Ten-Hour Time-Restricted Eating Reduces Weight, Blood Pressure, and Atherogenic Lipids in Patients with Metabolic Syndrome

•10 h time-restricted eating (TRE) in metabolic syndrome (MetS) promotes weight loss•TRE in MetS reduces waist circumference, percent body fat, and visceral fat•TRE in MetS lowers blood pressure, atherogenic lipids, and glycated hemoglobin•Benefits of TRE are “add-ons” to statin and anti-hypertensive medications In animal models, time-restricted feeding (TRF) can prevent and reverse aspects of metabolic diseases. Time-restricted eating (TRE) in human pilot studies reduces the risks of metabolic diseases in otherwise healthy individuals. However, patients with diagnosed metabolic syndrome often undergo pharmacotherapy, and it has never been tested whether TRE can act synergistically with pharmacotherapy in animal models or humans. In a single-arm, paired-sample trial, 19 participants with metabolic syndrome and a baseline mean daily eating window of ≥14 h, the majority of whom were on a statin and/or antihypertensive therapy, underwent 10 h of TRE (all dietary intake within a consistent self-selected 10 h window) for 12 weeks. We found this TRE intervention improves cardiometabolic health for patients with metabolic syndrome receiving standard medical care including high rates of statin and anti-hypertensive use. TRE is a potentially powerful lifestyle intervention that can be added to standard medical practice to treat metabolic syndrome.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJhZjU1M2M2Yzk0OWIwYjE2OWUwZGM1NjVlMzU0YTc0MCIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc4MjQxOTU5fQ.qunJ9rhNbAXM2ZsrmL_UEgEmxnm46WdS0H0dVwre1fyhICQEB_Y4TEGDHzGxGx9s1CKNYFosoCOTTQIJecg9eqK980f4iLymTeiEFgcFBBmkQp2kPucNvrdSuwwROnp9kjG5W54nhPpsK9ztAm52W-proae5qAdVVbhcrge1KK9kvkZfxCMOD5ZdxraZmSDcfYZb5o--kwhUHV7BhUrNDFOP-dqSu-MkUHRhbaBcdK9pmXL3JgsDAM9l350sqUmfLute0d76f3YPIprm6dnQMXRTUhB0HmU_6-jgBhD-NJjw73lfpKpTKVhuPCE27-RHK2xILfF5EhFvdJ8O9Fct6g(mp4, (17.28 MB) Download video In animal models, time-restricted feeding (TRF) can prevent and reverse aspects of metabolic diseases. Time-restricted eating (TRE) in human pilot studies reduces the risks of metabolic diseases in otherwise healthy individuals. However, patients with diagnosed metabolic syndrome often undergo pharmacotherapy, and it has never been tested whether TRE can act synergistically with pharmacotherapy in animal models or humans. In a single-arm, paired-sample trial, 19 participants with metabolic syndrome and a baseline mean daily eating window of ≥14 h, the majority of whom were on a statin and/or antihypertensive therapy, underwent 10 h of TRE (all dietary intake within a consistent self-selected 10 h window) for 12 weeks. We found this TRE intervention improves cardiometabolic health for patients with metabolic syndrome receiving standard medical care including high rates of statin and anti-hypertensive use. TRE is a potentially powerful lifestyle intervention that can be added to standard medical practice to treat metabolic syndrome. People with metabolic syndrome are at risk for diabetes and heart disease. Current treatment requires weight loss and lifestyle changes that are challenging; thus, new behavioral interventions are needed. Ten-hour time-restricted eating (TRE) limits daily dietary intake to a consistent 10-h window, creating a 14-h nightly fast. Researchers studied whether TRE for 12 weeks in people with metabolic syndrome receiving standard medical care (including medications to lower cholesterol and blood pressure) improves markers of health. TRE led to weight loss, healthier body composition (including decreased waist circumference), lower blood pressure and levels of cardiovascular disease-promoting lipids (i.e., “bad cholesterol” levels), and more restful sleep. TRE could be an effective dietary intervention to help those with metabolic syndrome. Metabolic syndrome is defined by the presence of multiple related risk factors for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) (Alberti et al., 2009Alberti K.G. Eckel R.H. Grundy S.M. Zimmet P.Z. Cleeman J.I. Donato K.A. Fruchart J.C. James W.P. Loria C.M. Smith Jr., S.C. International Diabetes Federation Task Force on Epidemiology and PreventionHational Heart, Lung, and Blood InstituteAmerican Heart AssociationWorld Heart FederationInternational Atherosclerosis SocietyInternational Association for the Study of ObesityHarmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity.Circulation. 