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Chronobiology of Exercise: Evaluating the Best Time to Exercise for Greater Cardiovascular and Metabolic Benefits

Leandro C. Brito, Thais C. Marin, Luan Azevêdo, Julia M. Rosa‐Silva, Steven A. Shea, Saurabh S. Thosar

10.1002/cphy.c210036

Source: Volume 12, Issue 3, July 2022

Published online: June 2022

Full Article on Wiley Online Library



Abstract

Physiological function fluctuates across 24 h due to ongoing daily patterns of behaviors and environmental changes, including the sleep/wake, rest/activity, light/dark, and daily temperature cycles. The internal circadian system prepares the body for these anticipated behavioral and environmental changes, helping to orchestrate optimal cardiovascular and metabolic responses to these daily changes. In addition, circadian disruption, caused principally by exposure to artificial light at night (e.g., as occurs with night‐shift work), increases the risk for both cardiovascular and metabolic morbidity and mortality. Regular exercise is a countermeasure against cardiovascular and metabolic risk, and recent findings suggest that the cardiovascular benefits on blood pressure and autonomic control are greater with evening exercise compared to morning exercise. Moreover, exercise can also reset the timing of the circadian system, which raises the possibility that appropriate timing of exercise could be used to counteract circadian disruption. This article introduces the overall functional relevance of the human circadian system and presents the evidence surrounding the concepts that the time of day that exercise is performed can modulate the cardiovascular and metabolic benefits. Further work is needed to establish exercise as a tool to appropriately reset the circadian system following circadian misalignment to preserve cardiovascular and metabolic health. © 2022 American Physiological Society. Compr Physiol 12:3621‐3639, 2022.

Figure 1. Figure 1. Diurnal variations in baseline cardiovascular parameters and their responses to exercise. Typical responses during the morning are shown on the left, and those in the evening on the right. Arrows indicate the pattern of a variable at the time of day for diurnal variation, and it indicates the chronic effect of exercise: (increase); (decrease); (no changes); (greater increase) (lower decrease); ? (no data in the literature). Environmental light primarily synchronizes the central circadian clock (SCN), which drives the diurnal variation in cardiovascular regulation. Daily changes in cardiovascular regulation lead to increased cardiovascular workload in the morning, while these patterns change, leading to lower cardiovascular workload in the early evening. Exercise in the early evening (6‐9 PM) appears relatively advantageous in terms of reduced cardiovascular workload, as evidenced by a greater postexercise decrease in blood pressure 8,13,25,56,57,93,103 and systemic vascular resistance 25,56,57 at this time of the day. Additionally, a recent randomized controlled trial demonstrated the superiority of aerobic training conducted in the evening than in the morning for improvements in the subsequent clinic and ambulatory blood pressure, cardiac baroreflex sensitivity, and sympathetic vasomotor modulation in treated hypertensive patients (men) 12. This result suggests that evening exercising may promote greater benefits compared to morning exercise. Created with biorender.com.
Figure 2. Figure 2. Hypothetical interactions among exercise and the circadian clock. (A) Exercise influences the neuronal activity in the suprachiasmatic nucleus (SCN), and the central clock synchronizes the peripheral clocks advancing or delaying the rhythmic functions; (B) Exercise influences the peripheral clocks, and they inform the SCN by afferent signaling to resynchronize the central clock advancing or delaying the rhythmic functions; (C) Exercise influences both the SCN and peripheral clocks to resynchronize the clock advancing or delaying their rhythmic functions. Created with biorender.com.


Figure 1. Diurnal variations in baseline cardiovascular parameters and their responses to exercise. Typical responses during the morning are shown on the left, and those in the evening on the right. Arrows indicate the pattern of a variable at the time of day for diurnal variation, and it indicates the chronic effect of exercise: (increase); (decrease); (no changes); (greater increase) (lower decrease); ? (no data in the literature). Environmental light primarily synchronizes the central circadian clock (SCN), which drives the diurnal variation in cardiovascular regulation. Daily changes in cardiovascular regulation lead to increased cardiovascular workload in the morning, while these patterns change, leading to lower cardiovascular workload in the early evening. Exercise in the early evening (6‐9 PM) appears relatively advantageous in terms of reduced cardiovascular workload, as evidenced by a greater postexercise decrease in blood pressure 8,13,25,56,57,93,103 and systemic vascular resistance 25,56,57 at this time of the day. Additionally, a recent randomized controlled trial demonstrated the superiority of aerobic training conducted in the evening than in the morning for improvements in the subsequent clinic and ambulatory blood pressure, cardiac baroreflex sensitivity, and sympathetic vasomotor modulation in treated hypertensive patients (men) 12. This result suggests that evening exercising may promote greater benefits compared to morning exercise. Created with biorender.com.


Figure 2. Hypothetical interactions among exercise and the circadian clock. (A) Exercise influences the neuronal activity in the suprachiasmatic nucleus (SCN), and the central clock synchronizes the peripheral clocks advancing or delaying the rhythmic functions; (B) Exercise influences the peripheral clocks, and they inform the SCN by afferent signaling to resynchronize the central clock advancing or delaying the rhythmic functions; (C) Exercise influences both the SCN and peripheral clocks to resynchronize the clock advancing or delaying their rhythmic functions. Created with biorender.com.
