Alkaline Phosphatase

Alkaline phosphatase (ALP) is a vital biomarker used to assess various health conditions. This enzyme plays a crucial role in several physiological processes, primarily bone formation, liver function, and bile duct health. 

Clinicians rely on ALP measurements obtained through routine blood tests to diagnose and monitor liver and bone disorders, as well as to evaluate the efficacy of treatments. 

Understanding the significance of ALP levels aids healthcare providers in identifying underlying medical conditions and guiding appropriate interventions to promote patient health.

What is Alkaline Phosphatase?

Definition and Function of Alkaline Phosphatase

Alkaline phosphatase (ALP) is an enzyme found in various tissues throughout the body, including the liver and bile duct, bones, kidneys, and intestines.  It is also present in the placenta of pregnant people.

Alkaline phosphatase (ALP) functions primarily in dephosphorylation reactions, removing phosphate groups from molecules such as nucleotides and proteins. In the liver, ALP helps in the metabolism of lipids and detoxification processes, while in bones, it is involved in mineralization and bone formation. Additionally, ALP plays a role in intestinal function, aiding in the absorption of nutrients.

ALP requires zinc and magnesium to function.  [6.]

Alkaline Phosphatase in Blood Tests

Testing alkaline phosphatase (ALP) levels in the blood involves a simple blood draw, typically from a vein in the arm. The blood sample is then sent to a laboratory for analysis. ALP levels are measured using automated clinical chemistry analyzers, which detect the enzyme activity in the sample.

The patient should be fasting for a minimum of 8 hours prior to the blood draw.  [6.]

Normal Range of ALP

The reference range for ALP in children and teens is higher than it is for adults, primarily because their bones are growing and remodeling. Additionally, reference ranges may vary slightly depending on the laboratory and testing methods used.  

Results are typically reported as units/L (U/L).

Common reference ranges include [5., 12.]

Adults: 30 units/L-120 units/L to 44-147 U/L

Children: < 350 units/L 

Adolescent (male): < 500 units/L 

Adolescent (female > 15 years): 25 units/L-100 units/L 

Interpretation of ALP Levels in Blood Tests

Interpreting ALP test results involves considering the patient's age, gender, and medical history. Elevated levels may indicate liver or bone diseases, while decreased levels can suggest malnutrition or certain genetic conditions. 

It is also important to note that certain normal physiological conditions can cause a normal, transient increase in ALP, notably in adolescence and/or pregnancy.  [4.]

Additional testing and clinical assessment are often needed to determine the underlying cause of ALP abnormalities.

Causes of low Alkaline Phosphatase Levels

Low levels of alkaline phosphatase (ALP) in the blood, while less common than elevated levels, can indicate various underlying conditions. 

Hypophosphatasia, a rare genetic disorder characterized by defective bone mineralization, is a primary cause of low ALP levels, as the enzyme plays a crucial role in bone development. 

Conditions such as malnutrition, severe anemia, magnesium deficiency, hypothyroidism, and Wilson's disease can lead to reduced ALP levels. 

Certain medications, including oral contraceptives, have also been linked to decreased ALP levels. Understanding the potential causes of low ALP levels is essential for clinicians to interpret test results accurately and initiate appropriate diagnostic evaluations and treatment plans for affected individuals.

Causes of High Alkaline Phosphatase Levels

Underlying Medical Conditions

Liver diseases (e.g., hepatitis, cirrhosis): Alkaline phosphatase (ALP) levels increase due to liver cell damage, causing leakage of the enzyme into the bloodstream.

Bone diseases (e.g., Paget's disease, bone metastasis): Elevated ALP results from increased osteoblastic activity associated with bone remodeling or metastatic lesions.

Biliary obstruction (e.g., gallstones, bile duct obstruction): ALP levels rise due to increased synthesis and release from bile duct epithelial cells in response to cholestasis.

Pregnancy (due to placental origin): ALP is normally produced by the placenta during pregnancy, contributing to elevated levels in maternal blood.

Adolescence (due to bone growth): ALP is released during bone growth and remodeling, leading to higher levels in adolescents.

Drug-induced liver injury: Certain medications can cause cholestasis or liver cell damage, resulting in elevated ALP levels.

Inflammatory bowel disease (associated with primary sclerosing cholangitis): Elevated ALP may indicate liver involvement secondary to cholestasis associated with primary sclerosing cholangitis.  [2.]

