Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Food as a circadian time cue — evidence from human studies

Nature Reviews Endocrinology volume 16, pages 213–223 (2020)Cite this article

Subjects

Abstract

Meal timing and composition are frequently reported in the literature as zeitgebers (that is, time cues) for the circadian system of humans and animal models, albeit secondary to light. Although widely assumed to be true, evidence for food zeitgeber effects specific to humans is notably scarce. Fostering zeitgeber hygiene in the general population as the development and practice of healthy use of zeitgebers could potentially reduce chronobiological strain, which is defined as disruption or misalignment within the circadian system. Such chronobiological strain is associated with modern 24/7 lifestyles (for example, shift work) and several negative health outcomes. Adjustments to meal timing and composition are an attractive strategy to synchronize circadian rhythms and develop zeitgeber hygiene. Thus, clarifying the actual effect of meal timing and composition on the human circadian system is a crucial piece of the human chronobiology puzzle. This Review weighs the evidence from human studies pertaining to the hypothesis that food is a circadian zeitgeber by comparing findings against formal zeitgeber criteria put forward by Jürgen Aschoff in the 1950s.

Key points

  • Fostering zeitgeber hygiene as the practice of healthy use of ‘zeitgebers’ (circadian time cues) could reduce the chronobiological strain (disruption or misalignment within the circadian system) that is associated with modern 24/7 lifestyles and several negative health outcomes.

  • Meal timing and composition are described as ‘zeitgebers’ for humans in the literature, despite a notably paucity of clear, direct evidence from human studies.

  • Only one study has demonstrated that meal timing sufficiently fulfils at least one of the zeitgeber criteria put forward by Jürgen Aschoff in the 1950s.

  • Targeted human research should be prioritized to properly ascertain multifaceted relationships between food intake and human chronobiology.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Example illustration of Aschoff criteria.

Similar content being viewed by others

References

  1. Halberg, F. Physiologic 24-hour periodicity; general and procedural considerations with reference to the adrenal cycle [German]. Int. Z. Vitaminforsch Beih. 10, 225–296 (1959).

    CAS  PubMed  Google Scholar 

  2. Aschoff, J. Die 24-Stunden-Periodik der Maus unter konstanten Umgebungsbedingungen [German]. Die Naturwissenschaften 38, 506–507 (1951).

    Article  Google Scholar 

  3. Aschoff, J. Zeitgeber der tierischen Tagesperiodik [German]. Die Naturwissenschaften 41, 49–56 (1954). An article describing zeitgeber criteria.

    Article  Google Scholar 

  4. Duffy, J. F., Kronauer, R. E. & Czeisler, C. A. Phase-shifting human circadian rhythms: influence of sleep timing, social contact and light exposure. J. Physiol. 495, 289–297 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pittendrigh, C. S. Circadian rhythms and the circadian organization of living systems. Cold Spring Harb. Symp. Quant. Biol. 25, 159–184 (1960).

    Article  CAS  PubMed  Google Scholar 

  6. Panda, S. Circadian physiology of metabolism. Science 354, 1008–1015 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Stenvers, D. J., Scheer, F. A. J. L., Schrauwen, P., la Fleur, S. E. & Kalsbeek, A. Circadian clocks and insulin resistance. Nat. Rev. Endocrinol. 15, 75–89 (2019).

    Article  PubMed  CAS  Google Scholar 

  8. Challet, E. The circadian regulation of food intake. Nat. Rev. Endocrinol. 15, 393–405 (2019).

    Article  PubMed  Google Scholar 

  9. Russell, G. & Lightman, S. The human stress response. Nat. Rev. Endocrinol. 15, 525–534 (2019).

    Article  PubMed  Google Scholar 

  10. Ikegami, K., Refetoff, S., Van Cauter, E. & Yoshimura, T. Interconnection between circadian clocks and thyroid function. Nat. Rev. Endocrinol. 15, 590–600 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gabriel, B. M. & Zierath, J. R. Circadian rhythms and exercise — re-setting the clock in metabolic disease. Nat. Rev. Endocrinol. 15, 197–206 (2019).

    Article  PubMed  Google Scholar 

  12. Lewis, P., Foster, R. G. & Erren, T. C. Ticking time bomb? High time for chronobiological research. EMBO Rep. 19, e46073 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Vetter, C., Fischer, D., Matera, J. L. & Roenneberg, T. Aligning work and circadian time in shift workers improves sleep and reduces circadian disruption. Curr. Biol. 25, 907–911 (2015).

