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Publication
Journal: Journal of the Academy of Nutrition and Dietetics
October/25/2015
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Journal: Frontiers in Endocrinology
September/30/2021
Abstract
Keywords: Parkinsons disease; intermittent fasting; metabolic syndrome; type 1 diabetes; type 2 diabetes.
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Journal: Cell Research
November/13/2017
Abstract
Intermittent fasting (IF) has been shown to promote metabolic health in several organisms. Two recent papers show that IF induces white adipose tissue beiging and increases thermogenesis, which improves metabolic health in mice.
Publication
Journal: Nutrients
March/22/2019
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, 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).
Publication
Journal: CMAJ
September/12/2013
Publication
Journal: Frontiers in Neurology
June/17/2021
Abstract
Keywords: Parkinson's disease; alpha synuclein; intermittent fasting; mitochondrial dysfunction; neuronal loss; oxidative stress.
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Journal: Nutrients
May/29/2019
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 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.
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Journal: Current obesity reports
October/1/2018
Abstract
OBJECTIVE
We review the underlying mechanisms and potential benefits of intermittent fasting (IF) from animal models and recent clinical trials.
RESULTS
Numerous variations of IF exist, and study protocols vary greatly in their interpretations of this weight loss trend. Most human IF studies result in minimal weight loss and marginal improvements in metabolic biomarkers, though outcomes vary. Some animal models have found that IF reduces oxidative stress, improves cognition, and delays aging. Additionally, IF has anti-inflammatory effects, promotes autophagy, and benefits the gut microbiome. The benefit-to-harm ratio varies by model, IF protocol, age at initiation, and duration. We provide an integrated perspective on potential benefits of IF as well as key areas for future investigation. In clinical trials, caloric restriction and IF result in similar degrees of weight loss and improvement in insulin sensitivity. Although these data suggest that IF may be a promising weight loss method, IF trials have been of moderate sample size and limited duration. More rigorous research is needed.
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Journal: Medicine
July/18/2021
Abstract
Diet is a significant factor in determining human well-being. Excessive eating and/or diets with higher than needed amounts of carbohydrates, salt, and fat are known to cause metabolic disorders and functional changes in the body. To compensate the ill effects, many designer diets including the Mediterranean diet, the Okinawa diet, vegetarian/vegan diets, keto diet, anti-inflammatory diet, and the anti-oxidant diet have been introduced in the past 2 decades. While these diets are either enriched or devoid of one or more specific components, a better way to control diet is to limit the amount of food consumed. Caloric restriction (CR), which involves limiting the amount of food consumed rather than eliminating any specific type of food, as well as intermittent fasting (IF), which entails limiting the time during which food can be consumed on a given day, have gained popularity because of their positive effects on human health. While the molecular mechanisms of these 2 dietary regimens have not been fully deciphered, they are known to prolong the life span, control blood pressure, and blood glucose levels. Furthermore, CR and IF were both shown to decrease the incidence of heart attack and stroke, as well as their ill effects. In particular, IF is thought to promote metabolic switching by altering gene expression profiles leading to reduced inflammation and oxidative stress, while increasing plasticity and regeneration.
Keywords: Brain; Dietary restriction; Inflammation; Neuroprotection; Oxidative stress; Stroke.
Publication
Journal: Journal of Proteome Research
March/20/2019
Abstract
Intermittent fasting (IF) increases lifespan and decreases metabolic disease phenotypes and cancer risk in model organisms, but the health benefits of IF in humans are less clear. Human plasma derived from clinical trials is one of the most difficult sample sets to analyze using mass spectrometry-based proteomics due to the extensive sample preparation required and the need to process many samples to achieve statistical significance. Here, we describe an optimized and accessible device (Spin96) to accommodate up to 96 StageTips, a widely used sample preparation medium enabling efficient and consistent processing of samples prior to LC-MS/MS. We have applied this device to the analysis of human plasma from a clinical trial of IF. In this longitudinal study employing 8-weeks IF, we identified significant abundance differences induced by the IF intervention, including increased apolipoprotein A4 (APOA4) and decreased apolipoprotein C2 (APOC2) and C3 (APOC3). These changes correlated with a significant decrease in plasma triglycerides after the IF intervention. Given that these proteins have a role in regulating apolipoprotein particle metabolism, we propose that IF had a positive effect on lipid metabolism through modulation of HDL particle size and function. In addition, we applied a novel human protein variant database to detect common protein variants across the participants. We show that consistent detection of clinically relevant peptides derived from both alleles of many proteins is possible, including some that are associated with human metabolic phenotypes. Together, these findings illustrate the power of accessible workflows for proteomics analysis of clinical samples to yield significant biological insight.