2009; 120: 1640-1645Crossref PubMed Scopus (9986) Google Scholar, Sperling et al., 2015Sperling L.S. Mechanick J.I. Neeland I.J. Herrick C.J. Després J.P. Ndumele C.E. Vijayaraghavan K. Handelsman Y. Puckrein G.A. Araneta M.R. et al.The CardioMetabolic Health Alliance: working toward a new care model for the metabolic syndrome.J. Am. Coll. Cardiol. 2015; 66: 1050-1067Crossref PubMed Scopus (176) Google Scholar). It is highly prevalent, affecting ∼30% of the U.S. population, and confers a 5-fold increase in the risk of T2DM and doubles the risk for CVD over 5–10 years (Alberti et al., 2009Alberti K.G. Eckel R.H. Grundy S.M. Zimmet P.Z. Cleeman J.I. Donato K.A. Fruchart J.C. James W.P. Loria C.M. Smith Jr., S.C. International Diabetes Federation Task Force on Epidemiology and PreventionHational Heart, Lung, and Blood InstituteAmerican Heart AssociationWorld Heart FederationInternational Atherosclerosis SocietyInternational Association for the Study of ObesityHarmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity.Circulation. 2009; 120: 1640-1645Crossref PubMed Scopus (9986) Google Scholar, Ervin, 2009Ervin R.B. Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003-2006.Natl. Health Stat. Report. 2009; : 1-7PubMed Google Scholar). Features of metabolic syndrome include abdominal obesity, elevated blood pressure, insulin resistance, a proinflammatory and prothrombotic state, and atherogenic dyslipidemia (high triglycerides, high apolipoprotein B, high low-density lipoprotein particle [LDL-p] number, and low high-density lipoprotein cholesterol [HDL-C]). The first line of therapy for metabolic syndrome is aggressive diet and lifestyle interventions: reducing caloric intake, adopting a healthy diet, and increasing physical activity (Sperling et al., 2015Sperling L.S. Mechanick J.I. Neeland I.J. Herrick C.J. Després J.P. Ndumele C.E. Vijayaraghavan K. Handelsman Y. Puckrein G.A. Araneta M.R. et al.The CardioMetabolic Health Alliance: working toward a new care model for the metabolic syndrome.J. Am. Coll. Cardiol. 2015; 66: 1050-1067Crossref PubMed Scopus (176) Google Scholar). However, these approaches are often insufficient to effectively manage the disease, the disease gradually worsens, and patients are commonly put on medications to treat their symptoms. Treating metabolic syndrome is of crucial importance in preventing progression to T2DM and in reducing morbidity and mortality from T2DM and CVD. Thus, there is a critical unmet need for lifestyle interventions in metabolic syndrome that are effective, easy for clinicians to teach to patients during routine care, and intuitive for patients to adopt and maintain, either to prevent or work as an “add-on” to pharmacological treatment. Time-restricted eating (TRE) is an emerging dietary intervention that aims to maintain a consistent daily cycle of feeding and fasting to support robust circadian rhythms (Panda, 2016Panda S. Circadian physiology of metabolism.Science. 2016; 354: 1008-1015Crossref PubMed Scopus (517) Google Scholar). Circadian regulation of the endocrine system, autonomic nervous system, and nutrient metabolism contributes to metabolic and physiological homeostasis (Asher and Sassone-Corsi, 2015Asher G. Sassone-Corsi P. Time for food: the intimate interplay between nutrition, metabolism, and the circadian clock.Cell. 2015; 161: 84-92Abstract Full Text Full Text PDF PubMed Scopus (507) Google Scholar, Panda, 2016Panda S. Circadian physiology of metabolism.Science. 