The effects of diurnal intermittent fasting on proinflammatory cytokine levels while controlling for sleep/wake pattern, meal composition and energy expenditure

Autoři: Aljohara S. Almeneessier aff001;  Abdulrahman A. BaHammam aff003;  Mohammed Alzoghaibi aff004;  Awad H. Olaish aff002;  Samar Z. Nashwan aff002;  Ahmed S. BaHammam aff002
Působiště autorů: Department of Family Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia aff001;  University Sleep Disorders Center, College of Medicine, King Sau University, Riyadh, Saudi Arabia aff002;  King Abdulaziz & his companies Foundation for giftedness & creativity, Manarat Al Riyadh School, Ministry of Education, Riyadh, Saudi Arabia aff003;  Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia aff004;  The Strategic Technologies Program of the National Plan for Sciences and Technology and Innovation, Saudi Arabia (MED511-02-08), Riyadh, Saudi Arabia aff005
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article



This study aimed to assess the effect of diurnal intermittent fasting (DIF) during and outside of the month of Ramadan on plasma levels of interleukin (IL)-1β, IL-6, and IL-8, while controlling for sleep/wake pattern, sleep length and quality, meal composition, energy consumption and expenditure, and light exposure. DIF outside of the month of Ramadan was performed to evaluate the effect of DIF in the absence of the way of life accompanying Ramadan.


Twelve healthy male volunteers with a mean age of 25.1 ± 2.5 years arrived to the sleep laboratory on 4 times: 1) adaptation, 5 weeks before Ramadan; 2) 4 weeks before Ramadan while performing DIF for 1 week (fasting outside of Ramadan; FOR); 3) 1 week before Ramadan (non-fasting baseline; non-fasting BL); and 4) After completing 2 weeks of Ramadan while performing DIF. Plasma levels of cytokines were assessed using enzyme-linked immunoassays at 22:00, 02:00, 04:00, 06:00, and 11:00.


During DIF, there was a significant decrease in the levels of cytokines, particularly, IL-1β and IL-6, in most measurements compared to non-fasting BL. This reduction was more obvious during the FOR period. There were no significant changes in the circadian phase of the measured cytokines reflected by the acrophase of the measured variables during fasting (FOR and Ramadan) compared to non-fasting BL.


Under controlled conditions, DIF led to significantly decreased plasma levels of cytokines (IL-1β, IL-6, and IL-8), particularly IL-1β and IL-6 across 24 h. DIF had no effect on the circadian patterns of the measured cytokines as shown by cosinor analysis.

Klíčová slova:

Bioenergetics – Biomarkers – Circadian rhythms – Cytokines – Chronobiology – Inflammatory diseases – Sleep – Sunset


1. Almeneessier AS, Pandi-Perumal SR, BaHammam AS. Intermittent fasting, insufficient sleep, and circadian rhythm: Interaction and effects on the cardiometabolic system. Curr Sleep Med Rep. 2018;4:179–95. doi: 10.1007/s40675-018-0124-5

2. Almeneessier AS, BaHammam AS. How does diurnal intermittent fasting impact sleep, daytime sleepiness, and markers of the biological clock? Current insights. Nat Sci Sleep. 2018;10:439–52. Epub 2018/12/24. doi: 10.2147/NSS.S165637 30573998; PubMed Central PMCID: PMCPMC6292409.

3. Mindikoglu AL, Opekun AR, Gagan SK, Devaraj S. Impact of Time-Restricted Feeding and Dawn-to-Sunset Fasting on Circadian Rhythm, Obesity, Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease. Gastroenterol Res Pract. 2017;2017:3932491. Epub 2018/01/20. doi: 10.1155/2017/3932491 29348746; PubMed Central PMCID: PMC5733887.

4. Yu SL, Kuan WP, Wong CK, Li EK, Tam LS. Immunopathological roles of cytokines, chemokines, signaling molecules, and pattern-recognition receptors in systemic lupus erythematosus. Clin Dev Immunol. 2012;2012:715190. Epub 2012/02/09. doi: 10.1155/2012/715190 22312407; PubMed Central PMCID: PMC3270521.

5. Gonzalez O, Tobia C, Ebersole J, Novak MJ. Caloric restriction and chronic inflammatory diseases. Oral Dis. 2012;18(1):16–31. Epub 2011/07/14. doi: 10.1111/j.1601-0825.2011.01830.x 21749581; PubMed Central PMCID: PMCPMC3193874.

