Intermittent Fasting and Human Metabolic Health

ArticleinJournal of the American Academy of Nutrition and Dietetics 115(8) · April 2015with 9,765 Reads
Cite this publication
Abstract
Periods of voluntary abstinence from food and drink (i.e., intermittent fasting) has been practiced since earliest antiquity by peoples around the globe. Books on ethnology and religion describe a remarkable variety of fasting forms and practices.1 Renewed interest in fasting regimens is evidenced by a plethora of popular press publications and diet recommendations. For example, in 2013, Mosley and Spencer published a best-selling book titled “The Fast Diet,” which touts the benefits of restricting energy intake severely for two days a week while eating normally the rest of the week.2 Dozens of books promote various fasting dietary patterns and the web offers hundreds of fasting-related sites. However, scientific evidence for the health benefits of intermittent fasting in humans is often extrapolated from animal studies, based on observational data on religious fasting (particularly Ramadan), or derived from experimental studies with modest sample sizes. The overall objective of this paper is to provide an overview of intermittent fasting regimens (Table 1) and summarize the evidence on the health benefits of intermittent fasting with a focus on human intervention studies. Because much of the data on intermittent fasting is from research in animal models, we briefly summarize key rodent studies and reviews. Health outcomes of interest are changes in weight and metabolic parameters associated with type 2 diabetes, cardiovascular disease, and cancer. We also present an overview of the major mechanisms hypothesized to link fasting regimens with human health: (1) circadian biology, (2) the gastrointestinal microbiota, and (3) modifiable lifestyle behaviors such as diet, activity, and sleep. Finally, we present conclusions regarding the evidence-base for intermittent fasting as an intervention for improving human health and propose a research agenda. Table 1 Types of intermittent fasting regimens that are hypothesized to impact health outcomes This paper provides a uniquely broad synthesis of the scientific evidence linking intermittent fasting with human health and a framework for future research on this topic.

Do you want to read the rest of this article?

Request full-text
Request Full-text Paper PDF
  • Article
    Mechanistic studies suggest benefits of intermittent calorie restriction (ICR) in chronic disease prevention that may exceed those of continuous calorie restriction (CCR), even at equal net calorie intake. Despite promising results from first trials, it remains largely unknown whether ICR-induced metabolic alterations reported from experimental studies can also be observed in humans, and whether ICR diets are practicable and effective in real life situations. Thus, we initiated the HELENA Trial to test the effects of ICR (eu-caloric diet on five days and very low energy intake on two days per week) on metabolic parameters and body composition over one year. We will assess the effectiveness of ICR compared to CCR and a control diet over a 12-week intervention, 12-week maintenance phase and 24-week follow-up in 150 overweight or obese non-smoking adults (50 per group, 50% women). Our primary endpoint is the difference between ICR and CCR with respect to fold-changes in expression levels of 82 candidate genes in abdominal subcutaneous adipose tissue biopsies (SATb) during the intervention phase. The candidate genes represent pathways, which may link obesity-related metabolic alterations with the risk for major chronic diseases. In secondary and exploratory analyses, changes in metabolic, hormonal, inflammatory and metagenomic parameters measured in different biospecimens (SATb, blood, urine, stool) are investigated and effects of ICR/CCR/control on imaging-based measures of subcutaneous, visceral and hepatic fat are evaluated. Our study is the first randomized trial over one year testing the effects of ICR on metabolism, body composition and psychosocial factors in humans.
  • Article
    Background: Menopause is associated with significant hormonal changes that result in increased total body fat and abdominal fat, amplifying the risk for metabolic syndrome and diseases such as diabetes, cardiovascular disease and cancer in postmenopausal women. Intermittent fasting regimens hold significant health benefit promise for obese humans, however, regimens that include extreme daytime calorie restriction or daytime fasting are generally associated with hunger and irritability, hampering long-term compliance and adoption in the clinical setting. Time-restricted feeding (TRF), a regimen allowing eating only during a specific period in the normal circadian feeding cycle, without calorie restriction, may increase compliance and provide a more clinically viable method for reducing the detrimental metabolic consequences associated with obesity. Methods: We tested TRF as an intervention in a mouse model of postmenopausal obesity. Metabolic parameters were measured using Clinical Laboratory Animal Monitoring System (CLAMS) and we carried out glucose tolerance tests. We also stained liver sections with oil red O to examine steatosis and measured gene expression related to gluconeogenesis. Results: Preexisting metabolic disease was significantly attenuated during 7 weeks of TRF. Despite having access to the same high fat diet (HFD) as ad libitum fed (ALF) mice, TRF mice experienced rapid weight loss followed by a delayed improvement in insulin resistance and a reduced severity of hepatic steatosis by having access to the HFD for only 8h during their normal nocturnal feeding period. The lower respiratory exchange ratio in the TRF group compared with the ALF group early in the dark phase suggested that fat was the predominant fuel source in the TRF group and correlated with gene expression analyses that suggested a switch from gluconeogenesis to ketogenesis. In addition, TRF mice were more physically active than ALF fed mice. Conclusions: Our data support further analysis of TRF as a clinically viable form of intermittent fasting to improve metabolic health due to obesity.
  • Article
    Meta-analyses often find similarities in tolerance between first and second generation antipsychotics. In terms of major barriers to treatment adherence, the extrapyramidal symptoms associated with the first generation antipsychotics have be replaced by the devastating association of weight gain and metabolic syndrome. Dietary and exercise prescriptions are currently being recommended for patients beginning treatment with atypical antipsychotics, although the details of this intervention are often left unclear. Intermittent fasting through time-restricted feeding windows is a practical lifestyle modification that has been shown to increase insulin sensitivity, prevent obesity and decrease risk of type II diabetes, thus making it a useful tool in the prevention of common metabolic issues surrounding atypical antipsychotics. In this review, we have combined the findings from the CATIE and CUtLASS trials with recent research on intermittent fasting and submit that the effectiveness of atypical antipsychotics may be enhanced via reductions in metabolic abnormalities associated with their usage. Our aim is to highlight intermittent fasting as a supplemental protocol to combat the metabolic consequences most prevalent with antipsychotics and to outline a prescription of how to utilize intermittent fasting in this patient population.
  • Article
    While activation of beige thermogenesis is a promising approach for treatment of obesity-associated diseases, there are currently no known pharmacological means of inducing beiging in humans. Intermittent fasting is an effective and natural strategy for weight control, but the mechanism for its efficacy is poorly understood. Here, we show that an every-other-day fasting (EODF) regimen selectively stimulates beige fat development within white adipose tissue and dramatically ameliorates obesity, insulin resistance, and hepatic steatosis. EODF treatment results in a shift in the gut microbiota composition leading to elevation of the fermentation products acetate and lactate and to the selective upregulation of monocarboxylate transporter 1 expression in beige cells. Microbiota-depleted mice are resistance to EODF-induced beiging, while transplantation of the microbiota from EODF-treated mice to microbiota-depleted mice activates beiging and improves metabolic homeostasis. These findings provide a new gut-microbiota-driven mechanism for activating adipose tissue browning and treating metabolic diseases.
  • Article
    Importance: Rodent studies demonstrate that prolonged fasting during the sleep phase positively influences carcinogenesis and metabolic processes that are putatively associated with risk and prognosis of breast cancer. To our knowledge, no studies in humans have examined nightly fasting duration and cancer outcomes. Objective: To investigate whether duration of nightly fasting predicted recurrence and mortality among women with early-stage breast cancer and, if so, whether it was associated with risk factors for poor outcomes, including glucoregulation (hemoglobin A1c), chronic inflammation (C-reactive protein), obesity, and sleep. Design, setting, and participants: Data were collected from 2413 women with breast cancer but without diabetes mellitus who were aged 27 to 70 years at diagnosis and participated in the prospective Women's Healthy Eating and Living study between March 1, 1995, and May 3, 2007. Data analysis was conducted from May 18 to October 5, 2015. Exposures: Nightly fasting duration was estimated from 24-hour dietary recalls collected at baseline, year 1, and year 4. Main outcomes and measures: Clinical outcomes were invasive breast cancer recurrence and new primary breast tumors during a mean of 7.3 years of study follow-up as well as death from breast cancer or any cause during a mean of 11.4 years of surveillance. Baseline sleep duration was self-reported, and archived blood samples were used to assess concentrations of hemoglobin A1c and C-reactive protein. Results: The cohort of 2413 women (mean [SD] age, 52.4 [8.9] years) reported a mean (SD) fasting duration of 12.5 (1.7) hours per night. In repeated-measures Cox proportional hazards regression models, fasting less than 13 hours per night (lower 2 tertiles of nightly fasting distribution) was associated with an increase in the risk of breast cancer recurrence compared with fasting 13 or more hours per night (hazard ratio, 1.36; 95% CI, 1.05-1.76). Nightly fasting less than 13 hours was not associated with a statistically significant higher risk of breast cancer mortality (hazard ratio, 1.21; 95% CI, 0.91-1.60) or a statistically significant higher risk of all-cause mortality (hazard ratio, 1.22; 95% CI, 0.95-1.56). In multivariable linear regression models, each 2-hour increase in the nightly fasting duration was associated with significantly lower hemoglobin A1c levels (β = -0.37; 95% CI, -0.72 to -0.01) and a longer duration of nighttime sleep (β = 0.20; 95% CI, 0.14-0.26). Conclusions and relevance: Prolonging the length of the nightly fasting interval may be a simple, nonpharmacologic strategy for reducing the risk of breast cancer recurrence. Improvements in glucoregulation and sleep may be mechanisms linking nightly fasting with breast cancer prognosis.
  • Article
    Full-text available
    The National Cancer Institute (NCI) and the National Institutes of Health (NIH) Office of Disease Prevention held a workshop titled, “Extending Methods in Dietary Patterns Research”, in May of 2016. The workshop’s goal was to articulate, refine, and prioritize methodological questions to advance the science of dietary patterns in epidemiological research. Although the focus was on how to improve methods for assessing the relationship between dietary patterns and cancer risk, many, if not all, of the discussions and conclusions are relevant for other health outcomes as well. Recognizing that dietary intake is both multidimensional (i.e., it is a complex, multi-layered exposure and behavior) and dynamic (i.e., it varies over time and the life course), workshop presenters and participants discussed methodological advances required to include these concepts in dietary patterns research. This commentary highlights key needs that were identified to extend methods in dietary patterns research by integrating multidimensionality and dynamism into how dietary patterns are measured and defined, and how relationships with dietary patterns and health outcomes are modeled.
  • Article
    Full-text available
    A growing body of evidence suggests that meal timing is an important factor for metabolic regulation and that the circadian clock tightly interacts with metabolic functions. The proper functioning of the circadian clock is critical for maintaining metabolic health. Therefore, chrononutrition, a novel discipline which investigates the relation between circadian rhythms, nutrition, and metabolism, has attracted increasing attention in recent years. Circadian rhythms are strongly affected by obesity, type 2 diabetes, and other dietary-induced metabolic diseases. With increasing age, the circadian system also undergoes significant changes which contribute to the dysregulation of metabolic rhythms. Metabolic diseases are a major health concern, particularly in light of a growing aging population, and effective approaches for their prevention and treatment are urgently needed. Recently, animal studies have impressively shown beneficial effects of several dietary patterns (e.g., caloric restriction or time-restricted feeding) on circadian rhythms and metabolic outcomes upon nutritional challenges. Whether these dietary patterns show the same beneficial effects in humans is, however, less well studied. As indicated by recent studies, dietary approaches might represent a promising, attractive, and easy-to-adapt strategy for the prevention and therapy of circadian and metabolic disturbances in humans of different age.
  • Article
    Aims: To establish whether the risk of hypoglycaemia is greater with 2 consecutive days of very-low-calorie diet compared with 2 non-consecutive days of very-low-calorie diet in people with Type 2 diabetes. Methods: This was a non-blinded randomized parallel group interventional trial of intermittent fasting in adults. The participants had a BMI of 30-45 kg/m2 , Type 2 diabetes treated with metformin and/or hypoglycaemic medications and an HbA1c concentration of 50-86 mmol/mol (6.7-10%). The participants followed a 2092-2510-kJ diet on 2 days per week for 12 weeks. A total of 41 participants were randomized 1:1 to consecutive (n=19) or non-consecutive (n=22) day fasts, of whom 37 (n=18 and n=19, respectively) were included in the final analysis. The primary outcome was difference in the rate of hypoglycaemia between the two study arms. Secondary outcomes included change in diet, quality of life, weight, lipid, glucose and HbA1c levels, and liver function. Results: The mean hypoglycaemia rate was 1.4 events over 12 weeks. Fasting increased the rate of hypoglycaemia despite medication reduction (relative rate 2.05, 95% CI 1.17 to 3.52). There was no difference between fasting on consecutive days and fasting on non-consecutive days (relative rate 1.54, 95% CI 0.35 to 6.11). Improvements in weight, HbA1c , fasting glucose and quality of life were experienced by participants in both arms. Conclusions: In individuals with Type 2 diabetes on hypoglycaemic medications, fasting of any type increased the rate of hypoglycaemia. With education and medication reduction, fewer than expected hypoglycaemic events occurred. Although it was not possible to determine whether fasting on consecutive days increased the risk of hypoglycaemia, an acceptable rate was observed in both arms. This article is protected by copyright. All rights reserved.
