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Special Issue "Health Effects of Intermittent Fasting: How Broad are the Benefits?"

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (18 April 2019).

Special Issue Editor

Guest Editor
Dr. Benjamin D. Horne

1. Director, Cardiovascular and Genetic Epidemiology, Intermountain Medical Center Heart Institute, Salt Lake City, UT, USA
2. Adjunct Assistant Professor, Department of Biomedical Informatics, University of Utah, Salt Lake City, UT, USA
Website | E-Mail
Phone: 001-801-507-4708
Interests: intermittent fasting, epidemiology, genetics, coronary heart disease, diabetes/metabolism

Special Issue Information

Dear Colleagues,

The objective of this Special Issue, “Health Effects of Intermittent Fasting: How Broad are the Benefits?” is to explore the wide variety of health effects that may be possible through the use of various regimens of energy restriction that are performed intermittently. Such intermittent fasting may include consumption of no food or of some minimal level of calories during a fast that is interrupted by hours to days of usual levels of caloric intake. Regimens include alternate-day fasting, fasting once or twice per week, fasting multiple days in succession once per month, time-restricted feeding, and others. These regimens’ mechanisms of action may include a myriad of biological pathways and their distinct health impacts or levels of impact require further exploration and validation. Intermittent fasting’s safe use and its efficacy in causing changes in human health may vary depending on whether the people to which it is applied are healthy, diseased, or at-risk of a chronic disease. The optimal fasting regimen and fasting’s health effects may differ between individuals depending on additional characteristics, and these differences need to be understood for the appropriate use of fasting. Fasting can be a long-term lifestyle, as evidenced by historical religious and cultural use, and research is required to further reveal the frequency, duration, and intensity of fasting that may be most feasible for use in a healthy lifestyle. In this issue, the many facets of intermittent fasting will be explored from biological and clinical perspectives to move the field toward meaningful health improvements for humans.

Dr. Benjamin D. Horne
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Therapeutic fasting
  • Atherosclerosis
  • Insulin resistance
  • Cognitive dysfunction
  • Blood pressure
  • Cholesterol
  • Prevention
  • Healthy aging
  • Longevity

Published Papers (8 papers)

