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A peer-reviewed article of this preprint also exists.
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Authors (year) | Study design | Main results | Comments |
---|---|---|---|
Nakamura K. et al. (2021) [109] | A Randomized Cross-Over Trial: To assess the effect of the early evening meal on 24-h blood glucose levels and postprandial lipid metabolism in healthy adults. Twelve participants (2 males and 10 females) participated in a 3-day randomized cross-over study: eating a late dinner (at 21:00) or an early dinner (at 18:00), monitoring blood glucose levels by continuous blood glucose measuring device, metabolic measurements by indirect calorimetry method on the morning of day 3. | Significant differences between the two groups were observed in mean 24-h blood glucose levels on day 2 (p = 0.03). There was a significant decrease in the postprandial respiratory quotient 30 min and 60 min after breakfast on day 3 in the early dinner group compared with the late dinner group (p < 0.05). | Even a small difference 3 h, eating dinner early (at 18:00) has a positive effect on blood glucose level fluctuation and substrate oxidation compared with eating dinner late (at 21:00). No of the subjects is very small studied acute effects. |
Xie Z. et al. (2022) [113] | Randomized controlled trial: To compare the effects of the two TRF regimens (early and midday) in healthy individuals without obesity. Ninety participants were randomized to eTRF (n=30), mTRF (n=30), or control groups (n=30). Eighty-two participants completed the entire five-week trial and were analyzed (28 in eTRF, 26 in mTRF, 28 in control groups). The primary outcome was the change in insulin resistance. | eTRF was more effective than mTRF at improving insulin sensitivity; eTRF, but not mTRF, improved fasting glucose, reduced total body mass and adiposity, ameliorated inflammation, and increased gut microbial diversity. |
Demonstrates a positive effect of meal timings (from early to midday) on metabolism during TRF regimen, although the study had multiple level biases (participant selection meal plan etc.). |
Bo S. et al. (2015) [105] | A randomized cross-over study: To assess food-induced thermogenesis in the morning and evening. Twenty subjects were enrolled and randomly received the same standard meal in the morning and, 7 days after, in the evening, or vice versa. A 30-min basal, a further 60-min and 120-min calorimetry was performed after the beginning of the meal. Blood samples were drawn every 30-min for 180-min. General linear models, adjusted for period and carry-over, were used to evaluate the ‘morning effect’, that is, the difference of morning delta (after-meal minus fasting values) minus evening delta (after-meal minus fasting values) of the variables. | Fasting resting metabolic rate (RMR) did not change from morning to evening; after-meal RMR values were significantly higher after the morning meal (1916; 95% confidence interval (CI) = 1792, 2041 vs. 1756; 1648, 1863 kcal; P<0.001). RMR was significantly increased after the morning meal (90.5; 95% CI = 40.4, 140.6 kcal; P<0.001), whereas differences in areas-under-the curve for glucose (−1800; − 2564, − 1036 mg /dlx h, P<0.001), log-insulin (−0.19; − 0.30, − 0.07 μUml /h; P = 0.001) and fatty free acid concentrations (−16.1; − 30.0, − 2.09 mmol/ l xh; P = 0.024) were significantly lower. Delayed and larger increases in glucose and insulin concentrations were found after the evening meals. | The same meal consumed in the evening determined a lower RMR, and increased glycemic/insulinemic responses, suggesting circadian variations in the energy expenditure and metabolic pattern of healthy individuals. Conditions were experimental in terms of food selection and interval. |
Bandin C. et al. (2015 [104] | A randomized, cross-over trial: Thirty-two women completed two randomized, cross-over protocols: one protocol (P1) includes an assessment of resting energy expenditure (indirect-calorimetry) and glucose tolerance (mixed-meal test) (n = 10), and the other (P2) includes circadian-related measurements based on profiles in salivary cortisol and Wrist temp. (T wrist) (n = 22). In each protocol, participants were provided with standardized meals during the two meal intervention weeks and were studied under two lunch-eating conditions: Early Eating (EE; lunch at 01:00 pm) and Late Eating (LE; lunch at 04:30 pm). | LE, as compared with EE, resulted in decreased pre-meal resting-energy expenditure (P = 0.048), a lower pre-meal protein-corrected respiratory quotient (CRQ) and a changed post-meal profile of CRQ (P = 0.019). These changes reflected a significantly lower pre-meal utilization of carbohydrates in LE versus EE (P = 0.006). LE also increased glucose area under the curve above baseline by 46%, demonstrating decreased glucose tolerance (P = 0.002). Changes in the daily profile of cortisol and T wrist were also found with LE blunting the cortisol profile, with lower morning and afternoon values, and suppressing the postprandial. T wrist peak (P<0.05). |