  • Article
    Full-text available
    Background: Peroxisome proliferator-activated receptor alpha (PPARA) is a major regulator of fatty acid oxidation and severe hepatic steatosis occurs during acute fasting in Ppara-null mice. Thus, PPARA is considered an important mediator of the fasting response; however, its role in other fasting regiments such as every-other-day fasting (EODF) has not been investigated. Methods: Mice were pre-conditioned using either a diet containing the potent PPARA agonist Wy-14643 or an EODF regimen prior to acute fasting. Ppara-null mice were used to assess the contribution of PPARA activation during the metabolic response to EODF. Livers were collected for histological, biochemical, qRT-PCR, and Western blot analysis. Results: Acute fasting activated PPARA and led to steatosis, whereas EODF protected against fasting-induced hepatic steatosis without affecting PPARA signaling. In contrast, pretreatment with Wy-14,643 did activate PPARA signaling but did not ameliorate acute fasting-induced steatosis and unexpectedly promoted liver injury. Ppara ablation exacerbated acute fasting-induced hypoglycemia, hepatic steatosis, and liver injury in mice, whereas these detrimental effects were absent in response to EODF, which promoted PPARA-independent fatty acid metabolism and normalized serum lipids. Conclusions: These findings indicate that PPARA activation prior to acute fasting cannot ameliorate fasting-induced hepatic steatosis, whereas EODF induced metabolic adaptations to protect against fasting-induced steatosis without altering PPARA signaling. Therefore, PPARA activation does not mediate the metabolic adaptation to fasting, at least in preventing acute fasting-induced steatosis.
  • Chapter
    Full-text available
    The dramatic increase in obesity within one or two generations cannot possibly be due to a change in genetics. It is the processing, distribution, and availability of foods that have changed, not the brain. For most people, in the presence of pleasant tasting (high calorie) foods, the brain’s reward circuitry overwhelms the satiety signals. For 2 million years, overeating (on the occasional basis when that was possible) had adaptive value, and it has only been since the rise of an omnipresent obesogenic environment that such behavior has become maladaptive, resulting in widespread obesity. Long-term weight loss is, at minimum, a two-part process: (1) initial weight loss and (2) relapse prevention. All weight loss programs (diet, pharmacology, or surgical) work in the short run, but none used alone have proven widely effective in the long term. After initial weight loss, relapse is common because until recently interventions failed to consider our evolutionary history and thus have underestimated the sensory/reward aspects of feeding behavior. Strongly heritable behavioral characteristics that differentiate obesity-prone individuals from others (e.g., food cue responsiveness, satiety responsiveness) have now been identified and can potentially be targeted to help people learn how to better interact with an obesogenic environment. In actuality, the brain is reacting to present-day environmental stimuli exactly in the manner in which it evolved during 2 million years of environmental selective pressures since the appearance of the genus Homo [23]. Considerable evidence has accrued that in obesity-prone individuals, it is the reward circuitry of the brain, not the hypothalamic homeostatic nuclei, that developed during human evolution which control feeding behavior when there is an abundance of good-tasting foods [21]. As expected, initial brain fMRI studies found activation of hypothalamic nuclei in response to changes in glucose and insulin levels [32–34]. However, more recent brain fMRI studies also reveal hyperactivation of the cortico-limbic-striatal structures in the reward circuitry of obese children and adults in response to pleasant food stimuli (see Refs. [35–37] for reviews). Genetically obesity-prone children display hyperactivation of the reward circuitry before they become obese [38, 39]. Previously obese adults who have dieted and lost their excess weight continue to show hyperactivity in the reward circuits in response to food [40]. It must be noted that brain fMRI studies of obesity are still in their initial stages, and attempts to identify the specific reward circuitry associated with obesity are inconsistent [37].
  • Article
    Full-text available
    Globally, the aging population is growing rapidly, creating an urgent need to attenuate age-related health conditions, including metabolic disease and disability. A promising strategy for healthy aging based on consistently positive results from studies with a variety of species, including non-human primates (NHP), is calorie restriction (CR), or the restriction of energy intake while maintaining intake of essential nutrients. The burgeoning evidence for this approach in humans is reviewed and the major study to date to address this question, CALERIE (Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy), is described. CALERIE findings indicate the feasibility of CR in non-obese humans, confirm observations in NHP, and are consistent with improvements in disease risk reduction and potential anti-aging effects. Finally, the mechanisms of CR in humans are reviewed which sums up the fact that evolutionarily conserved mechanisms mediate the anti-aging effects of CR. Overall, the prospect for further research in both NHP and humans is highly encouraging.
  • Article
    Full-text available
    Data from epidemiological and experimental studies have shown that diet and eating patterns have a major role in the pathogenesis of many age-associated diseases. Since 1935, calorie restriction (CR) has been identified as one of the most effective nongenetic dietary interventions that can increase lifespan. It involves reducing calorie intake by about 20%–40% below ad libitum, without malnutrition. Restricting food intake has been observed to increase lifespan and prevent many age-associated diseases in rats, mice, and many other species. Understanding the metabolic, molecular, and cellular mechanisms involved in the anti-aging effects of CR can help us to find dietary interventions that can mimic its effects. Recently, different studies have shown that intermittent fasting, protein restriction, and an epigenetic diet can have similar effects to those of CR. These approaches were selected because it has been indicated that they act through a similar molecular pathway and also, are safe and effective in delaying or preventing diseases. In this review, we focus on the mechanistic pathway involved in CR. Then, we review the mimicking interventions through the mechanistic approach. For this purpose, we reviewed both animal and human articles, mainly available through the PubMed online database. We then selected the most relevant full texts which are summarized in this article.
  • Article
    Objective: 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). Methods: Adults with obesity (BMI ≥30 kg/m(2) , age 18-55) were randomized to either zero-calorie ADF (n = 14) or CR (-400 kcal/day, n = 12) for 8 weeks. Outcomes were measured at the end of the 8-week intervention and after 24 weeks of unsupervised follow-up. Results: No adverse effects were attributed to ADF, and 93% completed the 8-week ADF protocol. At 8 weeks, ADF achieved a 376 kcal/day greater energy deficit; however, there were no significant between-group differences in change in weight (mean ± SE; ADF -8.2 ± 0.9 kg, CR -7.1 ± 1.0 kg), body composition, lipids, or Si. After 24 weeks of unsupervised follow-up, there were no significant differences in weight regain; however, changes from baseline in % fat mass and lean mass were more favorable in ADF. Conclusions: ADF is a safe and tolerable approach to weight loss. ADF produced similar changes in weight, body composition, lipids, and Si at 8 weeks and did not appear to increase risk for weight regain 24 weeks after completing the intervention.
  • Article
    Full-text available
    Carbohydrates (e.g., glucose) and lipids (e.g., free fatty acids or FFAs) are the most important sources of energy for most organisms, including humans. Lipoprotein lipase (LPL) is an extracellular enzyme (EC 3.1.1.34) that is essential in lipoprotein metabolism. LPL is a glycoprotein that is synthesized and secreted in several tissues (e.g., adipose tissue, skeletal muscle, cardiac muscle, and macrophages). At the luminal surface of the vascular endothelium (site of the enzyme action), LPL hydrolyzes triglyceride-rich lipoproteins (e.g., chylomicrons, very lowdensity lipoproteins), providing FFAs and glycerol for tissue use. Therefore, LPL plays a key metabolic role in providing substrates for lipogenesis and lipid storage, and in supplying immediate energy for different tissues. Knowledge about this enzyme has greatly increased over the past decade. A detailed understanding of the fascinating, although complex, apparatus by which LPL exerts its catalytic activity in the turbulent bloodstream is just one of the examples. Additionally, interest in LPL activity has been reinforced by its pathophysiological relevance in chronic degenerative diseases such as dyslipidemia, obesity, type 2 diabetes mellitus, and Alzheimer's disease, and in other contexts of disordered lipid metabolism such as severe hypertriglyceridemia and the (potentially) associated acute pancreatitis as well as in non-alcoholic fatty liver disease. This work aimed at critically reviewing the current knowledge of historical, terminological, biochemical, pathophysiological, and therapeutic aspects of human LPL activity.
  • Article
    Full-text available
    Intermittent fasting, whose proposed benefits include the improvement of lipid profile and the body weight loss, has gained considerable scientific and popular repercussion. This review aimed to consolidate studies that analyzed the lipid profile in humans before and after intermittent fasting period through a detailed review; and to propose the physiological mechanism, considering the diet and the body weight loss. Normocaloric and hypocaloric intermittent fasting may be a dietary method to aid in the improvement of the lipid profile in healthy, obese and dyslipidemic men and women by reducing total cholesterol, LDL, triglycerides and increasing HDL levels. However, the majority of studies that analyze the intermittent fasting impacts on the lipid profile and body weight loss are observational based on Ramadan fasting, which lacks large sample and detailed information about diet. Randomized clinical trials with a larger sample size are needed to evaluate the IF effects mainly in patients with dyslipidemia.
  • Article
    Full-text available
    In the present scenario, the literature is available regarding different challenging matters; however, some horizons still need to be elucidated and “Intermittent Fasting” is one of such examples. For millennia, several scientific interventions were carried out to probe the effect of fasting on human metabolic activities. There are three common strategies of fasting like caloric restriction (CR), dietary restriction (DR) and Intermittent fasting (IF) but IF has emerged as an avenue of potential benefit and wellbeing of the consumer. Intermittent fasting is the prehistoric surreptitious of human health as this powerful habit has been virtually forgotten. Nowadays, numerous researchers are reviving this dietary intervention. It carries enormous consequences such as increased energy, weight loss, and reversal of type-II diabetes. Moreover, it encloses the important evidence validating the health claims of IF with special reference to cancer, coronary heart diseases, biomarkers of oxidative stress and insulin sensitivity. Conclusively, the impact of intermittent fasting on human health based upon metabolic case studies are the limelight of the current manuscript.
  • Article
    Full-text available
    Background & Objective: Islamic fasting is observed by millions of Muslims across the world during the holy month of Ramadan and other specific days of the lunar year. Fasting Muslims abstain from eating and drinking from dawn until sunset. Depending on season and geographical location, Muslims maintain fasting for approximately 13-18 hours per day. The present study aimed to review the benefits of Islamic fasting. Materials and Methods: This literature review was conducted via searching in databases like Medline, PubMed, PMC, Google Scholar, ScienceDirect, and reference lists of relevant articles using keywords like health benefits, Islamic fasting, intermittent fasting, alternate-day fasting, time-restricted feeding, and Ramadan intermittent fasting. Results: Islamic fasting could be considered as intermittent fasting as it is similar to alternate-day fasting and time-restricted feeding. Intermittent fasting is associated with numerous health benefits. Conclusion: According to this review, some of the main health benefits of Islamic fasting include weight loss, attenuation of metabolic markers (e.g., insulin resistance, blood glucose, and blood pressure), improved lipid profile, prevention of chronic problems (e.g., obesity, diabetes, cardiovascular diseases, and cancer), protection against neurodegeneration, and diminished inflammation.
  • Article
    Full-text available
    Intermittent fasting (IF) is an effective dietary intervention to counteract obesity-associated metabolic abnormalities. Previously, we and others have highlighted white adipose tissue (WAT) browning as the main underlying mechanism of IF-mediated metabolic benefits. However, whether IF retains its efficacy in different models, such as genetically obese/diabetic animals, is unknown. Here, leptin-deficient ob/ob mice were subjected to 16 weeks of isocaloric IF, and comprehensive metabolic phenotyping was conducted to assess the metabolic effects of IF. Unlike our previous study, isocaloric IF-subjected ob/ob animals failed to exhibit reduced body weight gain, lower fat mass, or decreased liver lipid accumulation. Moreover, isocaloric IF did not result in increased thermogenesis nor induce WAT browning in ob/ob mice. These findings indicate that isocaloric IF may not be an effective approach for regulating body weight in ob/ob animals, posing the possible limitations of IF to treat obesity. However, despite the lack of improvement in insulin sensitivity, isocaloric IF-subjected ob/ob animals displayed improved glucose tolerance as well as higher postprandial insulin level, with elevated incretin expression, suggesting that isocaloric IF is effective in improving nutrient-stimulated insulin secretion. Together, this study uncovers the insulinotropic effect of isocaloric IF, independent of adipose thermogenesis, which is potentially complementary for the treatment of type 2 diabetes.
