Calorie restriction improves lipid-related emerging cardiometabolic risk factors in healthy adults without obesity: Distinct influences of BMI and sex from CALERIE™ a multicentre, phase 2, randomised controlled trial
Summary: Background: For many cardiovascular risk factors there is no lower limit to which further reduction will result in decreased disease risk; this includes values within ranges considered normal for healthy adults. This seems to be true for new emerging metabolic risk factors identified by in...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | EClinicalMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537021005423 |
| _version_ | 1819283869157818368 |
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| author | Kim M. Huffman Daniel C. Parker Manjushri Bhapkar Susan B. Racette Corby K. Martin Leanne M. Redman Sai Krupa Das Margery A. Connelly Carl F. Pieper Melissa Orenduff Leanna M. Ross Megan E. Ramaker James L. Dorling Clifford J Rosen Irina Shalaurova James D. Otvos Virginia B. Kraus William E. Kraus |
| author_facet | Kim M. Huffman Daniel C. Parker Manjushri Bhapkar Susan B. Racette Corby K. Martin Leanne M. Redman Sai Krupa Das Margery A. Connelly Carl F. Pieper Melissa Orenduff Leanna M. Ross Megan E. Ramaker James L. Dorling Clifford J Rosen Irina Shalaurova James D. Otvos Virginia B. Kraus William E. Kraus |
| author_sort | Kim M. Huffman |
| collection | DOAJ |
| description | Summary: Background: For many cardiovascular risk factors there is no lower limit to which further reduction will result in decreased disease risk; this includes values within ranges considered normal for healthy adults. This seems to be true for new emerging metabolic risk factors identified by innovative technological advances. Further, there seems to be ever evolving evidence of differential responses to lifestyle interventions by sex and body compositions in the normal range. In this secondary analysis, we had the opportunity to test these principles for newly identified molecular biomarkers of cardiometabolic risk in a young (21–50 years), normal weight healthy population undergoing calorie restriction for two years. Methods: The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) was a 24-month, multicenter, randomized controlled trial (May 2007-November 2012) in healthy, adults without obesity to evaluate the potential for calorie restriction (CR) to promote anti-aging adaptations, including those associated with disease risk. 218 participants (age 37.9 ± 7.2 years and body mass index (BMI) 25.1 ± 1.7 kg/m2, mean±SD) were randomized 2:1 to 24 months of CR (prescribed as 25% reduction from baseline calorie intake) versus ad libitum (AL). Fasting plasma from baseline, 12, and 24 months was used for assessments of lipoproteins, metabolites, and inflammatory markers using nuclear magnetic resonance spectroscopy. Findings: Averaging 11.9% CR, the CR group had reductions at 12 and 24 months in the cardiovascular disease risk markers, apolipoprotein B and GlycA, and risks for insulin resistance and type 2 diabetes—Lipoprotein Insulin Resistance Index and Diabetes Risk Index (all PCRvsAL≤0.0009). Insulin resistance and diabetes risk improvements resulted from CR-induced alterations in lipoproteins, specifically reductions in triglyceride-rich lipoprotein particles and low-density lipoprotein particles, a shift to larger high-density lipoprotein particles (more effective cholesterol transporters), and reductions in branched chain amino acids (BCAAs) (all PCRvsAL≤0.004). These CR responses were more pronounced in overweight than normal weight participants and greater in men than women. Interpretation: In normal to slightly overweight adults without overt risk factors or disease, 12 months of ∼12% CR improved newly identified risk markers for atherosclerotic cardiovascular disease, insulin resistance and type 2 diabetes. These markers suggest that CR improves risks by reducing inflammation and BCAAs and shifting lipoproteins from atherogenic to cholesterol transporting. Additionally, these improvements are greater for men and for those with greater BMIs indicating sex and BMI-influences merit attention in future investigations of lifestyle-mediated improvements in disease risk factors. Funding: The CALERIE™ trial design and implementation were supported by a National Institutes of Health (NIH) U-grant provided to four institutions, the three intervention sites and a coordinating center (U01 AG022132, U01 AG020478, U01 AG020487 U01 AG020480). For this secondary analysis including sample acquisition and processing, data analysis and interpretation, additional funding was provided by the NIH to authors as follows: R01 AG054840 (MO, VBK); R33 AG070455 (KMH, DCP, MB, SBR, CKM, LMR, SKD, CFP, CJR, WEK); P30 DK072476 (CKM, LMR); and U54 GM104940 (CKM, LMR). |