Publication
Journal: Journal of the American Heart Association
February/18/2019
Abstract
See Article by Ma et al.
Publication
Journal: CMAJ
July/18/2013
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Journal: Epilepsy Research
November/13/2013
Abstract
In antiquity, fasting was a treatment for epilepsy and a rationale for the ketogenic diet (KD). Preclinical data indicate the KD and intermittent fasting do not share identical anticonvulsant mechanisms. We implemented an intermittent fasting regimen in six children with an incomplete response to a KD. Three patients adhered to the combined intermittent fasting/KD regimen for 2 months and four had transient improvement in seizure control, albeit with some hunger-related adverse reactions.
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Publication
Journal: Atherosclerosis
August/21/2020
Abstract
Vascular dementia is the most common neuropsychiatric syndrome and is characterized by synaptic dysfunction, neuroinflammation, and cognitive dysfunction. Vascular dementia is associated with various environmental, genetic, and lifestyle risk factors. Recent research has focused on the association between vascular dementia and dietary patterns, suggesting that dietary regulation leads to better control of energy metabolism, improvements in brain insulin resistance, and the suppression of neuroinflammation. Intermittent fasting is a calorie-restriction method known to be more effective in promoting fat loss and regulating the impairment of glucose metabolism as compared with other dietary restriction regimens. Herein, the authors review the effects of intermittent fasting with regard to vascular dementia based on recent evidence and propose that intermittent fasting could be a therapeutic approach for ameliorating vascular dementia pathology and preventing its onset.
Keywords: Cognitive function; Intermittent fasting; Vascular dementia.
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Publication
Journal: Nutrients
October/22/2021
Abstract
This review examines the effects of two popular intermittent fasting regimens on sleep in adults with overweight and obesity. Specifically, the effects of time restricted eating (TRE; eating all food within a 4-10 h window) and alternate day fasting (ADF; 600 kcal fast day alternated with ad libitum feast day) on sleep quality, sleep duration, sleep latency, sleep efficiency, insomnia severity, and risk of obstructive sleep apnea, will be summarized. The role of weight loss will also be discussed. Results from our review reveal that the majority of these trials produced weight loss in the range of 1-6% from baseline. Sleep quality and sleep duration remained unaltered with TRE and ADF, as assessed by the Pittsburgh Sleep Quality Index (PSQI). The effects of intermittent fasting on sleep latency and sleep efficiency are mixed, with one study showing worsening of these parameters, and others showing no effect. Insomnia severity and the risk of obstructive sleep apnea remained unchanged in the trials assessing these metrics. Taken together, these preliminary findings suggest that TRE and ADF produce mild to moderate weight loss (1-6%) but their effects on sleep remain unclear. Solid conclusions are difficult to establish since participants in the studies had healthy sleep durations and no clinical insomnia at baseline, leaving little room for improvement in these metrics. Moreover, none of the trials were adequately powered to detect statistically significant changes in any measure of sleep. Future well-powered trials, conducted in individuals with diagnosed sleep disturbances, will be necessary to elucidate the effect of these popular diets on sleep.
Keywords: alternate day fasting; insomnia; intermittent fasting; obesity; sleep apnea; sleep duration; sleep quality; time restricted eating.
Publication
Journal: Contemporary Clinical Trials Communications
January/12/2022
Abstract
There is increasing evidence from animal and human studies suggesting that fasting can play a role in disease prevention, weight control and longevity. However, few studies have compared exercise performances in individuals adhering to an intermittent fasting (IF) in comparison to individuals who are not. Given the rising popularity of IF we aim to investigate whether this type eating pattern will improve cardiovascular performance over a period of 12 weeks through VO2 max measurements in participants from a Lebanese community. Additionally, we will study the variation of different health parameters, physical performance and biomarkers potentially affected by IF. Participants will be recruited from a large university community and randomized into 4 arms. Baseline information will be collected from all participants, which includes biological, physical, nutritional, medical and psychological data. Two arms will follow a time-restricted fasting diet with and without physical exercise, one arm will exercise without fasting, and one will act as a control group. Throughout the study, measurements will be repeated, and data analysis will follow to evaluate results.
