Alkaline phosphatase (ALP)
Alkaline phosphatase is an enzyme that comes mainly from liver and bone. US survey laboratory manuals print adult upper limits of 104 to 129 U/L, and limits up to 382 U/L for growing children. Higher adult values go with more deaths and slightly more heart disease. About 17% of raised results were normal on retest.
- Status
- Part of routine comprehensive metabolic and liver blood panels, ordered by a clinician and also sold direct to consumers by some US laboratories. FDA classifies alkaline phosphatase or isoenzymes test systems as class II devices [1]. Reports print the unit as U/L or IU/L.
- Measures
- The activity of alkaline phosphatase enzymes in serum or plasma. The enzyme is present in liver, bone, kidney, intestine and placenta, and the liver, bone and kidney type has the most clinical importance [2].
- Also called
- ALP, alkaline phosphatase, alk phos, ALKP, ALK PHOS, AP, alkaline phosphatase serum, total alkaline phosphatase
- Tested for
- liver health, bile duct problems, bone disease, bone turnover, vitamin D deficiency, liver enzymes check
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Linked in research2
Reported risks0
No risks sourced yet.
Reference ranges
Each range is the one its source published, in U/L. Also reported in µkat/L. Where sources differ, each is shown.
US national survey laboratory procedure manual, 2017 to 2018, women
Women, as the reference range printed for the assay · [2], [3]
| Range | What the source calls it |
|---|---|
| below 35 U/L | No name given |
| 35 to 104 U/L | "reference range" |
| above 104 U/L | No name given |
The reference range listed in the laboratory manual for the method used in the 2017 to 2018 US National Health and Nutrition Examination Survey (Roche Cobas 6000). It is the range attached to that assay, not one derived from survey participants. The manual prints the range for female and male plasma without an age band, and notes separately that children and juveniles can show significant increases [2]. The conversion factor above is the one a US medical journal prints for alkaline phosphatase [3].
US national survey laboratory procedure manual, 2017 to 2018, men
Men, as the reference range printed for the assay · [2]
| Range | What the source calls it |
|---|---|
| below 40 U/L | No name given |
| 40 to 129 U/L | "reference range" |
| above 129 U/L | No name given |
From the same manual and method as the range for women [2].
US national survey laboratory procedure manual, 2015 to 2016
People older than 16, both sexes, as the reference range printed for the assay · [4]
| Range | What the source calls it |
|---|---|
| below 36 U/L | No name given |
| 36 to 113 U/L | "reference range" |
| above 113 U/L | No name given |
From the manual for the method used in the 2015 to 2016 survey (Beckman UniCel DxC 800, run by Collaborative Laboratory Services). It prints one range for both sexes, where the later manual prints one per sex. The manual lists no critical value for alkaline phosphatase [4][2].
US national survey laboratory procedure manual, 2015 to 2016, adolescents aged 12 to 16
Adolescents aged 12 to 16, both sexes · [4]
| Range | What the source calls it |
|---|---|
| below 67 U/L | No name given |
| 67 to 382 U/L | "reference range" |
| above 382 U/L | No name given |
The manual attributes its pediatric ranges to a 1995 multicenter guideline for the analyzer, built on data from Montreal, Miami and Denver. It prints one range for boys and girls. The upper limit is more than 3 times the limit the same manual prints for people older than 16 [4]. The later manual explains that children and juveniles can show significant increases from bone-forming cell activity during accelerated bone growth [2].
US national survey laboratory procedure manual, 2015 to 2016, children aged 10 to 12
Children aged 10 to 12, both sexes · [4]
| Range | What the source calls it |
|---|---|
| below 103 U/L | No name given |
| 103 to 373 U/L | "reference range" |
| above 373 U/L | No name given |
From the same manual and the same 1995 pediatric guideline for the analyzer. Neighboring age bands share their boundary ages in the manual [4].