  • Preprint
    Full-text available
    Restricted feeding is well known to affect expression profiles of both clock and metabolic genes. However, it is unknown whether these changes in metabolic gene expression result from changes in the molecular clock or in feeding behavior. Here we eliminated the daily rhythm in feeding behavior by providing 6-meals evenly distributed over the light/dark-cycle. Animals on this 6-meals-a-day feeding schedule retained the normal day/night difference in physiological parameters including body temperature and locomotor activity. The daily rhythm in respiratory exchange ratio (RER), however, was significantly phase-shifted through increased utilization of carbohydrates during the light phase and increased lipid oxidation during the dark phase. This 6-meals-a-day feeding schedule did not have a major impact on the clock gene expression rhythms in the master clock but did have mild effects on peripheral clocks. By contrast, genes involved in glucose and lipid metabolism showed differential expression. Concluding, eliminating the daily rhythm in feeding behavior in rats does not affect the master clock and only mildly affects peripheral clocks, but disturbs metabolic rhythms in liver, skeletal muscle and brown adipose tissue in a tissue-dependent manner. Thereby a clear daily rhythm in feeding behavior strongly regulates timing of peripheral metabolism, separately from circadian clocks.
  • Article
    Full-text available
    Restricted feeding is well known to affect expression profiles of both clock and metabolic genes. However, it is unknown whether these changes in metabolic gene expression result from changes in the molecular clock or in feeding behavior. Here we eliminated the daily rhythm in feeding behavior by providing 6 meals evenly distributed over the light/dark-cycle. Animals on this 6-meals-a-day feeding schedule retained the normal day/night difference in physiological parameters including body temperature and locomotor activity. The daily rhythm in respiratory exchange ratio (RER), however, was significantly phase-shifted through increased utilization of carbohydrates during the light phase and increased lipid oxidation during the dark phase. This 6-meals-a-day feeding schedule did not have a major impact on the clock gene expression rhythms in the master clock, but did have mild effects on peripheral clocks. In contrast, genes involved in glucose and lipid metabolism showed differential expression. In conclusion, eliminating the daily rhythm in feeding behavior in rats does not affect the master clock and only mildly affects peripheral clocks, but disturbs metabolic rhythms in liver, skeletal muscle and brown adipose tissue in a tissue-dependent manner. Thereby, a clear daily rhythm in feeding behavior strongly regulates timing of peripheral metabolism, separately from circadian clocks.
  • Article
    Full-text available
    Özet: Bu çalışmada, dünyada görülme sıklığı artan inflamatuvar bağırsak hastalıklarının (İBH) bir tanesi olan Ülseratif kolit (ÜK) hastalığının Wistar albino türü ratlarda deneysel oluşumu üzerine beslenme şekli ve sıklığının karşılaştırmalı olarak araştırılması amaçlanmıştır. Bu amaçla; Kontrol (n=7), Kolit (n=7), Kolit-Yüksek Karbonhidratlı Diyet (K-YKD) (n=7), Kolit–Yüksek Karbonhidratlı Aralıklı Diyet (K-YKAD) (n=7), Kolit–Yüksek Yağlı Diyet (K-YYD) (n=7), Kolit-Yüksek Yağlı Aralıklı Diyet (K-YYAD) (n=7) olacak şekilde çalışma grupları oluşturuldu. Gruplardan aralıklı besleme gruplarına haftada sadece 2 gün (ardarda olmayan) diyet verilmesine 24 saat ara verildi. 7 haftalık beslemeden sonra deneysel kolit modeli; kolit ve tedavi gruplarındaki (Kolit, K-YKD, K-YKAD, K-YYD, K-YYAD) ratlara anestezi altında 30o trendelenburg pozisyonunda 8 mm’lik kateterin rektal yoldan 8 cm ileriye asetik asidin (pH 2.4, % 4) intrarektal (i.r.) olarak uygulanması ile oluşturuldu. 72 saat sonra ratlar sakrifiye edilerek histopatolojik örnekler %10 tamponlu formaldehite alındı. Histopatolojik incelemelere göre asetik asitin ciddi kolit hasarlarına neden olduğu buna karşın aralıklı olarak verilen diyet gruplarında bu hasarların oldukça minimal düzeyde kaldığı görülmüştür. Sonuç olarak kolit modelinde aralıklı diyet uygulamasının olumlu etkileri olduğu kanısına varıldı. Anahtar Kelimeler: Yüksek Karbonhidratlı, Yağlı ve Aralıklı Diyet, Kolit, Rat. Effect of High Carbohydrate, Fat and Intermittent Fasting Diet on Experimental Ulcerative Colitis Abstract: In this study, it was aimed to comparatively investigate the effect of diet type and feeding frequency on occurence of experimental ulcerative colitis (UC), in Wistar albino rats. For this purpose, 7 rats were randomly selected and 6 groups were formed as Control (n=7), Colitis (n=7), Colitis-High Carbohydrate Diet (C-HCD) (n=7), Colitis - High Carbohydrate Diet with Intermittent Feeding (CHCIFD) (n=7), Colitis -High Fat Diet (C-HFD) (n=7), Colitis-High Fat Diet with Intermittent Feeding (C-HFIFD) (n=7). In intermittent feeding groups the feeding was interrupted twice in a week for 24 hours . After 7 weeks of feeding, experimental colitis model was induced in colitis and treatment groups rats by intrarectal administration of acetic acid (pH 2.4, 4 %). After the 72 hours rats were sacrificed and colon samples were taken into 10% formalin solution. Histopathological studies have shown that acetic acid caused severe colitis damage, whereas the damage remained at minimal levels in groups with intermittent feeding. As a result, it was concluded that intermittent feeding administration in the colitis model had positive effects. Keywords: High Carbohydrate, Fat and Intermittent Fasting Diet, Colitis, Rat.
  • Article
    Full-text available
    Caloric restriction and intermittent fasting are emerging therapeutic strategies against obesity, insulin resistance and their complications. However, the effectors that drive this response are not completely defined. Here we identify arginase 2 (Arg2) as a fasting-induced hepatocyte factor that protects against hepatic and peripheral fat accumulation, hepatic inflammatory responses, and insulin and glucose intolerance in obese murine models. Arg2 is upregulated in fasting conditions and upon treatment with the hepatocyte glucose transporter inhibitor trehalose. Hepatocyte-specific Arg2 overexpression enhances basal thermogenesis, and protects from weight gain, insulin resistance, glucose intolerance, hepatic steatosis and hepatic inflammation in diabetic mouse models. Arg2 suppresses expression of the regulator of G-protein signalling (RGS) 16, and genetic RGS16 reconstitution reverses the effects of Arg2 overexpression. We conclude that hepatocyte Arg2 is a critical effector of the hepatic glucose fasting response and define a therapeutic target to mitigate the complications of obesity and non-alcoholic fatty liver disease.
  • Article
    Full-text available
    Muslim hemodialysis (HD) patients are motivated to practice fasting in Ramadan. Health-care providers may be unable to make a recommendation based on lack of evidence. The aim of the present study was to investigate patients’ and medical professionals’ opinion toward fasting in 4 HD centers in Egypt as well as the impact of physicians’ attitude on their patient behavior.
  • Article
    Despite major improvements in the treatment of patients with diabetes mellitus, many patients still suffer from progressive diabetic kidney disease. More research is needed to improve treatment and to understand why some patients develop complications while others do not. Mitochondrial dysfunction has turned out to be central to the pathogenesis of diabetes, and we will review some new aspects in this field and the potential for treatment. The conventional theory has been that the intracellular surplus of glucose leads to mitochondrial overproduction of superoxide that contributes to general cell damage and activation of deleterious pathways specific for diabetes complications. However, recent data suggests that reduced mitochondrial activity could be the basis for disease progression and complications through increased inflammation and pro-fibrotic factors. Physical exercise is a very strong stimulus to mitochondrial biogenesis, and we now understand many of the underlying signaling pathways. Clinical trials have also shown that training, especially high-intensity training, can delay the onset of diabetes and improve insulin resistance. Furthermore, intermittent fasting and various pharmacological agents are other potential options for stimulating mitochondrial function and reducing the risk of development and progression of diabetic kidney disease.
  • Article
    Aims/hypothesis Ketones may be regarded as a thrifty fuel for peripheral tissues, but their clinical prognostic significance remains unclear. We investigated the association between spontaneous fasting ketonuria and incident diabetes in conjunction with changes in metabolic variables in a large population-based observational study. Methods We analysed 8703 individuals free of diabetes at baseline enrolled in the Korean Genome and Epidemiology Study, a community-based 12 year prospective study. Individuals with (n = 195) or without fasting ketonuria were matched 1:4 by propensity score. Incident diabetes was defined as fasting plasma glucose ≥7.0 mmol/l, post-load 2 h glucose ≥11.1 mmol/l on biennial OGTTs, or current use of glucose-lowering medication. Using Cox regression models, HRs for developing diabetes associated with the presence of ketonuria at baseline were analysed. Results Over 12 years, of the 925 participants in the propensity score-matched cohort, 190 (20.5%) developed diabetes. The incidence rate of diabetes was significantly lower in participants with spontaneous ketonuria compared with those without ketonuria (HR 0.63; 95% CI 0.41, 0.97). Results were virtually identical when participants with fasting ketonuria were compared against all participants without ketonuria (after multivariate adjustment, HR 0.66; 95% CI 0.45, 0.96). During follow-up, participants with baseline ketonuria maintained lower post-load 1 h and 2 h glucose levels and a higher insulinogenic index despite comparable baseline values. Conclusions/interpretation The presence of spontaneous fasting ketonuria was significantly associated with a reduced risk of diabetes, independently of metabolic variables. Our findings suggest that spontaneous fasting ketonuria may have a potential preventive role in the development of diabetes.
  • Chapter
    The ageing trajectory is plastic and can be slowed down by lifestyle factors, including good nutrition, adequate physical activity and avoidance of smoking. In humans, plant-based diets such as the Mediterranean dietary pattern are associated with healthier ageing and lower risk of age-related disease, whereas obesity accelerates ageing and increases the likelihood of most common complex diseases including CVD, T2D, dementia, musculoskeletal diseases and several cancers. As yet, there is only weak evidence in humans about the molecular mechanisms through which dietary factors modulate ageing but evidence from cell systems and animal models suggest that it is probable that better dietary choices influence all 9 hallmarks of ageing. It seems likely that better eating patterns retard ageing in at least two ways including (i) by reducing pervasive damaging processes such as inflammation, oxidative stress/redox changes and metabolic stress and (ii) by enhancing cellular capacities for damage management and repair. From a societal perspective, there is an urgent imperative to discover, and to implement, cost-effective lifestyle (especially dietary) interventions which enable each of us to age well, i.e. to remain physically and socially active and independent and to minimise the period towards the end of life when individuals suffer from frailty and multi-morbidity.
  • Article
    Intermittent fasting (IMF) is a relatively new dietary approach to weight management although the efficacy and adverse effects have not been full elucidated and the optimal diets for IMF are unknown. We tested the hypothesis that a one-meal-per-day intermittent fasting with high fat (HF) or protein (HP) diets can modify energy, lipid, and glucose metabolism in normal young male Sprague–Dawley rats with diet-induced obesity or overweight. Male rats aged 5 weeks received either HF (40% fat) or HP (26% protein) diets ad libitum (AL) or for 3 h at the beginning of the dark cycle (IMF) for 5 weeks. Epidydimal fat pads and fat deposits in the leg and abdomen were lower with HP and IMF. Energy expenditure at the beginning of the dark cycle, especially from fat oxidation, was higher with IMF than AL, possibly due to greater activity levels. Brown fat content was higher with IMF. Serum ghrelin levels were higher in HP-IMF than other groups and accordingly, cumulative food intake was also higher in HP-IMF than HF-IMF. HF-IMF exhibited higher area under the curve (AUC) of serum glucose at the first part (0–40 min) during oral glucose tolerance test, whereas AUC of serum insulin levels in both parts were higher in IMF and HF. During intraperitoneal insulin tolerance test, serum glucose levels were higher with IMF than AL. Consistently, hepatic insulin signaling (GLUT2, pAkt) was attenuated and PEPCK expression was higher with IMF and HF than other groups, and HOMA-IR revealed significantly impaired attenuated insulin sensitivity in the IMF groups. However, surprisingly, hepatic and skeletal muscle glycogen storage was higher in IMF groups than AL. The higher glycogen storage in the IMF groups was associated with the lower expression of glycogen phosphorylase than the AL groups. In conclusion, IMF especially with HF increased insulin resistance, possibly by attenuating hepatic insulin signaling, and lowered glycogen phosphorylase expression despite decreased fat mass in young male rats. These results suggest that caution may be warranted when recommending intermittent fasting, especially one-meal-per-day fasting, for people with compromised glucose metabolism.