2016; 354: 1008-1015Crossref PubMed Scopus (517) Google Scholar). Both erratic eating patterns and eating over an extended period of time during the 24-h day can disrupt circadian rhythms. Chronic circadian disruption can increase the risk for components of metabolic syndrome including obesity, hypertension, insulin resistance, inflammation, and dyslipidemia (Lunn et al., 2017Lunn R.M. Blask D.E. Coogan A.N. Figueiro M.G. Gorman M.R. Hall J.E. Hansen J. Nelson R.J. Panda S. Smolensky M.H. et al.Health consequences of electric lighting practices in the modern world: A report on the National Toxicology Program’s workshop on shift work at night, artificial light at night, and circadian disruption.Sci. Total Environ. 2017; 607-608: 1073-1084Crossref PubMed Scopus (193) Google Scholar, Mohebbi et al., 2012Mohebbi I. Shateri K. Seyedmohammadzad M. The relationship between working schedule patterns and the markers of the metabolic syndrome: comparison of shift workers with day workers.Int. J. Occup. Med. Environ. Health. 2012; 25: 383-391Crossref PubMed Google Scholar, Puttonen et al., 2010Puttonen S. Härmä M. Hublin C. Shift work and cardiovascular disease - pathways from circadian stress to morbidity.Scand. J. Work Environ. Health. 2010; 36: 96-108Crossref PubMed Scopus (381) Google Scholar). Observational studies in humans have also shown a correlation between irregular eating times and increased risk for metabolic syndrome and other cardiometabolic diseases (Pot et al., 2016Pot G.K. Almoosawi S. Stephen A.M. Meal irregularity and cardiometabolic consequences: results from observational and intervention studies.Proc. Nutr. Soc. 2016; 75: 475-486Crossref PubMed Scopus (56) Google Scholar, Sierra-Johnson et al., 2008Sierra-Johnson J. Undén A.L. Linestrand M. Rosell M. Sjogren P. Kolak M. De Faire U. Fisher R.M. Hellénius M.L. Eating meals irregularly: a novel environmental risk factor for the metabolic syndrome.Obesity (Silver Spring). 2008; 16: 1302-1307Crossref PubMed Scopus (91) Google Scholar, Wennberg et al., 2016Wennberg M. Gustafsson P.E. Wennberg P. Hammarström A. Irregular eating of meals in adolescence and the metabolic syndrome in adulthood: results from a 27-year prospective cohort.Public Health Nutr. 2016; 19: 667-673Crossref PubMed Scopus (22) Google Scholar). Conversely, in animal models, maintaining a daily rhythm of feeding and fasting by TRF (time-restricted feeding refers to animal studies, TRE in human studies) sustains robust daily rhythms and prevents as well as reverses metabolic diseases (Mattson et al., 2014Mattson M.P. Allison D.B. Fontana L. Harvie M. Longo V.D. Malaisse W.J. Mosley M. Notterpek L. Ravussin E. Scheer F.A. et al.Meal frequency and timing in health and disease.Proc. Natl. Acad. Sci. USA. 2014; 111: 16647-16653Crossref PubMed Scopus (330) Google Scholar, Sulli et al., 2018Sulli G. Manoogian E.N.C. Taub P.R. Panda S. Training the circadian clock, clocking the drugs, and drugging the clock to prevent, manage, and treat chronic diseases.Trends Pharmacol. Sci. 2018; 39: 812-827Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar, Zarrinpar et al., 2016Zarrinpar A. Chaix A. Panda S. Daily eating patterns and their impact on health and disease.Trends Endocrinol. Metab. 2016; 27: 69-83Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar). TRF is effective in reversing aspects of metabolic syndrome in mice in both sexes by reducing body weight, adiposity, glucose intolerance, plasma cholesterol, and plasma triglycerides (Chaix et al., 2014Chaix A. Zarrinpar A. Miu P. Panda S. Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges.Cell Metab. 2014; 20: 991-1005Abstract Full Text Full Text PDF PubMed Scopus (553) Google Scholar, Chung et al., 2016Chung H. Chou W. Sears D.D. Patterson R.E. Webster N.J. Ellies L.G. Time-restricted feeding improves insulin resistance and hepatic steatosis in a mouse model of postmenopausal obesity.Metabolism. 2016; 65: 1743-1754Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar), and improving heart function in Drosophila (Gill et al., 2015Gill S. Le H.D. Melkani G.C. Panda S. Time-restricted feeding attenuates age-related cardiac decline in Drosophila.Science. 