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Research

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Open AccessArticle
The Safety and Impact of a Model of Intermittent, Time-Restricted Circadian Fasting (“Ramadan Fasting”) on Hidradenitis Suppurativa: Insights from a Multicenter, Observational, Cross-Over, Pilot, Exploratory Study
Nutrients 2019, 11(8), 1781; https://doi.org/10.3390/nu11081781
Received: 5 June 2019 / Revised: 25 July 2019 / Accepted: 30 July 2019 / Published: 1 August 2019
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Abstract
Hidradenitis suppurativa (HS) is a chronic-relapsing and debilitating disease, which affects the components of the folliculopilosebaceous unit and severely impacts on the perceived health-related quality of life. Among the possible treatments, dietary interventions, such as fasting, have been described to positively impact on [...] Read more.
Hidradenitis suppurativa (HS) is a chronic-relapsing and debilitating disease, which affects the components of the folliculopilosebaceous unit and severely impacts on the perceived health-related quality of life. Among the possible treatments, dietary interventions, such as fasting, have been described to positively impact on HS. However, nothing is known about the effects of circadian, intermittent fasting, such as the Ramadan fasting. A sample of 55 HS patients (24 males (43.6%) and 31 females (56.4%), mean age 39.65 ± 8.39 years, average disease duration 14.31 ± 7.03 years) was recruited in the present study. The “Severity of International Hidradenitis Suppurativa Severity Score System” (IHS4) decreased significantly from 11.00 ± 5.88 (before Ramadan) to 10.15 ± 6.45 (after Ramadan), with a mean difference of −0.85 ± 0.83 (p < 0.0001). At the univariate analyses, the improvement was associated with HS phenotype (with a prominent improvement among those with ectopic type), treatment (with the improvement being higher in patients receiving topical and systemic antibiotics compared to those treated with biologics), the “Autoinflammatory Disease Damage Index” (ADDI), and Hurley scores. At the multivariate regression analysis, only the Hurley score (regression coefficient = 0.70, p = 0.0003) was found to be an independent predictor of change in the IHS4 score after fasting. The improvement in the IHS4 score was not, however, associated with weight loss. In conclusion, the Ramadan fasting proved to be safe and effective in HS patients. Considering the small sample size and the exploratory nature of the present investigation, further studies in the field are warranted, especially longitudinal, prospective and randomized ones. Full article
(This article belongs to the Special Issue Health Effects of Intermittent Fasting: How Broad are the Benefits?)
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Open AccessArticle
The Effects of Time Restricted Feeding on Overweight, Older Adults: A Pilot Study
Nutrients 2019, 11(7), 1500; https://doi.org/10.3390/nu11071500
Received: 15 April 2019 / Revised: 18 June 2019 / Accepted: 28 June 2019 / Published: 30 June 2019
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Abstract
A growing body of evidence indicates that time restricted feeding (TRF), a popular form of intermittent fasting, can activate similar biological pathways as caloric restriction, the only intervention consistently found to extend healthy lifespan in a variety of species. Thus, TRF may have [...] Read more.
A growing body of evidence indicates that time restricted feeding (TRF), a popular form of intermittent fasting, can activate similar biological pathways as caloric restriction, the only intervention consistently found to extend healthy lifespan in a variety of species. Thus, TRF may have the potential to also improve function in older adults. Given the challenges many individuals have in following calorie restriction regimens over long-time periods, evaluation of alternative approaches that may produce weight loss and improve function in overweight, older adults is important. Ten overweight, sedentary older adults (≥65 years) at risk for, or with mobility impairments, defined by slow gait speed (<1.0 m/s) participated in this trial. All participants received the intervention and were instructed to fast for approximately 16 h per day over the entire four-week intervention. Outcomes included changes in body weight, waist circumference, cognitive and physical function, health-related quality of life, and adverse events. Adherence levels were high (mean = 84%) based on days goal was met, and mean weight loss was 2.6 kg (p < 0.01). Since body composition was not measured in this study, it is unclear if the observed weight loss was due to loss of fat mass, muscle mass, or the combination of fat and muscle mass. There were no significant changes in other outcomes; however, there were clinically meaningful changes in walking speed and improvements in quality of life, with few reported adverse events. The findings of this pilot study suggest that time restricted feeding is an acceptable and feasible eating pattern for overweight, sedentary older adults to follow. Full article
(This article belongs to the Special Issue Health Effects of Intermittent Fasting: How Broad are the Benefits?)
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Open AccessArticle
Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans
Nutrients 2019, 11(6), 1234; https://doi.org/10.3390/nu11061234
Received: 18 April 2019 / Revised: 20 May 2019 / Accepted: 22 May 2019 / Published: 30 May 2019
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Abstract
Time-restricted feeding (TRF) is a form of intermittent fasting that involves having a longer daily fasting period. Preliminary studies report that TRF improves cardiometabolic health in rodents and humans. Here, we performed the first study to determine how TRF affects gene expression, circulating [...] Read more.
Time-restricted feeding (TRF) is a form of intermittent fasting that involves having a longer daily fasting period. Preliminary studies report that TRF improves cardiometabolic health in rodents and humans. Here, we performed the first study to determine how TRF affects gene expression, circulating hormones, and diurnal patterns in cardiometabolic risk factors in humans. Eleven overweight adults participated in a 4-day randomized crossover study where they ate between 8 am and 2 pm (early TRF (eTRF)) and between 8 am and 8 pm (control schedule). Participants underwent continuous glucose monitoring, and blood was drawn to assess cardiometabolic risk factors, hormones, and gene expression in whole blood cells. Relative to the control schedule, eTRF decreased mean 24-hour glucose levels by 4 ± 1 mg/dl (p = 0.0003) and glycemic excursions by 12 ± 3 mg/dl (p = 0.001). In the morning before breakfast, eTRF increased ketones, cholesterol, and the expression of the stress response and aging gene SIRT1 and the autophagy gene LC3A (all p < 0.04), while in the evening, it tended to increase brain-derived neurotropic factor (BNDF; p = 0.10) and also increased the expression of MTOR (p = 0.007), a major nutrient-sensing protein that regulates cell growth. eTRF also altered the diurnal patterns in cortisol and the expression of several circadian clock genes (p < 0.05). eTRF improves 24-hour glucose levels, alters lipid metabolism and circadian clock gene expression, and may also increase autophagy and have anti-aging effects in humans. Full article
(This article belongs to the Special Issue Health Effects of Intermittent Fasting: How Broad are the Benefits?)
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Open AccessArticle
Pilot Study of Novel Intermittent Fasting Effects on Metabolomic and Trimethylamine N-oxide Changes During 24-hour Water-Only Fasting in the FEELGOOD Trial
Nutrients 2019, 11(2), 246; https://doi.org/10.3390/nu11020246
Received: 7 January 2019 / Revised: 18 January 2019 / Accepted: 20 January 2019 / Published: 23 January 2019
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Abstract
Intermittent fasting (IF) has been connected with health benefits such as weight loss, lower risk of coronary artery disease (CAD) and diabetes, increased longevity, and improved quality of life. However, the mechanisms of these IF benefits in humans require further investigation. This study [...] Read more.
Intermittent fasting (IF) has been connected with health benefits such as weight loss, lower risk of coronary artery disease (CAD) and diabetes, increased longevity, and improved quality of life. However, the mechanisms of these IF benefits in humans require further investigation. This study sought to elucidate some of these mechanisms through secondary analyses of the Fasting and ExprEssion of Longevity Genes during fOOD abstinence (FEELGOOD) trial, in which apparently healthy participants were randomized in a Latin square design to a 24-h water-only fast and a 24-h ad libitum fed day. Two pathways were investigated, with trimethylamine N-oxide (TMAO) levels measured due to their association with elevated risk of CAD, along with conductance of a broad panel of metabolic analytes. Measurements were made at baseline, at the end of the fasting day, and at the end of the fed day. A fasting mean of 14.3 ng in TMAO was found versus the baseline mean of 27.1 ng with p = 0.019, although TMAO levels returned to baseline on refeeding. Further, acute alterations in levels of proline, tyrosine, galactitol, and urea plasma levels were observed along with changes in 24 other metabolites during the fasting period. These acute changes reveal short-term mechanisms which, with consistent repeated episodes of IF, may lead to improved health and reduced risk of CAD and diabetes. Full article
(This article belongs to the Special Issue Health Effects of Intermittent Fasting: How Broad are the Benefits?)
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Review