Eating late is associated with decreased resting-energy expenditure, decreased fasting carbohydrate oxidation, decreased glucose tolerance, blunted daily profile in free cortisol concentrations, and decreased thermal effect of food on T wrist. These results may be implicated in the differential effects of meal timing on metabolic health. |
Manoogian ENC. et al. (2022) [107] | A randomized control trial: It included 137 firefighters who work 24-h shifts (23-59 years old, 9% female), 12 weeks of 10-h time-restricted eating (TRE) was feasible, with TRE participants decreasing their eating window (baseline, mean 02:13 pm, 95% CI 13.78-14.47 h; intervention, 11:13 am, 95% CI 10:73-11:54 h, p = 3.29E-17) | Compared to the standard of care (SOC) arm, TRE significantly decreased VLDL particle size. In participants with elevated cardiometabolic risks at baseline, there were significant reductions in TRE compared to SOC in glycated hemoglobin A1C and diastolic blood pressure | 10-h time-restricted eating is feasible for shift workers on a 24-h schedule. TRE improved very low-density lipoprotein size and quality of life measures. TRE decreased HbA1c and blood pressure for participants with cardiometabolic risk. A consistent 10-h eating window (TRE) had no adverse effects. However, it had a skewed gender ratio and heterogenous baseline health factors. |
Qian J. et al. (2018) [111] | Randomized, cross-over design trial: To determine the separate and relative impacts of the circadian system, behavioural/environmental cycles, and their interaction (i.e., circadian misalignment) on insulin sensitivity and β-cell function, the minimal oral model was used to quantitatively assess the major determinants of glucose control in 14 healthy adults using a randomized, cross-over design with two 8-day laboratory protocols. Both protocols involved 3 baseline inpatient days with habitual sleep/wake cycles, followed by 4 inpatient days with the same nocturnal bedtime (circadian alignment) or with 12-hour inverted behavioral/environmental cycles (circadian misalignment) | Data showed that the circadian phase and circadian misalignment affect glucose tolerance through different mechanisms. While the circadian system reduces glucose tolerance in the biological evening compared to the biological morning mainly by decreasing both dynamic and static β-cell responsivity, circadian misalignment reduced glucose tolerance mainly by lowering insulin sensitivity, not by affecting β-cell function. | Results revealed that the endogenous circadian system and circadian misalignment, after controlling for behavioral cycle influences, have independent and differential impacts on insulin sensitivity and β-cell function in healthy adults. |
Collado MC. et al. (2018) [106] | A randomized, cross-over study: It recruited 10 healthy normal-weight young women to test the effect of the timing of food intake on the human microbiota in the saliva and fecal samples to determine whether eating late alters the daily rhythms of human salivary microbiota; the researchers interrogated salivary microbiota in samples obtained at 4 specific time points over 24 h, to achieve a better understanding of the relationship between food timing and metabolic alterations in humans | A significant diurnal rhythm in salivary diversity and relative bacterial abundance (i.e., TM7 and Fusobacteria) across both early and late eating conditions. Meal timing affected diurnal rhythms in a diversity of salivary microbiota toward an inverted rhythm between the eating conditions, and eating late increased the number of putative pro-inflammatory taxa, showing a diurnal rhythm in the saliva | The impact of the timing of food intake on human salivary microbiota. Eating the main meal late inverts the daily rhythm of salivary microbiota diversity, which may have a deleterious effect on the metabolism of the host. |
Pizinger T. et al. (2018) [110] | Randomized control trial: It aimed to test the independent and interactive effects of sleep and mealtimes on insulin sensitivity (Si) in overweight adults, Six participants were enrolled (4 men, 2 women; (1 did not complete). Participants underwent a 4-phase randomized cross-over inpatient study differing in sleep times: normal (Ns: mid-night-08:00 am) or late (Ls: 03:30 am -11:30 am); and in meal times: normal (Nm: 1, 5, 11, and 12.5 hours after awakening) or late (Lm: 4.5, 8.5, 14.5, and 16 hours after awakening). An insulin-modified frequently sampled intravenous glucose tolerance test at scheduled breakfast time, and a meal tolerance test, at scheduled lunch time, were performed to assess Si after 3 days in each condition. | Meal time influenced concentrations of glucose (P = 0.012) and insulin (P = 0.069) during the overnight hours Average cortisol concentrations between 2200 and 0700 h tended to be affected by mealtime. Melatonin concentrations from the overnight sampling period showed no effect on mealtime. |