References
 1.Alibhai FJ, Tsimakouridze EV, Reitz CJ, Pyle WG, Martino TA. Consequences of circadian and sleep disturbances for the cardiovascular system. Can J Cardiol 31: 860‐872, 2015.
 2.Anea CB, Zhang M, Stepp DW, Simkins GB, Reed G, Fulton DJ, Rudic RD. Vascular disease in mice with a dysfunctional circadian clock. Circulation 119: 1510‐1517, 2009.
 3.Aoyama S, Shibata S. Time‐of‐day‐dependent physiological responses to meal and exercise. Front Nutr 7: 18, 2020.
 4.Atkinson G, Jones H, Ainslie PN. Circadian variation in the circulatory responses to exercise: relevance to the morning peaks in strokes and cardiac events. Eur J Appl Physiol 108: 15‐29, 2010.
 5.Barrett‐O'Keefe Z, Kaplon RE, Halliwill JR. Sustained postexercise vasodilatation and histamine receptor activation following small muscle‐mass exercise in humans. Exp Physiol 98: 268‐277, 2013.
 6.Boudreau P, Yeh WH, Dumont GA, Boivin DB. A circadian rhythm in heart rate variability contributes to the increased cardiac sympathovagal response to awakening in the morning. Chronobiol Int 29: 757‐768, 2012.
 7.Brito L, Pecanha T, Tinucci T, Silva‐Junior N, Costa L, Forjaz C. Time of day affects heart rate recovery and variability after maximal exercise in pre‐hypertensive men. Chronobiol Int 32: 1385‐1390, 2015.
 8.Brito LC, Azevedo L, Pecanha T, Fecchio RY, Rezende RA, da Silva GV, Pio‐Abreu A, Mion D, Halliwill JR, Forjaz CLM. Effects of ACEi and ARB on post‐exercise hypotension induced by exercises conducted at different times of day in hypertensive men. Clin Exp Hypertens 42: 722‐727, 2020.
 9.Brito LC, Ely MR, Sieck DC, Mangum JE, Larson EA, Minson CT, Forjaz CLM, Halliwill JR. Effect of time of day on sustained postexercise vasodilation following small muscle‐mass exercise in humans. Front Physiol 10: 762, 2019.
 10.Brito LC, Fecchio RY, Pecanha T, Andrade‐Lima A, Halliwill JR, Forjaz CLM. Postexercise hypotension as a clinical tool: a “single brick” in the wall. J Am Soc Hypertens 12: e59‐e64, 2018.
 11.Brito LC, Pecanha T, Fecchio RY, Pio‐Abreu A, Silva G, Mion‐Junior D, Halliwill JR, Forjaz CLM. Comparison of morning versus evening aerobic‐exercise training on heart rate recovery in treated hypertensive men: a randomized controlled trial. Blood Press Monit, 2021.
 12.Brito LC, Pecanha T, Fecchio RY, Rezende RA, Sousa P, N DAS‐J, Abreu A, Silva G, Mion‐Junior D, Halliwill JR, Forjaz CLM. Morning versus evening aerobic training effects on blood pressure in treated hypertension. Med Sci Sports Exerc 51: 653‐662, 2019.
 13.Brito LC, Rezende RA, Mendes C, Silva‐Junior ND, Tinucci T, Cipolla‐Neto J, de Moraes Forjaz CL. Separate aftereffects of morning and evening exercise on ambulatory blood pressure in prehypertensive men. J Sports Med Phys Fitness 58: 157‐163, 2018.
 14.Buijs FN, Cazarez F, Basualdo MC, Scheer FA, Perusquia M, Centurion D, Buijs RM. The suprachiasmatic nucleus is part of a neural feedback circuit adapting blood pressure response. Neuroscience 266: 197‐207, 2014.
 15.Buijs RM, Wortel J, Van Heerikhuize JJ, Kalsbeek A. Novel environment induced inhibition of corticosterone secretion: physiological evidence for a suprachiasmatic nucleus mediated neuronal hypothalamo‐adrenal cortex pathway. Brain Res 758: 229‐236, 1997.
 16.Burgess HJ, Trinder J, Kim Y, Luke D. Sleep and circadian influences on cardiac autonomic nervous system activity. Am J Physiol 273: H1761‐H1768, 1997.
 17.Buxton OM, Frank SA, L'Hermite‐Baleriaux M, Leproult R, Turek FW, Van Cauter E. Roles of intensity and duration of nocturnal exercise in causing phase delays of human circadian rhythms. Am J Physiol 273: E536‐E542, 1997.
 18.Buxton OM, Lee CW, L'Hermite‐Baleriaux M, Turek FW, Van Cauter E. Exercise elicits phase shifts and acute alterations of melatonin that vary with circadian phase. Am J Physiol Regul Integr Comp Physiol 284: R714‐R724, 2003.
 19.Caspersen CJ, Powell KE, Christenson GM. Physical activity, exercise, and physical fitness: definitions and distinctions for health‐related research. Public Health Rep 100: 126‐131, 1985.
