Alphaketoglutarate (AKG) is an important component of energy metabolism and is involved in many physiological functions and processes in our body. Since AKG levels decrease with age and we cannot absorb this molecule through food, it was investigated as a promising molecule in longevity research. In animal studies alphaketoglutarate extended life by up to 50% and in humans AKG also reduced biological age in one study by up to 8 years. It also has positive influences on bone metabolism and promotes muscle growth. You can find out here exactly how AKG works in the body, what the current state of research is and what forms of the molecule there are.
Alphaketoglutarate at a glance
Alpha-ketoglutarate is a small molecule consisting of five carbon, six hydrogen and five oxygen atoms. AKG is constantly being built up and broken down in our body because, among other things, it plays an important role in energy metabolism. Since the AKG level decreases over time, the molecule became the focus of aging researchers. They see good opportunities in using AKG for the prevention of age-related diseases such as diabetes, obesity and cardiovascular diseases.
Let's now take a look at how exactly this can work.
Physiological function of alphaketoglutarate
Where does AKG actually occur in the body? To do this, we have 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 exactly where alphaketoglutarate plays an essential role. In the so-called citrate cycle the carbon structure of glucose is broken down. This happens through the conversion of several molecules. One of them is alpha ketoglutarate.
In addition, AKG is important for Nitrogen metabolism, i.e.a in the utilization of proteins through the diet.
As precursor of glutamate and glutamine alphaketoglutarate also plays a key role in the energy metabolism of the digestive tract on. There, AKG serves as a precursor to glutamine in the energy production of our intestinal cells.
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 muscles. According to the latest scientific findings, this effect offers a basis for clinical applications in the area of 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 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.
You can find out more about this topic Collagen in the corresponding article in our magazine.
Worth knowing: 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 even into old age
As we age, our bones become weaker. The large network of bone components is becoming increasingly thinner, which leads to an ever-increasing probability of fracture. In 2010, in Europe alone 22 million women and 5.5 million men met the WHO diagnostic criteria for osteoporosis, in German: bone loss. Ascending trend.
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 as we age.
So what can you do to ensure that bone loss is as low as possible? The European guidelines recommend Strength training, as it has been proven that the muscles pull on the bones Can increase bone density. In addition, regular Vitamin D substitution is recommended, as this hormone also has an impact on calcium metabolism .
Alphaketoglutarate can be another supporter of healthy bones in old age. In a 6-month study, 73 postmenopausal women took either calcium alone or in the form of calcium alphaketoglutarate. Calcium alone could not bring about any improvement - however, regular intake of 1000 mg Ca-AKG increased bone density. Together with strength training, a sufficient Magnesium supply and Vitamin D could Ca-AKG be a good precaution for healthy bones.
Milk ensures healthy bones? Myth or fact? This saying has been used by the advertising industry for a very long time. The calcium in milk is said to ensure stronger bones. In this study 96.000 older women and men tracked for 22 years. Interestingly, men with higher milk consumption in their youth had more fractures in old age. If you take the height out of the equation, the effect is no longer significant.
Alphaketoglutarate and the skin: Better wound healing and skin moisture
Collagen is one of the most important structural proteins in 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, among other things, in this study was able to significantly reduce wrinkles lead. In addition, the administration of AKG increased the moisture of the skin and improved its function. The antioxidant properties of alphaketoglutarate probably play a crucial role here.
The effect of AKG on wound healing has also been researched in humans, especially in burn victims. Alphaketoglutarate was able to contribute to faster wound healing and less scarring.
AKG a booster for the immune system
As a precursor to glutamine Alphaketoglutarate, 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 of these cells fight pathogens every day with their different weapons.
Glutamine is also needed for macrophages, which play an important role in our body as phagocytes in the defense against pathogens.
AKG can also directly increase the ability of phagocytosis . This means that the phagocytes (macrophages) are better able to “eat” (phagocytize) potential enemies. This is one of the possible ways AKG can boost the immune system.
Longevity Insights on Alpha Ketoglutarate
There are actually already the first studies in the context of longevity research. These were carried out on roundworms, i.e. nematodes. Studies with the model organism Caenorhabditis elegans show that alphaketoglutarate can extend the lifespan of these organisms by approximately 50%. This mechanism is triggered by inhibition of ATP synthase and mTOR . Especially mTOR has been the focus of longevity research for years in connection with autophagy and is also one of the four longevity paths.
