Alpha Ketoglutarate: Help for Brain, Gut, Bone, Muscle, and Aging Too

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Welcome to our comprehensive guide on Alpha-Ketoglutarate and its potential benefits as a dietary supplement. In this article, we will delve into the world of Alpha-Ketoglutarate supplements, exploring their uses, dosage recommendations, and potential effects on health and performance. Whether you are an athlete seeking to enhance muscle recovery or an individual looking to optimize overall well-being, understanding the role of Alpha-Ketoglutarate supplements is essential. Join us as we explore the science behind Alpha-Ketoglutarate and its potential impact on various aspects of health and performance. Discover how Alpha Ketoglutarate supplements can support your journey toward better health and vitality.

What is Alpha Ketoglutarate?

Alpha-ketoglutarate (α-KG or AKG) is a crucial molecule made within the body. It is an intermediate molecule in the citric acid cycle (aka the Krebs Cycle or TCA cycle) that turns food and oxygen into energy. Researchers believe that it’s the rate limiting molecule in the citric acid cycle, and therefore energy production, of the organism.

Besides its role in the citric acid cycle, alpha-ketoglutarate helps create the amino acids glutamine and glutamate (building blocks for proteins). It is also involved in other cell processes, such as controlling certain enzymes and responding to low oxygen levels.

Alpha-ketoglutarate (AKG) is a compound that plays a crucial role in several metabolic processes in the body. While it is not typically used as a dietary supplement in the same way as vitamins or minerals, some potential health benefits have been associated with AKG:

What Are the Health Benefits of Alpha-Ketoglutarate?

  • Energy Production: AKG is involved in the citric acid cycle, which is essential for generating energy in the form of adenosine triphosphate (ATP). This process is vital for overall cellular energy production.
  • Muscle Recovery: Some athletes and bodybuilders use AKG supplements for potential benefits in muscle recovery and reducing exercise-induced muscle damage. It is thought to support the removal of ammonia, a waste product produced during intense exercise.
  • Antioxidant Activity: AKG has antioxidant properties, which means it can help neutralize harmful free radicals in the body, potentially reducing oxidative stress and cellular damage.
  • Brain Health: There is some research suggesting that AKG may have neuroprotective effects and could play a role in supporting cognitive function and brain health, although more studies are needed in this area.
  • Immune Support: AKG may help regulate the immune system and contribute to a balanced immune response.
  • Wound Healing: In some clinical settings, AKG has been used in wound healing formulations and as part of nutritional support for patients recovering from surgery or trauma.
  • Detoxification: AKG may support the body’s natural detoxification processes by assisting in the removal of toxins and waste products.
  • Amino Acid Metabolism: It plays a role in the metabolism of amino acids, which are the building blocks of proteins. This could have implications for protein synthesis and overall muscle health.
  • Heart Health: Some studies have suggested that AKG may have a positive impact on cardiovascular health by potentially helping to regulate blood pressure and improve vascular function.
  • Anti-Aging: Some proponents of AKG supplements claim that it may have anti-aging properties, although scientific evidence supporting this claim is limited to animal models.

Alpha-ketoglutarate (α-KG or AKG) is thought to have some health benefits, but more research is needed to know for sure. Here are a few possible benefits:

  • Exercise performance: Some studies suggest that α-KG may help improve exercise performance by reducing muscle fatigue and increasing energy production. REFERENCE NEEDED
  • Aging: Some research shows that α-KG might help slow down the aging process. It could do this by improving cell health and reducing damage to cells. One study in mice found that α-KG extended their lifespan. [PMC8508957]
  • Kidney health: α-KG has been studied in people with kidney problems, but more research is needed before it can be considered safe or effective for people with kidney disease. People with kidney disease must not take nutritional supplements without discussing them with their physician. Nevertheless, one study showed that taking α-KG helped lower levels of harmful substances in the blood of patients with chronic kidney disease [PMC5419544].

Promotes Brown Fat

Alpha-ketoglutarate for adipose tissue rejuvenation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425480/

Dietary alpha‐ketoglutarate promotes beige adipogenesis and prevents obesity in middle‐aged mice https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974731/

AMPK/α-Ketoglutarate Axis Dynamically Mediates DNA Demethylation in the Prdm16 Promoter and Brown Adipogenesis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061633/

Aging

It may be fair to say that one of the primary theories about the fundamental causes for the symptoms of aging is defective energy production within the cells of the body. Metabolism (energy production) within the cells is tightly connected to aging, and Alpha-ketoglutarate is a key metabolite in the tricarboxylic acid (TCA) cycle, and its levels change with fasting, exercise, and aging. When a calcium salt of AKG was given to mice, it increased their lifespan and healthspan. To probe the relationship between healthspan and lifespan extension in mammals, we performed a series of longitudinal, clinically relevant measurements. We find that CaAKG promotes a longer, healthier life associated with a decrease in levels of systemic inflammatory cytokines. Researchers propose AKG suppresses chronic inflammation, leading to health benefits.