 20.Colberg SR, Zarrabi L, Bennington L, Nakave A, Thomas Somma C, Swain DP, Sechrist SR. Postprandial walking is better for lowering the glycemic effect of dinner than pre‐dinner exercise in type 2 diabetic individuals. J Am Med Dir Assoc 10: 394‐397, 2009.
 21.Cornelissen VA, Fagard RH. Effects of endurance training on blood pressure, blood pressure‐regulating mechanisms, and cardiovascular risk factors. Hypertension 46: 667‐675, 2005.
 22.Cugini P, Lucia P. Circadian rhythm of the renin‐angiotensin‐aldosterone system: a summary of our research studies. Clin Ter 155: 287‐291, 2004.
 23.Czeisler CA, Duffy JF, Shanahan TL, Brown EN, Mitchell JF, Rimmer DW, Ronda JM, Silva EJ, Allan JS, Emens JS, Dijk DJ, Kronauer RE. Stability, precision, and near‐24‐hour period of the human circadian pacemaker. Science 284: 2177‐2181, 1999.
 24.da Nobrega AC. The subacute effects of exercise: concept, characteristics, and clinical implications. Exerc Sport Sci Rev 33: 84‐87, 2005.
 25.de Brito LC, Rezende RA, da Silva Junior ND, Tinucci T, Casarini DE, Cipolla‐Neto J, Forjaz CL. Post‐exercise hypotension and its mechanisms differ after morning and evening exercise: a randomized crossover study. PLoS One 10: e0132458, 2015.
 26.Degaute JP, van de Borne P, Linkowski P, Van Cauter E. Quantitative analysis of the 24‐hour blood pressure and heart rate patterns in young men. Hypertension 18: 199‐210, 1991.
 27.Dickinson JM, D'Lugos AC, Naymik MA, Siniard AL, Wolfe AJ, Curtis DR, Huentelman MJ, Carroll CC. Transcriptome response of human skeletal muscle to divergent exercise stimuli. J Appl Physiol 124 (1529‐1540): 2018, 1985.
 28.Dos Santos ES, Asano RY, Filho IG, Lopes NL, Panelli P, Nascimento Dda C, Collier SR, Prestes J. Acute and chronic cardiovascular response to 16 weeks of combined eccentric or traditional resistance and aerobic training in elderly hypertensive women: a randomized controlled trial. J Strength Cond Res 28: 3073‐3084, 2014.
 29.Duffy JF, Wright KP Jr. Entrainment of the human circadian system by light. J Biol Rhythms 20: 326‐338, 2005.
 30.Edwards B, Waterhouse J, Atkinson G, Reilly T. Exercise does not necessarily influence the phase of the circadian rhythm in temperature in healthy humans. J Sports Sci 20: 725‐732, 2002.
 31.Engelmann M, Ebner K, Landgraf R, Wotjak CT. Swim stress triggers the release of vasopressin within the suprachiasmatic nucleus of male rats. Brain Res 792: 343‐347, 1998.
 32.Ezagouri S, Zwighaft Z, Sobel J, Baillieul S, Doutreleau S, Ladeuix B, Golik M, Verges S, Asher G. Physiological and molecular dissection of daily variance in exercise capacity. Cell Metab 30: 78‐91 e74, 2019.
 33.Francois ME, Baldi JC, Manning PJ, Lucas SJ, Hawley JA, Williams MJ, Cotter JD. ‘Exercise snacks’ before meals: a novel strategy to improve glycaemic control in individuals with insulin resistance. Diabetologia 57: 1437‐1445, 2014.
 34.Froy O, Garaulet M. The circadian clock in white and brown adipose tissue: mechanistic, endocrine, and clinical aspects. Endocr Rev 39: 261‐273, 2018.
 35.Golombek DA, Rosenstein RE. Physiology of circadian entrainment. Physiol Rev 90: 1063‐1102, 2010.
 36.Gomez AM, Gomez C, Aschner P, Veloza A, Munoz O, Rubio C, Vallejo S. Effects of performing morning versus afternoon exercise on glycemic control and hypoglycemia frequency in type 1 diabetes patients on sensor‐augmented insulin pump therapy. J Diabetes Sci Technol 9: 619‐624, 2015.
 37.Goodyear LJ, Chang PY, Sherwood DJ, Dufresne SD, Moller DE. Effects of exercise and insulin on mitogen‐activated protein kinase signaling pathways in rat skeletal muscle. Am J Physiol 271: E403‐E408, 1996.
 38.Gooley JJ, Lu J, Chou TC, Scammell TE, Saper CB. Melanopsin in cells of origin of the retinohypothalamic tract. Nat Neurosci 4: 1165, 2001.
 39.Grassi G, Bombelli M, Seravalle G, Dell'Oro R, Quarti‐Trevano F. Diurnal blood pressure variation and sympathetic activity. Hypertens Res 33: 381‐385, 2010.
 40.Grosbellet E, Gourmelen S, Pevet P, Criscuolo F, Challet E. Leptin normalizes photic synchronization in male ob/ob mice, via indirect effects on the suprachiasmatic nucleus. Endocrinology 156: 1080‐1090, 2015.
