Calcium Alpha Ketoglutarate
Also known as: Alpha-ketoglutarate, AKG, Alpha-ketoglutaric acid, 2-Oxoglutarate, Calcium Alpha-Ketoglutarate, Ca-AKG
Overview
Alpha-ketoglutarate (AKG) is a crucial intermediate in the tricarboxylic acid (TCA) cycle, essential for cellular energy metabolism, epigenetic regulation, and various signaling pathways. Naturally produced in the body, it can also be supplemented to potentially enhance muscle rebuilding, wound healing, and anti-aging processes. AKG plays a significant role in antioxidant functions, nitrogen and ammonia balance, and immune regulation. Research indicates that AKG supplementation may reduce systemic inflammatory cytokines, improve bone health, and enhance longevity. It influences the expression of pluripotency genes, affecting stem cell self-renewal and differentiation. Calcium salt forms (Ca-AKG) are often used to improve AKG's bioavailability. While research is advancing with animal models and some human trials, more extensive human studies are needed to fully validate its effects. AKG is considered generally safe for short-term use, but long-term safety data is limited.
Benefits
AKG supplementation has shown potential benefits in several areas. It supports muscle rebuilding and preservation, with animal models showing that 2% calcium-AKG (Ca-AKG) supplementation extended lifespan and healthspan by 9.6–12.8% and 16.6–19.7%, respectively. AKG may also have anti-aging effects by reducing systemic inflammatory cytokines and improving health outcomes; one human study suggested it reduced biological age by 8 years based on DNA methylation. In menopausal women with osteopenia, a daily dose of 6 g of oral Ca-AKG for 6 months increased bone mass density by 1.6% from baseline and decreased bone reabsorption markers. Additionally, AKG may improve reproductive health by modulating pluripotency genes and enhancing oocyte quality in animal models. It may also improve lab test results in hemodialysis patients with chronic kidney disease. These benefits are more pronounced in older adults, where AKG may improve protein metabolism and reduce frailty, and in menopausal women, where it enhances bone health.
How it works
Alpha-ketoglutarate (AKG) functions primarily within the tricarboxylic acid (TCA) cycle, a critical pathway for cellular energy production. It influences cellular energy metabolism, epigenetic regulation, and various signaling pathways. AKG is also involved in nitrogen and ammonia balance, helping to manage nitrogen waste in the body. As an antioxidant, it helps to neutralize free radicals, reducing oxidative stress. AKG interacts with metabolic, epigenetic, and immune systems, modulating the activity of enzymes like α-ketoglutarate dehydrogenase and glutamate dehydrogenase. It also influences epigenetic markers such as histone methylation, affecting gene expression. The calcium salt form (Ca-AKG) enhances its absorption and bioavailability, improving its utilization in the body.
Side effects
AKG is generally considered safe when taken orally for up to 3 years and topically for up to 8 weeks. However, comprehensive data on common side effects is lacking, though it is generally well-tolerated within the studied durations. Uncommon and rare side effects are not documented in the peer-reviewed literature. There is limited information on drug interactions, but caution should be exercised when using AKG with other metabolic or antioxidant supplements. Due to a lack of data, AKG should be avoided during pregnancy and breastfeeding. While older adults and individuals with chronic diseases may potentially benefit from AKG, consultation with a healthcare professional is recommended before starting supplementation. Long-term safety beyond 3 years has not been extensively studied, necessitating caution with prolonged use.
Dosage
While a minimum effective dose of AKG is not well-established, studies have used doses ranging from a few grams to 6 grams per day. Optimal dosages are not clearly defined, but 2% Ca-AKG in the diet or 6 grams of Ca-AKG per day have shown benefits in animal and human studies, respectively. There is no established maximum safe dose, but long-term use beyond 3 years has not been extensively studied. Consistent daily supplementation is typically used, but no specific timing recommendations are available. Calcium salt forms (Ca-AKG) may enhance bioavailability and absorption. Thiamine is a coenzyme for α-ketoglutarate dehydrogenase, and biotin is involved in the replenishment pathway of AKG, suggesting these may be beneficial cofactors.
FAQs
Is AKG safe to use?
AKG is generally safe for short-term use, but long-term safety and use in pregnancy or breastfeeding are not well-documented. Consult with a healthcare provider before use, especially if you have underlying health conditions.
When should I take AKG?
Consistent daily dosing is recommended, but specific timing is not critical. You can take it with or without food, depending on your preference and tolerance.
What results can I expect from taking AKG?
Improvements in muscle rebuilding, bone health, and anti-aging effects can be expected, but individual results may vary. Monitor your body's response and adjust dosage as needed.
What are common misconceptions about AKG?
AKG should not be confused with ornithine ketoglutarate. Its benefits are based on current research, which is mostly from animal studies and a few human trials. More human studies are needed.
Research Sources
- https://rep.bioscientifica.com/view/journals/rep/168/5/REP-24-0137.xml – This scoping review analyzed 21 studies, primarily in animal models, and found that exogenous AKG supplementation induced dose- and sex-dependent modifications, improving reproductive performance and mitigating oxidative stress. The review highlights the potential of AKG in enhancing reproductive capacity but notes the need for human studies to validate these findings.
- https://www.spandidos-publications.com/10.3892/mmr.2022.12667?text=fulltext – This review examines the potential clinical applications of alpha-ketoglutaric acid based on literature from the past three decades. It highlights AKG's involvement in various metabolic pathways, including the TCA cycle, and suggests its potential clinical applications in diseases related to metabolism and aging, emphasizing its role in metabolic regulation.
- https://www.webmd.com/vitamins/ai/ingredientmono-144/alpha-ketoglutarate-akg – WebMD provides general information on alpha-ketoglutarate (AKG), including its uses, potential benefits, and safety considerations. It serves as a basic overview for consumers, outlining the common applications and precautions associated with AKG supplementation.
- https://research.vu.nl/ws/portalfiles/portal/160079366/AlphaKetoglutarate_dietary_supplementation_to_improve_health_in_humans.pdf – This review assesses the impact of AKG supplementation on human health, noting that it extends lifespan and healthspan in animal models and shows promising effects on bone health and anti-aging in humans. The review underscores the pleiotropic functions of AKG but emphasizes the need for more human trials to confirm these benefits.
- https://patents.google.com/patent/WO2020252014A1/en – This patent application discusses methods and compositions involving alpha-ketoglutarate for improving health and wellness. It details specific formulations and applications of AKG, particularly in the context of dietary supplements and therapeutic interventions, highlighting its potential to enhance various physiological functions.