AKG deficiency in stem and progenitor cells increases with age [27]. As animals age, mitochondrial function is progressively impaired and cellular metabolic flux in the mitochondria declines, which exacerbates AKG deficiency. 

The authors showed that in the mice, AKG reduced frailty and enhanced longevity, indicating a compression of morbidity [PMCID: PMC8508957].

Keywords: IL-10; SASP; alpha-ketoglutarate; frailty; healthspan; inflammation; lifespan; longevity.

AKG may turn off mTOR and turn on AMPK https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629006/


Research Dose: Women-1000 mg AKG + 1000 IU Vitamin D Men-1000 mg AKG with 900 mg Vitamin A.

An epigenetic test (TruAge) was used to determine the effect of Alpha Ketoglutarate on biological aging. Fourty-two participants with an average age of 63 took 1000 mg calcium-AKG for 4 to 10 months (7 months on average). The men’s formula also contained 900 mg Vitamin A while the women’s formula contained an additional 1000 IU Vitamin D. TruAge measures the methylation of 9 areas of 3 genes to estimate biological age. The participants had an average 7.96 year younger biologic age score at the end than at baseline (8.44 years for men and 6.98 years for women).

The researchers note that there may not be using a valid test for biological ageing. Here’s why: AKG may demethylate DNA sites used by the TruAge test to estimate biological age. So this research may possibly be showing a larger effect on methylation-based aging clocks than it would on other indicators of biologic age.

Notes: One of the investigators is a consultant and board member for the company that sells the supplement used in this study. Two investigators are affiliated with the company that markets the TruAge test used in the study. [PMCID: PMC8660611]

Exercise

Alpha-ketoglutarate (AKG) is a key molecule in the Krebs cycle determining the overall rate of the citric acid cycle of the organism. It is a nitrogen scavenger and a source of glutamate and glutamine that stimulates protein synthesis and inhibits protein degradation in muscles. AKG as a precursor of glutamate and glutamine is a central metabolic fuel for cells of the gastrointestinal tract as well. AKG can decrease protein catabolism and increase protein synthesis to enhance bone tissue formation in the skeletal muscles and can be used in clinical applications. In addition to these health benefits, a recent study has shown that AKG can extend the lifespan of adult Caenorhabditis elegans by inhibiting ATP synthase and TOR. AKG not only extends lifespan, but also delays age-related disease. In this review, we will summarize the advances in AKG research field, in the content of its physiological functions and applications.

https://rejuvant.com/How-Rejuvant-Works

In a Youtube Video, Dr. Sinclair, a respected researcher in the field of aging, briefly explains that Alpha Ketoglutarate affects the OSK genes (OCT4, SOX2, KLF4). He explains that these are 3 genes that are usually switched on only in embryos and they play a part in keeping stem cells young. He explains that these 3 genes can be activated by Alpha Ketoglutarate. For those who are interested in the extremely technical details of this process, they are further discussed in this 2019 article. [PMC6462505]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703346/

Food Sources of Alpha Ketoglutarate

Alpha-ketoglutarate itself is not typically found in significant quantities in foods as it is not a direct dietary nutrient. Alpha-ketoglutarate is a key intermediate in the citric acid cycle (Krebs cycle) and is not typically obtained directly from foods as a dietary source. Glutamate, an amino acid building block of protein, can be converted into alpha-ketoglutarate within the body as part of the normal metabolic processes. Generally, protein foods are rich in glutamate. The actual amount of alpha-ketoglutarate produced from dietary sources of glutamate can vary depending on individual metabolism and overall dietary intake.

Is Alpha Ketoglutarate Safe?

Alpha-ketoglutarate supplements are generally considered safe when taken as directed. Numerous studies and clinical trials have demonstrated their safety profile, with few reported adverse effects. Alpha-ketoglutarate is a naturally occurring molecule in the body and plays a vital role in the citric acid cycle, a fundamental metabolic process. When used as a dietary supplement, it is typically well-tolerated and does not pose significant health risks for most individuals.

Medication Interactions with Alpha Ketoglutarate.

  • Anticoagulant Medications: Alpha-ketoglutarate may interact with anticoagulant medications, increasing the risk of bleeding. It is important to monitor blood clotting parameters and consult with a healthcare professional to ensure safe use.
  • Potassium-Sparing Diuretics: Alpha-ketoglutarate supplements, particularly those containing potassium, may interact with potassium-sparing diuretics, leading to high potassium levels in the body. Regular monitoring and dosage adjustments may be necessary.
  • Calcium Channel Blockers: Alpha-ketoglutarate may interact with calcium channel blockers, potentially affecting their effectiveness or absorption. Close monitoring and dosage adjustments may be required under healthcare professional guidance.
  • Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Alpha-ketoglutarate may interact with NSAIDs, which can impact the therapeutic effects of these medications. Follow healthcare professional advice on appropriate dosages and potential adjustments.
  • Potassium Supplements: Alpha-ketoglutarate supplements containing potassium may interact with other potassium supplements, potentially leading to high potassium levels. Monitor potassium levels and adjust dosages as recommended.