US national survey laboratory procedure manual, 2015 to 2016, children aged 5 to 10
Children aged 5 to 10, both sexes · [4]
| Range | What the source calls it |
|---|---|
| below 110 U/L | No name given |
| 110 to 360 U/L | "reference range" |
| above 360 U/L | No name given |
From the same manual and the same 1995 pediatric guideline for the analyzer [4].
US national survey laboratory procedure manual, 2015 to 2016, children under 5
Infants and children from birth to 5 years, both sexes · [4]
| Range | What the source calls it |
|---|---|
| below 60 U/L | No name given |
| 60 to 321 U/L | "reference range" |
| above 321 U/L | No name given |
From the same manual and the same 1995 pediatric guideline for the analyzer [4].
Šupak-Smolčić and colleagues, Croatian pregnancy cohort, 2025, first trimester
Pregnant women at 11 to 14 weeks of gestation · [5], [6], [7]
| Range | What the source calls it |
|---|---|
| below 34 U/L | No name given |
| 34 to 90 U/L | "reference interval" |
| above 90 U/L | No name given |
The central 95% of results in 299 women with singleton pregnancies at one Croatian center, measured on a Roche Cobas 6000. The authors compare it with the 54 to 119 U/L range that Croatian laboratories use for non-pregnant women and judge both limits to be lower in early pregnancy by a clinically relevant amount [5]. This block covers the first trimester only, and the direction reverses later. A study of 103 pregnant women and 103 matched controls found alkaline phosphatase significantly higher in the third trimester [6], and a Canadian study of about 135 pregnant people found substantial increases during gestation followed by a marked fall after delivery [7]. Neither abstract prints limits for late pregnancy, so none is given here.
What has been shown to move it
Shown to lower it2
Paget's disease of bone
Shown to relieve bone pain in Paget's disease more often than placebo, 31% against 9%, with one zoledronic acid infusion normalizing alkaline phosphatase in 89% at 6 months.
Compared with placebo and other bisphosphonates [12]; risedronate [13]
In two 6-month trials, one 5 mg infusion of zoledronic acid normalized serum alkaline phosphatase in 89% against 58% on risedronate 30 mg daily for 2 months, and a therapeutic response was seen in 96% against 74%.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Bone pain disappeared in 31% on a bisphosphonate and 9% on placebo (RR 3.42, 95% CI 1.31 to 8.90), a number needed to treat of 5. Fractures did not clearly differ. Zoledronate relieved pain more often than pamidronate or risedronate in single trials [12]. In two 6-month trials, one 5 mg infusion of zoledronic acid normalized serum alkaline phosphatase in 89% against 58% on risedronate 30 mg daily for 2 months, and a therapeutic response was seen in 96% against 74% [13].
- Population
- 3,168 people in 20 trials, mean age 66 to 74, 51% to 74% men, mostly with raised alkaline phosphatase [12]; 349 adults with moderate to severe Paget's disease, mean age 70 [13].
- Sources
- [12], [13]
- Caveats
- Moderate-quality evidence for pain, and mean follow-up was 6 months [12]. Treating to normalize alkaline phosphatase did not improve pain or quality of life over treating symptoms [12].
Liver and kidney markers in trials
Liver and kidney markers did not worsen in most trials. Creatinine rose slightly in 3 trials, and doses above 2,000 mg a day were linked to a BUN change.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- In 19 trials (1,295 participants), Nigella sativa lowered ALP by 10.8 U/L and BUN by 1.016. Creatinine rose by 0.070 in 3 trials with covariate-adjusted analyses, and doses above 2,000 mg a day were linked to a BUN change in 2 trials [11]. In 70 healthy adults given 200 mg a day of a thymoquinone-rich oil for 90 days, liver and kidney tests did not change and no serious adverse effects were reported [12].
- Population
- Adults in RCTs [11]. 70 healthy adults [12].
- Sources
- [11], [12]
- Caveats
- The safety trial's corresponding author is at Akay Natural Ingredients, the maker of the tested oil [12]. Heterogeneity for ALP and BUN was high [11]. In 16 RCTs in type 2 diabetes, AST, ALT and creatinine did not change significantly [7].
