Background: Weight loss from calorie restriction (CR) and/or endurance exercise training (EX) is cardioprotective. However CR and EX also have weight loss-independent benefits.

Objective: We tested the hypothesis that weight loss from calorie restriction and exercise combined (CREX) improves cardiovascular disease (CVD) risk factors more so than similar weight loss from CR or EX alone.

Design: Overweight, sedentary men and women (n = 52; aged 45-65 y) were randomly assigned to undergo 6-8% weight loss by using CR, EX, or CREX. Outcomes were measured before and after weight loss and included maximal oxygen consumption (VO2max), resting blood pressure, fasting plasma lipids, glucose, C-reactive protein, and arterial stiffness [carotid-femoral pulse wave velocity (PWV) and carotid augmentation index (AI)]. Values are means ± SEs.

Results: Reductions in body weight (∼7%) were similar in all groups. VO2max changed in proportion to the amount of exercise performed (CR, -1% ± 3%; EX, +22% ± 3%; and CREX, +11% ± 3%). None of the changes in CVD risk factors differed between groups. For all groups combined, decreases were observed for systolic and diastolic blood pressure (-5 ± 1 and -4 ± 1 mm Hg, respectively; both P < 0.0008), total cholesterol (-17 ± 4 mg/dL; P < 0.0001), non-HDL cholesterol (-16 ± 3 mg/dL; P < 0.0001), triglycerides (-18 ± 8 mg/dL; P = 0.03), and glucose (-3 ± 1 mg/dL; P = 0.0003). No changes were observed for HDL cholesterol (P = 0.30), C-reactive protein (P = 0.10), PWV (P = 0.30), or AI (P = 0.84). These changes would be expected to decrease the lifetime risk of CVD from 46% to 36%.

Conclusion: Matched weight losses from CR, EX, and CREX have substantial beneficial effects on CVD risk factors. However, the effects are not additive when weight loss is matched. This trial was registered at clinicaltrials.gov as NCT00777621.