Meal frequency and timing in health and disease

1. Casazza K, et al. Myths, presumptions, and facts about obesity. N Engl J Med. 2013;368(5):446–454. [PMC free article] [PubMed]

2. Longo VD, Mattson MP. Fasting: Molecular mechanisms and clinical applications. Cell Metab. 2014;19(2):181–192. [PMC free article] [PubMed]

3. Gervasi V, et al. Predicting the potential demographic impact of predators on their prey: A comparative analysis of two carnivore-ungulate systems in Scandinavia. J Anim Ecol. 2012;81(2):443–454. [PMC free article] [PubMed]

4. Metz MC, Smith DW, Vucetich JA, Stahler DR, Peterson RO. Seasonal patterns of predation for gray wolves in the multi-prey system of Yellowstone National Park. J Anim Ecol. 2012;81(3):553–563. [PubMed]

5. Cordain L, Eaton SB, Miller JB, Mann N, Hill K. The paradoxical nature of hunter-gatherer diets: Meat-based, yet non-atherogenic. Eur J Clin Nutr. 2002;56(Suppl 1):S42–S52. [PubMed]

6. Ströhle A, Hahn A, Sebastian A. Estimation of the diet-dependent net acid load in 229 worldwide historically studied hunter-gatherer societies. Am J Clin Nutr. 2010;91(2):406–412. [PubMed]

7. van Schaik CP, Deaner RO, Merrill MY. The conditions for tool use in primates: Implications for the evolution of material culture. J Hum Evol. 1999;36(6):719–741. [PubMed]

8. Allen JS. “Theory of food” as a neurocognitive adaptation. Am J Hum Biol. 2012;24(2):123–129. [PMC free article] [PubMed]

9. Tillotson JE. America’s obesity: Conflicting public policies, industrial economic development, and unintended human consequences. Annu Rev Nutr. 2004;24:617–643. [PubMed]

10. Zoran DL. Obesity in dogs and cats: A metabolic and endocrine disorder. Vet Clin North Am Small Anim Pract. 2010;40(2):221–239. [PubMed]

11. Martin B, Ji S, Maudsley S, Mattson MP. “Control” laboratory rodents are metabolically morbid: Why it matters. Proc Natl Acad Sci USA. 2010;107(14):6127–6133. [PMC free article] [PubMed]

12. Klimentidis YC, et al. Canaries in the coal mine: A cross-species analysis of the plurality of obesity epidemics. Proc Biol Sci. 2011;278(1712):1626–1632. [PMC free article] [PubMed]

13. Panda S, Hogenesch JB, Kay SA. Circadian rhythms from flies to human. Nature. 2002;417(6886):329–335. [PubMed]

14. Hatori M, Panda S. The emerging roles of melanopsin in behavioral adaptation to light. Trends Mol Med. 2010;16(10):435–446. [PMC free article] [PubMed]

15. Stokkan KA, Yamazaki S, Tei H, Sakaki Y, Menaker M. Entrainment of the circadian clock in the liver by feeding. Science. 2001;291(5503):490–493. [PubMed]

16. Stevens RG, Brainard GC, Blask DE, Lockley SW, Motta ME. Breast cancer and circadian disruption from electric lighting in the modern world. CA Cancer J Clin. 2014;64(3):207–218. [PMC free article] [PubMed]

17. Morris CJ, Yang JN, Scheer FA. The impact of the circadian timing system on cardiovascular and metabolic function. Prog Brain Res. 2012;199:337–358. [PMC free article] [PubMed]

18. Wright KP, Jr, et al. Entrainment of the human circadian clock to the natural light-dark cycle. Curr Biol. 2013;23(16):1554–1558. [PMC free article] [PubMed]

19. Gill S, Panda S. Feeding mistiming decreases reproductive fitness in flies. Cell Metab. 2011;13(6):613–614. [PMC free article] [PubMed]

20. Scheer FA, Hilton MF, Mantzoros CS, Shea SA. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci USA. 2009;106(11):4453–4458. [PMC free article] [PubMed]