| first_indexed | 2024-12-24T01:38:20Z |
| format | Article |
| id | doaj.art-145c300f5a294d82b2f7e3d692b9fa96 |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-12-24T01:38:20Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj.art-145c300f5a294d82b2f7e3d692b9fa962022-12-21T17:22:07ZengElsevierEClinicalMedicine2589-53702022-01-0143101261Calorie restriction improves lipid-related emerging cardiometabolic risk factors in healthy adults without obesity: Distinct influences of BMI and sex from CALERIE™ a multicentre, phase 2, randomised controlled trialKim M. Huffman0Daniel C. Parker1Manjushri Bhapkar2Susan B. Racette3Corby K. Martin4Leanne M. Redman5Sai Krupa Das6Margery A. Connelly7Carl F. Pieper8Melissa Orenduff9Leanna M. Ross10Megan E. Ramaker11James L. Dorling12Clifford J Rosen13Irina Shalaurova14James D. Otvos15Virginia B. Kraus16William E. Kraus17Divisions of Rheumatology and Immunology, Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA; Corresponding author.Geriatrics, Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USADuke Clinical Research Institute, Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USAProgram in Physical Therapy and Department of Medicine, Washington University School of Medicine, St. Louis, MO, USAPennington Biomedical Research Center, Baton Rouge, LA, USAPennington Biomedical Research Center, Baton Rouge, LA, USAJean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USALaboratory Corporation of America Holdings (Labcorp), Morrisville, NC, USADepartment of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USADuke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USADuke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USADuke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USAHuman Nutrition, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UKMaine Medical Center Research Institute 81 Research Drive Scarborough, Maine 04074 USALaboratory Corporation of America Holdings (Labcorp), Morrisville, NC, USALaboratory Corporation of America Holdings (Labcorp), Morrisville, NC, USADivisions of Rheumatology and Immunology, Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USADuke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA; Division of Cardiology, Duke University School of Medicine, Durham, NC, USASummary: Background: For many cardiovascular risk factors there is no lower limit to which further reduction will result in decreased disease risk; this includes values within ranges considered normal for healthy adults. This seems to be true for new emerging metabolic risk factors identified by innovative technological advances. Further, there seems to be ever evolving evidence of differential responses to lifestyle interventions by sex and body compositions in the normal range. In this secondary analysis, we had the opportunity to test these principles for newly identified molecular biomarkers of cardiometabolic risk in a young (21–50 years), normal weight healthy population undergoing calorie restriction for two years. Methods: The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) was a 24-month, multicenter, randomized controlled trial (May 2007-November 2012) in healthy, adults without obesity to evaluate the potential for calorie restriction (CR) to promote anti-aging adaptations, including those associated with disease risk. 218 participants (age 37.9 ± 7.2 years and body mass index (BMI) 25.1 ± 1.7 kg/m2, mean±SD) were randomized 2:1 to 24 months of CR (prescribed as 25% reduction from baseline calorie intake) versus ad libitum (AL). Fasting plasma from baseline, 12, and 24 months was used for assessments of lipoproteins, metabolites, and inflammatory markers using nuclear magnetic resonance spectroscopy. Findings: Averaging 11.9% CR, the CR group had reductions at 12 and 24 months in the cardiovascular