2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial

Authors: KRAUS, WILLIAM - Duke University; BHAPKAR, MANJUSHRI - Duke University; HUFFMAN, KIM - Duke University; PIEPER, CARL - Duke University; DAS, SAI KRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; REDMAN, LEANNE - Pennington Biomedical Research Center; VILLAREAL, DENNIS - Baylor University; ROCHON, JAMES - Rho; ROBERTS, SUSAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; RAVUSSIN, ERIC - Pennington Biomedical Research Center; HOLLOSZY, JOHN - Washington University; FONTANA, LUIGI - Washington University

Submitted to: Lancet Diabetes Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/23/2019
Publication Date: 7/11/2019
Citation: Kraus, W.E., Bhapkar, M., Huffman, K.M., Pieper, C.F., Das, S., Redman, L.M., Villareal, D.T., Rochon, J., Roberts, S., Ravussin, E., Holloszy, J.O., Fontana, L. 2019. 2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial. Lancet Diabetes Endocrinology. https://doi.org/10.1016/S2213-8587(19)30151-2.
DOI: https://doi.org/10.1016/S2213-8587(19)30151-2

Interpretive Summary: Emerging research shows that although clinical values for blood glucose, cholesterol and other risk factors are considered within the normal range, there remains an association of increased risk of cardiovascular morbidity and mortality within that range. The effects of caloric restriction (CR) with adequate nutrition on risk factors for cardiometabolic disease in healthy, lean or slightly overweight, young and middle-aged individuals, in whom clinical values are likely within the normal range, has not been clearly established. This study evaluated the response to a two-year 25% CR diet in a multicenter randomized controlled trial in 218 young and middle-aged (21 to 51 y), healthy non-obese (body mass index 22 to 27.9 kg/m^2) men and women. Participants in the CR group achieved 12% CR on average and a sustained 10% weight loss, of which 71% was fat mass loss. CR caused a significant and persistent reduction of all measured cardiometabolic risk factors, including LDL-cholesterol, total cholesterol to HDL-cholesterol ratio, systolic and diastolic blood pressure. In addition, CR resulted in a significant improvement in C-reactive protein, glucose tolerance, insulin sensitivity index, and metabolic syndrome score relative to the control participants. The finding from this research showed that two years of moderate caloric restriction significantly reduced multiple cardiometabolic risk factors in young, non-obese men and women. These findings suggest the potential for significant cardiovascular benefit of practicing moderate CR in young and middle aged healthy individuals.

Technical Abstract: BACKGROUND. For several cardiometabolic risk factors, values considered within normal range are associated with increased risks of cardiovascular morbidity and mortality. However, very little is known about the short- and long-term effects of caloric restriction (CR) with adequate nutrition on these risk factors in healthy lean or slightly overweight young and middle-aged individuals. METHODS. Cardiometabolic risk factor responses to a prescribed 25% CR diet for 2-years were evaluated in a multi-center randomized controlled trial in 218 young and middle-aged (21 to 51 y), healthy non-obese (body mass index 22 to 27.9 kg/m2) men and women. RESULTS. Over two years, participants in the CR group achieved 11.9% CR and a sustained 10% weight loss, of which 71% was fat mass loss. CR caused a significant and persistent reduction of all measured conventional cardiometabolic risk factors, including LDL-cholesterol, total cholesterol to HDL-cholesterol ratio, systolic and diastolic blood pressure. In addition, CR resulted in a significant improvement in C- reactive protein, glucose tolerance, insulin sensitivity index, and metabolic syndrome score relative to control. A secondary analysis revealed the responses to be robust after controlling for relative weight loss changes. CONCLUSIONS. Two years of moderate caloric restriction significantly reduced multiple cardiometabolic risk factors in young, non-obese men and women. These findings suggest the potential for significant cardiovascular advantage of practicing moderate CR in young and middle aged healthy individuals, and they offer promise for significant long term population health benefits.