21. Liu Z, et al. PER1 phosphorylation specifies feeding rhythm in mice. Cell Rep. 2014;7(5):1509–1520. [PubMed]

22. Kohsaka A, et al. High-fat diet disrupts behavioral and molecular circadian rhythms in mice. Cell Metab. 2007;6(5):414–421. [PubMed]

23. Hatori M, et al. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 2012;15(6):848–860. [PMC free article] [PubMed]

24. Garaulet M, et al. Timing of food intake predicts weight loss effectiveness. Int J Obes (Lond) 2013;37(4):604–611. [PMC free article] [PubMed]

25. 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 (Silver Spring) 2013;21(12):2504–2512. [PubMed]

26. Vollmers C, et al. Circadian oscillations of protein-coding and regulatory RNAs in a highly dynamic mammalian liver epigenome. Cell Metab. 2012;16(6):833–845. [PMC free article] [PubMed]

27. Cho H, et al. Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β Nature. 2010;485(7396):123–127. [PMC free article] [PubMed]

28. Zhang EE, et al. Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis. Nat Med. 2010;16(10):1152–1156. [PMC free article] [PubMed]

29. Gachon F, Olela FF, Schaad O, Descombes P, Schibler U. The circadian PAR-domain basic leucine zipper transcription factors DBP, TEF, and HLF modulate basal and inducible xenobiotic detoxification. Cell Metab. 2006;4(1):25–36. [PubMed]

30. Jeyaraj D, et al. Klf15 orchestrates circadian nitrogen homeostasis. Cell Metab. 2006;15(3):311–323. [PMC free article] [PubMed]

31. Bass J, Takahashi JS. Circadian integration of metabolism and energetics. Science. 2010;330(6009):1349–1354. [PMC free article] [PubMed]

32. Scheer FA, Morris CJ, Shea SA. The internal circadian clock increases hunger and appetite in the evening independent of food intake and other behaviors. Obesity (Silver Spring) 2013;21(3):421–423. [PMC free article] [PubMed]

33. Goodrick CL, Ingram DK, Reynolds MA, Freeman JR, Cider NL. Effects of intermittent feeding upon growth, activity, and lifespan in rats allowed voluntary exercise. Exp Aging Res. 1983;9(3):203–209. [PubMed]

34. Honjoh S, Yamamoto T, Uno M, Nishida E. Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans. Nature. 2009;457(7230):726–730. [PubMed]

35. Colman RJ, et al. Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat Commun. 2014;5:3557. [PMC free article] [PubMed]

36. Rizza W, Veronese N, Fontana L. What are the roles of calorie restriction and diet quality in promoting healthy longevity? Ageing Res Rev. 2014;13:38–45. [PubMed]

37. Pieri C, et al. Food restriction in female Wistar rats: V. Lipid peroxidation and antioxidant enzymes in the liver. Arch Gerontol Geriatr. 1992;14(1):93–99. [PubMed]

38. Rodríguez-Bies E, Navas P, López-Lluch G. Age-dependent effect of every-other-day feeding and aerobic exercise in ubiquinone levels and related antioxidant activities in mice muscle. J Gerontol A Biol Sci Med Sci. 2014 doi: 10.1093/gerona/glu002. [PubMed] [Cross Ref]

39. Mattson MP. Energy intake and exercise as determinants of brain health and vulnerability to injury and disease. Cell Metab. 2012;16(6):706–722. [PMC free article] [PubMed]

40. Ahmet I, Wan R, Mattson MP, Lakatta EG, Talan M. Cardioprotection by intermittent fasting in rats. Circulation. 2005;112(20):3115–3121. [PubMed]

41. Arumugam TV, et al. Age and energy intake interact to modify cell stress pathways and stroke outcome. Ann Neurol. 2010;67(1):41–52. [PMC free article] [PubMed]

42. Poon HF, et al. Proteomics analysis provides insight into caloric restriction mediated oxidation and expression of brain proteins associated with age-related impaired cellular processes: Mitochondrial dysfunction, glutamate dysregulation and impaired protein synthes-is. Neurobiol Aging. 2006;27(7):1020–1034. [PubMed]

43. Marosi K, Mattson MP. BDNF mediates adaptive brain and body responses to energetic challenges. Trends Endocrinol Metab. 2014;25(2):89–98. [PMC free article] [PubMed]

