Bile Acid Sequestrants

These are treatments for diagnosed high cholesterol or type 2 diabetes, prescribed by a doctor, not tools for healthy people. The everyday version of the same mechanism is soluble fibre: oats and legumes bind bile acids too.

What they are

The liver makes bile acids from cholesterol and normally recycles them: they return from the end of the small intestine to the liver. Sequestrants — cholestyramine is the older one, colesevelam a newer one — bind bile acids in the gut and carry them out. To replace them, the liver pulls more cholesterol out of the blood, and LDL cholesterol falls. Soluble fibre works the same way, which is why oats and legumes lower LDL. The wider biology is on Bile, microbiome and metabolic health.

The heart trial: real, but one trial in men

Cholestyramine has a heart-outcome trial. Over about seven years, 3,806 middle-aged men with high cholesterol took it or a placebo, alongside a cholesterol-lowering diet. LDL fell about 13% more on the drug than on placebo, and coronary deaths plus nonfatal heart attacks fell from 8.6% to 7% of men — a 19% relative reduction. Deaths from all causes were not clearly lower: the drug group had more violent and accidental deaths.^[1]

The trial's statistics were borderline, it included only men, and it is decades old. It is best read as early evidence that lowering LDL prevents heart attacks, rather than as evidence about bile signaling.

Blood sugar: a real effect, an unknown route

Colesevelam is also approved as an add-on for type 2 diabetes. Pooling six randomised trials of 8 to 26 weeks (1,450 people in all), colesevelam added to standard diabetes drugs lowered HbA1c, a measure of average blood sugar, by about half a percentage point, and LDL as well. Low blood sugar episodes were infrequent and not severe. Colesevelam has no heart-outcome trial of its own.^[2]

How it lowers glucose is unknown. The popular explanation is that trapping bile acids takes a brake off GLP-1 (glucagon-like peptide-1), the gut hormone that modern weight-loss drugs mimic. Two small human studies point away from that:

• In a 17-day trial in 15 adults with type 2 diabetes, sevelamer, a phosphate-binding drug that also traps bile acids, lowered fasting and after-meal glucose, and blocking the GLP-1 receptor did not take that away. Only a modest gain in how the insulin-making cells responded to glucose depended on GLP-1.^[3]
• A single dose of colesevelam did not raise GLP-1.^[4]

GLP-1 looks like a minor part of the story, though both studies were small and short, and one used a stand-in drug.

Other uses

Sequestrants have also been tested for lowering blood levels of the "forever chemicals" PFAS; they lowered the levels, with no health benefit shown. See PFAS.

What to do

1. Don't take a sequestrant without a prescription. They are drugs for diagnosed disease, not a metabolic tune-up, and they have digestive and nutrient-absorption side effects.
2. If you want the same mechanism from food, eat soluble fibre daily, such as oats and legumes. See Fibre.
3. If your doctor suggests one, for high cholesterol or type 2 diabetes, the evidence above is what it rests on: solid for LDL and blood sugar, thin for heart outcomes beyond the one trial in men.

Further reading

• Lipid Research Clinics Program. The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA 1984.^[5]
• Ooi CP, Loke SC. Colesevelam for Type 2 diabetes mellitus: an abridged Cochrane review. Diabet Med 2014.^[6]
• Nerild HH, et al. Elucidating the glucose-lowering effect of the bile acid sequestrant sevelamer. Diabetes Obes Metab 2024.^[7]
• Hansen M, et al. Effect of chenodeoxycholic acid and the bile acid sequestrant colesevelam on glucagon-like peptide-1 secretion. Diabetes Obes Metab 2016.^[8]