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Mechanisms and Health Effects of Periodic and Intermittent Fasting

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrition and Public Health".

Deadline for manuscript submissions: closed (25 April 2023) | Viewed by 92026

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Dr. Olga Pivovarova-Ramich

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Guest Editor

Molecular Nutritional Medicine Research Group, German Institute of Human Nutrition, Potsdam-Rehbrücke, 14558 Nuthetal, Germany
Interests: diabetes; obesity; nutrition; metabolism; chronobiology
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Andreas Michalsen

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Charité Universitätsmedizin Berlin, Institute of Social Medicine, Epidemiology and Health Economics and Immanuel Hospital Berlin, 14109 Berlin, Germany
Interests: fasting; caloric restriction; nutrition; metabolism; obesity; integrative medicine

Special Issue Information

Dear Colleagues,

There is an increasing body of experimental and clinical evidence indicating that fasting and caloric restriction are powerful interventions to prevent, postpone, and treat the globally increasing burden of chronic diseases associated with ageing and metabolic dysfunction. On the other hand, there are worldwide traditions of fasting methods and fasting rituals that are widely known and established in the population. It is time to bring together the knowledge of innovative fasting science and the experience of traditional medicine.

We invite authors worldwide to contribute to this issue focussing on the mechanisms and effects of the full spectrum of existing fasting interventions, including periodic and prolonged fasting, fasting-mimicking diets and intermittent fasting, and fasting-like interventions including fasting mimetics. The Special Issue welcomes original research and reviews, also including observational data, secondary analyses of trials, systematic reviews, and qualitative research elucidating following topics:

Effects of fasting on clinical outcomes;
Physiological and metabolic effects including microbiome and metabolomics;
Fasting and ageing;
Digital health and fasting;
Comparative effects of different fasting methods;
Psychological effects of fasting;
Fasting and aging;
Medical effects of fasting;
Fasting and quality of life;
Feasibility, adherence, and safety.

Dr. Olga Pivovarova-Ramich
Prof. Dr. Andreas Michalsen
Guest Editors

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Keywords

intermittent fasting
periodic fasting
prolonged fasting
fasting-mimicking diet
religious fasting
starvation
caloric restriction
chronic diseases
fasting mimetics

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Published Papers (9 papers)

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20 pages, 2854 KiB

Open AccessArticle

Effects of Prolonged Fasting during Inpatient Multimodal Treatment on Pain and Functional Parameters in Knee and Hip Osteoarthritis: A Prospective Exploratory Observational Study

by Daniela A. Koppold, Farid I. Kandil, Oliver Güttler, Anna Müller, Nico Steckhan, Sara Meiß, Carolin Breinlinger, Esther Nelle, Anika M. Hartmann, Michael Jeitler, Etienne Hanslian, Jan Moritz Fischer, Andreas Michalsen and Christian S. Kessler

Nutrients 2023, 15(12), 2695; https://doi.org/10.3390/nu15122695 - 9 Jun 2023

Cited by 4 | Viewed by 3710

Abstract

Preliminary clinical data suggest that pain reduction through fasting may be effective for different diagnoses. This uncontrolled observational clinical study examined the effects of prolonged modified fasting on pain and functional parameters in hip and knee osteoarthritis. Patients admitted to the inpatient department of Internal Medicine and Nature-based Therapies of the Immanuel Hospital Berlin between February 2018 and December 2020 answered questionnaires at the beginning and end of inpatient treatment, as well as at 3, 6, and 12 months after discharge. Additionally, selected blood and anthropometric parameters, as well as subjective pain ratings, were routinely assessed during the inpatient stay. Fasting was the only common intervention for all patients, being performed as part of a multimodal integrative treatment program, with a daily caloric intake of <600 kcal for 7.7 ± 1.7 days. N = 125 consecutive patients were included. The results revealed an amelioration of overall symptomatology (WOMAC Index score: −14.8 ± 13.31; p < 0.001; d = 0.78) and pain alleviation (NRS Pain: −2.7 ± 1.98, p < 0.001, d = 1.48). Pain medication was reduced, stopped, or replaced by herbal remedies in 36% of patients. Improvements were also observed in secondary outcome parameters, including increased quality of life (WHO-5: +4.5 ± 4.94, p < 0.001, d = 0.94), reduced anxiety (HADS-A: −2.1 ± 2.91, p < 0001, d = 0.55) and depression (HADS-D: −2.3 ± 3.01, p < 0.001, d = 0.65), and decreases in body weight (−3.6 kg ± 1.65, p < 0.001, d = 0.21) and blood pressure (systolic: −6.2 ± 15.93, p < 0.001, d = 0.43; diastolic: −3.7 ± 10.55, p < 0.001, d = 0.43). The results suggest that patients with osteoarthritis of the lower extremities may benefit from prolonged fasting as part of a multimodal integrative treatment to improve quality of life, pain, and disease-specific functional parameters. Confirmatory randomized controlled trials are warranted to further investigate these hypotheses. Full article