 41.Halliwill JR, Taylor JA, Hartwig TD, Eckberg DL. Augmented baroreflex heart rate gain after moderate‐intensity, dynamic exercise. Am J Physiol 270: R420‐R426, 1996.
 42.Harfmann BD, Schroder EA, Kachman MT, Hodge BA, Zhang X, Esser KA. Muscle‐specific loss of Bmal1 leads to disrupted tissue glucose metabolism and systemic glucose homeostasis. Skelet Muscle 6: 12, 2016.
 43.Hargreaves M, Spriet LL. Skeletal muscle energy metabolism during exercise. Nat Metab 2: 817‐828, 2020.
 44.Hecksteden A, Grutters T, Meyer T. Association between postexercise hypotension and long‐term training‐induced blood pressure reduction: a pilot study. Clin J Sport Med 23: 58‐63, 2013.
 45.Heden TD, Winn NC, Mari A, Booth FW, Rector RS, Thyfault JP, Kanaley JA. Postdinner resistance exercise improves postprandial risk factors more effectively than predinner resistance exercise in patients with type 2 diabetes. J Appl Physiol 118 (624‐634): 2015, 1985.
 46.Heffernan KS, Collier SR, Kelly EE, Jae SY, Fernhall B. Arterial stiffness and baroreflex sensitivity following bouts of aerobic and resistance exercise. Int J Sports Med 28: 197‐203, 2007.
 47.Hellsten Y, Nyberg M. Cardiovascular adaptations to exercise training. Compr Physiol 6: 1‐32, 2015.
 48.Hermida RC, Ayala DE, Fernandez JR, Mojon A. Sleep‐time blood pressure: prognostic value and relevance as a therapeutic target for cardiovascular risk reduction. Chronobiol Int 30: 68‐86, 2013.
 49.Hermida RC, Ayala DE, Mojon A, Fernandez JR. Blunted sleep‐time relative blood pressure decline increases cardiovascular risk independent of blood pressure level—the “normotensive non‐dipper” paradox. Chronobiol Int 30: 87‐98, 2013.
 50.Hermida RC, Crespo JJ, Dominguez‐Sardina M, Otero A, Moya A, Rios MT, Sineiro E, Castineira MC, Callejas PA, Pousa L, Salgado JL, Duran C, Sanchez JJ, Fernandez JR, Mojon A, Ayala DE, Hygia Project I. Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial. Eur Heart J, 2019.
 51.Hu K, Scheer FA, Laker M, Smales C, Shea SA. Endogenous circadian rhythm in vasovagal response to head‐up tilt. Circulation 123: 961‐970, 2011.
 52.Iwayama K, Kurihara R, Nabekura Y, Kawabuchi R, Park I, Kobayashi M, Ogata H, Kayaba M, Satoh M, Tokuyama K. Exercise increases 24‐h fat oxidation only when it is performed before breakfast. EBioMedicine 2: 2003‐2009, 2015.
 53.Johnson CH, Elliott JA, Foster R. Entrainment of circadian programs. Chronobiol Int 20: 741‐774, 2003.
 54.Johnson DA, Reid M, Vu TT, Gallo LC, Daviglus ML, Isasi CR, Redline S, Carnethon M. Associations of sleep duration and social jetlag with cardiometabolic risk factors in the study of Latino youth. Sleep Health, 2020.
 55.Jones H, Atkinson G, Leary A, George K, Murphy M, Waterhouse J. Reactivity of ambulatory blood pressure to physical activity varies with time of day. Hypertension 47: 778‐784, 2006.
 56.Jones H, Pritchard C, George K, Edwards B, Atkinson G. The acute post‐exercise response of blood pressure varies with time of day. Eur J Appl Physiol 104: 481‐489, 2008.
 57.Jones HG, K; Edwards, B; Atkinson, G. Effects of time of day on post‐exercise blood pressure: circadian or sleep‐related influences? Chronobiol Int 25: 987‐998, 2008.
 58.Kalsbeek A, Palm IF, La Fleur SE, Scheer FA, Perreau‐Lenz S, Ruiter M, Kreier F, Cailotto C, Buijs RM. SCN outputs and the hypothalamic balance of life. J Biol Rhythms 21: 458‐469, 2006.
 59.Kanabrocki EL, George M, Hermida RC, Messmore HL, Ryan MD, Ayala DE, Hoppensteadt DA, Fareed J, Bremner FW, Third JL, Shirazi P, Nemchausky BA. Day‐night variations in blood levels of nitric oxide, T‐TFPI, and E‐selectin. Clin Appl Thromb Hemost 7: 339‐345, 2001.
 60.Kaneko M, Zechman FW, Smith RE. Circadian variation in human peripheral blood flow levels and exercise responses. J Appl Physiol 25: 109‐114, 1968.
 61.Kantermann T, Eastman CI. Circadian phase, circadian period and chronotype are reproducible over months. Chronobiol Int 35: 280‐288, 2018.
 62.Kenney MJ, Seals DR. Postexercise hypotension. Key features, mechanisms, and clinical significance. Hypertension 22: 653‐664, 1993.