6. Faris MAE, A.Jahrami H, Obaideen AA, Madkour MI. Impact of diurnal intermittent fasting during Ramadan on inflammatory and oxidative stress markers in healthy people: Systematic review and meta-analysis. J Nutrition Intermediary Metabolism. 2019;15:18–26. doi: 10.1016/j.jnim.2018.11.005

7. Kiecolt-Glaser JK. Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge. Psychosomatic medicine. 2010;72(4):365–9. Epub 2010/04/23. doi: 10.1097/PSY.0b013e3181dbf489 20410248; PubMed Central PMCID: PMC2868080.

8. Buxton OM, Broussard JL, Zahl AK, Hall M. Effects of Sleep Defi ciency on Hormones, Cytokines, and Metabolism. In: Redline S, Berger RA, editors. Impact of Sleep and Sleep Disturbances on Obesity and Cancer, Energy Balance and Cancer. New York: Springer Science+Business Media; 2014. p. 25–50.

9. BaHammam A, Alrajeh M, Albabtain M, Bahammam S, Sharif M. Circadian pattern of sleep, energy expenditure, and body temperature of young healthy men during the intermittent fasting of Ramadan. Appetite. 2010;54(2):426–9. Epub 2010/01/27. S0195-6663(10)00034-6 [pii] doi: 10.1016/j.appet.2010.01.011 20100529.

10. Lange T, Dimitrov S, Born J. Effects of sleep and circadian rhythm on the human immune system. Ann N Y Acad Sci. 2010;1193:48–59. Epub 2010/04/20. doi: 10.1111/j.1749-6632.2009.05300.x 20398008.

11. Smart NA, Steele M. The effect of physical training on systemic proinflammatory cytokine expression in heart failure patients: a systematic review. Congest Heart Fail. 2011;17(3):110–4. Epub 2011/05/26. doi: 10.1111/j.1751-7133.2011.00217.x 21609383.

12. Nakao A. Temporal regulation of cytokines by the circadian clock. J Immunol Res. 2014;2014:614529. Epub 2014/05/09. doi: 10.1155/2014/614529 24809063; PubMed Central PMCID: PMCPMC3997878.

13. Dominguez Rodriguez A, Abreu Gonzalez P, Garcia MJ, de la Rosa A, Vargas M, Marrero F. [Circadian variations in proinflammatory cytokine concentrations in acute myocardial infarction]. Rev Esp Cardiol. 2003;56(6):555–60. Epub 2003/06/05. doi: 10.1016/s0300-8932(03)76916-4 12783730.

14. Leon-Pedroza JI, Gonzalez-Tapia LA, del Olmo-Gil E, Castellanos-Rodriguez D, Escobedo G, Gonzalez-Chavez A. [Low-grade systemic inflammation and the development of metabolic diseases: from the molecular evidence to the clinical practice]. Cir Cir. 2015;83(6):543–51. Epub 2015/07/15. doi: 10.1016/j.circir.2015.05.041 26159364.

15. Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 2018;281(1):8–27. Epub 2017/12/17. doi: 10.1111/imr.12621 29247995; PubMed Central PMCID: PMCPMC5756628.

16. Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6(10):a016295. Epub 2014/09/06. doi: 10.1101/cshperspect.a016295 25190079; PubMed Central PMCID: PMCPMC4176007.

17. Jiang WG, Sanders AJ, Ruge F, Harding KG. Influence of interleukin-8 (IL-8) and IL-8 receptors on the migration of human keratinocytes, the role of PLC-gamma and potential clinical implications. Exp Ther Med. 2012;3(2):231–6. Epub 2012/09/13. doi: 10.3892/etm.2011.402 22969874; PubMed Central PMCID: PMCPMC3438606.

18. Bickel M. The role of interleukin-8 in inflammation and mechanisms of regulation. J Periodontol. 1993;64(5 Suppl):456–60. Epub 1993/05/01. 8315568.

19. Alzoghaibi MA, Pandi-Perumal SR, Sharif MM, BaHammam AS. Diurnal intermittent fasting during Ramadan: the effects on leptin and ghrelin levels. PLoS One. 2014;9(3):e92214. Epub 2014/03/19. doi: 10.1371/journal.pone.0092214 24637892; PubMed Central PMCID: PMC3956913.

20. Almeneessier AS, Alzoghaibi M, BaHammam AA, Ibrahim MG, Olaish AH, Nashwan SZ, et al. The effects of diurnal intermittent fasting on the wake-promoting neurotransmitter orexin-A. Ann Thorac Med. 2018;13(1):48–54. Epub 2018/02/02. doi: 10.4103/atm.ATM_181_17 29387256; PubMed Central PMCID: PMCPMC5772108.

