Bilirubin (total)
Bilirubin is formed when red blood cells are broken down. US laboratory sources print adult upper limits of 1.0 to 1.4 mg/dL. About 1 in 10 people in one Czech sample had a raised level with normal liver enzymes, the pattern of Gilbert syndrome. Higher levels went with less heart and lung disease. A 24-hour fast more than doubled results.
Checked 2026-11-13
- 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 bilirubin (total or direct) test systems as class II devices [1]. This page covers total bilirubin in blood. Direct bilirubin is reported as a separate line.
- Measures
- Total bilirubin in serum or plasma, covering the direct (conjugated) and the indirect (unconjugated) fractions. Bilirubin is formed during the normal and abnormal destruction of red blood cells [2].
- Also called
- bilirubin, total bilirubin, bilirubin total, TBIL, T bili, T. Bili, serum bilirubin, bilirubin blood test
- Tested for
- liver health, jaundice, yellow skin or eyes, gallbladder or bile duct problems, red blood cell breakdown, Gilbert syndrome
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 research3
- LimitedOne UK cohort of 504,206 adults linked higher bilirubin within the usual range to less lung cancer, less chronic obstructive lung disease and fewer deaths.
- LimitedOne genetic study found higher bilirubin went with 42% lower odds of type 2 diabetes per standard deviation in 3,381 adults.
- LimitedOne UK cohort found people with Gilbert syndrome had about half the death rate of people with normal bilirubin.
Reported risks0
No risks sourced yet.
Reference ranges
Each range is the one its source published, in mg/dL. Also reported in µmol/L. Where sources differ, each is shown.
US national survey laboratory procedure manual, 2017 to 2018
Adults, as the reference range printed for the assay · [2], [3]
| Range | What the source calls it |
|---|---|
| 1 or below mg/dL | "reference range" |
| above 1 mg/dL | No name given |
The manual for the method used in the 2017 to 2018 US National Health and Nutrition Examination Survey (Roche Cobas 6000, diazo method) prints the range as up to 1.0 mg/dL, with no lower limit, so this block does not classify low results. It is the range attached to that assay, not one derived from survey participants [2]. The survey's data file reports each result in both units, and its lowest and highest values, 0.1 and 3.7 mg/dL, appear as 1.71 and 63.27 µmol/L, which matches the conversion factor above [3].
US national survey laboratory procedure manual, 2015 to 2016
People older than 5 days, as the reference range printed for the assay · [4]
| Range | What the source calls it |
|---|---|
| below 0.2 mg/dL | No name given |
| 0.2 to 1.3 mg/dL | "reference range" |
| above 1.3 mg/dL | No name given |
From the manual for the method used in the 2015 to 2016 survey (Beckman UniCel DxC 800, diazo method, run by Collaborative Laboratory Services). The manual states that its reference ranges were established from wellness participants with an age mix similar to the laboratory's patients. It also prints ranges for the first days of life, 2.0 to 6.0 mg/dL on the first day, 6.0 to 10.0 on days 1 to 2 and 4.0 to 8.0 on days 3 to 5, which are not placed as bands here because they depend on age in days. Two assays used by the same national survey print different upper limits [4][2].
Zucker and colleagues, US national survey, 2004
US adults aged 17 and older in the third National Health and Nutrition Examination Survey · [5]
| Range | What the source calls it |
|---|---|
| 1.4 or below mg/dL | No name given |
| above 1.4 mg/dL | No name given |
The paper reports a 97.5% cut-off of 1.4 mg/dL for the US adult population and does not say which side a result of exactly 1.4 falls on. This block treats it as an upper limit. It gives no lower limit. Mean bilirubin was 0.72 mg/dL in men and 0.52 mg/dL in women, and levels were lower in non-Hispanic Black participants and in active smokers, but the abstract prints one cut-off for both sexes [5].
How it compares with the reference method
Mixed results2
Variation from one test to the next
One US study found 38% of adults with a raised bilirubin had a normal result about 17 days later, with within-person variation of 23%.
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, 38% of those with an initially elevated bilirubin had a normal result the second time, the largest share of the 5 liver tests studied. More than 95% of initially normal results stayed normal. The within-person coefficient of variation was 23.4% [16].
- Population
- 1,864 adults in the third US National Health and Nutrition Examination Survey [16].
