alpha-ketoglutarate (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 lack this molecule cannot absorb through food, it has been investigated as a promising molecule in longevity research. In animal studies Alphaketoglutarate extended life by up to 50% and also in humans In one study, AKG reduced biological age by up to 8 years. It also has a positive effect on bone metabolism and promotes muscle growth. Here you can find out exactly how AKG works in the body, what the current state of research is and what forms of the molecule exist.
Alphaketoglutarate at a glance
Alpha-ketoglutarate is a small molecule that consists of five carbon, six hydrogen and five oxygen atoms. In our body, AKG is constantly being built up and broken down because it plays an important role in energy metabolism, among other things. the AKG level decreases over time, the molecule has become the focus of age researchers. They see good opportunities in using AKG to Prevention of age-related diseases such as diabetes, obesity and cardiovascular diseases.
Let’s now look at how exactly this can work.
Physiological Function of Alphaketoglutarate
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. mitochondria The sugar from food is converted into energy in the form of ATP. This is where alphaketoglutarate plays an essential role. In the so-called citric acid cycle the carbon skeleton 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 the nitrogen metabolism, including the utilization of proteins through nutrition.
As precursor of glutamate and glutamine Alphaketoglutarate 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 wasn’t enough, Alphaketoglutarate is also able to minimize the breakdown of the body’s own proteins and increase protein synthesis. The molecule is involved in the 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 field of prevention of age-related diseases.
hormones and immune system
Alphaketoglutarate (AKG) also has an influence on the endocrine system. Glutamine and glutamate are metabolized into 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 convert pro-collagen into collagenAccordingly, the molecule is a supplier for collagen production in our body.
More on the topic collagen You can find out more in the corresponding article in our magazine.
Worth knowing: 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 risk of fracture. In 2010, in Europe alone, 22 million women and 5.5 million men meet the WHO diagnostic criteria for osteoporosis, in German: bone loss. The trend is increasing.
Osteoporosis is estimated to be 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 keep bone loss as low as possible? The European guidelines recommend weight training, as it can demonstrably increase bone density through the pull of the muscles on the bones. In addition, regular vitamin D substitution recommended because this hormone also affects calcium metabolism.
Alphaketoglutarate can be another supporter of healthy bones in old ageIn a 6-month study, 73 postmenopausal women took calcium either alone or in the form of calcium alpha-ketoglutarate. Calcium alone did not bring about any improvement – the However, regular intake of 1000 mg Ca-AKG increased bone density. Together with strength training, sufficient magnesium supply and vitamin D could Ca-AKG therefore represent a good precaution for healthy bones.
Milk ensures healthy bones? Myth or fact? This slogan has been used by the advertising industry for a long time. The calcium in milk is said to make bones stronger. In this study 96,000 older women and men were followed for 22 years. Interestingly, men who consumed more milk in their youth had more fractures in old age. However, if height is taken into account, 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 precisely where AKG can help by stimulating the conversion of pro-collagen to collagen.
Alphaketoglutarate was tested as a skin cream on humans and was able to study to a significant reduction of wrinkles 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 crucial role here.
Also, in humans, the Effect of AKG on wound healing, especially in burn victims. Alphaketoglutarate was able to faster wound healing and reduce scarring.
AKG a booster for the immune system
As a precursor of glutamine has alpha-ketoglutarate, as already mentioned at the beginning, also has a hand in the immune systemGlutamine 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 with their different weapons every day.
In addition, 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 ability of phagocytosis This means that the phagocytic cells (macrophages) can better “eat up” (phagocytose) potential enemies. This is one of the possible ways AKG can boost the immune system.
Longevity findings on alpha ketoglutarate
There are already initial 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 alpha-ketoglutarate can extend the lifespan of these organisms by about 50%This mechanism is achieved by inhibiting ATP synthase and mTOR triggered. Just mTOR is associated with the autophagy has been the focus of longevity research for years and is also one of the four longevity pathways.
