biorhythms, and chinese medicine - NCBI

PSYCHON EUROENDOCRINOLOGY, BIORHYTHMS, AND CHINESE MEDICINE Carl C. Bell, MD Chicago, Illinois The discovery of an endogenously formed opioid substance in the body which is intimately related to corticotrophin and, thus, a major consideration in the body's response to stress already has demonstrated the impact that psychoneuroendocrinology can have on the practice of medicine. The psychoneuroendocrinologic system is characterized by a daily rhythm; because of this rhythmic variation, the body is in different physiologic states at different times of the day. This has raised some important questions for clinical practice. Western medical science and Chinese medicine are compared and suggestions are made on how to best utilize the knowledge currently being gained in psychoneuroendocrinology and biorhythms.

Corticotrophin (ACTH) is a large polypeptide produced in the pituitary. It causes the adrenal cortex to increase the production of adrenocortical hormones such as cortisol. ACTH has been found to follow a rhythmic pattern of release known as circadian (one cycle of release being approximately 24 hours). It is the intent of this paper to review some important physiologic changes produced by ACTH rhythms and to examine how this naturally occurring phenomenon might be used to improve the practice of medicine. Finally, the knowledge of modern medicine, with regard to biological rhythms, is discussed in relationship to

Requests for reprints should be addressed to Dr. Carl C. Bell, Jackson Park Hospital, 7531 Stony Island Avenue, Chicago, IL 60649.

the phenomenologic art of Chinese medicine which originated in 200 BC.

PHYSIOLOGY OF ACTH In recent years, there has been increasing documentation that ACTH production is influenced by a circadian rhythm, resulting in higher levels of ACTH being available to the body in the morning hours than in the afternoon or evening. Krieger and Allen, using immunoassay techniques, have demonstrated ACTH was highest in the hour preceding awakening (6:30-7:30 AM), at a level of approximately 12.5 ug/hour. Between 10:00 and 11:00 AM and 9:00 and 10:00 PM, ACTH levels were 4.7 ,ug/hour and 1.6 ug/hour, respectively.' As a result of the morning increase in ACTH production, cortisol also has been shown to be in high concentrations in plasma between 6:00-8:00 AM, at a level of about 12 + 2 ,g/100 ml.1-4 Plasma cortisol levels decline to 5 + 1 ,ug/100 ml from 6:00-8:00 PM.2-4 Thus, there is a variation in plasma cortisol concentration of 50 percent (it has been reported that this variation may be as high as 70 percent5). As ACTH has been shown to increase production of cortisol, it is generally held that this rhythmic pattern of cortisol is caused by the rhythmic production of ACTH. ACTH has been shown to be produced by the cleavage of a larger precursor peptide known as "big ACTH," which in addition to ACTH contains /8-lipotrophin.6 It is interesting to note that the end third of ,8-lipotrophin has an amino acid sequence which contains both enkephalin and ,8-endorphin-two substances which replicate opiate activity in the body. Thus, it has been shown that approximately equimolar concentra-

JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 73, NO. 1, 1981

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PSYCHONEUROENDOCRINOLOGY AND CHINESE MEDICINE

tions of ACTH and ,/-endorphin are released in the body simultaneously.4 The production of ACTH (and, therefore, ,l-endorphin) appears to be regulated by several factors. ACTH and 83-lipotrophin (which rises in parallel with /8-endorphin) are released in human subjects by hypoglycemic stress.7 Pain has been associated with increases in ACTH levels.8 Depression tends to cause an increase in cortisol and failure of suppression from dexamethasone, suggesting increased ACTH in patients.9 Finally, job pressures and noon meals appear to influence cortisol circadian rhythms and, thus, may also influence ACTH production.10'11 However, as many of these factors are still unclear, it is the author's purpose to look at the early morning high level of ACTH, ,B-lipotrophin (thus, f3-endorphin), and cortisol and how this naturally occurring, light regulated, circadian rhythm could be of clinical use.