  • Article
    Background: Synchronizing eating schedules to daily circadian rhythms may improve metabolic health, but its association with gestational glycemia is unknown. Objective: This study examined the association of maternal night-fasting intervals and eating episodes with blood glucose concentrations during pregnancy. Methods: This was a cross-sectional study within a prospective cohort in Singapore. Maternal 24-h dietary recalls, fasting glucose, and 2-h glucose concentrations were ascertained at 26-28 wk gestation for 1061 women (aged 30.7 ± 5.1 y). Night-fasting intervals were based on the longest fasting duration during the night (1900-0659). Eating episodes were defined as events that provided >50 kcal, with a time interval between eating episodes of ≥15 min. Multiple linear regressions with adjustment for confounders were conducted. Results: Mean ± SD night-fasting intervals and eating episodes per day were 9.9 ± 1.6 h and 4.2 ± 1.3 times/d, respectively; fasting and 2-h glucose concentrations were 4.4 ± 0.5 and 6.6 ± 1.5 mmol/L, respectively. In adjusted models, each hourly increase in night-fasting intervals was associated with a 0.03 mmol/L decrease in fasting glucose (95% CI: -0.06, -0.01 mmol/L), whereas each additional daily eating episode was associated with a 0.15 mmol/L increase in 2-h glucose (95% CI: 0.03, 0.28 mmol/L). Conversely, night-fasting intervals and daily eating episodes were not associated with 2-h and fasting glucose, respectively. Conclusions: Increased maternal night-fasting intervals and reduced eating episodes per day were associated with decreased fasting glucose and 2-h glucose, respectively, in the late-second trimester of pregnancy. This points to potential alternative strategies to improve glycemic control in pregnant women. This study was registered at www.clinicaltrials.gov as NCT01174875.
  • Article
    Full-text available
    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.
  • Article
    Full-text available
    Fasting influences the overall physiology of fish, and the knowledge how the gut microbiota, growth performances, and immune function in response to intermittent and long-term fasting is still insufficient. Here, we characterized the effects of fasting on the host-gut microbiota in crucian carp, which would enhance our insight into physiological adaptation to fasting. To achieve this, we investigated the gut microbial communities of crucian carp with different fasting stress, and corresponding immune and growth parameters. The gut microbial communities were structured into four clusters according to different fasting stress, namely one control group (feed regularly), two intermittent fasting groups (fasting period and re-feeding period, respectively), and one long-term fasting group. Intermittent fasting significantly improved the activity of superoxide dismutase (SOD) and lysozyme (LZM) (ANOVA, p < 0.05) and significantly increased alpha diversity and ecosystem stability of gut microbiota (ANOVA, p < 0.05). Gut length (GL) and condition factor (CF) showed no significant difference between the control group (CG) and intermittent fasting group under re-feeding period (RIF) (ANOVA, p = 0.11), but relative gut length (RGL) in group RIF was higher than that in the CG (ANOVA, p = 0.00). The bacterial genera Bacteroides, Akkermansia, and Erysipelotrichaceae were enriched in fishes under intermittent fasting. Two Bacteroides OTUs (OTU50 and OTU1292) correlated positively with immune (SOD, complement, and LZM) and growth (GL and RGL) parameters. These results highlight the possible interplay between growth performances, immune function, and gut microbiota in response to fasting.
  • Article
    Background: Synchrony between daily feeding-fasting signals and circadian rhythms has been shown to improve metabolic health in animals and adult humans, but the potential programming effect on fetal growth is unknown. Objective: We examined the associations of the maternal night-fasting interval during pregnancy with offspring birth size and adiposity. Methods: This was a cross-sectional study of mother-offspring dyads within the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. For 384 mothers aged 30.8 ± 4.8 y (mean ± SD), the night-fasting interval at 26–28 wk of gestation was determined from a 3-d food diary based on the average of the fasting duration at night (1900–0659). Offspring birth weight, length, and head circumference were measured and converted to weight-for-gestational age (GA), length-for-GA, and head circumference–for-GA z scores, respectively, by using local customized percentile charts. The percentage of neonatal total body fat (TBF) was derived by using a validated prediction equation. Multivariable general linear models, stratified by child sex, were performed. Results: The mean ± SD maternal night-fasting interval was 9.9 ± 1.3 h. In infant girls, each 1-h increase in the maternal night-fasting interval was associated with a 0.22-SD (95% CI: 0.05-, 0.40-SD; P = 0.013) increase in birth head circumference–for-GA and a 0.84% (95% CI: 0.19%, 1.49%; P = 0.012) increase in TBF at birth, after adjustment for confounders. In infant boys, no associations were observed between the maternal night-fasting interval and birth size or TBF. Conclusions: An increased maternal night-fasting interval in the late second trimester of pregnancy is associated with increased birth head circumference and TBF in girls but not boys. Our findings are in accordance with previous observations that suggest that there are sex-specific responses in fetal brain growth and adiposity, and raise the possibility of the maternal night-fasting interval as an underlying influence
  • Article
    The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved health outcomes. A MEDLINE search was performed using PubMed and the terms "intermittent fasting," "fasting," "time-restricted feeding," and "food timing." Modified fasting regimens appear to promote weight loss and may improve metabolic health. Several lines of evidence also support the hypothesis that eating patterns that reduce or eliminate nighttime eating and prolong nightly fasting intervals may result in sustained improvements in human health. Intermittent fasting regimens are hypothesized to influence metabolic regulation via effects on (a) circadian biology, (b) the gut microbiome, and (c) modifiable lifestyle behaviors, such as sleep. If proven to be efficacious, these eating regimens offer promising nonpharmacological approaches to improving health at the population level, with multiple public health benefits. Expected final online publication date for the Annual Review of Nutrition Volume 37 is August 21, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
  • Article
    Full-text available
    Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders.
  • Article
    Full-text available
    The feeding of critically ill patients has recently become a controversial issue, as several studies have provided unexpected and contradictory results. Earlier beliefs regarding energy requirements in critical illness—especially during the initial phase—have been challenged. In the current review, we summarize existing evidence about fasting and the impact of early vs. late feeding on the sick organism’s responses. The most important points are the non-nutritional advantages of using the intestine, and recognition that early endogenous energy production as an important player in the response must be integrated in the nutrient prescription. There is as of yet no bedside tool to monitor dynamics in metabolism and the magnitude of the endogenous energy production. Hence, an early “full-feeding strategy” exposes patients to involuntary overfeeding, due to the absence of an objective measure enabling the adjustment of the nutritional therapy. Suggestions for future research and clinical practice are proposed.
  • Article
    Full-text available
    p>Lifestyle therapy is an integral part of type 2 diabetes (T2D) management, but there remains no consensus on an optimal diet. The objective of this study is to evaluate the efficacy of therapeutic fasting as a treatment for T2D. This case follows a male T2D patient treated at the Intensive Dietary Management Clinic in Scarborough, Ontario, over a 4-month period. The patient’s initial fasting regimen consisted of a 24-h fast, three times a week. Over the course of treatment, the patient gradually extended his fasting period, eventually fasting for 42 h, two to three times a week. By the end of treatment, the patient’s weight was reduced by 17.8% and his waist circumference was reduced by 11.0%. In addition, the patient’s glycated haemoglobin levels decreased from 7.7% to 7.2%, and he was able to completely discontinue his insulin treatment, despite over a decade of insulin usage. The patient did not find it difficult to adhere to the fasting schedule and did not experience any hypoglycaemic episodes or other significant adverse effects. These observations suggest that therapeutic fasting may be a viable treatment option for T2D patients.</p
  • Article
    Full-text available
    Objective: To examine the effectiveness of intermittent energy restriction in the treatment for overweight and obesity in adults, when compared to usual care treatment or no treatment. Introduction: Intermittent energy restriction encompasses dietary approaches including intermittent fasting, alternate day fasting, and fasting for two days per week. Despite the recent popularity of intermittent energy restriction and associated weight loss claims, the supporting evidence base is limited. Inclusion criteria: This review included overweight or obese (BMI ≥25 kg/m) adults (≥18 years). Intermittent energy restriction was defined as consumption of ≤800 kcal on at least one day, but no more than six days per week. Intermittent energy restriction interventions were compared to no treatment (ad libitum diet) or usual care (continuous energy restriction ∼25% of recommended energy intake). Included interventions had a minimum duration of 12 weeks from baseline to post outcome measurements. The types of studies included were randomized and pseudo-randomized controlled trials. The primary outcome of this review was change in body weight. Secondary outcomes included: i) anthropometric outcomes (change in BMI, waist circumference, fat mass, fat free mass); ii) cardio-metabolic outcomes (change in blood glucose and insulin, lipoprotein profiles and blood pressure); and iii) lifestyle outcomes: diet, physical activity, quality of life and adverse events. Methods: A systematic search was conducted from database inception to November 2015. The following electronic databases were searched: MEDLINE, Embase, CINAHL, Cochrane Library, ClinicalTrials.gov, ISRCTN registry, and anzctr.org.au for English language published studies, protocols and trials. Two independent reviewers evaluated the methodological quality of included studies using the standardized critical appraisal instruments from the Joanna Briggs Institute. Data were extracted from papers included in the review by two independent reviewers using the standardized data extraction tool from the Joanna Briggs Institute. Effect sizes were expressed as weighted mean differences and their 95% confidence intervals were calculated for meta-analyses. Results: Six studies were included in this review. The intermittent energy restriction regimens varied across studies and included alternate day fasting, fasting for two days, and up to four days per week. The duration of studies ranged from three to 12 months. Four studies included continuous energy restriction as a comparator intervention and two studies included a no treatment control intervention. Meta-analyses showed that intermittent energy restriction was more effective than no treatment for weight loss (-4.14 kg; 95% CI -6.30 kg to -1.99 kg; p ≤ 0.001). Although both treatment interventions achieved similar changes in body weight (approximately 7 kg), the pooled estimate for studies that investigated the effect of intermittent energy restriction in comparison to continuous energy restriction revealed no significant difference in weight loss (-1.03 kg; 95% CI -2.46 kg to 0.40 kg; p = 0.156). Conclusions: Intermittent energy restriction may be an effective strategy for the treatment of overweight and obesity. Intermittent energy restriction was comparable to continuous energy restriction for short term weight loss in overweight and obese adults. Intermittent energy restriction was shown to be more effective than no treatment, however, this should be interpreted cautiously due to the small number of studies and future research is warranted to confirm the findings of this review.
  • Conference Paper
    SLOWbot is a research project conducted via a collaboration between iaso health and FBK (Fondazione Bruno Kessler). There are now thousands of available healthy aging apps, but most don't deliver on their promise to support a healthy aging process in people that need it the most. The neediest include the over-fifties age group, particularly those wanting to prevent the diseases of aging or whom already have a chronic disease. Even the motivated "quantified selfers" discard their health apps after only a few months. Our research aims to identify new ways to ensure adherence to a healthy lifestyle program tailored for an over fifties audience which is delivered by a chatbot. The research covers the participant onboarding process and examines barriers and issues with gathering predictive data that might inform future improved uptake and adherence as well as an increase in health literacy by the participants. The healthy lifestyle program will ultimately be delivered by our "SLOWbot" which guides the participant to make informed and enhanced health decision making, specifically around food choices (a "longevity eating plan").
  • Article
    Full-text available
    Food and obesity are undoubtedly linked but the relation is complex. Michael Lean and colleagues discuss what we know, and what we don't know, about weight management © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to.
  • Article
    Full-text available
    Emerging evidence suggests that there is interplay between the frequency and circadian timing of eating and metabolic health. We examined the associations of eating frequency and timing with metabolic and inflammatory biomarkers putatively associated with breast cancer risk in women participating in the National Health and Nutrition Examination 2009-2010 Survey. Eating frequency and timing variables were calculated from 24-hour food records and included (1) proportion of calories consumed in the evening (5pm-midnight), (2) number of eating episodes per day, and (3) nighttime fasting duration. Linear regression models examined each eating frequency and timing exposure variable with C-reactive protein (CRP) concentrations and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Each 10 percent increase in the proportion of calories consumed in the evening was associated with a 3 percent increase in CRP. Conversely, eating one additional meal or snack per day was associated with an 8 percent reduction in CRP. There was a significant interaction between proportion of calories consumed in the evening and fasting duration with CRP (p = 0.02). A longer nighttime fasting duration was associated with an 8 percent lower CRP only among women who ate less than 30% of their total daily calories in the evening (p = 0.01). None of the eating frequency and timing variables were significantly associated with HOMA-IR. These findings suggest that eating more frequently, reducing evening energy intake, and fasting for longer nightly intervals may lower systemic inflammation and subsequently reduce breast cancer risk. Randomized trials are needed to validate these associations.
