Alkaline Phosphatase (ALP)

Optimal Result: 44 - 121 U/L, or 44.00 - 121.00 IU/L.

What is Alkaline phosphatase (ALP)?

Alkaline phosphatase (ALP) is an enzyme (= enzymes are proteins that act as biological catalysts by accelerating chemical reactions) found in the blood that helps break down proteins and that plays a role in numerous processes in the human body. Any abnormalities in blood concentrations (either high or low) may be indicative of diseases ranging from gallstones and thyroid disease to hepatitis and cancer.

ALP is found in all tissues of the body but, not surprisingly, is found in its highest concentration in the liver, bones, kidneys, and intestines as well as the bile ducts (that drain bile from the liver) and gallbladder (that stores bile).

Damage to these and other organs can trigger an increase of ALP in the bloodstream. By contrast, certain diseases or conditions can impair ALP synthesis and lead to a drop in the blood concentration.

What are the functions of ALP?

Scientists have not yet identified the full range of biochemical reactions that ALP initiates, but the enzyme is known to contribute to the following processes:

1. Transporting:

  • nutrients and enzymes to and from the liver
  • calcium and phosphate from the intestines to bones, muscles, and nerve cells to ensure normal function
  • fatty acids to store energy in adipose tissues and help maintain the structural integrity of cells

2. Aiding in the development, growth, and maintenance of bone

3. Regulating cell growth in fetuses during pregnancy

Where is ALP produced?

ALP is produced mainly by the liver and bones but is also synthesized in smaller quantities by the intestines and kidneys. ALP is also secreted from the placenta during pregnancy.

What is the ALP test?

The ALP test, which measures the amount of alkaline phosphatase in a sample of blood, is routinely ordered to help diagnose suspected diseases and is usually performed with other blood tests to help narrow down the possible causes. ALP is made mostly in the liver and in bone with some made in the intestines and kidneys. It also is made by the placenta of a pregnant woman.

ALP can be tested alone, but because many conditions can affect ALP levels, it is common to test it alongside other enzymes, such as in a liver panel test, to obtain more information about the most likely cause of abnormal results. An ALP isoenzyme test can identify the part of the body where ALP in the blood originated, but this testing is complex and not widely available.

The purpose of testing ALP is to determine if you have normal levels of this enzyme. An ALP blood test can be used for screening, diagnosis, and monitoring of liver or bone diseases and other health conditions.

ALP is most often tested for diagnosis when there are signs of possible liver problems, such as nausea and vomiting, jaundice, fatigue, abdominal pain, or unexplained weight loss.

It is also often prescribed if you have symptoms of a possible bone disorder, such as bone pain, susceptibility to bone fractures, or abnormal bone shape. ALP measurement as part of a liver panel or CMP (= Comprehensive Metabolic Panel) may help identify the cause of general symptoms.

While ALP levels alone are insufficient to diagnose an underlying condition, they can be an important part of the diagnostic process. The degree of ALP elevation may reflect the type or severity of a condition.

The typical measurement for this test is international units per liter (IU/L), a standardized measurement utilized by most laboratories based on the biological activity of ALP.

The ALP test can be helpful in identifying conditions such as:

→ blockage of bile ducts (from a gallstone, inflammation, or cancer)

→ cholecystitis (inflammation of the gallbladder)

→ cirrhosis (scarring of the liver)

→ some forms of hepatitis (inflammation of the liver)

You may also need an ALP test if you’re taking a medication that has the potential to damage your liver, such as acetaminophen (Tylenol).

The ALP test can be helpful in the diagnosis of bone concerns such as:

→ rickets, a weakening or softening of the bones in children that’s most commonly due to a significant deficiency of vitamin D or calcium

→ osteomalacia, a softening of the bones in adults usually due to significant vitamin D deficiency, but also possibly due to the body’s inability to process and use vitamin D properly.

→ Paget’s disease of the bone, a condition causing serious concerns with bone destruction and regrowth

ALP testing may also be helpful in investigating the presence of cancer tumors, unusual bone growth, or vitamin D deficiency. It can also be used to check the progress of treatment for any of the above conditions.

Drugs can interfere with results:

There are certain drugs that can interfere with the results. If your ALP levels are modestly raised, it may be due to the drugs you are taking rather than an underlying disease or medical condition.

