What causes gallstones to form

    For bile to stay fluid and prevent gallstone formation, there must be a proper balance between cholesterol and phosphatidylcholine, ideally at a 1:10 ratio.

    Typical bile solids consist of around 80% bile salts. Cholesterol is converted into bile salts in the liver. When the proportion of bile salts and/or phospholipids decreases and cholesterol levels remain too high, the bile thickens, making it sluggish. This happens because excess cholesterol solidifies, leading to gallstones. These gallstones block the bile ducts, stopping bile from reaching the small intestine.

    Gallstones are significantly more common in women than in men. This is because estrogen increases cholesterol production while reducing bile acid synthesis.

    The most common type of gallstone is the cholesterol stone. Over 70-85% of gallstones are predominantly cholesterol. The phosphatidylethanolamine N-methyltransferase (PEMT) enzyme synthesizes phosphatidylcholine, which is necessary to transport cholesterol from the liver. Once removed from the liver, cholesterol is packaged into bile, maintaining healthy cholesterol levels. When PEMT slows down or is impaired, cholesterol can accumulate in the liver, leading to various health issues, including an increased risk of gallstone formation.

    Pregnant women are particularly vulnerable to gallstone formation due to several physiological changes. One major factor is choline deficiency. Over 90% of pregnant women are deficient in choline, a nutrient crucial for maintaining PEMT enzyme function and phosphatidylcholine production. SNP PEMT and low choline contribute to higher cholesterol in the liver, more sluggish bile, and thus increased risk for gallstones.