  • Article
    Background and aims: Routine, periodic fasting is associated with a lower prevalence of coronary artery disease (CAD). Animal studies show that fasting may increase longevity and alter biological parameters related to longevity. We evaluated whether fasting initiates acute changes in biomarker expression in humans that may impact short- and long-term health. Methods and results: Apparently-healthy volunteers (N = 30) without a recent history of fasting were enrolled in a randomized cross-over trial. A one-day water-only fast was the intervention and changes in biomarkers were the study endpoints. Bonferroni correction required p ≤ 0.00167 for significance (p < 0.05 was a trend that was only suggestively significant). The one-day fasting intervention acutely increased human growth hormone (p = 1.1 × 10⁻⁴), hemoglobin (p = 4.8 × 10⁻⁷), red blood cell count (p = 2.5 × 10⁻⁶), hematocrit (p = 3.0 × 10⁻⁶), total cholesterol (p = 5.8 × 10⁻⁵), and high-density lipoprotein cholesterol (p = 0.0015), and decreased triglycerides (p = 1.3 × 10⁻⁴), bicarbonate (p = 3.9 × 10⁻⁴), and weight (p = 1.0 × 10⁻⁷), compared to a day of usual eating. For those randomized to fast the first day (n = 16), most factors including human growth hormone and cholesterol returned to baseline after the full 48 h, with the exception of weight (p = 2.5 × 10⁻⁴) and (suggestively significant) triglycerides (p = 0.028). Conclusion: Fasting induced acute changes in biomarkers of metabolic, cardiovascular, and general health. The long-term consequences of these short-term changes are unknown but repeated episodes of periodic short-term fasting should be evaluated as a preventive treatment with the potential to reduce metabolic disease risk. Clinical trial registration (ClinicalTrials.gov): NCT01059760 (Expression of Longevity Genes in Response to Extended Fasting [The Fasting and Expression of Longevity Genes during Food abstinence {FEELGOOD} Trial]).
  • Article
    All domains of life feature diverse molecular clock machineries that synchronize physiological processes to diurnal environmental fluctuations. However, no mechanisms are known to cross-regulate prokaryotic and eukaryotic circadian rhythms in multikingdom ecosystems. Here, we show that the intestinal microbiota, in both mice and humans, exhibits diurnal oscillations that are influenced by feeding rhythms, leading to time-specific compositional and functional profiles over the course of a day. Ablation of host molecular clock components or induction of jet lag leads to aberrant microbiota diurnal fluctuations and dysbiosis, driven by impaired feeding rhythmicity. Consequently, jet-lag-induced dysbiosis in both mice and humans promotes glucose intolerance and obesity that are transferrable to germ-free mice upon fecal transplantation. Together, these findings provide evidence of coordinated metaorganism diurnal rhythmicity and offer a microbiome-dependent mechanism for common metabolic disturbances in humans with aberrant circadian rhythms, such as those documented in shift workers and frequent flyers.
  • Article
    Full-text available
    Background/Objectives: It has been hypothesized that assuming most of the caloric intake later in the day leads to metabolic disadvantages, but few studies are available on this topic. Aim of our study was to prospectively examine whether eating more of the daily caloric intake at dinner leads to an increased risk of obesity, hyperglycemia, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD). Subjects/Methods: 1245 non-obese, non-diabetic middle-aged adults from a population-based cohort underwent a 3-day food record questionnaire at enrollment. Anthropometric values, blood pressure, blood metabolic variables, and estimated liver fat were measured at baseline and at 6-year follow-up. Design: Prospective cohort study. Results: Subjects were divided according to tertiles of percent daily caloric intake at dinner. A significant increase in the incidence rate of obesity (from 4.7 to 11.4%), metabolic syndrome (from 11.1 to 16.1%), and estimated NAFLD (from 16.5 to 23.8%) was observed from the lower to higher tertile. In a multiple logistic regression model adjusted for multiple covariates, subjects in the highest tertile showed an increased risk of developing obesity (OR = 2.33; 95% CI 1.17-4.65; p = 0.02), metabolic syndrome (OR = 1.52; 95% CI 1.01-2.30; p = 0.04), and NAFLD (OR = 1.56; 95% CI 1.10-2.22; p = 0.01). Conclusions: Consuming more of the daily energy intake at dinner is associated with an increased risk of obesity, metabolic syndrome, and NAFLD.
  • Article
    Intermittent fasting (IF) regimens have gained considerable popularity in recent years, as some people find these diets easier to follow than traditional calorie restriction (CR) approaches. IF involves restricting energy intake on 1-3 days per week, and eating freely on the non-restriction days. Alternate day fasting (ADF) is a subclass of IF, which consists of a “fast day” (75% energy restriction) alternating with a “feed day” (ad libitum food consumption). Recent findings suggest that IF and ADF are equally as effective as CR for weight loss and cardio-protection. What remains unclear, however, is whether IF/ADF elicits comparable improvements in diabetes risk indicators, when compared to CR. Accordingly, the goal of this review was to compare the effects of IF and ADF to daily CR on body weight, fasting glucose, fasting insulin, and insulin sensitivity in overweight and obese adults. Results reveal superior decreases in body weight by CR versus IF/ADF regimens, yet comparable reductions in visceral fat mass, fasting insulin, and insulin resistance. None of the interventions produced clinically meaningful reductions in glucose concentrations. Taken together, these preliminary findings show promise for the use of IF and ADF as alternatives to CR for weight loss and type 2 diabetes risk reduction in overweight and obese populations, but more research is required before solid conclusions can be reached.
  • Article
    Full-text available
    We pooled data from 5 large validation studies of dietary self-report instruments that used recovery biomarkers as references to clarify the measurement properties of food frequency questionnaires (FFQs) and 24-hour recalls. The studies were conducted in widely differing US adult populations from 1999 to 2009. We report on total energy, protein, and protein density intakes. Results were similar across sexes, but there was heterogeneity across studies. Using a FFQ, the average correlation coefficients for reported versus true intakes for energy, protein, and protein density were 0.21, 0.29, and 0.41, respectively. Using a single 24-hour recall, the coefficients were 0.26, 0.40, and 0.36, respectively, for the same nutrients and rose to 0.31, 0.49, and 0.46 when three 24-hour recalls were averaged. The average rate of under-reporting of energy intake was 28% with a FFQ and 15% with a single 24-hour recall, but the percentages were lower for protein. Personal characteristics related to under-reporting were body mass index, educational level, and age. Calibration equations for true intake that included personal characteristics provided improved prediction. This project establishes that FFQs have stronger correlations with truth for protein density than for absolute protein intake, that the use of multiple 24-hour recalls substantially increases the correlations when compared with a single 24-hour recall, and that body mass index strongly predicts under-reporting of energy and protein intakes.
  • Article
    Time-restricted feeding (TRF), a key component of intermittent fasting regimens, has gained considerable attention in recent years. TRF allows ad libitum energy intake within controlled time frames, generally a 3–12 hour range each day. The impact of various TRF regimens on indicators of metabolic disease risk has yet to be investigated. Accordingly, the objective of this review was to summarize the current literature on the effects of TRF on body weight and markers of metabolic disease risk (i.e., lipid, glucoregulatory, and inflammatory factors) in animals and humans. Results from animal studies show TRF to be associated with reductions in body weight, total cholesterol, and concentrations of triglycerides, glucose, insulin, interleukin 6, and tumor necrosis factor-α as well as with improvements in insulin sensitivity. Human data support the findings of animal studies and demonstrate decreased body weight (though not consistently), lower concentrations of triglycerides, glucose, and low-density lipoprotein cholesterol, and increased concentrations of high-density lipoprotein cholesterol. These preliminary findings show promise for the use of TRF in modulating a variety of metabolic disease risk factors.
  • Article
    Shift workers are affected by diet- and inflammation-related diseases, including cardiovascular disease, diabetes, and cancer. We examined a dietary inflammatory index (DII) in relation to shift work from the National Health and Nutrition Examination Survey data (2005 to 2010). The DII was calculated using data from a 24-hour dietary recall. Shift work categories included day workers, evening/night shift workers, or rotating shift workers. General linear models were fit to examine the relationship between shift work and adjusted mean DII values. Among all shift workers and specifically rotating shift workers, higher (ie, more pro-inflammatory) mean DII scores (1.01 and 1.07 vs 0.86; both P ≤ 0.01) were observed compared with day workers. Women tended to express strong evening/night shift effects. More proinflammatory diets observed among shift workers may partially explain increased inflammation-related chronic disease risk observed in other studies among shift workers compared with their day-working counterparts.
  • Article
    Fasting has been practiced for millennia, but, only recently, studies have shed light on its role in adaptive cellular responses that reduce oxidative damage and inflammation, optimize energy metabolism, and bolster cellular protection. In lower eukaryotes, chronic fasting extends longevity, in part, by reprogramming metabolic and stress resistance pathways. In rodents intermittent or periodic fasting protects against diabetes, cancers, heart disease, and neurodegeneration, while in humans it helps reduce obesity, hypertension, asthma, and rheumatoid arthritis. Thus, fasting has the potential to delay aging and help prevent and treat diseases while minimizing the side effects caused by chronic dietary interventions.
  • Article
    Circadian rhythms and cellular metabolism are intimately linked. Here, we reveal that a high-fat diet (HFD) generates a profound reorganization of specific metabolic pathways, leading to widespread remodeling of the liver clock. Strikingly, in addition to disrupting the normal circadian cycle, HFD causes an unexpectedly large-scale genesis of de novo oscillating transcripts, resulting in reorganization of the coordinated oscillations between coherent transcripts and metabolites. The mechanisms underlying this reprogramming involve both the impairment of CLOCK:BMAL1 chromatin recruitment and a pronounced cyclic activation of surrogate pathways through the transcriptional regulator PPARγ. Finally, we demonstrate that it is specifically the nutritional challenge, and not the development of obesity, that causes the reprogramming of the clock and that the effects of the diet on the clock are reversible.
  • Article
    Full-text available
    Alternate day fasting (ADF; ad libitum "feed day", alternated with 25% energy intake "fast day"), is effective for weight loss and cardio-protection in obese individuals. Whether these effects occur in normal weight and overweight individuals remains unknown. This study examined the effect of ADF on body weight and coronary heart disease risk in non-obese subjects. Thirty-two subjects (BMI 20--29.9 kg/m2) were randomized to either an ADF group or a control group for 12 weeks. Body weight decreased (P < 0.001) by 5.2 +/- 0.9 kg (6.5 +/- 1.0%) in the ADF group, relative to the control group, by week 12. Fat mass was reduced (P < 0.001) by 3.6 +/- 0.7 kg, and fat free mass did not change, versus controls. Triacylglycerol concentrations decreased (20 +/- 8%, P < 0.05) and LDL particle size increased (4 +/- 1 A, P < 0.01) in the ADF group relative to controls. CRP decreased (13 +/- 17%, P < 0.05) in the ADF group relative to controls at week 12. Plasma adiponectin increased (6 +/- 10%, P < 0.01) while leptin decreased (40 +/- 7%, P < 0.05) in the ADF group versus controls by the end of the study. LDL cholesterol, HDL cholesterol, homocysteine and resistin concentrations remained unchanged after 12 weeks of treatment. These findings suggest that ADF is effective for weight loss and cardio-protection in normal weight and overweight adults, though further research implementing larger sample sizes is required before solid conclusion can be reached.
  • Article
    Full-text available
    The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding fecal bacterial culture collections. Cohousing mice harboring an obese twin’s microbiota (Ob) with mice containing the lean co-twin’s microbiota (Ln) prevented the development of increased body mass and obesity-associated metabolic phenotypes in Ob cage mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln microbiota into Ob microbiota and was diet-dependent. These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.
  • Article
    The purpose of this study was to evaluate the associations between dietary factors and sleep-wake regularity in the Japanese population. We analyzed 1368 eligible subjects (931 men and 437 women) aged 35-69 years who had participated in the baseline survey of a cohort study in Tokushima Prefecture, Japan. Information on individual lifestyle characteristics, including dietary habits and sleep-wake regularity, was obtained by a selfadministrated questionnaire. Logistic regression analyses were performed to evaluate adjusted associations of the intake energy ratios of macronutrients, as well as intake frequency, and the amount of staple foods with sleepwake regularity. The lowest quartile of protein intake as well as the highest quartile of carbohydrates showed significantly higher multivariable-adjusted odds ratios of 2.1 (95% confidence interval, 1.3-3.3) and 2.1 (1.3-3.5), respectively, for poor sleep-wake regularity compared with the respective second quartile that is thought to be moderate intake. Regarding intake of staple foods, low weekly intake frequency at breakfast (<5 times/week), the lowest intake amount (<1 bowl or slice/roll) at breakfast, and the highest intake amount (>=2 bowls or slices/ rolls) at lunch and dinner exhibited significantly high adjusted odds ratios for poor sleep-wake regularity. Additionally adjusting for sleep duration, these results did not substantially alter. Our results suggested that low intake energy ratio of proteins and high intake energy ratio of carbohydrates, skipping intake of the staple foods at breakfast, and excessive intake amount of the staple foods at lunch and dinner may be associated with poor sleep-wake regularity.
