Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans

Humaira Jamshed, Robbie A Beyl, Deborah L Della Manna, Eddy S Yang, Eric Ravussin, Courtney M Peterson, Humaira Jamshed, Robbie A Beyl, Deborah L Della Manna, Eddy S Yang, Eric Ravussin, Courtney M Peterson

Abstract

Time-restricted feeding (TRF) is a form of intermittent fasting that involves having a longer daily fasting period. Preliminary studies report that TRF improves cardiometabolic health in rodents and humans. Here, we performed the first study to determine how TRF affects gene expression, circulating hormones, and diurnal patterns in cardiometabolic risk factors in humans. Eleven overweight adults participated in a 4-day randomized crossover study where they ate between 8 am and 2 pm (early TRF (eTRF)) and between 8 am and 8 pm (control schedule). Participants underwent continuous glucose monitoring, and blood was drawn to assess cardiometabolic risk factors, hormones, and gene expression in whole blood cells. Relative to the control schedule, eTRF decreased 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 and the autophagy gene LC3A (all p < 0.04), while in the evening, it tended to increase brain-derived neurotropic factor (BNDF; p = 0.10) and also increased the expression of MTOR (p = 0.007), a major nutrient-sensing protein that regulates cell growth. eTRF also altered the diurnal patterns in cortisol and the expression of several circadian clock genes (p < 0.05). eTRF improves 24-hour glucose levels, alters lipid metabolism and circadian clock gene expression, and may also increase autophagy and have anti-aging effects in humans.

Keywords: circadian rhythms; circadian system; intermittent fasting; meal timing; time-restricted feeding.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Study Protocol. Eleven participants were randomized to eat between 08:00 and 20:00 (control arm) or between 08:00 and 14:00 (early time-restricted feeding (eTRF) arm) for 4 days and then crossed over to the other arm after a 3.5–5-week washout period. On day 4, they consumed 3 identical meals that constituted one-third of their daily energy requirements, while undergoing 24-hour continuous glucose monitoring. In addition, blood was drawn in the evening (PM) on day 3 and in the morning (AM) on day 5 to measure serum analytes and gene expression.
Figure 2
Figure 2
24-Hour Glucose Levels. Relative to the control schedule, early time-restricted feeding (eTRF) (A) changed the temporal profile of 24-hour glucose levels, as measured by continuous glucose monitoring, particularly in the evening, (B) lowered mean glucose levels while asleep and decreased 24-hour mean glucose levels, and (C) lowered glycemic excursions as measured by Mean Amplitude of Glycemic Excursions (MAGE). Error bars on panel (A) are suppressed for visual clarity. * p < 0.05.
Figure 3
Figure 3
Glycemic Markers. Relative to the control schedule, early time-restricted feeding (eTRF) decreased (A) fasting glucose, (B) fasting insulin, and (C) Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in the morning (AM) and increased (B) fasting insulin and (C) HOMA-IR in the evening (PM). (D) eTRF also increased the expression of the IRS2 and AKT2 genes in the morning and evening, respectively. Data for GLUT1 and GLUT4 are shown excluding a participant whose expression levels were ~10× higher than the sample mean. * p < 0.05.
Figure 4
Figure 4
Lipids. Relative to the control arm, early time-restricted feeding (eTRF) increased fasting levels of (A) total cholesterol, (B) LDL cholesterol, (C) HDL cholesterol, and (F) β-hydroxybutyrate (ketones) in the morning (AM) but did not affect levels of (D) triglycerides or (E) free fatty acids. (A–F). Levels of all lipids were unaffected in the evening (PM). * p < 0.05.
Figure 5
Figure 5
Hormones. Relative to the control arm, early time-restricted feeding (eTRF) tended to increase (F) cortisol levels in the morning (AM). In the evening, it lowered (F) cortisol and tended to increase (E) brain-derived neurotrophic factor (BDNF). The hormones (A) insulin-like growth factor (IGF-1), (B) IGF-binding protein 1 (IGFBP-1), (C) IGF-binding protein 3 (IGFBP-3), and (D) human growth hormone (HGH) were not significantly different between arms. * p < 0.05, #p < 0.10.