Shown to raise it2
Liver enzyme changes
Shown to raise mean GGT and alkaline phosphatase in placebo-controlled trials, mostly within the normal range. ALT and AST did not differ.
The numbers and sources
- How common
- Common: between 1 in 100 and 1 in 10 people.
- Effect
- Mean GGT and alkaline phosphatase were higher after modafinil but not placebo, and rose over time, with few values outside the normal range. ALT, AST, albumin and total bilirubin did not differ. "Abnormal liver function" was reported as an adverse reaction in 2% vs 1% on placebo [3].
- Population
- Adults in placebo-controlled label trials [3].
- Sources
- [3]
- Caveats
- The label gives no size for the mean change. The band above is the adverse-reaction rate.
Liver enzymes and liver injury
The label reports rises in AST, ALT and alkaline phosphatase in 1% or more of people, and cases of reversible liver injury.
The numbers and sources
- How common
- Common: between 1 in 100 and 1 in 10 people.
- Effect
- The label lists increases in AST, ALT and alkaline phosphatase among reactions occurring in 1% or more, and states that cases of reversible liver injury have occurred, with hepatic necrosis and granulomatous hepatitis reported in under 1% [5]. In a dose-escalation trial, mild rises in liver tests were frequent in both the escalation and control groups [3].
- Population
- People taking allopurinol, as described in the label [5]; 183 people with gout [3].
- Sources
- [5], [3]
- Caveats
- The label gives no placebo rate and no size for the enzyme rises.
Tested, and not shown to change it2
Liver enzymes
Liver enzymes did not change significantly across 16 controlled trials. Alkaline phosphatase fell at doses above 1 g a day.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- A 2026 meta-analysis of 16 controlled trials (1,171 participants) found no significant change in ALT (-1.41 IU/L, 95% CI -3.07 to 0.26), AST (0.03 IU/L, 95% CI -0.12 to 0.18) or alkaline phosphatase (SMD -0.21, 95% CI -0.44 to 0.03). Alkaline phosphatase fell at doses above 1 g a day [10].
- Population
- Participants in 16 controlled clinical trials [10].
- Sources
- [10]
- Caveats
- Liver enzymes are a marker, not a count of liver injury. The authors call for trials in more uniform populations [10].
Fatty liver and liver enzymes
Shown to lower the liver enzymes ALT and AST slightly in adults with fatty liver disease, but not in people with diabetes or with piperine added.
The numbers and sources
- Effect
- In 15 RCTs (905 patients with nonalcoholic fatty liver disease), curcumin lowered ALT by 4.10 (95% CI -7.16 to -1.04) and AST by 3.27 (95% CI -5.16 to -1.39), with no change in ALP. Curcumin with piperine did not change ALT or AST significantly [36]. In 10 RCTs in prediabetes and diabetes, ALT and AST did not change significantly and GGT fell 2.35 IU/L [37]. Across 18 RCTs of curcuminoids with piperine, AST fell 2.29 IU and the ALT change was not significant (p 0.053) [18].
- Population
- Adults with nonalcoholic fatty liver disease [36]; adults with prediabetes or diabetes [37]; adults in curcumin with piperine trials [18].
- Sources
- [36], [37], [18]
- Caveats
- These are blood enzymes, not measures of liver fat or fibrosis. Results differed by population and formulation [36][37].
How it compares with the reference method
Mixed results1
Variation from one test to the next
Shown to vary less than other liver tests: 17% of US adults with a raised result were normal about 17 days later, and within-person variation was 5% to 7%.
The numbers and sources
- Compared with
- A repeat measurement in the same person
- Effect
- Among 1,864 US adults measured twice a mean of 17.5 days apart, 17% of those with an initially elevated alkaline phosphatase had a normal result the second time, against 31% for ALT and 38% for bilirubin. More than 95% of initially normal results stayed normal. The within-person coefficient of variation was 6.7% [12]. In 91 European adults sampled weekly for 10 weeks under a tightly controlled protocol, within-person biological variation was 5.3% and variation between people was 24.9% [13].