 63.Kiviniemi AM, Hautala AJ, Karjalainen JJ, Piira OP, Lepojarvi S, Ukkola O, Huikuri HV, Tulppo MP. Acute post‐exercise change in blood pressure and exercise training response in patients with coronary artery disease. Front Physiol 5: 526, 2015.
 64.Kjobsted R, Hingst JR, Fentz J, Foretz M, Sanz MN, Pehmoller C, Shum M, Marette A, Mounier R, Treebak JT, Wojtaszewski JFP, Viollet B, Lantier L. AMPK in skeletal muscle function and metabolism. FASEB J 32: 1741‐1777, 2018.
 65.Knaier R, Qian J, Roth R, Infanger D, Notter T, Wang W, Cajochen C, Scheer F. Diurnal variation in maximum endurance and maximum strength performance: a systematic review and meta‐analysis. Med Sci Sports Exerc 54: 169‐180, 2022.
 66.Kowalski GM, Moore SM, Hamley S, Selathurai A, Bruce CR. The effect of ingested glucose dose on the suppression of endogenous glucose production in humans. Diabetes 66: 2400‐2406, 2017.
 67.Lamia KA, Sachdeva UM, DiTacchio L, Williams EC, Alvarez JG, Egan DF, Vasquez DS, Juguilon H, Panda S, Shaw RJ, Thompson CB, Evans RM. AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science 326: 437‐440, 2009.
 68.Lassiter DG, Sjogren RJO, Gabriel BM, Krook A, Zierath JR. AMPK activation negatively regulates GDAP1, which influences metabolic processes and circadian gene expression in skeletal muscle. Mol Metab 16: 12‐23, 2018.
 69.Lehmkuhl LA, Park S, Zakutansky D, Jastremski CA, Wallace JP. Reproducibility of postexercise ambulatory blood pressure in Stage I hypertension. J Hum Hypertens 19: 589‐595, 2005.
 70.Liu C, Li S, Liu T, Borjigin J, Lin JD. Transcriptional coactivator PGC‐1alpha integrates the mammalian clock and energy metabolism. Nature 447: 477‐481, 2007.
 71.Liu S, Goodman J, Nolan R, Lacombe S, Thomas SG. Blood pressure responses to acute and chronic exercise are related in prehypertension. Med Sci Sports Exerc 44: 1644‐1652, 2012.
 72.Luttrell MJ, Halliwill JR. Recovery from exercise: vulnerable state, window of opportunity, or crystal ball? Front Physiol 6: 204, 2015.
 73.Mancilla R, Brouwers B, Schrauwen‐Hinderling VB, Hesselink MKC, Hoeks J, Schrauwen P. Exercise training elicits superior metabolic effects when performed in the afternoon compared to morning in metabolically compromised humans. Physiol Rep 8: e14669, 2021.
 74.Mancilla R, Krook A, Schrauwen P, Hesselink MKC. Diurnal regulation of peripheral glucose metabolism: potential effects of exercise timing. Obesity (Silver Spring) 28 (Suppl 1): S38‐S45, 2020.
 75.Manfredini R, Boari B, Smolensky MH, Salmi R, la Cecilia O, Maria Malagoni A, Haus E, Manfredini F. Circadian variation in stroke onset: identical temporal pattern in ischemic and hemorrhagic events. Chronobiol Int 22: 417‐453, 2005.
 76.Manohar C, Levine JA, Nandy DK, Saad A, Dalla Man C, McCrady‐Spitzer SK, Basu R, Cobelli C, Carter RE, Basu A, Kudva YC. The effect of walking on postprandial glycemic excursion in patients with type 1 diabetes and healthy people. Diabetes Care 35: 2493‐2499, 2012.
 77.Manohar S, Thongprayoon C, Cheungpasitporn W, Mao MA, Herrmann SM. Associations of rotational shift work and night shift status with hypertension: a systematic review and meta‐analysis. J Hypertens 35: 1929‐1937, 2017.
 78.Marcheva B, Ramsey KM, Buhr ED, Kobayashi Y, Su H, Ko CH, Ivanova G, Omura C, Mo S, Vitaterna MH, Lopez JP, Philipson LH, Bradfield CA, Crosby SD, JeBailey L, Wang X, Takahashi JS, Bass J. Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature 466: 627‐631, 2010.
 79.McQuaid SE, Hodson L, Neville MJ, Dennis AL, Cheeseman J, Humphreys SM, Ruge T, Gilbert M, Fielding BA, Frayn KN, Karpe F. Downregulation of adipose tissue fatty acid trafficking in obesity: a driver for ectopic fat deposition? Diabetes 60: 47‐55, 2011.
 80.Mihai R, Coculescu M, Wakerley JB, Ingram CD. The effects of [Arg8]vasopressin and [Arg8]vasotocin on the firing rate of suprachiasmatic neurons in vitro. Neuroscience 62: 783‐792, 1994.
 81.Millar‐Craig MW, Bishop CN, Raftery EB. Circadian variation of blood‐pressure. Lancet 1: 795‐797, 1978.
 82.Moholdt T, Parr EB, Devlin BL, Debik J, Giskeodegard G, Hawley JA. The effect of morning vs evening exercise training on glycaemic control and serum metabolites in overweight/obese men: a randomised trial. Diabetologia 64: 2061‐2076, 2021.