- Sources
- [16]
- Caveats
- Only 2 measurements per person, and the study lacked a full liver disease history. It states no threshold for agreement, so the result is given as numbers only [16].
Direct bilirubin against the total
A US survey laboratory manual states the raised fraction differs by cause: direct in blocked bile flow, indirect in red cell breakdown, and both in hepatitis.
The numbers and sources
- Compared with
- Direct (conjugated) bilirubin measured on the same sample
- Effect
- The manual states that in obstructive jaundice the rise in total bilirubin comes mainly from direct bilirubin, in hemolytic jaundice mainly from the indirect (unconjugated) fraction, and in hepatitis from both. It adds that a direct result can read slightly above the total when nearly all the bilirubin is in the direct form [2]. In Gilbert syndrome the raised fraction is the unconjugated one [11]. In pregnancy, total and free bilirubin were significantly lower in all three trimesters than in matched controls, and conjugated bilirubin was lower in the second and third [18]. At 11 to 14 weeks of pregnancy one Croatian study found total bilirubin of 2 to 16 µmol/L and an upper limit for conjugated bilirubin of 5 µmol/L [15].
- Population
- 103 pregnant women and 103 matched controls [18]. 299 pregnant women [15].
- Sources
- [2], [11], [18], [15]
- Caveats
- Direct bilirubin is a different quantity from the total, so no direct bilirubin range is placed as a band on this page. The pregnancy figures are printed in µmol/L and are described here, not placed as bands [15].
Did not match the reference method3
A raised result without liver disease: Gilbert syndrome
Limited evidence: about 1 in 10 people in a Czech sample had bilirubin above 1 mg/dL with normal liver enzymes, the pattern of the inherited trait Gilbert syndrome.
The numbers and sources
- Compared with
- Liver disease or red blood cell breakdown as the explanation for a raised result
- Effect
- People with Gilbert syndrome have mild, chronic unconjugated hyperbilirubinemia in the absence of liver disease or overt hemolysis, with the liver's capacity to process bilirubin reduced to about 30% of normal. All 10 patients in the study that found the genetic basis carried two copies of a longer promoter in the UGT1A1 gene. The same variant was common in people without the syndrome, at an allele frequency of 40%, and the authors concluded that it is necessary but not sufficient for the syndrome [11]. In a Czech general population sample, 9.6% had bilirubin above 17 µmol/L (1 mg/dL) with normal liver enzymes, 12.6% of men and 6.7% of women [12].
- Population
- 10 unrelated patients with Gilbert syndrome and 55 unaffected subjects [11]. 2,594 people from the Czech general population, compared with 536 elite athletes [12].
- Sources
- [11], [12]
- Caveats
- The genetic study was small. The Czech study defined the syndrome by blood results alone, and its prevalence among elite athletes was 22% [12]. A raised total bilirubin has other causes, and total bilirubin alone does not show which fraction is raised [2].
Fasting
Small studies found fasting raised bilirubin: a 24-hour fast more than doubled it in 37 volunteers, with a rise already present at 12 hours.
The numbers and sources
- Compared with
- The same people when fed
- Effect
- In a crossover study, a 24-hour fast more than doubled total bilirubin from baseline, both in volunteers with normal levels and in those with consistently elevated levels. At 12 hours bilirubin was 17.3 µmol/L when fasting and 14.0 µmol/L when fed [13]. In volunteers screened for early-phase drug trials, fasting men had higher bilirubin than fed men and levels rose with fasting time, while no relation was found in women [14]. Among women in early pregnancy, those who were fasting had higher total bilirubin than those who had eaten (median 6 against 5 µmol/L) [15].
- Population
- 37 volunteers, 19 of them with consistently elevated bilirubin [13]. 105 men and 30 women aged 18 to 48 [14]. 299 pregnant women at 11 to 14 weeks [15].
- Sources
- [13], [14], [15]
- Caveats
- Small studies. The study in trial volunteers was retrospective and included only 30 women [14]. The authors of the pregnancy study judged the difference they found not clinically significant [15]. One US survey manual states that fasting is not required for the test [4].
Light and hemolysis in the sample
Limited evidence: light breaks down bilirubin in a blood sample, and hemolysis shifted results in one experiment on blood from 16 volunteers.