2015; 347: 1265-1269Crossref PubMed Scopus (175) Google Scholar). There is potential for humans to adopt TRE for health benefits. Objective longitudinal monitoring of human eating habits over several days has found that over 50% of people eat within a window of >15 h (Gill and Panda, 2015Gill S. Panda S. A smartphone app reveals erratic diurnal eating patterns in humans that can be modulated for health benefits.Cell Metab. 2015; 22: 789-798Abstract Full Text Full Text PDF PubMed Scopus (471) Google Scholar, Gupta et al., 2017Gupta N.J. Kumar V. Panda S. A camera-phone based study reveals erratic eating pattern and disrupted daily eating-fasting cycle among adults in India.PLoS One. 2017; 12: e0172852Crossref PubMed Scopus (60) Google Scholar) and only ∼10% of adults habitually maintain a ≥12 h window of fasting. Prior studies have shown that overweight or obese adults who habitually eat for ≥14 h can safely adopt an 8–10 h interval of TRE over several weeks and achieve weight loss (Gabel et al., 2018Gabel K. Hoddy K.K. Haggerty N. Song J. Kroeger C.M. Trepanowski J.F. Panda S. Varady K.A. Effects of 8-hour time restricted feeding on body weight and metabolic disease risk factors in obese adults: a pilot study.Nutr. Healthy Aging. 2018; 4: 345-353Crossref PubMed Scopus (267) Google Scholar, Gabel et al., 2019Gabel K. Hoddy K.K. Varady K.A. Safety of 8-h time restricted feeding in adults with obesity.Appl. Physiol. Nutr. Metab. 2019; 44: 107-109Crossref PubMed Scopus (38) Google Scholar, Gill and Panda, 2015Gill S. Panda S. A smartphone app reveals erratic diurnal eating patterns in humans that can be modulated for health benefits.Cell Metab. 2015; 22: 789-798Abstract Full Text Full Text PDF PubMed Scopus (471) Google Scholar, Hutchison et al., 2019Hutchison A.T. Regmi P. Manoogian E.N.C. Fleischer J.G. Wittert G.A. Panda S. Heilbronn L.K. Time-restricted feeding improves glucose tolerance in men at risk for type 2 diabetes: a randomized crossover trial.Obesity (Silver Spring). 2019; 27: 724-732PubMed Google Scholar). To date, TRE has primarily been studied in healthy humans (Antoni et al., 2018Antoni R. Robertson T.M. Robertson M.D. Johnston J.D. A pilot feasibility study exploring the effects of a moderate time-restricted feeding intervention on energy intake, adiposity and metabolic physiology in free-living human subjects.J. Nutr. Sci. 2018; 7: e22Crossref Scopus (89) Google Scholar, LeCheminant et al., 2013LeCheminant J.D. Christenson E. Bailey B.W. Tucker L.A. Restricting night-time eating reduces daily energy intake in healthy young men: a short-term cross-over study.Br. J. Nutr. 2013; 110: 2108-2113Crossref PubMed Scopus (74) Google Scholar, Moro et al., 2016Moro T. Tinsley G. Bianco A. Marcolin G. Pacelli Q.F. Battaglia G. Palma A. Gentil P. Neri M. Paoli A. Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males.J. Transl. Med. 2016; 14: 290Crossref PubMed Scopus (327) Google Scholar, Tinsley et al., 2017Tinsley G.M. Forsse J.S. Butler N.K. Paoli A. Bane A.A. La Bounty P.M. Morgan G.B. Grandjean P.W. Time-restricted feeding in young men performing resistance training: a randomized controlled trial.Eur. J. Sport Sci. 2017; 17: 200-207Crossref PubMed Scopus (164) Google Scholar), or in those who are overweight or obese but who are otherwise without metabolic disease (Gabel et al., 2018Gabel K. Hoddy K.K. Haggerty N. Song J. Kroeger C.M. Trepanowski J.F. Panda S. Varady K.A. Effects of 8-hour time restricted feeding on body weight and metabolic disease risk factors in obese adults: a pilot study.Nutr. Healthy Aging. 2018; 4: 345-353Crossref PubMed Scopus (267) Google Scholar, Gabel et al., 2019Gabel K. Hoddy K.K. Varady K.A. Safety of 8-h time restricted feeding in adults with obesity.Appl. Physiol. Nutr. Metab. 2019; 44: 107-109Crossref PubMed Scopus (38) Google Scholar, Gill and Panda, 2015Gill S. Panda S. A smartphone app reveals erratic diurnal eating patterns in humans that can be modulated for health benefits.Cell Metab. 