Circadian clock…biological clock…alarm clock… Face it. We are subjects to the clock whether mechanical or the one existing within us. This could not be truer than when it comes to how well we respond to medication.

The topic of time and when to take medication has appeared even in reading material geared to the interests of the general population. In Reader’s Digest, a recent article talks about “chronotherapy” (Simon, 2018), or taking medications based on a person’s circadian rhythm to maximize the effectiveness of the drugs and minimize the side effects. Suggestions are even made for the best time of day to take some popular forms of medications, such as allergy medications.

Chronotherapy is a bit more complicated than the Reader’s Digest article suggests. The fact is that many factors can affect a person’s circadian rhythm. Not too surprisingly, our choice of bedtime can affect our internal clock (Potter et al., 2016). Also, not surprisingly, what we shove into our mouths (in the form of food) can certainly alter our circadian rhythm (Oosterman, Kalsbeek, la Fleur, & Belsham, 2015). Our gender influences our internal clock (Santhi et al., 2016). Even the ravages of time (aging) adjust our clocks (Hood & Amir, 2017).

With so many factors affecting how our circadian rhythm functions, it seems like a Herculean task to make chronotherapy a reality. But it is necessary. As the oncologist Francis Lévi stated, “We have found that the timing is sometimes more important than the dose (Peeples, 2018).” A recent Nature article details just how important and invaluable chronotherapy can be to positive outcomes in treating diseases, particularly in performing cardiac surgery or treating cancer (Peeples, 2018).

But if chronotherapy demonstrably improves patient outcomes, why do only a small fraction of clinical trials incorporate it (Selfridge et al., 2016)? The Nature article suggests a few reasons why chronotherapy is not used more often; however, cost and complexity could also be reasons why. But with advances in technology, these reasons may disappear.

One such emerging technology is the SOMAscan platform. In a pilot study involving six individuals, researchers investigated using the SOMAscan platform (and other techniques) to watch the circadian rhythm of the individuals (Skarke et al., 2017). They found a small fraction of proteins that associated with inflammation and cancer changed during the day. It is tempting to think that if a larger number of people had been used in this study a larger fraction of proteins would have shown a temporal relationship. Maybe this will motivate a larger study?

Now that a technology exists which can show us how our proteins fluctuate during the day, we have a new opportunity at hand: the further realization of the promise of precision medicine by the wider application of chronotherapy across many diseases and conditions. It will be exciting to see how adoption of this technology could make chronotherapy more realistic even though so many things affect our clocks. Future therapies may have to include lifestyle adjustments to reduce day-to-day variability in our circadian rhythm. Time will tell.

 

References

Hood, S., & Amir, S. (2017). The aging clock: circadian rhythms and later life. J Clin Invest, 127(2), 437-446. doi:10.1172/JCI90328

Oosterman, J. E., Kalsbeek, A., la Fleur, S. E., & Belsham, D. D. (2015). Impact of nutrients on circadian rhythmicity. Am J Physiol Regul Integr Comp Physiol, 308(5), R337-350. doi:10.1152/ajpregu.00322.2014

Peeples, L. (2018). Medicine’s secret ingredient – it’s in the timing. Nature, 556(7701), 290-292. doi:10.1038/d41586-018-04600-8

Potter, G. D., Skene, D. J., Arendt, J., Cade, J. E., Grant, P. J., & Hardie, L. J. (2016). Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures. Endocr Rev, 37(6), 584-608. doi:10.1210/er.2016-1083

Santhi, N., Lazar, A. S., McCabe, P. J., Lo, J. C., Groeger, J. A., & Dijk, D. J. (2016). Sex differences in the circadian regulation of sleep and waking cognition in humans. Proc Natl Acad Sci U S A, 113(19), E2730-2739. doi:10.1073/pnas.1521637113

Selfridge, J. M., Gotoh, T., Schiffhauer, S., Liu, J., Stauffer, P. E., Li, A., . . . Finkielstein, C. V. (2016). Chronotherapy: Intuitive, Sound, Founded…But Not Broadly Applied. Drugs, 76(16), 1507-1521. doi:10.1007/s40265-016-0646-4

Simon, N. Actually. There’s a Right Time to Take “Once a Day” Meds. Readers Digest. Retrieved on May 3, 2018 at https://www.rd.com/health/conditions/medication-timing/.

Skarke, C., Lahens, N. F., Rhoades, S. D., Campbell, A., Bittinger, K., Bailey, A., . . . FitzGerald, G. (2017). A Pilot Characterization of the Human Chronobiome. Sci Rep, 7(1), 17141. doi:10.1038/s41598-017-17362-6