PHYSIOLOGIC STATE OF THE BODY IN THE MORNING To a great extent, the physiologic state of the body in the morning is a function of the increased production of ACTH, which stimulates the production of cortisol. Cortisol has a generalized effect on body metabolism and causes gluconeogenesis leading to an increase in liver glycogen and blood glucose, which in turn causes an increase in the secretion of insulin. Cortisol also increases blood amino acids. This may be the most important function of this hormone and results in the reduction of protein stores of the body (with the exception of those in the liver). It is well known, for instance, that the different cells continually synthesize a multitude of chemical substances from amino acids. Furthermore, since the normal concentration of amino acids in the body fluids totals only 30 Ag percent, mobilization of amino acids from the tissues might play a valuable function in providing an available supply of amino acids for damaged cells in time of need.8

In the liver, cortisol increases the deamination of amino acids, protein synthesis, the formation of plasma proteins, and the change of amino acids

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into glucose. Furthermore, cortisol causes the mobilization of fatty acids from adipose tissue, increasing unesterfied fatty acids in plasma and making them available for energy use. Finally, cortisol blocks the process of inflammation and prevents fluids from leaking into damaged areas; it thus blocks inflammatory responses to allergic reactions. In observing the physiologic state of the body in the morning hours, one finds a manifestation of high biologic levels of ACTH, 8-lipotrophin (thus, ,3-endorphin), and cortisol. In the early hours of the morning (3:00-6:00 AM), the liver has used up much of its glycogen, due to the lack of food intake during the night. As is true with most of the other amino acids, tryosine concentrations reach a high point at 10:00 AM. (It is interesting to note that this pattern is not dependent on whether or not an individual is receiving a high or low protein diet and the same holds true for the glycogen rhythm, regardless of whether or not the individual is on a starvation diet.) Triglycerides are also at their highest level at 6:00 AM. In addition to these biochemical parameters, vital signs may change. The respiratory rate is usually increased and blood pressure tends to be lower. Individuals documented to have hypertension may show high blood pressure levels at 6:00 PM, but have normal levels at 8:00 AM. Furthermore, a person taking a glucose tolerance test in the morning may be shown to be "normal," but if the same individual gets the same test in the afternoon, the results may indicate that he/she is "diabetic." Probably as a result of the early morning release of 8-endorphin, individuals are more insensitive to pain, noise, taste, and smell (sensory acuity is at its maximum at 3:00 AM when corticosteroid levels are at the lowest and then it begins to decrease as steroid levels rise). Finally, as histamine levels show the reverse pattern of release of cortisol, in the early morning, histamine levels are at their lowest for the day.5 As a result of this different physiologic state of the body in the morning, responses to various medications change. Aspirin has its longest halflife in the body when taken at 7:00 AM. The effects of antihistaminic medication last longest in morning dosages (17 hours); when antihistamines are taken in the evening the effects last only for a few hours. Dexamethasone, when given to asthmatic patients in the morning, has its greatest effects in the increasing lung vital capacity and one-second



forced-expiratory volume. Furthermore, it has been shown that there is a circadian responsiveness of the pituitary gland to exogenously administered steroids'2 and that, if 1/2 mg of synthetic cortisone is injected at 8:00 AM, there is a transient drop in blood cortisol levels, but if the same dose is given at 12:00 midnight, cortisol production would tend to be suppressed for 24 hours.5

CHINESE MEDICINE AND CIRCADIAN RHYTHMS The Yellow Emperors' classic on internal disease (200 BC) was the first book on acupuncture. 13 The Chinese were not more concerned with the scientific elaboration of anatomy or organ systems than with the system of forces in the body which caused physiologic homeostasis and illness. As a result, their conceptualizations tend to be symbolic of bodily processes. They conceptualized the existence of a life energy (chi) and felt that this energy activated all bodily processes. It was through the regulation of this life energy that the Chinese physician sought not only to combat disease but, more importantly, to prevent it. In addition to laws which represented the interplay between the energy of one "organ" and another, there was a law called "middaymidnight"' 3 which described the rhythm of life's energy. This law proposed that the chi flowed through 12 energy channels (acupuncture meridians) at regular times over a period of 24 hours. Thus, it was felt that there was a daily rhythm which determined when organs received their maximum or minimum chi, or energy supply. With this knowledge, an acupuncturist would coordinate his treatments with the time of day yielding best results. From this evidence, it is clear that ancient Chinese had phenomenologic understanding of circadian biorhythms which they utilized to better treat and prevent illness. The law of "midday-midnight" (Chinese biological-clock pattern) has many parallels with the circadian rhythm patterns demonstrated in modern Western laboratories. The acupuncture meridian cycle (ie, the path of life's energy in the course of a day) begins with the