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Open AccessReview
Energy Metabolism and Intermittent Fasting: The Ramadan Perspective
Nutrients 2019, 11(5), 1192; https://doi.org/10.3390/nu11051192
Received: 18 April 2019 / Revised: 6 May 2019 / Accepted: 9 May 2019 / Published: 27 May 2019
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Abstract
Intermittent fasting (IF) has been gaining popularity as a means of losing weight. The Ramadan fast (RF) is a form of IF practiced by millions of adult Muslims globally for a whole lunar month every year. It entails a major shift from normal [...] Read more.
Intermittent fasting (IF) has been gaining popularity as a means of losing weight. The Ramadan fast (RF) is a form of IF practiced by millions of adult Muslims globally for a whole lunar month every year. It entails a major shift from normal eating patterns to exclusive nocturnal eating. RF is a state of intermittent liver glycogen depletion and repletion. The earlier (morning) part of the fasting day is marked by dominance of carbohydrate as the main fuel, but lipid becomes more important towards the afternoon and as the time for breaking the fast at sunset (iftar) gets closer. The practice of observing Ramadan fasting is accompanied by changes in sleeping and activity patterns, as well as circadian rhythms of hormones including cortisol, insulin, leptin, ghrelin, growth hormone, prolactin, sex hormones, and adiponectin. Few studies have investigated energy expenditure in the context of RF including resting metabolic rate (RMR) and total energy expenditure (TEE) and found no significant changes with RF. Changes in activity and sleeping patterns however do occur and are different from non-Ramadan days. Weight changes in the context of Ramadan fast are variable and typically modest with wise inter-individual variation. As well as its direct relevance to many religious observers, understanding intermittent fasting may have implications on weight loss strategies with even broader potential implications. This review examines current knowledge on different aspects of energy balance in RF, as a common model to learn from and also map out strategies for healthier outcomes in such settings. Full article
(This article belongs to the Special Issue Health Effects of Intermittent Fasting: How Broad are the Benefits?)
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Open AccessReview
The Influence of Meal Frequency and Timing on Health in Humans: The Role of Fasting
Nutrients 2019, 11(4), 719; https://doi.org/10.3390/nu11040719
Received: 11 February 2019 / Revised: 19 March 2019 / Accepted: 26 March 2019 / Published: 28 March 2019
Cited by 4 | PDF Full-text (1679 KB) | HTML Full-text | XML Full-text
Abstract
The influence of meal frequency and timing on health and disease has been a topic of interest for many years. While epidemiological evidence indicates an association between higher meal frequencies and lower disease risk, experimental trials have shown conflicting results. Furthermore, recent prospective [...] Read more.
The influence of meal frequency and timing on health and disease has been a topic of interest for many years. While epidemiological evidence indicates an association between higher meal frequencies and lower disease risk, experimental trials have shown conflicting results. Furthermore, recent prospective research has demonstrated a significant increase in disease risk with a high meal frequency (≥6 meals/day) as compared to a low meal frequency (1–2 meals/day). Apart from meal frequency and timing we also have to consider breakfast consumption and the distribution of daily energy intake, caloric restriction, and night-time eating. A central role in this complex scenario is played by the fasting period length between two meals. The physiological underpinning of these interconnected variables may be through internal circadian clocks, and food consumption that is asynchronous with natural circadian rhythms may exert adverse health effects and increase disease risk. Additionally, alterations in meal frequency and meal timing have the potential to influence energy and macronutrient intake.A regular meal pattern including breakfast consumption, consuming a higher proportion of energy early in the day, reduced meal frequency (i.e., 2–3 meals/day), and regular fasting periods may provide physiological benefits such as reduced inflammation, improved circadian rhythmicity, increased autophagy and stress resistance, and modulation of the gut microbiota Full article
(This article belongs to the Special Issue Health Effects of Intermittent Fasting: How Broad are the Benefits?)
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Open AccessReview
Intermittent Fasting in Cardiovascular Disorders—An Overview
Nutrients 2019, 11(3), 673; https://doi.org/10.3390/nu11030673
Received: 12 February 2019 / Revised: 15 March 2019 / Accepted: 18 March 2019 / Published: 20 March 2019
Cited by 1 | PDF Full-text (329 KB) | HTML Full-text | XML Full-text
Abstract
Intermittent fasting is a form of time restricted eating (typically 16 h fasting and 8 h eating), which has gained popularity in recent years and shows promise as a possible new paradigm in the approach to weight loss and the reduction of inflammation, [...] Read more.
Intermittent fasting is a form of time restricted eating (typically 16 h fasting and 8 h eating), which has gained popularity in recent years and shows promise as a possible new paradigm in the approach to weight loss and the reduction of inflammation, and has many potential long term health benefits. In this review, the authors will incorporate many aspects of fasting, mainly focusing on its effects on the cardiovascular system, involving atherosclerosis progression, benefits for diabetes mellitus type 2, lowering of blood pressure, and exploring other cardiovascular risk factors (such as lipid profile and inflammation). Full article
(This article belongs to the Special Issue Health Effects of Intermittent Fasting: How Broad are the Benefits?)
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Other