Keywords: Aerobic exercise; Exercise performance; FATMAX; Health biomarkers; Intermittent fasting; Maximal oxygen consumption; Nutrition; Sports medicine; VO2max; Weight loss.
Publication
Journal: Journal of Neuroinflammation
November/30/2014
Abstract
BACKGROUND
Systemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown.
METHODS
Rats on IF for 30 days received 1 mg/kg of lipopolysaccharide (LPS) or saline intravenously. Half of the rats were subjected to behavioral tests and the other half were euthanized two hours after LPS administration and the hippocampus was dissected and frozen for analyses.
RESULTS
Here, we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-κB activation, suppression of the expression of pro-inflammatory cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS resulted in deficits in cognitive performance in the Barnes maze and inhibitory avoidance tests, without changing locomotor activity, that were ameliorated in rats that had been maintained on the IF diet. IF also resulted in reduced levels of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL-1α, IL-1β and TNF-α levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1β, IFN-γ, RANTES, TNF-α and IL-6 levels.
CONCLUSIONS
Taken together, our results suggest that IF induces adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection.
Publication
Journal: Ageing Research Reviews
August/23/2017
Abstract
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.
Publication
Journal: Epilepsia
October/21/2010
Abstract
OBJECTIVE
Calorie restriction can be anticonvulsant in animal models. The ketogenic diet was designed to mimic calorie restriction and has been assumed to work by the same mechanisms. We challenged this assumption by profiling the effects of these dietary regimens in mice subjected to a battery of acute seizure tests.
METHODS
Juvenile male NIH Swiss mice received ketogenic diet or a normal diet fed in restricted quantities (continuously or intermittently) for ∼12 days, starting at 3-4 weeks of age. Seizures were induced by the 6 Hz test, kainic acid, maximal electroshock, or pentylenetetrazol.
RESULTS
The ketogenic and calorie-restricted diets often had opposite effects depending on the seizure test. The ketogenic diet protected from 6 Hz-induced seizures, whereas calorie restriction (daily and intermittent) increased seizure activity. Conversely, calorie restriction protected juvenile mice against seizures induced by kainic acid, whereas the ketogenic diet failed to protect. Intermittent caloric restriction worsened seizures induced by maximal electroshock but had no effect on those induced by pentylenetetrazol.
CONCLUSIONS
In contrast to a longstanding hypothesis, calorie restriction and the ketogenic diet differ in their acute seizure test profiles, suggesting that they have different underlying anticonvulsant mechanisms. These findings highlight the importance of the 6 Hz test and its ability to reflect the benefits of ketosis and fat consumption.
Publication
Journal: Clinics
December/12/2018
Abstract
Cancer is a leading cause of death worldwide, and its incidence is continually increasing. Although anticancer therapy has improved significantly, it still has limited efficacy for tumor eradication and is highly toxic to healthy cells. Thus, novel therapeutic strategies to improve chemotherapy, radiotherapy and targeted therapy are an important goal in cancer research. Macroautophagy (herein referred to as autophagy) is a conserved lysosomal degradation pathway for the intracellular recycling of macromolecules and clearance of damaged organelles and misfolded proteins to ensure cellular homeostasis. Dysfunctional autophagy contributes to many diseases, including cancer. Autophagy can suppress or promote tumors depending on the developmental stage and tumor type, and modulating autophagy for cancer treatment is an interesting therapeutic approach currently under intense investigation. Nutritional restriction is a promising protocol to modulate autophagy and enhance the efficacy of anticancer therapies while protecting normal cells. Here, the description and role of autophagy in tumorigenesis will be summarized. Moreover, the possibility of using fasting as an adjuvant therapy for cancer treatment, as well as the molecular mechanisms underlying this approach, will be presented.
Publication
Journal: Nutrients
April/20/2019
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 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.