Furthermore, in another study with nematodes, administration of alpha-ketoglutarate delayed the onset of age-related phenotypes associated with a decline in the worms' coordination ability and motility.
The first studies with alpha-ketoglutarate (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 longevity research for years – published new research results from a mouse study in September 2020. They found that the mice given alpha-ketoglutarate were healthier and in some cases also had a longer lifespan. In addition, administration of AKG inflammatory markersChronic inflammation has been associated with age-related diseases for years and is known under the name Inflammaging recognized sign of aging.
A clinical trial is planned at the National University of Singapore (NUS) to test the Effect of alpha-ketoglutarate 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 also showed that the administration of alpha-ketoglutarate in a formulation with other substances (e.g. vitamins) the biological age rejuvenated 42 subjects by a full 8 yearsThe DNA methylation level was measured to determine the biological age. This confirmed the theory that alpha-ketoglutarate has a positive effect on epigenetics affects.
The application time 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 activityExercise may be a good strategy to increase AKG levels, but 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.
Our bodies are constantly producing Oxygen radicals, so-called ROS. 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 the glutathioneTo 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 is the connection with fertility? As we age, oxygen radicals increase and this seems to be one of the factors why the egg cells in the ovaries are increasingly damaged. 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 break down harmful substances. However, with age, glutathione levels decrease. The obvious idea of simply substituting glutathione is, however, not always effective.Another molecule, GlyNAC, was significantly more effective in the studies and was also able to Hallmarks of Aging have a positive effect on humans.
Alphaketoglutarate and Heart Function
In 2023, researchers will have a potentially revolutionary discovery on mouse hearts and involved them Alpha-ketoglutarate.
After birth, our heart loses the ability to regenerate. This is the reason why, for example, after a heart attack, the heart can never recover properly. Instead of new heart muscle cells, scar tissue forms. The researchers of the Max Planck Institute for Heart and Lung Research wanted to change this and have a Gene called Cpt1b is blocked. 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 Levels of alpha-ketoglutarate were 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 they arrive at this result? It is suspected that alpha-ketoglutarate 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 spaces on the DNA and other genes can 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 their normal heart function after a few weeks.
Ca-AKG, Na-AKG, O-AKG, A-AKG – what lies behind the abbreviations
We have already had some abbreviations for alpha-ketoglutarate. AKG, Ca-AKG, Calcium-AKG or sometimes in the English spelling as alpha-ketoglutarate. Depending on which molecule alphaketoglutarate is combined with, new abbreviations are created. Calcium and alphaketoglutarate become Ca-AKG. To avoid too much confusion, we will show you what the abbreviations mean:
- Na-AKG: Alphaketoglutarate together with sodium
- O-AKG: Stands for the compound of alpha-ketoglutarate with the amino acid L-ornithine
- A-AKG: The combination of the amino acid arginine and alpha-ketoglutarate results in A-AKG. Arginine as a precursor to NO synthesis was able to dilate blood vessels in studies
Which forms of alpha-ketoglutarate are good for supplementation?
Alpha-ketoglutarate is produced in the body and is not found in food. However, studies show that fasting and exercise can increase the level of alpha-ketoglutarate in the blood. Another way to take in 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. In addition, AKG is known to be better absorbed in the small intestine and at a low pH and in the presence of iron and sulfur oxide ions.
In general, one should ensure that the calcium alphaketoglutarate is free of unwanted additives and fillers.
Conclusion on Calcium Alphaketoglutarate
Alphaketoglutarate is an exciting molecule in age research. In studies it has not only been shown turn back the biological age, but also contributed to a better bone density and stronger stem cells What is particularly interesting is the fact that we do not naturally absorb alpha-ketoglutarate through food and the levels fall with age. Supplementation in animals could lead to sometimes drastic jumps in lifespanWhether this will also be the case for us remains to be seen.