(This article belongs to the Special Issue Mechanisms and Health Effects of Periodic and Intermittent Fasting)

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12 pages, 998 KiB

Open AccessArticle

Post Hoc Analysis of a Randomized Controlled Trial on Fasting and Plant-Based Diet in Rheumatoid Arthritis (NutriFast): Nutritional Supply and Impact on Dietary Behavior

by Anika M. Hartmann, Marina D’Urso, Melanie Dell’Oro, Daniela A. Koppold, Nico Steckhan, Andreas Michalsen, Farid I. Kandil and Christian S. Kessler

Nutrients 2023, 15(4), 851; https://doi.org/10.3390/nu15040851 - 7 Feb 2023

Cited by 6 | Viewed by 3558

Abstract

This study aimed at comparing the nutrient supply and dietary behaviors during a plant-based diet (PBD) combined with time-restricted eating (TRE) to standard dietary recommendations in rheumatoid arthritis patients. In this open-label, randomized, controlled clinical trial, patients were assigned to either a 7-day fast followed by an 11-week PBD including TRE (A) or a 12-week anti-inflammatory diet following official German guidelines (German Nutrition Society, DGE) (B). Dietary habits were assessed by 3-day food records at weeks -1, 4 and 9 and food frequency questionnaires. 41 out of 53 participants were included in a post-hoc per protocol analysis. Both groups had similar energy, carbohydrate, sugar, fiber and protein intake at week 4. Group A consumed significantly less total saturated fat than group B (15.9 ± 7.7 vs. 23.2 ± 10.3 g/day; p = 0.02). Regarding micronutrients, group B consumed more vitamin A, B₁₂, D, riboflavin and calcium (each p ≤ 0.02). Zinc and calcium were below recommended intakes in both groups. Cluster analysis did not show clear group allocation after three months. Hence, dietary counselling for a PBD combined with TRE compared to a standard anti-inflammatory diet does not seem to lead to two different dietary clusters, i.e., actual different dietary behaviors as expected. Larger confirmatory studies are warranted to further define dietary recommendations for RA. Full article

(This article belongs to the Special Issue Mechanisms and Health Effects of Periodic and Intermittent Fasting)

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14 pages, 1665 KiB

Open AccessArticle

Glucose Metabolism and Metabolomic Changes in Response to Prolonged Fasting in Individuals with Obesity, Type 2 Diabetes and Non-Obese People—A Cohort Trial

by Norbert J. Tripolt, Sebastian J. Hofer, Peter N. Pferschy, Faisal Aziz, Sylvère Durand, Fanny Aprahamian, Nitharsshini Nirmalathasan, Mara Waltenstorfer, Tobias Eisenberg, Anna M. A. Obermayer, Regina Riedl, Harald Kojzar, Othmar Moser, Caren Sourij, Heiko Bugger, Abderrahim Oulhaj, Thomas R. Pieber, Matthias Zanker, Guido Kroemer, Frank Madeo and Harald Sourij Show full author list Hide full author list

Nutrients 2023, 15(3), 511; https://doi.org/10.3390/nu15030511 - 18 Jan 2023

Cited by 3 | Viewed by 4004

Abstract

Metabolic regulation of glucose can be altered by fasting periods. We examined glucose metabolism and metabolomics profiles after 12 h and 36 h fasting in non-obese and obese participants and people with type 2 diabetes using oral glucose tolerance (OGTT) and intravenous glucose tolerance testing (IVGTT). Insulin sensitivity was estimated by established indices and mass spectrometric metabolomics was performed on fasting serum samples. Participants had a mean age of 43 ± 16 years (62% women). Fasting levels of glucose, insulin and C-peptide were significantly lower in all cohorts after 36 h compared to 12 h fasting (p < 0.05). In non-obese participants, glucose levels were significantly higher after 36 h compared to 12 h fasting at 120 min of OGTT (109 ± 31 mg/dL vs. 79 ± 18 mg/dL; p = 0.001) but insulin levels were lower after 36 h of fasting at 30 min of OGTT (41.2 ± 34.1 mU/L after 36 h vs. 56.1 ± 29.7 mU/L; p < 0.05). In contrast, no significant differences were observed in obese participants or people with diabetes. Insulin sensitivity improved in all cohorts after 36 h fasting. In line, metabolomics revealed subtle baseline differences and an attenuated metabolic response to fasting in obese participants and people with diabetes. Our data demonstrate an improved insulin sensitivity after 36 h of fasting with higher glucose variations and reduced early insulin response in non-obese people only. Full article