Figure 6
Figure 6
Gene Expression in Whole Blood. (A) Early time-restricted feeding (eTRF) changed the expression of several circadian clock genes, including BMAL1, PER1, CRY1, CRY2, REV-ERBA, and RORA in the morning (AM) and/or evening (PM). It also increased the expression of (B) the longevity genes SIRT1 in the morning and MTOR in the evening. (C) The autophagy genes LC3A and ATG12 were elevated in the morning and evening, respectively, although the latter was no longer significant after adjustment for multiple comparisons. (D) The expression of oxidative stress genes was unaffected. Genes in panel A were pre-specified outcomes, while genes in panels B–D were exploratory and had their p-values adjusted for multiple comparisons. #p < 0.10 (applied only to pre-specified genes in panel A), * p < 0.05, ** p < 0.007 (significant after adjustment for multiple comparisons, applied only to exploratory genes in panels B–D).

References

    1. Mattson M.P., Longo V.D., Harvie M. Impact of intermittent fasting on health and disease processes. Ageing Res. Rev. 2017;39:46–58. doi: 10.1016/j.arr.2016.10.005.
    1. Harvie M., Howell A. Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects-A Narrative Review of Human and Animal Evidence. Behav. Sci. 2017;7:4. doi: 10.3390/bs7010004.
    1. Tinsley G.M., Horne B.D. Intermittent fasting and cardiovascular disease: Current evidence and unresolved questions. Fut. Cardiol. 2018;14:47–54. doi: 10.2217/fca-2017-0038.
    1. Patterson R.E., Sears D.D. Metabolic Effects of Intermittent Fasting. Annu. Rev. Nutr. 2017;37:371–393. doi: 10.1146/annurev-nutr-071816-064634.
    1. Antoni R., Johnston K.L., Collins A.L., Robertson M.D. Effects of intermittent fasting on glucose and lipid metabolism. Proc. Nutr. Soc. 2017;76(3):361–368. doi: 10.1017/S0029665116002986.
    1. Longo V.D., Mattson M.P. Fasting: Molecular mechanisms and clinical applications. Cell Metab. 2014;19:181–192. doi: 10.1016/j.cmet.2013.12.008.
    1. Anton S.D., Moehl K., Donahoo W.T., Marosi K., Lee S.A., Mainous A.G., 3rd, Leeuwenburgh C., Mattson M.P. Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity. 2018;26:254–268. doi: 10.1002/oby.22065.
    1. Cioffi I., Evangelista A., Ponzo V., Ciccone G., Soldati L., Santarpia L., Contaldo F., Pasanisi F., Ghigo E., Bo S. Intermittent versus continuous energy restriction on weight loss and cardiometabolic outcomes: A systematic review and meta-analysis of randomized controlled trials. J. Transl. Med. 2018;16:371. doi: 10.1186/s12967-018-1748-4.
    1. Seimon R.V., Roekenes J.A., Zibellini J., Zhu B., Gibson A.A., Hills A.P., Wood R.E., King N.A., Byrne N.M., Sainsbury A. Do intermittent diets provide physiological benefits over continuous diets for weight loss? A systematic review of clinical trials. Mol. Cell Endocrinol. 2015;418:153–172. doi: 10.1016/j.mce.2015.09.014.
    1. Hatori M., Vollmers C., Zarrinpar A., DiTacchio L., Bushong E.A., Gill S., Leblanc M., Chaix A., Joens M., Fitzpatrick J.A., et al. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 2012;15:848–860. doi: 10.1016/j.cmet.2012.04.019.
    1. Zarrinpar A., Chaix A., Yooseph S., Panda S. Diet and feeding pattern affect the diurnal dynamics of the gut microbiome. Cell Metab. 2014;20:1006–1017. doi: 10.1016/j.cmet.2014.11.008.
