Gallstone disease in athletes: causes and links with training load and pharmacology

Gallstone disease is usually associated with excess weight and a sedentary lifestyle, so for many athletes a diagnosis of 'gallbladder stones' comes as a surprise. In reality, regular training lowers the risk, but some habits typical of sport - sharp 'cutting', starvation diets, certain drugs - can raise it. Our editorial team examined how stones form and what is linked to this in the sporting environment.

How gallstones form

Bile is a mixture of water, bile acids, phospholipids, cholesterol and bilirubin produced by the liver. Between meals it accumulates and concentrates in the gallbladder, and after eating, especially fatty food, the bladder contracts under the action of the hormone cholecystokinin and pushes bile into the duodenum.

In most patients in Western countries, cholesterol stones occur. They arise when bile becomes supersaturated with cholesterol while there are not enough bile acids and phospholipids to keep it dissolved. Excess cholesterol crystallizes, the crystals clump into 'sludge', and later into solid concretions.

The third key element is bladder motility. If it contracts rarely or incompletely, bile stagnates and the crystals have more time to grow. That is why the classic model of pathogenesis describes a triad: cholesterol supersaturation, accelerated crystal nucleation and gallbladder hypomotility.

Pigment stones, linked to the breakdown of red blood cells or infection of the bile ducts, occur less often. They are less typical for athletes, but it is important to understand: 'stones' are not one disease with one cause, but the end result of several different processes.

Physical activity: a protective factor

Large cohort studies show that regular physical activity is associated with a lower risk of symptomatic gallstone disease. In the well-known work of Leitzmann and co-authors among male health professionals, the most active participants had a markedly lower risk than those who moved the least, and this association persisted after accounting for body weight.

There are several mechanisms. Training improves insulin sensitivity, lowers triglyceride levels and raises HDL, which affects the composition of bile. In addition, active people are less likely to be obese - one of the strongest risk factors for cholesterol stones.

There are also data that physical activity speeds up intestinal transit and may indirectly affect bile acid metabolism. The exact contribution of each mechanism is still being clarified, but the overall conclusion is stable: movement is prevention, not a cause.

So when gallstones are found in an athlete, one should look not for 'excessive training' but for specific circumstances: sharp weight fluctuations, dietary features, use of certain drugs or hereditary predisposition.

Diets, 'cutting' and rapid weight loss

The most documented 'sporting' risk factor is rapid weight loss. Studies in patients after bariatric surgery and on very low-calorie diets showed that over a few months of intensive weight loss new stones or sludge appear in a significant proportion of people. The EASL guidelines directly name rapid weight loss as a risk factor.

The reason is that during weight loss the liver mobilizes cholesterol and excretes it with bile, while with a very low fat content in the diet the bladder barely contracts. Bile becomes both supersaturated and stagnant - an ideal environment for crystallization.

• very low-calorie diets and fasting for weeks;
• a diet with almost no fat, because of which the bladder does not contract for a long time;
• rapid weight loss after bariatric interventions or drug-induced weight loss;
• repeated sharp fluctuations in body weight ('yo-yo').

For athletes this is relevant during pre-competition preparation in bodybuilding, physique and combat sports with weight categories. Very low-calorie diets with minimal fat, long periods of fasting and repeated 'bulking - cutting' cycles potentially reproduce the same physiology.

The editorial team emphasizes: a calorie deficit itself is not harmful; the problem becomes the pace and the extreme. Moderate weight loss while keeping a certain amount of fat in every meal is, according to studies, associated with a lower risk of sludge formation.

Pharmacology: which drugs can have an effect

Estrogens increase cholesterol secretion into bile. This is well known from studies of hormone replacement therapy in women, in particular from the analysis of the Women's Health Initiative. In the context of sport this concerns situations where high doses of androgens are aromatized into estradiol, as well as the use of estrogen-containing contraception by female athletes.

GLP-1 receptor agonists (semaglutide, liraglutide) and similar drugs for treating obesity carry warnings about gallbladder disease in their official labels. A meta-analysis by He and co-authors in JAMA Internal Medicine (2022) demonstrated an increased risk of gallstone and biliary events, especially at higher doses and when used for weight loss.

Anabolic steroids, especially oral 17-alpha-alkylated ones, are known primarily for hepatotoxicity and cholestasis rather than classic cholesterol stones. However, they lower HDL and alter the lipid profile, so their role in biliary pathology is discussed, although quality data are lacking.

Among other drugs with a known association are octreotide (suppresses bladder contraction), ceftriaxone (can form sediment in bile) and fibrates. For athletes there is one main rule: any prescription drug must be prescribed by a doctor who will take these risks into account.

Other risk factors worth knowing

Genetics plays a substantial role: twin studies estimate the contribution of heredity at about a quarter of cases, and the ABCG8 gene variant is one of the best-known genetic factors. If parents had stones, an athlete's risk is higher regardless of training.

Female sex, age over 40, pregnancy, obesity, insulin resistance and type 2 diabetes are classic factors that do not disappear just because a person plays sport. Veteran female athletes who combine these factors need special attention.

A diet high in refined carbohydrates and low in fiber is associated with a higher risk, whereas consumption of fiber, nuts and a moderate amount of coffee is associated with a lower risk in observational studies. These associations are observational in nature, so they should be interpreted with caution.

A separate point is prolonged parenteral nutrition and long periods without food, for example during injuries and hospitalizations. During such periods the bladder barely works, which promotes sludge formation.

Editorial conclusions

Gallstone disease in athletes is not a paradox but the result of a combination of ordinary risk factors with the features of a sporting lifestyle. Regular training generally protects, while the threat is created by drastic diets, rapid weight loss and certain drugs.

The most practically significant points are a controlled pace of weight loss, keeping fat in the diet and caution with medications that affect hormonal balance and appetite. Any weight-loss drugs or hormonal agents must be prescribed and monitored by a doctor.

If you have a family history or episodes of pain after fatty food, discuss this with a gastroenterologist and get an ultrasound. Early detection helps avoid complications.

The editorial team also recommends reading our materials on the prevention and diagnosis of gallstone disease, on safe 'cutting' before competitions and on the effect of anabolic steroids on the liver.

References

1. European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines on the prevention, diagnosis and treatment of gallstones. J Hepatol. 2016;65(1):146–181.
2. Lammert F, Gurusamy K, Ko CW, et al. Gallstones. Nat Rev Dis Primers. 2016;2:16024.
3. Stinton LM, Shaffer EA. Epidemiology of gallbladder disease: cholelithiasis and cancer. Gut Liver. 2012;6(2):172–187.
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5. Cirillo DJ, Wallace RB, Rodabough RJ, et al. Effect of estrogen therapy on gallbladder disease. JAMA. 2005;293(3):330–339.
6. He L, Wang J, Ping F, et al. Association of glucagon-like peptide-1 receptor agonist use with risk of gallbladder and biliary diseases: a systematic review and meta-analysis of randomized clinical trials. JAMA Intern Med. 2022;182(5):513–519.
7. Shiffman ML, Sugerman HJ, Kellum JM, et al. Gallstone formation after rapid weight loss: a prospective study in patients undergoing gastric bypass surgery for treatment of morbid obesity. Am J Gastroenterol. 1991;86(8):1000–1005.