Alkaline Phosphatase - Kresser Institute Membership Site

Marker Name: Alkaline phosphatase

REFERENCE RANGES FOR ALKALINE PHOSPHATASE:

Laboratory reference range: 39–117 IU/L

Functional reference range: 42–107 IU/L

DESCRIPTION:

Alkaline phosphatase refers to the family of related zinc metalloenzymes present in liver, bone, kidney, and placenta.^1-3 The biological importance of alkaline phosphatase in humans is largely unknown, although the enzyme appears to play a role in bone mineralization and fat absorption.^4-6 While the enzymatic function of alkaline phosphatase is of comparatively little clinical importance, the level of alkaline phosphatase in the blood is an important biomarker of disease.⁴

Serum alkaline phosphatase levels predominantly increase in one of two circumstances, either due to biliary stasis or increased osteoblastic activity in bone.³ In both cases, the expression of alkaline phosphatase in the respective tissues is stimulated by some inciting event. In hepatobiliary disease, serum alkaline phosphatase biosynthesis is stimulated by bile acids retained in the hepatobiliary system.^7,8 Increased synthesis plus liver cell destruction subsequent to hepatobiliary disease leads to regurgitation and leaking of alkaline phosphatase into the blood, which is detected by laboratory assay.

In diseases of the bone, alkaline phosphatase activity is stimulated by increased osteoblastic activity. In fact, alkaline phosphatase is the principal glycosylated protein found in bone, where it is bound to the cell surface of osteoblasts.⁹ Normal physiologic processes or diseases that stimulate bone growth reflexively increase osteoblastic activity and, by extension, alkaline phosphatase activity. Since alkaline phosphatase levels vary depending on osteoblastic activity, levels of the enzyme are generally higher in children and adolescents since these are periods of rapid bone growth.⁴ Moreover, diseases that result in increased bone turnover, such as Paget’s disease, can increase alkaline phosphatase levels in blood.¹⁰

Elevated alkaline phosphatase levels are also noted in other non-disease states.¹¹ Alkaline phosphatase levels may also increase to a lesser degree in the third trimester of normal pregnancy. This increase is presumably due to an influx of the placental alkaline phosphatase into the serum.⁴ Curiously, individuals with O or B blood types may have transient elevations in serum alkaline phosphatase after consuming a fatty meal.^4,11 Regardless of the tissue source, alkaline phosphatase is cleared from the serum at a steady rate regardless of the functional capacity of the liver or health of the bile ducts.¹² It has a half-life in the serum of seven days.¹³

Elevations in serum alkaline phosphatase are usually a more pressing clinical concern than abnormally low levels.¹⁴ Nevertheless, several disease processes can reduce serum alkaline phosphatase below the normal range. Decreased alkaline phosphatase activity in the serum occurs in greater than 50 percent of patients who had cardiac surgery requiring a cardiac bypass pump.¹⁴ This may be due at least in part to magnesium deficiency, since deficient levels of this element can directly decrease alkaline phosphatase levels.¹⁵ Zinc deficiency is probably the most well-known cause of low alkaline phosphatase levels, although this may not be a common cause in Western countries.¹⁴ Anemia and various endocrine disturbances can lower serum alkaline phosphatase levels.

Alkaline phosphatase is one of the core measurements in a standard liver panel, which also includes alanine aminotransferase (ALT), acetate aminotransferase (AST), bilirubin, albumin, and total protein.¹⁶ Gamma-glutamyl transpeptidase (GGT) may be ordered to confirm that elevated alkaline phosphatase levels come from a hepatobiliary source.¹² GGT levels correlate with alkaline phosphatase levels in hepatobiliary disease (i.e., both are elevated).¹⁷ Bone-specific alkaline phosphatase may be used to monitor treatment in individuals with Paget’s disease, osteoporosis, or osteomalacia.¹⁸

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:¹¹

Pregnancy (normal in third trimester)
Endocrine disease
- Hyperthyroidism
- Hyperparathyroidism
Hepatic cholestasis
Biliary cholestasis
Bone disease
- Vitamin D insufficiency
- Rickets
- Healing bone fracture
- Paget’s disease
- Osteomalacia
- Malignancy involving bone
Fatty meal (B and O blood groups only)
Drugs
- Estrogens
- Androgens
- Albumin
- Phenothiazines
- Erythromycin
- Oral hypoglycemic agents

Low in:^{11,14,15,19,20}

Severe anemia
Pernicious anemia
Malnutrition
Nutrient imbalance
- Phosphate deficiency
- Zinc deficiency
- Magnesium deficiency
- Vitamin C deficiency
- Hypervitaminosis D
Wilson disease
Hypothyroidism
Hypoparathyroidism
Celiac disease
Estrogen replacement therapy
Cardiac surgery (especially with cardiac bypass pump use)
Large-volume blood transfusions
Milk-alkali syndrome

FUNCTIONAL RANGE INDICATIONS:

High in:

Same as conventional indications

Low in:

Same as conventional indications, and:
Folate deficiency
Vitamin B6 deficiency

References: