Bilirubin in Athletes: Causes, Gilbert’s Syndrome, and Exercise-Induced Hemolysis

Introduction

Bilirubin in athletes is observed more frequently than in the general population. In my clinical practice, isolated mild elevations are typically benign and seldom require intervention. Higher levels, however, may prompt further evaluation. 

Overall, mild elevations of bilirubin in athletes are relatively common and are rarely associated with clinically significant pathology. Two of the most common benign explanations in otherwise healthy, well-trained individuals are Gilbert’s syndrome and exercise-induced hemolysis. Understanding how to distinguish these from each other, and from genuinely concerning pathology, can save athletes from unnecessary investigations and unnecessary worry.

I wrote this article to help athletes better understand and interpret elevated bilirubin levels. However, it is important to emphasise that if your bilirubin is elevated, you should consult your own doctor. It is not possible to determine the cause based on online information alone — proper evaluation always requires assessment by your treating physician.

What Is Bilirubin and Why Does It Rise?

Bilirubin is the yellow breakdown product of heme — the iron-containing component of haemoglobin in red blood cells. When ageing red blood cells are cleared from circulation, their haemoglobin is dismantled: approximately 80% of daily bilirubin production originates from the degradation of haemoglobin in senescent erythrocytes, with the remainder arising from ineffective erythropoiesis and other haem-containing proteins [1].

The resulting product — unconjugated (indirect) bilirubin — is fat-soluble and cannot be excreted directly. It travels in the bloodstream bound to albumin, is taken up by the liver, and undergoes enzymatic conjugation by the enzyme UDP-glucuronosyltransferase (encoded by the UGT1A1 gene). This conjugated (direct) bilirubin is water-soluble and is excreted into the bile and ultimately into stool [2].

This distinction between conjugated and unconjugated fractions is clinically fundamental. Elevated unconjugated (indirect) bilirubin points to increased red blood cell turnover — whether from hemolysis or impaired hepatic conjugation, as in Gilbert’s syndrome. Elevated conjugated (direct) bilirubin signals a problem further downstream: hepatocellular damage, bile duct obstruction, or cholestatic disease [2]. In athletes presenting with isolated mild hyperbilirubinaemia and no other symptoms, the fraction is almost invariably unconjugated — and the clinical stakes are very different.

Bilirubin is part of routine laboratory testing when evaluating liver function and is typically assessed alongside markers such as ALT, AST, ALP, and GGT, with additional tests like amylase included when clinically indicated.

In clinical practice, I do occasionally encounter patients with clearly elevated bilirubin levels, and in some cases — even in Gilbert’s syndrome — mild jaundice may occur. However, the presence of jaundice generally warrants prompt clinical evaluation, as it may indicate a more serious underlying condition.

Jaundice is a clinically significant finding that tends to raise immediate concern among clinicians. Acute causes may include hepatitis, while cholestasis — often due to mechanical obstruction of bile flow — is another key consideration. This may be related to a surgical condition or, in some cases, malignancy. If not recognised and managed in a timely manner, such conditions can become life-threatening.

For this reason, jaundice should always be evaluated without delay, and clinicians approach it with particular caution, especially in the initial assessment. Once Gilbert’s syndrome has been confirmed, however, patients can be reassured that mild and intermittent jaundice may occur and is not necessarily a cause for concern.

Gilbert’s Syndrome: Prevalent, Benign, and Over-Investigated

Gilbert’s syndrome (GS) is the most common hereditary disorder of bilirubin metabolism. It arises from a variant in the promoter region of the UGT1A1 gene — typically a TA repeat insertion — which reduces hepatic conjugation activity to approximately 30–50% of normal, without causing liver damage [3]. The result is chronic mild unconjugated hyperbilirubinaemia, usually below 3 mg/dL but occasionally rising up to around 5 mg/dL, with otherwise normal liver enzymes and no evidence of liver disease [3].

