Effects of alternate day fasting and exercise on cholesterol metabolism in overweight or obese adults: A pilot randomized controlled trial

Background and Purpose: The objective of this pilot randomized controlled trial was to investigate the effect of alternate day fasting (ADF) and exercise on serum sterol signatures, which are surrogate markers of cholesterol absorption and biosynthesis. Methods: We randomly assigned 112 overweight or obese participants to four groups: 1) ADF and exercise (E-ADF); 2) ADF; 3) exercise; and 4) control. We studied 31 completers in this exploratory analysis and measured their serum sterol signatures using gas chromatography–mass spectrometry. Results: After intervention, most serum sterol signatures that correspond to cholesterol metabolism were significantly different between groups (p < 0.05 by analysis of covariance [ANCOVA]). We found no differences in plant sterols, which are markers of cholesterol absorption. In the exercise group, desmosterol, cholesteryl esters, and oxysterols decreased significantly. Furthermore, only changes in physical activity levels negatively correlated with changes in the metabolic ratios of desmosterol and 7-dehydrocholesterol to cholesterol, which reflect cholesterol biosynthesis (r = −0.411; p = 0.030, and r = −0.540; p = 0.003, respectively). Conclusion: These findings suggest that exercise with or without ADF improves cholesterol metabolism as measured by serum sterol signatures, and increased physical activity has a greater effect on cholesterol biosynthesis than weight reduction or calorie restriction.