Caloric Restriction as a Therapeutic Approach to Heart Failure
Can Less Be More in (Mice) and Men?
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Caloric 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