Significant improvement in cardiometabolic health in healthy nonobese individuals during caloric restriction-induced weight loss and weight loss maintenance.

Calorie restriction (CR) triggers benefits for healthspan including decreased risk of cardiometabolic disease (CVD). In an ancillary study to CALERIE 2, a 24-mo 25% CR study, we assessed the cardiometabolic effects of CR in 53 healthy, nonobese (BMI: 22-28 kg/m2) men ( n = 17) and women ( n = 36). The aim of this study was to investigate whether CR can reduce risk factors for CVD and insulin resistance in nonobese humans and, moreover, to assess whether improvements are exclusive to a period of weight loss or continue during weight maintenance. According to the energy balance method, the 25% CR intervention ( n = 34) produced 16.5 ± 1.5% (mean ± SE) and 14.8 ± 1.5% CR after 12 and 24 mo (M12, M24), resulting in significant weight loss (M12 -9 ± 0.5 kg, M24 -9 ± 0.5 kg, P < 0.001). Weight was maintained in the group that continued their habitual diet ad libitum (AL, n = 19). In comparison to AL, 24 mo of CR decreased visceral (-0.5 ± 0.01 kg, P < 0.0001) and subcutaneous abdominal adipose tissue (-1.9 ± 0.2kg, P < 0.001) as well as intramyocellular lipid content (-0.11 ± 0.05%, P = 0.031). Furthermore, CR decreased blood pressure (SBP -8 ± 3 mmHg, P = 0.005; DBP -6 ± 2 mmHg, P < 0.001), total cholesterol (-13.6 ± 5.3 mg/dl, P = 0.001), and LDL-cholesterol (-12.9 ± 4.4 mg/dl, P = 0.005), and the 10-yr risk of CVD-disease was reduced by 30%. Homeostasis model assessment of insulin resistance (HOMA-IR) decreased during weight loss in the CR group (-0.46 ± 0.15, P = 0.003), but this decrease was not maintained during weight maintenance (-0.11 ± 0.15, P = 0.458). In conclusion, sustained CR in healthy, nonobese individuals is beneficial in improving risk factors for cardiovascular and metabolic disease such as visceral adipose tissue mass, ectopic lipid accumulation, blood pressure, and lipid profile, whereas improvements in insulin sensitivity were only transient.

[1]  G. Shulman,et al.  Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases. , 2018, Cell metabolism.

[2]  Corby K. Martin,et al.  Effects of Two Years of Calorie Restriction on Aerobic Capacity and Muscle Strength , 2017, Medicine and science in sports and exercise.

[3]  L. Redman,et al.  Calorie restriction in humans: An update , 2017, Ageing Research Reviews.

[4]  Corby K. Martin,et al.  Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: a 2-y randomized controlled trial of calorie restriction in nonobese humans. , 2017, The American journal of clinical nutrition.

[5]  D. Allison,et al.  Caloric restriction improves health and survival of rhesus monkeys , 2017, Nature Communications.

[6]  Ashutosh Kumar Singh,et al.  Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015 , 2016, The Lancet.

[7]  D. Reeds,et al.  Effects of matched weight loss from calorie restriction, exercise, or both on cardiovascular disease risk factors: a randomized intervention trial. , 2016, The American journal of clinical nutrition.

[8]  M. Fernández-Alfonso,et al.  Caloric Restriction as a Strategy to Improve Vascular Dysfunction in Metabolic Disorders , 2016, Nutrients.

[9]  Andrew E Moran,et al.  Global and Regional Patterns in Cardiovascular Mortality From 1990 to 2013 , 2015, Circulation.

[10]  Corby K. Martin,et al.  A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity. , 2015, The journals of gerontology. Series A, Biological sciences and medical sciences.

[11]  R. Weindruch,et al.  Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys , 2014, Nature Communications.

[12]  F. Karpe,et al.  Structural and Functional Properties of Deep Abdominal Subcutaneous Adipose Tissue Explain Its Association With Insulin Resistance and Cardiovascular Risk in Men , 2014, Diabetes Care.

[13]  Udo Hoffmann,et al.  Body fat distribution, incident cardiovascular disease, cancer, and all-cause mortality. , 2013, Journal of the American College of Cardiology.

[14]  E. Cava,et al.  Will calorie restriction work in humans? , 2013, Aging.

[15]  David B. Allison,et al.  Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study , 2012, Nature.

[16]  P. Stein,et al.  Caloric restriction may reverse age‐related autonomic decline in humans , 2012, Aging cell.

[17]  W. Kraus,et al.  Approaches for quantifying energy intake and %calorie restriction during calorie restriction interventions in humans: the multicenter CALERIE study. , 2012, American journal of physiology. Endocrinology and metabolism.

[18]  Corby K. Martin,et al.  The CALERIE Study: design and methods of an innovative 25% caloric restriction intervention. , 2011, Contemporary clinical trials.

[19]  Corby K. Martin,et al.  Development of adherence metrics for caloric restriction interventions , 2011, Clinical trials.

