Biomarkers · Liver & Nutritional

Alkaline Phosphatase (ALP)

Lower values go with lower risk of death. In NHANES 1999–2018 with linked mortality to 2019, each standard deviation above average goes with 25% higher risk of death. We found the same pattern in NHANES

ALP and risk of death

NHANES, our fit with 95% CIPublished curve

Published curve higher than the NHANES fitNHANES fit higher

Risk of death relative to each curve's own reference value, so the two curves need not cross 1 at the same point. The dotted vertical line marks the NHANES median.

Risk of death per SD (NHANES)1.25×95% CI 1.23–1.28 · 43,812 adults, 5,900 deaths

Published risk of death1.03×per 5 U/l increment in ALP (95% CI 1.01–1.06) · Meta-analysis of 19 prospective cohort studies in general populations (over 9.24 million participants)

Value of the measurement+0.024gain in concordance within age bands; rank 13 of 56 · all tests

ALP by age and sex

Each bar runs from the 5th to the 95th percentile, the darker part from the 25th to the 75th, and the tick is the median. Not a reference range or a target.

The percentiles as a table

Each row is one sex and age band: the values below which 5%, 25%, 50%, 75% and 95% of people fall (U/L), from the survey named in the row. Not a reference range or a target.
Sex	Age	5th	25th	Median	75th	95th	n	Cycle / source
All	20-39	42.0	57.0	69.0	83.0	109	1,431	NHANES 2017-2018
All	40-59	45.0	62.0	74.0	90.0	121	1,547	NHANES 2017-2018
All	60+	48.0	64.0	79.0	96.0	127	1,890	NHANES 2017-2018
All	all	45.0	61.0	74.0	89.0	121	4,868	NHANES 2017-2018
Men	20-39	45.9	60.0	71.0	84.0	111	684	NHANES 2017-2018
Men	40-59	45.0	63.0	72.0	86.0	116	722	NHANES 2017-2018
Men	60+	47.0	63.0	76.0	93.0	123	958	NHANES 2017-2018
Men	all	46.0	61.0	73.0	87.0	118	2,364	NHANES 2017-2018
Women	20-39	38.0	53.9	66.0	81.0	109	747	NHANES 2017-2018
Women	40-59	45.5	61.0	78.0	93.0	124	825	NHANES 2017-2018
Women	60+	51.0	66.0	81.0	99.0	131	932	NHANES 2017-2018
Women	all	44.0	60.0	75.0	90.0	124	2,504	NHANES 2017-2018

What studies found when this marker was changed

They describe what happened in those study groups, not a recommendation. See all catalogued interventions.

Measured changes in ALP, study by study

4 effects with a numeric size, each from one study arm: the dot is the reported change, the line its 95% interval where one was given. Green points move the marker the way lower risk of death lies; amber the other way. Study results in the groups studied, not predictions for a person.

Each row is one study: what was changed, the effect it reported on this marker, and the source.
Type	Intervention	Reported effect	Evidence	Source
pharmacologic	Ursodeoxycholic acid (14 mg/kg/day) in primary biliary cirrhosis	Significant fall in serum alkaline phosphatase vs placebo over 24 months (effect size not reported)	RCT	Heathcote EJ, et al. The Canadian Multicenter Double-blind Randomized…
pharmacologic	Bisphosphonates (single 5 mg zoledronic acid infusion vs oral risedronate) in Paget's disease of bone	Alkaline phosphatase normalized in 88.6% with single 5 mg zoledronic acid infusion vs 57.9% with risedronate at six months	RCT	Reid IR, et al. N Engl J Med. 2005;353:898-908.
pharmacologic	Elafibranor 80 mg once daily for 12 weeks in PBC with incomplete response to ursodeoxycholic acid	Reduces ALP by 48.3% (SD 14.8) at 12 weeks vs +3.2% with placebo	RCT	Schattenberg JM, et al. J Hepatol. 2021. A randomized placebo-controlled trial…
pharmacologic	Elafibranor 80 mg once daily for 52 weeks as second-line therapy in PBC (ELATIVE phase III)	Mean ALP change from baseline -38.9% at week 52 (overall elafibranor arm)	RCT	Levy C, et al. Liver Int. 2026. Baseline Alkaline Phosphatase Impacts Response…
pharmacologic	Bezafibrate 400 mg once daily for 21 days in PSC/PBC/SSC with moderate-severe pruritus	Reduces serum ALP by 35% vs placebo at 21 days	RCT	de Vries E, et al. Gastroenterology. 2021. Fibrates for Itch (FITCH) in…

Things that worsen it

Each row is one study: what was changed, the effect it reported on this marker, and the source.
Type	Condition or exposure	Reported effect	Evidence	Source
clinical	Biliary ductal obstruction, choledocholithiasis, or primary sclerosing cholangitis	Cholestatic injury defined by disproportionate ALP elevation vs AST/ALT; hepatic ALP elevation warrants PBC/PSC work-up (effect size not reported)	clinical guideline	Kwo PY, et al. ACG Clinical Guideline: Evaluation of Abnormal Liver…
clinical	Active Paget's disease of bone	Serum total ALP recommended as first-line biochemical marker of metabolically active Paget's disease (effect size not reported)	clinical guideline	Ralston SH, et al. J Bone Miner Res. 2019;34:579-604.

What else moves this marker

They describe those study groups, not an individual, and an association is not a cause.

Diseases and conditions

Each row is one study: what it compared and the change it reported in this marker.
What	Effect on the marker	Comparison · population	Source
↓ Hypophosphatasia (adult, untreated) · Adults with confirmed HPP not on enzyme replacement vs adults in whom HPP was excluded	-21.5 U/L	median plasma ALP 24.0 U/L (IQR 15.0-29.5) in HPP vs 45.5 U/L (IQR 34.0-62.0) in non-HPP · Adults referred to a metabolic bone clinic for possible hypophosphatasia (USA)	case control · PMID 35878747

Sources

Risk curve: Kunutsor SK 2014 (PMID 24585856): all-cause RR 1.03 (1.01-1.06) per 5 U/l increment in ALP. Scaled to US values (NHANES).
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. Int J Epidemiol. 2014;43(1):187-201.
NHANES curve: our Cox model adjusted for age and sex, NHANES 1999–2018 with linked mortality to 2019.

Map Alkaline Phosphatase (ALP) against another biomarker.

Map ALP against another marker