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Ornithine Akg

Also known as: OKG, ornithine AKG, ornithine alpha-ketoglutarate, Ornithine α-ketoglutarate

Overview

Ornithine α-ketoglutarate (OKG) is a synthetic compound formed by the ionic bonding of the amino acid ornithine and α-ketoglutaric acid (alpha-ketoglutarate). Ornithine is a non-proteinogenic amino acid involved in the urea cycle, while α-ketoglutarate is a central metabolic intermediate in energy production via the Krebs cycle. OKG is primarily used as a supplement to support nitrogen metabolism, promote protein synthesis, and reduce muscle catabolism, particularly in individuals experiencing catabolic states such as trauma, surgery, or chronic illness. It is also investigated for its potential to enhance wound healing, improve recovery, and exert anti-inflammatory effects. OKG acts as a precursor for several important compounds, including arginine, citrulline, proline, and polyamines, which are crucial for growth hormone secretion, tissue repair, and maintaining intestinal mucosal integrity. While its biochemical rationale is strong, the research supporting its broad efficacy is moderate, with many studies having small sample sizes or methodological limitations.

Benefits

OKG offers several potential benefits, primarily in conditions of increased metabolic stress. It promotes protein synthesis and nitrogen retention, which can help reduce muscle wasting in catabolic states like trauma or surgery, with some studies showing statistically significant improvements in nitrogen balance and muscle mass preservation, though clinical significance can be modest. In animal models, dietary OKG has been shown to improve weight gain, feed intake, and muscle development, as well as enhance intestinal health and modulate gut microbiota. Furthermore, OKG exhibits anti-inflammatory properties, reducing systemic inflammatory cytokines and potentially alleviating intestinal inflammation in models of colitis. It also demonstrates antioxidant activity and reduced tissue damage in animal studies. For specific populations, surgical and trauma patients may experience improved nitrogen balance and potentially reduced infection rates. Intravenous OKG has shown promise in improving consciousness and neurological scores in stroke patients, linked to enhanced brain oxygen and glucose utilization. However, the overall evidence quality is moderate to low, with a need for more large-scale, well-designed human trials.

How it works

Ornithine α-ketoglutarate (OKG) exerts its effects through the metabolic pathways of its two constituent molecules. Ornithine primarily functions within the urea cycle, facilitating the detoxification of ammonia. Alpha-ketoglutarate, a key intermediate in the Krebs cycle, is crucial for energy production and serves as a precursor for the synthesis of important amino acids like glutamate and glutamine. Together, OKG supports protein synthesis and nitrogen metabolism by providing substrates for these processes. It also enhances the synthesis of polyamines, which are vital for cell growth, differentiation, and tissue repair. Additionally, OKG modulates inflammatory pathways and oxidative stress, contributing to its anti-inflammatory and tissue-protective effects. Its components are absorbed orally and are bioavailable, supporting cellular energy and nitrogen balance.

Side effects

Ornithine α-ketoglutarate (OKG) is generally considered well-tolerated in both clinical and animal studies. There are no consistent reports of common adverse effects occurring in more than 5% of users. Uncommon side effects (1-5%) are not well-documented, though mild gastrointestinal discomfort is a possibility. Rare side effects (less than 1%) are also not well-documented in the available literature. Regarding drug interactions, no well-established interactions have been identified, but caution is advised when combining OKG with other agents that affect nitrogen metabolism. Contraindications are not clearly defined, but individuals with severe metabolic disorders should exercise caution. Data on special populations, such as pregnant women, children, and patients with renal impairment, are limited, and therefore, its use in these groups should be approached with caution and under medical supervision.

Dosage

The optimal dosage for Ornithine α-ketoglutarate (OKG) is not yet standardized, and clinical doses have varied significantly depending on the application and route of administration. In human clinical studies, intravenous doses of up to 25 g per day have been used safely in stroke patients. For animal models, oral doses have ranged from 0.2% to 1% of the diet weight. While a minimum effective oral dose for humans is not clearly established, these animal studies and intravenous human data provide some context. OKG is typically used during catabolic states or recovery phases, suggesting that timing relative to injury or surgery may be important for maximizing its benefits. Oral supplementation is generally used for long-term growth and recovery support, whereas intravenous administration is reserved for acute clinical conditions. The oral bioavailability of OKG is considered adequate, with its components, alpha-ketoglutarate and ornithine, being metabolized in the gut and liver.

FAQs

Is OKG effective for muscle wasting?

Evidence suggests modest benefits in nitrogen retention and muscle preservation in catabolic states like trauma or surgery, but results are not uniformly positive across all studies.

Is OKG safe?

OKG is generally considered safe with few reported side effects in clinical trials. Mild gastrointestinal discomfort is possible, but severe adverse effects are rare.

When should OKG be taken?

OKG is typically recommended during periods of increased catabolism, such as post-surgery, after trauma, or during chronic illness, to support recovery and reduce muscle breakdown.

How quickly do effects appear?

Effects on nitrogen balance and recovery may become apparent within days to weeks of consistent supplementation, particularly in clinical settings.

Does OKG improve exercise performance?

There is limited evidence to support the use of OKG for improving exercise performance. Systematic reviews do not strongly endorse its use for this purpose.

Research Sources

https://research.vu.nl/ws/files/160079366/AlphaKetoglutarate_dietary_supplementation_to_improve_health_in_humans.pdf – This review discusses AKG supplementation, noting that intravenous OKG (1 g/kg) improved brain oxygen and glucose utilization in dogs and stroke patients. It highlights that 25 g/day IV improved neurological outcomes post-stroke, linking the mechanism to glutamate metabolism and protein synthesis. The study acknowledges limitations due to small clinical samples and acute settings.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10255407/ – This PMC article summarizes animal studies demonstrating that dietary OKG (0.2%-1%) improved growth, feed intake, and intestinal health in piglets and chicks. It also found that OKG modulated gut microbiota and reduced inflammation in colitis models, though it notes the need for human trials as these were animal data.
https://caringsunshine.com/relationships/relationship-debility-and-ornithine-alpha-ketoglutarate/ – This source, a systematic review summary, indicates moderate evidence for OKG in reducing muscle wasting and improving nitrogen balance in surgical and trauma patients. It mentions some RCTs showing improved healing and reduced infections, but rates the overall evidence as 2/5 due to small sample sizes and heterogeneity.
https://caringsunshine.com/relationships/relationship-exercise-and-ornithine-alpha-ketoglutarate/ – This systematic review summary finds no strong evidence to support the use of OKG for general debility or exercise enhancement. It suggests that while some benefits exist in specific contexts, broad efficacy for these applications is not well-supported by current research.
https://pubmed.ncbi.nlm.nih.gov/8814202/ – This PubMed abstract describes a study on the effects of ornithine alpha-ketoglutarate (OKG) on protein metabolism in patients with severe burns. It suggests that OKG can improve nitrogen balance and reduce protein catabolism in these highly catabolic states, indicating a potential role in nutritional support for critical illness.