Alkaline phosphatase (ALP) is an important enzyme found in the liver, bones, bile ducts, and other tissues. ALP plays a key role in numerous bodily functions from bone formation to liver health and nutrient absorption. Because of this, it’s also an important biomarker that can reveal imbalances in various parts of the body.
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 certain treatments.
This article will provide patients and healthcare providers with a comprehensive understanding of ALP, its significance in health, the meaning of abnormal levels, and actionable steps to address these issues.
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Introduction to 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.
ALP is involved in a cellular process called dephosphorylation, which removes phosphate groups from molecules such as proteins and nucleotides. This process is essential for many important activities in the body, including:
- Bone formation: ALP contributes to bone growth and remodeling by aiding mineralization.
- Liver function: it supports the liver’s detoxification and fat metabolism.
- Bile duct health: ALP helps manage bile flow and waste removal.
- Nutrient absorption: in the intestines, ALP facilitates nutrient uptake.
- Cell growth and division: ALP is involved in cell growth, division, and development, and affects normal cell functions like reproduction, repair, and differentiation.
Clinical Importance of Alkaline Phosphatase
Healthcare providers use ALP as a biomarker to diagnose and monitor liver and bone disorders and to evaluate treatment progress in certain settings. Understanding ALP levels helps identify possible underlying conditions and direct additional testing and assessment, enabling timely interventions to improve health.
Understanding Alkaline Phosphatase Levels
ALP blood tests are often used as part of a general or routine screening of overall health. While ALP can be found in various parts of the body, the majority of ALP in the blood comes from the liver and bones.
Testing
ALP levels are measured through a simple blood test. Preparation often involves fasting for 8-12 hours to ensure accurate results.
Normal Ranges
The reference range for ALP in children and teens is higher than it is for adults, primarily because their bones are growing and remodeling. Pregnancy can also temporarily increase ALP blood test results.
Additionally, reference ranges may vary slightly depending on the laboratory and testing methods used. It is always important to consult with the laboratory company used to interpret reference ranges.
Results are typically reported as international units/L (IU/L).
Common reference ranges include:
- Adults: 30-120 IU/L to 44-147 IU/L
- Children: according to one study of 873 healthy children, the range of healthy ALP levels was:
- 1–4 years: 474.14–517.71 IU/L
- 5–8 years: 273.47–871.44 IU/L
- 9–13 years: 215.04–893.69 IU/L
- 14–18 years: 228.9–739.22 IU/L
Causes of High Alkaline Phosphatase
A finding of high alkaline phosphatase may prompt further evaluation into its source. Common causes of high alkaline phosphatase include:
Liver-Related Causes
Elevated ALP often indicates liver conditions such as:
- Bile duct obstruction: gallstones or bile duct blockages increase ALP production
- Liver cancer or metastasis: cancer cells invading the liver can raise ALP levels
- Primary biliary cholangitis: autoimmune damage to bile ducts leads to ALP elevation
Bone-Related Causes
Bone diseases can also elevate ALP, including:
- Paget’s disease: abnormal bone remodeling increases ALP activity
- Osteomalacia: soft or weakened bones lead to heightened enzyme levels
- Bone metastases: cancer spreading to bones can elevate ALP
- Fractures: healing bones temporarily increase ALP production
Other Causes
Additional factors contributing to elevated ALP levels include:
- Pregnancy: normal ALP production by the placenta raises the mother’s blood levels of ALP
- Granulomatous disorders: diseases like sarcoidosis can elevate ALP due to liver involvement
- Lifestyle factors: excessive alcohol use, obesity, and certain medications can impact ALP levels
- Infections: some infections can raise ALP levels
- Some hormone conditions: some conditions involving the thyroid or parathyroid gland can affect ALP levels, often because of their effects on the bones
- Some medications: certain medications such as statins can cause ALP levels to rise, often due to their effects on the liver
- Some people may have elevated ALP levels not due to any disease or pathological process. Regular monitoring may be recommended by the ordering provider in these cases.
Causes of Low Alkaline Phosphatase
While less common, low ALP levels may also be seen. Causes of low ALP include:
Medical Conditions
Medical conditions that can cause low levels of ALP include:
- Hypophosphatasia: a rare genetic disorder leading to defective bone mineralization
- Hypothyroidism: slowed metabolic processes affect enzyme production
- Wilson’s disease: copper accumulation in the liver impairs enzyme synthesis
Medications
- Oral contraceptives: hormonal medications may suppress ALP production.
Diagnostic Context
ALP is not a diagnostic test, but rather an indication of an underlying imbalance that may need additional assessment.