  • Circadian rhythmicity that has been shaped by evolution over millions of years generates an internal timing controlling the sleep-wake and metabolism cycles. The daily variations between sleep/fasting/catabolism and wakefulness/feeding/anabolism are coordinated by a master hypothalamic clock, mainly reset by ambient light. Secondary clocks, including liver and adipose tissue, are normally synchronized by the master clock, but they are also sensitive to feeding time, especially when meals take place during the usual resting period. Cellular metabolism and circadian clocks are tightly interconnected at the molecular levels. Although the suprachiasmatic clock is not shifted by mealtime under light-dark conditions, nutritional cues can feedback onto it and modulate its function under hypo- and hypercaloric (high-fat) conditions. Food-related reward cues are other modulators of the master clock. Circadian disturbances (e.g., desynchronization induced by shift work or chronic jet lag) are frequently associated with metabolic dysfunctions (chronobesity) and vice versa. Pharmacological tools and natural synchronizers (i.e., light and mealtime) can be useful as chronotherapeutic treatments to limit the occurrence of metabolic risk factors.
  • Article
    Among adults, skipping meals is associated with excess body weight, hypertension, insulin resistance, and elevated fasting lipid concentrations. However, it remains unknown whether specific eating habits regardless of dietary composition influence coronary heart disease (CHD) risk. The objective of this study was to prospectively examine eating habits and risk of CHD. Eating habits, including breakfast eating, were assessed in 1992 in 26 902 American men 45 to 82 years of age from the Health Professionals Follow-up Study who were free of cardiovascular disease and cancer. During 16 years of follow-up, 1527 incident CHD cases were diagnosed. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals for CHD, adjusted for demographic, diet, lifestyle, and other CHD risk factors. Men who skipped breakfast had a 27% higher risk of CHD compared with men who did not (relative risk, 1.27; 95% confidence interval, 1.06-1.53). Compared with men who did not eat late at night, those who ate late at night had a 55% higher CHD risk (relative risk, 1.55; 95% confidence interval, 1.05-2.29). These associations were mediated by body mass index, hypertension, hypercholesterolemia, and diabetes mellitus. No association was observed between eating frequency (times per day) and risk of CHD. Eating breakfast was associated with significantly lower CHD risk in this cohort of male health professionals.
  • Article
    Full-text available
    Objective: To examine the form of the relationship between sleep duration and anthropometric measures and possible differences in these relationships by gender and race or ethnicity. Design and methods: Data for 13,742 participants aged ≥20 years from the National Health and Nutrition Examination Survey 2005-2010 were used. Sleep duration was categorized as ≤6 (short sleepers), 7-9, and ≥10 hours (long sleepers). Results: Short sleepers were as much as 1.7 kg/m² (SE 0.4) heavier and had 3.4 cm (SE 1.0) more girth than long sleepers. Among participants without depression or a diagnosed sleep disorder, sleep duration was significantly associated with body mass index (BMI) and waist circumference in an inverse linear association in the entire sample, men, women, whites, African Americans, and participants aged 20-39 years. No evidence for statistical interaction by gender and race or ethnicity was observed. Regression coefficients were notably stronger among adults aged 20-39 years. Compared to participants who reported sleeping 7-9 hours per night, short sleepers were more likely to be obese and have abdominal obesity. Conclusions: In this nationally representative sample of US adults, an inverse linear association most consistently characterized the association between sleep duration and BMI and waist circumference.
  • Article
    Full-text available
    Long-term night work has been suggested as a risk factor for breast cancer; however, additional studies with more comprehensive methods of exposure assessment to capture the diversity of shift patterns are needed. As well, few previous studies have considered the role of hormone receptor subtype. Relationships between night shift work and breast cancer were examined among 1134 breast cancer cases and 1179 controls, frequency-matched by age in Vancouver, British Columbia, and Kingston, Ontario. Self-reported lifetime occupational histories were assessed for night shift work, and hormone receptor status obtained from tumour pathology records. With approximately one-third of cases and controls ever employed in night shift work, associations with duration demonstrated no relationship between either 0-14 or 15-29 years, while an association was apparent for ≥30 years (OR=2.21, 95% CI 1.14 to 4.31). This association with long-term night shift work is robust to alternative definitions of prolonged shift work, with similar results for both health and non-health care workers. Long-term night shift work in a diverse mix of occupations is associated with increased breast cancer risk and not limited to nurses, as in most previous studies.
  • Article
    Few experimental data are available to support the notion that reducing night-time eating changes total daily energy intake (EI) or body weight in healthy adults. The present study primarily examined the short-term effect of night eating restriction (NER) on daily EI in healthy young men. It secondarily examined body weight and moods associated with NER. Using a cross-over design, twenty-nine men (20·9 (sd 2·5) years; 24·4 (sd 2·5) kg/m2) initiated a 2-week NER intervention (elimination of EI from 19.00 to 06.00 hours) and a 2-week control condition, counterbalanced and separated by a 1-week washout period. EI and macronutrient intake were assessed using computerised, multiple-pass 24 h food recalls, body weight via a digital scale and mood using the Profile of Mood States survey. Of the twenty-nine participants, twenty-seven (93 %) completed all aspects of the study. During the NER condition, the participants consumed less total energy per d than during the control condition (10 125 v. 11 146 kJ/d; F= 6·41; P= 0·018). During the NER condition, no energy was reported consumed between 19.00 and 06.00 hours; however, during the control condition, the energy intake of participants was 2920 (sd 1347) kJ/d between 19.00 and 06.00 hours. There was a significant difference in weight change between the NER ( - 0·4 (sd 1·1) kg) and control (+0·6 (sd 0·9) kg) conditions (F= 22·68; P< 0·001). Differences in total mood score or mood subscales between the NER and control conditions were not apparent (P>0·05). These findings provide support for NER decreasing short-term EI in healthy young men.
  • Article
    Intermittent energy restriction may result in greater improvements in insulin sensitivity and weight control than daily energy restriction (DER). We tested two intermittent energy and carbohydrate restriction (IECR) regimens, including one which allowed ad libitum protein and fat (IECR+PF). Overweight women (n 115) aged 20 and 69 years with a family history of breast cancer were randomised to an overall 25 % energy restriction, either as an IECR (2500-2717 kJ/d, < 40 g carbohydrate/d for 2 d/week) or a 25 % DER (approximately 6000 kJ/d for 7 d/week) or an IECR+PF for a 3-month weight-loss period and 1 month of weight maintenance (IECR or IECR+PF for 1 d/week). Insulin resistance reduced with the IECR diets (mean - 0·34 (95 % CI - 0·66, - 0·02) units) and the IECR+PF diet (mean - 0·38 (95 % CI - 0·75, - 0·01) units). Reductions with the IECR diets were significantly greater compared with the DER diet (mean 0·2 (95 % CI - 0·19, 0·66) μU/unit, P= 0·02). Both IECR groups had greater reductions in body fat compared with the DER group (IECR: mean - 3·7 (95 % CI - 2·5, - 4·9) kg, P= 0·007; IECR+PF: mean - 3·7 (95 % CI - 2·8, - 4·7) kg, P= 0·019; DER: mean - 2·0 (95 % CI - 1·0, 3·0) kg). During the weight maintenance phase, 1 d of IECR or IECR+PF per week maintained the reductions in insulin resistance and weight. In the short term, IECR is superior to DER with respect to improved insulin sensitivity and body fat reduction. Longer-term studies into the safety and effectiveness of IECR diets are warranted.
  • Article
    Objective: Few studies examined the association between time-of-day of nutrient intake and the metabolic syndrome. Our goal was to compare a weight loss diet with high caloric intake during breakfast to an isocaloric diet with high caloric intake at dinner. Design and methods: Overweight and obese women (BMI 32.4 ± 1.8 kg/m(2) ) with metabolic syndrome were randomized into two isocaloric (~1400 kcal) weight loss groups, a breakfast (BF) (700 kcal breakfast, 500 kcal lunch, 200 kcal dinner) or a dinner (D) group (200 kcal breakfast, 500 kcal lunch, 700 kcal dinner) for 12 weeks. Results: The BF group showed greater weight loss and waist circumference reduction. Although fasting glucose, insulin, and ghrelin were reduced in both groups, fasting glucose, insulin, and HOMA-IR decreased significantly to a greater extent in the BF group. Mean triglyceride levels decreased by 33.6% in the BF group, but increased by 14.6% in the D group. Oral glucose tolerance test led to a greater decrease of glucose and insulin in the BF group. In response to meal challenges, the overall daily glucose, insulin, ghrelin, and mean hunger scores were significantly lower, whereas mean satiety scores were significantly higher in the BF group. Conclusions: High-calorie breakfast with reduced intake at dinner is beneficial and might be a useful alternative for the management of obesity and metabolic syndrome.
  • Article
    Full-text available
    Obesity is a worldwide health problem with increasing prevalence. Decrease in energy intake has been shown to lower the risk of coronary artery disease in obese subjects. The common form of dietary restriction is daily calorie restriction (CR). Another form is alternate-day fasting (ADF). This study examined the ability of modified ADF to facilitate weight loss and lower cardiovascular risk factors in overweight and obese women. 15 adult subjects completed an 8 weeks trial (2 weeks observed and 6 weeks ADF). All women consumed very low calorie diet on the fast day and usually diet in every other day. Body weight (BW), fat mass and blood pressure (BP) were measured. Fasting blood samples were collected at the first and 57th day of trial for biochemical analysis. During the course of the trial, BW of the subjects decreased (p < 0/0001) from 84/3 ± 11/44 kg to 78/3 ± 10/18 kg. Waist Circumference decreased from 87/87 ± 9/74 to 82/86 ± 9/68(p < 0/001). Reduction in systolic BP was seen from 114.8 ± 9.16 to 105.13 ± 10.19 mmHg (p < 0/001) and diastolic BP changed from 82.86 ± 10.6 to 74.5 ± 10.8 (P < 0.05). Total cholesterol decreased from 227/73 ± 49/96 to 214/67 ± 43/27, TG from 160/5 ± 46/18 to 143/9 ± 22/77, LDL from 149/46 ± 49/81 to 131/3 ± 50/97, and FBS from 102 ± 14/7 to 96 ± 11/79 mg/dl but were not significant. HDL increased from 42/32 ± 18/01 to 50/58 ± 19/46 and was not significant. These finding suggest that short time ADF is a viable dietary option to help obese individuals lose weight and decrease some CAD risk factors. More and longer-term studies in human subjects are needed to support this important result.
  • Article
    Full-text available
    In this study, we conducted a meta-analysis of self-controlled cohort studies comparing body weights, blood levels of lipids and fasting blood glucose levels before and after Ramadan taking into account gender differences. Several databases were searched up to June 2012 for studies showing an effect of Ramadan fasting in healthy subjects, yielding 30 articles. The primary finding of this meta-analysis was that after Ramadan fasting, low-density lipoprotein (SMD = -1.67, 95 % CI = -2.48 to -0.86) and fasting blood glucose levels (SMD = -1.10, 95 % CI = -1.62 to -0.58) were decreased in both sex groups and also in the entire group compared to levels prior to Ramadan. In addition, in the female subgroup, body weight (SMD = -0.04, 95 % CI = -0.20, 0.12), total cholesterol (SMD = 0.05, 95 % CI = -0.51 to 0.60), and triglyceride levels (SMD = 0.03, 95 % CI = -0.31, 0.36) remained unchanged, while HDL levels (SMD = 0.86, 95 % CI = 0.11 to 1.61, p = 0.03) were increased. In males, Ramadan fasting resulted in weight loss (SMD = -0.24, 95 % CI = -0.36, -0.12, p = 0.001). Also, a substantial reduction in total cholesterol (SMD = -0.44, 95 % CI = -0.77 to -0.11) and LDL levels (SMD = -2.22, 95 % CI = -3.47 to -0.96) and a small decrease in triglyceride levels (SMD = -0.35, 95 % CI = -0.67 to -0.02) were observed in males. In conclusion, by looking at this data, it is evident that Ramadan fasting can effectively change body weight and some biochemical parameters in healthy subjects especially in males compared to pre-Ramadan period.
