Aspartate Aminotransferase

Aspartate aminotransferase (AST) is an enzyme found primarily in the liver, heart, skeletal muscle, and kidneys, though it's also present in smaller quantities in other tissues. 

Clinically, AST testing plays a pivotal role in assessing liver and heart health. When cells in these organs are damaged or inflamed, AST is released into the bloodstream, making it a valuable biomarker for detecting conditions such as liver disease, myocardial infarction (heart attack), and muscle injury. 

Understanding the testing procedure and the significance of AST levels is essential for clinicians in diagnosing and monitoring various medical conditions. 

What is AST (Aspartate Aminotransferase)?

Aspartate aminotransferase (AST), also known as serum glutamic-oxaloacetic transaminase (SGOT), is a crucial enzyme present in various tissues throughout the body, with particularly high concentrations in the liver, heart, skeletal muscle, and kidneys. 

It plays a pivotal role in amino acid metabolism, facilitating the conversion of aspartate and alpha-ketoglutarate into glutamate and oxaloacetate. 

While AST and ALT are both considered liver enzymes on many blood tests, elevated ALT is more specific to the liver while elevated AST may indicate damage in other organs such as the heart or muscle.

AST exists in two isoforms, cytoplasmic (cAST) and mitochondrial (mAST), each predominantly located in different cellular compartments, offering insights into tissue-specific damage when released into the bloodstream.

AST’s Role in the Body

In the body, AST serves multiple vital functions, primarily participating in energy metabolism and protein synthesis. 

In hepatocytes (liver cells), AST aids in the urea cycle by facilitating the conversion of aspartate and alpha-ketoglutarate into oxaloacetate and glutamate, a process crucial for ammonia detoxification and the production of urea. Additionally, AST plays a key role in the Krebs cycle, contributing to cellular respiration by transferring amino groups between amino acids. 

AST is also integral to cardiac muscle function, where it supports the synthesis of the amino acid glutamate, crucial for maintaining myocardial energy levels and contractile function. 

Its presence in skeletal muscle underscores its role in muscle metabolism, with elevated levels observed in conditions involving muscle injury or breakdown. 

Understanding AST's multifaceted roles provides valuable insights into its significance as a clinical biomarker for liver disease, myocardial injury, and muscle disorders.

Testing AST Levels

Test Procedure

AST is commonly ordered as part of a comprehensive metabolic panel, which includes other biomarkers of health and liver function.  

The standard laboratory testing procedure for aspartate aminotransferase (AST) involves collecting a blood sample from a vein, typically in the arm. 

Fasting is not necessary for an AST test, but it is commonly ordered with other tests that recommend or require fasting.  Speak with your healthcare provider if you have questions about how to perform your AST test.

Reference Range for AST Levels

While reference ranges for AST are given below, it's essential to note that the specific reference range may vary slightly depending on the testing method and laboratory standards. Additionally, normal ranges differ according to age, and according to some experts, by gender.  [2., 3.]

Adults: 0-35 units/L or 0-0.58 μKat/L (SI units) (Values tend to be slightly lower in females than males.)

Elderly: Values are slightly higher than those of other adults. 

Children:

0-5 days: 35-140 units/L

< 3 years: 15-60 units/L

3-6 years: 15-50 units/L

6-12 years: 10-50 units/L

12-18 years: 10-40 units/L 

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What Does Low Aspartate Aminotransferase Mean?

Causes and Implications of Low AST Levels

Low AST (aspartate aminotransferase) levels in the blood are relatively rare but can indicate severe liver disease, such as advanced cirrhosis or end-stage liver failure, where the liver's ability to produce enzymes is significantly compromised. 

Additionally, nutritional deficiencies, particularly in vitamin B6 (pyridoxine), which is a cofactor for AST activity, can lead to reduced enzyme levels. 

Other potential causes of low AST levels include uremia, and the use of metronidazole and/or trifluoperazine.  [1.]

What Does High Aspartate Aminotransferase Mean?

Causes and Risk Factors for Elevated AST Levels

Alcohol-induced liver damage: chronic alcohol ingestion and cirrhosis can elevate AST levels, typically below 300 units/L in alcoholic hepatitis.

Hepatitis: hepatitis may display a high AST:LD (LDH) ratio (>3) with AST peaking at 500−3000 units/L in acute viral hepatitis.

Other liver disease: other liver diseases like early hemochromatosis and chemical injury can also cause AST increases.

Other medical conditions: Reye syndrome and infectious mononucleosis can lead to elevated AST and ALT levels.  [8.]

Trauma, muscle diseases (such as dystrophy, dermatomyositis), and myocardial infarction: skeletal or cardiac muscle damage can cause AST elevation, with AST peaking around 24 hours post-infarction.

Various inflammatory states: pericarditis, pancreatitis, and Legionnaires' disease may increase AST levels, as can renal infarction and lung infarction.

Cholestasis: cholestasis can cause high AST levels due to the impairment of bile flow leading to hepatocellular injury and subsequent leakage of AST from damaged liver cells into the bloodstream.

Some drugs: isoniazid, phenothiazines, erythromycin, progesterone, anabolic-androgenic steroids, halothane, methyldopa, opiates, indomethacin, salicylates in children, and others, with hepatotoxicity from drugs sometimes causing a high AST:ALT ratio. [10.]

‍Acetaminophen hepatotoxicity: this can result in severe liver damage, with AST levels reaching 1960−29,700 units/L and a characteristic pattern of AST elevation greater than ALT.

