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Beneficial Effects of Time-Restricted Eating on Metabolic Diseases: A Systemic Review and Meta-Analysis.
Moon, S, Kang, J, Kim, SH, Chung, HS, Kim, YJ, Yu, JM, Cho, ST, Oh, CM, Kim, T
Nutrients. 2020;(5)
Abstract
Various behavioral and physiological pathways follow a pre-determined, 24 hour cycle known as the circadian rhythm. Metabolic homeostasis is regulated by the circadian rhythm. Time-restricted eating (TRE) is a type of intermittent fasting based on the circadian rhythm. In this study, we aim to analyze systemically the effects of TRE on body weight, body composition, and other metabolic parameters. We reviewed articles from PubMed, EMBASE, and the Cochrane Library to identify clinical trials that compared TRE to a regular diet. We included 19 studies for meta-analysis. Participants following TRE showed significantly reduced body weight (mean difference (MD), -0.90; 95% confidence interval (CI): -1.71 to -0.10) and fat mass (MD: -1.58, 95% CI: -2.64 to -0.51), while preserving fat-free mass (MD, -0.24; 95% CI: -1.15 to 0.67). TRE also showed beneficial effects on cardiometabolic parameters such as blood pressure (systolic BP, MD, -3.07; 95% CI: -5.76 to -0.37), fasting glucose concentration (MD, -2.96; 95% CI, -5.60 to -0.33), and cholesterol profiles (triglycerides, MD: -11.60, 95% CI: -23.30 to -0.27). In conclusion, TRE is a promising therapeutic strategy for controlling weight and improving metabolic dysfunctions in those who are overweight or obese. Further large-scale clinical trials are needed to confirm these findings and the usefulness of TRE.
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Factors Disrupting Melatonin Secretion Rhythms During Critical Illness.
Maas, MB, Lizza, BD, Abbott, SM, Liotta, EM, Gendy, M, Eed, J, Naidech, AM, Reid, KJ, Zee, PC
Critical care medicine. 2020;(6):854-861
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Abstract
OBJECTIVES The circadian system modulates many important physiologic processes, synchronizing tissue-specific functions throughout the body. We sought to characterize acute alterations of circadian rhythms in critically ill patients and to evaluate associations between brain dysfunction, systemic multiple organ dysfunction, environmental stimuli that entrain the circadian rhythm (zeitgebers), rest-activity rhythms, and the central circadian rhythm-controlled melatonin secretion profile. DESIGN Prospective study observing a cohort for 24-48 hours beginning within the first day of ICU admission. SETTING Multiple specialized ICUs within an academic medical center. PATIENTS Patients presenting from the community with acute onset of either intracerebral hemorrhage as a representative neurologic critical illness or sepsis as a representative systemic critical illness. Healthy control patients were studied in using modified constant routine in a clinical research unit. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Light, feeding, activity, medications, and other treatment exposures were evaluated along with validated measures of encephalopathy (Glasgow Coma Scale), multiple organ system function (Sequential Organ Failure Assessment score), and circadian rhythms (profiles of serum melatonin and its urinary metabolite 6-sulphatoxymelatonin). We studied 112 critically ill patients, including 53 with sepsis and 59 with intracerebral hemorrhage. Environmental exposures were abnormal, including light (dim), nutritional intake (reduced or absent and mistimed), and arousal stimuli (increased and mistimed). Melatonin amplitude and acrophase timing were generally preserved in awake patients but dampened and delayed with increasing encephalopathy severity. Melatonin hypersecretion was observed in patients exposed to catecholamine vasopressor infusions, but unaffected by sedatives. Change in vasopressor exposure was the only factor associated with changes in melatonin rhythms between days 1 and 2. CONCLUSIONS Encephalopathy severity and adrenergic agonist medication exposure were the primary factors contributing to abnormal melatonin rhythms. Improvements in encephalopathy and medical stabilization did not rapidly normalize rhythms. Urinary 6-sulphatoxymelatonin is not a reliable measure of the central circadian rhythm in critically ill patients.