2015; 22: 789-798Abstract Full Text Full Text PDF PubMed Scopus (471) Google Scholar, Hutchison et al., 2019Hutchison A.T. Regmi P. Manoogian E.N.C. Fleischer J.G. Wittert G.A. Panda S. Heilbronn L.K. Time-restricted feeding improves glucose tolerance in men at risk for type 2 diabetes: a randomized crossover trial.Obesity (Silver Spring). 2019; 27: 724-732PubMed Google Scholar). In these studies, TRE inadvertently reduced energy intake and led to a reduction in body weight. In men with prediabetes, 6 h TRE, without reducing caloric intake, reduced signs of insulin resistance (Sutton et al., 2018Sutton E.F. Beyl R. Early K.S. Cefalu W.T. Ravussin E. Peterson C.M. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes.Cell Metab. 2018; 27: 1212-1221.e3Abstract Full Text Full Text PDF PubMed Scopus (593) Google Scholar). In men who were overweight, a 9 h TRE decreased triglycerides, improved glycemic response to meals, and reduced mean fasting glucose assessed by a continuous glucose monitor (CGM) (Hutchison et al., 2019Hutchison A.T. Regmi P. Manoogian E.N.C. Fleischer J.G. Wittert G.A. Panda S. Heilbronn L.K. Time-restricted feeding improves glucose tolerance in men at risk for type 2 diabetes: a randomized crossover trial.Obesity (Silver Spring). 2019; 27: 724-732PubMed Google Scholar). An extensive literature review on the effect of meal timing on cardiometabolic health has prompted the American Heart Association (AHA) to suggest that nightly fasting may reduce the risk for CVD (St-Onge et al., 2017St-Onge M.P. Ard J. Baskin M.L. Chiuve S.E. Johnson H.M. Kris-Etherton P. Varady K. American Heart Association Obesity Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular Disease in the Young; Council on Clinical Cardiology; and Stroke CouncilMeal timing and frequency: implications for cardiovascular disease prevention: a scientific statement from the American Heart Association.Circulation. 2017; 135: e96-e121Crossref PubMed Scopus (363) Google Scholar). Self-reported adverse effects of TRE are rare, but one crossover study (6 h TRE, 8 a.m.–2 p.m. compared to 12 h, 8 a.m.–8 p.m., 5 weeks in each arm) included reports of vomiting (n = 1), headaches, increased thirst, and diarrhea (n = 2) (Sutton et al., 2018Sutton E.F. Beyl R. Early K.S. Cefalu W.T. Ravussin E. Peterson C.M. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes.Cell Metab. 2018; 27: 1212-1221.e3Abstract Full Text Full Text PDF PubMed Scopus (593) Google Scholar). Another study (8 h TRE, 10 a.m.–6 p.m., 12 weeks) reported a non-significant increase in mean percent occurrences of nausea, diarrhea, constipation, and dizziness (Gabel et al., 2019Gabel K. Hoddy K.K. Varady K.A. Safety of 8-h time restricted feeding in adults with obesity.Appl. Physiol. Nutr. Metab. 2019; 44: 107-109Crossref PubMed Scopus (38) Google Scholar). Resistance training combined with 8 h TRE led to significant reductions in total testosterone and total triiodothyronine (T3) with TRE after 8 weeks (Moro et al., 2016Moro T. Tinsley G. Bianco A. Marcolin G. Pacelli Q.F. Battaglia G. Palma A. Gentil P. Neri M. Paoli A. Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males.J. Transl. Med. 2016; 14: 290Crossref PubMed Scopus (327) Google Scholar); total testosterone remained within the reference range and T3 was just below the lower limit of normal. TRE of 13 h (6 a.m.–7 p.m.) compared to ad libitum (a cross-over study, 2 weeks per arm) reported increased hunger before breakfast and a trend toward increased fatigue with TRE (driven in part by a reduction in fatigue during control) (LeCheminant et al., 2013LeCheminant J.D. Christenson E. Bailey B.W. Tucker L.A. Restricting night-time eating reduces daily energy intake in healthy young men: a short-term cross-over study.Br. J. Nutr. 2013; 110: 2108-2113Crossref PubMed Scopus (74) Google Scholar). However, decreased hunger at bedtime and increased morning and overall energy were reported after 16 weeks of 10–12 h TRE (time of day decided by the participant). After a 1-year follow-up, energy levels were still significantly increased, but hunger at bedtime was no longer significantly different, although still less than at baseline (Gill and Panda, 2015Gill S. Panda S. A smartphone app reveals erratic diurnal eating patterns in humans that can be modulated for health benefits.Cell Metab. 