 83.Montaruli A, Roveda E, Calogiuri G, La Torre A, Carandente F. The sportsman readjustment after transcontinental flight: a study on marathon runners. J Sports Med Phys Fitness 49: 372‐381, 2009.
 84.Moraes MR, Bacurau RF, Ramalho JD, Reis FC, Casarini DE, Chagas JR, Oliveira V, Higa EM, Abdalla DS, Pesquero JL, Pesquero JB, Araujo RC. Increase in kinins on post‐exercise hypotension in normotensive and hypertensive volunteers. Biol Chem 388: 533‐540, 2007.
 85.Moreira SR, Cucato GG, Terra DF, Ritti‐Dias RM. Acute blood pressure changes are related to chronic effects of resistance exercise in medicated hypertensives elderly women. Clin Physiol Funct Imaging 36: 242‐248, 2014.
 86.Mores N, Martire M, Pistritto G, Volpe AR, Menini E, Folli G, Cardillo C. Platelet alpha 2‐adrenoceptors and diurnal changes of platelet aggregability in hypertensive patients. J Hypertens 12: 939‐945, 1994.
 87.Morris CJ, Purvis TE, Hu K, Scheer FA. Circadian misalignment increases cardiovascular disease risk factors in humans. Proc Natl Acad Sci U S A 113: E1402‐E1411, 2016.
 88.Morris CJ, Purvis TE, Mistretta J, Hu K, Scheer F. Circadian misalignment increases C‐reactive protein and blood pressure in chronic shift workers. J Biol Rhythms 32: 154‐164, 2017.
 89.Muller JE, Stone PH, Turi ZG, Rutherford JD, Czeisler CA, Parker C, Poole WK, Passamani E, Roberts R, Robertson T, et al. Circadian variation in the frequency of onset of acute myocardial infarction. N Engl J Med 313: 1315‐1322, 1985.
 90.Nicholls SK, Casiraghi LP, Wang W, Weber ET, Harrington ME. Evidence for internal desynchrony caused by circadian clock resetting. Yale J Biol Med 92: 259‐270, 2019.
 91.Ohmori M, Fujimura A. ACE inhibitors and chronotherapy. Clin Exp Hypertens 27: 179‐185, 2005.
 92.Otto ME, Svatikova A, Barretto RB, Santos S, Hoffmann M, Khandheria B, Somers V. Early morning attenuation of endothelial function in healthy humans. Circulation 109: 2507‐2510, 2004.
 93.Park S, Jastremski CA, Wallace JP. Time of day for exercise on blood pressure reduction in dipping and nondipping hypertension. J Hum Hypertens 19: 597‐605, 2005.
 94.Paschos GK, FitzGerald GA. Circadian clocks and vascular function. Circ Res 106: 833‐841, 2010.
 95.Peek CB, Levine DC, Cedernaes J, Taguchi A, Kobayashi Y, Tsai SJ, Bonar NA, McNulty MR, Ramsey KM, Bass J. Circadian clock interaction with HIF1alpha mediates oxygenic metabolism and anaerobic glycolysis in skeletal muscle. Cell Metab 25: 86‐92, 2017.
 96.Perrin L, Loizides‐Mangold U, Chanon S, Gobet C, Hulo N, Isenegger L, Weger BD, Migliavacca E, Charpagne A, Betts JA, Walhin JP, Templeman I, Stokes K, Thompson D, Tsintzas K, Robert M, Howald C, Riezman H, Feige JN, Karagounis LG, Johnston JD, Dermitzakis ET, Gachon F, Lefai E, Dibner C. Transcriptomic analyses reveal rhythmic and CLOCK‐driven pathways in human skeletal muscle. Elfie 7, 2018.
 97.Phillips AJK, Clerx WM, O'Brien CS, Sano A, Barger LK, Picard RW, Lockley SW, Klerman EB, Czeisler CA. Irregular sleep/wake patterns are associated with poorer academic performance and delayed circadian and sleep/wake timing. Sci Rep 7: 3216, 2017.
 98.Poirier P, Mawhinney S, Grondin L, Tremblay A, Broderick T, Cleroux J, Catellier C, Tancrede G, Nadeau A. Prior meal enhances the plasma glucose lowering effect of exercise in type 2 diabetes. Med Sci Sports Exerc 33: 1259‐1264, 2001.
 99.Poirier P, Tremblay A, Catellier C, Tancrede G, Garneau C, Nadeau A. Impact of time interval from the last meal on glucose response to exercise in subjects with type 2 diabetes. J Clin Endocrinol Metab 85: 2860‐2864, 2000.
 100.Portaluppi FS, M. H. Circadians rhythms and enviromental determinants of blood pressure regulation in normal and hypertensive conditions. In: Press H, editor. Blood Pressure Monitoring in Cardiovascular Medicine and Therapeutics. Totowa: Humana Press, 2007, p. 133‐156.
 101.Proper KI, van de Langenberg D, Rodenburg W, Vermeulen RCH, van der Beek AJ, van Steeg H, van Kerkhof LWM. The relationship between shift work and metabolic risk factors: a systematic review of longitudinal studies. Am J Prev Med 50: e147‐e157, 2016.