In addition, in another study with nematodes, the administration of alphaketoglutarate delayed the appearance of age-related phenotypes associated with a decline in the worms' coordination ability and mobility.
The first studies with alphaketoglutarate (AKG) were carried out on the nematode Caenorhabditis elegans - with promising results.
Alpha-ketoglutarate (AKG) in human research
The globally renowned Buck Institute for Research on Aging – a leader in the field of longevity research for years – published new research results from a mouse study in September 2020. They found that the mice that were given alphaketoglutarate were healthier and in some cases also had a longer lifespan. In addition, administration of AKG lowered inflammatory markers. Chronic inflammation has been associated with age-related diseases for years and is a recognized hallmark of aging under the name Inflammaging .
A clinical trial is planned at the National University of Singapore (NUS) to examine the effects of alphaketoglutarate on people aged 45 to 65 years should be investigated. 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 alphaketoglutarate in a formulation with other substances (e.g.b vitamins) the biological age was able to rejuvenate 42 test subjects by a full 8 years. The level of DNA methylation was measured to determine the biological age. This confirmed the theory that alphaketoglutarate has a positive effect on epigenetics effects.
The duration of use of the alphaketoglutarate-based formulation was on average 7 months to achieve this effect.
Did you know? A study from 2012 found that increased alphaketoglutarate levels were detectable after physical activity. Exercise may be a good strategy to increase AKG values. 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 quick look at the biochemistry behind it.
Oxygen radicals, so-called 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. To put it simply, the more oxygen radicals are produced, the more glutathione is consumed. AKG helps our body keep glutathione levels at a healthy level.
And what connection is there with fertility? With age, oxygen radicals increase and this seems to be one of the factors why the eggs in the ovaries are increasingly affected by damage. AKG was able to ensure, at least in animal studies, that the eggs remained healthy for longer.
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 of simply substituting glutathione is not always effective. Another molecule, GlyNAC, was significantly more effective in the studies and was also capable of various Hallmarks of Aging at Influence people positively.
Alphaketoglutarate and cardiac function
In 2023, researchers made a potentially revolutionary discovery on mouse hearts involving alphaketoglutarate.
Our heart loses its ability to regenerate after birth. This is the reason why e.g.b After a heart attack, the heart can never recover properly. Instead of new heart muscle cells, scar tissue forms. The researchers at the Max Planck Institute for Heart and Lung Research wanted to change this and blocked 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 in this group the level of alphaketoglutarate was 20 times higher than in the comparison group.
New heart muscle cells through 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 ensures the activation of other genes. The exact mechanism is complicated, but KDM5 removes methyl groups from histones. This frees up spots on the DNA and allows other genes to be read. 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 scar, the mice regained normal heart function after a few weeks.
Ca-AKG, Na-AKG, O-AKG, A-AKG – what lies behind the abbreviations
We already had some abbreviations for alphaketoglutarate. AKG, Ca-AKG, Calcium-AKG or sometimes in the English spelling as Alpha-ketoglutarate. Depending on which molecule alphaketoglutarate is connected to, new abbreviations are created. Ca-AKG is made from calcium and alpha ketoglutarate. So that there isn't too much confusion, we'll show you what the abbreviations mean:
- Na-AKG: Alphaketoglutarate together with sodium
- O-AKG: Stands for the connection of alphaketoglutarate 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 to NO synthesis was able to dilate blood vessels
Which forms of alphaketoglutarate are good for supplementation?
Alphaketoglutarate is made 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 for alphaketoglutarate is calcium alphaketoglutarate. The calcium combination ensures better bioavailability compared to the pure form. In addition, AKG is known to be better absorbed in the small intestine and at a low pH and the presence of iron and sulfur oxide ions.
In general, you should ensure that the calcium alphaketoglutarate is free of unwanted additives and fillers.
Conclusion on calcium alphaketoglutarate
Alphaketoglutarate is an exciting molecule in aging research. In studies, it could not only reverse biological age, but also contributed to better bone density and stronger stem cells at. What is particularly interesting is the fact that we do not naturally absorb alphaketoglutarate through food and levels fall with age. Supplementation in animals could lead to sometimes drastic jumps in lifespan. Whether this will also be the case for us remains to be seen.