(This article belongs to the Special Issue Mechanisms and Health Effects of Periodic and Intermittent Fasting)

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15 pages, 1218 KiB

Open AccessArticle

Intermittent Fasting—Short- and Long-Term Quality of Life, Fatigue, and Safety in Healthy Volunteers: A Prospective, Clinical Trial

by Katharina Anic, Mona W. Schmidt, Larissa Furtado, Lina Weidenbach, Marco J. Battista, Marcus Schmidt, Roxana Schwab, Walburgis Brenner, Christian Ruckes, Johannes Lotz, Karl J. Lackner, Annbalou Hasenburg and Annette Hasenburg

Nutrients 2022, 14(19), 4216; https://doi.org/10.3390/nu14194216 - 10 Oct 2022

Cited by 14 | Viewed by 41063

Abstract

Background: Intermittent fasting (IF) is defined as an eating pattern without calorie restrictions, alternating between periods of fasting and eating. In the past decades IF has not only become a popular weight-reducing diet but is thought to improve Quality of Life (QoL) and fatigue. However, very little evidence exists for the general population. Thus, we aimed to assess the impact of a 16-h fasting period per day over a three-month study period on QoL and especially fatigue in healthy people. Methods: We conducted a prospective cohort study including healthy subjects. All participants fasted 16 h for at least five days a week while maintaining their normal lifestyle. In the study, we analysed blood samples as well as QoL through standardized questionnaires (WHO-5 questionnaire, Short Form Health 36). Furthermore, we measured the degree of fatigue with the Fatigue Assessment Scale (FAS) and Fatigue Severity Scale (FSS) as well as compliance, activity records, and weight alterations. All endpoints were evaluated at baseline, after two weeks, four weeks, and three months of IF. Results: A total of 30 participants fasted for the entire study period. The results of the WHO-5 questionnaire (15.6 ± 4.6 vs. 18 ± 3.6, p < 0.0019) demonstrated a significant increase in QoL. For long-term QoL six out of eight domains measured by the Short Form Health 36 (SF-36) significantly improved (e.g., physical health: 92.3 ± 11.6 vs. 96.5 ± 6.3, p = 0.015; mental health: 75.5 ± 12.0 vs. 81.7 ± 9.0; p < 0.001 and body pain: 74.1 ± 31.8 vs. 89.5 ± 14.9; p = 0.008) after three months. Fatigue significantly decreased from 10.3 ± 3.2 to 8.4 ± 2.5; p = 0.002 for mental fatigue and from 12.6 ± 3.8 to 10.7 ± 3.3; p = 0.002 measured by the FAS. The mean FSS-Score at baseline was 3.5 ± 1.2 compared to 2.9 ± 1.1 (scale 1–7) after three months (p < 0.001). Notably, the proliferation marker IGF-1 was significantly reduced. No clinically significant changes in laboratory parameters were observed that would have endangered a participant’s safety. Conclusions: IF according to the 16:8 regime over a fasting period of three months significantly improved several aspects of the QoL and decreased fatigue in healthy people, while maintaining a good safety profile. The practicability of this diet was also demonstrated for shift workers and people with a high percentage of active labour. Apart from the improvement in QoL and fatigue, the significant reduction in IGF-1, which can act as an accelerator of tumour development and progression, might be an indicator of the potential benefits of IF for patients with cancer. Full article

(This article belongs to the Special Issue Mechanisms and Health Effects of Periodic and Intermittent Fasting)

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13 pages, 1289 KiB

Open AccessFeature PaperArticle

Validation of a Smartphone Application for the Assessment of Dietary Compliance in an Intermittent Fasting Trial

by Isabella Baum Martinez, Beeke Peters, Julia Schwarz, Bettina Schuppelius, Nico Steckhan, Daniela A. Koppold-Liebscher, Andreas Michalsen and Olga Pivovarova-Ramich