44. Johnson JB, et al. Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radic Biol Med. 2007;42(5):665–674. [PMC free article] [PubMed]

45. Harvie MN, et al. The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: A randomized trial in young overweight women. Int J Obes (Lond) 2011;35(5):714–727. [PMC free article] [PubMed]

46. Klempel MC, Kroeger CM, Varady KA. Alternate day fasting (ADF) with a high-fat diet produces similar weight loss and cardio-protection as ADF with a low-fat diet. Metabolism. 2013;62(1):137–143. [PubMed]

47. Varady KA, et al. Alternate day fasting for weight loss in normal weight and overweight subjects: A randomized controlled trial. Nutr J. 2013;12(1):146. [PMC free article] [PubMed]

48. Kashiwaya Y, et al. A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer’s disease. Neurobiol Aging. 2013;34(6):1530–1539. [PMC free article] [PubMed]

49. Newman JC, Verdin E. Ketone bodies as signaling metabolites. Trends Endocrinol Metab. 2014;25(1):42–52. [PMC free article] [PubMed]

50. Anson RM, et al. Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci USA. 2003;100(10):6216–6220. [PMC free article] [PubMed]

51. Harvie M, et al. The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. Br J Nutr. 2013;110(8):1534–1547. [PMC free article] [PubMed]

52. Martin-Montalvo A, de Cabo R. Mitochondrial metabolic reprogramming induced by calorie restriction. Antioxid Redox Signal. 2013;19(3):310–320. [PMC free article] [PubMed]

53. Cheng A, et al. Involvement of PGC-1α in the formation and maintenance of neuronal dendritic spines. Nat Commun. 2012;3:1250. [PMC free article] [PubMed]

54. Seyfried TN, Flores RE, Poff AM, D’Agostino DP. Cancer as a metabolic disease: Implications for novel therapeutics. Carcinogenesis. 2014;35(3):515–527. [PMC free article] [PubMed]

55. Lee C, et al. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci Transl Med. 2012;4(124):124ra27. [PMC free article] [PubMed]

56. Safdie FM, et al. Fasting and cancer treatment in humans: A case series report. Aging (Albany, NY Online) 2009;1(12):988–1007. [PMC free article] [PubMed]

57. Zuccoli G, et al. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case report. Nutr Metab (Lond) 2010;7:33. [PMC free article] [PubMed]

58. Seyfried TN. Cancer as a Metabolic Disease: On the Origin, Management and Prevention of Cancer. John Wiley & Sons; Hoboken, NJ: 2012. pp. 261–275.

59. McDade TW. Early environments and the ecology of inflammation. Proc Natl Acad Sci USA. 2012;109(Suppl 2):17281–17288. [PMC free article] [PubMed]

60. Kroeger CM, et al. Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: Relationship to adipokine modulations. Nutr Metab (Lond) 2012;9(1):98. [PMC free article] [PubMed]

61. Müller H, de Toledo FW, Resch KL. Fasting followed by vegetarian diet in patients with rheumatoid arthritis: A systematic review. Scand J Rheumatol. 2001;30(1):1–10. [PubMed]

62. Esquifino AI, Cano P, Jimenez-Ortega V, Fernández-Mateos MP, Cardinali DP. Immune response after experimental allergic encephalomyelitis in rats subjected to calorie restriction. J Neuroinflammation. 2007;4:6. [PMC free article] [PubMed]

63. Muthukumar A, Zaman K, Lawrence R, Barnes JL, Fernandes G. Food restriction and fish oil suppress atherogenic risk factors in lupus-prone (NZB x NZW) F1 mice. J Clin Immunol. 2003;23(1):23–33. [PubMed]

64. Belkacemi L, et al. Intermittent fasting modulation of the diabetic syndrome in streptozotocin-injected rats. Int J Endocrinol. 2012;2012:962012. [PMC free article] [PubMed]

65. Elinav E, et al. Inflammation-induced cancer: Crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer. 2013;13(11):759–771. [PubMed]

66. Maupin-Furlow J. Proteasomes and protein conjugation across domains of life. Nat Rev Microbiol. 2012;10(2):100–111. [PMC free article] [PubMed]

