Valine: Uses, Benefits, and Genetics

1) Studied Conditions

Valine, as a branched-chain amino acid (BCAA), has been studied for conditions such as:

• Liver disease
• Muscle wasting
• Metabolic disorders
• Phenylketonuria (as part of a BCAA supplement)
• Exercise performance enhancement

2) Efficacy in Treating Conditions

While valine is essential for human health, its efficacy in treating specific conditions varies:

• Liver disease: It may help improve symptoms in some cases.
• Muscle wasting: Valine may contribute to muscle synthesis, but more research is needed.
• Metabolic disorders: Its role is unclear and requires more study.
• Exercise performance: Some evidence suggests it might help reduce fatigue during exercise.

3) Health Benefits

The health benefits of valine include:

• Supporting muscle growth and repair
• Maintaining proper nitrogen balance in the body
• Improving metabolic function
• Supporting immune system

4) Downsides

Potential downsides of valine, especially when taken in excess, include:

• Imbalance of BCAAs leading to potential negative effects on health
• Possible contribution to conditions such as ALS in excessive amounts
• Risk of hypoglycemia in some individuals

5) Genetic Variations

Valine's impact can vary depending on genetic makeup:

• Individuals with certain genetic mutations that affect BCAA metabolism may require adjusted levels of valine.
• For example, individuals with the Maple Syrup Urine Disease (MSUD) lack the ability to break down valine and other BCAAs, making supplementation harmful.

Valine Research Summary

The research investigates the effects of branched-chain amino acids with a focus on valine on various health aspects in both animal models and human cells.

Impact on Blood Sugar Levels and Muscle Cells

Valine did not lower blood glucose levels in rats during an oral glucose tolerance test, unlike isoleucine. In C2C12 myotubes, valine did not increase glucose consumption in the absence of insulin, contrasting with isoleucine's effect. However, valine, along with leucine, did increase glycogen synthesis in these muscle cells.

Metabolic Pathways in Rats

In rats with skeletal trauma, valine oxidation increased, suggesting a role in nitrogen excretion post-injury. Valine-depleted total parenteral nutrition (TPN) in rats led to fatty liver, but infusing valine directly into the portal vein while maintaining systemic depletion prevented this issue.

Dendritic Cell Function in Cirrhosis

Monocyte-derived dendritic cells (MoDCs) from patients with liver cirrhosis showed impaired maturation and function, which was linked to reduced plasma levels of branched-chain amino acids such as valine. Supplementing valine improved dendritic cell function in these patients.

Valine and Hepatitis C Virus (HCV)

Valine supplementation in a patient with advanced liver cirrhosis due to HCV resulted in a decrease in liver fibrosis markers, a reduction in serum alpha-fetoprotein levels, and a decrease in HCV viral load, suggesting a potential role for valine in treating HCV.

Valine-Depleted Diets in Animals

A valine-depleted diet inhibited tumor growth in rats, but caused fatty liver development. A diet lacking valine but with excess leucine reduced feed intake in pigs, indicating a response to an unbalanced branched-chain amino acid supply.

Conclusion

The research highlights the complex roles valine plays in metabolism, immune function, and disease processes. While valine did not directly improve glucose uptake in muscle cells or lower blood glucose levels in rats, it contributed to glycogen synthesis and influenced dendritic cell function in cirrhosis. Valine supplementation showed potential therapeutic benefits for HCV and helped prevent complications from valine-depleted diets in animal models.

References:

1. Isoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose uptake in C2C12 myotubes
2. Severely increased risk of amyotrophic lateral sclerosis among Italian professional football players
3. Increased persistent sodium current determines cortical hyperexcitability in a genetic model of amyotrophic lateral sclerosis
4. Amino acid effects on translational repressor 4E-BP1 are mediated primarily by L-leucine in isolated adipocytes
5. The conversion of L-valine to glycogen and carbon dioxide in rats receiving p-dimethylaminoazobenzene
6. Amyotrophic lateral sclerosis and sports: a case-control study
7. Isoleucine and valine oxidation following skeletal trauma in rats
8. Branched chain amino acids enhance the maturation and function of myeloid dendritic cells ex vivo in patients with advanced cirrhosis
9. Regulation of amino acid-sensitive TOR signaling by leucine analogues in adipocytes
10. mTOR integrates amino acid- and energy-sensing pathways
11. Insulin production following intravenous glucose, arginine, and valine: different pattern in patients with impaired glucose tolerance and non-insulin-dependent diabetes mellitus
12. Sports and trauma in amyotrophic lateral sclerosis revisited
13. Anti-cancer therapy with valine-depleted amino acid imbalance solution
14. Providing a diet deficient in valine but with excess leucine results in a rapid decrease in feed intake and modifies the postprandial plasma amino acid and α-keto acid concentrations in pigs
15. Prevention of fatty liver and maintenance of systemic valine depletion using a newly developed dual infusion system
16. Increased levels of p70S6 phosphorylation in the G93A mouse model of Amyotrophic Lateral Sclerosis and in valine-exposed cortical neurons in culture
17. The conversion of D-valine to glycogen in the rat
18. Proportionate mortality of Italian soccer players: is amyotrophic lateral sclerosis an occupational disease?
19. Effect of valine-depleted total parenteral nutrition on fatty liver development in tumor-bearing rats
20. Neonatal neuronal circuitry shows hyperexcitable disturbance in a mouse model of the adult-onset neurodegenerative disease amyotrophic lateral sclerosis
21. Changes in motor cortex inhibition over time in patients with amyotrophic lateral sclerosis
22. Extracellular branched-chain amino acids, especially valine, regulate maturation and function of monocyte-derived dendritic cells
23. Valine, a branched-chain amino Acid, reduced HCV viral load and led to eradication of HCV by interferon therapy in a decompensated cirrhotic patient
24. Cortical excitability testing distinguishes Kennedy's disease from amyotrophic lateral sclerosis
25. Monocyte-derived dendritic cell function in chronic hepatitis C is impaired at physiological numbers of dendritic cells
26. The conversion of L-valine to glucose and glycogen in the rat

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