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Skipping Breakfast for 6 Days Delayed the Circadian Rhythm of the Body Temperature without Altering Clock Gene Expression in Human Leukocytes.
Ogata, H, Horie, M, Kayaba, M, Tanaka, Y, Ando, A, Park, I, Zhang, S, Yajima, K, Shoda, JI, Omi, N, et al
Nutrients. 2020;(9)
Abstract
Breakfast is often described as "the most important meal of the day" and human studies have revealed that post-prandial responses are dependent on meal timing, but little is known of the effects of meal timing per se on human circadian rhythms. We evaluated the effects of skipping breakfast for 6 days on core body temperature, dim light melatonin onset, heart rate variability, and clock gene expression in 10 healthy young men, with a repeated-measures design. Subjects were provided an isocaloric diet three times daily (3M) or two times daily (2M, i.e., breakfast skipping condition) over 6 days. Compared with the 3M condition, the diurnal rhythm of the core body temperature in the 2M condition was delayed by 42.0 ± 16.2 min (p = 0.038). On the other hand, dim light melatonin onset, heart rate variability, and clock gene expression were not affected in the 2M condition. Skipping breakfast for 6 days caused a phase delay in the core body temperature in healthy young men, even though the sleep-wake cycle remained unchanged. Chronic effects of skipping breakfast on circadian rhythms remain to be studied.
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Early Morning Food Intake as a Risk Factor for Metabolic Dysregulation.
Stothard, ER, Ritchie, HK, Birks, BR, Eckel, RH, Higgins, J, Melanson, EL, Wright, KP, McHill, AW
Nutrients. 2020;(3)
Abstract
Increased risk of obesity and diabetes in shift workers may be related to food intake at adverse circadian times. Early morning shiftwork represents the largest proportion of shift workers in the United States, yet little is known about the impact of food intake in the early morning on metabolism. Eighteen participants (9 female) completed a counterbalanced 16 day design with two conditions separated by ~1 week: 8 h sleep opportunity at habitual time and simulated early morning shiftwork with 6.5 h sleep opportunity starting ~1 h earlier than habitual time. After wake time, resting energy expenditure (REE) was measured and blood was sampled for melatonin and fasting glucose and insulin. Following breakfast, post-prandial blood samples were collected every 40 min for 2 h and the thermic effect of food (TEF) was assessed for 3.25 h. Total sleep time was decreased by ~85 min (p < 0.0001), melatonin levels were higher (p < 0.0001) and post-prandial glucose levels were higher (p < 0.05) after one day of simulated early morning shiftwork compared with habitual wake time. REE was lower after simulated early morning shiftwork; however, TEF after breakfast was similar to habitual wake time. Insufficient sleep and caloric intake during a circadian phase of high melatonin levels may contribute to metabolic dysregulation in early morning shift workers.
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Stability of the timing of food intake at daily and monthly timescales in young adults.
McHill, AW, Hilditch, CJ, Fischer, D, Czeisler, CA, Garaulet, M, Scheer, FAJL, Klerman, EB
Scientific reports. 2020;(1):20849
Abstract
Cross-sectional observations have shown that the timing of eating may be important for health-related outcomes. Here we examined the stability of eating timing, using both clock hour and relative circadian time, across one semester (n = 14) at daily and monthly time-scales. At three time points ~ 1 month apart, circadian phase was determined during an overnight in-laboratory visit and eating was photographically recorded for one week to assess timing and composition. Day-to-day stability was measured using the Composite Phase Deviation (deviation from a perfectly regular pattern) and intraclass correlation coefficients (ICC) were used to determine individual stability across months (weekly average compared across months). Day-to-day clock timing of caloric events had poor stability within individuals (~ 3-h variation; ICC = 0.12-0.34). The timing of eating was stable across months (~ 1-h variation, ICCs ranging from 0.54-0.63), but less stable across months when measured relative to circadian timing (ICC = 0.33-0.41). Our findings suggest that though day-to-day variability in the timing of eating has poor stability, the timing of eating measured for a week is stable across months within individuals. This indicates two relevant timescales: a monthly timescale with more stability in eating timing than a daily timescale. Thus, a single day's food documentation may not represent habitual (longer timescale) patterns.
