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.