Caloric Restriction as a Therapeutic Approach to Heart Failure

aloric restriction (CR) is a dietary intervention that involves reduction of total calories below ad libitum intake without nutritional insufficiency or malnutrition.A form of CR, intermittent fasting (IF), involves significant energy restriction on alternate days or 2 days a week (5:2 diet) with ad libitum consumption on nonfasting days. 1 In the mid-1930s, McCay and colleagues first described the potential benefits of CR when they demonstrated prolongation of the mean and maximal lifespan of rats. 2 Since then, CR has been the subject of considerable investigation across a spectrum of species including yeast, worms, flies, fish, rodents, and nonhuman primates to better understand possible biological and molecular benefits on aging and longevity.Perhaps the most well-known studies of CR were initiated in the late 1980s involving rhesus monkeys at the National Institute on Aging and the University of Wisconsin Madison. 3 Rhesus monkeys are a useful model as their anatomy, physiology, eating patterns, and aging processes are similar to humans.The University of Wisconsin Madison study reported a positive impact on survival, but the National Institute on Aging study did not find a similar benefit.Significant differences in the 2 study designs likely contributed to the observed mortality differences.3 Other nonhuman studies over the past decade support the potential for CR to delay the onset of age-related chronic diseases, protect against cancer and neurodegenerative diseases, and exert direct cardioprotective effects.4 CR may have a favorable impact on the cardiovascular system, mediated by improvement in cardiovascular risk factors such as obesity, hypertension, and diabetes mellitus.As well, CR may reduce inflammation, myocardial fibrosis, oxidative stress, and development of atherosclerosis, and improve myocardial ischemic tolerance.4 The effects of CR have also been studied in humans with promising results.In the CALERIE 2 (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy Phase 2) study of healthy, nonobese adults, 2 years of CR was associated with greater weight loss, in addition to improved quality of life, global health, and mood compared with those randomized to ad libitum diet.5 In another randomized controlled trial of obese older adults with heart failure (HF) with preserved ejection fraction, CR in addition to exercise increased peak oxygen consumption.6 In this issue of Circulation: Heart Failure, de Lucia et al 7 examined the impact of a 12-month CR regimen on cardiac function, sympathetic innervation, and β-AR (β-adrenergic receptor) responsiveness in a postmyocardial infarction rat model of left ventricular systolic dysfunction.Two-month-old male Sprague-Dawley rats (n=44) were randomized to surgically-induced myocardial infarction by ligation of the proximal left anterior descending artery (n=34) or sham procedure (n=10).The diagnosis of HF was established by echocardiography 4 weeks postprocedure, and the rats were then randomized to CR using an IF protocol alternating a complete Caloric Restriction(definition) as a Therapeutic Approach to Heart FailureCan Less Be More in (Mice) and Men?