Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants
2.2. Study Design
2.3. Continuous Glucose Monitoring
2.4. Serum Chemistry
2.5. Gene Expression
2.6. Statistical Methods
3. Results
3.1. Participant Characteristics
3.2. 24-Hour Glucose Levels
3.3. Glycemic Markers
3.4. Lipids
3.5. Hormones
3.6. Gene Expression
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Mattson, M.P.; Longo, V.D.; Harvie, M. Impact of intermittent fasting on health and disease processes. Ageing Res. Rev. 2017, 39, 46–58. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef]
- Tinsley, G.M.; Horne, B.D. Intermittent fasting and cardiovascular disease: Current evidence and unresolved questions. Fut. Cardiol. 2018, 14, 47–54. [Google Scholar] [CrossRef] [PubMed]
- Patterson, R.E.; Sears, D.D. Metabolic Effects of Intermittent Fasting. Annu. Rev. Nutr. 2017, 37, 371–393. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- 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. [Google Scholar] [CrossRef]
- Longo, V.D.; Mattson, M.P. Fasting: Molecular mechanisms and clinical applications. Cell Metab. 2014, 19, 181–192. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef] [Green Version]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [Green Version]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef]
- Sundaram, S.; Yan, L. Time-restricted feeding reduces adiposity in mice fed a high-fat diet. Nutr. Res. 2016, 36, 603–611. [Google Scholar] [CrossRef] [Green Version]
- 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. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef] [Green Version]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- Sundaram, S.; Yan, L. Time-restricted feeding mitigates high-fat diet-enhanced mammary tumorigenesis in MMTV-PyMT mice. Nutr. Res. 2018, 59, 72–79. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [Green Version]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef] [Green Version]
- Poggiogalle, E.; Jamshed, H.; Peterson, C.M. Circadian regulation of glucose, lipid, and energy metabolism in humans. Metabolism 2018, 84, 11–27. [Google Scholar] [CrossRef] [Green Version]
- 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. [Google Scholar] [CrossRef] [Green Version]
- Gamble, K.L.; Berry, R.; Frank, S.J.; Young, M.E. Circadian clock control of endocrine factors. Nat. Rev. Endocrinol. 2014, 10, 466–475. [Google Scholar] [CrossRef] [Green Version]
- Tsang, A.H.; Astiz, M.; Friedrichs, M.; Oster, H. Endocrine regulation of circadian physiology. J. Endocrinol. 2016, 230, R1–R11. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef]
- Reid, K.J.; Baron, K.G.; Zee, P.C. Meal timing influences daily caloric intake in healthy adults. Nutr. Res. 2014, 34, 930–935. [Google Scholar] [CrossRef] [Green Version]
- 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. [Google Scholar] [CrossRef] [Green Version]
- 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. [Google Scholar] [CrossRef] [Green Version]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- 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. [Google Scholar] [CrossRef] [Green Version]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- EasyGV. Available online: https://www.phc.ox.ac.uk/research/technology-outputs/easygv (accessed on 13 December 2018).
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef] [Green Version]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [Green Version]
- Rahman, S.; Islam, R. Mammalian Sirt1: Insights on its biological functions. Cell Commun. Signal 2011, 9, 11. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
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Jamshed, H.; Beyl, R.A.; Della Manna, D.L.; Yang, E.S.; Ravussin, E.; Peterson, C.M. Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans. Nutrients 2019, 11, 1234. https://doi.org/10.3390/nu11061234
Jamshed H, Beyl RA, Della Manna DL, Yang ES, Ravussin E, Peterson CM. Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans. Nutrients. 2019; 11(6):1234. https://doi.org/10.3390/nu11061234
Chicago/Turabian StyleJamshed, Humaira, Robbie A. Beyl, Deborah L. Della Manna, Eddy S. Yang, Eric Ravussin, and Courtney M. Peterson. 2019. "Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans" Nutrients 11, no. 6: 1234. https://doi.org/10.3390/nu11061234
APA StyleJamshed, H., Beyl, R. A., Della Manna, D. L., Yang, E. S., Ravussin, E., & Peterson, C. M. (2019). Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans. Nutrients, 11(6), 1234. https://doi.org/10.3390/nu11061234