The numbers and sources
- Compared with
- Samples protected from light and free of hemolysis
- Effect
- One survey manual states that bilirubin in a specimen degrades when exposed to light for prolonged periods and instructs the laboratory to protect specimens from light [2]. The other reports an increase of less than 0.24 mg/dL at the lowest grade of visible hemolysis [4]. In blood from 16 volunteers hemolyzed in the laboratory, clinically meaningful changes in total bilirubin appeared at moderate hemolysis, with free hemoglobin above 1 g/L [17].
- Population
- 16 volunteers [17].
- Sources
- [2], [4], [17]
- Caveats
- The manuals describe their own assays and give no figure for how much light exposure lowers a result. The later manual reports no interference from hemolysis on its assay up to a high hemolysis index, so the effect differs between methods [2].
What studies tie it to
Linked in research3
Lung disease and death from any cause
One UK cohort of 504,206 adults linked higher bilirubin within the usual range to less lung cancer, less chronic obstructive lung disease and fewer deaths.
The numbers and sources
- Effect
- For each 0.1 mg/dL higher bilirubin, the adjusted rate of lung cancer was 8% lower in men (95% CI 5% to 11%) and 11% lower in women (7% to 14%). In men the rate of chronic obstructive pulmonary disease was 6% lower (5% to 7%) and the death rate 3% lower (2% to 3%), with very similar results in women. Median bilirubin was 0.64 mg/dL in men and 0.53 mg/dL in women [8].
- Population
- 504,206 adults in a UK primary care database with no evidence of liver, bile duct or hemolytic disease, with 1,341 lung cancers, 5,863 cases of chronic obstructive pulmonary disease and 23,103 deaths [8].
- Sources
- [8]
- Caveats
- One cohort, observational, in people whose bilirubin was within the normal range [8]. Bilirubin was lower in active smokers in US survey data, so how fully smoking was accounted for matters to this result [5].
Type 2 diabetes
One genetic study found higher bilirubin went with 42% lower odds of type 2 diabetes per standard deviation in 3,381 adults.
The numbers and sources
- Effect
- Per standard deviation higher log bilirubin, the observed odds of type 2 diabetes were 25% lower (OR 0.75, 95% CI 0.62 to 0.92). Using a UGT1A1 gene variant that explained 19.5% of the variation in bilirubin, the genetically estimated odds ratio was 0.58 (95% CI 0.39 to 0.84) [9].
- Population
- 3,381 adults aged 28 to 75 without diabetes at baseline, 210 of whom developed type 2 diabetes over a median of 7.8 years [9].
- Sources
- [9]
- Caveats
- One cohort with 210 cases and one gene variant. The same kind of genetic analysis found no effect on heart disease in a larger sample [7].
Death in people with Gilbert syndrome
One UK cohort found people with Gilbert syndrome had about half the death rate of people with normal bilirubin.
The numbers and sources
- Effect
- Mortality was 24 per 10,000 person-years in people with a diagnosis of Gilbert syndrome and a raised bilirubin, and 50 per 10,000 in a comparison cohort with normal bilirubin. After accounting for sociodemographic factors and general health indicators, the mortality rate ratio was 0.5 (95% CI 0.4 to 0.7) [10].
- Population
- 4,266 patients with Gilbert syndrome and 21,968 comparison patients in a UK primary care database, with 1,174 deaths over 350,000 person-years [10].
- Sources
- [10]
- Caveats
- One cohort, observational. It counted people whose Gilbert syndrome had been diagnosed and recorded, who may differ from people with the same trait and no diagnosis.
Mixed results1
Heart disease and stroke
Mixed results: pooled cohorts linked higher bilirubin to 7% less cardiovascular disease per standard deviation, while genetic studies found no effect on heart disease.
The numbers and sources
- Effect
- In a meta-analysis of 12 population cohorts, the adjusted relative risk of cardiovascular disease was 0.93 (95% CI 0.90 to 0.97) per standard deviation higher total bilirubin, 0.95 (0.92 to 0.99) for coronary heart disease and 0.93 (0.88 to 0.98) for stroke. Adding bilirubin to a risk model built on established risk factors did not improve prediction [6]. In three Danish studies, people with the UGT1A1 genotype that raised bilirubin by 95% had no lower odds of ischemic heart disease (OR 1.03, 95% CI 0.96 to 1.11) or heart attack (1.01, 0.92 to 1.12). A meta-analysis of genetic studies gave an odds ratio of 1.01 (0.88 to 1.16) for genotypes with about twice the bilirubin [7].
