Conclusions and Recommendations
Based on the existing evidence from animal and human studies described, we conclude that there is great potential for lifestyles that incorporate periodic fasting during adult life to promote optimal health and reduce the risk of many chronic diseases, particularly for those who are overweight and sedentary. Animal studies have documented robust and replicable effects of fasting on health indicators including greater insulin sensitivity, and reduced levels of blood pressure, body fat, IGF-I, insulin, glucose, atherogenic lipids and inflammation. Fasting regimens can ameliorate disease processes and improve functional outcome in animal models of disorders that include myocardial infarction, diabetes, stroke, AD and PD. One general mechanism of action of fasting is that it triggers adaptive cellular stress responses, which result in an enhanced ability to cope with more severe stress and counteract disease processes. In addition, by protecting cells from DNA damage, suppressing cell growth and enhancing apoptosis of damaged cells, fasting could retard and/or prevent the formation and growth of cancers.
However, studies of fasting regimens have not been performed in children, the very old and underweight individuals, and it is possible that IF and PF would be harmful to these populations. Fasting periods lasting longer than 24 hours and particularly those lasting 3 or more days should be done under the supervision of a physician and preferably in a clinic. IF- and PF-based approaches towards combating the current epidemics of overweight, diabetes and related diseases should be pursued in human research studies and medical treatment plans. Several variations of potential ‘fasting prescriptions’ that have been adopted for overweight subjects revolve around the common theme of abstaining from food and caloric beverages for at least 12 – 24 hours on one or more days each week or month, depending on the length, combined with regular exercise. For those who are overweight, physicians could ask their patients to choose a fasting-based intervention that they believe they could comply with based upon their daily and weekly schedules. Examples include the ‘5:2’ IF diet (
Harvie et al., 2011), the alternate day modified fasting diet (
Johnson et al., 2007;
Varady et al., 2009), a 4–5 day fast or low calorie but high nourishment fasting mimicking diets once every 1–3 months followed by the skipping of one major meal every day if needed (V. Longo, clinical trial in progress). One of the concerns with unbalanced alternating diets such as those in which low calorie intake is only observed for 2 days a week are the potential effects on circadian rhythm and the endocrine and gastrointestinal systems, which are known to be influenced by eating habits. During the first 4 – 6 weeks of implementation of the fasting regimen, a physician or registered dietitian should be in regular contact with the patient to monitor their progress and to provide advice and supervision.
Fasting regimens could also be tailored for specific diseases as stand-alone or adjunct therapies. Results of initial trials of IF (fasting 2 days per week or every other day) in human subjects suggest that there is a critical transition period of 3 – 6 weeks during which time the brain and body adapt to the new eating pattern and mood is enhanced (
Harvie et al., 2011;
Johnson et al., 2007). Though speculative, it is likely that during the latter transition period brain neurochemistry changes so that the ‘addiction’ to regular consumption of food throughout the day is overcome. Notably, the various fasting approaches are likely to have limited efficacy particularly on aging and conditions other than obesity unless combined with diets such as the moderate calorie intake and mostly plant-based Mediterranean or Okinawa low protein diets (0.8 g protein/Kg of body weight), consistently associated with health and longevity.
In the future, it will be important to combine epidemiological data, studies of long-lived populations and their diets, results from model organisms connecting specific dietary components to pro-aging and pro-disease factors, with data from studies on fasting regimens in humans, to design large clinical studies that integrate fasting with diets recognized as protective and enjoyable. A better understanding of the molecular mechanisms by which fasting affects various cell types and organ systems should lead to the development of novel prophylactic and therapeutic interventions for a wide range of disorders.