Mealtimes may be relevant for health. |
Morris C.J et al. (2016) [108] | A randomized cross-over study: The study aimed to test the hypothesis that the endogenous circadian system and circadian misalignment separately affect glucose tolerance in shift workers, both independently from behavioral cycle effects; 9 healthy. The intervention included simulated night work comprised of 12-hour inverted behavioral and environmental cycles (circadian misalignment) or simulated day work (circadian alignment). Postprandial glucose and insulin responses to identical meals given at 8:00 am and 8:00 pm in both protocols | Circadian misalignment increased postprandial glucose by 5.6%, independent of behavioral and circadian effects (P =.0042). | Internal circadian time affects glucose tolerance in shift workers. Separately, circadian misalignment reduces glucose tolerance in shift workers, providing a mechanism to help explain the increased diabetes risk in shift workers. |
Sharma A. et al. (2017) [112] | Randomized control trial: It aimed to determine the effect of rotational shift work on glucose metabolism. 12 healthy nurses performing rotational shift work using a randomized cross-over study design, underwent an isotope-labeled mixed meal test during a simulated day shift and a simulated night shift, enabling simultaneous measurement of glucose flux and beta cell function using the oral minimal model. | The postprandial glycaemic excursion was higher during the night shift (381±33 vs. 580±48 mmol/l per 5 h, p<0.01). The time to peak insulin, C-peptide, and nadir glucagon suppression in response to meal ingestion was also delayed during the night shift. While insulin action did not differ between study days, the beta cell responsivity to glucose (59±5 vs. 44±4 × 10-9 min-1; p<0.001) and disposition index were decreased during the night shift. | Impaired beta cell function during the night shift may result from normal circadian variation, the effect of rotational shift-work or a combination of both. As a consequence, higher postprandial glucose concentrations are observed during the night shift. |
Vujovic N. et al. (2022) [126] | A randomized, controlled, cross-over trial with 18 subjects to determine the effects of late versus early eating while rigorously controlling for nutrient intake, physical activity, sleep, and light exposure. The parameters measured were subjective (hunger) and objective (hormones related to metabolism) | Late eating increased hunger (p < 0.0001) and altered appetite-regulating hormones, increasing waketime and 24-h ghrelin leptin ratio (p < 0.0001 and p = 0.006, respectively). Furthermore, late eating decreased waketime energy expenditure (p = 0.002) and 24-h core body temperature (p = 0.019) | These findings show converging mechanisms by which late eating may result in positive energy balance and increased obesity risk. |
Jamshed H et al. (2019) [71] | This study employed a 4-day randomized crossover design to investigate the impact of time-restricted feeding (TRF) on gene expression, circulating hormones, and diurnal patterns in cardiometabolic risk factors. Eleven overweight adults participated in the study, following two different eating schedules: early TRF (eTRF) from 8 am to 2 pm and a control schedule from 8 am to 8 pm. Continuous glucose monitoring was conducted, and blood samples were collected to assess various factors. | Compared to the control schedule, eTRF led to a significant decrease in mean 24-hour glucose levels by 4 ± 1 mg/dl (p = 0.0003) and glycemic excursions by 12 ± 3 mg/dl (p = 0.001). In the morning, before breakfast, eTRF increased ketones, cholesterol, and the expression of the stress response and aging gene SIRT1, as well as the autophagy gene LC3A (all p < 0.04). In the evening, eTRF showed a tendency to increase brain-derived neurotropic factor (BNDF; p = 0.10) and significantly increased the expression of MTOR (p = 0.007), a key protein involved in nutrient sensing and cell growth. Moreover, eTRF resulted in altered diurnal patterns in cortisol levels and the expression of several circadian clock genes (p < 0.05). | The findings of this study indicate that eTRF improves 24-hour glucose levels, modifies lipid metabolism and circadian clock gene expression, and may enhance autophagy while potentially exerting anti-aging effects in humans. |
