Ornithine Overview

1) Studied Conditions

Ornithine has been studied for a variety of conditions, including but not limited to:

• Improving sleep quality
• Reducing fatigue, especially related to physical exercise
• Enhancing liver function and supporting liver health
• Ammonia detoxification, particularly in individuals with a urea cycle disorder
• Wound healing
• Promoting muscle growth and body composition

2) Efficacy in Treating Conditions

The effectiveness of ornithine in treating these conditions varies:

• Some studies suggest that ornithine may help improve sleep quality and reduce stress.
• It may also reduce fatigue associated with extended physical activity, but more research is needed.
• Its role in improving liver function and aiding in ammonia detoxification is significant, particularly in those with urea cycle disorders.
• There is less evidence for its effectiveness in wound healing and muscle growth, and results from studies have been mixed.

3) Health Benefits

Ornithine is associated with several potential health benefits, including:

• Stimulating the release of growth hormone, which might contribute to muscle growth and increased metabolism.
• Potentially aiding in weight loss due to its effects on metabolism and body composition.
• Supporting the urea cycle by removing excess ammonia from the body, which is crucial for individuals with certain metabolic conditions.
• Improving sleep and reducing stress, which can have broad implications for overall health.

4) Downsides

While ornithine is generally considered safe for most people, there are some potential downsides to consider:

• Excessive use may cause gastrointestinal distress, such as bloating, abdominal pain, and diarrhea.
• People with preexisting conditions, particularly kidney or liver diseases, should exercise caution and consult a healthcare provider before supplementing with ornithine.
• As with any supplement, there is a potential for interactions with other medications.
• Long-term effects and safety of ornithine supplementation have not been thoroughly studied.

5) Genetic Variations

The impact of ornithine on specific genetic variations can vary:

• Individuals with genetic mutations that affect the urea cycle, such as ornithine transcarbamylase (OTC) deficiency, may benefit from ornithine supplementation to help manage their condition.
• However, the supplementation should be carefully monitored by a healthcare professional to avoid adverse effects and ensure proper dosage.
• There is limited research on the broader implications of ornithine supplementation in relation to other genetic variations.

Ornithine Research Summary

Effects on Exercise Performance and Ammonia Metabolism

L-ornithine hydrochloride was assessed for its impact on exercise performance and ammonia metabolism in healthy adults. While it did not enhance aerobic capacity, it significantly increased plasma ammonia and glutamate post-exercise, suggesting improved ammonia management.

Enzymatic Production of L-Ornithine

An enzymatic process using arginase, activated by manganese ions and stabilized by ascorbic acid, was developed for large-scale production of L-ornithine, showing promise for parenteral nutrition and active peptides manufacturing.

Liver Cell Transport of Ornithine and its Role in Urea Cycle

Research indicates that the transport of ornithine into liver cells and mitochondria is critical for urea production. Inadequate ornithine availability within mitochondria may limit urea cycle efficiency, suggesting a potential bottleneck in ammonia detoxification.

Management of Urea Cycle Disorders (UCDs)

European guidelines were developed for the diagnosis and management of UCDs, aiming to standardize care and improve patient outcomes despite the nonspecific symptoms and low disease awareness.

Late-Onset Ornithine Carbamoyltransferase Deficiency

A case study highlighted the successful treatment of hyperammonemia in a patient with late-onset OTC deficiency using a combination of arginine, sodium benzoate, and hemodialysis.

Genetic Mutations and OTC Deficiency

Updates on genetic mutations associated with OTC deficiency included 244 mutations and 13 polymorphisms, offering insights into the variable disease severity and highlighting the need for identifying mutations in non-coding regions.

Ornithine Supplementation and Physical Fatigue

L-ornithine supplementation showed promise in reducing fatigue by enhancing lipid metabolism and stimulating the urea cycle, as evidenced by subjective fatigue measurement and blood marker changes in a study with healthy volunteers.

Ornithine Alpha-Ketoglutarate and Amino Acid Metabolism

Research on OKG showed its ability to influence plasma amino acid levels differently when combined, suggesting a unique impact on amino acid metabolism and insulin levels in healthy male subjects.

Gastrointestinal Side Effects of Amino Acid Supplements

Intake of arginine and related amino acids such as ornithine can lead to gastrointestinal side effects like diarrhea, with studies suggesting dosage strategies to mitigate these effects.

Ammonia's Role in Exercise-Associated Fatigue

Ammonia production during physical activity and its potential contribution to fatigue have been examined, drawing parallels with clinical conditions involving elevated blood ammonia.

Methodological Approaches for Producing L-Ornithine

The enzymatic process for L-ornithine production from arginine using arginase from calf liver was detailed, highlighting enzyme stability and the potential for industrial-scale production.

Ornithine and its Implications in Various Contexts

Various studies explore ornithine's role in metabolic pathways, nutritional supplementation, fatigue reduction, ammonia detoxification, and potential therapeutic applications in conditions such as urea cycle disorders and hepatic encephalopathy.

