The human body is a fascinating machine kept running by a myriad of different forces. Of special significance among these is our circadian rhythm, an internal clock that regulates many of our body’s essential functions, ranging from wakefulness and sleep to hormonal release and body temperature.
Even in the absence of external cues, our circadian rhythms persist, which allows our bodies to anticipate environmental demands, opportunities, and challenges.
This branch of science which studies biological rhythms in living organisms is called chronobiology. Using this field of research as a framework, researchers are calling for a new look at medicinal treatment that integrates chronobiology into medical practice.
“The human circadian system plays a vital role in many physiological processes, and circadian rhythms are found in virtually all tissues and organs,” wrote a team of researchers from Northwestern University Feinberg School of Medicine in Chicago. “The disruption of circadian rhythms may lead to adverse health outcomes.”
Called chronotherapy, scientists believe that a whole field of medicine with the potential for more effective treatment could potentially lie at our fingertips. By compiling data from numerous observational studies, it is believed that the role of chronotherapy in health and behavior within real-world settings could be better understood.
What processes does our circadian rhythm control?
In a 24 hour day, our body undergoes many changes that help us function, all regulated by our internal biological clock. Every morning, our body temperature rises and we are jolted with a spike of the stress hormone cortisol to stimulate our muscles and rouse us into a state of wakefulness and alertness.
As the day progresses, we are drawn to consume food when our body indicates that we’re hungry. At night, our pineal gland begins the production of the hormone melatonin to help our body and mind prepare for sleep while our body temperature also drops about two degrees Celsius.
“Our internal rhythms are synchronized with the external world primarily through light signals that reach the suprachiasmatic nucleus through the eye via retinal ganglion cells,” said Velarie Ansu Baidoo and Kristen Knutson in their study published in Obesity: A Research Journal. “The central clock, in turn, regulates peripheral clocks through several mechanisms, including controlling rhythms in body temperature, autonomic nervous system activity, and various hormones.”
All of this is to say that the biochemical state of our bodies varies throughout the day. Not surprisingly, the disruption of your circadian rhythm can have very ill consequences for one’s health. For example, according to the International Agency for Research on Cancer, night shift work is classified as “carcinogenic” in humans. “Maintaining synchrony is key to optimal health, and this includes synchrony between our internal clocks and the external world, as well as synchrony among all the internal clocks,” wrote Baidoo and Knutson.
As our modern society continually introduces new ways to break free from the “archaic” rhythms of day and night, it is important now more than ever to learn about our biology and take responsibility for our health — chronotherapy can help us do this.
“Chronotherapy’s potential is largely untapped,” stated Robert Dallmann, associate professor of cancer biomedicine and chronotherapy at Warwick Medical School in the UK in an interview with Mark Greener in Perscriber.
Dallmann is researching the interplay between the timings of various bodily processes with disease and pharmacology. More specifically, he is trying to mechanistically understand how circadian disruption can lead to and influence disease progression and treatment. “Although understanding the underlying mechanisms has led to more activity in this space, clinical practice is changing only glacially.”
One reason for this slow change is the simple lack of education and resourcing in clinical spaces. “We need to educate the medical community and make circadian medicine part of the curriculum,” Dallmann said. “Resourcing may be less of a concern for oral medications. But in the context of recording symptoms by GPs, or hospital treatments such as injectables, resourcing may be a concern.”
Where is chronotherapy already being used?
Despite the aforementioned challenges in education and resourcing, chronotherapy is already being implemented in various clinical settings.
Some preliminary research has shown that drugs, such as aspirin and simvastatin (a medication used to aid in weight loss), become much more effective when taken in low doses in the evening. For cancer patients, chemotherapy drugs such as capecitabine and oxaliplatin, immune checkpoint inhibitors, and cancer vaccines have also been demonstrated to be more effective depending on the time of day that they are administered.
There are also prescription medications designed to target genes that control our circadian rhythms. Sildenafil, for example, is the main ingredient in Viagra, but it can also be used to help with jet lag as it inhibits an enzyme found in the brain, enhancing the body’s circadian response to light.
This reduces the amount of time needed to reset after changes in the sun rising and setting, which occur during travel, which could be greatly beneficial for eastward bound travelers looking to beat the jet lag.
In people with asthma, symptoms are often worse in the early morning, when the airways are narrowest and white blood cell counts are highest in the lungs. Delayed-release formulations of theophylline have been used to successfully treat nocturnal asthma, relieving many patients of their symptoms.
One of the main benefits of chronotherapy is that treatment can be tailored to a disease’s oscillating signs and symptoms. In the case of cardiovascular disorders, chronotherapy can also be extremely beneficial. When we wake up in the morning, our blood pressure rises rapidly in anticipation of the day ahead, and at night, it dips about 10-20% to help us prepare for sleep. Individuals who do not experience this healthy dip in blood pressure are much more likely to suffer from cardiovascular disease or hypertensive diseases, such as kidney or eye disease. Therefore, taking blood pressure medication at night vs. the morning improves the efficacy of the medicine.
By utilizing our knowledge of circadian biology and applying it to situations such as these, it allows us to fine tune our approach to more effectively improve health outcomes.
Challenges for chronotherapy
Despite all that chronotherapy promises, there are obstacles that still need to be overcome. One of the most pressing issues is the need for reliable biomarkers, which are physiological indicators or biological molecules that provide a snapshot of a patient’s medical state. These include blood pressure, body temperature, blood cell counts, and body mass index.
Indeed, finding reliable ways of measuring biomarkers linked to our biological clocks is the key to standardizing chronotherapeutic solutions for a wide range of medical challenges. But this isn’t so straightforward with chronotherapy.
“How can we reliably measure ‘the clock’ in patients’ tissues, tumors, and so on?,” stated Dallmann in the article. “We know these differ from healthy humans and that disease and some drugs may interfere with circadian patterns.”
Then there come the complexities that pharmaceutical companies will have to consider when advertising specific dose timings on their labels. A generic prescription simply may not be adequate enough due to all of the variables involved.
“If a drug is to be taken ‘in the morning’, what happens if the person is an extreme late chronotype? Has jet lag? Works shifts? The industry would need to consider this and regulators would probably ask for data,” Dallmann commented. In addition, these unknowns make it difficult for pharmaceutical companies to embrace chronotherapy due to the cost implications during development as well as possible legal exposure and liabilities that may arise later on.
As we continue to push forward into this new scientific territory, there are sure to be roadblocks, but with determination the health and wellbeing of many will be improved. It is humbling to be reminded that we are still beholden to our biology despite our godly technological advances.
In time, it will be interesting to see how chronotherapy is utilized to improve medicine and save lives.
Feature image credit: Abdülkadir Vardi on Unsplash