"lungs" as the chi enters there first. Chi is also supplied by digestion of food and water in the "stomach" and is transferred from the "stomach" by the "spleen" to the "lungs." From the "lungs," the chi enters the lung meridian (recorded as most active from 3:00-5:00 AM) and is transmitted to its "coupled organ," the "large intestine" (an "organ" is coupled to another "organ" when the stimulation of that "organ's" meridian has a stimulatory effect on the other "organ's" meridian). From the large intestine meridian (at its highest peak from 5:00-7:00 AM) the vital energy is transferred to the stomach meridian (most active at 7:00-9:00 AM), and from there the chi moves on to the "stomach's coupled organ," the "spleen" (most highly energized between 9:00-11:00 AM). As a result of this metaphoric understanding of circadian rhythms, the Chinese felt that the best time to do breathing exercises was early in the morning from 3:00-7:00 AM, when the lung meridian and its coupled organ (large intestine) meridian were most active. It was best to eat when the stomach meridian, and its coupled organ (spleen) meridian were most active, 7:00-11:00 AM. According to Chinese medicine tenets, these were optimal times to increase the body's chi and, thus, prevent illness. Chinese physicians recommended that in order to remain healthy, one should do Tai Chi exercises14 ("soft" aerobic exercises designed to generate and distribute chi in the body) in the early morning. Using modern knowledge of the physiologic state of the body in the morning, nothing could make more sense. While the body is resting in the morning, the blood, which is rich in amino acids, free fatty acids, /8-endorphin, and cortisol, perfused the body at a very slow rate compared with blood flow in the body which is active. At rest, the blood flows through the muscles in the quantity of 4-7 ml/100 gm of muscle, while with extreme exercise, the amount of blood flow may go as high as 100 ml/100 gm-a 15- to 20-fold increase. This apparently is due to the fact that strenuous exercise causes all muscle capillaries to open as compared to only three percent being open at rest. Furthermore, strenuous exercise may increase blood pressure 50-70 percent, thus doubling available blood supply to muscles.8 In addition, exercise causes an increase in body temperature which, in turn, causes an increase in perfusion to the skin in an attempt to regulate body heat.


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Clearly, soft exercises, which do not produce oxygen debt, also increase the blood perfusion to the body, but with an additional advantage. Strenuous exercise derives most of its energy from anaerobic metabolism-blood glucose is converted from glycogen into lactic acid. After exercise, oxidative metabolism reconverts five sixths of the lactic acid into glucose and the other one sixth is oxidized in the tricarboxylic acid cycle. Soft exercises, while increasing blood perfusion, derive their energy from aerobic metabolism, and, thus, derive their energy not only from carbohydrates, as does anaerobic exercise, but from fats and proteins as well. Therefore, soft exercises in the morning not only cause increased perfusion of nutrient- and hormone-rich blood, but also promote metabolism which can best utilize those ingredients. Brandenberger and Follenius found that "physical exercise in man produces an increase in cortisol concentration affecting the normal diurnal pattern and reverses the morning decline in plasma cortisol concentrations. "15 In addition, several other studies have demonstrated rises in plasma cortisol in response to athletics.16"17 Regarding the Chinese concept of eating when the stomach meridian is most active (7:00-9:00 AM), it has been shown that 500 gm of liver eaten at 8 AM led to a very swift rise of amino acid levels. Yet, the same protein meal eaten at 8 PM did not elevate blood levels of amino acids above the fasting value generally found at that time."5 Finally, further linkage between Chinese medicine and ACTH/,8-endorphin has been shown by Chapman at Johns Hopkins, who demonstrated that the analgesic effect of acupuncture was destroyed when patients were given an opioid blocker; this suggests an endogenous opioid mechanism resulting from this ancient Chinese procedure. 18

CONCLUSION The discovery of the formation of an endogenously formed opioid (f3-endorphin), which is closely related to the body's stress hormones, ACTH and cortisol, has already caused the expanding field of psychoneuroendocrinology to have a considerable impact on medicine. While 34

there is considerably more to be learned, sufficient data are available to improve the present quality of medical care. Clearly, the Chinese had an understanding of body physiology and biorhythms and sought to harmonize their medical treatment with the natural laws of the body. The administration of medication, without taking into account the biorhythms of the body, may well cause a disruption of the body's natural rhythms that will result in an illness which is more chronic and severe than the illness for which the patient initially presented himself to the physician. An illustrative case is that of a 23-year-old black woman referred to this author by her dermatologist, as he thought that if attention were given to the psychosomatic component of her illness, she might improve. Her history revealed that the dermatologist had attempted to control her dermatitis with oral steroids (in a pattern which did not mimic the normal circadian rhythm of cortisol). Her reaction to this regimen was total disruption of her normal biological rhythms: ie, her sleeping pattern was disturbed; she often felt tired and irritable during times when she usually felt relaxed and calm; and she began to develop a Cushing-like syndrome. As a result, the prednisone was discontinued and she was given diphenhydramine hydrochloride, 50 mg three times a day, with the psychiatric referral. The patient was asked to reduce the dosage of diphenhydramine to 25 mg at 6:00 AM and 50 mg at 6:00 PM. The patient subsequently reported that her itching was substantially reduced, despite her taking one half as much medication. Other precepts which follow from a rudimentary knowledge of biorhythms include (1) advising patients seeking to lose weight to exercise in the morning when the body's biorhythm allows fat to be more easily metabolized and (2) advising patients with allergic problems to take advantage of the early morning high biologic levels of cortisol by increasing the perfusion of this steroid-rich blood to the body. As modern medicine continues to unravel the mysteries of psychoneuroendocrinology and biorhythms, it may be found that the ancient claims of Chinese medicine and Tai Chi of being able to cure allergies, asthma, neurodermatitis, hypertension, and mental illness might not have been so farfetched, and it may be discovered that those "primitive" people knew more than they are generally credited with knowing.



