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L-ALANINE

L-Alanine is an amino acid being investigated in several clinical trials for its potential therapeutic benefits. Current research focuses on two main areas: as a standalone treatment for nonalcoholic steatohepatitis (a severe form of fatty liver disease) and as part of a dipeptide compound with glutamine for protecting the heart during cardiac surgery. These trials aim to assess L-alanine’s safety, tolerability, and effectiveness in improving organ function and reducing damage during medical procedures. This article summarizes the current clinical research on L-alanine and its potential benefits for patients with liver disease and those undergoing cardiac procedures.

Table of Contents

What is L-Alanine?

L-Alanine is an amino acid, which is a building block for proteins in the human body. It’s considered a non-essential amino acid because your body can produce it naturally, though it can also be obtained through diet or supplements. In medical settings, L-Alanine is being studied for its potential therapeutic benefits in various conditions.[1]

L-Alanine is sometimes used in combination with other substances, particularly in the form of N(2)-L-Alanine L-Glutamine dipeptide (also known as Dipeptiven), which combines L-Alanine with glutamine to enhance stability and therapeutic effects.[2][3]

Therapeutic Uses of L-Alanine

Research indicates that L-Alanine may have several therapeutic applications, particularly in liver disorders and cardiac conditions. Clinical trials have focused on investigating its effects in specific health conditions:[1][2][3]

  • Liver disease – particularly nonalcoholic steatohepatitis (a type of liver inflammation caused by fat accumulation)
  • Cardiac protection – during heart surgeries involving cardiopulmonary bypass
  • Anti-oxidant effects – potentially reducing damage from harmful free radicals
  • Anti-inflammatory properties – possibly reducing inflammation in various tissues

L-Alanine for Nonalcoholic Steatohepatitis

One important application being studied is the use of L-Alanine in treating nonalcoholic steatohepatitis (NASH). This is a liver condition characterized by inflammation and fat accumulation in people who drink little to no alcohol. NASH can progress to more serious liver diseases, including cirrhosis and liver failure.[1]

A clinical trial investigated the therapeutic effects of L-Alanine supplementation in patients with NASH. The study aimed to assess both the safety and effectiveness of long-term L-Alanine supplementation on liver function. The treatment protocol involved gradually increasing doses:[1]

  1. 6g of L-Alanine powder once per day for the first month
  2. Twice per day (12g total) for the second month
  3. Three times per day (18g total) from the third month onward for 10 months

This study was designed to evaluate changes in liver biochemistry (blood tests that measure liver function) and histological findings (examination of tissue samples). Additionally, researchers aimed to understand L-Alanine’s effects on gene expression, anti-oxidant response, and inflammatory processes in liver cells.[1]

L-Alanine in Cardiovascular Applications

L-Alanine, particularly when combined with glutamine as N(2)-L-Alanine L-Glutamine dipeptide, is being studied for its potential protective effects during heart surgeries.[2][3]

Two clinical trials have investigated the benefits of this combination in patients undergoing cardiac surgery:

1. For patients with coronary artery disease: This study examined whether glutamine (in the form of N(2)-L-Alanine L-Glutamine dipeptide) could protect the heart and intestines in patients with coronary atherosclerosis (narrowing of heart arteries) who underwent surgery with cardiopulmonary bypass. The treatment involved intravenous infusion during surgery and for 24 hours afterward.[2]

2. For patients with aortic valve stenosis: Another study looked at whether glutamine administration could provide myocardial (heart muscle) protection in patients undergoing aortic valve replacement surgery. Aortic stenosis is a condition where the heart’s aortic valve narrows, obstructing blood flow from the heart to the body. These patients are at high risk for ischemia-reperfusion injury (damage that occurs when blood supply returns to tissue after a period without oxygen).[3]

In these cardiac applications, researchers measured various markers of heart damage (like Troponin T and CK-MB, which are proteins released when heart muscle is damaged) to assess whether L-Alanine/glutamine combination provided protective effects during and after surgery.[2][3]