References:

1. The effect of L-ornithine hydrochloride ingestion on performance during incremental exhaustive ergometer bicycle exercise and ammonia metabolism during and after exercise
2. An enzymatic route to L-ornithine from L-arginine--activation and stabilization studies on L-arginase
3. An enzymatic route to L-ornithine from arginine--activation, selectivity and stabilization of L-arginase
4. Urea cycle disorders: diagnosis, pathophysiology, and therapy
5. A possible rate limiting factor in urea synthesis by isolated hepatocytes: the transport of ornithine into hepatocytes and mitochondria
6. Suggested guidelines for the diagnosis and management of urea cycle disorders
7. Hyperammonemia in a patient with late-onset ornithine carbamoyltransferase deficiency
8. Mutations and polymorphisms in the human ornithine transcarbamylase gene
9. Incidence of inborn errors of metabolism in British Columbia, 1969-1996
10. The physiological role of the polyamines
11. A perspective of polyamine metabolism
12. Conversion of glutamate to ornithine and proline: pyrroline-5-carboxylate, a possible modulator of arginine requirements
13. Adverse gastrointestinal effects of arginine and related amino acids
14. L-ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism
15. Action of ornithine alpha-ketoglutarate, ornithine hydrochloride, and calcium alpha-ketoglutarate on plasma amino acid and hormonal patterns in healthy subjects
16. Plasma and muscle amino acid and ammonia responses during prolonged exercise in humans
17. Tricarboxylic acid cycle intermediates in human muscle during prolonged exercise
18. Ammonia metabolism in exercise and fatigue: a review
19. Cerebral ammonia uptake and accumulation during prolonged exercise in humans
20. Ammonia and amino acid metabolism in human skeletal muscle during exercise
21. Metabolic inter-organ relations by exercise of fed rat: carbohydrates, ketone body, and nitrogen compounds in splanchnic vessels
22. Effects of arginine and ornithine on strength, lean body mass and urinary hydroxyproline in adult males
23. Effect of ammonium ions on synaptic transmission in the mammalian central nervous system
24. Synaptic transmission in ammonia intoxication
25. Hepatic encephalopathy and brain edema in acute hepatic failure: does glutamate play a role?
26. Treatment of hepatic encephalopathy with metronidazole
27. Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis. A double-blind, randomized study using a four-fold crossover design
28. Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double-blind study
29. L-ornithine-L-aspartate infusion efficacy in hepatic encephalopathy
30. Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy: results of a placebo-controlled double-blind study
31. A critical analysis of studies assessing L-ornithine-L-aspartate (LOLA) in hepatic encephalopathy treatment
32. Effect of L-ornithine-L-aspartate on patients with and without TIPS undergoing glutamine challenge: a double blind, placebo controlled trial
33. L-Ornithine-l-aspartate in the management of hepatic encephalopathy: a meta-analysis
34. Simultaneous study of somatotrophic and corticotrophic pituitary secretions during ornithine infusion test
35. Arginine and ornithine supplementation increases growth hormone and insulin-like growth factor-1 serum levels after heavy-resistance exercise in strength-trained athletes
36. A randomized, double-masked, placebo-controlled crossover trial on the effects of L-ornithine on salivary cortisol and feelings of fatigue of flushers the morning after alcohol consumption
37. Metabolic interaction between ornithine and alpha-ketoglutarate as a basis for the action of ornithine alpha-ketoglutarate
38. The synthesis of glutamic acid in the absence of enzymes: implications for biogenesis
39. Does formate reduce alpha-ketoglutarate and ammonia to glutamate?
40. Ornithine uptake by rat liver mitochondria: effect of calcium and arginine
41. Stimulation of L-ornithine uptake and L-citrulline and urea biosynthesis by D-arginine
42. Efficacy of L-ornithine L-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study
43. The effect of L-ornithine L-aspartate and branch chain amino acids on encephalopathy and nutritional status in liver cirrhosis with malnutrition
44. Regulation of enzymes of the urea cycle and arginine metabolism
45. Accumulation of amino acids by the perfused rat liver in the presence of ethanol
46. Ammonia potentiates the lethal effect of ethanol on rats
47. Effect of chronic ethanol or acetaldehyde on hepatic alcohol and aldehyde dehydrogenases, aminotransferases and glutamate dehydrogenase
48. Urea-cycle enzymes in normal liver and in patients with alcoholic hepatitis
49. Racial differences in alcohol sensitivity: a new hypothesis
50. Glutamine and ornithine-alpha-ketoglutarate but not branched-chain amino acids reduce the loss of muscle glutamine after surgical trauma
51. Ornithine alpha-ketoglutarate metabolism after enteral administration in burn patients: bolus compared with continuous infusion
52. Arginine stimulates wound healing and immune function in elderly human beings
53. A randomized trial of isonitrogenous enteral diets after severe trauma. An immune-enhancing diet reduces septic complications
54. Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. A randomized, double-blind, controlled study
55. Glutamine
56. Nutritional and clinical efficacy of ornithine alpha-ketoglutarate in severe burn patients
57. Ornithine alpha-ketoglutarate improves wound healing in severe burn patients: a prospective randomized double-blind trial versus isonitrogenous controls
58. The use of alpha-ketoglutarate salts in clinical nutrition and metabolic care

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