Picture this: a tiny dynamo with a big attitude. No, we’re not talking about your Gen Alpha kid. This one boosts your energy levels, speeds up muscle recovery, and might even help you look and feel younger.
Wait, there’s more. At a cellular level, this molecule can ensure that your body’s engines—your mitochondria—are running smoothly, turning the foods you eat into fuel and keeping your cells in top shape.
Meet alpha-ketoglutarate, or AKG, a longevity-star ingredient, that may even reduce your biological age.
In this Avea article, we will take a deep dive into the science of AKG, exploring why this molecule is capturing the attention of longevity researchers, and what it could mean for your future health.
Should you be supplementing with AKG? You tell us by the end of this article.
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What is AKG?
Alpha-ketoglutarate (AKG) is a vital compound that plays a central role in your body’s energy production.
It’s an important part of the Krebs cycle, the cellular process that converts the food you eat into energy. Ringing any bells from those high school biology nightmares, perhaps?
As a metabolic intermediate, AKG ensures that your energy production runs efficiently, supporting various other critical functions in your body.
Discovered by Hans Adolf Krebs and William Arthur Johnson during their research on the citric acid cycle—work that earned Krebs the Nobel Prize in 1953—AKG remains a key player in the body’s energy-producing mechanisms.
It is known for being highly soluble in water, non-toxic, and stable. Let’s dive into the science behind AKG’s role in your body.
The role of AKG in the body
1. AKG in the Tricarboxylic Acid (TCA) cycle
By now, you should already know that AKG is a central molecule in the Tricarboxylic Acid (TCA) cycle, also known as the Krebs cycle. This is one of the most important metabolic pathways occurring in the mitochondria of your cells [1].
The TCA cycle is fundamental to cellular respiration, where it plays a pivotal role in converting nutrients from carbohydrates, fats, and proteins into adenosine triphosphate (ATP)—the primary energy currency of your cells.
AKG basically acts as a key intermediate, facilitating the transfer of carbon atoms through a series of reactions that ultimately lead to the production of ATP.
2. How AKG supports cellular energy metabolism
Now, AKG is not only for energy production. It is also deeply involved in maintaining the balance of various metabolic processes.
Specifically, AKG is decarboxylated to form succinyl-CoA and carbon dioxide (see in above graph), a step that is crucial for the continuation of the cycle and efficient ATP production.
AKG also serves as a precursor for glutamate, which can further be converted into other amino acids or used in the synthesis of neurotransmitters.
This dual function allows AKG to support both the energetic and biosynthetic needs of cells, making it indispensable for sustaining cellular metabolism and overall energy homeostasis [2].
Should you supplement with AKG?
AKG is one of the most promising compounds in the field of anti-ageing research.
Its levels naturally decline with age, particularly in stem and progenitor cells, leading to impaired mitochondrial function and reduced cellular energy.
Research has shown that AKG supplementation can extend lifespan and improve health span in animal models, making it a strong candidate for human longevity studies.
But what does this mean for you? Should you consider adding AKG to your daily routine?
Let’s explore the specific benefits of AKG supplementation and see how this powerful molecule might transform your approach to ageing and wellness.
Benefits of AKG supplementation
1. AKG and ageing
Recent research indicates that alpha-ketoglutarate may contribute to extending lifespan and enhancing health as we age.
In a study, AKG was found to extend the lifespan of a small organism called Caenorhabditis elegans (a type of nematode, which is a small, free-living roundworm) by approximately 50%.
It inhibited a crucial enzyme known as mitochondrial ATP synthase, which plays a central role in cellular energy production. By reducing the activity of this enzyme, AKG lowers ATP levels, which might seem counterintuitive, but it actually promotes autophagy—a process where cells remove damaged components, enabling them to function more effectively and remain healthy for longer.
AKG also impacts the TOR (target of rapamycin) pathway, a key regulator of growth and metabolism in the body. Although AKG does not directly interact with TOR, it reduces TOR activity through its effect on ATP synthase.
This reduction in TOR activity is further supported by proteins like AMPK and FoxO, which are crucial for managing energy and regulating lifespan.
Interestingly, these effects mimic the pathways activated by exercise, fasting, and other stressors known to promote longevity. These findings suggest that AKG could be a promising supplement for slowing down the ageing process and managing age-related diseases by enhancing how your cells produce energy and maintain themselves over time.
