Everybody wants lower cholesterol and many of us take cholesterol-lowering statin drugs, but is it possible to go too low?

Many studies show that lowering low-density lipoprotein (LDL, or "bad" cholesterol) is one of the most important things we can do to prevent heart disease. New research, however, has found a disturbing association between low LDL levels and cancer risk.

The authors of the study, published in the July 31, 2007 Journal of the American College of Cardiology (JACC), originally set out to investigate how and why statins cause side effects, particularly damage to the liver and muscle cells. They did not expect to find an increased cancer risk from low LDL levels. But they did.

Already, additional studies have begun to investigate this potential risk further. What is hoped is that future studies will be to confirm the risk and identify whether it is a side effect of statins or low LDL.

"This analysis doesn't implicate the statin in increasing the risk of cancer," said lead author Richard H. Karas, M.D., F.A.C.C., professor of medicine at Tufts University School of Medicine. "The demonstrated benefits of statins in lowering the risk of heart disease remain clear; however, certain aspects of lowering LDL with statins remain controversial and merit further research."

The researchers found one additional incident of cancer per 1,000 patients with low LDL levels when compared to patients with higher LDL levels.

They also assessed LDL reduction in relation to rates of newly diagnosed cancer.

The results? There were higher rates of newly diagnosed cancer in patients with lower LDL levels. The new cancers were not of any specific type or location.

Recent data from large-scale statin trials have shown that more intensive LDL lowering can help those at high risk for heart disease. In response, recent national guidelines have advocated for lower LDL goals and higher doses of statins to reach them. However, informal observations linking intensive LDL lowering and a higher incidence of liver and muscle toxicity and cancer has caused concerns about the safety of higher-dose statins.

"While these results raise important new questions about statin use, they do not demonstrate a causal relationship between statins and cancer," said James Dove, M.D., F.A.C.C., president of the American College of Cardiology. "This study is hypothesis-generating, not hypothesis-proving."