    1. Sherman H., Genzer Y., Cohen R., Chapnik N., Madar Z., Froy O. Timed high-fat diet resets circadian metabolism and prevents obesity. FASEB J. 2012;26:3493–3502. doi: 10.1096/fj.12-208868.
    1. Wu T., Sun L., ZhuGe F., Guo X., Zhao Z., Tang R., Chen Q., Chen L., Kato H., Fu Z. Differential roles of breakfast and supper in rats of a daily three-meal schedule upon circadian regulation and physiology. Chronobiol. Int. 2011;28:890–903. doi: 10.3109/07420528.2011.622599.
    1. Olsen M.K., Choi M.H., Kulseng B., Zhao C.M., Chen D. Time-restricted feeding on weekdays restricts weight gain: A study using rat models of high-fat diet-induced obesity. Physiol. Behav. 2017;173:298–304. doi: 10.1016/j.physbeh.2017.02.032.
    1. Chaix A., Lin T., Le H.D., Chang M.W., Panda S. Time-Restricted Feeding Prevents Obesity and Metabolic Syndrome in Mice Lacking a Circadian Clock. Cell Metab. 2019;29:303–319. doi: 10.1016/j.cmet.2018.08.004.
    1. Cote I., Toklu H.Z., Green S.M., Morgan D., Carter C.S., Tumer N., Scarpace P.J. Limiting feeding to the active phase reduces blood pressure without the necessity of caloric reduction or fat mass loss. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2018;315:R751–R758. doi: 10.1152/ajpregu.00076.2018.
    1. Delahaye L.B., Bloomer R.J., Butawan M.B., Wyman J.M., Hill J.L., Lee H.W., Liu A.C., McAllan L., Han J.C., van der Merwe M. Time-restricted feeding of a high-fat diet in male C57BL/6 mice reduces adiposity but does not protect against increased systemic inflammation. Appl. Physiol. Nutr. Metab. 2018;43:1033–1042. doi: 10.1139/apnm-2017-0706.
    1. Sutton 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. doi: 10.1016/j.cmet.2018.04.010.
    1. Ravussin E., Beyl R.A., Poggiogalle E., Hsia D.S., Peterson C.M. Early Time-Restricted Feeding Reduces Appetite and Increases Fat Oxidation but Does Not Affect Energy Expenditure in Humans. Obesity. 2019 in press.
    1. Kant A.K., Graubard B.I. Association of self-reported sleep duration with eating behaviors of American adults: NHANES 2005–2010. Am. J. Clin. Nutr. 2014;100:938–947. doi: 10.3945/ajcn.114.085191.
    1. Belkacemi L., Selselet-Attou G., Louchami K., Sener A., Malaisse W.J. Intermittent fasting modulation of the diabetic syndrome in sand rats. II. In vivo investigations. Int. J. Mol. Med. 2010;26:759–765.
    1. Sherman H., Frumin I., Gutman R., Chapnik N., Lorentz A., Meylan J., le Coutre J., Froy O. Long-term restricted feeding alters circadian expression and reduces the level of inflammatory and disease markers. J. Cell. Mol. Med. 2011;15:2745–2759. doi: 10.1111/j.1582-4934.2010.01160.x.
    1. Belkacemi L., Selselet-Attou G., Bulur N., Louchami K., Sener A., Malaisse W.J. Intermittent fasting modulation of the diabetic syndrome in sand rats. III. Post-mortem investigations. Int. J. Mol. Med. 2011;27:95–102. doi: 10.3892/ijmm.2010.556.
    1. Duncan M.J., Smith J.T., Narbaiza J., Mueez F., Bustle L.B., Qureshi S., Fieseler C., Legan S.J. Restricting feeding to the active phase in middle-aged mice attenuates adverse metabolic effects of a high-fat diet. Physiol. Behav. 2016;167:1–9. doi: 10.1016/j.physbeh.2016.08.027.
    1. Sundaram S., Yan L. Time-restricted feeding reduces adiposity in mice fed a high-fat diet. Nutr. Res. 2016;36:603–611. doi: 10.1016/j.nutres.2016.02.005.