2. AKG and protein synthesis
Alpha-ketoglutarate plays a pivotal role in the synthesis of proteins and the development of bone tissue.
As a major source of glutamine and glutamate (see above graph), AKG stimulates protein synthesis, prevents muscle protein breakdown, and serves as an essential energy source for cells in the gastrointestinal tract.
- Glutamine, derived from AKG, is crucial for various cells, making up over 60% of the total amino acid pool. This makes AKG a primary energy source for intestinal cells and a preferred substrate for rapidly dividing cells.
- Glutamate, which is produced from AKG in the liver, is vital for proline synthesis—a key building block in collagen production, which is essential for strong and healthy bones.
In the liver, glutamine acts as a precursor for several critical processes, including ureagenesis, gluconeogenesis, and the synthesis of acute phase proteins, all of which are vital for maintaining the balance of nitrogen and carbon in your body.
Although glutamine is usually considered a non-essential amino acid, it becomes essential during periods of stress, providing crucial support to immune cells such as leucocytes and macrophages.
AKG also enhances the absorption of iron (Fe²⁺), which is particularly beneficial for those with iron deficiencies.
3. AKG and collagen metabolism
Alpha-ketoglutarate is deeply involved in collagen metabolism through several key mechanisms.
Firstly, AKG acts as a cofactor for prolyl-4-hydroxylase (P4H), an enzyme found in the endoplasmic reticulum that is essential for the formation of 4-hydroxyproline.
In short, this compound helps create the collagen triple helix, a structure necessary for strong and stable collagen fibres.
Without adequate hydroxylation of proline residues, collagen helices are improperly formed and subsequently degraded, leading to weakened tissue structures.
Second, AKG supports collagen synthesis by increasing the availability of proline, a primary building block for collagen. This occurs through the conversion of glutamate to pyrroline-5-carboxylate (P5C), which is then transformed into proline.
Recent studies also suggest that P5C not only adds to the proline pool, but actively stimulates collagen production by activating prolidase, an enzyme crucial for recycling proline.
The link between AKG and proline metabolism is further highlighted by studies in growing pigs, where AKG supplementation significantly increased proline levels in the bloodstream, thereby promoting bone tissue formation.
Introducing Avea’s Collagen Activator
At Avea, we’ve harnessed the power of CaAKG and combined it with three key amino acids—glycine, proline, and hydroxyproline—to create our 100% vegan Collagen Activator.
Developed with ETH Zurich scientists, this formula goes beyond traditional collagen supplements by using direct amino acids for better absorption and enhanced collagen production.
Paired with CaAKG, these amino acids not only boost optimal collagen synthesis, but also amplify AKG’s anti-ageing benefits.
We’ve also included Vitamin C from Acerola cherries, which enhances natural collagen production, and Astaxanthin, a powerful antioxidant that protects your skin from ageing.
Experience the synergy of the ingredients in Avea’s Collagen Activator—where longevity meets rejuvenation.
Why choose the Collagen Activator?
Our commitment to scientifically validated results is clear. In a clinical trial conducted at Hautwerk Clinic in Zurich with 58 participants, the Collagen Activator demonstrated remarkable outcomes.
After just one month, participants experienced an 18% improvement in skin texture and a 91% increase in hydration levels. By day 90, skin elasticity had improved by 6%.
These results, validated through advanced Visia, Corneometer, and Cutometer analyses, reflect the efficacy of our carefully selected ingredients and precise dosages.
Last but not least, the Avea Collagen Activator is the ultimate solution for those seeking a 100% vegan approach to boosting collagen levels.
Many collagen supplements derive their collagen from animal sources like bone broth or marine collagen, which can be problematic for vegetarians and vegans.
Colgevity™, our innovative vegan collagen precursor, ensures you get all the benefits of collagen without compromising your values.
4. AKG and bone health
Alpha-ketoglutarate influences bone tissue through its effects on the endocrine system.
Glutamine and glutamate, which are both derived from AKG, are converted into ornithine and then into arginine—both of which are known to stimulate the secretion of growth hormone (GH) and insulin-like growth factor I (IGF-I).
The GH-IGF-I axis is crucial for bone metabolism, playing a significant role in maintaining bone health and structure.
Besides, AKG may impact bone structure through its interactions with glutamate receptors (GluR) on osteoblasts and osteoclasts, the cells responsible for bone formation and resorption. These interactions suggest that AKG plays a part in regulating bone tissue metabolism.
