The currently most recognized strategy to fight overweight/obesity is to reduce daily calorie intake, based on individual energy needs [1]. However, the most important limitation of this approach is that it produces modest weight loss (5-10% sustained for ≥1 year) and that adherence to the diet generally decreases within 4-6 months, with the result that most people who lose weight regain significant weight within 1 year if the diet is not accompanied by a substantial lifestyle change including the implementation of physical activity [2,3].
Due to the relative ineffectiveness of traditional approaches to achieving and sustaining weight loss, there has been growing interest in recent years in identifying alternative dietary strategies for achieving weight loss in overweight/obese people. One of the most widely used approaches in the scientific literature is fasting, or rather intermittent calorie restriction [4]. This generic term refers to various regimes that implement an energy restriction for alternate days of the week, or a limitation of energy intake for only a few hours of the day, alternating with days or hours when the caloric intake is free or ad libitum. The premise of these approaches is that studies on rodents and preclinical models have shown that energy reduction at a daily and/or weekly level is able to activate biochemical cascades that lead through intermediate steps to the stimulation of the sirtuin class, implicated in various metabolic adaptations that favour a greater loss of fat mass, a preservation of lean mass and a greater capacity to support weight loss, as well as an optimal state of health and healthy longevity [5].
However, clinical studies comparing weight loss with intermittent or continuous calorie restriction regimens in adults with overweight and obesity are limited and do not agree with the results reported by experimental studies on preclinical models. Overall, the available evidence from clinical trials suggests that the different calorie restriction regimens result in equivalent weight loss compared to classical calorie restriction that is performed with the standard approach of implementing low-calorie diets [6]. A meta-analysis conducted by Harris et al. reported studies comparing the two different regimens, finding no significant differences in body weight, body fat mass composition [7]. In addition, studies in the literature comparing the two different regimens convincingly demonstrate that the intermittent fasting approach in its different regimens does not lead to beneficial effects on the metabolic and cardiovascular risk profile, leading on the other hand to nutritional defects in terms of micro and macronutrients [7]. A very recent umbrella review carried out by our society through the “Young Members”, and recently published in the journal Advances in Nutrition, including all the meta-analyses published to date on the use of various types of diets on anthropometric and metabolic risk parameters, allowed to find the presence of only 10 randomized clinical trials including 660 participants who performed the intermittent caloric restriction diet for about 8 weeks [8].
The results of all meta-analyses in the literature report no significantly different effects than the nutritional strategy of comparison, with only a meta-analysis of intervention studies reporting an increase in body weight in those who were following an intermittent caloric restriction diet. The studies in the literature on the subject suffer from several methodological problems. One of the most important problems is the lack of standardization of the terminology used to describe different energy restriction regimens, with the result that the few clinical studies in the literature do not compare the same nutritional regimens. Another problem is the duration of the studies, which in most cases does not exceed 8 weeks, leaving many doubts about the use of these regimens in a medium to long term approach. A last, but not least, problem is the non-individualization of the dietary strategy on the person, based on energy needs or basic energy requirements.
In addition to the strategy of intermittent fasting in its various forms and applications, in recent years, also thanks to the publication of several books by its main author Dr. Valter Longo, has been brought to the knowledge of the population and then later on to the scientific world an alternative approach called fasting-mimicking diet that is based on some pre-clinical and experimental scientific studies that have hypothesized a possible beneficial effect of alternating fasting on life expectancy and optimal health status. The hypotheses underlying these possible beneficial mechanisms are those mentioned above of intermittent caloric restriction. The only clinical intervention study in the literature on the possible beneficial effect of this nutritional profile designed and proposed by Dr. Longo was published in the journal Science Translational Medicine in 2017 [9]. In this clinical intervention study, the efficacy of 3 months of fasting-mimicking cycles was tested on about 100 overweight/obese subjects in order to evaluate the effect on cardiovascular risk parameters. The result of this study was not entirely positive, finding few and no significant effects on weight, percentage of fat mass and other metabolic risk parameters such as cholesterol, blood glucose and LDL cholesterol levels, highlighting on the other hand a significant percentage of side effects in subjects who followed the planned diet. The study also highlighted several methodological problems that undermine its validity, including the significant number of people who left the intervention study, as well as the lack of clarity of the experimental protocol and the nutritional inadequacy of the prescribed plan. In addition, of course, to the inability to define the diet to be followed for normal feeding days, which should be interspersed with calorie restriction days.