    1. Chung 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;65:1743–1754. doi: 10.1016/j.metabol.2016.09.006.
    1. Philippens K.M., von Mayersbach H., Scheving L.E. Effects of the scheduling of meal-feeding at different phases of the circadian system in rats. J. Nutr. 1977;107:176–193. doi: 10.1093/jn/107.2.176.
    1. Kudo T., Akiyama M., Kuriyama K., Sudo M., Moriya T., Shibata S. Night-time restricted feeding normalises clock genes and Pai-1 gene expression in the db/db mouse liver. Diabetologia. 2004;47:1425–1436. doi: 10.1007/s00125-004-1461-0.
    1. Manzanero S., Erion J.R., Santro T., Steyn F.J., Chen C., Arumugam T.V., Stranahan A.M. Intermittent fasting attenuates increases in neurogenesis after ischemia and reperfusion and improves recovery. J. Cereb. Blood Flow Metab. 2014;34:897–905. doi: 10.1038/jcbfm.2014.36.
    1. Garcia-Luna C., Soberanes-Chavez P., de Gortari P. Prepuberal light phase feeding induces neuroendocrine alterations in adult rats. J. Endocrinol. 2017;232:15–28. doi: 10.1530/JOE-16-0402.
    1. Park S., Yoo K.M., Hyun J.S., Kang S. Intermittent fasting reduces body fat but exacerbates hepatic insulin resistance in young rats regardless of high protein and fat diets. J. Nutr. Biochem. 2017;40:14–22. doi: 10.1016/j.jnutbio.2016.10.003.
    1. Belkacemi L., Selselet-Attou G., Hupkens E., Nguidjoe E., Louchami K., Sener A., Malaisse W.J. Intermittent fasting modulation of the diabetic syndrome in streptozotocin-injected rats. Int. J. Endocrinol. 2012;2012:962012. doi: 10.1155/2012/962012.
    1. Chaix A., Zarrinpar A., Miu P., Panda S. Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab. 2014;20:991–1005. doi: 10.1016/j.cmet.2014.11.001.
    1. Mitchell S.J., Bernier M., Mattison J.A., Aon M.A., Kaiser T.A., Anson R.M., Ikeno Y., Anderson R.M., Ingram D.K., de Cabo R. Daily Fasting Improves Health and Survival in Male Mice Independent of Diet Composition and Calories. Cell Metab. 2019;29:221–228. doi: 10.1016/j.cmet.2018.08.011.
    1. Smith N.J., Caldwell J.L., van der Merwe M., Sharma S., Butawan M., Puppa M., Bloomer R.J. A Comparison of Dietary and Caloric Restriction Models on Body Composition, Physical Performance, and Metabolic Health in Young Mice. Nutrients. 2019;11(2):350. doi: 10.3390/nu11020350.
    1. Sun S., Hanzawa F., Umeki M., Ikeda S., Mochizuki S., Oda H. Time-restricted feeding suppresses excess sucrose-induced plasma and liver lipid accumulation in rats. PLoS ONE. 2018;13:e0201261. doi: 10.1371/journal.pone.0201261.
    1. Woodie L.N., Luo Y., Wayne M.J., Graff E.C., Ahmed B., O’Neill A.M., Greene M.W. Restricted feeding for 9h in the active period partially abrogates the detrimental metabolic effects of a Western diet with liquid sugar consumption in mice. Metabolism. 2018;82:1–13. doi: 10.1016/j.metabol.2017.12.004.
    1. Sundaram S., Yan L. Time-restricted feeding mitigates high-fat diet-enhanced mammary tumorigenesis in MMTV-PyMT mice. Nutr. Res. 2018;59:72–79. doi: 10.1016/j.nutres.2018.07.014.
    1. Li X.M., Delaunay F., Dulong S., Claustrat B., Zampera S., Fujii Y., Teboul M., Beau J., Levi F. Cancer inhibition through circadian reprogramming of tumor transcriptome with meal timing. Cancer Res. 2010;70:3351–3360. doi: 10.1158/0008-5472.CAN-09-4235.
