Effect of fasting on plasma levels of 7-alpha-hydroxy-4-cholesten-3-one – a marker for bile acid synthesis in humans

Magnus Axelson1,*, Kerstin Brismar2

1Clinical Chemistry, Karolinska University Laboratory / Hospital, Stockholm, 2Endocrinology and Diabetology, Karolinska University Hospital, Stockholm , Sweden

Introduction: We have previously shown that plasma levels of 7-alpha-hydroxy-4-cholesten-3-one (C4) reflect rates of bile acid synthesis in humans. Clinically, analysis of C4 has mainly been used to diagnose patients with chronic diarrhoea caused by bile acid malabsorption.

Objectives: To characterize different factors and conditions that can affect plasma levels of C4 (bile acid production) in patients in addition to bile acid malabsorption. In this case the effect of fasting was studied.

Methods: Diurnal rates of bile acid production under normal and fasting conditions in seven healthy human subjects have been studied. Blood samples were collected with 2-hour intervals during 24-hour periods prior to, during and after a 3-day fast and C4 was analyzed.

Results: Under normal conditions the plasma levels of C4 were relatively constant or mildly fluctuating throughout the day, and the median level of C4 was about 14 ng/mL.

Fasting for 2-3 days resulted in a marked decrease of C4 in plasma (by more than 75%), consistent with a significant reduction of bile acid production. Two days after the fast had ended, the plasma levels of C4 remained low, whereas those of bile acids were elevated. At this time cholesterol production, hormone levels and the metabolism were apparently normalized.

Conclusion: The results show that fasting reduces bile acid production and suggest that there is a delayed normalization of this after a period of fasting. This may be considered when C4 analysis is used for diagnosing bile acid malabsorption in patients.

Keywords: Biomarker, Liver