Eating Around the Clock: Circadian Rhythms of Eating and Metabolism.

The time of day that we eat is increasingly recognized as contributing as importantly to overall health as the amount or quality of the food we eat. The endogenous circadian clock has evolved to promote intake at optimal times when an organism is intended to be awake and active; but electric lights and abundant food allow eating around the clock with deleterious health outcomes. In this review, we highlight literature pertaining to the effects of food timing on health, beginning with animal models and then translation into human experiments. We emphasize the pitfalls and opportunities that technological advances bring in bettering understanding of eating behaviors and their association with health and disease. There is great promise for restricting the timing of food intake both in clinical interventions and in public health campaigns for improving health via nonpharmacological therapies.

Circadian misalignment disrupts biomarkers of cardiovascular disease risk and promotes a hypercoagulable state.

The circadian system regulates 24-h time-of-day patterns of cardiovascular physiology, with circadian misalignment resulting in adverse cardiovascular risk. Although many proteins in the coagulation-fibrinolysis axis show 24-h time-of-day patterns, it is not understood if these temporal patterns are regulated by circadian or behavioral (e.g., sleep and food intake) cycles, or how circadian misalignment influences these patterns. Thus, we utilized a night shiftwork protocol to analyze circadian versus behavioral cycle regulation of 238 plasma proteins linked to cardiovascular physiology. Six healthy men aged 26.2 ± 5.6 years (mean ± SD) completed the protocol involving two baseline days with 8-h nighttime sleep opportunities (circadian alignment), a transition to shiftwork day, followed by 2 days of simulated night shiftwork with 8-h daytime sleep opportunities (circadian misalignment). Plasma was collected for proteomics every 4 h across 24 h during baseline and during daytime sleep and the second night shift. Cosinor analyses identified proteins with circadian or behavioral cycle-regulated 24-h time-of-day patterns. Five proteins were circadian regulated (plasminogen activator inhibitor-1, angiopoietin-2, insulin-like growth factor binding protein-4, follistatin-related protein-3, and endoplasmic reticulum resident protein-29). No cardiovascular-related proteins showed regulation by behavioral cycles. Within the coagulation pathway, circadian misalignment decreased tissue factor pathway inhibitor, increased tissue factor, and induced a 24-h time-of-day pattern in coagulation factor VII (all FDR < 0.10). Such changes in protein abundance are consistent with changes observed in hypercoagulable states. Our analyses identify circadian regulation of proteins involved in cardiovascular physiology and indicate that acute circadian misalignment could promote a hypercoagulable state, possibly contributing to elevated cardiovascular disease risk among shift workers.

Identifying an acceptable number of ambulatory blood pressure measurements for accuracy of average blood pressure and nocturnal dipping status.

We aimed to identify the minimum number of ambulatory blood pressure (ABP) measures to accurately determine daytime and nighttime systolic blood pressure (BP) averages and nocturnal dipping status (i.e., relative daytime:nighttime change). A total of 43 midlife participants wore an ABP monitor for 24 h with measurements every 20/30 min during the daytime/nighttime, as identified by a sleep diary. We calculated daytime/nighttime systolic BP average and dipping status from all available measurements per participant (i.e., normative data). We then calculated daytime and nighttime BP per participant based on a random selection of 8-20 and 4-10 measurements and replicated random selections 1,000 times. We calculated accuracy by checking the proportion from 1,000 different randomly selected samples for a particular number of measurements that systolic BP was ±5 mmHg of normative data, and dipping status remained unchanged for each participant compared with the normative value. The best fit for the regression model estimated the minimal number of measurements for an accuracy of 95% in BP averages. For a 95% accuracy in estimating daytime and nighttime systolic BP, 11 daytime and 8 nighttime measurements were required. The highest accuracy for dipping status was 91.6 ± 13.4% using 20 daytime and 10 nighttime measures, while the lowest was (83.4 ± 15.1%) using 8 daytime and 4 nighttime measures. In midlife adults, 11 daytime and 8 nighttime measurements are likely enough to calculate average systolic BPs accurately. However, no minimum number is suggested to accurately calculate dipping status.NEW & NOTEWORTHY We found that a minimum of 11 blood pressure (BP) measures are necessary to calculate an accurate average daytime BP, and 8 nighttime measures are necessary to calculate an accurate nighttime average if 95% accuracy is acceptable. Regarding BP dipping status, the current recommendations (20 daytime/7 nighttime) inaccurately classified the dipping status 10.5% of the time, suggesting that guidelines may need to be updated to classify patients as nocturnal dippers or nondippers correctly.

Association Between Adverse Childhood Experiences and Sleep Duration in US Children: Analysis of 2020-2021 National Survey of Children's Health.

