Alkaline phosphatase (ALP) blood test: what it measures, normal levels, and what high or low ALP means

Alkaline phosphatase is a family of enzymes that remove phosphate groups from molecules, most active in alkaline conditions, hence the name. The blood level is the sum of several forms, called isoenzymes, from different tissues: the liver form, made by the cells lining the small bile ducts and released when bile flow is obstructed or irritated; the bone form, made by osteoblasts as they build bone; an intestinal form that rises after a fatty meal in people with blood types O and B; and a placental form in the second half of pregnancy. Some tumors also produce it.

Because the routine test cannot tell these forms apart, a high ALP is interpreted with company. GGT, another enzyme from the bile ducts, rises with liver ALP and not with bone ALP; a high ALP with a high GGT is the liver, a high ALP with a normal GGT is usually bone or placenta. Laboratories can also separate the isoenzymes directly or measure bone-specific ALP when the source is unclear.

ALP is on every comprehensive metabolic panel and hepatic panel and so is checked routinely. It is ordered deliberately in suspected bile duct problems, with symptoms such as itching, pale stools, dark urine or jaundice; in known liver diseases that affect the ducts, including primary biliary cholangitis and primary sclerosing cholangitis; in bone conditions, including Paget's disease, healing fractures, osteomalacia and cancer that has spread to bone; in vitamin D deficiency and hyperparathyroidism, both of which speed bone turnover; and to monitor treatments that affect either system.

Children and adolescents have high ALP as a normal consequence of bone growth, often two to three times adult values around growth spurts, and their reference ranges differ. Pregnant women have a rising ALP from the placenta in the second and third trimesters that returns to normal after delivery.

ALP comes with the comprehensive metabolic panel and the hepatic function panel and can be ordered alone, from your doctor or online through TestWell for a draw at a Quest or Labcorp patient service center, with a licensed physician reviewing the order and results in your portal within one to three business days. Adding GGT to the same draw is the single most useful pairing when ALP is the question; a vitamin D level and calcium with parathyroid hormone cover the bone causes.

Fast for the draw. In people with blood types O and B, a fatty meal raises intestinal ALP for several hours, and a non-fasting sample is a common reason for a mildly high result that disappears on repeat. Mention pregnancy, recent fractures or bone surgery, and medications, particularly antiseizure drugs, some antibiotics and hormonal treatments, which raise ALP, and bisphosphonates, which lower bone turnover and ALP.

Most laboratories report a normal adult ALP of about 40 to 129 units per liter; some ranges begin at 30 or 44 and end near 120 or 147, and the range on your report applies. Men run slightly higher than women before menopause; ALP rises in women after menopause as bone turnover increases; and values rise slightly with age. Children, adolescents and pregnant women have their own, higher ranges.

Interpretation starts with the pairing. A high ALP with a high GGT and a high bilirubin describes a cholestatic pattern, in which bile flow is obstructed or the ducts are inflamed. A high ALP with a normal GGT, especially with a high calcium, a low vitamin D or bone pain, points to bone. A mildly high ALP with everything else normal in a fasting sample is common and is repeated before it is investigated; a persistent isolated elevation is worked up with GGT, isoenzymes and the bone tests below.

From the liver, a high ALP means bile is not flowing normally through the ducts. Gallstones lodged in the common bile duct, strictures, and tumors of the bile ducts, pancreas or liver obstruct flow mechanically; primary biliary cholangitis and primary sclerosing cholangitis inflame the ducts from within; and many medications and some infections cause a cholestatic reaction. Liver metastases and infiltrating diseases such as sarcoidosis and lymphoma raise ALP even without jaundice. In each of these GGT rises too, and bilirubin rises when the obstruction is significant.

From bone, a high ALP means osteoblasts are unusually active: normal growth in children and adolescents, healing of a fracture, Paget's disease of bone, osteomalacia from vitamin D deficiency, hyperparathyroidism, bone metastases (especially from prostate and breast cancer), and an overactive thyroid. Vitamin D deficiency is the most common and most correctable of these in adults. Pregnancy raises the placental form; heart failure, mononucleosis and some other infections raise ALP modestly.

Symptoms follow the source: itching, pale stools, dark urine and jaundice with bile duct causes; bone pain, deformity or fractures with bone causes; often nothing with mild elevations. A high ALP with jaundice or abdominal pain needs prompt imaging rather than a scheduled repeat.

A low ALP is uncommon and, unlike a low ALT or AST, occasionally meaningful. Malnutrition and deficiencies of zinc, magnesium or vitamin B12, an underactive thyroid, celiac disease, Wilson's disease and pernicious anemia lower it, as do bisphosphonate medications and the after-effects of heart surgery or transfusion. A persistently very low ALP with a history of fractures, dental problems or bone pain raises the possibility of hypophosphatasia, a rare inherited disorder of bone mineralization that is often diagnosed late precisely because a low ALP is dismissed. A single mildly low value in a well person needs only a repeat; a persistent low value is worth a nutrition review, thyroid function and, where the history fits, a specialist opinion.

For a high ALP: repeat fasting with GGT. If GGT is high, a full hepatic panel, viral hepatitis and autoimmune liver markers (antimitochondrial antibodies for primary biliary cholangitis), and an ultrasound of the liver and bile ducts, followed by MRI of the ducts if the ultrasound is unrevealing. If GGT is normal, vitamin D, calcium, phosphorus and parathyroid hormone, ALP isoenzymes or bone-specific ALP, and imaging of any painful bone. For a low ALP: repeat; zinc, magnesium, B12 and thyroid function; and, if it persists with bone or dental history, a specialist evaluation for hypophosphatasia.