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Open AccessPerspective
Clinical Management of Intermittent Fasting in Patients with Diabetes Mellitus
Nutrients 2019, 11(4), 873; https://doi.org/10.3390/nu11040873
Received: 13 March 2019 / Revised: 11 April 2019 / Accepted: 16 April 2019 / Published: 18 April 2019
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Abstract
Intermittent fasting is increasing in popularity as a means of losing weight and controlling chronic illness. Patients with diabetes mellitus, both types 1 and 2, comprise about 10% of the population in the United States and would likely be attracted to follow one [...] Read more.
Intermittent fasting is increasing in popularity as a means of losing weight and controlling chronic illness. Patients with diabetes mellitus, both types 1 and 2, comprise about 10% of the population in the United States and would likely be attracted to follow one of the many methods of intermittent fasting. Studies on the safety and benefits of intermittent fasting with diabetes are very limited though, and health recommendations unfortunately today arise primarily from weight loss gurus and animal studies. Medical guidelines on how to manage therapeutic intermittent fasting in patients with diabetes are non-existent. The evidence to build such a clinical guideline for people with a diabetes diagnosis is almost non-existent, with just one randomized trial and several case reports. This article provides an overview of the available knowledge and a review of the very limited pertinent literature on the effects of intermittent fasting among people with diabetes. It also evaluates the known safety and efficacy issues surrounding treatments for diabetes in the fasting state. Based on those limited data and a knowledge of best practices, this paper proposes expert-based guidelines on how to manage a patient with either type 1 or 2 diabetes who is interested in intermittent fasting. The safety of each relevant pharmaceutical treatment during a fasting period is considered. When done under the supervision of the patient’s healthcare provider, and with appropriate personal glucose monitoring, intermittent fasting can be safely undertaken in patients with diabetes. Full article
(This article belongs to the Special Issue Health Effects of Intermittent Fasting: How Broad are the Benefits?)
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