L-Alanine Formulations and Administration

In clinical studies, L-Alanine has been administered in different forms:[1][2][3]

  • Oral powder form – for liver disease treatment, taken by mouth at doses ranging from 6-18g daily[1]
  • Intravenous (IV) formulation – as part of N(2)-L-Alanine L-Glutamine dipeptide, administered directly into a vein during and after cardiac surgeries[2][3]

The dosing schedules varied based on the condition being treated and the specific protocol of each clinical trial. For example, in cardiac surgery patients, the dipeptide was typically administered before, during, and shortly after surgery to provide protection during the critical period of potential heart damage.[2][3]

Safety and Side Effects

One of the primary goals of the clinical trials was to assess the safety profile of L-Alanine, particularly with long-term use. The NASH study specifically aimed to evaluate “the safety and toxicity profile of long-term administration of L-alanine” over a one-year period.[1]

The available information from these clinical trials does not specifically list common side effects. However, it’s important to note that safety was a primary outcome measure in these studies, indicating that researchers were carefully monitoring for any adverse effects.[1][2][3]

As with any medical treatment, patients should only use L-Alanine supplements under the guidance of a healthcare provider, who can monitor for potential side effects and adjust dosing as needed. This is particularly important since these applications of L-Alanine are still being researched and may not yet be approved as standard treatments for these conditions.[1][2][3]

Study Aspect NASH Trial (NCT00586885) Coronary Artery Disease Trial (NCT01478126) Aortic Stenosis Trial (NCT03341169)
Purpose Assess therapeutic efficacy of L-alanine in nonalcoholic steatohepatitis Evaluate protective properties of glutamine on heart and gut during cardiopulmonary bypass Confirm myocardial protection effect of glutamine in aortic valve replacement
Drug Formulation L-alanine powder (standalone) N(2)-L-Alanine L-Glutamine dipeptide (Dipeptiven) N(2)-L-Alanine L-Glutamine dipeptide
Dosage 6g once daily (month 1), twice daily (month 2), three times daily (months 3-12) 2g/kg/day intravenous infusion 0.25g/kg before surgery + 0.25g/kg after surgery
Treatment Duration 12 months During surgery and 24 hours after 8 hours before and 10 hours after anesthesia induction
Primary Outcomes Safety, tolerability, liver biochemistry, histological findings Various cardiac markers measured at different timepoints Myocardial damage (CK-MB, Troponin-T levels)
Secondary Outcomes Gene profiles, anti-oxidant response, inflammatory response Organ-specific markers (liver, intestine), liver enzymes Cardiovascular index, infections, complications
Control/Comparison Single arm study (no control group) Placebo (0.9% NaCl solution) Placebo (0.9% NaCl solution)

FAQ

  • What is L-alanine and how is it being used in clinical trials? L-alanine is a naturally occurring amino acid (a building block of proteins) that's being studied in clinical trials for two main purposes: 1) As a standalone treatment for nonalcoholic steatohepatitis (NASH), a severe form of fatty liver disease, and 2) As part of a dipeptide with glutamine (N(2)-L-Alanine L-Glutamine) to protect the heart and other organs during cardiac surgery procedures.
  • What dosage of L-alanine is being used in the NASH clinical trial? In the clinical trial for nonalcoholic steatohepatitis (NASH), patients receive L-alanine powder starting at 6g once per day for the first month, then increasing to twice per day for the second month, and finally three times per day (18g total daily) from the third month onward for a total treatment period of one year.
  • How is L-alanine being administered in cardiac surgery trials? In cardiac surgery trials, L-alanine is not used alone but as part of a dipeptide compound with glutamine (N(2)-L-Alanine L-Glutamine). It's administered through intravenous infusion, typically starting before surgery and continuing for hours after the procedure. The exact dosing varies by study, with one trial using 2g/kg/day and another using 0.25g/kg before surgery and another 0.25g/kg after surgery.
  • What outcomes are researchers measuring in these L-alanine clinical trials? For the NASH trial, researchers are measuring liver biochemistry and histological (tissue) findings to assess therapeutic efficacy, along with safety and tolerability of long-term L-alanine supplementation. In cardiac surgery trials, researchers measure markers of heart damage (like CK-MB and Troponin T), organ protection indicators, cardiovascular function, inflammatory responses, and clinical outcomes including complications and infections.
  • What potential benefits might L-alanine offer for patients? Based on the clinical trials, L-alanine may potentially offer benefits such as improved liver function and reduced liver inflammation in NASH patients. For cardiac surgery patients, the L-alanine-glutamine combination may provide organ protection (particularly for the heart) during procedures that involve temporary reduced blood flow, potentially reducing damage from ischemia-reperfusion injury and improving recovery outcomes.