BACKGROUND: Adverse childhood experiences (ACEs) and suboptimal sleep both negatively associate with cardiovascular health. Although an association between ACEs and suboptimal sleep in youth has been reported, there has been no investigation for differential effects among ACE subdomains. OBJECTIVE: We examined associations between total and subdomain ACEs and sleep duration, and age as a moderator. METHODS: Using the 2020-2021 National Survey of Children's Health and the American Heart Association Life's Essential 8 scoring algorithm, we created 3 sleep subgroups: (1) optimal, (2) suboptimal (≥1 to <2 hours below or ≥1 hour above optimal), and (3) very suboptimal (≥2 hours below optimal). We assessed association between ACEs (total and subdomains) and sleep duration using multinomial logistic regression, controlling for sex, age, race/ethnicity, caregiver's education, household income, habitual bedtime, and physical activity. We tested the interactions between ACEs and child's age. RESULTS: In children aged 6 to 17 years (N = 58 964), mean sleep duration score was 77.2 (95% confidence interval, 76.6-77.9). The mean number of ACEs was 0.89 (95% confidence interval, 0.87-0.91). Adjusting for covariates, each additional ACE increased the likelihood of falling into the suboptimal subgroup by 8% and the very suboptimal subgroup by 26%. There was an association between each subdomain of ACE and suboptimal sleep duration, with no significant interaction with age. CONCLUSIONS: Our findings show a dose-response relationship between ACEs and suboptimal sleep duration-a new cardiovascular health indicator in Life's Essential 8. Healthcare providers should screen for ACEs and suboptimal sleep in children to reduce future cardiovascular disease risk.

Dietary fasting and time-restricted eating in Huntington's disease: therapeutic potential and underlying mechanisms.

Huntington's disease (HD) is a devastating neurodegenerative disorder caused by aggregation of the mutant huntingtin (mHTT) protein, resulting from a CAG repeat expansion in the huntingtin gene HTT. HD is characterized by a variety of debilitating symptoms including involuntary movements, cognitive impairment, and psychiatric disturbances. Despite considerable efforts, effective disease-modifying treatments for HD remain elusive, necessitating exploration of novel therapeutic approaches, including lifestyle modifications that could delay symptom onset and disease progression. Recent studies suggest that time-restricted eating (TRE), a form of intermittent fasting involving daily caloric intake within a limited time window, may hold promise in the treatment of neurodegenerative diseases, including HD. TRE has been shown to improve mitochondrial function, upregulate autophagy, reduce oxidative stress, regulate the sleep-wake cycle, and enhance cognitive function. In this review, we explore the potential therapeutic role of TRE in HD, focusing on its underlying physiological mechanisms. We discuss how TRE might enhance the clearance of mHTT, recover striatal brain-derived neurotrophic factor levels, improve mitochondrial function and stress-response pathways, and synchronize circadian rhythm activity. Understanding these mechanisms is critical for the development of targeted lifestyle interventions to mitigate HD pathology and improve patient outcomes. While the potential benefits of TRE in HD animal models are encouraging, future comprehensive clinical trials will be necessary to evaluate its safety, feasibility, and efficacy in persons with HD.

Circadian alignment, cardiometabolic disease, and sex specific differences in adults with overweight/obesity.

OBJECTIVE: Circadian disruption promotes weight gain and poor health. The extent to which sex plays a role in the relationship between the circadian timing of behaviors and health outcomes in individuals with overweight/obesity is unclear. We investigated the sex-specific associations between circadian alignment and cardiometabolic health markers in females and males with overweight/obesity. METHODS: Thirty volunteers with overweight/obesity (15 female; BMI≥25.1kg/m2) underwent an evening in-laboratory assessment for dim-light melatonin onset (DLMO), body composition via dual energy x-ray absorptiometry, and a fasted blood sample. Circadian alignment was determined as the time difference between DLMO and average sleep onset over 7-days (phase angle), with participants categorized into narrow/wide phase angle groups based on median phase angle split. Due to known differences in metabolic markers between sexes, participants were subdivided based on sex into narrow and wide phase angle groups. RESULTS: Males in the narrow phase angle group had higher android/gynoid body fat distribution, triglycerides, and Metabolic Syndrome risk scores, while females had higher overall body fat percentage, glucose, and resting heart rates (all p<0.04). Furthermore, a narrower phase angle in males was negatively associated with android/gynoid body fat (r=-0.53, p=0.04) and negatively associated with body fat (r=-0.62, p=0.01) and heart rate (r=-0.73, p<0.01) in females. CONCLUSION: Circadian disruption may not only promote a trajectory of weight gain but could also contribute to negative health consequences in a sex-dependent manner in those already with overweight/obesity. These data may have implications for clinical utility in sex-specific sleep and circadian interventions for adults with overweight/obesity.