Publication
Journal: Cureus
June/28/2019
Abstract
Intermittent fasting, in which individuals fast periodically, is an increasingly popular weight loss regimen. To understand the short-term effects of such a regimen, we present a case of intermittent fasting with data collection that mimics the single-case design. A healthy but slightly overweight adult male underwent complete fast for two full days and resumed with normal eating for five days, and repeated the cycle three times. Data were collected from three periods: baseline (one week); fasting (three weeks); post-fasting (one week). Measurements taken daily include weight, body fat ratio, temperature, blood pressure, blood glucose, as well as waist and hip circumferences. Blood tests were conducted weekly for safety screening and to obtain observations on lipid profile, high-sensitive C-reactive protein (hsCRP), hemoglobin A1c (HbA1c), and uric acid. The participant lost 1.3 kilograms (kg) in body weight (W̅b = 65.9kg vs W̅p = 64.6kg). Body fat ratio did not differ much (F̅Rb = 19.1% vs F̅Rp = 18.8%). Fasting caused an acute drop in the blood glucose level, which was restored upon resuming normal eating. Total cholesterol dropped drastically immediately after the first fasting cycle but rebounded 15% higher than baseline before dropping down. Fasting also temporarily raised uric acid levels, blood pressure, and body temperature. HbA1c and waist and hip circumferences were not affected by fasting. Improvement in inflammatory marker (hsCRP) was observed (2.0 to 0.3 milligrams per liter, mg/L). This case demonstrates that intermittent fasting can induce short-term weight loss and reduce acute inflammatory marker in a healthy adult, but not body fat ratio and lipid profile. Similar single-case study design can be applied across a practice-based network for inter-case replication.
Publication
Journal: Trends in Endocrinology and Metabolism
July/18/2021
Abstract
Obesity is strongly and independently associated with an increased risk of severe illness and death from coronavirus disease 2019 (COVID-19). The pathophysiological changes that result from elevated body weight lead to metabolic dysfunction, chronic inflammation, impaired immunological responses, and multisystem disorders, which increase vulnerability to severe illness from COVID-19. While vaccination strategies are under way across the world, the second and third waves of the pandemic, along with the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains, continue to threaten the stability of medical systems worldwide. Furthermore, evidence from previous pandemics suggests that vaccines are less effective in obese individuals than in their healthy-weight counterparts over the long term. Therefore, a consideration of lifestyle changes that can boost metabolic health and immunity is critical to reduce the risk of complications and severe illness from viral infection. In this review, we discuss the potential mechanisms linking excess body weight with COVID-19 morbidity. We also present evidence that intermittent fasting (IF), a dietary program that has gained popularity in recent years, may be an effective strategy to improve metabolic health and immunity and thus reduce the impact of obesity on COVID-19 morbidity and mortality.
Keywords: COVID-19; diabetes; immune response; intermittent fasting; obesity.
Publication
Journal: BMC Cardiovascular Disorders
May/29/2019
Abstract
Information on the role of intermittent fasting (IF) on pathologic cardiac remodeling is scarce. We compared the effects of IF before and after myocardial infarction (MI) on rat cardiac remodeling and survival.Wistar rats were intermittently fasted (food available every other day) or fed ad libitum for 12 weeks and then divided into three groups: AL - fed ad libitum; AL/IF - fed AL before MI and IF after MI; and IF - fed IF before and after MI. Echocardiogram was performed before MI and 2 and 12 weeks after surgery. Isolated hearts were evaluated in Langendorff preparations.Before surgery, body weight (BW) was lower in IF than AL. Final BW was lower in AL/IF and IF than AL. Perioperative mortality did not change between AL (31.3%) and IF (27.3%). Total mortality was lower in IF than AL. Before surgery, echocardiographic parameters did not differ between groups. Two weeks after surgery, MI size did not differ between groups. Twelve weeks after MI, left ventricular (LV) diastolic posterior wall thickness was lower in AL/IF and IF than AL. The percentage of variation of echocardiographic parameters between twelve and two weeks showed that MI size decreased in all groups and the reduction was higher in IF than AL/IF. In Langendorff preparations, LV volume at zero end-diastolic pressure (V0; AL: 0.41 ± 0.05; AL/IF: 0.34 ± 0.06; IF: 0.28 ± 0.05 mL) and at 25 mmHg end-diastolic pressure (V25; AL: 0.61 ± 0.05; AL/IF: 0.54 ± 0.07; IF: 0.44 ± 0.06 mL) was lower in AL/IF and IF than AL and V25 was lower in IF than AL/IF. V0/BW ratio was lower in IF than AL and LV weight/V0 ratio was higher in IF than AL. Myocyte diameter was lower in AL/IF and IF than AL (AL: 17.3 ± 1.70; AL/IF: 15.1 ± 2.21; IF: 13.4 ± 1.49 μm). Myocardial hydroxyproline concentration and gene expression of ANP, Serca 2a, and α- and β-myosin heavy chain did not differ between groups.Intermittent fasting initiated before or after MI reduces myocyte hypertrophy and LV dilation. Myocardial fibrosis and fetal gene expression are not modulated by feeding regimens. Benefit is more evident when intermittent fasting is initiated before rather than after MI.
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