    Article  CAS  PubMed  Google Scholar 

  14. IARC. Painting, firefighting, and shiftwork. IARC Monogr. Eval. Carcinog. Risks Hum. 98, 9–764 (2010).

    Google Scholar 

  15. West, A. C. et al. Misalignment with the external light environment drives metabolic and cardiac dysfunction. Nat. Commun. 8, 417 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. IARC. Carcinogenicity of night shift work. Lancet Oncol. 20, 1058–1059 (2019).

    Article  Google Scholar 

  17. Kerenyi, N. A., Pandula, E. & Feuer, G. Why the incidence of cancer is increasing: the role of ‘light pollution’. Med. Hypotheses 33, 75–78 (1990).

    Article  CAS  PubMed  Google Scholar 

  18. Czeisler, C. A. Duration, timing and quality of sleep are each vital for health, performance and safety. Sleep. Health 1, 5–8 (2015).

    Article  PubMed  Google Scholar 

  19. Czeisler, C. A. Perspective: casting light on sleep deficiency. Nature 497, S13 (2013).

    Article  CAS  PubMed  Google Scholar 

  20. Stevens, R. G. et al. Meeting report: the role of environmental lighting and circadian disruption in cancer and other diseases. Environ. Health Perspect. 115, 1357–1362 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Erren, T. C. & Reiter, R. J. Revisiting chronodisruption: when the physiological nexus between internal and external times splits in humans. Naturwissenschaften 100, 291–298 (2013).

    Article  CAS  PubMed  Google Scholar 

  22. Erren, T. C. & Lewis, P. Hypothesis: ubiquitous circadian disruption can cause cancer. Eur. J. Epidemiol. 34, 1–4 (2019).

    Article  PubMed  Google Scholar 

  23. Erren, T. C. & Reiter, R. J. Light hygiene: time to make preventive use of insights—old and new—into the nexus of the drug light, melatonin, clocks, chronodisruption and public health. Med. Hypotheses 73, 537–541 (2009).

    Article  PubMed  Google Scholar 

  24. Erren, T. C., Falaturi, P. & Reiter, R. J. Research into the chronodisruption-cancer theory: the imperative for causal clarification and the danger of causal reductionism. Neuro. Endocrinol. Lett. 31, 1–3 (2010).

    PubMed  Google Scholar 

  25. Lewis, P., Korf, H. W., Kuffer, L., Gross, J. V. & Erren, T. C. Exercise time cues (zeitgebers) for human circadian systems can foster health and improve performance: a systematic review. BMJ Open. Sport. Exerc. Med. 4, e000443 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Richter, C. P. A behavioristic study of the activity of the rat. Comp. Psychol. Monogr. 1, 56 (1922). The first study noting food anticipatory activity in rodents in response to food restriction.

    Google Scholar 

  27. Mistlberger, R. E. et al. Comment on “Differential rescue of light- and food-entrainable circadian rhythms”. Science 322, 675 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Challet, E. & Mendoza, J. Metabolic and reward feeding synchronises the rhythmic brain. Cell Tissue Res. 341, 1–11 (2010).

    Article  PubMed  Google Scholar 

  29. Escobar, C. et al. Scheduled meals and scheduled palatable snacks synchronize circadian rhythms: consequences for ingestive behavior. Physiol. Behav. 104, 555–561 (2011).

    Article  CAS  PubMed  Google Scholar 

  30. Mistlberger, R. E. & Skene, D. J. Nonphotic entrainment in humans? J. Biol. Rhythm. 20, 339–352 (2005).

    Article  Google Scholar 

  31. Stephan, F. K. The “other” circadian system: food as a Zeitgeber. J. Biol. Rhythm. 17, 284–292 (2002).

    Article  Google Scholar 

  32. Collado, M. C. et al. Timing of food intake impacts daily rhythms of human salivary microbiota: a randomized, crossover study. FASEB J. 32, 2060–2072 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Bandin, C. et al. Meal timing affects glucose tolerance, substrate oxidation and circadian-related variables: a randomized, crossover trial. Int. J. Obes. 39, 828–833 (2015).

    Article  CAS  Google Scholar 

  34. Wehrens, S. M. T. et al. Meal timing regulates the human circadian system. Curr. Biol. 27, 1768–1775.e3 (2017). This study demonstrates fulfilment of an Aschoff criterion by meal timing in humans; importantly, effects were observed at the level of circadian genes in a peripheral clock.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Schoeller, D. A., Cella, L. K., Sinha, M. K. & Caro, J. F. Entrainment of the diurnal rhythm of plasma leptin to meal timing. J. Clin. Invest. 100, 1882–1887 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sinha, M. K. et al. Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects. J. Clin. Invest. 97, 1344–1347 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cella, L. K., Van Cauter, E. & Schoeller, D. A. Effect of meal timing on diurnal rhythm of human cholesterol synthesis. Am. J. Physiol. 269, E878–E883 (1995).