Autoimmune cholestatic liver diseases (e.g., primary biliary cirrhosis, primary sclerosing cholangitis): ALP levels rise due to damage to bile ducts caused by autoimmune processes.

Metastatic liver cancer: ALP elevation can occur as a result of liver involvement by metastatic cancer cells.

Lymphoma: Elevated ALP may reflect liver involvement in cases of lymphoma metastasis or infiltration.

Infiltrative diseases (e.g., sarcoidosis): ALP levels can increase due to granulomatous infiltration of the liver in diseases like sarcoidosis.

Granulomatous disorders: Granulomatous inflammation in various organs, including the liver, can lead to ALP elevation.

Medications and Lifestyle Factors

Various medications and lifestyle factors can cause elevated ALP levels, including: 

Oral contraceptives: Hormonal contraceptives may induce cholestasis, leading to elevated ALP levels.  [3.]

Antihypertensives (e.g., angiotensin-converting enzyme inhibitors): Some antihypertensive drugs can cause cholestasis, resulting in increased ALP levels.  [1.]

Alcohol consumption: Excessive alcohol intake can cause liver damage, leading to elevated ALP levels due to hepatocellular injury.

Obesity: Obesity is associated with nonalcoholic fatty liver disease (NAFLD), which can result in liver cell damage and increased ALP.

Sedentary lifestyle: Lack of physical activity may contribute to obesity and metabolic disturbances, which can lead to NAFLD and elevated ALP.

Understanding Elevated Levels of ALP

Clinicians may order followup testing including a serum bone isoenzyme ALP measurement to determine if elevated levels are due to extensive bone remodeling.  

Dangerous Levels of Alkaline Phosphatase

Individuals who receive an elevated ALP test result may wonder if this signals a dangerous level of ALP.  

One study demonstrated that extremely high levels of ALP (above 1,000 U/L) in hospital patients was due to three main causes outside of bone remodeling due to metastasis or Paget’s disease:  [7.]

• Sepsis (infection of the blood)
• Malignant obstruction
• AIDS

Dietary and Lifestyle Considerations for High Alkaline Phosphatase

Dietary Considerations for High Alkaline Phosphatase

While there are no specific foods that directly lower ALP levels, adopting a healthy diet can support overall liver health and may indirectly help manage elevated ALP levels. 

• Focus on consuming a balanced diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats. 
• Consider following the Mediterranean diet, which has shown benefit in NALFD (nonalcoholic fatty liver disease).  [11.]
• Drink plenty of water, as proper hydration supports liver function and overall health.

Always consult with a healthcare professional for personalized dietary recommendations tailored to your specific health needs.

Foods to Avoid or Limit

• Avoid excessive intake of processed foods, sugary beverages, and foods high in saturated fats and refined carbohydrates, as these can contribute to liver inflammation and damage. 
• Limit alcohol consumption, as excessive alcohol intake can impair liver function and elevate ALP levels. 

Lifestyle Modifications for High Alkaline Phosphatase

• Maintain a healthy weight through regular exercise and a balanced diet to support liver health.
• Avoid smoking and exposure to secondhand smoke, as smoking can impair liver function and exacerbate liver damage.
• Manage stress through relaxation techniques such as meditation, yoga, or deep breathing exercises, as chronic stress can negatively impact liver health.
• Get regular exercise, as physical activity can help improve liver function and overall health.

Supplement Considerations for High Alkaline Phosphatase

While supplements are not a first-line therapy for elevated ALP due to impaired liver function, some supplements may support liver health:

• Omega-3 fatty acids: Found in fish oil supplements, omega-3 fatty acids have anti-inflammatory properties and may support liver health.
• Milk thistle: Known for its liver-protective properties, milk thistle supplements may help reduce inflammation and promote liver function.
• Turmeric: Contains curcumin, a compound with antioxidant and anti-inflammatory properties that may support liver health.
• Green tea extract: Rich in antioxidants, green tea extract may help reduce liver inflammation and support overall liver function.
• N-acetylcysteine (NAC): Known for its antioxidant properties, NAC may help protect liver cells from damage and support detoxification processes.
• Alpha-lipoic acid: Acts as a powerful antioxidant and may help reduce liver inflammation and improve liver function.