Hi Kathy @kathyhg. The Big 3 don't cause high cholesterol. The problem is that Rifampicin can, for some people, interact with anti-cholesterol drugs, making those drugs stop working. As a result, because the anti-cholesterol drugs stop working, people with a cholesterol problem before they took the Big 3, can find they have high cholesterol again. That's what happened for me. I hope this expalantion helps, Annie