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      Intermittent versus continuous energy restriction on weight loss and cardiometabolic outcomes: a systematic review and meta-analysis of randomized controlled trials

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          Abstract

          Background

          This systematic review and meta-analysis summarized the most recent evidence on the efficacy of intermittent energy restriction (IER) versus continuous energy restriction on weight-loss, body composition, blood pressure and other cardiometabolic risk factors.

          Methods

          Randomized controlled trials were systematically searched from MEDLINE, Cochrane Library, TRIP databases, EMBASE and CINAHL until May 2018. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence intervals (CI).

          Results

          Eleven trials were included (duration range 8–24 weeks). All selected intermittent regimens provided ≤ 25% of daily energy needs on “fast” days but differed for type of regimen (5:2 or other regimens) and/or dietary instructions given on the “feed” days (ad libitum energy versus balanced energy consumption). The intermittent approach determined a comparable weight-loss (WMD: − 0.61 kg; 95% CI − 1.70 to 0.47; p = 0.87) or percent weight loss (WMD: − 0.38%, − 1.16 to 0.40; p = 0.34) when compared to the continuous approach. A slight reduction in fasting insulin concentrations was evident with IER regimens (WMD = − 0.89 µU/mL; − 1.56 to − 0.22; p = 0.009), but the clinical relevance of this result is uncertain. No between-arms differences in the other variables were found.

          Conclusions

          Both intermittent and continuous energy restriction achieved a comparable effect in promoting weight-loss and metabolic improvements. Long-term trials are needed to draw definitive conclusions.

          Electronic supplementary material

          The online version of this article (10.1186/s12967-018-1748-4) contains supplementary material, which is available to authorized users.

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          Most cited references29

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          The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women.

          The problems of adherence to energy restriction in humans are well known. To compare the feasibility and effectiveness of intermittent continuous energy (IER) with continuous energy restriction (CER) for weight loss, insulin sensitivity and other metabolic disease risk markers. Randomized comparison of a 25% energy restriction as IER (∼ 2710 kJ/day for 2 days/week) or CER (∼ 6276 kJ/day for 7 days/week) in 107 overweight or obese (mean (± s.d.) body mass index 30.6 (± 5.1) kg m(-2)) premenopausal women observed over a period of 6 months. Weight, anthropometry, biomarkers for breast cancer, diabetes, cardiovascular disease and dementia risk; insulin resistance (HOMA), oxidative stress markers, leptin, adiponectin, insulin-like growth factor (IGF)-1 and IGF binding proteins 1 and 2, androgens, prolactin, inflammatory markers (high sensitivity C-reactive protein and sialic acid), lipids, blood pressure and brain-derived neurotrophic factor were assessed at baseline and after 1, 3 and 6 months. Last observation carried forward analysis showed that IER and CER are equally effective for weight loss: mean (95% confidence interval ) weight change for IER was -6.4 (-7.9 to -4.8) kg vs -5.6 (-6.9 to -4.4) kg for CER (P-value for difference between groups = 0.4). Both groups experienced comparable reductions in leptin, free androgen index, high-sensitivity C-reactive protein, total and LDL cholesterol, triglycerides, blood pressure and increases in sex hormone binding globulin, IGF binding proteins 1 and 2. Reductions in fasting insulin and insulin resistance were modest in both groups, but greater with IER than with CER; difference between groups for fasting insulin was -1.2 (-1.4 to -1.0) μU ml(-1) and for insulin resistance was -1.2 (-1.5 to -1.0) μU mmol(-1) l(-1) (both P = 0.04). IER is as effective as CER with regard to weight loss, insulin sensitivity and other health biomarkers, and may be offered as an alternative equivalent to CER for weight loss and reducing disease risk.
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            A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity.

            To evaluate the safety and tolerability of alternate-day fasting (ADF) and to compare changes in weight, body composition, lipids, and insulin sensitivity index (Si) with those produced by a standard weight loss diet, moderate daily caloric restriction (CR).
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              Alternate-day fasting and chronic disease prevention: a review of human and animal trials.

              Calorie restriction (CR) and alternate-day fasting (ADF) represent 2 different forms of dietary restriction. Although the effects of CR on chronic disease prevention were reviewed previously, the effects of ADF on chronic disease risk have yet to be summarized. Accordingly, we review here animal and human evidence concerning ADF and the risk of certain chronic diseases, such as type 2 diabetes, cardiovascular disease, and cancer. We also compare the magnitude of risk reduction resulting from ADF with that resulting from CR. In terms of diabetes risk, animal studies of ADF find lower diabetes incidence and lower fasting glucose and insulin concentrations, effects that are comparable to those of CR. Human trials to date have reported greater insulin-mediated glucose uptake but no effect on fasting glucose or insulin concentrations. In terms of cardiovascular disease risk, animal ADF data show lower total cholesterol and triacylglycerol concentrations, a lower heart rate, improved cardiac response to myocardial infarction, and lower blood pressure. The limited human evidence suggests higher HDL-cholesterol concentrations and lower triacylglycerol concentrations but no effect on blood pressure. In terms of cancer risk, there is no human evidence to date, yet animal studies found decreases in lymphoma incidence, longer survival after tumor inoculation, and lower rates of proliferation of several cell types. The findings in animals suggest that ADF may effectively modulate several risk factors, thereby preventing chronic disease, and that ADF may modulate disease risk to an extent similar to that of CR. More research is required to establish definitively the consequences of ADF.
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                Author and article information

                Contributors
                iolanda.cioffi@unina.it
                andrea.evangelista@cpo.it
                valeponzo1@yahoo.it
                gianni.ciccone@cpo.it
                laura.soldati@unimi.it
                lidia.santarpia@unina.it
                contaldo@unina.it
                pasanisi@unina.it
                ezio.ghigo@unito.it
                0039 11 6336036 , simona.bo@unito.it
                Journal
                J Transl Med
                J Transl Med
                Journal of Translational Medicine
                BioMed Central (London )
                1479-5876
                24 December 2018
                24 December 2018
                2018
                : 16
                : 371
                Affiliations
                [1 ]ISNI 0000 0004 1754 9702, GRID grid.411293.c, Interuniversity Center for Obesity and Eating Disorders, Department of Medicine and Surgery, , Federico II University Hospital, ; Pansini, 5, Naples, 80131 Italy
                [2 ]Unit of Clinical Epidemiology, CPO, “Città della Salute e della Scienza” Hospital of Turin, Turin, Italy
                [3 ]ISNI 0000 0001 2336 6580, GRID grid.7605.4, Department of Medical Sciences, , University of Turin, ; c.so AM Dogliotti 14, 10126 Turin, Italy
                [4 ]ISNI 0000 0004 1757 2822, GRID grid.4708.b, Department of Health Sciences, , University of Milan, ; Milan, Italy
                Author information
                http://orcid.org/0000-0001-6862-8628
                Article
                1748
                10.1186/s12967-018-1748-4
                6304782
                30583725
                0c179734-414d-4c98-b8f1-405026921915
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 31 October 2018
                : 14 December 2018
                Categories
                Review
                Custom metadata
                © The Author(s) 2018

                Medicine
                continuous energy restriction,intermittent energy restriction,fasting glucose,triglycerides,weight loss

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