2015; 22: 789-798Abstract Full Text Full Text PDF PubMed Scopus (471) Google Scholar). Although not considered a medically relevant adverse effect, a separate study that delayed breakfast and advanced dinner by 1.5 h each (resulting in an ∼8.5 h eating interval) reported that TRE affected opportunities for people to engage in evening social eating and drinking activities (Antoni et al., 2018Antoni R. Robertson T.M. Robertson M.D. Johnston J.D. A pilot feasibility study exploring the effects of a moderate time-restricted feeding intervention on energy intake, adiposity and metabolic physiology in free-living human subjects.J. Nutr. Sci. 2018; 7: e22Crossref Scopus (89) Google Scholar), which could conceivably have implications for long-term adherence. It is also important to note that in all TRE studies in which negative effects were reported, the timing of the TRE was pre-determined for the participant. Taking an individual’s schedule and personal preference into consideration and letting the participants choose their own TRE interval are likely important factors for adherence, efficacy, and reducing adverse effects. As part of routine medical care, patients with metabolic syndrome are counseled by healthcare providers to adopt increased physical activity and reduced caloric intake (Sperling et al., 2015Sperling L.S. Mechanick J.I. Neeland I.J. Herrick C.J. Després J.P. Ndumele C.E. Vijayaraghavan K. Handelsman Y. Puckrein G.A. Araneta M.R. et al.The CardioMetabolic Health Alliance: working toward a new care model for the metabolic syndrome.J. Am. Coll. Cardiol. 2015; 66: 1050-1067Crossref PubMed Scopus (176) Google Scholar). However, TRE as a behavioral intervention has never been studied in patients with metabolic syndrome. Components of metabolic syndrome (i.e., elevated blood pressure, abnormal lipids) are also frequently treated with pharmacotherapy. It is not known whether this high-risk group of patients with metabolic syndrome, who have already received standard medical care including diet/physical activity counseling and pharmacotherapy, will benefit from adopting TRE as an additional therapy. Based on TRF studies in rodents with pre-existing diet-induced obesity (Chaix et al., 2014Chaix A. Zarrinpar A. Miu P. Panda S. Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges.Cell Metab. 2014; 20: 991-1005Abstract Full Text Full Text PDF PubMed Scopus (553) Google Scholar), we hypothesized that a 10 h TRE intervention in patients with metabolic syndrome (and a ≥14 h/day baseline eating interval) would result in a significant improvement in mean blood glucose, fasting insulin, triglycerides, and the inflammatory marker high sensitivity C-reactive protein (hs-CRP). We also anticipated weight loss and improvements in cardiometabolic health including a reduction in blood pressure and atherogenic lipid levels. We observed significant reductions (p < 0.05) in body weight (mean ± SD, −3.3 ± 3.20 kg [−3%]), waist circumference (−4.5 ± 6.72 cm [−4%]), body mass index (BMI; −1.1 ± 0.97 kg/m2 [−3%]), percent body fat (−1.0% ± 0.91% [−3%]), visceral fat rating (−0.6 ± 0.77 [−3%]), systolic and diastolic blood pressure (−5.1 ± 9.51 mmHg [−4%] and −6.5 ± 7.94 mmHg [−8%], respectively), total cholesterol (−13.2 ± 24.29 mg/dL [−7%]), low-density lipoprotein cholesterol (LDL-C; −11.9 ± 19.01 mg/dL [−11%]), and non-high-density lipoprotein cholesterol (non-HDL-C; −11.6 ± 22.94 mg/dL [−9%]). Although we did not detect a significant improvement in average glucose, fasting insulin, triglycerides, and hs-CRP in the entire cohort, with the exception of hs-CRP these parameters modestly changed in the desirable direction. Participants with elevated fasting glucose (≥100 mg/dL) and/or HbA1c (≥5.7%) at baseline (n = 12) had a significant reduction in HbA1c (−0.22% ± 0.32% [3.7%], p = 0.04). Improvements were observed despite no change in physical activity and were independent of change in weight. This study was conducted with approval from the Institutional Review Board at UC San Diego (UCSD) and The Salk Institute for Biological Studies. All participants provided written informed consent. Participants were recruited from UCSD clinics, were diagnosed with metabolic syndrome (using AHA/National Heart, Lung, and Blood Institute cut points for waist circumference) (Alberti et al., 2009Alberti K.G. Eckel R.H. Grundy S.M. Zimmet P.Z. Cleeman J.I. Donato K.A. Fruchart J.C. James W.P. Loria C.M. Smith Jr., S.C. International Diabetes Federation Task Force on Epidemiology and PreventionHational Heart, Lung, and Blood InstituteAmerican Heart AssociationWorld Heart FederationInternational Atherosclerosis SocietyInternational Association for the Study of ObesityHarmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity.Circulation. 2009; 120: 1640-1645Crossref PubMed Scopus (9986) Google Scholar), and had a self-reported eating interval of ≥14 h per day. Our study design is summarized in Figure 1A. Thirty-five participants were enrolled. After screening to meet eligibility criteria, 25 began the TRE intervention, and 19 were included in the final analysis (Figure 1B): 13 men and 6 women, 63% non-Hispanic white, age 59 ± 11.14 (mean ± SD) years. All participants met 3 or more metabolic syndrome criteria at the time of enrollment (Table S1). Sixteen participants (84%) were taking at least one medication, and 3 (16%) were taking no medications. Overall, statin and antihypertensive use were high (79% and 63%, respectively; Table S2). Most participants were obese, with a body weight of 97.84 ± 19.73 kg and a BMI of 33.06 ± 4.76 kg/m2. Twelve of the 19 participants had an elevated fasting glucose of ≥100 mg/dL (107.2 ± 16.62 mg/dL) and/or elevated HbA1c of ≥5.7% (5.90% ± 0.41%) at baseline (Table S1). Time-of-day data for fasting lab draws were available for all 19 participants, while the time-of-day data for last dietary intake prior to overnight fasting for lab draws (and thus, fasting duration prior to lab draws) were available for n = 8. Baseline fasting labs were drawn at 09:31 ± 1:30 h (after a 13.75 ± 0.76 h fast), and at the end of intervention fasting labs were drawn at 09:03 ± 1:14 h (after a 13.38 ± 0.84 h fast). Participants used a validated app—myCircadianClock (mCC)—to log their caloric intake during the 2-week baseline and 12-week intervention periods. Mean percent adherence to logging (a minimum of two calorie-containing entries over a minimum of 5 h for a given day) was 94.30% ± 7.25% during the 2-week baseline, and 85.61% ± 12.39% during the 12-week intervention. Unlike a 6 h TRE intervention which reported several adverse events including vomiting, headaches, increased thirst, and diarrhea (Sutton et al., 2018Sutton E.F. Beyl R. Early K.S. Cefalu W.T. Ravussin E. Peterson C.M. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes.Cell Metab. 2018; 27: 1212-1221.e3Abstract Full Text Full Text PDF PubMed Scopus (593) Google Scholar), participants in our 10 h TRE intervention did not report any of these adverse events. One participant reported muscle discomfort associated with implantation and use of the CGM, but no other adverse events occurred. Missing data and data excluded from our final analysis are described in STAR Methods. As seen in previous longitudinal monitoring of daily eating patterns (Gill and Panda, 2015Gill S. Panda S. A smartphone app reveals erratic diurnal eating patterns in humans that can be modulated for health benefits.Cell Metab. 2015; 22: 789-798Abstract Full Text Full Text PDF PubMed Scopus (471) Google Scholar, Gupta et al., 2017Gupta N.J. Kumar V. Panda S. A camera-phone based study reveals erratic eating pattern and disrupted daily eating-fasting cycle among adults in India.PLoS One. 2017; 12: e0172852Crossref PubMed Scopus (60) Goog