    Article  CAS  PubMed  Google Scholar 

  38. Fogteloo, A. J., Pijl, H., Roelfsema, F., Frolich, M. & Meinders, A. E. Impact of meal timing and frequency on the twenty-four-hour leptin rhythm. Horm. Res. 62, 71–78 (2004).

    CAS  PubMed  Google Scholar 

  39. Goetz, F. et al. Timing of single daily meal influences relations among human circadian rhythms in urinary cyclic AMP and hemic glucagon, insulin and iron. Experientia 32, 1081–1084 (1976).

    Article  CAS  PubMed  Google Scholar 

  40. 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. Rhythm. 17, 364–376 (2002).

    Article  Google Scholar 

  41. Fukuda, T. et al. A randomized, double-blind and placebo-controlled crossover trial on the effect of l-ornithine ingestion on the human circadian clock. Chronobiol. Int. 35, 1445–1455 (2018).

    Article  CAS  PubMed  Google Scholar 

  42. Yasuo, S. et al. l-Serine enhances light-induced circadian phase resetting in mice and humans. J. Nutr. 147, 2347–2355 (2017).

    Article  CAS  PubMed  Google Scholar 

  43. Pivovarova, O. et al. Changes of dietary fat and carbohydrate content alter central and peripheral clock in humans. J. Clin. Endocrinol. Metab. 100, 2291–2302 (2015).

    Article  CAS  PubMed  Google Scholar 

  44. Bergendahl, M., Vance, M. L., Iranmanesh, A., Thorner, M. O. & Veldhuis, J. D. Fasting as a metabolic stress paradigm selectively amplifies cortisol secretory burst mass and delays the time of maximal nyctohemeral cortisol concentrations in healthy men. J. Clin. Endocrinol. Metab. 81, 692–699 (1996).

    CAS  PubMed  Google Scholar 

  45. Cugini, P. et al. Effects of a mild and prolonged restriction in sodium or food intake on the circadian rhythm of aldosterone and related variables. Chronobiol. Int. 4, 245–250 (1987).

    Article  CAS  PubMed  Google Scholar 

  46. Trotti, R., Rondanelli, M., Cuzzoni, G., Ferrari, E. & d’Eril, G. M. Circadian temporal organization of lipidic fractions in elderly people. Entrainment to the dietary schedule. Aging Clin. Exp. Res. 14, 94–99 (2002).

    Article  PubMed  Google Scholar 

  47. Bogdan, A., Bouchareb, B. & Touitou, Y. Ramadan fasting alters endocrine and neuroendocrine circadian patterns. Meal-time as a synchronizer in humans? Life Sci. 68, 1607–1615 (2001).

    Article  CAS  PubMed  Google Scholar 

  48. Iraki, L. et al. Ramadan diet restrictions modify the circadian time structure in humans. A study on plasma gastrin, insulin, glucose, and calcium and on gastric pH. J. Clin. Endocrinol. Metab. 82, 1261–1273 (1997).

    CAS  PubMed  Google Scholar 

  49. Nakade, M., Takeuchi, H., Taniwaki, N., Noji, T. & Harada, T. An integrated effect of protein intake at breakfast and morning exposure to sunlight on the circadian typology in Japanese infants aged 2–6 years. J. Physiol. Anthropol. 28, 239–245 (2009).

    Article  PubMed  Google Scholar 

  50. Harada, T., Hirotani, M., Maeda, M., Nomura, H. & Takeuchi, H. Correlation between breakfast tryptophan content and morning-evening in Japanese infants and students aged 0–15 years. J. Physiol. Anthropol. 26, 201–207 (2007).

    Article  PubMed  Google Scholar 

  51. Cubero, J. et al. The circadian rhythm of tryptophan in breast milk affects the rhythms of 6-sulfatoxymelatonin and sleep in newborn. Neuro Endocrinol. Lett. 26, 657–661 (2005).

    CAS  PubMed  Google Scholar 

  52. Almeneessier, A. S. & BaHammam, A. S. How does diurnal intermittent fasting impact sleep, daytime sleepiness, and markers of the biological clock? Current insights. Nat. Sci. Sleep. 10, 439–452 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Skene, D. J. et al. Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism. Proc. Natl Acad. Sci. USA 115, 7825–7830 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Skene, D. J. Optimization of light and melatonin to phase-shift human circadian rhythms. J. Neuroendocrinol. 15, 438–441 (2003).

