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Intermittent fasting: promising premises or broken promises?

Over the last decade, intermittent fasting (better defined as “intermittent energy restriction”) has been considered of major interest as an alternative strategy to continuous caloric restriction for weight loss (Rynders et al. 2019). In fact, while dietary energy reduction (relatively to one’s energy requirements) may lead to a relative small effect on body weight (about 5–10% weight reduction over a year) with substantial weight regain once the caloric restriction is interrupted, an intermittent fasting approach has been supposed to improve the patient compliance by limiting the caloric restriction to certain days and allowing ad libitum feeding over the remaining weekly days (Rynders et al. 2019). The rationale for the enthusiasm regarding this potential strategy lies in the results of preclinical studies, in which it has been observed that fasting would induce sirtuin pathway and stimulate a metabolic adaptation towards weight loss (Madeo et al. 2019). However, the findings from clinical studies are not as striking as those from animal studies: recent meta-analyses of randomised controlled trials conducted on overweight/obese individuals showed that intermittent fasting would lead to similar results than continuous energy restriction, especially in the short term, with insufficient evidence to support its long-term effects (Harris, Hamilton, et al. 2018; Harris, McGarty, et al. 2018). In this issue of International Journal of Food Sciences and Nutrition, a systematic review from Sandoval et al provided an overview of studies conducted on trained or overweight individuals younger than 60 years old showing potential effects on body composition (i.e. decreasing fat mass and maintaining muscle mass) irrespective of body weight, as well as potential effects on biomarkers of metabolic health (including GLP-1, insulin, and glucose levels) (Sandoval et al. 2021). These findings are still limited by the design of the studies included (some observational) and the not univocal definitions for the intervention. Moreover, the long-term effects of such strategy are still to be elucidated, failing to result superior in patients’ compliance compared to other weightloss approaches. More acceptable forms of intermittent fasting have been proposed as alternatives, including the fasting-mimicking diet (characterised by a low caloric intake with a small contribution of carbohydrates and proteins and a high fat intake) (Sofi 2020) and the time restricted feeding (characterised by feeding time restricted to 8–10 h per day, with no real recommendation on energy intake) (Currenti et al. 2020). While both such approaches have been extensively discussed in review articles underlying strengths and limitations of current evidence (Hoddy et al. 2020; Fanti et al. 2021), our journal also published interesting original articles showing the potential for a time-restricted feeding approach in the context of Mediterranean populations, which could benefit from both diet quality and restricted eating window of time. Specifically, time-restricted eating was associated with better anthropometric profiles (Karras, Koufakis, Adamidou, Antonopoulou, et al. 2021; Karras, Koufakis, Adamidou, Polyzos, et al. 2021) and improved plasma levels of adiponectin (Karras, Koufakis, Adamidou, Dimakopoulos, et al. 2021) and vitamin D (Rodopaios et al. 2021) in Greek Ortodox older individuals. Similar observations have been reported by our research group on older Southern Italian adults, concerning better metabolic (Currenti, Buscemi, et al. 2021) and mental health status (Currenti, Godos, et al. 2021a; Currenti, Godos, et al. 2021b) in individuals eating within a restricted window of time (<10 h). Although not yet supported by clinical trials, we may hypothesise that the reasons for such significant findings might rely on the observation for such behaviour (reduced eating window of time) embedded within the context of the overall lifestyle, characterised by chronicity and longterm adoption, in good balance with moderate physical activity and adequate not excessive calorie intake. There is no further scientific evidence on this matter, and additional studies are needed to clarify such hypotheses. However, it is crucial to understand whether the effects obtained by intermittent fasting (as time restricted feeding or other approaches) are related to the caloric restriction, to physiological changes in body hormonal and gut microbial homeostasis, or whether, on the contrary, the desired effects cannot be reached until the intervention becomes a lifestyle.