It’s Time for Your Medicine. Or, Is It?

“One in the morning, one in the afternoon and one before dinner.” Everyone of us has heard this at the doctor’s office. However, can this process be optimized? Are we consuming more drugs than need?

These questions rose due to the increase in antibiotic resistance which is also an alarming concern in the community. Many scientists hypothesize antibiotic resistance may become the leading cause of death in the next decade. Overuse of antibiotics is one of the sole reasons for the rise of this phenomenon. Multiple alternative strategies have been postulated to overcome and avoid antibiotic resistance. Chrono-medicine is one such approach which sprung to light from the past.

How does the time at which medicine is consumed matter? 

The environment we live in is periodic in nature. Living organisms have adjusted and adapted their internal periodicity to the environmental periodicity. Adapting to the 24 hour day-night cycle is called the circadian rhythm. It is one of the most widely understood and studied behavioral rhythms as it’s effects lie in multiple physiological processes.

In the past decade, numerous studies have been carried out in identifying the regulation of circadian rhythm in different processes including immunology, disease progression, stress and anxiety to name a few. With the Nobel prize in 2017 awarded to discovery of molecular machinery of the circadian clock, the research in chronobiology has spurred up. Recent research has shown that around 60% of our genes have an oscillation of nearly 24 hours either dependent or independent of the circadian rhythm.

What is chrono-medicine? How does it work?

Chrono-medicine (chronos ∽ time) is an age old concept postulated by the pioneers in chronobiology-Ashoff and Pittendrigh. They believed that timing of medicine mattered in ensuring its efficacy. A classic example of the importance of timing in disease manifestation is the increased coughing fits during the evenings. This is because macrophages which clear the bacterial load in the system are highly expressed in the evening. Apart from these interleukins, a class of cytokines are also have a daily oscillation.

As time plays a big role in our physiological well being, the action of medicines can best manifested if it is taken at the time point when its target is highly expressed. Based on the disease presentation and known factors about medicines targets, doses are given based on the daily oscillations of proteins either involved in drug absorption or metabolism. In a nutshell, chrono-medicine tries to achieve this.

Chrono-medicine: Are we there yet?

Chrono-medicine explores the interaction of biological rhythms, disease, drugs and time of the day. Several examples of chrono-medicine are seen in the medical field. Consuming non-steroidal anti-inflammatory drugs (NSAID) are far less dangerous to the stomach lining when consumed during night rather than day. Another exmaple is the use of melatonin, as a chemotherapeutic target for Diabetes.

Further, chrono-medicine was used in treatment of cancers. Dr.Levi and a group of scientists in 2017 ran the largest clinical trial for chronotherapy on metastatic colorectal cancer with 564 patients. The patients were treated with time dependent chemotherapy based on chronobiology or traditional chemotherapy. Although there was no clear difference between the two treatments, they found out that, in general, female patients experience more toxic effects to chemotherapy drugs.

The mixed results obtained in different treatments made scientists realize that the precision required for chrono-medicine is yet to be achieved. Although chrono-medicine is promising, the practical usage is far more compelling than visualized. With the advent of precision medicine, optimizing it with chrono-medicine can be highly beneficial. Owing to the cost factor these treatments, it might not be available to most of the populations but the importance of the field cannot be unseen.

Author

 Aishwarya Segu is a PhD student from IISER Trivandrum who is fascinated with the working of the brain. She is a curious scientist, an avid reader and a trying writer.