    1. Wu M.W., Li X.M., Xian L.J., Levi F. Effects of meal timing on tumor progression in mice. Life Sci. 2004;75:1181–1193. doi: 10.1016/j.lfs.2004.02.014.
    1. Gabel 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;4:345–353. doi: 10.3233/NHA-170036.
    1. Antoni R., Robertson T.M., Robertson M., Johnston J. 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;7:1–6. doi: 10.1017/jns.2018.13.
    1. Gasmi M., Sellami M., Denham J., Padulo J., Kuvacic G., Selmi W., Khalifa R. Time-restricted feeding influences immune responses without compromising muscle performance in older men. Nutrition. 2018;51–52:29–37. doi: 10.1016/j.nut.2017.12.014.
    1. Moro 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;14:290. doi: 10.1186/s12967-016-1044-0.
    1. Gill S., Panda S. A Smartphone App Reveals Erratic Diurnal Eating Patterns in Humans that Can Be Modulated for Health Benefits. Cell Metab. 2015;22:789–798. doi: 10.1016/j.cmet.2015.09.005.
    1. Tinsley 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;17:200–207. doi: 10.1080/17461391.2016.1223173.
    1. Stote K.S., Baer D.J., Spears K., Paul D.R., Harris G.K., Rumpler W.V., Strycula P., Najjar S.S., Ferrucci L., Ingram D.K., et al. A controlled trial of reduced meal frequency without caloric restriction in healthy, normal-weight, middle-aged adults. Am. J. Clin. Nutr. 2007;85:981–988. doi: 10.1093/ajcn/85.4.981.
    1. Carlson O., Martin B., Stote K.S., Golden E., Maudsley S., Najjar S.S., Ferrucci L., Ingram D.K., Longo D.L., Rumpler W.V., et al. Impact of reduced meal frequency without caloric restriction on glucose regulation in healthy, normal-weight middle-aged men and women. Metabolism. 2007;56:1729–1734. doi: 10.1016/j.metabol.2007.07.018.
    1. Poggiogalle E., Jamshed H., Peterson C.M. Circadian regulation of glucose, lipid, and energy metabolism in humans. Metabolism. 2018;84:11–27. doi: 10.1016/j.metabol.2017.11.017.
    1. Dallmann R., Viola A.U., Tarokh L., Cajochen C., Brown S.A. The human circadian metabolome. Proc. Natl. Acad. Sci. USA. 2012;109:2625–2629. doi: 10.1073/pnas.1114410109.
    1. Gamble K.L., Berry R., Frank S.J., Young M.E. Circadian clock control of endocrine factors. Nat. Rev. Endocrinol. 2014;10:466–475. doi: 10.1038/nrendo.2014.78.
    1. Tsang A.H., Astiz M., Friedrichs M., Oster H. Endocrine regulation of circadian physiology. J. Endocrinol. 2016;230:R1–R11. doi: 10.1530/JOE-16-0051.
    1. Rabinovitz H.R., Boaz M., Ganz T., Jakubowicz D., Matas Z., Madar Z., Wainstein J. Big breakfast rich in protein and fat improves glycemic control in type 2 diabetics. Obesity. 2014;22:E46–E54. doi: 10.1002/oby.20654.
    1. Jakubowicz D., Barnea M., Wainstein J., Froy O. High caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women. Obesity. 2013;21:2504–2512. doi: 10.1002/oby.20460.
    1. Reid K.J., Baron K.G., Zee P.C. Meal timing influences daily caloric intake in healthy adults. Nutr. Res. 2014;34:930–935. doi: 10.1016/j.nutres.2014.09.010.
    1. Ruiz-Lozano T., Vidal J., de Hollanda A., Scheer F.A., Garaulet M., Izquierdo-Pulido M. Timing of food intake is associated with weight loss evolution in severe obese patients after bariatric surgery. Clin. Nutr. 2016;35:1308–1314. doi: 10.1016/j.clnu.2016.02.007.