Preliminary evidence also indicates that dietary AKG might help counteract bone loss in experimental models of osteopenia, such as those caused by ovariectomy or fundectomy in rats.
Whilst these studies highlight the potential of AKG in supporting collagen metabolism and bone health, further research is needed to fully understand its direct effects on collagen production in humans.
5. AKG and the immune system support
Alpha-ketoglutarate is often referred to as an immune nutrient factor due to its crucial role in maintaining and stabilising immune system balance.
As a key source of glutamine and glutamate, AKG is recognised as a vital component in immune metabolism.
Glutamine, derived from AKG, acts as an essential fuel for lymphocytes and macrophages—the primary cells involved in immune responses.
Macrophages and neutrophils, in particular, are critical to your body’s early, non-specific defence mechanisms and play a vital role in protecting against conditions like sepsis.
Research has shown that during inflammatory states, such as sepsis or injury, the demand for glutamine by immune cells significantly increases.
This increased consumption is essential for sustaining immune cell function under stress.
Supplemental glutamine has been proven to enhance the bactericidal activity of neutrophils, especially in patients recovering from burns or surgery.
Studies have also linked reduced glutamine levels with decreased phagocytic activity in macrophages, which are essential for engulfing and destroying pathogens.
One study highlighted that oral glutamine supplementation could reduce bacterial translocation in experimental models of gut-origin sepsis.
This suggests that AKG, as a glutamine homologue, has immune-enhancing properties that help maintain gut barrier integrity, increase immune cell activity, and strengthen neutrophil function and phagocytosis.
By reducing bacterial translocation in the body, AKG supports the immune system’s ability to fight off infections and maintain overall stability, making it a valuable nutrient for immune health.
Through these mechanisms, AKG not only provides fuel for your immune cells, but also enhances their capacity to function, contributing to a stronger and more responsive immune defence.
6. AKG and biological age
A recent study has revealed that CaAKG might hold the key to reducing biological age.
The research involved 42 individuals who took Rejuvant®—a supplement containing sustained-release CaAKG with added vitamins [3].
After just seven months, these participants saw an impressive reduction in their biological age, averaging about eight years, as measured by the TruAge DNA methylation test. Learn how to test your biological age here.
The most significant improvements were noted in those whose biological age was higher than their actual age, suggesting that CaAKG could be particularly beneficial for people who are ageing faster than expected.
Whilst more research, including controlled trials, is needed to fully understand its potential, these findings hint at CaAKG being a strong contender in the fight against ageing.
Calcium AKG supplement for longevity
As a dietary supplement, AKG is available in the form of AKG salts, such as calcium or potassium alpha-ketoglutarate.
CaAKG is preferred in supplement form due to its improved stability and absorption compared to AKG alone.
The calcium component helps to protect AKG from rapid degradation in the digestive system, ensuring that a higher percentage of AKG reaches the bloodstream and is available for the body to use.
Besides, the gradual release of AKG from the CaAKG compound provides sustained benefits, making it an ideal choice for those looking to enhance their energy metabolism, support longevity, and maintain overall health.
Studies have shown how CaAKG supplementation in mice not only extends lifespan, but also compresses morbidity, leading to a healthier life with decreased levels of inflammatory cytokines.
AKG dosage and safety
In research settings, the dosage of alpha-ketoglutarate typically ranged from 3.6 g to 6 g per day, with higher amounts often administered to those recovering from burns.
However, a precise recommended daily dose for general use has yet to be firmly established.
Avea provides 1g of CaAKG per sachet of the Collagen Activator, striking a balance that aligns with current research whilst ensuring safety for daily use.
Our study, conducted in collaboration with scientists at ETH Zurich, demonstrated that combining CaAKG with Colgevity—an Avea patent-pending blend of 5g glycine, 1.7g proline, and 1.7g hydroxyproline—can contribute to even greater lifespan extension, as shown in model organisms like C. elegans.
Avea’s formula thus, enhances collagen synthesis and supports overall longevity, offering a comprehensive approach to health and vitality.
AKG side effects
Alpha-ketoglutarate supplementation on its own does not seem to carry significant side effects.
Research has determined the no observed adverse effect level (NOAEL) for AKG to be at 1g/kg of body weight in rats, indicating a high level of safety.
Yet, we do not recommend for pregnant or breast-feeding women, as not enough is known about the use of AKG in these groups.
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