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      Effects of alternate-day fasting on body weight and dyslipidaemia in patients with non-alcoholic fatty liver disease: a randomised controlled trial

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          Abstract

          Background

          Alternate-day fasting (ADF) is a novel diet therapy that may achieve reduction in body weight and improvement of dyslipidaemia, but the impact of this diet on patients with non-alcoholic fatty liver disease (NAFLD) remains unknown. The aim of this study was to evaluate the effects of ADF on the body weight and lipid profile of individuals with NAFLD.

          Methods

          NAFLD patients ( n = 271) were randomised to the ADF group, time-restricted feeding (TRF) group, or the control group and subjected to the respective diet for 12 weeks. Anthropometric measurements (body weight, fat mass/fat-free mass) were performed, and plasma lipids were analysed enzymatically.

          Results

          Within 4 weeks, the body weight decreased significantly ( P < 0.001) in the ADF group by 4.56 ± 0.41 kg (6.1 ± 0.5%) and the TRF group by 3.62 ± 0.65 kg (4.83 ± 0.9%) compared to the control group, and it decreased even more after 12 weeks in both groups (ADF: − 4.04 ± 0.54 kg, 5.4 ± 0.7%; TRF: − 3.25 ± 0.67 kg, 4.3 ± 0.9%). Fat mass was significantly reduced by ADF (− 3.49 ± 0.37 kg; 11 ± 1.2%) and TRF (− 2.91 ± 0.41 kg; 9.6 ± 1.3%), with ADF leading to a further reduction in fat mass after 12 weeks (− 3.48 ± 0.38 kg; 11 ± 1.2%). Total cholesterol was significantly decreased at both time points in the ADF group (− 0.91 ± 0.07 mmol/L; 18.5 ± 1.5%) compared to the control and TRF groups. Both ADF (− 0.64 ± 0.06 mmol/L; 25 ± 1.9%) and TRF (0.58 ± 0.07 mmol/L; 20 ± 1.7%) achieved a significant reduction in serum triglycerides ( P < 0.001) after 12 weeks. Changes in fat free mass, HDL, LDL, fasting insulin, glucose, liver stiffness, and systolic or diastolic blood pressure did not differ between the groups.

          Conclusions

          ADF appears to be an effective diet therapy for individuals with NAFLD that can achieve weight loss and improvement of dyslipidaemia within a relatively short period of time (4 to 12 weeks). Potential preventive effects of ADF on cardiovascular disease need to be confirmed by future investigations.

          Trial registration

          ChiCTR1900024411, this trial was retrospectively registered on July 10, 2019.

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          Most cited references28

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          Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet.

          While diet-induced obesity has been exclusively attributed to increased caloric intake from fat, animals fed a high-fat diet (HFD) ad libitum (ad lib) eat frequently throughout day and night, disrupting the normal feeding cycle. To test whether obesity and metabolic diseases result from HFD or disruption of metabolic cycles, we subjected mice to either ad lib or time-restricted feeding (tRF) of a HFD for 8 hr per day. Mice under tRF consume equivalent calories from HFD as those with ad lib access yet are protected against obesity, hyperinsulinemia, hepatic steatosis, and inflammation and have improved motor coordination. The tRF regimen improved CREB, mTOR, and AMPK pathway function and oscillations of the circadian clock and their target genes' expression. These changes in catabolic and anabolic pathways altered liver metabolome and improved nutrient utilization and energy expenditure. We demonstrate in mice that tRF regimen is a nonpharmacological strategy against obesity and associated diseases. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan.

            Most animals alternate periods of feeding with periods of fasting often coinciding with sleep. Upon >24 hr of fasting, humans, rodents, and other mammals enter alternative metabolic phases, which rely less on glucose and more on ketone body-like carbon sources. Both intermittent and periodic fasting result in benefits ranging from the prevention to the enhanced treatment of diseases. Similarly, time-restricted feeding (TRF), in which food consumption is restricted to certain hours of the day, allows the daily fasting period to last >12 hr, thus imparting pleiotropic benefits. Understanding the mechanistic link between nutrients and the fasting benefits is leading to the identification of fasting-mimicking diets (FMDs) that achieve changes similar to those caused by fasting. Given the pleiotropic and sustained benefits of TRF and FMDs, both basic science and translational research are warranted to develop fasting-associated interventions into feasible, effective, and inexpensive treatments with the potential to improve healthspan.
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              Impact of intermittent fasting on health and disease processes.

              Humans in modern societies typically consume food at least three times daily, while laboratory animals are fed ad libitum. Overconsumption of food with such eating patterns often leads to metabolic morbidities (insulin resistance, excessive accumulation of visceral fat, etc.), particularly when associated with a sedentary lifestyle. Because animals, including humans, evolved in environments where food was relatively scarce, they developed numerous adaptations that enabled them to function at a high level, both physically and cognitively, when in a food-deprived/fasted state. Intermittent fasting (IF) encompasses eating patterns in which individuals go extended time periods (e.g., 16-48h) with little or no energy intake, with intervening periods of normal food intake, on a recurring basis. We use the term periodic fasting (PF) to refer to IF with periods of fasting or fasting mimicking diets lasting from 2 to as many as 21 or more days. In laboratory rats and mice IF and PF have profound beneficial effects on many different indices of health and, importantly, can counteract disease processes and improve functional outcome in experimental models of a wide range of age-related disorders including diabetes, cardiovascular disease, cancers and neurological disorders such as Alzheimer's disease Parkinson's disease and stroke. Studies of IF (e.g., 60% energy restriction on 2days per week or every other day), PF (e.g., a 5day diet providing 750-1100kcal) and time-restricted feeding (TRF; limiting the daily period of food intake to 8h or less) in normal and overweight human subjects have demonstrated efficacy for weight loss and improvements in multiple health indicators including insulin resistance and reductions in risk factors for cardiovascular disease. The cellular and molecular mechanisms by which IF improves health and counteracts disease processes involve activation of adaptive cellular stress response signaling pathways that enhance mitochondrial health, DNA repair and autophagy. PF also promotes stem cell-based regeneration as well as long-lasting metabolic effects. Randomized controlled clinical trials of IF versus PF and isoenergetic continuous energy restriction in human subjects will be required to establish the efficacy of IF in improving general health, and preventing and managing major diseases of aging.
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                Author and article information

                Contributors
                965343605@qq.com
                912542420@qq.com
                675740759@qq.com
                67730904@qq.com
                1600869909@qq.com
                8014273@qq.com
                357042151@qq.com
                chenzhiyuan@hunnu.edu.cn
                Journal
                BMC Gastroenterol
                BMC Gastroenterol
                BMC Gastroenterology
                BioMed Central (London )
                1471-230X
                18 December 2019
                18 December 2019
                2019
                : 19
                : 219
                Affiliations
                Department of Gastroenterology, Hunan Provincial People’ Hospital, The First Affiliated Hospital of Human Normal University, Jiefang Road West, Changsha, 410005 Hunan China
                Article
                1132
                10.1186/s12876-019-1132-8
                6921505
                31852444
                5030f26d-8df9-44a6-9efe-8caf1c8eba86
                © The Author(s). 2019

                Open Access This 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
                : 22 September 2019
                : 1 December 2019
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Gastroenterology & Hepatology
                alternate-day fasting,weight loss,dyslipidaemia,non-alcoholic fatty liver disease

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