Advise your healthcare provider or the lab if you take any of the following:

  • Anabolic steroids
  • Antibiotics, including penicillins and sulfonamides
  • Anti-epilepsy drugs like Dilantin (phenytoin) and phenobarbital
  • Antihypertensives like Verelan (verapamil), captopril, and methyldopa
  • Birth control pills and other hormonal contraceptives
  • Cortisone
  • Hormone-replacement therapy, including estrogen and testosterone
  • Monoamine oxidase inhibitors (MAOIs)
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin, Advil (ibuprofen), Aleve (naproxen), and Celebrex (celecoxib)
  • Inderal LA (Propranolol)
  • Chlorpromazine
  • Tricyclic antidepressants
  • Zyloprim (allopurinol)
  • Zyrtec Allergy (cetirizine)

Your ALP results:

Your test report will show your measured ALP level, usually reported in international units per liter (IU/L). The report may also list a reference range, which can vary from laboratory to laboratory. One common reference range is from 44 to 147 IU/L, but some professional organizations recommend a range of 39 - 117 IU/L. For this reason, it’s important to check your test report for the lab’s reference range that analyzed your sample. The normal range runs higher in children and decreases with age.

Normal levels of ALP:

Adults: 39 to 117 IU/L

Children: Under 350 U/L

Pregnancy (first trimester): 17 to 88 U/L

Pregnancy (second trimester): 25 to 126 U/L

Pregnancy (third trimester): 38 to 229 U/L

ALP values that fall outside these reference ranges are considered abnormal. On their own, abnormal ALP values are not diagnostic but can provide a clue as to the underlying cause.

References:

Verma J, Gorard DAPersistently elevated alkaline phosphataseCase Reports 2012;2012:bcr2012006768.

Sharma, U., Pal, D. & Prasad, R. Alkaline Phosphatase: An Overview. Ind J Clin Biochem 29, 269–278 (2014). https://doi.org/10.1007/s12291-013-0408-y

Brichacek AL, Brown CM. Alkaline phosphatase: a potential biomarker for stroke and implications for treatment. Metab Brain Dis. 2019 Feb;34(1):3-19. doi: 10.1007/s11011-018-0322-3. Epub 2018 Oct 4. PMID: 30284677; PMCID: PMC6351214.

Links:

https://medlineplus.gov/lab-tests/alkaline-phosphatase

https://www.testing.com/tests/alkaline-phosphatase-alp/

What does it mean if your Alkaline Phosphatase (ALP) result is too low?

Abnormally low ALP levels are less common but can occur due to: 

→ malnutrition

→ nutrient deficiencies

→ hypothyroidism

→ and some rare inherited disorders that affect ALP or liver function

Persistently low levels of ALP could indicate hypophosphatasia (HPP), a rare genetic disorder characterized by impaired mineralization (“calcification”) of bones and teeth.

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Although high levels of ALP are more common than low levels, low levels may be medically meaningful in some circumstances. For example, low levels of ALP are sometimes found in the following medical situations:

  • Wilson’s disease (a rare genetic condition where copper builds up in your body)
  • Zinc deficiency
  • Pernicious anemia (a decrease in red blood cells that occurs when the intestines cannot properly absorb vitamin B12.)
  • Celiac disease (a serious autoimmune disease that occurs in genetically predisposed people where the ingestion of gluten leads to damage in the small intestine.)
  • Congenital hypophosphatasia [absence or low levels of serum alkaline phosphatase due to mutations in the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP)]

ALP can be used in diagnosis of these and related conditions. It is also sometimes used to monitor these conditions after treatment.

Abnormally low ALP values may be the result of:

  • Achondroplasia (a form of dwarfism)
  • Aplastic anemia (anemia caused by bone marrow failure)
  • Congenital iodine deficiency
  • Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease

What does it mean if your Alkaline Phosphatase (ALP) result is too high?

Elevated ALP can be indicative of liver or bone diseases as well as many other types of conditions. But high ALP levels are not always a sign of a problem. Interpretation of your test results can involve consideration of multiple factors:

→ The degree of elevation: Very high levels are often seen with blockages of the bile ducts, but these levels alone cannot distinguish between liver problems and other conditions.

→ Other test measurements: ALP is often measured along with other enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), and/or 5′-nucleotidase (5’-NT), and the levels of ALP relative to these enzymes can help determine the significance of your test result.

→ Your overall health: Any symptoms you are experiencing will be considered alongside your ALP levels.

Your doctor can account for the fact that ALP levels can be elevated without any underlying illness. For example, ALP is usually higher in pregnant women, growing children and adolescents, and older adults. ALP produced in the intestine can also increase after fatty meals for people with certain blood types.

Some conditions cause large amounts of ALP in the blood. These conditions include: 

→ rapid bone growth (during puberty)

→ bone disease (such as Paget's disease or cancer that has spread to the bones)

→ a disease that affects how much calcium is in the blood (hyperparathyroidism)

→ vitamin D deficiency

→ or damaged liver cells.

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Higher-than-normal levels of ALP in your blood may indicate a health concern with your liver or gallbladder. This could include a blockage in your bile ducts, gallstones, cirrhosis, liver cancer, and some forms of hepatitis.

High levels may also indicate a concern related to the bones such as rickets, Paget’s disease, bone cancer, or an overactive parathyroid gland.

