By nature, people are active during the day, and the night is used for regeneration. Messenger substances, organs, every single cell follow a 24-hour cycle, the circadian rhythm (from the Latin: “about a day”). It is an alternation between activity and rest. The body starts it up again every day.
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Before waking up, levels of cortisol and other wake-up hormones rise. Shortly after getting up, the blood pressure shoots up and the heartbeat accelerates.
Around noon, the production of red blood cells is in full swing. Body temperature reaches its daily high in the late afternoon. The entire organism is programmed for activity.
When it gets dark, the sleep hormone melatonin begins to be released. Most bodily functions switch to economy mode. Blood pressure, pulse, respiratory rate, body temperature decrease. Skin and hair regenerate, the organism releases growth hormones.
Chronomedicine directs its attention to the rhythmic processes in the body. When is the right time to give medication or have surgery? How can diseases be prevented with the help of the internal clock? These are the questions the discipline deals with.
The chronobiologist Achim Kramer from the Berlin Charité is investigating how drugs can use the internal clocks. He states: “A therapy that respects the 24-hour cycle of the organism is superior to a standard therapy in many cases.”
Complaints and illnesses also follow a timetable. At certain times they appear more frequently. Patients with rheumatoid arthritis, for example, suffer from stiff joints and pain in the morning and therefore usually take cortisone in the morning to combat the inflammation.
Researchers at the Charité discovered that the optimal time for the drug to take effect was between two and four in the morning. This is when the concentration of pro-inflammatory cytokines, especially interleukin-6, is highest.
However, since taking it in the middle of the night is impractical, the rheumatologists developed a tablet that releases the active ingredient with a delay. Swallowed before bedtime, hours later the cortisone caps the nocturnal interleukin-6 spike. A study confirmed: The preparation reduces the duration of morning joint stiffness by almost half.
Cholesterol-lowering drugs, the statins, have also long sat in the morning drawer of pill boxes. However, cholesterol levels are higher at night than during the day. Therefore, taking the tablets in the evening is now recommended. “If you take chronobiological processes into account, this often increases the effectiveness of medication and reduces undesirable side effects,” Kramer is convinced.
Years ago, the French oncologist Francis Lévi was able to show in clinical studies that chemotherapy is better tolerated if it is administered at certain times of the day. Tumor cells are always dividing, they no longer have a rhythm, but healthy cells do.
Lévi gave chemotherapy drugs at times when the healthy cells weren’t dividing. Of the colon cancer patients treated in this way, only 14 percent suffered from mucosal inflammation compared to 76 percent in patients with standard therapy. The dosage of the chemo could also be increased by a fifth.
A meta-study published in the journal “Lancet Oncology” in 2022 confirms that the timing of chemotherapy based on the body clock reduces undesirable side effects while the drugs are equally and sometimes more effective.
In a recent interview with the “Schweizerische Ärztezeitung”, Lévi expressed his disappointment that findings from chronotherapy are not being taken more into account in everyday clinical practice.
Positive effects can be demonstrated in many areas. For heart valve operations, for example. If these take place in the afternoon, they are associated with fewer complications than the same procedure in the morning. The body probably tolerates the lack of oxygen better later in the day as a result of the reduced blood flow.
Pain sensitivity also fluctuates throughout the day. For a few hours after 1 p.m. it hurts a third less than in the morning. The body’s own pain hormones, the endorphins, are less active at night and in the morning.
The increased nocturnal sensitivity prevents the body from oversleeping alarm signals. Pain in the morning signals that the body needs rest. The mechanism also influences the duration of action of local anesthesia. At 4 p.m. it lasts twice as long as in the morning.
The internal clock is an impressive pacemaker. But how is it set? “In each cell there is a counter that starts or stops the bodily processes,” says Henrik Oster. The chronophysiologist researches at the University of Lübeck how body clocks communicate with each other.
The network of timekeepers coordinates a “master clock”, a nerve node the size of a grain of rice. The suprachi-asmatic nucleus (SCN) is located in the brain at the junction of the optic nerve and receives signals from sensory cells in the eye that respond to daylight.
The SCN sets the pace for the clocks in the cells. There, genes start the respective programs for their tissue, analogous to the course of the day. “The aim is for the clocks to tick in unison and run in sync with the daily rhythm,” says Oster. The most important zeitgeber is the light. But food, physical exercise and much more also influence the clocks.
The inner rhythm is not the same for everyone. Genes determine whether someone is fresh early in the day or only shows up in top form late in the evening. The chronobiologist Kramer and his team have developed a test that determines the individual chronotype.
In the blood or in the hair roots, they examine twelve genes that are active at different times of the day. “For example, if we find mainly six o’clock genes active in a sample taken at nine o’clock, we are dealing with a late chronotype,” explains Kramer.
It often happens that the internal clock deviates from the external time by three hours. The prescription to take tablets “in the evening” means 7 p.m. for some and 10 p.m. for others. “Determining the chronotype is a further step towards personalized medicine,” says Kramer. The test is currently offered as a lifestyle product by BodyClock Technologies, a Charité spin-off. Approval as a medical device is still pending.
Living against the natural daily rhythm is unhealthy in the long run. “People who work shifts have an increased risk of any disease for which they have a genetic predisposition,” observes sleep doctor Dieter Kunz. The psychiatrist treats in the clinic for sleep
Like many chronobiologists, Kunz pursues the idea of preventing or delaying diseases by turning the internal clocks. He is concerned with the prevention of Parkinson’s. A precursor to shaking palsy is REM sleep behavior disorder. Those affected jump out of bed during the dream sleep phase, and some thrash about. Four out of five develop Parkinson’s within 15 years.
Kunz treats the sleep disorder with melatonin. According to him, patients are less likely to develop Parkinson’s. In the case of chronic insomnia, the expert relies on light. It irradiates people with a disturbed day-night rhythm for three hours in the morning with low-intensity full-spectrum light.
The expert reports that the quality of REM sleep was already significantly improved the following night in the laboratory. From now on, the patients should be outside in the daylight for about half an hour before noon in order to synchronize their internal clocks. “The effect is stunning,” enthuses Kunz. “People sleep better. Some even report that their cardiac arrhythmias have improved.”
Doctors in the intensive care unit at the Charité also rely on the regulating power of light. Intensive care patients usually do not have a stable internal rhythm. Designers have installed a skylight above some of the beds, and special programs simulate the change from day to night.
An accompanying study shows that patients from these rooms suffered significantly less often from postoperative confusion, so-called delirium. The rate was lower by half.
“We’re still at the very beginning,” emphasizes Kramer. “But it has long been undisputed that the inner clock is a powerful force.” Not only as a clock for the organism, but also as an efficient tool for therapy.
This article was written by Susanne Wittlich, medical editor
The original of this article “Chronomedicine: The right time for treatments and therapies” comes from FOCUS doctor search.