In conclusion, therefore, the results of the clinical intervention studies do not allow us to establish a possible effectiveness of these nutritional approaches, whether they are related to intermittent caloric restriction in terms of days or hours of the day, or related to the fasting-mimicking diet with respect to anthropometric parameters and metabolic risk parameters, but allow us to point out the danger of encountering side effects and nutritional inadequacy due to lack of macro- and micronutrients in the diet following these dietary restriction models.
References
Julia C, Péneau S, Andreeva VA, Méjean C, Fezeu L, Galan P, Hercberg S. Weight-loss strategies used by the general population: how are they perceived? PLoS One 2014; 9: e97834.
Delbridge EA, Prendergast LA, Pritchard JE, Proietto J. One-year weight maintenance after significant weight loss in healthy overweight and obese subjects: does diet composition matter? Am J Clin Nutr 2009; 90: 1203-14. Dansinger ML, Tatsioni A, Wong JB, Chung M, Balk EM. Meta-analysis: the effect of dietary counseling for weight loss. Ann Intern Med 2007; 147: 41-50.
Madeo F, Carmona-Gutierrez D, Hofer SJ, Kroemer G. Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential. Cell Metab 2019; 29: 592-610.
Fontana L, Partridge L. Promoting health and longevity through diet: from model organisms to humans. Cell. 2015; 161: 106-118.
Rynders CA, Thomas EA, Zaman A, Pan Z, Catenacci VA, Melanson EL. Effectiveness of Intermittent Fasting and Time-Restricted Feeding Compared to Continuous Energy Restriction for Weight Loss. Nutrients 2019; 11. pii: E2442.
Harris L, Hamilton S, Azevedo LB, Olajide J, De Brún C, Waller G, Whittaker V, Sharp T, Lean M, Hankey C, Ells L. Intermittent fasting interventions for treatment of overweight and obesity in adults: a systematic review and meta-analysis. JBI Database System Rev Implement Rep 2018; 16: 507-547.
Dinu M, Pagliai G, Angelino D, Rosi A, Dall’Asta M, Bresciani L, Ferraris C, Guglielmetti M, Godos J, Del Bò C, Nucci D, Meroni E, Landini L, Martini D, Sofi F. Effects of popular diets on anthropometric and cardiometabolic parameters: an umbrella review of meta-analyses of randomized controlled trials. Adv Nutr 2020 (in press).
Wei M, Brandhorst S, Shelehchi M, Mirzaei H, Cheng CW, Budniak J, Groshen S, Mack WJ, Guen E, Di Biase S, Cohen P, Morgan TE, Dorff T, Hong K, Michalsen A, Laviano A, Longo VD. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med 2017; 9. pii: eaai8700.
However, clinical studies comparing weight loss with intermittent or continuous calorie restriction regimens in adults with overweight and obesity are limited and do not agree with the results reported by experimental studies on preclinical models. Overall, the available evidence from clinical trials suggests that the different calorie restriction regimens result in equivalent weight loss compared to classical calorie restriction that is performed with the standard approach of implementing low-calorie diets [6]. A meta-analysis conducted by Harris et al. reported studies comparing the two different regimens, finding no significant differences in body weight, body fat mass composition [7]. In addition, studies in the literature comparing the two different regimens convincingly demonstrate that the intermittent fasting approach in its different regimens does not lead to beneficial effects on the metabolic and cardiovascular risk profile, leading on the other hand to nutritional defects in terms of micro and macronutrients [7]. A very recent umbrella review carried out by our society through the “Young Members”, and recently published in the journal Advances in Nutrition, including all the meta-analyses published to date on the use of various types of diets on anthropometric and metabolic risk parameters, allowed to find the presence of only 10 randomized clinical trials including 660 participants who performed the intermittent caloric restriction diet for about 8 weeks [8].
The results of all meta-analyses in the literature report no significantly different effects than the nutritional strategy of comparison, with only a meta-analysis of intervention studies reporting an increase in body weight in those who were following an intermittent caloric restriction diet. The studies in the literature on the subject suffer from several methodological problems. One of the most important problems is the lack of standardization of the terminology used to describe different energy restriction regimens, with the result that the few clinical studies in the literature do not compare the same nutritional regimens. Another problem is the duration of the studies, which in most cases does not exceed 8 weeks, leaving many doubts about the use of these regimens in a medium to long term approach. A last, but not least, problem is the non-individualization of the dietary strategy on the person, based on energy needs or basic energy requirements.