    Article  CAS  PubMed  Google Scholar 

  55. Kennaway, D. J. et al. Phase delay of the rhythm of 6-sulphatoxy melatonin excretion by artificial light. J. Pineal Res. 4, 315–320 (1987).

    Article  CAS  PubMed  Google Scholar 

  56. Grant, C. L. et al. Timing of food intake during simulated night shift impacts glucose metabolism: a controlled study. Chronobiol. Int. 34, 1003–1013 (2017).

    Article  PubMed  Google Scholar 

  57. Srour, B. et al. Circadian nutritional behaviours and cancer risk: new insights from the NutriNet-sante prospective cohort study: disclaimers. Int. J. Cancer 143, 2369–2379 (2018).

    Article  CAS  PubMed  Google Scholar 

  58. Kogevinas, M. et al. Effect of mistimed eating patterns on breast and prostate cancer risk (MCC-Spain study). Int. J. Cancer 143, 2380–2389 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ekhart, D. et al. Dynamics of core body temperature cycles in long-term measurements under real life conditions in women. Chronobiol. Int. 35, 8–23 (2018).

    Article  CAS  PubMed  Google Scholar 

  60. Foster, R. G. et al. Circadian photoreception in the retinally degenerate mouse (rd/rd). J. Comp. Physiol. A 169, 39–50 (1991).

    Article  CAS  PubMed  Google Scholar 

  61. Freedman, M. S. et al. Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors. Science 284, 502–504 (1999).

    Article  CAS  PubMed  Google Scholar 

  62. Lucas, R. J., Freedman, M. S., Munoz, M., Garcia-Fernandez, J. M. & Foster, R. G. Regulation of the mammalian pineal by non-rod, non-cone, ocular photoreceptors. Science 284, 505–507 (1999).

    Article  CAS  PubMed  Google Scholar 

  63. Soni, B. G., Philp, A. R., Foster, R. G. & Knox, B. E. Novel retinal photoreceptors. Nature 394, 27–28 (1998).

    Article  CAS  PubMed  Google Scholar 

  64. Hattar, S., Liao, H. W., Takao, M., Berson, D. M. & Yau, K. W. Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 295, 1065–1070 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Sekaran, S., Foster, R. G., Lucas, R. J. & Hankins, M. W. Calcium imaging reveals a network of intrinsically light-sensitive inner-retinal neurons. Curr. Biol. 13, 1290–1298 (2003).

    Article  CAS  PubMed  Google Scholar 

  66. Provencio, I., Jiang, G., De Grip, W. J., Hayes, W. P. & Rollag, M. D. Melanopsin: an opsin in melanophores, brain, and eye. Proc. Natl Acad. Sci. USA 95, 340–345 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kalsbeek, A. et al. SCN outputs and the hypothalamic balance of life. J. Biol. Rhythm. 21, 458–469 (2006).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute and Policlinic for Occupational Medicine, Environmental Medicine and Prevention Research, University Hospital of Cologne, University of Cologne, Cologne, Germany

    Philip Lewis & Thomas C. Erren

  2. Institute of Neurobiology, University of Lübeck, Lübeck, Germany

    Henrik Oster

  3. Institute of Anatomy I, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany

    Horst W. Korf

  4. Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK

    Russell G. Foster

Authors
  1. Philip Lewis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Henrik Oster
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Horst W. Korf
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Russell G. Foster
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas C. Erren
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to Philip Lewis.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Misalignment

Circadian rhythms are out of sync either with each other or with the external environment; for example, Aschoff criterion 2: upon Zeitgeber reversal, the circadian rhythm is in a transient period of misalignment with regard to the Zeitgeber.

Internal time

The phase of entrained circadian rhythm (for example, dim-light melatonin onset).

External time

Phase of the Zeitgeber rhythm (for example, dawn or dusk).

Zeitgeber hygiene

The practice of synergistic use of Zeitgebers to potentially reduce the chronobiological strain (disruption or misalignment within the circadian system) that is associated with modern 24/7 lifestyles, conflicting Zeitgeber information and several negative health outcomes.

Masking

A direct change in a circadian rhythm caused by another factor, such that it hides the true responsible endogenous component; for example, in humans, pulses of light can inhibit melatonin secretion even if the circadian component is in the acrophase.

Acrophase

The time period during which a rhythm peaks (for example, the crest of a sine wave).

Mesor

The mean of circadian rhythm measurements computed using a cosine function and based on distribution of measurements across cycles.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lewis, P., Oster, H., Korf, H.W. et al. Food as a circadian time cue — evidence from human studies. Nat Rev Endocrinol 16, 213–223 (2020). https://doi.org/10.1038/s41574-020-0318-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41574-020-0318-z

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing