What is P-glycoprotein (P-gp)?

P-glycoprotein explained simply

Picture P-gp as a bouncer in the cell wall. If a foreign substance gets into the cell, P-gp can use energy to pump it back out. Technically it is an efflux pump encoded by the ABCB1 gene. It protects the body from toxins, but it also treats many drugs as if they were unwanted.

Where P-gp is found

• Small intestine: pumps substances back into the gut and so reduces absorption
• Liver and kidney: promotes excretion via bile and urine
• Blood-brain barrier: keeps many substances away from the brain

Together with the metabolising enzyme CYP3A4, P-gp forms a kind of double barrier that limits the bioavailability of many orally taken compounds.

P-gp, piperine and curcumin

In laboratory findings, piperine, the pungent compound in black pepper, inhibits both CYP3A4 and P-gp. The well-known piperine study (Shoba et al., 1998: 8 healthy volunteers, 2 g curcumin with or without 20 mg piperine) found about 20 times higher blood curcumin levels. It proposed mainly inhibition of glucuronidation as the mechanism; P-gp inhibition was not established as the cause. The study is small and old; later work (e.g. Fança-Berthon et al., 2021) did not confirm a significant effect.

The same applies to medicines, however. Drugs that use P-gp as an exit route may reach higher blood levels with piperine than expected. A frequently cited example of a P-gp substrate is digoxin, a heart medication. Assessing an individual case belongs in a doctor's hands.

Some drugs and foods also inhibit or induce P-gp, which is a common reason for drug interactions.

Why P-gp matters for supplements

Piperine is not the only thing that can influence P-gp. Other plant compounds and some foods are discussed in research as possible inhibitors or inducers, with partly unclear relevance in humans. There are also differences between people: the amount of P-gp in the gut wall varies genetically and individually.

An important point: laboratory findings show what is possible, not necessarily what happens with a normal diet. With the amounts of pepper you usually add to food, effects are far smaller than with high-dose piperine extracts.

Frequently asked questions

What does P-gp stand for? Permeability glycoprotein; it is also called MDR1 or ABCB1.

Why is P-gp important for medication? It helps determine how much of a drug is absorbed and excreted. Inhibition or induction can change drug levels.

Do I need to avoid black pepper? Normal culinary amounts are generally considered unproblematic. With high-dose piperine products and drugs with a narrow therapeutic range you should check with your doctor.