Summary
Alkaline Phosphatase (ALP) is an enzyme produced by the liver, bone, gut, and placenta. Elevated ALP in adults is most commonly caused by liver or bone disease. When raised in combination with elevated GGT (but normal or mildly elevated ALT), it points to bile duct disease. When GGT is normal, the source is usually bone — making GGT the essential companion test for interpreting ALP.
ALP has multiple tissue isoforms; the liver and bone isoforms account for the vast majority of serum ALP in adults. The bone isoform reflects osteoblast (bone-forming cell) activity and rises in conditions with high bone turnover (Paget’s disease, osteomalacia, bone metastases, fractures). The liver isoform rises in cholestatic conditions — any process that impairs bile flow, from gallstones to primary biliary cholangitis to infiltrative liver diseases.
In children and adolescents, ALP is normally very high due to rapid bone growth, which can confuse interpretation in younger adults.
Isolated ALP elevation (with normal GGT and ALT) in a postmenopausal woman is most likely from bone; in older men it warrants investigation for Paget’s disease of bone or bone metastases.
What It Is
Alkaline phosphatase (ALP) is a hydrolase enzyme that cleaves phosphate groups from a variety of substrates in an alkaline environment. It is expressed on the cell membranes of several tissues: biliary epithelial cells, osteoblasts, intestinal epithelium, kidney tubules, and the placenta.
In routine liver function tests, ALP is measured as total activity — a combination of liver and bone isoforms. When ALP is elevated, GGT measurement distinguishes liver from bone source: GGT is elevated in liver/bile duct disease but not in bone disease.
Reference range in adults: 44–147 U/L in most UK laboratories. ALP is physiologically elevated in pregnancy (third trimester, placental isoform) and in children (bone growth). A transient benign elevation of intestinal-origin ALP can occur after a fatty meal — this is not pathological.
Functions
Bone turnover indicator
Bone-origin ALP reflects osteoblast activity — elevated in Paget's disease, fractures, osteomalacia, and bone metastases.
Biliary disease marker
Liver-origin ALP rises in bile duct obstruction and cholestatic liver disease — including gallstones, primary biliary cholangitis, and drug-induced cholestasis.
Liver infiltration detector
ALP rises in hepatic infiltration by tumour, sarcoidosis, or amyloid — disproportionate to other liver enzymes.
Tissue source differentiator
Combined with GGT, ALP distinguishes liver from bone pathology — a critical step before further investigation.
Reference Ranges
Alkaline Phosphatase (ALP)
Measured in U/L| Status | Range (U/L) | What it means |
|---|---|---|
| Low | < 44 | Rarely clinically significant — consider hypothyroidism or zinc deficiency. |
| Normal | 44–147 | Normal bone and liver ALP activity. |
| Elevated | > 147 | Elevated — check GGT to identify liver vs bone source and investigate accordingly. |
Reference ranges vary by sex, age, and laboratory. ALP is naturally high in children, pregnancy, and after fatty meals. Always interpret alongside GGT to identify source.
Symptoms of Imbalance
ALP elevation is often discovered incidentally; symptoms depend on the underlying cause.
- Low ALP is rarely clinically significant
- May be seen in hypothyroidism, zinc deficiency, or pernicious anaemia
- Often asymptomatic
- Itching (pruritus) — from bile salt accumulation in cholestasis
- Jaundice — in significant biliary obstruction
- Bone pain — if elevated from bone disease
- Right upper quadrant discomfort
- Fatigue and malaise
Causes of Imbalance
- Hypothyroidism
- Zinc deficiency (zinc is a required cofactor for ALP)
- Pernicious anaemia
- Rarely: hypophosphatasia (genetic condition)
- Cholestatic liver disease (gallstones, primary biliary cholangitis, drug cholestasis)
- Paget's disease of bone — the classic cause of very high ALP from bone
- Bone metastases
- Osteomalacia (vitamin D deficiency)
- Healing fractures
- Liver infiltration (tumour, sarcoidosis)
- Pregnancy (placental ALP — physiological)
FAQs
Test GGT alongside ALP. GGT is elevated by liver and bile duct disease but not by bone disease. If GGT is elevated: investigate the liver/bile ducts (ultrasound, further liver function). If GGT is normal: investigate bone — check vitamin D, calcium, and consider bone imaging or dedicated bone turnover markers.
Yes. ALP is physiologically elevated in: (1) children and adolescents — rapidly growing bone always produces high ALP; (2) the third trimester of pregnancy — placental ALP; (3) after a fatty meal — intestinal-origin ALP rises transiently. In these contexts, elevated ALP does not require investigation.
Paget’s disease of bone is a common disorder (affecting 1–2% of UK adults over 55) in which localised areas of bone undergo rapid, disorganised turnover. The intense osteoblast activity involved produces very high ALP — often 10× the upper limit of normal. It is often asymptomatic and discovered incidentally on blood tests, though it can cause bone pain, deformity, and complications.
No. Many causes of elevated ALP have nothing to do with liver disease — including bone pathology (Paget’s, osteomalacia, fractures), pregnancy, and normal growth in children. Always check GGT alongside ALP to identify the source before assuming liver disease.
Yes. Severe vitamin D deficiency causes osteomalacia (softening of the bones) — a condition where inadequate calcium and phosphate deposition in bone matrix leads to compensatory increases in osteoblast activity and bone-origin ALP. Vitamin D and calcium supplementation normalises ALP in this context. Testing vitamin D when ALP is elevated (with normal GGT) is always worthwhile.
References
- Lum G, Gambino SR. A comparison of serum alkaline phosphatase isoenzymes. Clin Chem. 1972;18(5):470–473. View source
- Dufour DR, et al. Diagnosis and monitoring of hepatic injury: recommendations for use of laboratory tests in screening, diagnosis, and monitoring. Clin Chem. 2000;46(12):2050–2068. View source
- Whyte MP. Hypophosphatasia: nature's window on alkaline phosphatase function in humans. Prog Mol Biol Transl Sci. 2016;142:149–163. View source