In the general population, GS affects an estimated 2–12% of individuals [3]. In some elite athlete cohorts, this figure is substantially higher. A 2022 study of 536 elite Czech athletes found a GS prevalence of 22%, compared to 9.6% in the general Czech population (p<0.001) [4]. Male elite athletes showed the highest prevalence at 27.7%, versus 12.6% in the general male population [4]. A 2023 study of 1,492 Italian Olympic athletes reported GS in 6% overall (9% in males, 2.4% in females), with endurance athletes showing higher bilirubin concentrations — a pattern hypothesised to reflect an adaptive antioxidant response to training-induced oxidative stress [5].

Several mechanisms likely contribute to higher bilirubin in trained athletes. Regular exercise is associated with oxidative stress and with higher bilirubin concentrations in athlete cohorts, though the precise mechanistic relationship remains under investigation [4]. Athletes also typically carry lower body fat — and serum bilirubin is inversely correlated with adiposity [4]. Exercise-induced hemolysis contributes transiently as well. These associations are well-documented across multiple elite cohorts. GS bilirubin elevation is worsened by several triggers athletes encounter routinely: fasting, physical exertion, stress, and illness [3].

Patients with Gilbert’s syndrome are often aware of their condition, as an initial presentation — sometimes jaundice — typically leads to a relatively prompt diagnostic evaluation and diagnosis. From that point onward, patients generally recognise their condition and may inform clinicians when bilirubin elevations are noted, whether in the context of jaundice or as an incidental finding in routine liver function tests.

Exercise-Induced Hemolysis and Bilirubin

The second major cause of elevated bilirubin in athletes is exercise-induced intravascular hemolysis — the mechanical destruction of red blood cells during exercise. In runners, exercise-induced hemolysis is primarily attributed to mechanical trauma from repetitive foot-strike impact [6]. In addition, other mechanisms such as muscle contractions, shear stress, and metabolic factors have been proposed in the broader literature [6].

After haemolysis, free haemoglobin is released into circulation. This haemoglobin is catabolised through the same heme degradation pathway, producing a surge of unconjugated bilirubin. When the rate of red blood cell destruction outpaces the liver’s conjugation capacity, indirect bilirubin rises in the bloodstream [1]. The pattern is characteristic: unconjugated bilirubin rises, haptoglobin falls (as it binds and clears free haemoglobin), and lactate dehydrogenase (LDH) increases from red blood cell lysis.

The haematological impact of this process was quantified in a 2024 scoping review of marathon and ultramarathon runners: across 267 runners, reticulocyte count increased by 16% post-race and haptoglobin fell by 21%, confirming intravascular hemolysis — while haemoglobin levels remained within accepted normal limits, reflecting adequate compensatory erythropoiesis [6]. Earlier research on 100-km ultramarathon runners documented total bilirubin increases of +106% post-race, with unconjugated bilirubin rising 96% — driven by haptoglobin reductions of 66% indicating haemolysis [7]. Notably, conjugated bilirubin also rose substantially in that extreme event (+283%), illustrating that at the upper end of race distances, even conjugated fractions can be transiently perturbed — a point to bear in mind when interpreting post-ultramarathon panels.

Exercise-induced hemolysis is generally transient and self-limiting, and clinically relevant anaemia appears uncommon in the available studies. Bilirubin typically returns toward baseline during early recovery, though the exact normalisation window varies across individuals and race distances. The clinical picture that accompanies hemolysis — elevated LDH, low haptoglobin, normal ALT, normal GGT — is very different from hepatocellular injury.

Patients rarely develop visible jaundice purely as a result of exercise. While bilirubin levels may rise and this is often detectable in laboratory tests, it seldom leads to a clinically apparent icteric appearance.

For this reason, if an athlete does develop jaundice — especially without a known history of Gilbert’s syndrome or another explanation — it should be evaluated promptly in a clinical setting. Initial assessment typically includes standard liver function tests, and even a routine general practitioner visit often leads to further investigations, sometimes extending to specialist care.