Lowe DA. et a. (2020) [205] | This 12-week randomized clinical trial aimed to investigate the impact of 16:8-hour time-restricted eating (TRE) on weight loss and metabolic risk markers. Participants (n=116) were divided into two groups: the consistent meal timing (CMT) group, instructed to consume three structured meals per day, and the TRE group, instructed to eat ad libitum from 12:00 pm until 8:00 pm and observe a complete caloric intake abstention from 8:00 pm until 12:00 pm the following day. The study was conducted using a custom mobile study application, with in-person testing for a subset of 50 participants located near San Francisco, California. | The TRE group showed a significant decrease in weight (-0.94 kg; 95% CI, -1.68 to -0.20; P = 0.01). However, there was no significant change in the CMT group (-0.68 kg; 95% CI, -1.41 to 0.05, P = 0.07) or between the two groups (-0.26 kg; 95% CI, -1.30 to 0.78; P = 0.63). In the in-person cohort (n = 25 TRE, n = 25 CMT), the TRE group exhibited a significant within-group decrease in weight (-1.70 kg; 95% CI, -2.56 to -0.83; P < 0.001). Additionally, the two groups had a significant difference in the appendicular lean mass index (-0.16 kg/m2; 95% CI, -0.27 to -0.05; P = 0.005). However, no significant changes were observed in any of the other secondary outcomes within or between the groups. Estimated energy intake did not differ significantly between the groups. | These findings suggest that the effectiveness of time-restricted feeding for weight loss may depend on factors such as meal timing. Specifically, skipping the early morning meal may not lead to weight loss benefits. |
Hutchison AT, et a. (2019) [114] | This study employed a randomized controlled trial design to assess the impact of 9-hour time-restricted feeding (TRF) on glucose tolerance in men at risk for type 2 diabetes. Fifteen male participants with an average age of 55 ± 3 years and a BMI of 33.9 ± 0.8 kg/m2 were enrolled in the study. The participants wore a continuous glucose monitor for 7 days during the baseline assessment and two 7-day TRF conditions. They were randomly assigned to either early TRF (TRFe) from 8 am to 5 pm or delayed TRF (TRFd) from 12 pm to 9 pm, with a 2-week washout phase between the two conditions. Glucose, insulin, triglycerides, nonesterified fatty acids, and gastrointestinal hormone levels were measured and analyzed based on incremental areas under the curve following a standard meal at specific time points. | The results demonstrated that both TRFe and TRFd improved glucose tolerance, as evidenced by a reduction in glucose incremental area under the curve (P = 0.001) and fasting triglycerides (P = 0.003) on day 7 compared to day 0. However, no significant interactions between mealtime and TRF existed for any of the variables examined. TRF did not significantly affect fasting and postprandial insulin, nonesterified fatty acids, or gastrointestinal hormone levels. As measured by continuous glucose monitoring, mean fasting glucose was lower in TRFe (P = 0.02) but not in TRFd (P = 0.17) compared to baseline, with no significant difference observed between the two TRF conditions. | This study’s findings suggest that early and delayed time-restricted feeding (TRFe and TRFd) improve glycemic responses to a test meal in men at risk for type 2 diabetes. Although only TRFe resulted in a lower mean fasting glucose level, reflecting better results with early feeding time. |
Jones R, et al. (2020) [115] | This study employed a randomized controlled trial to investigate the chronic effects of early time-restricted feeding (eTRF) compared to an energy-matched control on insulin and anabolic sensitivity in healthy males. Sixteen participants with an average age of 23 ± 1 years and a BMI of 24.0 ± 0.6 kg·m-2 were assigned to two groups: eTRF (n = 8) and control/caloric restriction (CON:CR; n = 8). The eTRF group followed the eTRF diet for 2 weeks, while the CON:CR group underwent a calorie-matched control diet after the eTRF intervention. During eTRF, daily energy intake was restricted to the period between 08:00 and 16:00, which extended the overnight fasting period by approximately 5 hours. Metabolic responses were assessed before and after the interventions, following a 12-hour overnight fast, using a carbohydrate/protein drink. | The results showed that eTRF improved whole-body insulin sensitivity compared to CON:CR, with a between-group difference of 1.89 (95% CI: 0.18, 3.60; P = 0.03; η2p = 0.29). eTRF also enhanced skeletal muscle uptake of glucose (between-group difference: 4266 μmol·min-1·kg-1·180 min; 95% CI: 261, 8270; P = 0.04; η2p = 0.31) and branched-chain amino acids (BCAAs) (between-group difference: 266 nmol·min-1·kg-1·180 min; 95% CI: 77, 455; P = 0.01; η2p = 0.44). The eTRF group experienced a reduction in energy intake (approximately 400 kcal·d-1) and weight loss (-1.04 ± 0.25 kg; P = 0.01), which was comparable to the weight loss observed in the CON:CR group (-1.24 ± 0.35 kg; P = 0.01). | Under free-living conditions, eTRF demonstrated improvements in whole-body insulin sensitivity and increased skeletal muscle glucose and BCAA uptake. These metabolic benefits were observed independent of weight loss and reflect chronic adaptations rather than the immediate effects of the last overnight fast, suggesting that eTRF can have positive effects on metabolic health. |
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Submitted:
27 June 2023
Posted:
28 June 2023
You are already at the latest version
A peer-reviewed article of this preprint also exists.
