Guide to Total Bilirubin
Summary
Bilirubin is a natural product of old red blood cell breakdown (hemolysis); it can reflect both liver function and hemolysis (excessive red blood cell destruction) and can serve as an antioxidant.
Why It Matters
Total bilirubin provides insight into both liver health and red blood cell turnover in your body.
When red blood cells complete their lifecycle (approximately 120 days), they're broken down in the spleen and liver. During this process, hemoglobin is converted into bilirubin. This "unconjugated" or indirect bilirubin travels through your bloodstream attached to protein albumin. When it reaches your liver, it's processed into a more water-soluble form called "conjugated" or direct bilirubin. At this point, it can be excreted into bile and eventually passed through your stool.
High total bilirubin levels (hyperbilirubinemia) can indicate several potential issues:
- Liver dysfunction or disease, which may affect the organ's ability to process bilirubin
- Blockages in the bile ducts that prevent proper elimination of bilirubin
- Excessive breakdown of red blood cells (hemolytic anemia)
- Genetic conditions that affect bilirubin processing and transport
Very low bilirubin levels might suggest:
- Metabolic dysfunction
- Potential cardiovascular risks
- Certain medications or supplements affecting bilirubin metabolism
Slightly elevated bilirubin levels aren't always cause for concern. Although the research is early, there's evidence that mildly elevated bilirubin may actually serve as an antioxidant in the body.
Associated Symptoms
Bilirubin levels themselves are laboratory findings rather than medical conditions. However, abnormal levels may be associated with various health conditions, each with their own symptoms.
Common symptoms that may indicate conditions associated with elevated bilirubin:
- Yellowish skin and eyes (jaundice): The most recognizable sign of high bilirubin, occurs when excess bilirubin deposits in tissues
- Dark urine: May be caused by increased excretion of water-soluble bilirubin through the kidneys
- Lightly colored stool: May result from decreased bilirubin in the intestines due to bile duct obstruction
- Severe abdominal pain or tenderness: May indicate liver inflammation, gallstones, or bile duct blockage
- Mental changes: Drowsiness or confusion can occur in severe cases as bilirubin affects brain function
- Bloody or tarry black stool: May suggest gastrointestinal bleeding that can increase bilirubin from red blood cell breakdown
- Bloody vomit: Another potential sign of gastrointestinal bleeding causing increased bilirubin
- Fever: Can accompany liver inflammation or infection that can disrupt bilirubin processing
- Itchy skin: May result from bile salts depositing in the skin when bile flow is obstructed
- Easy bruising: May reflect potential liver dysfunction affecting clotting factor production
Very low bilirubin levels typically don't cause noticeable symptoms but may be associated with underlying conditions that have their own symptoms.
It's important to understand that many factors can cause these symptoms, and bilirubin levels are just one piece of diagnostic information. The presence of symptoms alongside abnormal bilirubin levels provides context for further investigation, but additional testing is typically needed to determine the underlying cause.
Clinical Ranges
Lab Reference Ranges:
- 10-19 Years: 0.2-1.1 mg/dL
- ≥20 Years: 0.2-1.2 mg/dL
Lifestyle Choices That Can Impact It
Activities that may improve bilirubin levels:
- Regular moderate exercise supports healthy liver blood flow and enhances the liver's ability to process bilirubin.
- Maintaining a healthy weight can reduce fat accumulation in the liver, which can interfere with bilirubin processing.
- Drinking enough fluids helps maintain blood volume and supports efficient transport of bilirubin to the liver.
- Getting enough sleep (7-9 hours) allows proper liver recovery and optimal bilirubin metabolism during rest periods.
- Limiting alcohol consumption minimizes stress on liver cells responsible for bilirubin processing.
Activities that may harm bilirubin levels:
- Prolonged fasting or extreme calorie restriction can stress liver function and alter bilirubin metabolism.
- Crash dieting and ketogenic diets can increase bilirubin due to altered fat metabolism
- Extreme physical exertion may increase red blood cell breakdown and overwhelm normal bilirubin processing.
- Dehydration concentrates bilirubin in the blood and makes it harder for the liver to process.
- Chronic stress impairs liver function through stress hormone effects and reduced blood flow.
Other Factors That Can Impact It
Genetic Conditions
The following factors can affect your body's ability to transport or break down bilirubin. This can lead to higher levels.
- Crigler-Najjar Type 1 - severe and requires lifelong treatment, while Type 2 is milder.
- Dubin-Johnson and Rotor syndromes cause elevated direct bilirubin but are usually benign.