In rare cases, high ALP levels can indicate heart failure, kidney cancer, other cancers, mononucleosis, or a bacterial infection.

Very high ALP levels:

Very high levels of ALP can be caused by liver problems, such as hepatitis, blockage of the bile ducts (obstructive jaundice), gallstones, cirrhosis, liver cancer, or cancer that has spread (metastasized) to the liver from another part of the body.

High ALP levels can be caused by bone diseases, such as Paget's disease, osteomalacia, rickets, bone tumors, or tumors that have spread from another part of the body to the bone, or by overactive parathyroid glands (hyperparathyroidism). Normal healing of a bone fracture can also raise ALP levels.

Heart failure, heart attack, mononucleosis, or kidney cancer can raise ALP levels. A serious infection that has spread through the body (sepsis) can also raise ALP levels.

Women in the third trimester of pregnancy have high ALP levels because the placenta makes ALP.

Abnormally high ALP values may be the result of:

  • Bacterial infections
  • Cholangiocarcinoma (bile duct cancer)
  • Cholelithiasis (gallstones)
  • Biliary obstruction or dyskinesia (lack of motility)
  • Bone cancers, including osteosarcoma and chondrosarcoma
  • Bone conditions, including osteomalacia and osteoporosis
  • Cholecystitis (gallbladder inflammation)
  • Cirrhosis (scarring of the liver)
  • Congestive heart failure
  • Drug-induced liver toxicity
  • Hepatitis, infectious and non-infectious
  • Hepatocarcinoma (liver cancer)
  • Hyperthyroidism (overactive thyroid gland)
  • Hyperparathyroidism (overactive parathyroid gland)
  • Kidney cancers, including renal cell carcinoma
  • Lymphoma (cancer of the lymphatic system)
  • Metastatic cancer to the liver or bone
  • Mononucleosis (a viral infection)
  • Myelofibrosis (a disease of the bone marrow)
  • Myocardial infarction (heart attack)
  • Paget's disease (a disorder causing accelerated bone growth)
  • Prostate cancer
  • Rickets (softening of bones usually due to vitamin D deficiency)
  • Sarcoidosis (a disease that causes granular masses)
  • Sepsis (an extreme inflammatory response to an infection)

Very high levels can also be found if significant liver damage is causing the poor flow of bile out of the ducts. This might happen due to the autoimmune disease primary biliary cholangitis, liver injury from drug use, or from severe hepatitis from alcohol use. Diseases that infiltrate the liver can also cause this issue, such as cancer, sarcoidosis, or amyloidosis.

Slightly elevated ALP levels:

If elevation is not quite that high, other possibilities are more likely. For example, this might happen due to:

  • Cirrhosis of the liver
  • Viral hepatitis
  • Congestive heart failure
  • Abdominal infections
  • Hodgkin lymphoma
  • Hyperparathyroidism
  • Hyperthyroidism
  • Osteomyelitis
  • Bone cancer or cancer spread to the bone
  • Osteomalacia (softening of the bones)

What are the next steps if your ALP levels are elevated?

If the ALP level is high, more tests may be done to find the cause. The amounts of different types of ALP in the blood may be measured and used to determine whether a high level is from the liver or bones. This is called an alkaline phosphatase isoenzymes test.

You might not need extensive medical evaluation if your ALP is only a little elevated. Instead, your clinician may choose to monitor you with repeated blood tests. Somewhat increased ALP can occur in some individuals, even though no real problem is present. However, high levels need further medical investigation.

Follow-up tests will depend on the medical context: your symptoms and physical exam, your other past and present medical conditions, other test findings, etc. You may have gotten your ALP test in the context of other tests that help evaluate the liver, which can provide more information about what your test results mean. If not, other blood tests that are often given to evaluate the liver may be needed.

Sometimes it’s helpful to get a specific blood test called γ-glutamyl peptidase (GGTP) if one’s ALP is elevated. This test can help determine if the liver is the source of the increase or if it’s probably coming from another place.

It is also sometimes helpful to run a different type of ALP test (electrophoresis). This test gives information about the fraction of ALP that comes from different organs, indicating the probable organ of concern. Most of the time, these tests find the increase coming from bone disease or liver or gallbladder problems.

Other blood tests may also be needed, depending on the context. For example, if your clinician is concerned that hepatitis might be the cause of your symptoms and ALP results, you might need to test for hepatitis B and hepatitis C virus. Additional blood tests may also be necessary, such as antimitochondrial antibody (AMA). AMA is a blood test that helps diagnose primary biliary cholangitis, which is a disease which damages bile ducts in the liver and predominantly affects women.

Abdominal ultrasound can also be useful as the first imaging modality to evaluate the liver, gallbladder, and related structures. If necessary, other techniques may be performed as well, like endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP).

Other investigations, like liver biopsy, might be needed under specific circumstances. Your clinician will work with you to identify the underlying cause.

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