Additional Testing to Consider
To pinpoint the cause of abnormal ALP levels, healthcare providers may order additional tests including:
- ALP isoenzyme test: this test measures specific types of alkaline phosphatase in the blood to identify whether elevated levels originate from the liver, bones, or other tissues.
- Liver function tests: this test is used to assess enzymes like GGT, ALT, and AST to confirm liver involvement. GGT is especially useful as it can also highlight gallbladder-related causes.
Clinicians may also consider specialized testing to assess for malignancy and/or imaging for liver, bone, or other organs.
Dangerous Levels
Extremely high ALP levels (>1,000 IU/L) warrant urgent medical evaluation. The main causes of ALP > 1000 IU/L are blocked bile ducts from cancer, liver diseases like metastases, and severe infections like sepsis.
Other causes include blood cancers, alcohol-related liver damage, and rare liver conditions.
The most common causes of ALP > 1000 IU/L are:
Blocked Bile Ducts (Obstructive Diseases):
- Cancer-related blockages: this includes cancers like bile duct cancer (cholangiocarcinoma), pancreatic cancer, and cancers that spread to the bile duct (metastases).
- Non-cancer blockages: usually caused by gallstones, sometimes with an infection called ascending cholangitis.
Liver Diseases:
- Primary liver cancer (hepatoma): this is often diagnosed with a special test (AFP) or a liver biopsy.
- Cancer that spreads to the liver (liver metastases): this can happen with cancers from other parts of the body, like the lungs, pancreas, breast, or colon.
Sepsis (Severe Infections):
- Bacterial infections: these can cause liver issues or abscesses (collections of pus in the liver).
- Fungal infections: fungal infections are seen sometimes in people receiving chemotherapy.
Key point: Sepsis can lead to very high ALP levels even if bilirubin (a liver-related test) is normal.
Other Causes:
Other, less common causes for high ALP >1000 IU/L include:
- Liver damage from alcohol
- Severe pregnancy complications, like preeclampsia
- Other liver problems: Includes conditions like liver cysts, sarcoidosis (a type of inflammation), poisoning from lead, or side effects of medications
Dietary and Lifestyle Considerations
Diet and lifestyle can go a long way in supporting overall health, including liver and bone health, which are key organs to consider when ALP levels increase. Supportive diet and lifestyle measures include:
A Healthy, Micronutrient-Rich Diet
A nutrient-rich diet can support overall health and help regulate ALP levels.
The liver requires numerous macronutrients and micronutrients for optimal health including fiber, protein, anti-inflammatory fats, as well as many key vitamins, minerals, and plant-based antioxidants.
Bones also require a variety of healthy nutrients including calcium, vitamin D, vitamin K, phosphorus, magnesium, adequate protein, and more.
Key dietary practices include:
- Mediterranean diet: the Mediterranean diet emphasizes whole foods like fruits, vegetables, whole grains, lean proteins, and healthy fats, benefiting liver and bone health.
- Hydration: adequate water intake supports proper liver function and aids in detoxification.
Foods to Avoid
Certain foods can negatively impact liver and bone health, such as:
- Processed foods, sugary drinks, and foods high in saturated fats, which are detrimental to overall health; they increase inflammation and can have negative effects on liver and bone health.
- Excessive alcohol, which damages liver cells and increases ALP, and has negative effects on bone health.
Lifestyle Practices
- Exercise: regular physical activity promotes liver function and bone strength.
- Stress management: techniques like yoga and meditation can support overall health.
- Smoking cessation: quitting smoking reduces risks of liver damage and metabolic issues.
Supplement Considerations
While not a first-line treatment, certain supplements may support liver and bone health. These and all supplements should be discussed with a licensed healthcare provider prior to use.
- Omega-3 fatty acids: reduce inflammation and may support liver function
- Milk thistle: known for its liver-supportive properties
- Turmeric (curcumin): offers antioxidant and anti-inflammatory benefits
- N-Acetylcysteine (NAC): supports detoxification and protects liver cells
- Alpha-lipoic acid: reduces oxidative stress and inflammation.
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Key Takeaways
- ALP (Alkaline Phosphatase) is an essential enzyme for liver and bone health.
- Abnormal ALP levels can indicate liver or bone disorders.
- Elevated ALP may signal liver issues (hepatitis, bile duct obstruction) or bone conditions (Paget's disease, healing fractures).
- Low ALP can result from nutritional deficiencies or genetic disorders.
- Healthy diet and lifestyle choices support normal ALP levels.
- Extremely high ALP levels (>1000 IU/L) require immediate medical evaluation.
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