- Gilbert's syndrome (affects 3--7 percent of the population)
- Rotor syndrome
Medications and Supplements
The following can increase bilirubin levels:
- Azathioprine
- Chlorpropamide
- Cholinergics
- Codeine
- Diuretics
- Epinephrine
- MAO inhibitors
- Meperidine
- Methotrexate
- Methyldopa
- Morphine
- Nicotinic acid
- Oral contraceptives
- Phenothiazines
- Quinidine
- Rifampin
- Salicylates
- Steroids
- Sulfonamides
- Theophylline
Others can lower bilirubin levels, including:
- Barbiturates
- Caffeine
- High-dose salicylates
- Penicillin
Other Factors
- Acute illness or infection
- Old age
- High altitude
- Gender (slightly higher in males)
- Recent surgery
- Seasonal variations
Testing Accuracy and Stability
Factors That Can Affect the Accuracy of Your Test
- Alcohol consumption should be avoided for at least 24 hours
- When you took the test (tests are typically performed in the morning for the most reliable result)
- Whether you recently had an intense workout
- You took certain medications within twenty-four hours of the test
- Exposure to light can affect the sample as bilirubin is light-sensitive
Best Practices for Testing
- Take the test in the morning, if possible (between 8--10 am).
- Fast for 8-12 hours before the test.
- Labs recommend fasting despite its tendency to increase values because it provides a standardized condition for testing, allowing for the comparison of values over time.
- Avoid intense exercise 24 hours before the test.
- Stay hydrated.
- Tell your provider about any medications or supplements you're taking.
- Consider taking the testing again if you have unexpected results.
How it Relates to Other Markers
Other tests can give clues about diseases or other conditions when they're combined with total bilirubin results. These tests include:
- Liver function tests (AST, ALT, ALP, GGT): High levels of these in addition to high bilirubin may point to liver damage or dysfunction.
- Direct/indirect bilirubin ratio: This measures how much direct (conjugated) and indirect (unconjugated) bilirubin is in your blood.
- Albumin: This is a protein your liver produces. High levels of albumin and bilirubin may indicate your gall bladder, liver, or bile duct is blocked, damaged or diseased.
- PT/INR: This test measures how quickly your blood clots. If your liver is damaged, it may not produce enough proteins to allow your blood to clot normally.
Follow-up Considerations
You should always talk to your doctor if you have medical concerns or questions.
When Re-Testing May be Appropriate
If your levels are mildly elevated but you don't have any symptoms, your doctor may recommend:
- Repeating the testing in 2-4 weeks.
- Observing whether levels vary based on fasting status.
- Tracking your patterns over time.
If your levels are significantly high or you have symptoms, your doctor may suggest:
- Taking a complete liver panel test.
- Scheduling any imaging studies your provider recommends.
- Monitoring more often.
If your levels are consistently low, they may suggest:
- Getting an oxidative stress evaluation. Low levels of bilirubin can indicate oxidative stress in the body, which can potentially damage cells.
- Considering a cardiovascular risk assessment. Very low levels of bilirubin can signal a risk of cardiovascular conditions.
- Getting a nutritional evaluation. Certain foods can increase or decrease your bilirubin levels.
Additional Testing Your Doctor May Consider
- Hepatitis panel
- Hemolysis workup
- Genetic testing for inherited conditions
- Imaging studies (ultrasound, CT, MRI) of liver and bile ducts
- Iron studies
- Autoimmune markers
Further Reading
The 2025 Levels Guide to the liver and metabolic health
Bibliography
References
1. Fevery J. (2008). Bilirubin in clinical practice: a review. Liver International, 28(5), 592-605.
2. Wagner KH, et al. (2015). Looking to the horizon: the role of bilirubin in the development and prevention of age-related chronic diseases. Clinical Science, 129(1), 1-25.
3. Watchko JF, Tiribelli C. (2013). Bilirubin-induced neurologic damage--mechanisms and management approaches. New England Journal of Medicine, 369(21), 2021-2030.
4. Vítek L. (2012). The role of bilirubin in diabetes, metabolic syndrome, and cardiovascular diseases. Frontiers in Pharmacology, 3, 55.
5. Neuzil J, Stocker R. (1994). Free and albumin-bound bilirubin are efficient co-antioxidants for alpha-tocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation. Journal of Biological Chemistry, 269(24), 16712-16719.
6. Fretzayas A, et al. (2012). Gilbert syndrome. European Journal of Pediatrics, 171(1), 11-15.
7. Strassburg CP. (2010). Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndrome). Best Practice & Research Clinical Gastroenterology, 24(5), 555-571.
8. Bosma PJ. (2003). Inherited disorders of bilirubin metabolism. Journal of Hepatology, 38(1), 107-117.
9. Roy-Chowdhury N, Roy-Chowdhury J. (2021). Classification and causes of jaundice or asymptomatic hyperbilirubinemia. UpToDate.
10. Jansen PL. (2017). Diagnosis and management of Crigler-Najjar syndrome. Current Treatment Options in Gastroenterology, 15(2), 292-297.
