Alanine Aminotransferase

Alanine aminotransferase (ALT) is a crucial enzyme primarily found in the liver, with minor amounts present in the kidneys, heart, and muscles. Clinically, ALT serves as a key biomarker for assessing liver health and function, as elevated levels often indicate liver injury or disease. Understanding ALT levels and their implications is essential for clinicians in diagnosing liver disorders, monitoring disease progression, and guiding treatment decisions for their patients.

What is ALT (Alanine Aminotransferase)?

ALT’s Role in the Body

Alanine aminotransferase (ALT) is an enzyme primarily found in liver cells.  ALT plays a vital role in converting proteins into energy. Specifically, ALT facilitates the conversion of alanine, an amino acid, into pyruvate, which is then used in the citric acid cycle to produce energy. 

Additionally, ALT is involved in the synthesis of glucose (gluconeogenesis) during periods of fasting or low carbohydrate intake, ensuring a steady supply of energy to tissues and organs. Overall, ALT's function is integral to various metabolic processes that support overall health and physiological function.

Normal range of ALT levels

The reference range for alanine aminotransferase (ALT) in serum testing typically falls between 7 to 56 units per liter (U/L) for adult males and 5 to 36 U/L for adult females. However, reference ranges may vary slightly depending on the laboratory and testing methods used.  Additionally, some organizations have recommended lowering ALT upper limit levels to <33 U/L for women, and <45 U/L for men, as necroinflammatory activity has been suggested in patients with untreated viral hepatitis at levels above 30 U/L.  [7., 8.]

Reference ranges for ALT vary among labs, but commonly range between:

Adult males: 7 to 56 U/L

Adult females: 5 to 36 U/L

Testing ALT Levels

ALT 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 alanine aminotransferase (ALT) involves collecting a blood sample from a vein, typically in the arm. 

Fasting is not necessary for an ALT 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 ALT test.

What Does Low Alanine Aminotransferase Mean?

Causes and Implications of Low ALT Levels

Low alanine aminotransferase (ALT) levels can occur due to various factors including chronic liver disease, malnutrition, and advanced liver cirrhosis. Additionally, conditions such as severe vitamin B6 deficiency, and genetic disorders affecting ALT production can lead to decreased levels. 

While low ALT levels are less common than elevated levels, they can signify significant liver damage or impairment of liver function, necessitating further evaluation and medical management.

Low ALT levels alone may not always indicate liver disease, and interpretation should consider other clinical parameters and diagnostic tests.

What Does High Alanine Aminotransferase Mean?

Causes and Risk Factors for Elevated ALT Levels

High levels of alanine aminotransferase (ALT) in the blood often indicate liver damage or injury, which can be either acute or chronic. The most common causes of elevated ALT levels include liver conditions such as hepatitis (viral or autoimmune), fatty liver disease (non-alcoholic or alcoholic), and liver cirrhosis. 

Other potential causes include certain medications, such as statins or acetaminophen, as well as excessive alcohol consumption, obesity, metabolic disorders like diabetes, and exposures to certain toxins including cigarette smoke.  [5.] 

Additionally, ALT levels may rise temporarily after strenuous exercise or due to muscle injury, although it is clinically accepted that ALT elevations are more specific to liver injury.   [2.]

Identifying the underlying cause of elevated ALT levels is crucial for appropriate management and treatment.

Understanding High ALT Levels

ALT elevations are understood as mild, moderate or marked.  [2.]

Marked elevations in aminotransferase levels, defined as exceeding 10 times the upper reference limit, often indicate acute hepatic injury.  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, and non-alcoholic fatty liver disease. 

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

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 ALT

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.  [3.]

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 Alanine Aminotransferase

Lifestyle modifications for reducing ALT levels

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

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 ALT 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 ALT 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 ALT levels to monitor liver health and implement necessary interventions. By closely monitoring ALT 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 ALT 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 ALT levels and reduce the risk of liver-related complications.