  • Article
    Objective: This study examined whether the combination of alternate day fasting (ADF) plus exercise produces superior changes in body composition and plasma lipid levels when compared to each intervention alone. Design and methods: Obese subjects (n = 64) were randomized to 1 of 4 groups for 12 weeks: 1) combination (ADF plus endurance exercise), 2) ADF, 3) exercise, or 4) control. Results: Body weight was reduced (P < 0.05) by 6 ± 4 kg, 3 ± 1 kg, and 1 ± 0 kg in the combination, ADF, and exercise groups, respectively. Fat mass and waist circumference decreased (P < 0.001), while lean mass was retained in the combination group. Low-density lipoprotein (LDL) cholesterol decreased (12 ± 5%, P < 0.05) and high-density lipoprotein (HDL) cholesterol increased (18 ± 9%, P < 0.05) in the combination group only. LDL particle size increased (P < 0.001) by 4 ± 1 Å and 5 ± 1 Å in the combination and ADF groups, respectively. The proportion of small HDL particles decreased (P < 0.01) in the combination group only. Conclusions: These findings suggest that the combination produces superior changes in body weight, body composition, and lipid indicators of heart disease risk, when compared to individual treatments.
  • Article
    Recent studies have suggested that there may be a strong link between the gut microbiota, energy extraction and body metabolism. Evidence is accumulating that the intestinal microbiota, in addition to other major factors such as diet and host genetics, contributes to obesity, metabolic dysfunction and diabetes. Both preclinical experimental and human studies have shown that obesity and metabolic dysfunction are characterized by a profound dysbiosis. Several human metagenome-wide association studies have demonstrated highly significant correlations of certain members of intestinal microbiota with obesity and type 2 diabetes. In addition dietary factors that substantially affect microbial composition, microbiota disruption, and the consequence of early-life antibiotic use, may contribute to childhood obesity and metabolic dysfunction. Further evidence for an association between microbiota and metabolic dysfunction has been derived from studies in pregnancy demonstrating that major gut microbial shifts occur during pregnancy thereby affecting host metabolism. In particular, the high rate of obesity following caesarean section could be partially explained by functional alterations in the intestinal microbiota. Obesity and associated metabolic dysfunction emerge from disturbed interactions between the intestinal microbiota, dietary changes and host immune functions. A better understanding of this relationship might lead to better therapies for human metabolic and inflammatory diseases in the future.
  • Article
    Full-text available
    Objective Shift work is associated with circadian rhythm disorder, impaired sleep and behavioural changes, including eating habits, predisposing to obesity and metabolic dysfunctions. It involves a neuro-hormonal dysregulation of appetite towards positive energy balance, including increased ghrelin and decreased leptin, but little is known about other hormones, such as xenin, derived from the upper gut (like ghrelin), and lower gut hormones. Our objective was to compare night workers with day workers in relation to appetite-regulating hormones and other metabolic parameters. DesignCross-sectional, observational study. ParticipantsTwenty-four overweight women, divided into night shift workers (n=12) and day shift workers (n=12). MeasurementsBMI, waist circumference, fat mass percentage; diet composition; Pittsburgh Sleep Quality Index; lipids; adipokines; meal tolerance test curves of glucose, insulin, ghrelin, PYY3-36, oxyntomodulin, xenin, GLP-1; insulin sensitivity (Stumvoll index). ResultsNight workers, as compared with day workers, had greater body fat mass percentage and tendency to greater waist circumference despite similar BMI; greater energy intake; impaired sleep; lower insulin sensitivity; increased triglycerides and tendency to increased C-reactive protein; similar levels of leptin and other adipokines. Night workers had a blunted post-meal suppression of ghrelin (AUCi(0-60min) 19 41399 vs -141 9 +/- 9 0 ng/ml 60 min, P<0 01 ); blunted rise of xenin (AUC(0-180min) 8690 9 +/- 2988 2 vs 28504 4 +/- 20308 3 pg/ml 180 min, P<0 01 ) and similar curves of PYY3-36, oxyntomodulin and GPL-1. Conclusion Compared with day workers within the same BMI range, night workers presented a disrupted control of ghrelin and xenin, associated with behavioural changes in diet and sleep and increased adiposity and related metabolic alterations.
  • Article
    Full-text available
    OBJECTIVE: Studies on the effects of Ramadan fasting on weight changes have been contradictory. We brought together all published data to comprehensively examine the effects in a systematic review and meta-analysis. DESIGN: Relevant studies were obtained through searches of PubMed and CINAHL and by independent screening of reference lists and citations without any time restriction. All searches were completed between October and November 2011. SETTING: Changes in body weight during and after Ramadan were extracted from thirty-five English-language studies and were meta-analysed. Most of the studies were conducted in West Asia (n 19); the remainder were conducted in Africa (n 7), East Asia (n 3) and North America/Europe (n 4). SUBJECTS: Healthy adults. RESULTS: Fasting during Ramadan resulted in significant weight loss (-1·24 kg; 95 % CI -1·60, -0·88 kg). However, most of the weight lost was regained within a few weeks and only a slight decrease in body weight was observed in the following weeks after Ramadan compared with that at the beginning of Ramadan. Weight loss at the end of Ramadan was significant in both genders (-1·51 kg for men and -0·92 kg for women); but again the weight loss lasted no longer than 2 weeks after Ramadan. Weight loss during Ramadan was greater among Asian populations compared with Africans and Europeans. CONCLUSIONS: Weight changes during Ramadan were relatively small and mostly reversed after Ramadan, gradually returning to pre-Ramadan status. Ramadan provides an opportunity to lose weight, but structured and consistent lifestyle modifications are necessary to achieve lasting weight loss.
  • Article
    The human gut is densely populated by commensal and symbiotic microbes (the “gut microbiota”), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflammation and insulin resistance. In this review we discuss molecular and cell biological mechanisms by which the microbiota participate in host functions that impact the development and maintenance of the obese state, including host ingestive behavior, energy harvest, energy expenditure and fat storage. We additionally explore the diverse signaling pathways that regulate gut permeability and bacterial translocation to the host and how these are altered in the obese state to promote the systemic inflammation (“metabolic endotoxemia”) that is a hallmark of obesity and its complications. Fundamental to our discussions is the concept of “crosstalk”, i.e., the biochemical exchange between host and microbiota that maintains the metabolic health of the superorganism and whose dysregulation is a hallmark of the obese state.
  • Article
    Full-text available
    Circadian rhythms show universally a 24-hour oscillation pattern, in metabolic, physiological and behavioral functions of almost all species, due to a fundamental adaptation to rotation of Earth round its own axis. Molecular mechanisms of generation of circadian rhythms organize a biochemical network in suprachiasmatic nucleus and peripheral tissues, building cell autonomous clock pacemakers. Rhythmicity is observed in transcriptional expression of a wide range of clock-controlled genes which regulate a variety of normal cell functions like cell division and proliferation. Desynchrony of this rhythmicity seems to be implicated in several pathologic conditions, including tumorigenesis and progression of cancer. In 2007, the International Agency for Research on Cancer (IARC) categorized shift work that involves circadian desynchrony, as being probably carcinogenic to humans (Group 2A). This review discusses the potential relation between disruptions of normal circadian rhythms with genetic driving machinery of cancer. Elucidation of role of clockwork disruption, like the exposure to light-at-night and sleep disruption, in cancer biology, could be important in the development of new targeted anticancer therapies, in optimization of individualized chronotherapy and in modification of lighting environment in working fields or home places.
  • Article
    Life in industrialized societies is primarily life inside buildings. Illumination from electric lighting in the built environment is quite different from solar radiation in intensity, spectral content, and timing during the 24-hour daily period. Humans evolved over millions of years with the day–night pattern of solar radiation as the primary circadian cue. This pattern maintained a 24-hour rhythm of melatonin release, as well as a host of other physiological rhythms including the sleep–wake cycle. Electric lighting in the built environment is generally more than sufficient for visual performance, but may be inappropriate for the maintenance of normal neuroendocrine rhythms in humans; e.g., insufficient during the day and too much at night. Lighting standards and engineering stress visual performance, whereas circadian function is not currently emphasized. The molecular biological research on the circadian clock and on mechanisms of phototransduction makes it clear that light for vision and light for circadian function are not identical systems. In particular, if electric lighting as currently employed contributes to `circadian disruption' it may be an important cause of `endocrine disruption' and thereby contribute to a high risk of breast cancer in industrialized societies.
  • Article
    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.
  • Article
    Clinical psychologists are increasingly called to participate in the treatment of obesity, a condition that affects about one-third of adults in the United States. A disorder gaining increased recognition for its role in the development and maintenance of obesity is Night Eating Syndrome (NES), a relatively novel disorder involving morning anorexia, evening hyperphagia and/or nocturnal ingestions, and insomnia. NES affects men and women from various racial groups and tends to run in families. NES tends to co-occur with mood, anxiety, eating, sleep, and substance use disorders and may have implications for weight and diabetes management. Relatively little is known about the successful treatment of NES. Limited evidence suggests that serotonergic-based pharmacological treatments may be beneficial. Psychological interventions, such as psychoeducation, eating modification, relaxation strategies, sleep hygiene, cognitive restructuring, physical activity, and social support facilitation may also yield beneficial results. The purpose of the present paper is to provide an introduction to NES, including diagnosis, clinical presentation, assessment, comorbidities, clinical implications, and pharmacological and psychological treatment approaches. Areas for further study and development are discussed. NES is an emerging area for clinical description, evaluation, and intervention.
  • Article
    To determine whether an intermittent very-low-calorie diet (VLCD) improves weight loss and glycemic control more than moderate caloric restriction alone. Individuals with type 2 diabetes (n = 54) who were > or = 20% over ideal body weight participated in a 20-week behavioral weight control program. Subjects were randomized to either a standard behavioral therapy (SBT) group or to one of two VLCD groups. SBT subjects received a 1,500-1,800 kcal/day diet throughout. Both VLCD groups followed a VLCD for 5 consecutive days during week 2, followed by either intermittent VLCD therapy for 1 day/week for 15 weeks (1-day) or for 5 consecutive days every 5 weeks (5-day), with a 1,500-1,800 kcal/day diet at other times. Both VLCD groups lost more weight than the SBT group over the 20 weeks (P = 0.04). Although the groups did not differ in fasting plasma glucose (FPG) changes at 20 weeks, more subjects in the 5-day group attained a normal HbA1c when compared with the SBT group (P = 0.04). This benefit was independent of the effects of weight loss. The best predictor of overall change in FPG and HbA1c was the FPG response during the first 3 weeks of the program. Periodic VLCDs improved weight loss in diabetic subjects. A regimen with intermittent 5-day VLCD therapy seemed particularly promising, because more subjects in this group attained a normal HbA1c. Moreover, the glucose response to a 3-week period of diet therapy predicted glycemic response at 20 weeks, and it was a better predictor of the 20-week response than initial or overall weight loss.
  • Article
    Shift work has been associated with a higher propensity for developing nutritional problems and obesity. However, the possible changes in leptin and ghrelin (2 hormones that contribute importantly to the central regulation of food intake) concentrations in this population are poorly described. The objective of the study was to evaluate the daily concentrations of leptin, nonacylated ghrelin, and acylated ghrelin and the appetite ratings in men working different shift schedules. Daily concentrations of nonacylated ghrelin, acylated ghrelin, and leptin and appetite were measured in 3 groups of subjects: workers on fixed night shifts (n = 9), fixed early morning shifts (n = 6), and fixed day shifts (n = 7). Appetite was evaluated by a validated questionnaire. Blood samples were collected every 4 hours over the course of 24 hours for a total of 6 samples. When comparing the 3 groups, leptin concentrations at 8:00 am and 4:00 pm for those workers on the day shift were significantly lower than for those on the early morning shift; and concentrations at noon for those workers on the day shift were significantly lower than for those on the night shift. Nonacylated and acylated ghrelin concentrations were significantly lower for those workers on the early morning shift than for those on the day shift. In general, appetite was the lowest in those working the early morning shift. Shift workers on the early morning shift have lower appetites and concentrations of leptin and nonacylated and acylated ghrelin than the workers on other shifts. Further studies are required to better understand the detailed needs of these individuals.
  • Article
    The prevalence of obesity and related disorders such as metabolic syndrome has vastly increased throughout the world. Recent insights have generated an entirely new perspective suggesting that our microbiota might be involved in the development of these disorders. Studies have demonstrated that obesity and metabolic syndrome may be associated with profound microbiotal changes, and the induction of a metabolic syndrome phenotype through fecal transplants corroborates the important role of the microbiota in this disease. Dietary composition and caloric intake appear to swiftly regulate intestinal microbial composition and function. As most findings in this field of research are based on mouse studies, the relevance to human biology requires further investigation.
