Since the seminal work of McCay et al. [1
], much interest has been shown in caloric restriction's ability to improve health and to extend lifespan. Caloric restriction (CR) is the reduction of caloric intake - typically by 20 - 40% of ad libitum
consumption - while maintaining adequate nutrient intake [2
]. In species as diverse as fruit flies [3
], guppies [4
], and dogs [5
], CR has been shown to increase longevity. Also, CR reduces the morbidity of a host of diseases, including (but not limited to), autoimmune diseases, atherosclerosis, cardiomyopathies, cancer, diabetes, renal diseases, neurodegenerative diseases, and respiratory diseases [6
]. Multiple metabolic pathways have been proposed to be involved in the health-promoting effects of CR, as described in detail previously [8
]. In addition to an actual reduction in kcal intake, selected nutrients (e.g., resveratrol) [12
] and drugs (e.g., rapamycin) [14
] proposed to mimic the longevity producing effects of CR, are actively being investigated as an alternative to restricting dietary energy.
An alternative to CR, alternate-day fasting (ADF) consists of two interchanging days; one day, subjects may consume food ad libitum
(sometimes equaling twice the normal intake); on the other day, food is reduced or withheld altogether [15
]. Interestingly, while CR regimens typically reduce body weight, ADF regimens often allow for the maintenance of normal body weight, because the subjects may gorge themselves during their feeding days [16
]. However, the life-extending benefits of ADF may rival those of CR, particularly in regard to reducing the respective risks of developing type 2 diabetes and cardiovascular disease [15
While CR reduces caloric intake, CR combined with exercise (CE) both reduces caloric intake (albeit to a lesser extent than CR-only protocols) and increases caloric expenditure. Within the last decade, considerable research has examined whether including exercise in a CR regimen augments the benefits elicited by CR or promotes additional benefits not observed in a CR-only regimen. The results of these studies have been mixed. Depending on the outcome measured, CE either augments a benefit elicited by CR alone [17
], fails to do so [21
], or elicits a benefit that was not elicited by CR alone [25
Dietary restriction (DR) - restriction of one or more components of intake (typically macronutrients) with minimal to no reduction in total caloric intake - is another alternative to CR. While research suggests that neither carbohydrate restriction nor lipid restriction extend life [26
], protein restriction increases maximum lifespan by roughly 20% [30
]. This extension of life may be solely due to the reduction of the amino acid methionine [33
Many religions incorporate fasting for both spiritual and physical benefits [34
]. During the holy month of Ramadan, which varies according to the lunar calendar, Muslims abstain from eating or drinking from sunrise (Sahur) to sunset (Iftar). Greek Orthodox Christians fast for a total of 180 - 200 days annually including the following main fasting periods: the Nativity Fast (40 days prior to Christmas), Lent (48 days prior to Easter), and the Assumption (15 days in August). The Biblical-based Daniel Fast typically incorporates a 21-day fasting period in which individuals refrain from consuming animal products, refined carbohydrates, food additives, preservatives, sweeteners, flavorings, caffeine, and alcohol. These above mentioned forms of fasting have been studied using a laboratory-based approach, with findings published in the scientific literature. Although limited objective data are available for other forms of religiously motivated fasts, including but not limited to practices observed in China, Tibet, and India, as well as those of Buddhist monks, it should be noted that fasting within these populations is commonplace. Hence, research investigating the health-specific effects of fasting within these samples is warranted.
The outline of this literature review is as follows: First, data related to CR in both animals and humans will be presented. Next, CE will be reviewed with regard to data obtained from both animal and human investigations. Data will then be presented in relation to ADF in both animals and humans. DR, in particular protein restriction and methionine restriction, will be considered as an alternative to CR. Finally, the three aforementioned forms of religious fasting will be presented. The paper concludes by providing a summary and suggestions for future research.