Once serious pathology has been excluded and the findings are confirmed to be benign, the elevation may be attributed to exercise-related factors. However, in cases of mild isolated bilirubin elevation, extensive investigations are not always necessary. In my own clinical practice, I often prefer to repeat bilirubin testing within one to two days when the elevation is modest, to assess whether the levels begin to normalise. Clinical history — particularly recent exercise — plays a key role in guiding this approach.

Bilirubin as an Antioxidant Advantage

Far from being an inert waste product, bilirubin is now recognised as a potent endogenous antioxidant. Unconjugated bilirubin operates through a continuous biliverdin-bilirubin redox cycle that amplifies its antioxidant capacity beyond what molar concentration alone would predict, and has been shown to be approximately 20 times more effective than the vitamin E analogue Trolox at preventing LDL oxidation in laboratory models [4].

This has meaningful implications for athletes with Gilbert’s syndrome. Individuals with GS demonstrate significantly elevated total antioxidant capacity and longer resistance to serum oxidation compared to controls — a mechanism that likely underpins the well-documented reduced prevalence of cardiovascular disease in GS populations [8]. One study found ischaemic heart disease prevalence of only 2% in GS subjects versus 12.1% in the general population [8].

For athletes specifically, higher baseline bilirubin appears to be a physiological advantage rather than a pathological concern. The Czech elite athlete study found that every one µmol/L increase in serum bilirubin was associated with a 4.6% greater probability of being classified as an elite athlete — suggesting bilirubin may contribute to exercise performance capacity through enhanced oxidative stress buffering during intense training [4].

In this context, despite its traditionally negative reputation, elevated bilirubin in athletes may represent a beneficial physiological adaptation with antioxidant properties. However, it is important to emphasise that potentially acute and serious underlying conditions must always be excluded before drawing this conclusion. Once appropriate initial investigations have been completed and no concerning pathology is identified, patients can be reassured that the finding is physiological in nature and may even confer some benefit.

Summary

Mild bilirubin elevation is a common finding in athletes and is usually benign. The two most common explanations in otherwise healthy individuals are Gilbert’s syndrome — a hereditary condition causing reduced bilirubin conjugation — and exercise-induced hemolysis, where red blood cells are transiently broken down during physical activity. Both typically lead to isolated increases in unconjugated bilirubin without signs of liver disease.

Understanding the difference between these benign causes and more serious conditions is essential. While mild elevations are rarely clinically significant, the presence of jaundice or abnormal liver markers should always prompt prompt medical evaluation, as they may indicate underlying pathology such as hepatitis or biliary obstruction.

In many cases, especially when bilirubin elevation is mild and isolated, a conservative approach is appropriate. Repeat testing and clinical context — particularly recent exercise — often clarify the situation without the need for extensive investigations. However, proper assessment by a physician is always necessary to exclude serious causes.

Interestingly, bilirubin may also have physiological benefits. It functions as a potent endogenous antioxidant, and higher baseline levels — particularly in individuals with Gilbert’s syndrome — have been associated with increased antioxidant capacity and potential cardiovascular protection. In athletes, this may represent a beneficial adaptation rather than a pathological finding.

Overall, elevated bilirubin in athletes is most often a reflection of normal physiology rather than disease. With appropriate evaluation and understanding, unnecessary concern and over-investigation can often be avoided.

References

1. https://link.springer.com/article/10.1186/s43162-024-00298-5
2. https://www.aafp.org/pubs/afp/issues/2017/0201/p164.html
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC11866151/
4. https://pmc.ncbi.nlm.nih.gov/articles/PMC9237193/
5. https://doi.org/10.1111/sms.14481
6. https://pmc.ncbi.nlm.nih.gov/articles/PMC11698231/
7. https://pubmed.ncbi.nlm.nih.gov/8614312/
8. https://pubmed.ncbi.nlm.nih.gov/11849670/
9. https://pmc.ncbi.nlm.nih.gov/articles/PMC2291230/