 102.Pullinger SA, Cocking S, Robertson CM, Tod D, Doran DA, Burniston JG, Varamenti E, Edwards BJ. Time‐of‐day variation on performance measures in repeated‐sprint tests: a systematic review. Chronobiol Int 37: 451‐468, 2020.
 103.Qian J, Scheer FA, Hu K, Shea SA. The circadian system modulates the rate of recovery of systolic blood pressure after exercise in humans. Sleep 43, 2020.
 104.Rabinovich‐Nikitin I, Lieberman B, Martino TA, Kirshenbaum LA. Circadian‐regulated cell death in cardiovascular diseases. Circulation 139: 965‐980, 2019.
 105.Racinais S. Different effects of heat exposure upon exercise performance in the morning and afternoon. Scand J Med Sci Sports 20 (Suppl 3): 80‐89, 2010.
 106.Reebs SG, Mrosovsky N. Effects of induced wheel running on the circadian activity rhythms of Syrian hamsters: entrainment and phase response curve. J Biol Rhythms 4: 39‐48, 1989.
 107.Roenneberg T, Allebrandt KV, Merrow M, Vetter C. Social jetlag and obesity. Curr Biol 22: 939‐943, 2012.
 108.Roenneberg T, Merrow M. The circadian clock and human health. Curr Biol 26: R432‐R443, 2016.
 109.Romero SA, Minson CT, Halliwill JR. The cardiovascular system after exercise. J Appl Physiol 122 (925‐932): 2017, 1985.
 110.Rudic RD, McNamara P, Reilly D, Grosser T, Curtis AM, Price TS, Panda S, Hogenesch JB, FitzGerald GA. Bioinformatic analysis of circadian gene oscillation in mouse aorta. Circulation 112: 2716‐2724, 2005.
 111.Saad A, Dalla Man C, Nandy DK, Levine JA, Bharucha AE, Rizza RA, Basu R, Carter RE, Cobelli C, Kudva YC, Basu A. Diurnal pattern to insulin secretion and insulin action in healthy individuals. Diabetes 61: 2691‐2700, 2012.
 112.Sato S, Basse AL, Schonke M, Chen S, Samad M, Altintas A, Laker RC, Dalbram E, Barres R, Baldi P, Treebak JT, Zierath JR, Sassone‐Corsi P. Time of exercise specifies the impact on muscle metabolic pathways and systemic energy homeostasis. Cell Metab 30: 92‐110 e114, 2019.
 113.Scheer FA, Hilton MF, Mantzoros CS, Shea SA. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A 106: 4453‐4458, 2009.
 114.Scheer FA, Hu K, Evoniuk H, Kelly EE, Malhotra A, Hilton MF, Shea SA. Impact of the human circadian system, exercise, and their interaction on cardiovascular function. Proc Natl Acad Sci U S A 107: 20541‐20546, 2010.
 115.Scheer FA, Shea SA. Human circadian system causes a morning peak in prothrombotic plasminogen activator inhibitor‐1 (PAI‐1) independent of the sleep/wake cycle. Blood 123: 590‐593, 2014.
 116.Scheer FA, Ter Horst GJ, van Der Vliet J, Buijs RM. Physiological and anatomic evidence for regulation of the heart by suprachiasmatic nucleus in rats. Am J Physiol Heart Circ Physiol 280: H1391‐H1399, 2001.
 117.Scheer FA, Van Doornen LJ, Buijs RM. Light and diurnal cycle affect autonomic cardiac balance in human; possible role for the biological clock. Auton Neurosci 110: 44‐48, 2004.
 118.Takahashi JS. Molecular components of the circadian clock in mammals. Diabetes Obes Metab 17 (Suppl 1): 6‐11, 2015.
 119.Taylor CE, Atkinson G, Willie CK, Jones H, Ainslie PN, Tzeng YC. Diurnal variation in the mechanical and neural components of the baroreflex. Hypertension 58: 51‐56, 2011.
 120.Teo SYM, Kanaley JA, Guelfi KJ, Marston KJ, Fairchild TJ. The effect of exercise timing on glycemic control: a randomized clinical trial. Med Sci Sports Exerc 52: 323‐334, 2020.
 121.Thosar SS, Berman AM, Herzig MX, McHill AW, Bowles NP, Swanson CM, Clemons NA, Butler MP, Clemons AA, Emens JS, Shea SA. Circadian rhythm of vascular function in midlife adults. Arterioscler Thromb Vasc Biol 39: 1203‐1211, 2019.
 122.Thosar SS, Berman AM, Herzig MX, Roberts SA, Lasarev MR, Shea SA. Morning impairment in vascular function is unrelated to overnight sleep or the inactivity that accompanies sleep. Am J Physiol Regul Integr Comp Physiol 315: R986‐R993, 2018.
 123.Thosar SS, Butler MP, Shea SA. Role of the circadian system in cardiovascular disease. J Clin Invest 128: 2157‐2167, 2018.