This version is not peer-reviewed
Submitted:
27 June 2023
Posted:
28 June 2023
You are already at the latest version
Authors (year) | Study design | Main results | Comments |
---|---|---|---|
Nakamura K. et al. (2021) [109] | A Randomized Cross-Over Trial: To assess the effect of the early evening meal on 24-h blood glucose levels and postprandial lipid metabolism in healthy adults. Twelve participants (2 males and 10 females) participated in a 3-day randomized cross-over study: eating a late dinner (at 21:00) or an early dinner (at 18:00), monitoring blood glucose levels by continuous blood glucose measuring device, metabolic measurements by indirect calorimetry method on the morning of day 3. | Significant differences between the two groups were observed in mean 24-h blood glucose levels on day 2 (p = 0.03). There was a significant decrease in the postprandial respiratory quotient 30 min and 60 min after breakfast on day 3 in the early dinner group compared with the late dinner group (p < 0.05). | Even a small difference 3 h, eating dinner early (at 18:00) has a positive effect on blood glucose level fluctuation and substrate oxidation compared with eating dinner late (at 21:00). No of the subjects is very small studied acute effects. |
Xie Z. et al. (2022) [113] | Randomized controlled trial: To compare the effects of the two TRF regimens (early and midday) in healthy individuals without obesity. Ninety participants were randomized to eTRF (n=30), mTRF (n=30), or control groups (n=30). Eighty-two participants completed the entire five-week trial and were analyzed (28 in eTRF, 26 in mTRF, 28 in control groups). The primary outcome was the change in insulin resistance. | eTRF was more effective than mTRF at improving insulin sensitivity; eTRF, but not mTRF, improved fasting glucose, reduced total body mass and adiposity, ameliorated inflammation, and increased gut microbial diversity. |
Demonstrates a positive effect of meal timings (from early to midday) on metabolism during TRF regimen, although the study had multiple level biases (participant selection meal plan etc.). |
Bo S. et al. (2015) [105] | A randomized cross-over study: To assess food-induced thermogenesis in the morning and evening. Twenty subjects were enrolled and randomly received the same standard meal in the morning and, 7 days after, in the evening, or vice versa. A 30-min basal, a further 60-min and 120-min calorimetry was performed after the beginning of the meal. Blood samples were drawn every 30-min for 180-min. General linear models, adjusted for period and carry-over, were used to evaluate the ‘morning effect’, that is, the difference of morning delta (after-meal minus fasting values) minus evening delta (after-meal minus fasting values) of the variables. | Fasting resting metabolic rate (RMR) did not change from morning to evening; after-meal RMR values were significantly higher after the morning meal (1916; 95% confidence interval (CI) = 1792, 2041 vs. 1756; 1648, 1863 kcal; P<0.001). RMR was significantly increased after the morning meal (90.5; 95% CI = 40.4, 140.6 kcal; P<0.001), whereas differences in areas-under-the curve for glucose (−1800; − 2564, − 1036 mg /dlx h, P<0.001), log-insulin (−0.19; − 0.30, − 0.07 μUml /h; P = 0.001) and fatty free acid concentrations (−16.1; − 30.0, − 2.09 mmol/ l xh; P = 0.024) were significantly lower. Delayed and larger increases in glucose and insulin concentrations were found after the evening meals. | The same meal consumed in the evening determined a lower RMR, and increased glycemic/insulinemic responses, suggesting circadian variations in the energy expenditure and metabolic pattern of healthy individuals. Conditions were experimental in terms of food selection and interval. |
Bandin C. et al. (2015 [104] | A randomized, cross-over trial: Thirty-two women completed two randomized, cross-over protocols: one protocol (P1) includes an assessment of resting energy expenditure (indirect-calorimetry) and glucose tolerance (mixed-meal test) (n = 10), and the other (P2) includes circadian-related measurements based on profiles in salivary cortisol and Wrist temp. (T wrist) (n = 22). In each protocol, participants were provided with standardized meals during the two meal intervention weeks and were studied under two lunch-eating conditions: Early Eating (EE; lunch at 01:00 pm) and Late Eating (LE; lunch at 04:30 pm). | LE, as compared with EE, resulted in decreased pre-meal resting-energy expenditure (P = 0.048), a lower pre-meal protein-corrected respiratory quotient (CRQ) and a changed post-meal profile of CRQ (P = 0.019). These changes reflected a significantly lower pre-meal utilization of carbohydrates in LE versus EE (P = 0.006). LE also increased glucose area under the curve above baseline by 46%, demonstrating decreased glucose tolerance (P = 0.002). Changes in the daily profile of cortisol and T wrist were also found with LE blunting the cortisol profile, with lower morning and afternoon values, and suppressing the postprandial. T wrist peak (P<0.05). |
