The Risks of Gallstone Formation in People with NAFLD

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD, still widely known as non-alcoholic fatty liver disease or NAFLD) is a growing health concern worldwide, primarily driven by the increasing rates of obesity and metabolic syndrome. That excess weight is not evenly distributed — the visceral fat behind a beer belly is the compartment most closely tied to both conditions. NAFLD encompasses a spectrum of liver conditions ranging from simple steatosis (fat accumulation in the liver) to non-alcoholic steatohepatitis (NASH), which can lead to fibrosis, cirrhosis, and liver failure.

Gallstones are more common in people with NAFLD, a link that is often overlooked. In a pooled analysis of 12 studies, about 17% of people with NAFLD had gallstone disease, and NAFLD was linked with roughly 1.4 times higher odds of gallstones (Shen 2017). The two conditions share the same risk factors, such as obesity, insulin resistance and diabetes, and each is more common in people who have the other (Jaruvongvanich 2016). Choline, inositol, methionine, and taurine take part in fat and bile metabolism, but much of the evidence on them comes from animal studies.

The Link Between NAFLD and Gallstones

Gallstones are hardened deposits that form in the gallbladder, most commonly made of cholesterol or bilirubin. The gallbladder stores bile, a substance produced by the liver to help digest fats. NAFLD can disrupt this process in several ways, increasing the risk of gallstone formation:

1. Bile Composition: Bile acids and phospholipids keep cholesterol dissolved in bile. When the liver releases more cholesterol than they can carry, bile becomes supersaturated and gallstones can form.
2. Altered Lipid Metabolism: NAFLD is associated with insulin resistance, which alters lipid metabolism and increases the concentration of cholesterol in the bile, another key factor in gallstone formation.
3. Slow Gallbladder Emptying: People with NAFLD may experience slower gallbladder motility, which means that bile stays in the gallbladder longer, increasing the likelihood of cholesterol crystallization and gallstone formation.
4. Obesity and Rapid Weight Loss: Obesity, a common feature of NAFLD, is a major risk factor for gallstones. Rapid weight loss, which is sometimes undertaken to reverse NAFLD, can paradoxically increase the risk of gallstones due to rapid changes in bile composition.

Choline, Inositol, Methionine and Taurine: What the Evidence Shows

All four nutrients—choline, inositol, methionine, and taurine—take part in liver and bile metabolism, but none has been tested in human trials for preventing gallstones.

1. Choline

• Role in Liver and Gallbladder Health: Choline is a crucial nutrient for liver function and fat metabolism. It is a precursor to phosphatidylcholine, a component of bile that helps emulsify fats for digestion. Inadequate choline intake causes fatty liver. People with an inherited defect in moving phosphatidylcholine into bile develop cholesterol gallstones early in life, which shows how important it is for bile; whether dietary choline affects gallstone risk has not been tested in humans.
• Impact on NAFLD and Gallstones: In choline-deficient patients on long-term intravenous feeding, giving choline reversed their fatty liver (Buchman 1995). Effects on bile flow or gallstone risk have not been shown.

2. Inositol

• Role in Lipid Metabolism: Inositol is involved in cell membrane formation and insulin signaling. It takes part in lipid metabolism, and insulin resistance is a shared risk factor for NAFLD and gallstones.
• Impact on NAFLD and Gallstones: In animal models of fatty liver, inositol supplementation reduced liver fat; the only human trial in a recent review (with pinitol, a related compound) also found less liver fat. Evidence on bile flow comes only from animal studies, and there are no human data on gallstones.

3. Methionine

• Role in Detoxification and Bile Production: Methionine is an essential amino acid that is a precursor to glutathione, one of the body’s most important antioxidants. It also plays a role in the production of S-adenosylmethionine (SAMe), which is involved in methylation reactions necessary for liver detoxification and bile production.
• Impact on NAFLD and Gallstones: The only direct gallstone evidence is from dogs: methionine prevented pigment gallstones in dogs on a low-protein diet (Christian & Rege 1996). Human cholesterol gallstones, the common type, are a different condition, and methionine has not been tested for them.

4. Taurine

• Role in Bile Acid Conjugation: Taurine is one of the two amino acids (with glycine) that the liver attaches to bile acids to make them more soluble. In humans, bile acids can be conjugated with either, so taurine is not strictly required.
• Impact on NAFLD and Gallstones: In the same dog study, taurine did not protect against gallstones, and there are no human trials of taurine for gallstone prevention.

Conclusion

Gallstones are more common in people with NAFLD, mainly because the two share the same drivers: excess weight, insulin resistance and changes in bile composition. What lowers the risk is the same as what helps the liver: gradual weight loss rather than crash dieting, regular physical activity and a balanced diet.

Of the four, choline is the one with EU-approved health claims: it contributes to normal lipid metabolism and to the maintenance of normal liver function. What else sits next to choline in LiverGuard, and in what amounts, is on its product page — no promises about gallstones, just the label.

Resources

1. NAFLD and gallstone disease — meta-analyses: Jaruvongvanich, V., Sanguankeo, A., & Upala, S. (2016). Significant association between gallstone disease and nonalcoholic fatty liver disease: a systematic review and meta-analysis. Digestive Diseases and Sciences, 61(8), 2389-2396. DOI: 10.1007/s10620-016-4125-2
2. Shen, S. S., Gong, J. J., Wang, X. W., et al. (2017). Promotional effect of nonalcoholic fatty liver disease on gallstone disease: a systematic review and meta-analysis. Turkish Journal of Gastroenterology, 28(1), 31-39. DOI: 10.5152/tjg.2016.0357
3. Choline and phosphatidylcholine metabolism: Zeisel, S. H. (2006). Choline: critical role during fetal development and dietary requirements in adults. Annual Review of Nutrition, 26, 229-250. DOI: 10.1146/annurev.nutr.26.061505.111156
4. Inositol and lipid metabolism: Croze, M. L., & Soulage, C. O. (2013). Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie, 95(10), 1811-1827. DOI: 10.1016/j.biochi.2013.05.011
5. Methionine, SAMe and liver function: Mato, J. M., & Lu, S. C. (2007). Role of S-adenosyl-L-methionine in liver health and injury. Hepatology, 45(5), 1306-1312. DOI: 10.1002/hep.21650
6. Taurine as a bile-acid conjugate: Schaffer, S. W., & Kim, H. W. (2018). Effects and mechanisms of taurine as a therapeutic agent. Biomolecules & Therapeutics, 26(3), 225-241. DOI: 10.4062/biomolther.2017.251
7. European Association for the Study of the Liver. (2016). EASL Clinical Practice Guidelines on the prevention, diagnosis and treatment of gallstones. Journal of Hepatology, 65(1), 146-181. DOI: 10.1016/j.jhep.2016.03.005
8. Buchman, A. L., Dubin, M. D., Moukarzel, A. A., et al. (1995). Choline deficiency: a cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation. Hepatology, 22(5), 1399-1403. DOI: 10.1016/0270-9139(95)90143-4
9. Pani, A., Giossi, R., Menichelli, D., et al. (2020). Inositol and non-alcoholic fatty liver disease: a systematic review on deficiencies and supplementation. Nutrients, 12(11), 3379. DOI: 10.3390/nu12113379
10. Christian, J. S., & Rege, R. V. (1996). Methionine, but not taurine, protects against formation of canine pigment gallstones. Journal of Surgical Research, 61(1), 275-281. DOI: 10.1006/jsre.1996.0116

Related reading

• Fatty liver disease (MASLD)
• High cholesterol and the liver
• How dangerous is liver fat