- Population
- 1,864 adults in the third US National Health and Nutrition Examination Survey [12]. 91 adults aged 21 to 69 at 6 European laboratories [13].
- Sources
- [12], [13]
- Caveats
- The US study had only 2 measurements per person and lacked a full liver disease history [12]. Neither study states a threshold for agreement. One survey manual notes that hemoglobin from a hemolyzed sample lowers the result [4].
Did not match the reference method1
Growth in children
Limited evidence: values in growing children run well above adult limits, and one series described temporary rises to 805 to 8,619 U/L lasting a mean 12 weeks.
The numbers and sources
- Compared with
- Adult reference limits
- Effect
- A German study built sex-specific percentile charts from birth to 18 years from 361,405 samples, and its authors write that interpretation in children is challenging because of extensive changes with growth and puberty [14]. The pediatric upper limits printed by one US survey manual, 321 to 382 U/L, are about 3 times its limit of 113 U/L for people older than 16 [4]. In 60 children diagnosed with transient hyperphosphatasemia, alkaline phosphatase ranged from 805 to 8,619 U/L (mean 2,311), the rise lasted a mean of 12 weeks, and the bone isoenzyme was elevated in most of the children in whom isoenzymes were measured [15].
- Population
- 124,440 patients from birth to 18 years at 6 German tertiary care centers and one laboratory service [14]. 60 children in Israel and 122 matched controls [15].
- Sources
- [14], [4], [15]
- Caveats
- The German charts were built from samples taken during clinical care, and the abstract prints no values [14]. The series of 60 children was retrospective and found no cause for the temporary rise [15].
What studies tie it to
Linked in research2
Death from any cause
Linked to more deaths at higher levels, 38% more in the top third than the bottom third across pooled general population cohorts.
The numbers and sources
- Effect
- In a meta-analysis of general population cohorts, the relative risk of death from any cause was 1.38 (95% CI 1.17 to 1.63) comparing the top and bottom thirds of alkaline phosphatase, and 1.03 (1.01 to 1.06) per 5 U/L higher [8]. A second meta-analysis, in people with normal or preserved kidney function, found a non-linear association with a relative risk of 1.57 (95% CI 1.27 to 1.95) for the high group against the reference group [9]. In survivors of a heart attack, the top third had an adjusted hazard ratio for death of 1.43 (95% CI 1.08 to 1.89) against the bottom third, and the association was repeated in a US national survey sample [10].
- Population
- 19 cohorts with over 9.24 million participants and 242,953 deaths, which also covered other liver enzymes [8]. 24 studies with 147,634 participants [9]. 4,115 people with a previous heart attack and 14,716 US adults [10].
- Sources
- [8], [9], [10]
- Caveats
- Observational. A raised total can come from liver or from bone [2]. In the heart attack cohort the excess risk was present in people without evidence of kidney disease and was highest in people with both alkaline phosphatase and serum phosphate raised [10].
Heart disease and stroke
Linked to slightly more cardiovascular disease, 8% more per standard deviation of log alkaline phosphatase in a meta-analysis of 29 cohorts.
The numbers and sources
- Effect
- The pooled, fully adjusted relative risk of cardiovascular disease was 1.08 (95% CI 1.03 to 1.14) per standard deviation of log baseline alkaline phosphatase, with a log-linear relation [11]. A second meta-analysis found a linear association with cardiovascular deaths (RR 1.02, 95% CI 1.01 to 1.04) [9].
- Population
- 29 cohorts with over 1.23 million participants and 20,406 cardiovascular outcomes, which also covered other liver enzymes [11]. 24 studies with 147,634 participants [9].
- Sources
- [11], [9]
- Caveats
- Observational. The authors of the second meta-analysis describe the relationship between alkaline phosphatase and cardiovascular disease as still ambiguous [9].