Eating late is associated with decreased resting-energy expenditure, decreased fasting carbohydrate oxidation, decreased glucose tolerance, blunted daily profile in free cortisol concentrations, and decreased thermal effect of food on T wrist. These results may be implicated in the differential effects of meal timing on metabolic health. |
Manoogian ENC. et al. (2022) [107] | A randomized control trial: It included 137 firefighters who work 24-h shifts (23-59 years old, 9% female), 12 weeks of 10-h time-restricted eating (TRE) was feasible, with TRE participants decreasing their eating window (baseline, mean 02:13 pm, 95% CI 13.78-14.47 h; intervention, 11:13 am, 95% CI 10:73-11:54 h, p = 3.29E-17) | Compared to the standard of care (SOC) arm, TRE significantly decreased VLDL particle size. In participants with elevated cardiometabolic risks at baseline, there were significant reductions in TRE compared to SOC in glycated hemoglobin A1C and diastolic blood pressure | 10-h time-restricted eating is feasible for shift workers on a 24-h schedule. TRE improved very low-density lipoprotein size and quality of life measures. TRE decreased HbA1c and blood pressure for participants with cardiometabolic risk. A consistent 10-h eating window (TRE) had no adverse effects. However, it had a skewed gender ratio and heterogenous baseline health factors. |
Qian J. et al. (2018) [111] | Randomized, cross-over design trial: To determine the separate and relative impacts of the circadian system, behavioural/environmental cycles, and their interaction (i.e., circadian misalignment) on insulin sensitivity and β-cell function, the minimal oral model was used to quantitatively assess the major determinants of glucose control in 14 healthy adults using a randomized, cross-over design with two 8-day laboratory protocols. Both protocols involved 3 baseline inpatient days with habitual sleep/wake cycles, followed by 4 inpatient days with the same nocturnal bedtime (circadian alignment) or with 12-hour inverted behavioral/environmental cycles (circadian misalignment) | Data showed that the circadian phase and circadian misalignment affect glucose tolerance through different mechanisms. While the circadian system reduces glucose tolerance in the biological evening compared to the biological morning mainly by decreasing both dynamic and static β-cell responsivity, circadian misalignment reduced glucose tolerance mainly by lowering insulin sensitivity, not by affecting β-cell function. | Results revealed that the endogenous circadian system and circadian misalignment, after controlling for behavioral cycle influences, have independent and differential impacts on insulin sensitivity and β-cell function in healthy adults. |
Collado MC. et al. (2018) [106] | A randomized, cross-over study: It recruited 10 healthy normal-weight young women to test the effect of the timing of food intake on the human microbiota in the saliva and fecal samples to determine whether eating late alters the daily rhythms of human salivary microbiota; the researchers interrogated salivary microbiota in samples obtained at 4 specific time points over 24 h, to achieve a better understanding of the relationship between food timing and metabolic alterations in humans | A significant diurnal rhythm in salivary diversity and relative bacterial abundance (i.e., TM7 and Fusobacteria) across both early and late eating conditions. Meal timing affected diurnal rhythms in a diversity of salivary microbiota toward an inverted rhythm between the eating conditions, and eating late increased the number of putative pro-inflammatory taxa, showing a diurnal rhythm in the saliva | The impact of the timing of food intake on human salivary microbiota. Eating the main meal late inverts the daily rhythm of salivary microbiota diversity, which may have a deleterious effect on the metabolism of the host. |
Pizinger T. et al. (2018) [110] | Randomized control trial: It aimed to test the independent and interactive effects of sleep and mealtimes on insulin sensitivity (Si) in overweight adults, Six participants were enrolled (4 men, 2 women; (1 did not complete). Participants underwent a 4-phase randomized cross-over inpatient study differing in sleep times: normal (Ns: mid-night-08:00 am) or late (Ls: 03:30 am -11:30 am); and in meal times: normal (Nm: 1, 5, 11, and 12.5 hours after awakening) or late (Lm: 4.5, 8.5, 14.5, and 16 hours after awakening). An insulin-modified frequently sampled intravenous glucose tolerance test at scheduled breakfast time, and a meal tolerance test, at scheduled lunch time, were performed to assess Si after 3 days in each condition. | Meal time influenced concentrations of glucose (P = 0.012) and insulin (P = 0.069) during the overnight hours Average cortisol concentrations between 2200 and 0700 h tended to be affected by mealtime. Melatonin concentrations from the overnight sampling period showed no effect on mealtime. |