  • Article
    Dietary restriction is an effective strategy for weight loss in obese individuals. The most common form of dietary restriction implemented is daily calorie restriction (CR), which involves reducing energy by 15-60% of usual caloric intake every day. Another form of dietary restriction employed is intermittent CR, which involves 24 h of ad libitum food consumption alternated with 24 h of complete or partial food restriction. Although both diets are effective for weight loss, it remains unknown whether one of these interventions produces superior changes in body weight and body composition when compared to the other. Accordingly, this review examines the effects of daily CR versus intermittent CR on weight loss, fat mass loss and lean mass retention in overweight and obese adults. Results reveal similar weight loss and fat mass loss with 3 to 12 weeks' intermittent CR (4-8%, 11-16%, respectively) and daily CR (5-8%, 10-20%, respectively). In contrast, less fat free mass was lost in response to intermittent CR versus daily CR. These findings suggest that these diets are equally as effective in decreasing body weight and fat mass, although intermittent CR may be more effective for the retention of lean mass.
  • Article
    Full-text available
    Circadian clocks align behavioral and biochemical processes with the day/night cycle. Nearly all vertebrate cells possess self-sustained clocks that couple endogenous rhythms with changes in cellular environment. Genetic disruption of clock genes in mice perturbs metabolic functions of specific tissues at distinct phases of the sleep/wake cycle. Circadian desynchrony, a characteristic of shift work and sleep disruption in humans, also leads to metabolic pathologies. Here, we review advances in understanding the interrelationship among circadian disruption, sleep deprivation, obesity, and diabetes and implications for rational therapeutics for these conditions.
  • Article
    Full-text available
    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.
  • Article
    Research associates short (and to a lesser extent long) sleep duration with obesity, diabetes, and cardiovascular disease; and although 7-8 h of sleep seems to confer the least health risk, these findings are often based on non-representative data. We hypothesize that short sleep (<7 h) and long sleep (>8 h) are positively associated with the risk of obesity, diabetes, hypertension, and cardiovascular disease; and analyze 2004-2005 US National Health Interview Survey data (n=56,507 observations, adults 18-85) to test this. We employ multilevel logistic regression, simultaneously controlling for individual characteristics (e.g., ethnoracial group, gender, age, education), other health behaviors (e.g., exercise, smoking), family environment (e.g., income, size, education) and geographic context (e.g., census region). Our model correctly classified at least 76% of adults on each of the outcomes studied, and sleep duration was frequently more strongly associated with these health risks than other covariates. These findings suggest a 7-8 h sleep duration directly and indirectly reduces chronic disease risk.
  • Article
    Full-text available
    Increased longevity and improved health can be achieved in mammals by two feeding regimens, caloric restriction (CR), which limits the amount of daily calorie intake, and intermittent fasting (IF), which allows the food to be available ad libitum every other day. The precise mechanisms mediating these beneficial effects are still unresolved. Resetting the circadian clock is another intervention that can lead to increased life span and well being, while clock disruption is associated with aging and morbidity. Currently, a large body of evidence links circadian rhythms with metabolism and feeding regimens. In particular, CR, and possibly also IF, can entrain the master clock located in the suprachiasmatic nuclei (SCN) of the brain hypothalamus. These findings raise the hypothesis that the beneficial effects exerted by these feeding regimens could be mediated, at least in part, through resetting of the circadian clock, thus leading to synchrony in metabolism and physiology. This hypothesis is reinforced by a transgenic mouse model showing spontaneously reduced eating alongside robust circadian rhythms and increased life span. This review will summarize recent findings concerning the relationships between feeding regimens, circadian rhythms, and metabolism with implications for ageing attenuation and life span extension.
  • Article
    Full-text available
    Overweight and obesity are the result of a chronic positive energy balance, and therefore the only effective therapies are a diet which, on the long term, provides lower calories than the daily expended energy and exercise. Because nearly every physiological and biochemical function of the body shows circadian variations it can be suggested that also different chronobiological aspects of food intake, like time of day, meal frequency and regularity, and also circadian desynchronizations like in shift work may affect energy metabolism and weight regulation. The aim of this review is therefore to summarize and discuss studies that have addressed these issues in the past and to also provide an overview about circadian variations of selected aspects of metabolism, gut physiology and also factors that may influence overall energy regulation. The results show that a chronic desynchronization of the circadian system like in shift work and also sleep deprivation can favour the development of obesity. Also, regarding energy balance, a higher meal frequency and regular eating pattern seem to be more advantageous than taking the meals irregularly and seldom. Additional studies are required to conclude whether time of day-dependent food intake significantly influences weight regulation in humans.
  • Article
    This review of the scientific literature examines the widely observed relationship between sleep duration and mortality. As early as 1964, data have shown that 7-h sleepers experience the lowest risks for all-cause mortality, whereas those at the shortest and longest sleep durations have significantly higher mortality risks. Numerous follow-up studies from around the world (e.g., Japan, Israel, Sweden, Finland, the United Kingdom) show similar relationships. We discuss possible mechanisms, including cardiovascular disease, obesity, physiologic stress, immunity, and socioeconomic status. We put forth a social-ecological framework to explore five possible pathways for the relationship between sleep duration and mortality, and we conclude with a four-point agenda for future research.
  • Article
    Full-text available
    The ability of modified alternate-day fasting (ADF; ie, consuming 25% of energy needs on the fast day and ad libitum food intake on the following day) to facilitate weight loss and lower vascular disease risk in obese individuals remains unknown. This study examined the effects of ADF that is administered under controlled compared with self-implemented conditions on body weight and coronary artery disease (CAD) risk indicators in obese adults. Sixteen obese subjects (12 women, 4 men) completed a 10-wk trial, which consisted of 3 phases: 1) a 2-wk control phase, 2) a 4-wk weight loss/ADF controlled food intake phase, and 3) a 4-wk weight loss/ADF self-selected food intake phase. Dietary adherence remained high throughout the controlled food intake phase (days adherent: 86%) and the self-selected food intake phase (days adherent: 89%). The rate of weight loss remained constant during controlled food intake (0.67 +/- 0.1 kg/wk) and self-selected food intake phases (0.68 +/- 0.1 kg/wk). Body weight decreased (P < 0.001) by 5.6 +/- 1.0 kg (5.8 +/- 1.1%) after 8 wk of diet. Percentage body fat decreased (P < 0.01) from 45 +/- 2% to 42 +/- 2%. Total cholesterol, LDL cholesterol, and triacylglycerol concentrations decreased (P < 0.01) by 21 +/- 4%, 25 +/- 10%, and 32 +/- 6%, respectively, after 8 wk of ADF, whereas HDL cholesterol remained unchanged. Systolic blood pressure decreased (P < 0.05) from 124 +/- 5 to 116 +/- 3 mm Hg. These findings suggest that ADF is a viable diet option to help obese individuals lose weight and decrease CAD risk. This trial was registered at clinicaltrials.gov as UIC-004-2009.
  • Article
    Epidemiologic studies have shown that sleep duration is associated with overall mortality. We conducted a systematic review of the associations between sleep duration and all-cause and cause-specific mortality. PubMed was systematically searched up to January, 2008 to identify studies examining the association between sleep duration and mortality (both all-cause and cause-specific) among adults. Data were abstracted serially in a standardized manner by two reviewers and analyzed using random-effects meta-analysis. Twenty-three studies assessing the associations between sleep duration and mortality were identified. All examined sleep duration measured using participant self-report. Among the 16 studies which had similar reference categories and reported sufficient data on short sleep and mortality for meta-analyses, the pooled relative risk (RR) for all-cause mortality for short sleep duration was 1.10 [95% confidence interval (CI): 1.06, 1.15]. For cardiovascular-related and cancer-related mortality, the RRs associated with short sleep were 1.06 (95% CI: 0.94, 1.18) and 0.99 (95% CI: 0.88, 1.13), respectively. Similarly, among the 17 studies reporting data on long sleep duration and mortality, the pooled RRs comparing the long sleepers with medium sleepers were 1.23 (95% CI: 1.17, 1.30) for all-cause mortality, 1.38 (95% CI: 1.13, 1.69) for cardiovascular-related mortality, and 1.21 (95% CI: 1.11, 1.32) for cancer-related mortality. Our findings indicate that both short sleepers and long sleepers are at increased risk of all-cause mortality. Further research using objective measures of sleep duration is needed to fully characterize these associations.
  • Article
    The relation between alternate-day fasting (ADF) and cardioprotection remains uncertain. In the present study, we examined the ability of modified ADF, with a low-fat (LF) vs high-fat (HF) background diet, to modulate adipose tissue physiology in a way that may protect against coronary heart disease. In a 4-week study, male C57BL/6 mice were randomized to 1 of 3 groups: (1) ADF-85%-LF (85% energy restriction on fast day, ad libitum fed on feed day, on an LF diet), (2) ADF-85%-HF (same protocol but HF diet), and (3) control (ad libitum fed). Throughout the study, body weight did not differ between ADF and control animals. Proportion of subcutaneous fat increased (P < .01), whereas the proportion of visceral fat decreased (P < .01), in both ADF groups. Triglyceride (TG) synthesis was augmented (P < .05) in subcutaneous fat, but remained unchanged in visceral fat. Adiponectin concentrations were elevated (P < .05), whereas leptin and resistin levels decreased (P < .05). Aortic vascular smooth muscle cell proliferation was reduced (P < .05) by 60% and 76% on the LF and HF diets, respectively. Plasma total cholesterol, TG, and free fatty acid concentrations also decreased (P < .05). In summary, modified ADF regimens alter adipose tissue physiology (ie, body fat distribution, TG metabolism, and adipokines) in a way that may protect against coronary heart disease. These beneficial effects were noted over a wide range of fat intake, suggesting that ADF may be protective even in the presence of HF diets.
  • Article
    Full-text available
    There is considerable epidemiological evidence that shift work is associated with increased risk for obesity, diabetes, and cardiovascular disease, perhaps the result of physiologic maladaptation to chronically sleeping and eating at abnormal circadian times. To begin to understand underlying mechanisms, we determined the effects of such misalignment between behavioral cycles (fasting/feeding and sleep/wake cycles) and endogenous circadian cycles on metabolic, autonomic, and endocrine predictors of obesity, diabetes, and cardiovascular risk. Ten adults (5 female) underwent a 10-day laboratory protocol, wherein subjects ate and slept at all phases of the circadian cycle-achieved by scheduling a recurring 28-h "day." Subjects ate 4 isocaloric meals each 28-h "day." For 8 days, plasma leptin, insulin, glucose, and cortisol were measured hourly, urinary catecholamines 2 hourly (totaling approximately 1,000 assays/subject), and blood pressure, heart rate, cardiac vagal modulation, oxygen consumption, respiratory exchange ratio, and polysomnographic sleep daily. Core body temperature was recorded continuously for 10 days to assess circadian phase. Circadian misalignment, when subjects ate and slept approximately 12 h out of phase from their habitual times, systematically decreased leptin (-17%, P < 0.001), increased glucose (+6%, P < 0.001) despite increased insulin (+22%, P = 0.006), completely reversed the daily cortisol rhythm (P < 0.001), increased mean arterial pressure (+3%, P = 0.001), and reduced sleep efficiency (-20%, P < 0.002). Notably, circadian misalignment caused 3 of 8 subjects (with sufficient available data) to exhibit postprandial glucose responses in the range typical of a prediabetic state. These findings demonstrate the adverse cardiometabolic implications of circadian misalignment, as occurs acutely with jet lag and chronically with shift work.
  • Article
    Coronary artery disease (CAD) is common and multifactorial. Members of the Church of Jesus Christ of Latter-day Saints (LDS, or Mormons) in Utah may have lower cardiac mortality than other Utahns and the US population. Although the LDS proscription of smoking likely contributes to lower cardiac risk, it is unknown whether other shared behaviors also contribute. This study evaluated potential CAD-associated effects of fasting. Patients (n(1) = 4,629) enrolled in the Intermountain Heart Collaborative Study registry (1994 to 2002) were evaluated for the association of religious preference with CAD diagnosis (> or = 70% coronary stenosis using angiography) or no CAD (normal coronaries, <10% stenosis). Consequently, another set of patients (n(2) = 448) were surveyed (2004 to 2006) for the association of behavioral factors with CAD, with routine fasting (i.e., abstinence from food and drink) as the primary variable. Secondary survey measures included proscription of alcohol, tea, and coffee; social support; and religious worship patterns. In population 1 (initial), 61% of LDS and 66% of all others had CAD (adjusted [including for smoking] odds ratio [OR] 0.81, p = 0.009). In population 2 (survey), fasting was associated with lower risk of CAD (64% vs 76% CAD; OR 0.55, 95% confidence interval 0.35 to 0.87, p = 0.010), and this remained after adjustment for traditional risk factors (OR 0.46, 95% confidence interval 0.27 to 0.81, p = 0.007). Fasting was also associated with lower diabetes prevalence (p = 0.048). In regression models entering other secondary behavioral measures, fasting remained significant with a similar effect size. In conclusion, not only proscription of tobacco, but also routine periodic fasting was associated with lower risk of CAD.