Supplements Interactions with Alpha Ketoglutarate

  • Creatine: Alpha-ketoglutarate may interact with creatine, a popular supplement used for athletic performance and muscle gain. This interaction can potentially enhance the effects of creatine.
  • Branched-Chain Amino Acids (BCAAs): Alpha-ketoglutarate may interact with BCAA supplements, which are commonly used for muscle recovery and athletic performance. This interaction can potentially enhance the effects of BCAAs. Monitor your response.
  • Nitric Oxide Boosters: Alpha-ketoglutarate is often included in nitric oxide boosting supplements, which are used for enhancing blood flow and exercise performance. This combination can potentially amplify the effects of nitric oxide boosters. Monitor your response.
  • Pre-Workout Supplements: Alpha-ketoglutarate is sometimes included in pre-workout supplements, which are used to enhance energy, focus, and exercise performance. This combination can potentially enhance the effects of pre-workout supplements.
  • Other Energy or Performance Supplements: Alpha-ketoglutarate may be found in various energy or performance-enhancing supplements. It is advisable to read product labels.

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Alpha Ketoglutarate

Assists removal of ammonia from central nervous system

Alpha-ketoglutaric acid (AKG) is a ketone derivative of the organic compound glutaric acid. It is important for the proper metabolism of all essential amino acids and the transfer of cellular energy in the citric acid, or Krebs, cycle. It is a precursor to glutamic acid, the non-essential amino acid involved in protein synthesis and the regulation of blood glucose metabolism. In combination with L-glutamate, AKG can reduce levels of ammonia formed in the brain, muscles and kidneys, as well as help balance the body’s nitrogen chemistry and prevent nitrogen excess in body tissues and fluids. Individuals with high protein intake or gastrointestinal microbiota imbalance may benefit from supplemental AKG to help balance ammonia levels and protect tissues.

Take 1 capsule daily or as directed by a healthcare professional

Serving Size: 1 Capsule

Amount Per Serving
Alpha-Ketoglutaric Acid … 300mg


To Sum It Up

Alpha Ketoglutarate supplements offer a promising avenue for people who want to enhance their health and performance. Throughout this article, we have explored the benefits of Alpha Ketoglutarate supplements. From supporting muscle recovery to optimizing overall well-being, these supplements have shown potential in various areas. By understanding the potential benefits and limitations of Alpha Ketoglutarate supplements, you can make informed decisions on how they may fit into your health and fitness goals.


This Article is Not a Substitute for Medical Advice

Dietary supplements are not designed to diagnose, treat, cure, or prevent any disease. The Supplement Sciences website seeks to provide comprehensive access to the most relevant supplement information along with convenient online ordering. We do not provide medical advice and cannot guarantee that every product suggested is completely without risk. Since each person is unique in their health history and medication use, it is important to discuss supplements with your personal physician. Specifically, pregnant women and individuals being treated for cancer or liver or kidney problems must consult their physician about every nutritional supplement they plan to take. People taking medications for the treatment of HIV or with a history of organ transplant must not take supplements without consulting with their physician.


More Technical Detail

Alpha Ketoglutarate is part of KGDHC pictured below–It’s the rate-limiting step in the Krebs/TCA cycle. But did you know that this classic energy cycle can run in reverse?

The “reductive pathway” can be thought of as a reverse or backward version of the TCA (tricarboxylic acid) cycle’s normal metabolism. In the context of the TCA cycle, there are two main phases: the oxidative phase, which generates energy through the oxidation of acetyl-CoA, and the reductive phase, which involves reactions where intermediates of the cycle can be used for biosynthetic purposes.

When people refer to the “reductive pathway,” they are often referring to a reversal of the TCA cycle’s oxidative phase. This can occur under specific conditions where certain intermediates of the TCA cycle are used in biosynthetic reactions to produce molecules such as amino acids and fatty acids. These biosynthetic reactions can effectively reverse some of the oxidative reactions of the TCA cycle.

One notable example is the conversion of oxaloacetate (an intermediate of the TCA cycle) to malate or pyruvate, which can then be used for biosynthesis. This reversal of TCA cycle reactions allows cells to use TCA cycle intermediates to produce the building blocks required for cell growth and proliferation.

So, in a sense, the reductive pathway can be seen as the TCA cycle running backward from its typical energy-producing metabolism to support the synthesis of essential molecules for cell growth and function.

Alpha-Ketoglutarate dietary supplementation to improve health in humans

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