History of Chronobiology
Most of us have very little knowledge about the human body’s inner clock. However, a young science from Europe called Chronobiology has been gaining importance over the past 30 years. Chronobiology refers to the day-night cycle that affects the human organism when the earth rotates. Since the beginning of mankind, human history has been shaped by light and darkness. Genetically manifested timers reside deep in our bodies that control this fundamental rhythm. The more intelligently we absorb their information, the more useful it is. This connection is important in the prevention and treatment of diseases, as well as for the healing process.
The beginnings of Chronobiology date back to the 18th century. The astronomer Jean Jacques d’Ortous de Mairan reported daily leaf movements of the mimosa. Through experimentation he was able to show that the leaves continue to swing in a circadian rhythm, even in permanent darkness. Renowned scientists like Georg Christoph Lichtenberg, Christoph Wilhelm Hufeland, Carl von Linné, and—most importantly—Charles Darwin reported similar rhythmic phenomena. Yet it wasn’t until the 20th century when chronobiology research truly began. Wilhelm Pfeffer, Erwin Bünning, Karl von Frisch, Jürgen Aschoff, Colin Pittendrigh and Arthur Winfree are among its pioneers.
The Three Basic Cycles of Chronobiology
Infradian Rhythms
(derived from the Latin word infra, meaning “below,” and the Latin word diem, meaning “day” – breaking down the origin of the word, Infradian means the period of this rhythm is longer than 24-hours, therefor, the frequency is below/under those of one day.)
These are rhythms that last more than 24 hours. These are repeated only every few days, weeks, months, or even once per year.
Good examples are seasonal rhythms such as bird migration, lunar rhythms (which follow the phases of the moon, or about 29.5 days) and semi-lunar rhythms (about 14 days) that are associated with tidal cycles. Another example is unpredictable rhythms (aka “non-circadian rhythms” that do not have any environmental correspondence) such as a woman’s menstrual cycle.
Ultradian Rhythms
(derived from the Latin ultra, meaning “beyond,” and from the Latin word diem, meaning “day” – breaking down the origin of the word, Ultradian means the period of this rhythm is shorter than 24-hours, and therefor has a frequency beyond/higher than one day.)
These are biological rhythms that are shorter than 24-hours. There are many physiological functions of the human body that exemplify an ultradian rhythm. These rhythms have multiple cycles in one day. An adult, for example, has an exertion and rest cycle about every two hours.
Ultradian rhythms regulate physical, emotional and spiritual functions. They often last several hours and include the ingestion of food, circulation of blood, excretion of hormones, different stages of sleep and the human performance curve. These processes are built into our bodies in millions of ways. Some last merely seconds, such as the control of breathing. Some last only milliseconds, such as the majority of processes that take place in the cell on a microcirculatory level. Tidal rhythms (about 12.4 hours) are often observed in marine life, follow the transition of the tides from high to low and back and have a special function for many people living inside a surf zone.
Circadian Rhythms
(from Latin “circa” meaning “around,” and “diem” meaning “day”)
These are rhythms that take approximately 24-hours, i.e. the human sleep/wake cycle or the leaf movements of plants. Many effects of circadian rhythms directly and immediately affect humans, therefore, they are the most extensively researched. Thus, all further explanations refer to circadian rhythms.
Chronobiology Today
The field of chronobiology is rapidly expanding around the world. Medical professionals, researchers and the general population are beginning to see the benefits of using chronobiological principles in everything from medication administration to determining the most effective time of day to exercise. Chronobiology is being used in the study of genetics, endocrinology, ecology, sports medicine and psychology, to name a few.
The chronopharmacology branch of chronobiology has been especially lucrative. Thousands of studies have yielded information on how the precise timing of a medication or supplement can decrease side effects, have a more potent effect on the target organ system or disease and even completely disrupt a physiological process.
Many renowned institutions have added departments, labs and curriculum centered on the study of chronobiology. These institutions have provided groundbreaking research and insights that have helped shape modern medicine and the understanding of our innate biological rhythms. Melatonin, also referred to as the “mother hormone of chronobiology,” the effects of light on a variety of diseases and the phenomenon of chronotypes have been areas of particular interest.