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Effect of diurnal intermittent fasting during Ramadan on ghrelin, leptin, melatonin, and cortisol levels among overweight and obese subjects: A prospective observational study.
Al-Rawi, N, Madkour, M, Jahrami, H, Salahat, D, Alhasan, F, BaHammam, A, Al-Islam Faris, M
PloS one. 2020;(8):e0237922
Abstract
BACKGROUND Levels of cortisol, melatonin, ghrelin, and leptin are highly correlated with circadian rhythmicity. The levels of these hormones are affected by sleep, feeding, and general behaviors, and fluctuate with light and dark cycles. During the fasting month of Ramadan, a shift to nighttime eating is expected to affect circadian rhythm hormones and, subsequently, the levels of melatonin, cortisol, ghrelin, and leptin. The present study aimed to examine the effect of diurnal intermittent fasting (DIF) during Ramadan on daytime levels of ghrelin, leptin, melatonin, and cortisol hormones in a group of overweight and obese subjects, and to determine how anthropometric, dietary, and lifestyle changes during the month of Ramadan correlate with these hormonal changes. METHODS Fifty-seven overweight and obese male (40) and female (17) subjects were enrolled in this study. Anthropometric measurements, dietary intake, sleep duration, and hormonal levels of serum ghrelin, leptin, melatonin, and salivary cortisol were assessed one week before the start of Ramadan fasting and after 28 days of fasting at fixed times of the day (11:00 am-1:00 pm). RESULTS At the end of Ramadan, serum levels of ghrelin, melatonin, and leptin significantly (P<0.001) decreased, while salivary cortisol did not change compared to the levels assessed in the pre-fasting state. CONCLUSIONS DIF during Ramadan significantly altered serum levels of ghrelin, melatonin, and serum leptin. Further, male sex and anthropometric variables were the most impacting factors on the tested four hormones. Further studies are needed to assess DIF's impact on the circadian rhythmicity of overweight and obese fasting people.
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Habitual Nightly Fasting Duration, Eating Timing, and Eating Frequency are Associated with Cardiometabolic Risk in Women.
Makarem, N, Sears, DD, St-Onge, MP, Zuraikat, FM, Gallo, LC, Talavera, GA, Castaneda, SF, Lai, Y, Mi, J, Aggarwal, B
Nutrients. 2020;(10)
Abstract
Nightly fasting duration (NFD) and eating timing and frequency may influence cardiometabolic health via their impact on circadian rhythms, which are entrained by food intake, but observational studies are limited. This 1-year prospective study of 116 US women (33 ± 12y, 45% Hispanic) investigated associations of habitual NFD and eating timing and frequency with cardiovascular health (CVH; American Heart Association Life's Simple 7 score) and cardiometabolic risk factors. NFD, eating timing and frequency, and nighttime eating levels were evaluated from 1-week electronic food records completed at baseline and 1 y. In multivariable-adjusted linear regression models, longer NFD was associated with poorer CVH (β = -0.22, p = 0.016 and β = -0.22, p = 0.050) and higher diastolic blood pressure (DBP) (β = 1.08, p < 0.01 and β = 1.74, p < 0.01) in cross-sectional and prospective analyses, respectively. Later timing of the first eating occasion at baseline was associated with poorer CVH (β = -0.20, p = 0.013) and higher DBP (β = 1.18, p < 0.01) and fasting glucose (β = 1.43, p = 0.045) at 1 y. After adjustment for baseline outcomes, longer NFD and later eating times were also associated with higher waist circumference (β = 0.35, p = 0.021 and β = 0.27, p < 0.01, respectively). Eating frequency was inversely related to DBP in cross-sectional (β = -1.94, p = 0.033) and prospective analyses (β = -3.37, p < 0.01). In cross-sectional analyses of baseline data and prospective analyses, a higher percentage of daily calories consumed at the largest evening meal was associated with higher DBP (β = 1.69, p = 0.046 and β = 2.32, p = 0.029, respectively). Findings suggest that frequent and earlier eating may lower cardiometabolic risk, while longer NFD may have adverse effects. Results warrant confirmation in larger multi-ethnic cohort studies with longer follow-up periods.