Mealtimes may be relevant for health. |
Morris C.J et al. (2016) [108] | A randomized cross-over study: The study aimed to test the hypothesis that the endogenous circadian system and circadian misalignment separately affect glucose tolerance in shift workers, both independently from behavioral cycle effects; 9 healthy. The intervention included simulated night work comprised of 12-hour inverted behavioral and environmental cycles (circadian misalignment) or simulated day work (circadian alignment). Postprandial glucose and insulin responses to identical meals given at 8:00 am and 8:00 pm in both protocols | Circadian misalignment increased postprandial glucose by 5.6%, independent of behavioral and circadian effects (P =.0042). | Internal circadian time affects glucose tolerance in shift workers. Separately, circadian misalignment reduces glucose tolerance in shift workers, providing a mechanism to help explain the increased diabetes risk in shift workers. |
Sharma A. et al. (2017) [112] | Randomized control trial: It aimed to determine the effect of rotational shift work on glucose metabolism. 12 healthy nurses performing rotational shift work using a randomized cross-over study design, underwent an isotope-labeled mixed meal test during a simulated day shift and a simulated night shift, enabling simultaneous measurement of glucose flux and beta cell function using the oral minimal model. | The postprandial glycaemic excursion was higher during the night shift (381±33 vs. 580±48 mmol/l per 5 h, p<0.01). The time to peak insulin, C-peptide, and nadir glucagon suppression in response to meal ingestion was also delayed during the night shift. While insulin action did not differ between study days, the beta cell responsivity to glucose (59±5 vs. 44±4 × 10-9 min-1; p<0.001) and disposition index were decreased during the night shift. | Impaired beta cell function during the night shift may result from normal circadian variation, the effect of rotational shift-work or a combination of both. As a consequence, higher postprandial glucose concentrations are observed during the night shift. |
Vujovic N. et al. (2022) [126] | A randomized, controlled, cross-over trial with 18 subjects to determine the effects of late versus early eating while rigorously controlling for nutrient intake, physical activity, sleep, and light exposure. The parameters measured were subjective (hunger) and objective (hormones related to metabolism) | Late eating increased hunger (p < 0.0001) and altered appetite-regulating hormones, increasing waketime and 24-h ghrelin leptin ratio (p < 0.0001 and p = 0.006, respectively). Furthermore, late eating decreased waketime energy expenditure (p = 0.002) and 24-h core body temperature (p = 0.019) | These findings show converging mechanisms by which late eating may result in positive energy balance and increased obesity risk. |
Jamshed H et al. (2019) [71] | This study employed a 4-day randomized crossover design to investigate the impact of time-restricted feeding (TRF) on gene expression, circulating hormones, and diurnal patterns in cardiometabolic risk factors. Eleven overweight adults participated in the study, following two different eating schedules: early TRF (eTRF) from 8 am to 2 pm and a control schedule from 8 am to 8 pm. Continuous glucose monitoring was conducted, and blood samples were collected to assess various factors. | Compared to the control schedule, eTRF led to a significant decrease in mean 24-hour glucose levels by 4 ± 1 mg/dl (p = 0.0003) and glycemic excursions by 12 ± 3 mg/dl (p = 0.001). In the morning, before breakfast, eTRF increased ketones, cholesterol, and the expression of the stress response and aging gene SIRT1, as well as the autophagy gene LC3A (all p < 0.04). In the evening, eTRF showed a tendency to increase brain-derived neurotropic factor (BNDF; p = 0.10) and significantly increased the expression of MTOR (p = 0.007), a key protein involved in nutrient sensing and cell growth. Moreover, eTRF resulted in altered diurnal patterns in cortisol levels and the expression of several circadian clock genes (p < 0.05). | The findings of this study indicate that eTRF improves 24-hour glucose levels, modifies lipid metabolism and circadian clock gene expression, and may enhance autophagy while potentially exerting anti-aging effects in humans. |