disease risk markers, apolipoprotein B and GlycA, and risks for insulin resistance and type 2 diabetes—Lipoprotein Insulin Resistance Index and Diabetes Risk Index (all PCRvsAL≤0.0009). Insulin resistance and diabetes risk improvements resulted from CR-induced alterations in lipoproteins, specifically reductions in triglyceride-rich lipoprotein particles and low-density lipoprotein particles, a shift to larger high-density lipoprotein particles (more effective cholesterol transporters), and reductions in branched chain amino acids (BCAAs) (all PCRvsAL≤0.004). These CR responses were more pronounced in overweight than normal weight participants and greater in men than women. Interpretation: In normal to slightly overweight adults without overt risk factors or disease, 12 months of ∼12% CR improved newly identified risk markers for atherosclerotic cardiovascular disease, insulin resistance and type 2 diabetes. These markers suggest that CR improves risks by reducing inflammation and BCAAs and shifting lipoproteins from atherogenic to cholesterol transporting. Additionally, these improvements are greater for men and for those with greater BMIs indicating sex and BMI-influences merit attention in future investigations of lifestyle-mediated improvements in disease risk factors. Funding: The CALERIE™ trial design and implementation were supported by a National Institutes of Health (NIH) U-grant provided to four institutions, the three intervention sites and a coordinating center (U01 AG022132, U01 AG020478, U01 AG020487 U01 AG020480). For this secondary analysis including sample acquisition and processing, data analysis and interpretation, additional funding was provided by the NIH to authors as follows: R01 AG054840 (MO, VBK); R33 AG070455 (KMH, DCP, MB, SBR, CKM, LMR, SKD, CFP, CJR, WEK); P30 DK072476 (CKM, LMR); and U54 GM104940 (CKM, LMR).http://www.sciencedirect.com/science/article/pii/S2589537021005423Nuclear magnetic resonance spectroscopyCardiovascular diseaseType 2 diabetes riskInsulin resistance |
| spellingShingle | Kim M. Huffman Daniel C. Parker Manjushri Bhapkar Susan B. Racette Corby K. Martin Leanne M. Redman Sai Krupa Das Margery A. Connelly Carl F. Pieper Melissa Orenduff Leanna M. Ross Megan E. Ramaker James L. Dorling Clifford J Rosen Irina Shalaurova James D. Otvos Virginia B. Kraus William E. Kraus Calorie restriction improves lipid-related emerging cardiometabolic risk factors in healthy adults without obesity: Distinct influences of BMI and sex from CALERIE™ a multicentre, phase 2, randomised controlled trial EClinicalMedicine Nuclear magnetic resonance spectroscopy Cardiovascular disease Type 2 diabetes risk Insulin resistance |
| title | Calorie restriction improves lipid-related emerging cardiometabolic risk factors in healthy adults without obesity: Distinct influences of BMI and sex from CALERIE™ a multicentre, phase 2, randomised controlled trial |
| title_full | Calorie restriction improves lipid-related emerging cardiometabolic risk factors in healthy adults without obesity: Distinct influences of BMI and sex from CALERIE™ a multicentre, phase 2, randomised controlled trial |
| title_fullStr | Calorie restriction improves lipid-related emerging cardiometabolic risk factors in healthy adults without obesity: Distinct influences of BMI and sex from CALERIE™ a multicentre, phase 2, randomised controlled trial |
| title_full_unstemmed | Calorie restriction improves lipid-related emerging cardiometabolic risk factors in healthy adults without obesity: Distinct influences of BMI and sex from CALERIE™ a multicentre, phase 2, randomised controlled trial |
| title_short | Calorie restriction improves lipid-related emerging cardiometabolic risk factors in healthy adults without obesity: Distinct influences of BMI and sex from CALERIE™ a multicentre, phase 2, randomised controlled trial |
| title_sort | calorie restriction improves lipid related emerging cardiometabolic risk factors in healthy adults without obesity distinct influences of bmi and sex from calerie™ a multicentre phase 2 randomised controlled trial |
| topic | Nuclear magnetic resonance spectroscopy Cardiovascular disease Type 2 diabetes risk Insulin resistance |
| url | http://www.sciencedirect.com/science/article/pii/S2589537021005423 |
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