11. Rockey DC, et al. (2015). Liver biopsy. Hepatology, 61(3), 1050-1058.
12. Carey EJ, Ali AH, Lindor KD. Primary biliary cirrhosis. Lancet. 2015 Oct 17;386(10003):1565-75.
13. Mölzer C, Huber H, Steyrer A, Ziesel GV, Wallner M, Hong HT, Blanchfield JT, Bulmer AC, Wagner KH. Bilirubin and related tetrapyrroles inhibit food-borne mutagenesis: a mechanism for antigenotoxic action against a model epoxide. J Nat Prod. 2013 Oct 25;76(10):1958-65.
14. Vitek L, et al. (2019). The role of bilirubin in diabetes, metabolic syndrome, and cardiovascular diseases. Frontiers in Pharmacology, 10, 549.
15. Stone, C. (2005). Medical encyclopedia: Bilirubin. Medline Plus.
16. Lala, V., et al. (2023). Liver function tests. StatPearls.
17. Tripathi, N., et al. (2023). Conjugated hyperbilirubinemia. StatPearls.
18. University of Rochester Medical Center. (n.d.). Liver panel.
19. Rawat, V., et al. (2018). Bilirubin-induced oxidative stress leads to DNA damage in the cerebellum of hyperbilirubinemic neonatal mice and activates DNA double-strand break repair pathways in human cells. Oxidative Medicine and Cellular Longevity.
20. U.S. Department of Veterans Affairs. (n.d.). INR (international normalized ratio).
21. Fujiwara R, et al. (2018). Systemic regulation of bilirubin homeostasis: potential benefits of hyperbilirubinemia. Hepatology, 67(4), 1609-1619.
22. Watchko JF. (2016). Bilirubin-induced neurotoxicity in the preterm neonate. Clinics in Perinatology, 43(2), 297-311.
23. Sticova E, Jirsa M. (2013). New insights in bilirubin metabolism and their clinical implications. World Journal of Gastroenterology, 19(38), 6398-6407.
24. Horsfall LJ, et al. (2012). Gilbert's syndrome and the risk of death: a population-based cohort study. Journal of Gastroenterology and Hepatology, 27(10), 1643-1647.
25. Ollinger R, et al. Bilirubin: a natural inhibitor of vascular smooth muscle cell proliferation. Circulation. 2005 Aug 16;112(7):1030-9.
26. Shapiro SM. (2010). Chronic bilirubin encephalopathy: diagnosis and outcome. Seminars in Fetal and Neonatal Medicine, 15(3), 157-163.
27. Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Boston: Butterworths; 1990. PMID: 21250045.
28. Mitra S, Rennie J. (2017). Neonatal jaundice: aetiology, diagnosis and treatment. British Journal of Hospital Medicine, 78(12), 699-704.
29. # Rinella, M.E., et al. (2023). From NAFLD to MASLD: updated naming and diagnosis criteria for fatty liver disease. Journal of Lipid Research, 14;65(1):100485.
30. Ge, X., et al. (2020). Plasma metals and serum bilirubin levels in workers from manganese-exposed workers healthy cohort (MEWHC). Environmental Pollution, Volume 258.
31. Shapira, U., et al. (2021). Association between elevated serum bilirubin levels with preserved lung function under conditions of exposure to air pollution. BMC Pulmonary Medicine, 13;21:119.
32. Pálešová, N., et al. (2023). Firefighters and the liver: Exposure to PFAS and PAHs in relation to liver function and serum lipids (CELSPAC-FIREexpo study). International Journal of Hygiene and Environmental Health, Volume 252.
33. Tholey, D. (2024). Jaundice in adults. Merck Manual, Consumer Version.
Additional sources:
42. Otnes S, Fogh-Andersen N, Rømsing J, Thomsen HS. Analytical Interference by Contrast Agents in Biochemical Assays. Contrast Media Mol Imaging. 2017 Apr 10;2017:1323802.
43. T.W. Sedlak, et al. Bilirubin and glutathione have complementary antioxidant and cytoprotective roles, Proc. Natl. Acad. Sci. U.S.A. 106 (13) 5171-5176,
44. Corrons JLV, Casafont LB, Frasnedo EF. Concise review: how do red blood cells born, live, and die? Ann Hematol. 2021 Oct;100(10):2425-2433.
45. Han HS, Park CM, Lee DS, Sinn DH, Gil E. Evaluating mortality and recovery of extreme hyperbilirubinemia in critically ill patients by phasing the peak bilirubin level: A retrospective cohort study. PLoS One. 2021 Aug 5;16(8):e0255230.
46. Creeden JF, Gordon DM, Stec DE, Hinds TD Jr. Bilirubin as a metabolic hormone: the physiological relevance of low levels. Am J Physiol Endocrinol Metab. 2021 Feb 1;320(2):E191-E207.