Lowe DA. et a. (2020) [205] | This 12-week randomized clinical trial aimed to investigate the impact of 16:8-hour time-restricted eating (TRE) on weight loss and metabolic risk markers. Participants (n=116) were divided into two groups: the consistent meal timing (CMT) group, instructed to consume three structured meals per day, and the TRE group, instructed to eat ad libitum from 12:00 pm until 8:00 pm and observe a complete caloric intake abstention from 8:00 pm until 12:00 pm the following day. The study was conducted using a custom mobile study application, with in-person testing for a subset of 50 participants located near San Francisco, California. | The TRE group showed a significant decrease in weight (-0.94 kg; 95% CI, -1.68 to -0.20; P = 0.01). However, there was no significant change in the CMT group (-0.68 kg; 95% CI, -1.41 to 0.05, P = 0.07) or between the two groups (-0.26 kg; 95% CI, -1.30 to 0.78; P = 0.63). In the in-person cohort (n = 25 TRE, n = 25 CMT), the TRE group exhibited a significant within-group decrease in weight (-1.70 kg; 95% CI, -2.56 to -0.83; P < 0.001). Additionally, the two groups had a significant difference in the appendicular lean mass index (-0.16 kg/m2; 95% CI, -0.27 to -0.05; P = 0.005). However, no significant changes were observed in any of the other secondary outcomes within or between the groups. Estimated energy intake did not differ significantly between the groups. | These findings suggest that the effectiveness of time-restricted feeding for weight loss may depend on factors such as meal timing. Specifically, skipping the early morning meal may not lead to weight loss benefits. |
Hutchison AT, et a. (2019) [114] | This study employed a randomized controlled trial design to assess the impact of 9-hour time-restricted feeding (TRF) on glucose tolerance in men at risk for type 2 diabetes. Fifteen male participants with an average age of 55 ± 3 years and a BMI of 33.9 ± 0.8 kg/m2 were enrolled in the study. The participants wore a continuous glucose monitor for 7 days during the baseline assessment and two 7-day TRF conditions. They were randomly assigned to either early TRF (TRFe) from 8 am to 5 pm or delayed TRF (TRFd) from 12 pm to 9 pm, with a 2-week washout phase between the two conditions. Glucose, insulin, triglycerides, nonesterified fatty acids, and gastrointestinal hormone levels were measured and analyzed based on incremental areas under the curve following a standard meal at specific time points. | The results demonstrated that both TRFe and TRFd improved glucose tolerance, as evidenced by a reduction in glucose incremental area under the curve (P = 0.001) and fasting triglycerides (P = 0.003) on day 7 compared to day 0. However, no significant interactions between mealtime and TRF existed for any of the variables examined. TRF did not significantly affect fasting and postprandial insulin, nonesterified fatty acids, or gastrointestinal hormone levels. As measured by continuous glucose monitoring, mean fasting glucose was lower in TRFe (P = 0.02) but not in TRFd (P = 0.17) compared to baseline, with no significant difference observed between the two TRF conditions. | This study’s findings suggest that early and delayed time-restricted feeding (TRFe and TRFd) improve glycemic responses to a test meal in men at risk for type 2 diabetes. Although only TRFe resulted in a lower mean fasting glucose level, reflecting better results with early feeding time. |
Jones R, et al. (2020) [115] | This study employed a randomized controlled trial to investigate the chronic effects of early time-restricted feeding (eTRF) compared to an energy-matched control on insulin and anabolic sensitivity in healthy males. Sixteen participants with an average age of 23 ± 1 years and a BMI of 24.0 ± 0.6 kg·m-2 were assigned to two groups: eTRF (n = 8) and control/caloric restriction (CON:CR; n = 8). The eTRF group followed the eTRF diet for 2 weeks, while the CON:CR group underwent a calorie-matched control diet after the eTRF intervention. During eTRF, daily energy intake was restricted to the period between 08:00 and 16:00, which extended the overnight fasting period by approximately 5 hours. Metabolic responses were assessed before and after the interventions, following a 12-hour overnight fast, using a carbohydrate/protein drink. | The results showed that eTRF improved whole-body insulin sensitivity compared to CON:CR, with a between-group difference of 1.89 (95% CI: 0.18, 3.60; P = 0.03; η2p = 0.29). eTRF also enhanced skeletal muscle uptake of glucose (between-group difference: 4266 μmol·min-1·kg-1·180 min; 95% CI: 261, 8270; P = 0.04; η2p = 0.31) and branched-chain amino acids (BCAAs) (between-group difference: 266 nmol·min-1·kg-1·180 min; 95% CI: 77, 455; P = 0.01; η2p = 0.44). The eTRF group experienced a reduction in energy intake (approximately 400 kcal·d-1) and weight loss (-1.04 ± 0.25 kg; P = 0.01), which was comparable to the weight loss observed in the CON:CR group (-1.24 ± 0.35 kg; P = 0.01). | Under free-living conditions, eTRF demonstrated improvements in whole-body insulin sensitivity and increased skeletal muscle glucose and BCAA uptake. These metabolic benefits were observed independent of weight loss and reflect chronic adaptations rather than the immediate effects of the last overnight fast, suggesting that eTRF can have positive effects on metabolic health. |
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