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.
In addition, AKG is important for nitrogen metabolism, i.e. u.a. in the utilization of proteins through nutrition.
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.
But that's not all, alphaketoglutarate 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 the 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 has a direct influence on bone metabolism as a result. 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.
Find out more about collagen in the corresponding article in our magazine.
What you need to know: Alpha-ketoglutarate is a stronger free 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
Our bones become weaker with age. The large network of bone components becomes thinner and thinner, which leads to an ever-increasing likelihood of fractures. in 2010 in Europe alone 22 million women and 5.5 million men met the WHO's diagnostic criteria for osteoporosis, or bone loss. And the trend is rising
Osteoporosis is estimated to be 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 vigorous exercise, as this has been shown to increase bone density by pulling the muscles against the bones. In addition, regular vitamin D substitution 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, a sufficient magnesium supply and vitamin D could Ca-AKG thus represents a good precaution for healthy bones.
Milk makes for healthy bones Myth or fact? This slogan was 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 with higher milk consumption in adolescence had more fractures in old age. However, the effect is no longer significant once body size is taken into account.
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 lead to a significant reduction in wrinkles in this study . In addition, the administration of AKG increased the moisture of the skin and improved its function. The antioxidant properties of alpha-ketoglutarate 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, as already mentioned at the beginning, also has a hand in the immune system. 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 and day out with their various weapons.
In addition, glutamine is also required for macrophages, which play an important role in our body as phagocytes in the defense against pathogens.
AKG can also directly increase the capability of phagocytosis . This means that the phagocytes (macrophages) can "eat" (phagocytose) potential enemies better. This is one of the possible ways in which AKG can boost the immune system.
Longevity findings on alpha ketoglutarate
In fact, initial studies have already been carried out in the context of longevity research. These were carried out on threadworms, i.e. nematodes. Studies with the model organism Caenorhabditis elegans show that alpha-ketoglutarate can extend the lifespan of these organisms by around 50%. This mechanism is triggered via inhibition of ATP synthase and mTOR . Especially mTOR is related to autophagy 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, alphaketoglutarate administration delayed the onset of age-related phenotypes associated with a decline in worm coordination and motility.
The first studies with alphaketoglutarate (AKG) were carried out on the nematode Caenorhabditis elegans - with promising results.
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. In addition, the administration of AKG reduced inflammatory markers. Chronic inflammation has been associated with age-related diseases for years and is known as inflammaging a recognized hallmark of aging.
A clinical trial 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 high 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 also showed that the administration of alphaketoglutarate in a formulation with other substances (z.B . vitamins) was able to rejuvenate biological age by a whole 8 years in 42 test subjects . 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 use of the alpha-ketoglutarate-based formulation was on average 7 monthsto 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 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 a balance is always needed 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 eggs in the ovaries are increasingly affected by damage. AKG was able to ensure that the eggs remained healthy for longer, at least in animal studies.
Did you know Glutathione is extremely important for our cells. In the liver, it helps us break down harmful substances. However, glutathione levels decrease with age.The obvious idea is to simply substitute glutathione, but this is not always effective. Another molecule, GlyNAC , was much more effective in the studies and was also able to positively influence various Hallmarks of Aging in humans.
Alphaketoglutarate and cardiac function
In 2023, researchers made a potentially revolutionary discoveryinvolving mouse hearts alphaketoglutarate.
Our heart loses the ability to regenerate after birth. This is the reason why z.Bthe heart can never recover properly after a heart attack. Instead of new heart muscle cells, scar tissue forms. Researchers at the Max Planck Institute for Heart and Lung Researchwanted to change this by blocking a gene called Cpt1b. This is important for fatty acid metabolism. In a second step, the researchers simulated a heart attack and compared the two groups of mice. The group with the blocked gene recovered significantly better after the heart attack, new heart muscle cells began to grow and the ability to regenerate returned. The scientists found that the level of alpha ketoglutarate was 20 times higher in this group than in the comparison group.
New heart muscle cells due to altered epigenetics?
The results of the study are impressive and give hope for new therapeutic approaches. But how exactly did the result come about? It is assumed that alphaketoglutarate activates the enzyme KDM5. This in turn activates other genes. The exact mechanism is complicated, but KDM5 removes methyl groups from histones. This frees up sites on the DNA and other genes can be transcribed. Due to the increased activity of KDM5, the heart muscle cells appear to become younger again and regain their ability to regenerate. Instead of the expected scarring, the mice regained their normal heart function after a few weeks.
Ca-AKG, Na-AKG, O-AKG, A-AKG - what's behind the abbreviations
We already had some 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. To avoid too much confusion, we'll show you what the abbreviations mean:
- Na-AKG: alpha-ketoglutarate 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 results in A-AKG. In studies, arginine as a precursor for NO synthesis was able to dilate the blood vessels
Which alpha-ketoglutarate forms 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 alphaketoglutarate levels in the blood. Another way to absorb AKG is through dietary supplements.
A particularly suitable form of 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 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 alpha ketoglutarate through food 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