While chronobiology is still considered a young science, the possibilities it presents are endless. Our methods of research are becoming more advanced and with that brings the reality that chronobiology will eventually become the leading scientific discipline.
External and internal clocks control our physical, mental and emotional functions without the need for us to interfere. The more intelligently we attune our life to these rhythms, the greater the benefit. Whether it is the oral mucosa or the liver, each physiological system has its own biological rhythm. This knowledge is of particular importance for disease and healing. Ailments such as asthma, arthritis, hypertension, depression, heart attacks, stomach ulcers, sleeping problems, cerebral metabolic disturbances and others have its own phases. The chronobiological factor of the active ingredients that are used in disease prevention or treatment is of crucial importance. To date, we may only divine a small fraction of the secrets underlying these substances. However, a number of important substances are already available as a chronobiologically meaningful formula, scientifically tested and proven. Initially, chronobiologists were dismissed. Today, their science is an acknowledged branch of research that investigates the interconnections of body, mind and time. You may be in for quite a surprise!
The most important conclusion drawn from a chronobiological viewpoint is that we possess a whole control package of genetically determined internal “time regulators.” Most importantly, our body follows an internal 24-hour cycle. Hormone release ultimately depends on the impulses of our inner clocks. Under the control of our brain, 150 messenger substances circulating in the blood inform our organs about the current situation and prescribe specific consequences. These hormones have a boosting and curbing effect. Our body temperature decreases during sleep, our blood pressure rises as we wake up, and so forth. These rhythms repeat every 24 hours, day after day, night after night. Scientists therefore speak of a “circadian” rhythm. The shortest up-and-down cycle is measured in the brain waves that last only fractions of milliseconds. The longest daily rhythms—such as hunger or need for sleep—extend over many hours.
Every moment, chronobiology transforms the actions inside our organs into a unique and distinctive spectacle. An hour later, nothing remains as it was an hour ago. It seems that with age, some of our inner clocks are ticking more slowly while others are ticking faster. They tend to go out of tune, and some of them stop ticking altogether over the years. Organs begin to develop their own rhythm and disturbances occur. If they remain untreated, diseases may develop.
Science distinguishes around 80 illnesses that are all deemed sleep-related. This is exactly the goal which chronopharmacology pursues: The right formulation at the right time. The current objective is to identify a circadian component in an increasing number of diseases or physical dysfunctions. This results in surprising options for treatment that are more effective and have fewer side effects. Chronobiological medicines or food supplements recalibrate our inner time regulator.
The light-darkness factor continuously adjusts our everyday functions to a 24-hour rhythm. Inside our body, this information is converted into a signaling hormone called melatonin. Melatonin already completes a multitude of tasks by daylight. Around 11 p.m. there is usually a sudden surge in melatonin levels to between eight and ten times the normal value. This is a signal for many organs to slow down their activity and regenerate themselves. Many elderly people, however, have largely lost this nocturnal melatonin surge. Many rhythms—including sleep, blood pressure, body temperature and hormones—remain uncontrolled. In these instances, a smart form of chronobiological support is needed. Exciting recent studies have come to valuable conclusions. Researchers are beginning to understand the hour at which tumor cells tend to divide. Time regulators that differ from those of healthy cells control tumors. Therefore, it is of vital importance that therapeutic cytotoxins be introduced into the target organ at a time when their impact on tumor growth is higher and when their effect is less detrimental to the remaining cells. Chronopharmacology, the search for therapeutic measures that are in harmony with our inner clocks, is currently the most fascinating area of medical research. We are gradually beginning to understand more and more diseases are rhythm disorders. This is the first step toward the principles of chronobiology.