Nutrients 2022, 14(18), 3697; https://doi.org/10.3390/nu14183697 - 7 Sep 2022

Cited by 5 | Viewed by 2793

Abstract

Accurate dietary analysis of energy, nutrient intake, and meal timing in human studies using traditional dietary assessment methods (e.g., food records) is challenging and time-consuming. The widespread use of smartphones, tablets, and nutrition applications (apps) can overcome some of these problems. The objective of this study was to evaluate the validity of an FDDB smartphone app and food database compared with PRODI^®—a professional platform for nutritional counselling using the German Nutrient Database. Dietary records were collected from 10 subjects participating in the crossover intermittent fasting trial for 2 weeks at baseline and during the eating timeframe of 8 h (early or late in the course of the day). The FDDB app and database enabled a quicker and less sophisticated analysis of food composition and timing than the PRODI^® software. Good agreement between the methods was found for energy and macronutrient intakes, while the FDDB data on most micronutrients and saturated/unsaturated fat intake were unreliable. In contrast to PRODI^®, FDDB provided effective assessment of timely compliance, making it a promising tool for chrononutritional studies. Thus, the FDDB app is comparable to the traditional PRODI^® dietary assessment method, and can be effectively used in human dietary trials and medical practice for specific goals. Full article

(This article belongs to the Special Issue Mechanisms and Health Effects of Periodic and Intermittent Fasting)

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14 pages, 1557 KiB

Open AccessArticle

A Randomized Controlled Trial of Fasting and Lifestyle Modification in Patients with Metabolic Syndrome: Effects on Patient-Reported Outcomes

by Michael Jeitler, Romy Lauche, Christoph Hohmann, Kyung-Eun (Anna) Choi, Nadia Schneider, Nico Steckhan, Florian Rathjens, Dennis Anheyer, Anna Paul, Christel von Scheidt, Thomas Ostermann, Elisabeth Schneider, Daniela Koppold-Liebscher, Christian S. Kessler, Gustav Dobos, Andreas Michalsen and Holger Cramer

Nutrients 2022, 14(17), 3559; https://doi.org/10.3390/nu14173559 - 29 Aug 2022

Cited by 6 | Viewed by 3936

Abstract

Lifestyle interventions can have a positive impact on quality of life and psychological parameters in patients with metabolic syndrome (MetS). In this randomized controlled trial, 145 participants with MetS (62.8% women; 59.7 ± 9.3 years) were randomized to (1) 5-day fasting followed by 10 weeks of lifestyle modification (F + LM; modified DASH diet, exercise, mindfulness; n = 73) or (2) 10 weeks of lifestyle modification only (LM; n = 72). Outcomes were assessed at weeks 0, 1, 12, and 24, and included quality of life (Short-Form 36 Health Survey Questionnaire, SF-36), anxiety/depression (Hospital Anxiety and Depression Scale, HADS), stress (Cohen Perceived Stress Scale, CPSS), mood (Profile of Mood States, POMS), self-efficacy (General Self-Efficacy Scale, GSE), mindfulness (Mindfulness Attention Awareness Scale, MAAS), and self-compassion (Self-Compassion Scale, SCS). At week 1, POMS depression and fatigue scores were significantly lower in F + LM compared to LM. At week 12, most self-report outcomes improved in both groups—only POMS vigor was significantly higher in F + LM than in LM. Most of the beneficial effects within the groups persisted at week 24. Fasting can induce mood-modulating effects in the short term. LM induced several positive effects on quality of life and psychological parameters in patients with MetS. Full article

(This article belongs to the Special Issue Mechanisms and Health Effects of Periodic and Intermittent Fasting)

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21 pages, 7849 KiB

Open AccessArticle

A Comparison of the Impact of Restrictive Diets on the Gastrointestinal Tract of Mice

by András Gregor, Laura Huber, Sandra Auernigg-Haselmaier, Felix Sternberg, Magdalena Billerhart, Andreas Dunkel, Veronika Somoza, Manfred Ogris, Barbara Kofler, Valter D. Longo, Jürgen König and Kalina Duszka