47. Adin CA. Bilirubin as a Therapeutic Molecule: Challenges and Opportunities. Antioxidants (Basel). 2021 Sep 28;10(10):1536.
48. Flack KD, Vítek L, Fry CS, Stec DE, Hinds TD Jr. Cutting edge concepts: Does bilirubin enhance exercise performance? Front Sports Act Living. 2023 Jan 11;4:1040687.
49. Gillaspie DB, Davis KA, Schuster KM. Total bilirubin trend as a predictor of common bile duct stones in acute cholecystitis and symptomatic cholelithiasis. Am J Surg. 2019 Jan;217(1):98-102.
50. Žiberna L, Jenko-Pražnikar Z, Petelin A. Serum Bilirubin Levels in Overweight and Obese Individuals: The Importance of Anti-Inflammatory and Antioxidant Responses. Antioxidants (Basel). 2021 Aug 26;10(9):1352.
51. Vitek L, Hinds TD Jr, Stec DE, Tiribelli C. The physiology of bilirubin: health and disease equilibrium. Trends Mol Med. 2023 Apr;29(4):315-328
52. Vítek L, Jirásková A, Malíková I, Dostálová G, Eremiášová L, Danzig V, Linhart A, Haluzík M. Serum Bilirubin and Markers of Oxidative Stress and Inflammation in a Healthy Population and in Patients with Various Forms of Atherosclerosis. Antioxidants (Basel). 2022 Oct 27;11(11):2118.
53. Suh S, Cho YR, Park MK, Kim DK, Cho NH, Lee MK. Relationship between serum bilirubin levels and cardiovascular disease. PLoS One. 2018 Feb 15;13(2):e0193041.
54. Jenko-Pražnikar Z, Petelin A, Jurdana M, Žiberna L. Serum bilirubin levels are lower in overweight asymptomatic middle-aged adults: an early indicator of metabolic syndrome? Metabolism. 2013 Jul;62(7):976-85.
55. Shah NM, Malhotra AM, Kaltsakas G. Sleep disorder in patients with chronic liver disease: a narrative review. J Thorac Dis. 2020 Oct;12(Suppl 2):S248-S260.
56. Goluch Z, Wierzbicka-Rucińska A, Książek E. Nutrition in Gilbert's Syndrome-A Systematic Review of Clinical Trials According to the PRISMA Statement. Nutrients. 2024 Jul 12;16(14):2247.
57. 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. J Clin Pathol. 2014 Jun;67(6):529-34.
58. Akmal M, Massry SG. Reversible hepatic dysfunction associated with rhabdomyolysis. Am J Nephrol. 1990;10(1):49-52.
59. Yamaguchi T, Shioji I, Sugimoto A, Yamaoka M. Psychological stress increases bilirubin metabolites in human urine. Biochem Biophys Res Commun. 2002 Apr 26;293(1):517-20.
60. Chertoff J, Alam S, Black M, Elgendy IY. Azathioprine-induced hepatitis and cholestasis occurring 1 year after treatment. BMJ Case Rep. 2014 Dec 3;2014:bcr2014206859.
61. Boland BS, Dong MH, Bettencourt R, Barrett-Connor E, Loomba R. Association of serum bilirubin with aging and mortality. J Clin Exp Hepatol. 2014 Mar;4(1):1-7.
62. Altland PD, Parker MG. Bilirubinemia and intravascular hemolysis during acclimatization to high altitude. Int J Biometeorol. 1977 Jun;21(2):165-70.
63. Zucker SD, Horn PS, Sherman KE. Serum bilirubin levels in the U.S. population: gender effect and inverse correlation with colorectal cancer. Hepatology. 2004 Oct;40(4):827-35.
64. Bansal S, Jain S, Rathi PM, Chandnani S, Debnath P, Nawghare P. Effects of high bilirubin level in pregnancy in Crigler-Najjar syndrome type 2: An extremely rare but important clinical entity to recognize. Med J Armed Forces India. 2023 Sep-Oct;79(5):597-600.
65. Nagae M, Egi M, Kubota K, Makino S, Mizobuchi S. Association of direct bilirubin level with postoperative outcome in critically ill postoperative patients. Korean J Anesthesiol. 2018 Feb;71(1):30-36.
66. Miyake K, Miyake N, Kondo S, Tabe Y, Ohsaka A, Miida T. Seasonal variation in liver function tests: a time-series analysis of outpatient data. Ann Clin Biochem. 2009 Sep;46(Pt 5):377-84.
67. Larsson A, Hassan M, Ridefelt P, Axelsson J. Circadian variability of bilirubin in healthy men during normal sleep and after an acute shift of sleep. Chronobiol Int. 2009 Dec;26(8):1613-21.
68. VanWagner LB, Green RM. Evaluating elevated bilirubin levels in asymptomatic adults. JAMA. 2015 Feb 3;313(5):516-7.




