The circadian rhythm of illness
The biorhythm of illness is not a new subject, with reports of the early morning symptoms of ischemic heart disease appearing in the literature as early as 1772 (Heberden, 1772). Recent research has emphasized not only the understanding of the diurnal variation of disease, but also the importance of timing treatment protocols accordingly, taking into account the circadian rhythms of the absorption, distribution, elimination and effects of medications on the gastrointestinal tract, liver, kidneys and other organs (Smoleknsy et al., 1995). Thousands of years ago, in ancient China, chronotherapy played an important and well-defined role in the diagnosis and treatment of illness.
Traditional Chinese Medicine (TCM) works on the premise that the human body has various forms of energy, or "Qi" (pronounced "chee"), which flow through a series of well-defined tracts on the limbs, trunk and face. These routes are called "meridians", which in turn correspond to internal organs responsible for the vital functions of the body. Any imbalance in Qi--whether it be excess, deficiency or improper flow--will lead to disease. Treatment entails proper diet, physical activity (such as Tai Qi, or "moving the Qi"), herbal therapy and the superficial insertion of needles in selected points on the imbalanced meridian. This last form of treatment is known as "acupuncture", whose purpose is to re-establish the normal circulation of Qi within the meridian, and, subsequently, the affected organ.
Chronotherapy in TCM encompasses the recognition of the diurnal variation in the flow of Qi throughout the internal organs and the treatment of imbalance, by acupuncture, at specific times. One of the classic and most important works written on TCM is "The Yellow Emperor's Classic of Medicine", thought to have been written by the emperor Huang Di, who reigned during the middle of the third millenium BCE (Ni, 1995). In this discourse, he explains that Qi takes its course through the 12 organ meridians over a period of 24 hours, spending two hours at maximal levels in each organ (referred to as the "twelve branches" theory) (Mao, 1993). In general, when treating a patient in accordance with this biorhythm, the best time to treat an excess of energy is at or shortly before the time of greatest meridian activity, while the best time to treat depleted energy is following the peak (Manaka and Urquhart, 1972). The peak times of Qi for each organ can be seen in Table 1. In TCM, the functions of the organs are not always the same as they are understood today. Still, when observing how ancient Chinese medicine understood chronotherapy, one cannot help but be impressed by the similarities with the discoveries of modern research. Presented are a few examples of such similarities.
Table 1. Two-Hour Peak Periods of the Twelve Organs in
Traditional Chinese Medicine (see text)
Time Period Time Branch Organ
03:00-05:00 Yin Lungs
05:00-07:00 Mao Large Intestine
07:00-09:00 Chen Stomach
09:00-11:00 Si Spleen
11:00-13:00 Wu Heart
13:00-15:00 Wei Small Intestine
15:00-17:00 Shen Bladder
17:00-19:00 You Kidneys
19:00-21:00 Xu Pericardium
21:00-23:00 Hai TripleWarmer
23:00-01:00 Zi Gallbladder
01:00-03:00 Chou Liver
1. Lungs (03:00-05:00)
In TCM, the lungs are responsible for breathing, as well as for controlling the protective Qi of the body (called the "Wei Qi"). This protective Qi prevents external pathogenic factors (such as viruses) from invading the body. Imbalance in the lungs will lead to respiratory disease, as well as recurrent infection, especially of the upper respiratory tract. In Western medicine, nocturnal worsening of asthma is a well-known and well-documented phenomenon, with peak flow values at their lowest at 04:00. Diurnal changes in the plasma levels of cortisol, epinephrine, cyclic AMP and histamine are thought to be the cause of this exacerbation (Barnes et al., 1980). As such, treatment with long-acting beta 2 agonists, theophylline, anticholinergics, corticosteroids and leukotriene-active drugs given at certain hours during the day have been found to decrease the incidence and severity of nocturnal asthma attacks (Martin and Banks-Shlegel, 1998). In TCM, treatment is aimed at this time slot, when symptoms are most severe.
