Genetic response to alpha-keto glutarate

Disclaimer: This article is for informational purposes only and is not intended for diagnostic use. LifeDNA does not provide diagnostic reports on any traits discussed. Genetics is just one piece of the puzzle; please consult a healthcare professional for comprehensive guidance on any health condition.

Overview

Your body needs energy to do everything, from moving your muscles to helping your brain think. That energy comes from the food you eat. But before your body can use food for energy, it has to break it down. One important step in this process is called the Krebs cycle (also known as the Citric Acid Cycle).

The Krebs cycle is a series of steps that happen inside your cells. It takes compounds derived from food, such as sugars (glucose), fatty acids and amino acids and turns them into energy. This happens in small organelles inside the cells called the mitochondria, which are often called the powerhouses of the cell. The main job of the Krebs cycle is to make energy in the form of ATP that your body can use. ATP or adenosine triphosphate is the fuel your cells use to work.

This is where Alpha-keto glutarate or AKG comes into play. AKG is an intermediate compound that mediates the conversion of food into adenosine triphosphate (ATP). AKG is gaining the interest of researchers for its wide-ranging benefits from supporting cellular energy to promoting longevity and healthy aging. Beyond energy metabolism, Alpha-keto glutarate or AKG is also involved in regulating gene expression, muscle health, immune function, and even lifespan. Interestingly, the way individuals respond to AKG supplementation may vary based on their genetics. Understanding this will help us know how to keep our cells healthy, how to boost energy naturally, and even how to slow down aging.

What Is Alpha-Ketoglutarate?

Alpha-keto glutarate is a special compound that helps our cells make energy. Our bodies make AKG naturally, but we can also take it as a supplement to help our bodies work better. AKG is important for making other things our bodies need, like building blocks for proteins. However, as we get older, our bodies may not use AKG as well, so taking it as a supplement might not work the same for everyone.

AKG also helps the body make two important substances called glutamine and glutamate. These are used to build proteins, help brain cells talk to each other, and keep your immune system strong. Because AKG is involved in so many body processes, scientists are studying it to see if it can help our cells make energy better, help us heal faster, lower swelling in the body, and maybe even help us live longer, as is suggested by studies in animals.

Alpha-Ketoglutarate Functions & Benefits

Helps Build Proteins and Muscles: AKG helps our bodies make two important amino acids—glutamine and glutamate. These are like tiny tools our bodies use to build proteins and keep muscles healthy. They also stop our bodies from breaking down muscle, which could happen when we’re sick or stressed. Glutamine is very important—it helps our gut, immune system, and muscles. Even though muscles store a lot of glutamine, we can run low during tough times. That’s why taking AKG might help us keep enough glutamine when we need it most.
Helps Us Absorb Iron: AKG can also help our bodies absorb more iron from food, especially when we don’t have enough iron or when we’re growing quickly. Iron is important for healthy blood and energy.
Helps Make Collagen: Collagen is a protein that holds our body together—it’s in our skin, bones, and joints. AKG helps an enzyme (P4H) in our body that makes collagen work properly by helping to produce hydroxyproline, a crucial amino acid needed for strong collagen structure. If this doesn’t happen, our bodies can’t make good collagen, and that can affect how long our skin and bones stay strong and stretchy.
AKG Helps Make and Reuse Proline: Proline is another important part of collagen. Our bodies can produce proline using AKG as a precursor. Most of the time, our bodies actually reuse proline from old collagen that’s been broken down. AKG helps with that too, by supporting an enzyme that recycles proline. This means AKG helps both make new proline and reuse old proline, which is great for keeping our skin and bones healthy.
AKG Affects Hormones and Bone Growth: AKG can help our bodies make more of certain hormones like insulin, growth hormone, and IGF-1. These hormones help us grow, heal, and stay strong. In animal studies, giving AKG increased the levels of proline in the blood. AKG works together with vitamin C and iron to help our bodies make collagen—a protein that builds strong bones and skin. So, AKG plays a part in keeping our bones strong and healthy.
Mitochondrial support: As a fuel for the Krebs cycle, AKG boosts cellular energy production, which is critical for tissues with high energy demands, such as muscles and the brain.
Immune regulation: AKG may help modulate the immune response by supporting T-cell function and reducing inflammatory cytokines.
Detoxification: AKGhelps the liver and kidneys clear excess nitrogen and toxins from the body, improving metabolic balance.