In addition to the strategy of intermittent fasting in its various forms and applications, in recent years, also thanks to the publication of several books by its main author Dr. Valter Longo, has been brought to the knowledge of the population and then later on to the scientific world an alternative approach called fasting-mimicking diet that is based on some pre-clinical and experimental scientific studies that have hypothesized a possible beneficial effect of alternating fasting on life expectancy and optimal health status. The hypotheses underlying these possible beneficial mechanisms are those mentioned above of intermittent caloric restriction. The only clinical intervention study in the literature on the possible beneficial effect of this nutritional profile designed and proposed by Dr. Longo was published in the journal Science Translational Medicine in 2017 [9]. In this clinical intervention study, the efficacy of 3 months of fasting-mimicking cycles was tested on about 100 overweight/obese subjects in order to evaluate the effect on cardiovascular risk parameters. The result of this study was not entirely positive, finding few and no significant effects on weight, percentage of fat mass and other metabolic risk parameters such as cholesterol, blood glucose and LDL cholesterol levels, highlighting on the other hand a significant percentage of side effects in subjects who followed the planned diet. The study also highlighted several methodological problems that undermine its validity, including the significant number of people who left the intervention study, as well as the lack of clarity of the experimental protocol and the nutritional inadequacy of the prescribed plan. In addition, of course, to the inability to define the diet to be followed for normal feeding days, which should be interspersed with calorie restriction days.
In conclusion, therefore, the results of the clinical intervention studies do not allow us to establish a possible effectiveness of these nutritional approaches, whether they are related to intermittent caloric restriction in terms of days or hours of the day, or related to the fasting-mimicking diet with respect to anthropometric parameters and metabolic risk parameters, but allow us to point out the danger of encountering side effects and nutritional inadequacy due to lack of macro- and micronutrients in the diet following these dietary restriction models.
References
Julia C, Péneau S, Andreeva VA, Méjean C, Fezeu L, Galan P, Hercberg S. Weight-loss strategies used by the general population: how are they perceived? PLoS One 2014; 9: e97834.
Delbridge EA, Prendergast LA, Pritchard JE, Proietto J. One-year weight maintenance after significant weight loss in healthy overweight and obese subjects: does diet composition matter? Am J Clin Nutr 2009; 90: 1203-14. Dansinger ML, Tatsioni A, Wong JB, Chung M, Balk EM. Meta-analysis: the effect of dietary counseling for weight loss. Ann Intern Med 2007; 147: 41-50.
Madeo F, Carmona-Gutierrez D, Hofer SJ, Kroemer G. Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential. Cell Metab 2019; 29: 592-610.
Fontana L, Partridge L. Promoting health and longevity through diet: from model organisms to humans. Cell. 2015; 161: 106-118.
Rynders CA, Thomas EA, Zaman A, Pan Z, Catenacci VA, Melanson EL. Effectiveness of Intermittent Fasting and Time-Restricted Feeding Compared to Continuous Energy Restriction for Weight Loss. Nutrients 2019; 11. pii: E2442.
Harris L, Hamilton S, Azevedo LB, Olajide J, De Brún C, Waller G, Whittaker V, Sharp T, Lean M, Hankey C, Ells L. Intermittent fasting interventions for treatment of overweight and obesity in adults: a systematic review and meta-analysis. JBI Database System Rev Implement Rep 2018; 16: 507-547.
Dinu M, Pagliai G, Angelino D, Rosi A, Dall’Asta M, Bresciani L, Ferraris C, Guglielmetti M, Godos J, Del Bò C, Nucci D, Meroni E, Landini L, Martini D, Sofi F. Effects of popular diets on anthropometric and cardiometabolic parameters: an umbrella review of meta-analyses of randomized controlled trials. Adv Nutr 2020 (in press).
Wei M, Brandhorst S, Shelehchi M, Mirzaei H, Cheng CW, Budniak J, Groshen S, Mack WJ, Guen E, Di Biase S, Cohen P, Morgan TE, Dorff T, Hong K, Michalsen A, Laviano A, Longo VD. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med 2017; 9. pii: eaai8700.