21. Bahammam A. Does Ramadan fasting affect sleep? Int J Clin Pract. 2006;60(12):1631–7. Epub 2006/05/04. IJCP811 [pii] doi: 10.1111/j.1742-1241.2005.00811.x 16669826.

22. Agnew HW Jr., Webb WB, Williams RL. The first night effect: an EEG study of sleep. Psychophysiology. 1966;2(3):263–6. Epub 1966/01/01. doi: 10.1111/j.1469-8986.1966.tb02650.x 5903579.

23. Qasrawi SO, Pandi-Perumal SR, BaHammam AS. The effect of intermittent fasting during Ramadan on sleep, sleepiness, cognitive function, and circadian rhythm. Sleep Breath. 2017;21:577–86. Epub 2017/02/13. doi: 10.1007/s11325-017-1473-x 28190167.

24. Cajochen C, Zeitzer JM, Czeisler CA, Dijk DJ. Dose-response relationship for light intensity and ocular and electroencephalographic correlates of human alertness. Behavioural brain research. 2000;115(1):75–83. Epub 2000/09/21. doi: 10.1016/s0166-4328(00)00236-9 10996410.

25. Malavolti M, Pietrobelli A, Dugoni M, Poli M, Romagnoli E, De Cristofaro P, et al. A new device for measuring resting energy expenditure (REE) in healthy subjects. Nutr Metab Cardiovasc Dis. 2007;17:338–43. doi: 10.1016/j.numecd.2005.12.009 17562571

26. Mignault D, St Onge M, Karelis AD, Allison DB, Rabasa-Lhoret R. Evaluation of the portable health wear armband, a device to measure total daily energy expenditure in free-living type 2 diabetic individuals. Diabetes Care. 2005;28:225–7.

27. Berry RB, Albertario CL, Harding SM, Lloyd RM, Plante DT, Quan SF, et al. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications, Version 2.5., Darien, Illinois: American Academy of Sleep Medicine, 2018. 2018.

28. Nelson W, Tong YL, Lee JK, Halberg F. Methods for cosinor-rhythmometry. Chronobiologia. 1979;6(4):305–23. Epub 1979/10/01. 548245.

29. BaHammam A. Assessment of sleep patterns, daytime sleepiness, and chronotype during Ramadan in fasting and nonfasting individuals. Saudi Med J. 2005;26(4):616–22. Epub 2005/05/19. 15900372.

30. Petrovsky N, Harrison LC. The chronobiology of human cytokine production. Int Rev Immunol. 1998;16(5–6):635–49. Epub 1998/07/01. doi: 10.3109/08830189809043012 9646180.

31. Emerson SR, Kurti SP, Harms CA, Haub MD, Melgarejo T, Logan C, et al. Magnitude and Timing of the Postprandial Inflammatory Response to a High-Fat Meal in Healthy Adults: A Systematic Review. Adv Nutr. 2017;8(2):213–25. Epub 2017/03/17. doi: 10.3945/an.116.014431 28298267; PubMed Central PMCID: PMCPMC5347112.

32. Manning PJ, Sutherland WH, McGrath MM, de Jong SA, Walker RJ, Williams MJ. Postprandial cytokine concentrations and meal composition in obese and lean women. Obesity (Silver Spring). 2008;16(9):2046–52. Epub 2009/02/03. doi: 10.1038/oby.2008.334 19186329.

33. Dror E, Dalmas E, Meier DT, Wueest S, Thevenet J, Thienel C, et al. Postprandial macrophage-derived IL-1beta stimulates insulin, and both synergistically promote glucose disposal and inflammation. Nat Immunol. 2017;18(3):283–92. Epub 2017/01/17. doi: 10.1038/ni.3659 28092375.

34. Devaraj S, Wang-Polagruto J, Polagruto J, Keen CL, Jialal I. High-fat, energy-dense, fast-food-style breakfast results in an increase in oxidative stress in metabolic syndrome. Metabolism. 2008;57(6):867–70. Epub 2008/05/27. doi: 10.1016/j.metabol.2008.02.016 18502272; PubMed Central PMCID: PMCPMC2692901.

35. Almeneessier AS, Bahammam AS, Sharif MM, Bahammam SA, Nashwan SZ, Pandi Perumal SR, et al. The influence of intermittent fasting on the circadian pattern of melatonin while controlling for caloric intake, energy expenditure, light exposure, and sleep schedules: A preliminary report. Ann Thorac Med. 2017;12(3):183–90. Epub 2017/08/16. doi: 10.4103/atm.ATM_15_17 28808490; PubMed Central PMCID: PMCPMC5541966.

