Gallstone Disease in Athletes: Causes and the Link to Training Load and Pharmacology

Gallstone disease is usually associated with excess weight and a sedentary lifestyle, so for many athletes a diagnosis of 'gallstones' comes as a surprise. In reality, regular training lowers the risk, but some habits typical of sport - rapid 'cutting,' crash diets, certain drugs - can raise it. The editorial team examined how stones form and what is linked to them 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 gallbladder contracts under the action of the hormone cholecystokinin and pushes the bile into the duodenum.

In most patients in Western countries, cholesterol stones occur. They arise when bile becomes supersaturated with cholesterol and 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 gallbladder motility. If it contracts rarely or incompletely, bile stagnates, and crystals have more time to grow. The classic model of pathogenesis therefore describes a triad: cholesterol supersaturation, accelerated crystal nucleation, and gallbladder hypomotility.

Pigment stones, associated with the breakdown of red blood cells or infection of the biliary tract, occur less often. They are less typical for athletes, but it is important to understand: 'stones' are not a single disease with a single 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 a well-known work by Leitzmann and colleagues 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 less often have obesity - one of the strongest risk factors for cholesterol stones.

There is also evidence that physical activity accelerates intestinal transit and may indirectly affect bile acid metabolism. The exact contribution of each mechanism is still being clarified, but the general 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 a hereditary predisposition.

Diets, 'Cutting,' and Rapid Weight Loss

The most documented 'sports' risk factor is rapid weight loss. Studies in patients after bariatric surgery and on very low-calorie diets have shown 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 into the bile, while with a very low fat content in the diet the gallbladder hardly 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 gallbladder does not contract for a long time;
• rapid weight loss after bariatric procedures 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 'bulk-cut' cycles potentially reproduce the same physiology.

The editorial team emphasizes: a calorie deficit itself is not harmful; the problem is the pace and the extremes. Moderate weight loss with some fat retained in each meal is, according to research, associated with a lower risk of sludge formation.

Pharmacology: Which Drugs Can Have an Effect

Estrogens increase the secretion of cholesterol 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 applies to situations where high doses of androgens are aromatized into estradiol, as well as to the use of estrogen-containing contraception by female athletes.

GLP-1 receptor agonists (semaglutide, liraglutide) and similar drugs for treating obesity carry a warning about gallbladder disease in their official labels. A meta-analysis by He and colleagues in JAMA Internal Medicine (2022) confirmed 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, not for 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 link are octreotide (suppresses gallbladder contraction), ceftriaxone (can form sediment in bile), and fibrates. For athletes there is one main rule: any prescription drug should be prescribed by a doctor who will take these risks into account.

Other Risk Factors Worth Knowing

Genetics play a significant role: twin studies estimate the contribution of heredity at about a quarter of cases, and a variant of the ABCG8 gene is one of the best-known genetic factors. If the parents had stones, the 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 sports. Veteran female athletes who combine these factors need special attention.

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

A separate point is long-term parenteral nutrition and long periods without food, for example during injuries and hospitalizations. During such periods the gallbladder hardly 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 comes from crash diets, rapid weight loss, and some drugs.

The most practically significant points are a controlled pace of weight loss, retaining fat in the diet, and caution with medications that affect the hormonal background and appetite. Any weight-loss or hormonal drugs 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

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