 124.Tibana RA, de Sousa NM, da Cunha Nascimento D, Pereira GB, Thomas SG, Balsamo S, Simoes HG, Prestes J. Correlation between acute and chronic 24‐hour blood pressure response to resistance training in adult women. Int J Sports Med 36: 82‐89, 2015.
 125.Tochikubo O, Kawano Y, Miyajima E, Toshihiro N, Ishii M. Circadian variation of hemodynamics and baroreflex functions in patients with essential hypertension. Hypertens Res 20: 157‐166, 1997.
 126.Torii J, Shinkai S, Hino S, Kurokawa Y, Tomita N, Hirose M, Watanabe S, Watanabe S, Watanabe T. Effect of time of day on adaptive response to a 4‐week aerobic exercise program. J Sports Med Phys Fitness 32: 348‐352, 1992.
 127.Torquati L, Mielke GI, Brown WJ, Kolbe‐Alexander T. Shift work and the risk of cardiovascular disease. A systematic review and meta‐analysis including dose‐response relationship. Scand J Work Environ Health 44: 229‐238, 2018.
 128.Van Cauter E, Blackman JD, Roland D, Spire JP, Refetoff S, Polonsky KS. Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep. J Clin Invest 88: 934‐942, 1991.
 129.van Moorsel D, Hansen J, Havekes B, Scheer F, Jorgensen JA, Hoeks J, Schrauwen‐Hinderling VB, Duez H, Lefebvre P, Schaper NC, Hesselink MKC, Staels B, Schrauwen P. Demonstration of a day‐night rhythm in human skeletal muscle oxidative capacity. Mol Metab 5: 635‐645, 2016.
 130.Van Reeth O, Sturis J, Byrne MM, Blackman JD, L'Hermite‐Baleriaux M, Leproult R, Oliner C, Refetoff S, Turek FW, Van Cauter E. Nocturnal exercise phase delays circadian rhythms of melatonin and thyrotropin secretion in normal men. Am J Physiol 266: E964‐E974, 1994.
 131.Verrillo A, De Teresa A, Martino C, Di Chiara G, Pinto M, Verrillo L, Torello F, Gattoni A. Differential roles of splanchnic and peripheral tissues in determining diurnal fluctuation of glucose tolerance. Am J Physiol 257: E459‐E465, 1989.
 132.Vetter C. Circadian disruption: What do we actually mean? Eur J Neurosci 51: 531‐550, 2020.
 133.Vetter C, Devore EE, Wegrzyn LR, Massa J, Speizer FE, Kawachi I, Rosner B, Stampfer MJ, Schernhammer ES. Association between rotating night shift work and risk of coronary heart disease among women. JAMA 315: 1726‐1734, 2016.
 134.Viola AU, Gabel V, Chellappa SL, Schmidt C, Hommes V, Tobaldini E, Montano N, Cajochen C. Dawn simulation light: a potential cardiac events protector. Sleep Med 16: 457‐461, 2015.
 135.Voutilainen S, Kupari M, Hippelainen M, Karppinen K, Ventila M. Circadian variation of left ventricular diastolic function in healthy people. Heart 75: 35‐39, 1996.
 136.Wolff G, Esser KA. Scheduled exercise phase shifts the circadian clock in skeletal muscle. Med Sci Sports Exerc 44: 1663‐1670, 2012.
 137.Wong PM, Hasler BP, Kamarck TW, Muldoon MF, Manuck SB. Social jetlag, chronotype, and cardiometabolic risk. J Clin Endocrinol Metab 100: 4612‐4620, 2015.
 138.Wright KP Jr, Gronfier C, Duffy JF, Czeisler CA. Intrinsic period and light intensity determine the phase relationship between melatonin and sleep in humans. J Biol Rhythms 20: 168‐177, 2005.
 139.Yi CX, van der Vliet J, Dai J, Yin G, Ru L, Buijs RM. Ventromedial arcuate nucleus communicates peripheral metabolic information to the suprachiasmatic nucleus. Endocrinology 147: 283‐294, 2006.
 140.Youngstedt SD, Elliott JA, Kripke DF. Human circadian phase‐response curves for exercise. J Physiol 597: 2253‐2268, 2019.
 141.Zambon AC, McDearmon EL, Salomonis N, Vranizan KM, Johansen KL, Adey D, Takahashi JS, Schambelan M, Conklin BR. Time‐ and exercise‐dependent gene regulation in human skeletal muscle. Genome Biol 4: R61, 2003.
 142.Zhang L, Prosdocimo DA, Bai X, Fu C, Zhang R, Campbell F, Liao X, Coller J, Jain MK. KLF15 establishes the landscape of diurnal expression in the heart. Cell Rep 13: 2368‐2375, 2015.

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Article Title: Chronobiology of Exercise: Evaluating the Best Time to Exercise for Greater Cardiovascular and Metabolic Benefits
 

How to Cite

Leandro C. Brito, Thais C. Marin, Luan Azevêdo, Julia M. Rosa‐Silva, Steven A. Shea, Saurabh S. Thosar. Chronobiology of Exercise: Evaluating the Best Time to Exercise for Greater Cardiovascular and Metabolic Benefits. Compr Physiol 2022, 12: 3621-3639. doi: 10.1002/cphy.c210036