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Circadian Host-Microbiome Interactions in Immunity.
Butler, TD, Gibbs, JE
Frontiers in immunology. 2020;:1783
Abstract
The gut microbiome plays a critical role in regulating host immunity and can no longer be regarded as a bystander in human health and disease. In recent years, circadian (24 h) oscillations have been identified in the composition of the microbiota, its biophysical localization within the intestinal tract and its metabolic outputs. The gut microbiome and its key metabolic outputs, such as short chain fatty acids and tryptophan metabolites contribute to maintenance of intestinal immunity by promoting barrier function, regulating the host mucosal immune system and maintaining the function of gut-associated immune cell populations. Loss of rhythmic host-microbiome interactions disrupts host immunity and increases risk of inflammation and metabolic complications. Here we review factors that drive circadian variation in the microbiome, including meal timing, dietary composition and host circadian clocks. We also consider how host-microbiome interactions impact the core molecular clock and its rhythmic outputs in addition to the potential impact of this relationship on circadian control of immunity.
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Diurnal Rhythmicity Programs of Microbiota and Transcriptional Oscillation of Circadian Regulator, NFIL3.
Kubo, M
Frontiers in immunology. 2020;:552188
Abstract
Circadian rhythms are a very exquisite mechanism to influence on transcriptional levels and physiological activities of various molecules that affect cell metabolic pathways. Long-term alteration of circadian rhythms increases the risk of cardiovascular diseases, hypertension, hypertriglyceridemia, and metabolic syndrome. A drastic change in dietary patterns can affect synchronizing the circadian clock within the metabolic system. Therefore, the interaction between the host and the bacterial community colonizing the mammalian gastrointestinal tract has a great impact on the circadian clock in diurnal programs. Here, we propose that the microbiota regulates body composition through the transcriptional oscillation of circadian regulators. The transcriptional regulator, NFIL3 (also called E4BP4) is a good example. Compositional change of the commensal bacteria influences the rhythmic expression of NFIL3 in the epithelium, which subsequently controls obesity and insulin resistance. Therefore, control of circadian regulators would be a promising therapeutic target for metabolic diseases.
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Control of 24-hour blood pressure with SGLT2 inhibitors to prevent cardiovascular disease.
Kario, K, Ferdinand, KC, O'Keefe, JH
Progress in cardiovascular diseases. 2020;(3):249-262
Abstract
The presence of hypertension (HTN) in patients with diabetes mellitus (DM) further worsens cardiovascular disease (CVD) prognosis. In addition, masked HTN and abnormal circadian blood pressure (BP) variability are common among patients with DM. Clinical trial data show that sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve CVD prognosis and prevent progression of renal dysfunction in high-risk patients with type 2 DM (T2DM). Consistent reductions in 24-hour, daytime and nocturnal BP have been documented during treatment with SGLT2i in patients with DM and HTN, and these reductions are of a magnitude that is likely to be clinically significant. SGLT2i agents also appear to have beneficial effects on morning, evening and nocturnal home BP. Greater reductions in BP during treatment with SGLT2i have been reported in patient subgroups with higher body mass index, and in those with higher baseline BP. Other documented beneficial effects of SGLT2i include reductions in arterial stiffness and the potential to decrease the apnea-hypopnea index in patients with DM and obstructive sleep apnea. Recent guidelines highlight the important role of SGLT2i as part of the pharmacological management of patients with DM and HTN, and recommend consideration of SGLT2i early in the clinical course to reduce all-cause and CVD mortality in patients with T2DM and CVD. Overall, available data support a role for SGLT2i as effective BP-lowering agents in patients with T2DM and poorly controlled HTN, irrespective of baseline glucose control status. Sustained improvements in 24-hour BP and the 24-hour BP profile are likely to contribute to the CVD benefits of SGLT2i treatment.