Each cell produces highly specific substances, such as the building blocks of amino acids. Once the desirable concentration is reached, production stops. Enzymes decompose the substances within hours. A new cycle begins. Certain genes (also referred to as “clock genes”) act as on/off switches for these processes. They can be found in nearly any type of human tissue and their impact is incredibly multifaceted, sophisticated and smart. All parts of the human body have receptors that take up the information of messenger substances and neuronal stimuli. The “clock genes” control their sensitivity. This also applies to the effect of vitamins, trace elements and other biologically effective substances, including medicines. The main switch is located in the diencephalon, a central part of the brain composed of two structures. The diencephalon receives messages from special photocells located in the retina. These sensors, which have been decoded only recently, do not recognize objects or colors, but the times of the day, the ambient atmosphere and the seasons. They are the starting point of a mechanism of action, which in its entirety may be described as a control room where all inner clocks are set. This control room transfers the change between daytime and nighttime from the world outside to innumerable rhythms in our body and attunes them to and among each other. Light is a powerful pulse generator. Whether a person survives a heart attack may depend on the sun’s rays that shine through the window of the intensive care unit. Beds in the northern wing of a hospital are mysteriously associated with a higher mortality rate.
Practice of Chronobiology
To perform its myriad of tasks, our body needs to take in valuable substances at very specific times of the day. Even people with a healthy diet may experience nutritional deficiencies, especially so when they are exposed to everyday stress, environmental toxins, or metabolic disorders. Scientific research has provided us with accurate information on which nutrients the body needs, when and what dosage provides optimal support for food digestibility. While some nutrients have a mutually enhancing effect, others may hamper the desired effect. Chronobiological practice improves the ability of our organs to take up vital bio substances. The vitamins, minerals, trace elements and phytopharmaceuticals provided are supplied in a smart combination at the right point in time. The morning capsule, for instance, helps the body to keep its energy balance. The evening capsule helps to burn fats during the night and remove toxins from the body. Gender-specific formulas take into account the different metabolism of the female and male organs.
Most people regard vitamins as the givers of good health and swallow them at any time, thinking that they can do no wrong. Far from it! The stringent rules of chronobiology also apply when you seek to remedy vitamin or mineral deficiencies. Vitamins? Look at the clock first! The time point is crucial: First of all, the effect of some vitamins in the morning simply differs from their effect in the evening. Secondly, their effect on the metabolism may disturb the 24-hour rhythm of our body’s organs. Taking a multi-component formulation in a chronobiological form is simply essential. Choosing a different regime for men and women is even better.
Mindless intake of vitamins and minerals without a clear concept bears its risks
The biological effects of vitamins and trace elements shows major daily fluctuations and influences the body’s shifts of activity.
Vitamins taken with food or in the form of food supplements require fats or water to be transported to their target areas. Let us look at the fat-soluble vitamins first: Once they have dissolved inside the fat molecules, these vitamins reach the lymphatic vessels, the primary vascular system of tissue fluid. The lymphatic vessels are directly linked to only a few organs. The relevant vitamins accumulate primarily in fatty tissue and in the liver. Once inside the body, they cannot be easily eliminated. As the storage capacity of fat is huge, such vitamins should only be taken with utmost care. There are only four fat-soluble vitamins: A, D, E and K. They are best taken in the morning after a plentiful breakfast and are less effective when taken later in the day. Water is distributed all over the body: inside the cells, in the blood and in the interstitial tissue. Vitamin substances dissolved in water are universally effective, but also much more volatile. They are regularly eliminated in the urine.
Consistent daily dosage helps to avoid vitamin deficiencies or metabolic disorders. There are seven water-soluble vitamins in the B group: folic acid (B9), pantothenic acid (B5), thiamine (B1), cyanocobalamin (B12), riboflavin (B2), niacin (B3) and pyridoxine (B6). Other water-soluble vitamins are vitamin C (ascorbic acid), biotin (vitamin H), choline and myo-inositol. Most vitamins have no direct effect and play only a contributory role in certain functions. This is why they are commonly classified as co-enzymes or co-factors. The remaining tasks are taken care of by other substances—and this only works if these are simultaneously available in their active form.
The more researchers become involved in this issue, the more criteria that have to be fulfilled. The challenge is to apply two strictly separate—but equally intelligent—multi-vitamin-mineral products: one in the morning, the other at bedtime.