Understanding High AST Levels

AST elevations are understood as mild, moderate or marked.  [4.]

Marked elevations in aminotransferase levels, defined as exceeding 10 times the upper reference limit, often indicate acute hepatic injury and/or tumor necrosis.  Severe elevations (> 75 times the upper limit) typically suggest ischemic or toxic liver injury, 

Research suggests that the most sensitive threshold for identifying acute injury lies within the moderate range of elevation, between 5 to 10 times the upper limit.  Moderate increases are more commonly associated with acute viral hepatitis, although it may also be seen with:

• Excessive drug or alcohol use
• Certain medications
• Non-alcoholic fatty liver disease
• Cholestasis
• High vitamin A consumption

Non-hepatic origins of moderate AST increases include: [2., 3.]

• Heart damage
• Kidney damage
• Muscle injury
• Hemolysis
• Heatstroke
• Pulmonary embolism

Mild elevations in liver enzymes like AST are common in clinical practice.  The clinician should evaluate potential causes, as they may be the first sign of early liver damage.  
Mild elevations may be caused by:

• Fatty change in the liver
• Alcohol abuse
• Cirrhosis
• Mononucleosis
• Certain drugs

The magnitude and rate of change in aminotransferase levels can also provide valuable initial insights into differential diagnoses, though interpretation can be complex due to overlapping causes and varying patterns of enzyme elevation. 

Understanding these nuances aids in the diagnostic process and helps guide appropriate management strategies.

Medical Conditions Associated with Elevations in AST

Drug, alcohol, medication use, and toxin exposure, should all be ruled out when elevations of liver enzymes are discovered.

Medical conditions associated with mild elevations in liver enzymes include: 

Nonalcoholic fatty liver disease: nonalcoholic fatty liver disease (NAFLD), affecting about 23% of American adults, often presents with mildly raised aminotransferase, especially in patients with metabolic syndrome and insulin resistance (although NAFLD can occur without these conditions).  NAFLD is the most common cause of mild liver enzyme elevations in the Western world.  [5., 9.]

Hepatitis: testing for hepatitis B or C infection is advisable for all patients with mild elevation in aminotransferase levels, considering the high prevalence worldwide and the potential lack of specific risk factors reported by infected individuals.

Hereditary Hemochromatosis: further diagnostic considerations for mild elevations include evaluating for HFE-related hereditary hemochromatosis, characterized by iron deposition in organs, especially in patients with high ferritin levels and transferrin saturation index greater than 45%.

Autoimmune hepatitis: autoimmune hepatitis should be considered in female patients with mild elevations and autoimmune disorders, with diagnosis involving autoantibody testing and liver biopsy, given the complex diagnostic criteria.

Wilson’s Disease: Wilson's disease may be suspected in young patients with signs of hemolysis or psychiatric/neurologic symptoms, confirmed through serum ceruloplasmin levels, copper metabolism testing, and examination for Kayser–Fleischer rings.

α-1-Antitrypsin Deficiency: α-1-antitrypsin deficiency, although uncommonly diagnosed in adulthood, should be considered in patients with pulmonary disease, confirmed through low serum α-1-antitrypsin levels and phenotype determination.

Celiac disease: celiac disease should be considered in patients with unexplained hypertransaminasemia, as up to 10% of such patients may have celiac disease, with diagnosis requiring tissue transglutaminase antibodies measurement and small bowel biopsy confirmation.

How to Lower Aspartate Aminotransferase

Lifestyle modifications for reducing AST levels

Simple diet and lifestyle interventions may help reduce elevations in AST.  

Dietary changes and recommendations:

• Reduce intake of processed foods, sugary beverages, and foods high in saturated and trans fats.
• Increase consumption of fruits, vegetables, whole grains, and lean proteins.
• Limit alcohol consumption or avoid it altogether.
• Maintain a healthy weight through portion control and balanced meals.
• Consider a low-carbohydrate or Mediterranean-style diet, which has shown benefits for liver health.

Exercise and physical activity:

• Aim for at least 30 minutes of moderate-intensity aerobic exercise most days of the week.
• Incorporate strength training exercises to build muscle mass and improve metabolism.
• Stay active throughout the day by taking walks, using stairs instead of elevators, or participating in recreational activities.
• Consult with a fitness professional or healthcare provider to develop a personalized exercise plan.

Medications and Medical Interventions for Reducing AST Levels

• Consult with a healthcare provider to assess the need for medications that may affect liver health, and discuss potential alternatives if necessary.
• If underlying conditions such as diabetes or high cholesterol are contributing to elevated AST levels, follow treatment plans to manage these conditions effectively.
• Consider liver-supportive supplements such as milk thistle or N-acetylcysteine under the guidance of a healthcare provider.
• Regularly monitor liver function through blood tests and follow up with healthcare providers for further evaluation and management as needed.

Importance of Further Evaluation and Management

Regular follow-up and management are crucial for individuals with elevated AST levels to monitor liver health and implement necessary interventions. By closely monitoring AST levels through periodic blood tests, healthcare providers can assess the effectiveness of interventions and make adjustments as needed. 

Implementing diet and lifestyle modifications, such as adopting a healthy eating plan, engaging in regular physical activity, and avoiding alcohol consumption can all help reduce elevated AST levels and improve overall liver function. 

Additionally, maintaining a healthy weight and managing underlying conditions such as diabetes and high cholesterol are essential for optimizing liver health. 

With ongoing support and guidance from healthcare professionals, individuals can take proactive steps to lower AST levels and reduce the risk of liver-related complications.