67. Rubinsztein DC, Mariño G, Kroemer G. Autophagy and aging. Cell. 2011;146(5):682–695. [PubMed]

68. Speakman JR, Mitchell SE. Caloric restriction. Mol Aspects Med. 2011;32(3):159–221. [PubMed]

69. Donati A, Recchia G, Cavallini G, Bergamini E. Effect of aging and anti-aging caloric restriction on the endocrine regulation of rat liver autophagy. J Gerontol A Biol Sci Med Sci. 2008;63(6):550–555. [PubMed]

70. Kume S, et al. Calorie restriction enhances cell adaptation to hypoxia through Sirt1-dependent mitochondrial autophagy in mouse aged kidney. J Clin Invest. 2010;120(4):1043–1055. [PMC free article] [PubMed]

71. Wohlgemuth SE, Seo AY, Marzetti E, Lees HA, Leeuwenburgh C. Skeletal muscle autophagy and apoptosis during aging: Effects of calorie restriction and life-long exercise. Exp Gerontol. 2010;45(2):138–148. [PMC free article] [PubMed]

72. Lee S, Notterpek L. Dietary restriction supports peripheral nerve health by enhancing endogenous protein quality control mechanisms. Exp Gerontol. 2013;48(10):1085–1090. [PMC free article] [PubMed]

73. Madorsky I, et al. Intermittent fasting alleviates the neuropathic phenotype in a mouse model of Charcot-Marie-Tooth disease. Neurobiol Dis. 2009;34(1):146–154. [PMC free article] [PubMed]

74. Moreno-Gonzalez I, Soto C. Misfolded protein aggregates: Mechanisms, structures and potential for disease transmission. Semin Cell Dev Biol. 2011;22(5):482–487. [PMC free article] [PubMed]

75. Jucker M, Walker LC. Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders. Ann Neurol. 2011;70(4):532–540. [PMC free article] [PubMed]

76. Ma D, Li S, Molusky MM, Lin JD. Circadian autophagy rhythm: A link between clock and metabolism? Trends Endocrinol Metab. 2012;23(7):319–325. [PMC free article] [PubMed]

77. Brown AW, Bohan Brown MM, Allison DB. Belief beyond the evidence: Using the proposed effect of breakfast on obesity to show 2 practices that distort scientific evidence. Am J Clin Nutr. 2013;98(5):1298–1308. [PMC free article] [PubMed]

78. Dhurandhar EJ, et al. The effectiveness of breakfast recommendations on weight loss: A randomized controlled trial. Am J Clin Nutr. 2014;100(2):507–513. [PMC free article] [PubMed]

79. Stote KS, 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(4):981–988. [PMC free article] [PubMed]

80. Carlson O, 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(12):1729–1734. [PMC free article] [PubMed]

81. Swindell WR. Dietary restriction in rats and mice: A meta-analysis and review of the evidence for genotype-dependent effects on lifespan. Ageing Res Rev. 2012;11(2):254–270. [PMC free article] [PubMed]

82. Pendergast JS, Oda GA, Niswender KD, Yamazaki S. Period determination in the food-entrainable and methamphetamine-sensitive circadian oscillator(s) Proc Natl Acad Sci USA. 2012;109(35):14218–14223. [PMC free article] [PubMed]

83. Mulder CK, Papantoniou C, Gerkema MP, Van Der Zee EA. Neither the SCN nor the adrenals are required for circadian time-place learning in mice. Chronobiol Int. 2014;31(9):1075–1092. [PMC free article] [PubMed]

84. Fryar CD, Carroll MD, Ogden CL. 2012 Prevalence of Overweight, Obesity, and Extreme Obesity Among Adults: United States, Trends 1960–1962 Through 2009–2010 (National Center for Health Statistics, Hyattsville, MD). Available at Accessed November 3, 2014.

85. United States Department of Agriculture . Agriculture Fact Book. US Department of Agriculture; Washington, DC: 2003. Profiling food consumption in America; pp. 13–21.

86. Day JC, Janus A, Davis J. 2005 Computer and Internet Use in the United States: 2003 (US Census Bureau, Washington, DC). Available at Accessed November 3, 2014.