[20]  Mary G. George,et al.  Forecasting the Future of Cardiovascular Disease in the United States: A Policy Statement From the American Heart Association , 2011, Circulation.

[21]  M. T. McIntosh,et al.  Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys , 2009, Science.

[22]  Corby K. Martin,et al.  Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals. , 2009, Atherosclerosis.

[23]  J. Rood,et al.  Effect of 6‐Month Calorie Restriction and Exercise on Serum and Liver Lipids and Markers of Liver Function , 2008, Obesity.

[24]  F. Toledo,et al.  Mitochondrial Capacity in Skeletal Muscle Is Not Stimulated by Weight Loss Despite Increases in Insulin Action and Decreases in Intramyocellular Lipid Content , 2008, Diabetes.

[25]  K. Yano,et al.  Caloric Restriction, the Traditional Okinawan Diet, and Healthy Aging , 2007, Annals of the New York Academy of Sciences.

[26]  S. Klein,et al.  Calorie restriction or exercise: effects on coronary heart disease risk factors. A randomized, controlled trial. , 2007, American journal of physiology. Endocrinology and metabolism.

[27]  J. DeLany,et al.  Long-term effects of 2 energy-restricted diets differing in glycemic load on dietary adherence, body composition, and metabolism in CALERIE: a 1-y randomized controlled trial. , 2007, The American journal of clinical nutrition.

[28]  Corby K. Martin,et al.  Effect of calorie restriction with or without exercise on body composition and fat distribution. , 2007, The Journal of clinical endocrinology and metabolism.

[29]  K. Schechtman,et al.  Lower extremity muscle size and strength and aerobic capacity decrease with caloric restriction but not with exercise-induced weight loss. , 2007, Journal of applied physiology.

[30]  K. Schechtman,et al.  One year of caloric restriction in humans: feasibility and effects on body composition and abdominal adipose tissue. , 2006, The journals of gerontology. Series A, Biological sciences and medical sciences.

[31]  E. Ravussin,et al.  Effect of calorie restriction with or without exercise on insulin sensitivity, beta-cell function, fat cell size, and ectopic lipid in overweight subjects. , 2006, Diabetes care.

[32]  Corby K. Martin,et al.  Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial. , 2006, JAMA.

[33]  S. Kovacs,et al.  Long-term caloric restriction ameliorates the decline in diastolic function in humans. , 2006, Journal of the American College of Cardiology.

[34]  S. Cummings,et al.  Biology of Aging , 2006, Reihe der Villa Vigoni.

[35]  E. Ravussin,et al.  Muscle‐associated Triglyceride Measured by Computed Tomography and Magnetic Resonance Spectroscopy , 2006, Obesity.

[36]  W. Cefalu,et al.  Caloric restriction and cardiovascular aging in cynomolgus monkeys (Macaca fascicularis): metabolic, physiologic, and atherosclerotic measures from a 4-year intervention trial. , 2004, The journals of gerontology. Series A, Biological sciences and medical sciences.

[37]  S. Klein,et al.  Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[38]  Elizabeth Johnson,et al.  Mortality and morbidity in laboratory-maintained Rhesus monkeys and effects of long-term dietary restriction. , 2003, The journals of gerontology. Series A, Biological sciences and medical sciences.

[39]  Taber MacCallum,et al.  Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period. , 2002, The journals of gerontology. Series A, Biological sciences and medical sciences.

[40]  L. Shaw,et al.  Comparison of the Asymptomatic Cardiac Ischemia Pilot and modified Asymptomatic Cardiac Ischemia Pilot versus Bruce and Cornell exercise protocols. , 1993, The American journal of cardiology.

[41]  R. Walford,et al.  The calorically restricted low-fat nutrient-dense diet in Biosphere 2 significantly lowers blood glucose, total leukocyte count, cholesterol, and blood pressure in humans. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[42]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

[43]  A. Strøm,et al.  Mortality from circulatory diseases in Norway 1940-1945. , 1951, Lancet.

[44]  M. Hindhede.  THE EFFECT OF FOOD RESTRICTION DURING WAR ON MORTALITY IN COPENHAGEN , 1920 .

[45]  Ashutosh Kumar Singh,et al.  Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015 , 2016, Lancet.

[46]  W. Kraus,et al.  Design and conduct of the CALERIE study: comprehensive assessment of the long-term effects of reducing intake of energy. , 2011, The journals of gerontology. Series A, Biological sciences and medical sciences.

[47]  Corby K. Martin,et al.  Caloric restriction with or without exercise: the fitness versus fatness debate. , 2010, Medicine and science in sports and exercise.

[48]  J. Holloszy.  The biology of aging. , 2000, Mayo Clinic proceedings.

[49]  R. Ross,et al.  Magnetic resonance imaging provides new insights into the characterization of adipose and lean tissue distribution. , 1996, Canadian journal of physiology and pharmacology.

[50]  K. Anderson,et al.  An updated coronary risk profile. A statement for health professionals. , 1991, Circulation.

[51]  J. Sallis,et al.  Physical activity assessment methodology in the Five-City Project. , 1985, American journal of epidemiology.