2. Large Intestine (05:00-07:00)
In TCM, the large intestine is responsible for digestion and excretion. However, it also has a role in the immune system of the upper respiratory tracts as the counterpart organ of the lungs (all of the internal organs are paired--the lungs with the large intestine, the stomach with the spleen, the heart with the small intestine, the bladder with the kidneys, the liver with the gallbladder, and the pericardium with an organ-like entity called the "triple warmer"). Often an acute viral illness can be felt in the pulse at the position of the large intestine (pulse diagnosis is one of the fundamentals of TCM). More recent research has shown that sufferers of viral and allergic rhinitis ("hay fever") have the most severe symptoms at this hour (Smolensky et al., 1995; Nicholson and Bogie, 1973), with "blocked nose" at 5:00 a.m. and "runny nose" at 6:45 a.m (Smolensky et al., 1995). Studies of HI-receptor antagonists showed maximal benefit when administered in the early evening (resulting in peak levels in the early morning) (Reinberg et al., 1985). According to TCM, treatment of this meridian is very effective for acute viral and allergic symptoms.
3. Stomach (07:00-09:00)
The stomach in TCM plays a role similar to that in Western medicine. Chinese medicine emphasizes the importance of a balanced diet, especially a proper breakfast, since this is the time the stomach has the most energy to digest the food. Interestingly, studies of gastric motility have shown that gastric emptying is maximal at this time of day (Goo et al., 1987). Conversely, acid secretion is at its peak in the evening (Moore and Englert, 1970), and therefore H2-blockers given in the early evening suppress intragastric acidity more than early morning dosing (Wilder-Smith and Merki, 1991). In TCM, it is at night when the stomach is weakest, with heartburn resulting from Qi moving upwards instead of downwards, referred to as "rebellious Qi".
4. Heart (11:00-13:00)
The heart in Chinese medicine is considered to be the "Emperor" of the internal organs. It is responsible not only for the proper flow of blood in the blood vessels, but also for spiritual peace and proper sleep. Daily rhythms in heart rate and blood pressure were being described at the end of the 18th and middle of the 19th centuries (Lemmer, 1998). Stroke volume, heart rate and, consequently, cardiac output and blood pressure, increase throughout the morning, peaking in the early afternoon (Lemmer, 1989). The TIMI III and IIIb studies found that more patients with acute ischemic syndromes of unstable angina and non-Q wave MI had onset of ischemic pain between 6 AM and 12 noon than in any other 6-hour interval. This circadian rhythm of disease is apparently due not only to the increased blood pressure and heart rate, but also to sympathetic tone, platelet aggregation, plasma cortisol and epinephrine levels and reduced endogenous fibrinolytic activity (Cannon et al., 1997). It has been proposed that beta-blocking drugs, known for their anti-ischemic effects, should be administered in such a way as to give coverage during the "ischemic" hours of the morning (Kraft and Martin, 1995).
5. Kidneys (17:00-19:00)
The kidneys in TCM are not only responsible for the proper flow of urine (along with the bladder, whose time is 15:00-17:00), but are also the fundamental source of innate energy and constitutional makeup vital for daily health. With aging, the kidneys grow weaker, with a general decrease in energy levels and difficulties with urinary flow and continence. Contemporary studies of excretory kidney function have found that different ions have different peak time occurrences in the urine; sodium and magnesium at 7:00 PM, calcium at 4:00 PM, and potassium at 1:00 PM (Kanabrocki et al., 1983). This information is important with respect to all medications which undergo renal excretion, as well as for maximizing the effect of diuretics such as thiazides and furosemide (Kraft and Martin, 1995).
6. Liver (01:00-03:00)
The liver in TCM is responsible for the proper flow of substances throughout the body, as well as movement of both physical and emotional aspects. Hepatic flow has been shown to be significantly greater during the late night and early morning than about noon or in the afternoon (Lemmer, 1991). Serum levels of drugs such as propanolol have been found to be relatively high when taken at 8:00 a.m., when liver metabolism is low (Langner and Lemmer, 1988).
The ancient Chinese understood the importance of the circadian rhythm of the body. The similarities between the hours designated to the organs by TCM and the findings of recent research are striking. It will be interesting to compare further discoveries in the field of chronotherapy with the biological clock as understood by Chinese medicine. Western medicine uses the understanding of chronotherapy to treat illness more effectively. TCM uses its understanding of biorhythms for this purpose as well, not only in acupuncture but also in diet therapy and physical activity.
The timing of Western medical therapies are, for the most part, patient-dependent. Thus, if it is preferred that a drug be taken in the late evening or early morning, the patient can easily alter his or her schedule. With acupuncture, both patient and doctor must meet, a logistically difficult feat when applying the chronotherapy principles of TCM. The result is that however desirable it may be to treat asthmatics with acupuncture at 3:00 in the morning, the treatment will invariably be performed during working hours. Still, much can be learned from the similarities between the various disciplines, hopefully improving general health and advancing the treatment of illness.