Sources
- US Food and Drug Administration. 21 CFR 862.1050, Alkaline phosphatase or isoenzymes test system. Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/section-862.1050
- Centers for Disease Control and Prevention, National Center for Health Statistics. National Health and Nutrition Examination Survey 2017-2018 Laboratory Procedure Manual: Alkaline Phosphatase (ALP), serum, Roche Cobas 6000. Performed by the University of Minnesota Advanced Research and Diagnostic Laboratory. https://wwwn.cdc.gov/nchs/data/nhanes/public/2017/labmethods/BIOPRO-J-MET-ALP-508.pdf
- Kleiner DE, Brunt EM, Wilson LA, et al. Association of Histologic Disease Activity With Progression of Nonalcoholic Fatty Liver Disease. JAMA Network Open. 2019. https://doi.org/10.1001/jamanetworkopen.2019.12565
- Centers for Disease Control and Prevention, National Center for Health Statistics. National Health and Nutrition Examination Survey 2015-2016 Laboratory Procedure Manual: Alkaline Phosphatase (ALP), refrigerated serum, Beckman UniCel DxC 800 Synchron. Performed by Collaborative Laboratory Services. https://wwwn.cdc.gov/nchs/data/nhanes/public/2015/labmethods/BIOPRO_I_MET_ALP_DXC800and660i.pdf
- Šupak-Smolčić V, Franin L, Antončić D, et al. Reference Intervals for Common Biochemistry and Hematology Parameters in Early Pregnancy: A Prospective Study. Diagnostics. 2025. https://doi.org/10.3390/diagnostics15040415
- Bacq Y, Zarka O, Bréchot JF, et al. Liver function tests in normal pregnancy: A prospective study of 103 pregnant women and 103 matched controls. Hepatology. 1996. https://doi.org/10.1002/hep.510230514
- Bohn MK, Sealey V, Schneider R, Adeli K. Closing the Evidence Gaps in Trimester-Specific Pregnancy Reference Intervals for Biochemical Markers of Health and Disease. Clinical Chemistry. 2025. https://doi.org/10.1093/clinchem/hvaf124
- Kunutsor SK, Apekey TA, Seddoh D, Walley J. Liver enzymes and risk of all-cause mortality in general populations: a systematic review and meta-analysis. International Journal of Epidemiology. 2014. https://doi.org/10.1093/ije/dyt192
- Li JW, Xu C, Fan Y, et al. Can Serum Levels of Alkaline Phosphatase and Phosphate Predict Cardiovascular Diseases and Total Mortality in Individuals with Preserved Renal Function? A Systemic Review and Meta-Analysis. PLoS ONE. 2014. https://doi.org/10.1371/journal.pone.0102276
- Tonelli M, Curhan G, Pfeffer M, et al. Relation Between Alkaline Phosphatase, Serum Phosphate, and All-Cause or Cardiovascular Mortality. Circulation. 2009. https://doi.org/10.1161/CIRCULATIONAHA.109.851873
- Kunutsor SK, Apekey TA, Khan H. Liver enzymes and risk of cardiovascular disease in the general population: A meta-analysis of prospective cohort studies. Atherosclerosis. 2014. https://doi.org/10.1016/j.atherosclerosis.2014.06.006
- Lazo M, Selvin E, Clark JM. Brief Communication: Clinical Implications of Short-Term Variability in Liver Function Test Results. Annals of Internal Medicine. 2008. https://doi.org/10.7326/0003-4819-148-5-200803040-00005
- Carobene A, Røraas T, Sølvik UØ, et al. Biological Variation Estimates Obtained from 91 Healthy Study Participants for 9 Enzymes in Serum. Clinical Chemistry. 2017. https://doi.org/10.1373/clinchem.2016.269811
- Zierk J, Arzideh F, Haeckel R, et al. Pediatric reference intervals for alkaline phosphatase. Clinical Chemistry and Laboratory Medicine. 2017. https://doi.org/10.1515/cclm-2016-0318
- Dori N, Levi L, Stam T, et al. Transient hyperphosphatasemia in children revisited. Pediatrics International. 2010. https://doi.org/10.1111/j.1442-200X.2010.03265.x