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. 2021 Aug 12;12:683140. doi: 10.3389/fendo.2021.683140

Table 1.

Clinical trials on TRE with outcomes regarding glucose and lipid metabolism.

Reference Cohort (Male/Female) Study design TRE Regimen(Fasting: Feeding) Study duration Calorie intake/weight change Glucose metabolism Lipid metabolism Other effects
Antoni et al. 2018 (62) n = 13 (1/12) healthy adults age: 29-57 years non-randomized controlled trial parallel armTRE: daily feeding duration shortened by 3 h 12 weeks: 2 weeks baseline10 weeks intervention − Ad libitum food access↓ daily energy intake
↔ distribution of macronutrients− ns body weight loss
↓ fasting glucose (primarily driven by an increase among controls) − ns reduction in LDL and increase in HDL ↓ body fat mass
Cai et al., 2019 (63) n = 174 (52/122) NAFLD patients age: 34,1 ± 6,6 years RCT parallel arm TRE (16: 8) self-selected feeding window 12 weeks intervention − Ad libitum food access− provided with a meal per day↔ energy intake↓ body weight ↔ fasting glucose and insulin ↓ serum TG↔LDL, HDL, and total cholesterol ↓ fat mass
Chow et al. 2020 (64) n = 20 (3/17) overweight adults with a prolonged eating window >15 h/day age: 45,5 ± 12,1 years RCT parallel arm TRE (13-16: 8-11) self-selected hour window ~16 weeks: ~ 4 weeks preintervention12 weeks intervention − ad libitum food intake− no measure of caloric intake (or not published) ↓ body weight vs. preintervention↓ fasting glucose↑ time blood glucose levels within target (70-180 mg/dL) (CGM measure) vs. preintervention↓ TG↔ LDL, HDL ↔ physical activity↓ number of eating occasions(a) vs. non-TRE group↓ visceral fat↓ lean mass(b) vs. preintervention↓ fat mass
↓ lean mass↓ visceral fat
Cienfuegos et al., 2020 (65) n = 49 (5/44) obese adults age: 47 ± 2 years RCT parallel arm (a) lTRE (18: 6) 1 pm–7 pm.(b) lTRE (20: 4) 3 pm to 7 pm 10 weeks: 2 weeks baseline8 weeks intervention − ad libitum food intake↓ energy intake ~550 kcal/day↓ body weight ↔ fasting glucose↓ fasting insulin↓ insulin resistance(partly driven by a worsening in control group) ↔ TG, HDL, and LDL ↓ fat mass↓ lean mass with (18: 6) vs. control and vs. (20: 4)
↓ 8-isoprostane
Gabel et al., 2018 (66) Gabel et al., 2020 (67) n = 23 (3/20) obese adults age: 50 ± 2 years historically controlled study TRE (16: 8) 10 am–6 pm 14 weeks: 2 weeks baseline12 weeks intervention − ad libitum food intake↓ caloric intake~ 350 kcal/day↔ macronutrients↓ body weight ↔ glucose, insulin, HOMAR-IR ↔ TG, HDL, and LDL ↓ systolic blood pressure
↔ physical activity↔ gut microbiome
Hutchison et al., 2019 (68) n = 15 (15/0) prediabetic men age: 55 ± 3 years RCT crossover design (a) eTRE (15: 9) 8 am to 5 pm (b) lTRE (15: 9) 12 pm–9 pm 5 weeks: 1 week baseline 1 week each intervention 2 weeks washout − ad libitum food intake− no measure of caloric intake (or not published) ↓ body weight ↓ glucose iAUC↔ fasting glucose and insulin↓ mean fasting glucose in eTRE (CGM data) ↓ fasting TG↔ NEFA ↔ physical activity
↔ gastrointestinal hormones
↔ perceived hunger, fullness, desire to eat
