William E Kraus1, Manjushri Bhapkar2, Kim M Huffman3, Carl F Pieper4, Sai Krupa Das5, Leanne M Redman6, Dennis T Villareal7, James Rochon8, Susan B Roberts5, Eric Ravussin6, John O Holloszy9, Luigi Fontana10. 1. Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA. Electronic address: william.kraus@duke.edu. 2. Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA. 3. Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA. 4. Duke Center for Aging and Human Development, Duke University School of Medicine, Durham, NC, USA. 5. Jean Mayer, US Department of Agriculture, Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA. 6. Pennington Biomedical Research Center, Baton Rouge, LA, USA. 7. Department of Medicine, Washington University School of Medicine, St Louis, MO, USA; Center for Translational Research on Inflammatory Diseases, Michael E DeBakey VA Medical Center, Houston, TX, USA; Baylor College of Medicine, Houston, TX, USA. 8. Rho Federal Systems, Chapel Hill, NC, USA. 9. Department of Medicine, Washington University School of Medicine, St Louis, MO, USA. 10. Department of Medicine, Washington University School of Medicine, St Louis, MO, USA; Department of Clinical and Experimental Sciences, Brescia University, Brescia, Italy; School of Medicine and Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
Abstract
BACKGROUND: For several cardiometabolic risk factors, values considered within normal range are associated with an increased risk of cardiovascular morbidity and mortality. We aimed to investigate the short-term and long-term effects of calorie restriction with adequate nutrition on these risk factors in healthy, lean, or slightly overweight young and middle-aged individuals. METHODS: CALERIE was a phase 2, multicentre, randomised controlled trial in young and middle-aged (21-50 years), healthy non-obese (BMI 22·0-27·9 kg/m2) men and women done in three clinical centres in the USA. Participants were randomly assigned (2:1) to a 25% calorie restriction diet or an ad libitum control diet. Exploratory cardiometabolic risk factor responses to a prescribed 25% calorie restriction diet for 2 years were evaluated (systolic, diastolic, and mean blood pressure; plasma lipids; high-sensitivity C-reactive protein; metabolic syndrome score; and glucose homoeostasis measures of fasting insulin, glucose, insulin resistance, and 2-h glucose, area-under-the curve for glucose, and insulin from an oral glucose tolerance test) analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00427193. FINDINGS: From May 8, 2007, to Feb 26, 2010, of 238 participants that were assessed, 218 were randomly assigned to and started a 25% calorie restriction diet (n=143, 66%) or an ad libitum control diet (n=75, 34%). Individuals in the calorie restriction group achieved a mean reduction in calorie intake of 11·9% (SE 0·7; from 2467 kcal to 2170 kcal) versus 0·8% (1·0) in the control group, and a sustained mean weight reduction of 7·5 kg (SE 0·4) versus an increase of 0·1 kg (0·5) in the control group, of which 71% (mean change in fat mass 5·3 kg [SE 0·3] divided by mean change in weight 7·5 kg [0·4]) was fat mass loss. Calorie restriction caused a persistent and significant reduction from baseline to 2 years of all measured conventional cardiometabolic risk factors, including change scores for LDL-cholesterol (p<0·0001), total cholesterol to HDL-cholesterol ratio (p<0·0001), and systolic (p<0·0011) and diastolic (p<0·0001) blood pressure. In addition, calorie restriction resulted in a significant improvement at 2 years in C-reactive protein (p=0·012), insulin sensitivity index (p<0·0001), and metabolic syndrome score (p<0·0001) relative to control. A sensitivity analysis revealed the responses to be robust after controlling for relative weight loss changes. INTERPRETATION: 2 years of moderate calorie restriction significantly reduced multiple cardiometabolic risk factors in young, non-obese adults. These findings suggest the potential for a substantial advantage for cardiovascular health of practicing moderate calorie restriction in young and middle-aged healthy individuals, and they offer promise for pronounced long-term population health benefits. FUNDING: National Institute on Aging and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.