    1. Garaulet M., Gomez-Abellan P., Alburquerque-Bejar J.J., Lee Y.C., Ordovas J.M., Scheer F.A. Timing of food intake predicts weight loss effectiveness. Int. J. Obes. 2013;37:604–611. doi: 10.1038/ijo.2012.229.
    1. Keim N.L., Van Loan M.D., Horn W.F., Barbieri T.F., Mayclin P.L. Weight loss is greater with consumption of large morning meals and fat-free mass is preserved with large evening meals in women on a controlled weight reduction regimen. J. Nutr. 1997;127:75–82. doi: 10.1093/jn/127.1.75.
    1. Scheer F.A., Hilton M.F., Mantzoros C.S., Shea S.A. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc. Natl. Acad. Sci. USA. 2009;106:4453–4458. doi: 10.1073/pnas.0808180106.
    1. Wefers J., van Moorsel D., Hansen J., Connell N.J., Havekes B., Hoeks J., van Marken Lichtenbelt W.D., Duez H., Phielix E., Kalsbeek A., et al. Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle. Proc. Natl. Acad. Sci. USA. 2018;115:7789–7794. doi: 10.1073/pnas.1722295115.
    1. Morris C.J., Purvis T.E., Hu K., Scheer F.A. Circadian misalignment increases cardiovascular disease risk factors in humans. Proc. Natl. Acad. Sci. USA. 2016;113:E1402–E1411. doi: 10.1073/pnas.1516953113.
    1. Morris C.J., Yang J.N., Garcia J.I., Myers S., Bozzi I., Wang W., Buxton O.M., Shea S.A., Scheer F.A. Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans. Proc. Natl. Acad. Sci. USA. 2015;112:E2225–E2234. doi: 10.1073/pnas.1418955112.
    1. EasyGV. [(accessed on 13 December 2018)]; Available online: .
    1. Van Cauter E., Polonsky K.S., Scheen A.J. Roles of circadian rhythmicity and sleep in human glucose regulation. Endocr. Rev. 1997;18:716–738. doi: 10.1210/edrv.18.5.0317.
    1. Hibi M., Masumoto A., Naito Y., Kiuchi K., Yoshimoto Y., Matsumoto M., Katashima M., Oka J., Ikemoto S. Nighttime snacking reduces whole body fat oxidation and increases LDL cholesterol in healthy young women. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2013;304:R94–R101. doi: 10.1152/ajpregu.00115.2012.
    1. Choi H.R., Kim J., Lim H., Park Y.K. Two-Week Exclusive Supplementation of Modified Ketogenic Nutrition Drink Reserves Lean Body Mass and Improves Blood Lipid Profile in Obese Adults: A Randomized Clinical Trial. Nutrients. 2018;10(11):1895. doi: 10.3390/nu10121895.
    1. Jakubowicz D., Wainstein J., Landau Z., Raz I., Ahren B., Chapnik N., Ganz T., Menaged M., Barnea M., Bar-Dayan Y. Influences of Breakfast on Clock Gene Expression and Postprandial Glycemia in Healthy Individuals and Individuals With Diabetes: A Randomized Clinical Trial. Diabetes Care. 2017;40:1573–1579. doi: 10.2337/dc16-2753.
    1. Rahman S., Islam R. Mammalian Sirt1: Insights on its biological functions. Cell Commun. Signal. 2011;9:11. doi: 10.1186/1478-811X-9-11.
    1. Martinez-Lopez N., Tarabra E., Toledo M., Garcia-Macia M., Sahu S., Coletto L., Batista-Gonzalez A., Barzilai N., Pessin J.E., Schwartz G.J., et al. System-wide Benefits of Intermeal Fasting by Autophagy. Cell Metab. 2017;26:856–871.e855. doi: 10.1016/j.cmet.2017.09.020.
    1. Mani K., Javaheri A., Diwan A. Lysosomes Mediate Benefits of Intermittent Fasting in Cardiometabolic Disease: The Janitor Is the Undercover Boss. Compr. Physiol. 2018;8:1639–1667. doi: 10.1002/cphy.c180005.

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