Jamshed et al., 2019 (69) Ravussin et al., 2019 (70) n = 11 (7/4) overweight adults age: 32 ± 7 years RCT crossover design eTRE (18: 6) 8 am–2 pm ~5-6 weeks: 4 days each intervention 3,5-5 weeks washout − isocaloric controlled feeding approach− days 1-2: participants followed eating schedule on their own− days 3-4: standardized meals eaten under supervision↔ weight between arms before respiratory chamber↓ body weight while respiratory chamber day in eTRE vs. controls ↓ mean 24-h glucose
↓ glycemic excursions (M age)
↓ morning fasting glucose, insulin, and HOMA-IR
↑ evening insulin and HOMA-IR↔ evening glucose
↑ morning total cholesterol, HDL, LDL↔ morning TG, free fatty acids↔ evening lipid levels ↔ 24 h energy expenditure
↓ mean ghrelin↓ morning levels of ghrelin, leptin, GLP-1↑ PYY in evening↑ metabolic flexibility
↑ ketones in morning↓ evening cortisol
Jones et al. 2020 (71) n = 16 (16/0) healthy men age: 23 ± years Non-randomized trial Two groups recruited & tested temporally apart(a) eTRE (16: 8) 8 am–4 pm(b) energy-matched control/caloric restriction intervention (CON : CR) 3 weeks: 1 week baseline 2 weeks intervention − ad libitum food intake in eTRE group− prescribed dietary plans and all dietary intakes provided in CON : CR group to match eTRE↓ caloric intake~ 400 kcal/day↓ body weight (matched in Con : CR) ↑ whole-body insulin sensitivity↑ glucose uptake of skeletal muscle↔ mean 24-h glucose↔ fasting insulin ↔ serum TG ↔ physical activity↑ fasting ghrelin
Karras et al., 2020 (72) ntotal = 60 (17/43) orthodox fasting n=37 (11/26) TRE n=23 (6/17) overweight, metabolically healthy adults age: 48.3 ± 8.9 years non-randomized, parallel arm trial(a) orthodox fasting (b) eTRE (16: 8) 8 am–4 pm 12 weeks: 7 weeks intervention follow up 5 weeks after intervention (a)  hypocaloric dietary plans based on orthodox fasting: no animal products, except for 2 days fish (b)  hypocaloric dietary plans with two meals (8 am and 1 pm) and two snacks (11 am and 3: 30 pm)
↔ caloric intake↓ body weight (both groups vs. pre-intervention)
↔ fasting glucose, fasting insulin↔ insulin resistance (HOMA-IR) and ß-cell function ↔ total cholesterol, LDL↑ TG↓ HDL vs. orthodox fasting: ↓ waist circumferencevs. pre-intervention: ↓ waist circumference↓ body fat↔ C-reactive protein
Kesztyüs et al., 2019 (73) n = 40 (9/31) abdominally obese adults age: 49,1 ± 12,4 years single arm trial TRE (15-16: 8-9) self-selected hour window 12 weeks intervention − ad libitum food intake− no measure of caloric intake↓ body weight ↓ HbA1c ↔ total cholesterol, HDL, LDL, TG ↓ waist circumference
Li et al., 2021 (74) n = 15 (0/15) women with anovulation and PCOS age: between 18 and 31 years single arm triale TRE (16: 8) 8 am–4 pm 6 weeks: 1 week baseline 5 weeks intervention − isocaloric approach (fluctuations for no more than 10% from baseline caloric intake) ↓ body weight  ↔ fasting glucose, glucose AUC↓ fasting insulin, insulin AUC↓HOMA-IR, AUCInsulin/AUCGlucose ↔ total cholesterol, LDL, TG ↓ body fat↓ visceral fat↓ C-reactive protein and alanine aminotransferase↑ IGF-1
Lowe et al. 2020 (75) ntotal = 116 (70/46) in-person tested: n = 50 (28/22) overweight, obese adults age: 46,5 ± 10,5 years RCT parallel arml TRE (16: 8) 12 pm–8 pm 12 weeks intervention − ad libitum food intake− no measure of caloric intake↓ body weight (vs. baseline ns from control group) ↔ fasting glucose, fasting insulin, HOMA-IR, HbA1c ↔ total cholesterol, HLD, LDL, TG ↓ appendicular lean mass