BACKGROUND: For several cardiometabolic risk factors, values considered within normal range are associated with an increased risk of cardiovascular morbidity and mortality. We aimed to investigate the short-term and long-term effects of calorie restriction with adequate nutrition on these risk factors in healthy, lean, or slightly overweight young and middle-aged individuals. METHODS: CALERIE was a phase 2, multicentre, randomised controlled trial in young and middle-aged (21-50 years), healthy non-obese (BMI 22·0-27·9 kg/m2) men and women done in three clinical centres in the USA. Participants were randomly assigned (2:1) to a 25% calorie restriction diet or an ad libitum control diet. Exploratory cardiometabolic risk factor responses to a prescribed 25% calorie restriction diet for 2 years were evaluated (systolic, diastolic, and mean blood pressure; plasma lipids; high-sensitivity C-reactive protein; metabolic syndrome score; and glucose homoeostasis measures of fasting insulin, glucose, insulin resistance, and 2-h glucose, area-under-the curve for glucose, and insulin from an oral glucose tolerance test) analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00427193. FINDINGS: From May 8, 2007, to Feb 26, 2010, of 238 participants that were assessed, 218 were randomly assigned to and started a 25% calorie restriction diet (n=143, 66%) or an ad libitum control diet (n=75, 34%). Individuals in the calorie restriction group achieved a mean reduction in calorie intake of 11·9% (SE 0·7; from 2467 kcal to 2170 kcal) versus 0·8% (1·0) in the control group, and a sustained mean weight reduction of 7·5 kg (SE 0·4) versus an increase of 0·1 kg (0·5) in the control group, of which 71% (mean change in fat mass 5·3 kg [SE 0·3] divided by mean change in weight 7·5 kg [0·4]) was fat mass loss. Calorie restriction caused a persistent and significant reduction from baseline to 2 years of all measured conventional cardiometabolic risk factors, including change scores for LDL-cholesterol (p<0·0001), total cholesterol to HDL-cholesterol ratio (p<0·0001), and systolic (p<0·0011) and diastolic (p<0·0001) blood pressure. In addition, calorie restriction resulted in a significant improvement at 2 years in C-reactive protein (p=0·012), insulin sensitivity index (p<0·0001), and metabolic syndrome score (p<0·0001) relative to control. A sensitivity analysis revealed the responses to be robust after controlling for relative weight loss changes. INTERPRETATION: 2 years of moderate calorie restriction significantly reduced multiple cardiometabolic risk factors in young, non-obese adults. These findings suggest the potential for a substantial advantage for cardiovascular health of practicing moderate calorie restriction in young and middle-aged healthy individuals, and they offer promise for pronounced long-term population health benefits. FUNDING: National Institute on Aging and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.
Authors: Thomas A Pearson; George A Mensah; R Wayne Alexander; Jeffrey L Anderson; Richard O Cannon; Michael Criqui; Yazid Y Fadl; Stephen P Fortmann; Yuling Hong; Gary L Myers; Nader Rifai; Sidney C Smith; Kathryn Taubert; Russell P Tracy; Frank Vinicor Journal: Circulation Date: 2003-01-28 Impact factor: 29.690
Authors: James H O'Keefe; Loren Cordain; William H Harris; Richard M Moe; Robert Vogel Journal: J Am Coll Cardiol Date: 2004-06-02 Impact factor: 24.094
Authors: Steven E Nissen; E Murat Tuzcu; Paul Schoenhagen; Tim Crowe; William J Sasiela; John Tsai; John Orazem; Raymond D Magorien; Charles O'Shaughnessy; Peter Ganz Journal: N Engl J Med Date: 2005-01-06 Impact factor: 91.245
Authors: Alistair M Senior; Shinichi Nakagawa; David Raubenheimer; Stephen J Simpson Journal: Proc Natl Acad Sci U S A Date: 2020-11-16 Impact factor: 11.205
Authors: Christy S Carter; Arlan Richardson; Derek M Huffman; Steven Austad Journal: J Gerontol A Biol Sci Med Sci Date: 2020-02-14 Impact factor: 6.053
Authors: James L Dorling; Stephan van Vliet; Kim M Huffman; William E Kraus; Manjushri Bhapkar; Carl F Pieper; Tiffany Stewart; Sai Krupa Das; Susan B Racette; Susan B Roberts; Eric Ravussin; Leanne M Redman; Corby K Martin Journal: Nutr Rev Date: 2021-01-01 Impact factor: 7.110
Authors: Susan B Roberts; Rachel E Silver; Sai Krupa Das; Roger A Fielding; Cheryl H Gilhooly; Paul F Jacques; Jennifer M Kelly; Joel B Mason; Nicola M McKeown; Meaghan A Reardon; Sheldon Rowan; Edward Saltzman; Barbara Shukitt-Hale; Caren E Smith; Allen A Taylor; Dayong Wu; Fang Fang Zhang; Karen Panetta; Sarah Booth Journal: Adv Nutr Date: 2021-07-30 Impact factor: 8.701
Authors: James L Dorling; Eric Ravussin; Leanne M Redman; Manju Bhapkar; Kim M Huffman; Susan B Racette; Sai K Das; John W Apolzan; William E Kraus; Christoph Höchsmann; Corby K Martin Journal: Eur J Nutr Date: 2020-08-14 Impact factor: 5.614