Nutrients 2022, 14(15), 3120; https://doi.org/10.3390/nu14153120 - 29 Jul 2022

Cited by 11 | Viewed by 5275

Abstract

The rate of gut inflammatory diseases is growing in modern society. Previously, we showed that caloric restriction (CR) shapes gut microbiota composition and diminishes the expression of inflammatory factors along the gastrointestinal (GI) tract. The current project aimed to assess whether prominent dietary restrictive approaches, including intermittent fasting (IF), fasting-mimicking diet (FMD), and ketogenic diet (KD) have a similar effect as CR. We sought to verify which of the restrictive dietary approaches is the most potent and if the molecular pathways responsible for the impact of the diets overlap. We characterized the impact of the diets in the context of several dietary restriction-related parameters, including immune status in the GI tract; microbiota and its metabolites; bile acids (BAs); gut morphology; as well as autophagy-, mitochondria-, and energy restriction-related parameters. The effects of the various diets are very similar, particularly between CR, IF, and FMD. The occurrence of a 50 kDa truncated form of occludin, the composition of the microbiota, and BAs distinguished KD from the other diets. Based on the results, we were able to provide a comprehensive picture of the impact of restrictive diets on the gut, indicating that restrictive protocols aimed at improving gut health may be interchangeable. Full article

(This article belongs to the Special Issue Mechanisms and Health Effects of Periodic and Intermittent Fasting)

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Review

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23 pages, 665 KiB

Open AccessReview

The Effects of Dietary Interventions on Brain Aging and Neurological Diseases

by Fleur Lobo, Jonathan Haase and Sebastian Brandhorst

Nutrients 2022, 14(23), 5086; https://doi.org/10.3390/nu14235086 - 30 Nov 2022

Cited by 14 | Viewed by 8195

Abstract

Dietary interventions can ameliorate age-related neurological decline. Decades of research of in vitro studies, animal models, and clinical trials support their ability and efficacy to improve behavioral outcomes by inducing biochemical and physiological changes that lead to a more resilient brain. Dietary interventions including calorie restriction, alternate day fasting, time restricted feeding, and fasting mimicking diets not only improve normal brain aging but also slow down, or even reverse, the progression of neurological diseases. In this review, we focus on the effects of intermittent and periodic fasting on improving phenotypic outcomes, such as cognitive and motor-coordination decline, in the normal aging brain through an increase in neurogenesis and synaptic plasticity, and decrease in neuroinflammation, mitochondrial dysfunction, and oxidative stress. We summarize the results of various dietary interventions in animal models of age-related neurological diseases such as Alzheimer’s disease, Parkinson’s disease, epilepsy, and Multiple Sclerosis and discuss the results of clinical trials that explore the feasibility of dietary interventions in the prevention and treatment of these diseases. Full article

(This article belongs to the Special Issue Mechanisms and Health Effects of Periodic and Intermittent Fasting)

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28 pages, 4050 KiB

Open AccessSystematic Review

The Effect of Intermittent Fasting on Appetite: A Systematic Review and Meta-Analysis

by Rebecca L. Elsworth, Angelica Monge, Rachel Perry, Elanor C. Hinton, Annika N. Flynn, Alex Whitmarsh, Julian P. Hamilton-Shield, Natalia S. Lawrence and Jeffrey M. Brunstrom

Nutrients 2023, 15(11), 2604; https://doi.org/10.3390/nu15112604 - 1 Jun 2023

Cited by 6 | Viewed by 15937

Abstract

Previously, narrative reviews have considered the effects of intermittent fasting on appetite. One suggestion is that intermittent fasting attenuates an increase in appetite that typically accompanies weight loss. Here, we conducted the first systematic review and meta-analysis to quantify the effects of intermittent fasting on appetite, when compared to a continuous energy restriction intervention. Five electronic databases and trial registers were searched in February 2021 and February 2022. Abstracts (N = 2800) were screened and 17 randomized controlled trials (RCTs), consisting of a variety of intermittent fasting regimes, met our inclusion criteria. The total number of participants allocated to interventions was 1111 and all RCTs were judged as having either some concerns or a high risk of bias (Cochrane RoB 2.0 tool). Random effects meta-analyses were conducted on change-from-baseline appetite ratings. There was no clear evidence that intermittent fasting affected hunger (WMD = −3.03; 95% CI [−8.13, 2.08]; p = 0.25; N = 13), fullness (WMD = 3.11; 95% CI [−1.46, 7.69]; p = 0.18; N = 10), desire to eat (WMD = −3.89; 95% CI [−12.62, 4.83]; p = 0.38; N = 6), or prospective food consumption (WMD = −2.82; 95% CI [−3.87, 9.03]; p = 0.43; N = 5), differently to continuous energy restriction interventions. Our results suggest that intermittent fasting does not mitigate an increase in our drive to eat that is often associated with continuous energy restriction. Full article

(This article belongs to the Special Issue Mechanisms and Health Effects of Periodic and Intermittent Fasting)

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