Martens et al., 2020 (76) n = 22 (10/12) healthy, non-obese adults age: 67 ± 1 years RCT crossover design lTRE (16: 8) consistent self-selected hour window starting between 10 and 11 am 7 weeks: 1 week baseline 6 weeks each intervention − ad libitum food intake↔ total energy intake↔ diet composition (healthy eating index) ↔ body weight ↔ fasting glucose↓ glucose AUC (during OGTT)
↔ plasma insulin
↑ total cholesterol and LDL ↔ total body composition
↔ bone density↓ sensation of hunger
McAllister et al., 2019 (77) n = 22 (22/0) physically active men age: 22 ± 2,5 years randomized two parallel arm trial (a) ad libitum TRE (16: 8) (b) isocaloric TRE (16: 8) self-selected hour window 4 weeks intervention (a) ad libitum food intake (b) isocaloric food intake = advised to eat <± 300 kcal from baseline measured caloric intakein both groups: − ns lower caloric intake↓ body weight ↔ blood glucose↔ plasma insulin ↑ HDL↔ mean TG ↓ body fat↓ blood pressure
↑ adiponectin
Moro et al., 2016 (78) n = 34 (34/0) healthy resistance trained men age: 29,21 ± 3,8 years RCT parallel arm (a) lTRE (16: 8) 1 pm–9 pm+ RT (b) control eating window: 8 am–9 pm + RT 8 weeks intervention − caloric intake consumed in 3 meals per day at standardized times within 1 h↔ caloric intake and macronutrient distribution↓ body weight TRE pre vs. post (not control) : ↓ blood glucose
↓ insulin andHOMA-IR
↓ TG↔ total cholesterol, LDL, HDL ↓ fat mass↔ lean mass
↓ testosterone↓ IGF-1
↑ adiponectin↓TNF-α, IL-1β
↓ respiratory ratio
Parr et al. 2020 (79) n = 19 (9/10) adults with T2D and eating window >12 h/day age: 50 ± 9 years single arm trial TRE (15: 9) 10 am–7 pm 6 weeks: 2 weeks baseline4 weeks intervention − ad libitum food intake↔ caloric intake and macronutrient distribution↔ body weight ↔ fasting glucose, insulin
↔ glucose and insulin AUC
↔ HbA1c
↔ total cholesterol, HDL, LDL, TG ↑ adherence to TRE reduced energy intake
↔ psychological well-being
Parr et al., 2020 (80) Lundell et al. 2020 (81) n = 11 (11/0) sedentary men with overweight/obesity age: 38 ± 5 years RCT crossover design (a) TRE (16: 8) 10 am–6 pm (b) extended feeding of 15 h/day7 am–10 pm 3 weeks: 5 days each intervention 10 days washout − isocaloric feeding, meals provided and consumed at standardized times within ± 30 min− no measure of weight loss ↓ nocturnal glucose AUC
↔ waking glucose AUC
↔ peak glucose↔ 24-h and peak glucose (CGM) ↔ peak insulin− ns tendency to ↓ AUC total insulin
↔ TG AUC total↑ peak TG↑ AUC total and peak NEFA ↓ C-Peptide AUC total↔ physical activity↓ evening hunger
↔ muscle core clock gene expression− alters rhythmicity of serum and muscle metabolites and amino acid transport
Peeke et al., 2021 (82) n = 60 (7/53) obese adults age: 44 ± 11 years RCT parallel arm, virtual trial (a)  control: (12: 12) (b) TRE: (14: 10) with fasting snack after 12 h on 5 days/weekin both groups fasting period began after dinner between 5 pm and 8 pm 8 weeks intervention − Hypocaloric dietary regimes based on Jenny Craig® Rapid Results program− 3 meals and 1 snack provided per day↓ body weight ↓ fasting plasma glucose n/a Fasting snack decreased hunger