Genetic Response to Alpha-Keto glutarate

A recent study investigated how alpha-keto glutarate (AKG) supplementation affects growth, nutrient use, antioxidant capacity, and gene expression in Nile tilapia when combined with different protein levels in the diet. Researchers tested five diet groups: four with 1% AKG at varying protein levels (20%, 25%, 30%, and 35%) and one control group with 35% protein and no AKG.

After 60 days, the group fed a diet with 30% protein and 1% AKG showed significantly better growth, nutrient utilization, and antioxidant enzyme activity (SOD and CAT) compared to regular diet. Notably, the expression of the growth-related gene IGF-1 was significantly upregulated in this group, indicating a genetic response to AKG that supports growth. Inflammatory markers like TNF-α were lower in the lower-protein AKG groups, suggesting improved immune status.

Interestingly, the 25% protein + AKG group ( achieved similar growth results as the 35% protein control group without AKG , highlighting that AKG may reduce the need for higher protein input in aquafeeds without compromising growth.

The findings suggest that AKG not only supports better physical growth but also activates genes related to growth and inflammation control, offering a promising dietary strategy for more sustainable fish farming.

People with certain genetic profiles may experience greater benefits from AKG supplementation, particularly if their natural AKG metabolism or mitochondrial function is suboptimal. Genetics plays a major role in how well AKG works in the body. With the help of personalized testing and informed supplementation, AKG may offer a science-backed way to enhance vitality and support healthy aging at the cellular level.

Sources of Alpha-Ketoglutarate

While AKG is naturally produced in the body, dietary intake can also support its levels. Foods high in protein, especially those rich in glutamate or glutamine (like meats, eggs, and dairy), may indirectly boost AKG production. However, these dietary sources typically don’t provide a significant amount of free AKG.

Supplemental AKG is often available in the form of calcium alpha-ketoglutarate (Ca-AKG), which is more stable and better absorbed. This form has been used in many aging and mitochondrial health studies, showing promising results.

Who Might Benefit from Alpha-Ketoglutarate?

Because AKG plays a foundational role in energy metabolism and cellular repair, the people who may benefit the most include:

Older adults: looking to preserve muscle, bone, and cognitive function
Athletes or active individuals: recovering from intense training
People with mitochondrial or metabolic dysfunction: including fatigue-related conditions
Those under chronic stress: who may have elevated inflammation and reduced recovery capacity
Biohackers and longevity enthusiasts: exploring ways to slow biological aging

Genetic testing may help identify whether someone has variants that could impair mitochondrial function or AKG metabolism, making supplementation especially useful.

Safety and Precautions of Using AKG

While alpha-ketoglutarate (AKG) is used by some people for conditions like long-term kidney disease and other health issues, it’s important to be careful when using it.

Safety: Taking AKG by mouth appears to be safe for most people when used for up to three years. Using AKG on the skin is also likely safe for up to eight weeks. However, it’s best not to use it for longer periods without checking with a healthcare professional.

Pregnancy and Breastfeeding: There isn’t enough reliable information about how safe AKG is for pregnant or breastfeeding women. To be safe, it’s recommended to avoid using AKG during pregnancy and while breastfeeding.

Other Uses: Although some people use AKG for things like aging skin, improving athletic performance, or helping with liver disease, there isn’t enough strong scientific evidence yet to prove that it works for these purposes.

Before starting AKG, especially if you have health conditions or are taking other medicines, talk to your doctor to make sure it’s safe for you. As more people turn to personalized health strategies, the importance of understanding genetic and biological responses to supplements like AKG is becoming clearer.

Emerging research suggests that tailoring AKG supplementation based on genetic markers could optimize benefits—especially in areas like muscle maintenance, cellular aging, and brain health.

How LifeDNA’s Nutrition Report

LifeDNA’s Nutrition Report doesn’t just help you understand your dietary tendencies—it can also offer insights into how your body might process and respond to key compounds like Alpha-Ketoglutarate (AKG). Because AKG is connected to several metabolic and cellular processes, your genetic profile, especially those genes influencing protein metabolism, mitochondrial efficiency, and nutrient absorption may affect how your body utilizes AKG.