Drinking your coffee black or decaffeinated to keep cholesterol in check? Think again.

Cafestol, a compound found in coffee, elevates cholesterol by hijacking a receptor in an intestinal pathway critical to its regulation, said researchers from Baylor College of Medicine in a report that appears in the July issue of the journal Molecular Endocrinology.

In fact, cafestol is the most potent dietary cholesterol-elevating agent known, said Dr. David Moore, professor of molecular and cellular biology at BCM, and Dr. Marie-Louise Ricketts, a postdoctoral student and first author of the report. Cafetiere, or French press coffee, boiled Scandinavian brew and espresso contain the highest levels of the compound, which is removed by paper filters used in most other brewing processes. Removing caffeine does not remove cafestol, however.

Studies by a co-author – Dr. Martijn B. Katan of Vriye Univeriteit Amsterdam, Institute for Health Sciences, The Netherlands – indicate that consuming five cups of French press coffee per day (30 milligrams of cafestol) for four weeks raises cholesterol in the blood 6 to 8 percent.

However, while the cholesterol increase associated with cafestol had been identified previously, mainly through the work of Katan and his colleagues, the mechanism by which it acted remained a mystery. It was a mystery that Moore and Ricketts decided to address in the laboratory.

For a long time, Ricketts said she was stymied because of paradoxical effects of cafestol in the liver. However, the discovery of a gene called fibroblast growth factor 15 or FGF 15 opened the door to understanding how cafestol affects farsenoid receptor X or FXR in the intestine. FXR was first identified as a bile acid receptor in studies in several laboratories, including Moore’s.

“It is part of the body’s own way of regulating levels of cholesterol,” said Ricketts.

Through research in the test tube and in mice, she and Moore found that in the intestine, cafestol activates FXR and induces FGF15, which reduces the effects of three liver genes that regulate cholesterol levels. While it is still unclear whether cafestol itself reaches the liver, the finding does confirm that the effect of the compound is in the intestine, which is directly involved in the transport of bile acids.

Moore’s interest in cafestol began several years ago when his wife read an article on coffee’s effect on cholesterol. She suggested that he might change his brewing method, which involved a permanent coffee filter. The paper filters, the article suggested, removed the coffee oils, which contain cafestol.

Moore researched the problem, and found papers by co-author Katan. He was already working on FXR, and began to think about whether cafestol might be affecting that signal in the cholesterol pathway.

Others who took part in the work include: Mark V. Boekschoten, Guido J.E.J. Hooiveld and Michael Müller of Wageningen University, Division of Human Nutrition, The Netherlands; Arja J. Kreeft, Corina J.A. Moen, Rune R. Frants of Center for Human and Clinical Genetics, LUMC, Leiden, The Netherlands; Soemini Kasanmoentalib of the Department of Medical Statistics, LUMC, Leiden, The Netherlands; Sabine M. Post and Hans MG Princen of TNO Pharma in Leiden, The Netherlands; J. Gordon Porter of Incyte Corporation, Palo Alto, CA.; and Marten H. Hofker of the Department of Pathology and Laboratory Medicine, University Medical Center in Groningen, The Netherlands.

Funding for this study came from the U.S. Department of Agriculture, National Institutes of Health, Wageningen Centre for Food Sciences, the Dutch Organization for Scientific Research and the Netherlands Heart Foundation.