- Population
- 12 prospective studies with 9,378 cardiovascular events, including 7,222 participants in the PREVEND cohort [6]. 67,068 genotyped Danish adults, and 14,711 cases with 60,324 controls in the genetic meta-analysis [7].
- Sources
- [6], [7]
- Caveats
- The cohort finding is observational. The authors of the genetic studies conclude that their data suggest bilirubin is not causally associated with the risk of ischemic heart disease [7].
Sources
- US Food and Drug Administration. 21 CFR 862.1110, Bilirubin (total or direct) test system. Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/section-862.1110
- Centers for Disease Control and Prevention, National Center for Health Statistics. National Health and Nutrition Examination Survey 2017-2018 Laboratory Procedure Manual: Total Bilirubin, 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-Total-Bilirubin-508.pdf
- Centers for Disease Control and Prevention, National Center for Health Statistics. National Health and Nutrition Examination Survey 2017-2018 Data Documentation, Codebook, and Frequencies: Standard Biochemistry Profile (BIOPRO_J). February 2020. https://wwwn.cdc.gov/Nchs/Data/Nhanes/Public/2017/DataFiles/BIOPRO_J.htm
- Centers for Disease Control and Prevention, National Center for Health Statistics. National Health and Nutrition Examination Survey 2015-2016 Laboratory Procedure Manual: Bilirubin, 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_BILIRUBIN_DXC800and660i.pdf
- Zucker SD, Horn PS, Sherman KE. Serum bilirubin levels in the U.S. population: Gender effect and inverse correlation with colorectal cancer. Hepatology. 2004. https://doi.org/10.1002/hep.20407
- Kunutsor SK, Bakker SJL, Gansevoort RT, et al. Circulating Total Bilirubin and Risk of Incident Cardiovascular Disease in the General Population. Arteriosclerosis, Thrombosis, and Vascular Biology. 2015. https://doi.org/10.1161/ATVBAHA.114.304929
- Stender S, Frikke-Schmidt R, Nordestgaard BG, et al. Genetically elevated bilirubin and risk of ischaemic heart disease: three Mendelian randomization studies and a meta-analysis. Journal of Internal Medicine. 2013. https://doi.org/10.1111/j.1365-2796.2012.02576.x
- Horsfall LJ, Rait G, Walters K, et al. Serum Bilirubin and Risk of Respiratory Disease and Death. JAMA. 2011. https://doi.org/10.1001/jama.2011.124
- Abbasi A, Deetman PE, Corpeleijn E, et al. Bilirubin as a Potential Causal Factor in Type 2 Diabetes Risk: A Mendelian Randomization Study. Diabetes. 2015. https://doi.org/10.2337/db14-0228
- Horsfall LJ, Nazareth I, Pereira SP, Petersen I. Gilbert's syndrome and the risk of death: A population-based cohort study. Journal of Gastroenterology and Hepatology. 2013. https://doi.org/10.1111/jgh.12279
- Bosma PJ, Chowdhury JR, Bakker C, et al. The Genetic Basis of the Reduced Expression of Bilirubin UDP-Glucuronosyltransferase 1 in Gilbert's Syndrome. New England Journal of Medicine. 1995. https://doi.org/10.1056/NEJM199511023331802
- Woronyczová J, Nováková M, Leníček M, et al. Serum Bilirubin Concentrations and the Prevalence of Gilbert Syndrome in Elite Athletes. Sports Medicine - Open. 2022. https://doi.org/10.1186/s40798-022-00463-6
- Meyer BH, Scholtz HE, Schall R, et al. The effect of fasting on total serum bilirubin concentrations. British Journal of Clinical Pharmacology. 1995. https://doi.org/10.1111/j.1365-2125.1995.tb04424.x
- Griffin PM, Elliott SL, Manton KJ. Fasting increases serum bilirubin levels in clinically normal, healthy males but not females: a retrospective study from phase I clinical trial participants. Journal of Clinical Pathology. 2014. https://doi.org/10.1136/jclinpath-2013-202155
- 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
- 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
- Koseoglu M, Hur A, Atay A, Cuhadar S. Effects of hemolysis interference on routine biochemistry parameters. Biochemia Medica. 2011. https://doi.org/10.11613/BM.2011.015
- 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