Literature Cited 1. Krieger DT, Allen W: Relationship of bioassayable and immunoassayable plasma ACTH and cortisol concentrations in normal subjects and in patients with Cushing's disease. J Clin Endocrinol Metabol 40:675-687, 1975 2. Jusko WJ, Slaunwhite WR, Aceto T: Partial pharmacodynamic model for the circadian episodic secretion of cortisol in man. J Clin Endocrinol Metabol 40:278-289, 1975 3. Gutai JP, Meyer WJ, Kowarski AA, et al: Twenty-four hour integrated concentrations of progesterone, 1 7-hydroxyprogesterone and cortisol in normal male subjects. J Clin Endocrinol Metabol 44:116-120, 1977 4. Tanaka K, Nicholson WE, Orth DN: Diurnal rhythm and disappearance half-time of endogenous plasma immunoreactive f3-MSH (LPH) and ACTH in man. J Clin Endocrinol Metabol 46:883-890, 1978 5. Luce GG: Biological Rhythms in Human and Animal Physiology. New York, Dover, 1971, p 52 6. Snyder SH: The opiate receptor and morphine-like peptides in the brain. Am J Psychiatry 135:645-652, 1978 7. Nakao K, Nakai Y, Jingami H, et al: Substantial rise of plasma f8-endorphin levels after insulin-induced hypoglycemia in human subjects. J Clin Endocrinol Metabol 49:838-841, 1979 8. Guyton AC: Textbook of Medical Physiology. Philadelphia, WB Saunders, 1966, p 1057 9. Ettiti P, Brown G: Psychoneuroendocrinology of af-

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fective disorders: An overview. Am J Psychiatry 134:493501, 1977 10. Caplan RD, Cobb S, French JR: White collar workload and cortisol: Disruption of circadian rhythm by job stress? J Psychosom Res 23:181-192, 1979 11. Quigley ME, Yen SC: A mid-day surge in cortisol levels. J Clin Endocrinol Metabol 49:945-947, 1979 12. Rastogi GK, Dash RJ, Sharma BR, et al: Circadian respQnsiveness of the hypothalamic-pituitary axis. J Clin Endocrinol Metabol 42:798-803, 1976 13. Mann F: Acupuncture: The Ancient Chinese Art of Healing and How It Works Scientifically. New York, Vintage Books, 1973, pp 1, 106 14. Bell C: Endurance, strength, and coordination exercises without cardiovascular or respiratory stress. J Natl Med Assoc 71:265-270, 1979 15. Brandenberger G, Follenius M: Influence on timing and intensity of muscular exercise on temporal patterns of plasma cortisol levels. J Clin Endocrinol Metabol 40:845849, 1975 16. Sutton JR, Casey JH: The adrenocortical response to competitive athletics in veteran athletes. J Clin Endocrinol Metabol 40:135-138, 1975 17. Newmark SR, Himatongkam T, Martin R, et al: Adrenocortical response to marathon running. J Clin Endocrinol Metabol 42:393-394, 1976 18. Benefits from acupuncture are primarily physiologic. Clin Psychiatry News 6:61, 1978

1981 NMA Convention

The 86th annual convention and scientific assembly of the National Medical Association will be held in Atlanta, Georgia from July 19-23, 1981. The scientific program will include Aerospace and Military Medicine, Anesthesiology, Basic Science, Community Medicine, Dermatology, Family Practice, Internal Medicine, Neurology and Psychiatry, Obstetrics and Gynecology, Ophthalmology, Orthopedics, Otolaryngology, Pediatrics, Physical Medicine and Rehabilitation, Radiology, Surgery, and Urology.


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