Ongoing Clinical Trials on L-ALANINE

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Glossary

  • Nonalcoholic Steatohepatitis (NASH): A severe form of fatty liver disease where fat accumulation in the liver is accompanied by inflammation and damage, not caused by alcohol consumption. It can lead to scarring (fibrosis), cirrhosis, and liver failure if untreated.
  • L-alanine: A non-essential amino acid (protein building block) that the body can produce naturally. It plays roles in glucose metabolism and protein synthesis and is being studied for therapeutic benefits in liver disease and other conditions.
  • Cardiopulmonary Bypass: A technique used during heart surgery where a machine temporarily takes over the function of the heart and lungs, maintaining circulation and oxygen supply while surgeons operate on the heart.
  • Ischemia-Reperfusion Injury: Tissue damage that occurs when blood supply returns to tissue after a period of oxygen deprivation. The restoration of blood flow can cause inflammation and oxidative damage, paradoxically causing more harm.
  • N(2)-L-Alanine L-Glutamine dipeptide: A compound containing two amino acids (alanine and glutamine) linked together, used in clinical trials to potentially protect organs during cardiac surgery. Also known by the brand name Dipeptiven.
  • Aortic Stenosis: A condition where the aortic valve in the heart narrows, restricting blood flow from the heart to the body and making the heart work harder to pump blood.
  • CK-MB (Creatine Kinase MB Isoenzyme): An enzyme found primarily in heart muscle cells that is released into the blood when there is damage to the heart. It's measured to assess the degree of heart muscle damage.
  • Troponin T (Tn-T): A protein found in heart muscle that is released into the bloodstream when heart cells are damaged. It's a highly specific marker for heart damage and is used to diagnose heart attacks and evaluate heart damage.
  • Liver Biochemistry: Blood tests that measure various enzymes and proteins to assess liver function and detect liver damage or disease. Examples include ALT, AST, and bilirubin levels.
  • Histological Findings: Results from examining tissue samples under a microscope to assess cellular structures and detect abnormalities or disease-related changes.
  • Alanine Aminotransferase (ALT): An enzyme found primarily in the liver that is released into the bloodstream when liver cells are damaged. Elevated levels indicate liver injury or disease.
  • Aspartate Transaminase (AST): An enzyme found in several tissues, including the liver, heart, and muscles. Elevated blood levels can indicate damage to these tissues.
  • Liver Fatty Acid Binding Protein: A protein that helps transport fatty acids within liver cells. When released into the blood, it can indicate liver cell damage.
  • Intestinal Fatty Acid Binding Protein: A protein found in cells lining the intestine that helps transport fatty acids. When found in the blood, it can indicate intestinal damage.
  • Glutathione S-Transferase: An enzyme involved in detoxification that helps protect cells from oxidative stress and toxic substances. Specific forms can indicate damage to particular organs.
  • Cardiovascular Index: A measurement or combination of measurements used to assess heart function and blood circulation efficiency.
  • HSP 70 (Heat Shock Protein 70): A protein that helps protect cells from stress and damage. In heart tissue, its expression can indicate activation of protective mechanisms against injury.

References

  1. https://clinicaltrials.gov/study/NCT00586885
  2. https://clinicaltrials.gov/study/NCT01478126
  3. https://clinicaltrials.gov/study/NCT03341169