Effect of 2 years of calorie restriction on liver biomarkers: results from the CALERIE phase 2 randomized controlled trial

Authors: DORLING, JAMES - Pennington Biomedical Research Center; RAVUSSIN, ERIC - Pennington Biomedical Research Center; REDMAN, LEANNE - Pennington Biomedical Research Center; BHAPKAR, MANJUSHRI - Duke University School Of Medicine; HUFFMAN, KIM - Duke University School Of Medicine; RACETTE, SUSAN - Washington University School Of Medicine; DAS, SAI KRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; APOLZAN, JOHN - Pennington Biomedical Research Center; KRAUS, WILLIAM - Duke University School Of Medicine; HOCHSMANN, CHRISTOPH - Pennington Biomedical Research Center; MARTIN, CORBY - Pennington Biomedical Research Center

Submitted to: European Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/5/2020
Publication Date: 8/14/2020
Citation: Dorling, J.L., Ravussin, E., Redman, L.M., Bhapkar, M., Huffman, K.M., Racette, S.B., Das, S.W., Apolzan, J.W., Kraus, W.E., Hochsmann, C., Martin, C.K. 2020. Effect of 2 years of calorie restriction on liver biomarkers: results from the CALERIE phase 2 randomized controlled trial. European Journal of Nutrition. https://doi.org/10.1007/s00394-020-02361-7.
DOI: https://doi.org/10.1007/s00394-020-02361-7

Interpretive Summary: Calorie restriction (CR), defined as a reduction in caloric intake while maintaining nutrition, is an effective treatment for obesity-related liver and metabolic disease. However, further research is needed to determine whether calorie restriction can delay the onset of disease in individuals without obesity. Specific biomarkers, or measurable biological features that indicate the presence or progress of disease, can be used to determine liver health and are linked with cardiometabolic disease. We examined the effects of a two-year calorie restriction program-known as the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) study-on five liver biomarkers in healthy individuals without obesity. Of the 218 study participants, 143 were randomly assigned to a calorie restriction group (aimed to consume 25% less calories than required) and 75 were randomly assigned to a control group (allowed to consume calories without restraint). In metabolically healthy individuals without obesity, two years of moderate calorie restriction improved several liver biomarkers, with potentially greater improvements in men. Our findings suggest that sustained calorie restriction may improve long-term liver and metabolic disease risk in healthy adults without obesity.

Technical Abstract: Purpose: Calorie restriction (CR) is an effective treatment for obesity-related liver and metabolic disease. However, CR studies in individuals without obesity are needed to see if CR could delay disease onset. Liver biomarkers indicate hepatic health and are linked to cardiometabolic disease. Our aim was to examine the effects of a 2-year CR intervention on liver biomarkers in healthy individuals without obesity. Methods: The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) study was a 2-year randomized controlled trial. Overall, 218 participants (body mass index: 25.1 +/-1.7 kg/m2) were enrolled into a control group (n=75) that ate ad libitum (AL), or a CR group (n=143) that aimed to decrease energy intake by 25%. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bilirubin were measured during the trial. Results: At month 24, relative to the AL group, ALP (-7 +/-1 IU/L; P<0.01) and GGT (-0.11 +/-0.04 log IU/L; P=0.02) decreased and bilirubin increased (0.21 +/-0.06 log mg/dL; P<0.01) in the CR group; no between-group differences in ALT (-1 +/-1 IU/L; P>0.99) or AST (2 +/-2 IU/L; P=0.68) were revealed. However, sex-by-treatment-by-time interactions (P<0.01) were observed, with CR (vs. control) inducing reduced ALT and GGT and increased AST in men only (P