Chronophysiology is the branch of chronobiology that studies the timely organization of physiological processes. Included in the study is the timing of natural biological processes. Chronophysiology deals with the phenomenon of chronotypes, or morning larks and night owls. Additionally, it explains how biological systems and the processes of organisms relate to each other with regard to timing. The human body is subject to a 24-hour rhythm. We have an inner clock (circadian clock), which enables us to anticipate events that are repeated daily and to adapt to different environmental circumstances in a physiologically optimal manner. Our lives are ruled by a day/night rhythm. Indicators such as light, darkness and temperature influence our biological rhythm, which is already set deep within our genes. Almost all vital processes of the body that have been studied are subject to various rhythms. Hormones, neurotransmitters and sugar molecules that are consumed and antibodies within the blood cells show variably alternating concentrations in the blood throughout the day. Several changes are also important pacemakers for different reactions in the organs. Even the occurrence of illness and the intensity of its symptoms follow the impulses of an inner clock. This is especially true for asthma, depression and epileptic seizures. When the circadian rhythm is disturbed, general health and wellbeing are strongly impacted. Time changes, for example, can have the same effect as jet lag, including problems sleeping and concentrating, or even depression. Problems can become even more serious and long-term among shift workers with evidence of chronic disturbance. Only when adapting our lifestyle to match our inner rhythms can we achieve the energy necessary to stay healthy.
Chronopathology deals with the subject of disrupted timing in vital biological processes. It describes different phenomena in the abnormality of chronological sequences, as well as its characteristics, causes, prognostic and diagnostic significance and therapeutic implications. Illnesses in specific organisms manifest at specific times. Annual and weekly rhythms have an impact on susceptibility to and frequency of illnesses, accident frequencies and mortality rate. Deviations in the biological rhythm are common. Blood pressure, for example, exhibits quite a few factors. Abnormalities occur under certain everyday conditions, as well as during phases of activity and rest. Chronopathology studies these changing phenomena in functional disturbances of organ performance and in illnesses, in relation to the role of the day/night rhythm. The most common areas of need for this science are in shift workers and jetlag, which are both marked by time shifting.
Chronopathology helps to identify different phases of deviation from the norm. Recognizing time-dependent characteristics can be of great importance in diagnosing and treating an illness. Intelligent anatomy is the foundation for medications that possess a therapeutic time frame.
Chronopharmacology is a branch in chronobiology that studies our inner clock in relation to its effect on drug therapy. It explores the behavior of drugs in the human body and the impact of the time structuring of the organs. The human body follows a 24-hour cycle and our inner clock regulates its functions. Biological rhythms are crucial for determining correct administration of medication. The effects and side effects of medications can vary according to the time that they are consumed. This knowledge is incredibly important for the treatment of a variety of illnesses. Not only the amount of the administered substance is important, but also the time of day that it is consumed. Important questions that are answered through chronopharmacology include:
- Which substance works best in the morning?
- Which substance works best towards evening?
- Which substances can be taken together and which need to be combined in order to work at all? Can a biological substance be hampered through certain substances?
- How does the effect of certain medications change in relation to the time of day that they are administered?
- How is it possible to optimize the effectiveness of medications?
Administering pharmaceuticals at the correct time can increase the effectiveness of therapy and keep side effects to a minimum. Blood pressure medication and cortisone preparations need special care when determining the time of administration. For example, certain antihypertensive drugs decrease blood pressure better when taken in the evening instead of the morning. Patients will benefit from the use of chronopharmacology, as it offers important information as to the timing of medications, which leads to higher tolerability and effectiveness in individual preparations. Chronopharmacological scientists are researching new findings with regard to the timing of medications that will improve efficiency and lessen side effects. Many substances already have a known optimal time of administration for effectiveness. A number of modern preparations can almost be designated as intelligent. These contain certain biological micro-substances for the entire day that need only to be taken once a day. They are effective from the point of administration well into the night as they are outfitted with either a time lock or with substances that release at differing speeds.