36. Vgontzas AN, Bixler EO, Lin HM, Prolo P, Trakada G, Chrousos GP. IL-6 and its circadian secretion in humans. Neuroimmunomodulation. 2005;12(3):131–40. Epub 2005/05/21. doi: 10.1159/000084844 15905620.

37. Chae JS, Paik JK, Kang R, Kim M, Choi Y, Lee SH, et al. Mild weight loss reduces inflammatory cytokines, leukocyte count, and oxidative stress in overweight and moderately obese participants treated for 3 years with dietary modification. Nutr Res. 2013;33(3):195–203. Epub 2013/03/20. doi: 10.1016/j.nutres.2013.01.005 23507225.

38. Fernandez-Sanchez A, Madrigal-Santillan E, Bautista M, Esquivel-Soto J, Morales-Gonzalez A, Esquivel-Chirino C, et al. Inflammation, oxidative stress, and obesity. Int J Mol Sci. 2011;12(5):3117–32. Epub 2011/06/21. doi: 10.3390/ijms12053117 21686173; PubMed Central PMCID: PMCPMC3116179.

39. Sadeghirad B, Motaghipisheh S, Kolahdooz F, Zahedi MJ, Haghdoost AA. Islamic fasting and weight loss: a systematic review and meta-analysis. Public Health Nutr. 2014;17(2):396–406. Epub 2012/11/28. doi: 10.1017/S1368980012005046 23182306.

40. Dogan S, Ray A, Cleary MP. The influence of different calorie restriction protocols on serum pro-inflammatory cytokines, adipokines and IGF-I levels in female C57BL6 mice: short term and long term diet effects. Meta Gene. 2017;12:22–32. Epub 2017/04/05. doi: 10.1016/j.mgene.2016.12.013 28373962; PubMed Central PMCID: PMCPMC5375115.

41. Che W, Lerner-Marmarosh N, Huang Q, Osawa M, Ohta S, Yoshizumi M, et al. Insulin-like growth factor-1 enhances inflammatory responses in endothelial cells: role of Gab1 and MEKK3 in TNF-alpha-induced c-Jun and NF-kappaB activation and adhesion molecule expression. Circ Res. 2002;90(11):1222–30. Epub 2002/06/18. doi: 10.1161/01.res.0000021127.83364.7d 12065326.

42. Lee C, Safdie FM, Raffaghello L, Wei M, Madia F, Parrella E, et al. Reduced levels of IGF-I mediate differential protection of normal and cancer cells in response to fasting and improve chemotherapeutic index. Cancer Res. 2010;70(4):1564–72. Epub 2010/02/11. doi: 10.1158/0008-5472.CAN-09-3228 20145127; PubMed Central PMCID: PMCPMC2836202.

43. Rahbar AR, Safavi E, Rooholamini M, Jaafari F, Darvishi S, Rahbar A. Effects of Intermittent Fasting during Ramadan on Insulin-like Growth Factor-1, Interleukin 2, and Lipid Profile in Healthy Muslims. Int J Prev Med. 2019;10:7. Epub 2019/02/19. doi: 10.4103/ijpvm.IJPVM_252_17 30774841; PubMed Central PMCID: PMCPMC6360844.

44. BaHammam A. Effect of fasting during Ramadan on sleep architecture, daytime sleepiness and sleep pattern. Sleep Biol Rhythm. 2004;2:135–43.

45. Roky R, Chapotot F, Hakkou F, Benchekroun MT, Buguet A. Sleep during Ramadan intermittent fasting. J Sleep Res. 2001;10(4):319–27. Epub 2002/03/21. 269 [pii]. doi: 10.1046/j.1365-2869.2001.00269.x 11903862.

46. Bogdan A, Bouchareb B, Touitou Y. Ramadan fasting alters endocrine and neuroendocrine circadian patterns. Meal-time as a synchronizer in humans? Life Sci. 2001;68(14):1607–15. Epub 2001/03/27. S0024320501009663 [pii]. doi: 10.1016/s0024-3205(01)00966-3 11263673.

47. Krauchi K, Cajochen C, Werth E, Wirz-Justice A. Alteration of internal circadian phase relationships after morning versus evening carbohydrate-rich meals in humans. J Biol Rhythms. 2002;17(4):364–76. Epub 2002/08/08. doi: 10.1177/074873040201700409 12164252.

Článek vyšel v časopise


2019 Číslo 12
Nejčtenější tento týden