Phillips et al., 2021 (83) n = 45control n=20adults with eating windows ≥14 h/day and at least one metabolic syndrome component age: 43.4 ± 13.3 years RCT parallel arm TRE (12: 12) self-selected hour window 7 months: 4 weeks baseline6 months intervention − ad libitum food intake− no quantitative measure of caloric intake↓ body weight ↔ fasting glucose, HbA1c ↔ HDL cholesterol, TG ↓ waist circumference
Sutton et al. 2018 (84) n = 8 (8/0) overweight men with prediabetes age: 56 ± 9 years RCT crossover design eTRE (18: 6) dinner before 3 pm 17 weeks: 5 weeks each intervention7 weeks washout − isocaloric controlled feeding approach with standardized meals eaten under supervision− ns weight loss ↓ insulin (fasting, mean and peak) ↑ insulin sensitivity↑ß-cell responsiveness↓ insulin resistance ↑ fasting TG↔ HDL and LDL cholesterol ↓blood pressure↓desire to eat in the evening↓8-isoprostane↓fasting PYY
Tinsley et al. 2019 (85) ITT: n = 40 (0/40) PP: n = 24 (0/24) healthy resistance trained females age: 22,1 ± 2,6 years RCT parallel arm (a) lTRE (16: 8) 12 pm–8 pm + placebo +RT(b)  lTRE (16: 8) 12 pm–8 pm + 3 mg/day HMB + RT(c) ND + placebo + RT 8 weeks intervention − ad libitum food intake+ provided supplemental whey protein↔ caloric intake (increase in all groups due to provided protein supplements) ↓ body weight ↔ fasting glucose, insulin ↔ total cholesterol, HLD, LDL, TG ↔ muscular improvements↓ fat mass in PP analysis in lTRE groups
Wilkinson et al., 2020 (86) n = 19 (13/6) adults with metabolic syndrome and eating window ≥14 h/day age: 59 ± 11 years single arm trial TRE (14: 10) consistent self-selected hour window 14 weeks: 2 weeks baseline12 weeks intervention − ad libitum food intake↓ caloric intake↓ body weight ns trend towards↓ fasting glucose, fasting insulin, and HbA1c↓ HbA1c in participants with elevated fasting glucose and HbA1c at baseline ↓ total cholesterol, LDL, and non-HDL↔ TGns tendency to lower HDL ↓ body fat↓ visceral fat↓ waist circumference↓ blood pressure
↑ restfulness↔ physical activity
Zeb et al., 2020 (87) n = 80 (80/0) control n=24young aged healthy men age: n/a RCT parallel arml TRE (16: 8) 7: 30 pm–3: 30 am 25 days intervention − ad libitum food intake↓ caloric intake↔ body weight n/a ↓ total cholesterol and TG↔ LDL
↑ HDL (in both: pre- vs. post-intervention and vs. control)
↑ liver function↑ gut microbial diversity↑ circadian gene expression (Bmal1, Clock, Sirt1)

Studies investigated effects of a single meal consumed at different times of the day are not included in the table. ↑, increase; ↓, decrease; ↔, no significant change. AUCtotal, total 24-h area under the curve; CGM, continuous glucose monitoring; CON, CR, control/caloric restriction intervention; eTRE, early time-restricted eating; EXF, extended feeding; HbA1c, glycated hemoglobin A1c; HDL, high density lipoprotein; HMB, β-hydroxy β-methylbutyrate; HOMA-IR, homeostatic model assessment of insulin resistance; iAUC, incremental area under the curve; ITT, intention to treat; LDL, low density lipoprotein; lTRE, late time-restricted eating; MAGE, mean amplitude of glycemic excursions; ND, normal diet; NEFA, nonesterified fatty acids; ns, non-significant modification (p > 0,05); OGTT, oral glucose tolerance test; PCOS, polycystic ovary syndrome; PP, per protocol; PYY, peptide YY; RCT, randomized controlled trial; RT, resistance training; T2D, type 2 diabetes; TG, triglycerides; TRE, time-restricted eating; n/a, not available.