Hi -- This is a rather long article, but was very interesting . . . talks about how pathogens/toxins can cause a constant stress response and people with CFS lack adaptation ability . . . talks a lot about the adrenals and our stress response. It also mentioned how we are exhausted, but also feel anxious inside. Terri ___________________________________________________ Given the ineffectiveness of currently available therapies for Chronic Fatigue Syndrome (CFS) it is clear that there is an urgent need for a fresh approach to the cause and treatment of this disorder. The following discussion is intended to offer, by adopting a more holistic and constitutional viewpoint, one such alternative approach. This constitutional approach, which reflects an increasingly prevalent view that "only a certain type of constitution is likely to develop this disorder" ( 1 ), is not intended as a definitive guide to the treatment of Chronic Fatigue Syndrome, but rather is intended to increase the awareness of this type of approach and stimulate interest in the recognition of possible constitutional strengths and weaknesses in those afflicted with this disorder. However, since this discussion requires a basic knowledge of the process of adaptation, and its relationship to adaptive energy and the adrenal gland, it is necessary to first consider these important matters and their relevance to Chronic Fatigue Syndrome. The relevance of adaptability to Chronic Fatigue Syndrome is evidenced by the fact that CFS frequently occurs following exposure to various stressors such as infections, vaccinations, chemicals, surgery, and physical or emotional stress ( 2, 3 ). Chronic forms of toxemia such as ciguatera fish poisoning have also been reported to cause Chronic Fatigue Syndrome ( see Ciguatera page ). In fact, recent evidence suggests that Chronic Fatigue Syndrome may be caused by the persistence of microbial toxins which closely resemble ciguatoxins ( 98 ; see also Ciguatera page ). Since many persons do not develop Chronic Fatigue Syndrome when exposed to these same stressors it would seem that those who do succumb to this disorder have somehow failed to successfully adapt to the initial event (infection, etc.). The important thing to recognise is the fact that such vastly different stressors are capable of triggering the same constellation of CFS symptoms. These facts raise some rather fundamental difficulties for the understanding of Chronic Fatigue Syndrome. For instance, how can the same symptoms be caused by so many different stressors? How is it possible for an infection to cause the same adverse effects as exercise or emotional stress? What is the physiological common denominator for all these events? Why do these same events have no effect on many people? In an attempt to answer these questions this discussion will consider the process of adaptation, and the possible results of stress or inappropriate adaptation. CFS, The Adrenal Gland and the General Adaptation Syndrome (GAS) Rather than consider specific aspects of immune function, this discussion will be confined to the more general aspects of adaptation. Fundamental to this process of adaptation is the adrenal gland and the process of adaptation named by Selye as the "General Adaptation Syndrome"( GAS ) ( 4, 5 ). Scientific evidence clearly indicates that the ability of the body to adapt to potentially harmful stimuli or stressors has a fundamental effect upon our health and vitality. In fact, according to Hans Selye, "many common diseases are largely due to errors in our adaptive response to stress rather than to direct damage by germs, poisons, or life experience" ( 6 ). The importance of the adrenal gland in enabling the body to cope with a diverse range of stressors is probably best illustrated by the effects of a deficiency of adrenal cortical hormones such as occurs in victims of Addison's disease. Adrenal deficient patients are remarkably intolerant of all forms of stress, and therefore cannot adapt to exercise, chemicals, temperature changes, drugs, surgery, or emotional stress. According to Murray and Pizzorno ( 7 ), symptoms of "adrenal exhaustion" or underactive adrenal glands include, being "stressed out", "tired", and "prone to allergies", or, according to Hadady ( 8 ), symptoms such as "mental fuzziness, poor memory, sexual problems, low immune strength and global overweight". Additionally, Cabot ( 3 ) states that underactive adrenal glands may also cause, "morning fatigue and depression, general achiness, poor resistance to infections, inability to cope with stress, low blood pressure, low blood sugar levels, allergies, inflammatory problems, poor libido and dizziness". According to Hanley and Deville ( 41 ), adrenal exhaustion or "burnout", which they claim has now reached epidemic proportions, is characterised by five stages, namely, "driven", "dragging", "losing it", "hitting the wall", and finally, "burned out". Hanley and Deville claim that this final stage is characterised by exhaustion of adrenal reserves with symptoms ranging from anxiety, insomnia and recurrent infections, through to CFS, autoimmune diseases and heart disease. In traditional Chinese medicine the syndrome of adrenal exhaustion may be described as a Kidney Yin or Yang (Qi) deficiency. The Chinese syndrome of Kidney Yin deficiency with heat signs, otherwise known as "Deficiency Heat" or "Empty Heat", implies a functional excess associated with insufficient fluid or reserves (ie. Essence); that is, relative Yang excess due to Yin deficiency. In Five Elements theory this could be explained by Water (Kidney/ adrenal) failing to quench Fire (Heart/ thyroid). In the West this would probably compare with mild adrenal insufficiency causing a hyperthyroid-like condition characterised by restlessness. The existence of the GAS, which describes only those common symptoms and physiological changes caused by a multitude of different stressors, became evident as a result of research into the physiological effects of many diverse stressors such as infections, surgery, trauma, burns and exposure to excessive cold ( 4, 5 ). All these stressors, if of significant magnitude and duration, produce various physiological changes which together constitute the GAS. In its complete form, the GAS is comprised of three stages, namely, the Alarm Stage, the Stage of Resistance, and the Stage of Exhaustion ( 1b, 4, 5, 30 ). Upon exposure to a sufficiently severe and prolonged (systemic) stressor, the body commences its attempt to adapt by suddenly increasing the output of adrenal cortical hormones. This is the Alarm Stage ( 1a, 4, 5, 30 ). In the case of exposure to a very sudden and severe stress, the Alarm Stage may be characterised by an initial "shock phase", followed by a "counter-shock phase"( 5 ). Continued exposure to a non-fatal stressor results in commencement of the second stage, the Stage of Resistance. This stage is the one in which adaptation occurs and, according to Selye ( 5 ), "is characterised by an increased resistance to the particular agent to which the body is exposed and a decreased resistance to other types of stress". This decreased resistance to other stresses may be particularly relevant to CFS, however this matter will be considered later. Even though specific adaptation has been acquired during the Stage of Resistance, there is a limit to just how long this adaptive response may be maintained. Continued exposure to a stressor will eventually result, if adaptation is unsuccessful, in a loss of adaptive capacity and the commencement of the final stage, the Stage of Exhaustion. According to Selye ( 4, 5 ), the adaptive capacity is dependent upon the amount of available adaptive energy, and therefore, when, in the Stage of Exhaustion, this energy becomes totally depleted, further adaptation becomes impossible. The GAS is characterised by numerous physiological changes including altered blood volume, blood sugar levels, and fluid metabolism, changes in blood circulation, body temperature, kidney function, blood pressure, metabolic rate, metabolism of carbohydrates, proteins, and fats, changes in the thyroid gland, enlarged adrenal glands and "shrunken" ( 9 ) immune system (thymus and lymph) ( 4, 5 ). It should also be noted that the process of adaptation, especially when this process results from exposure to severe or chronic stress, may involve the mobilisation of bodily reserves (ie. Yin) from the liver, muscles and bones . Although stress ( ie. activation of the adrenal anti-stress system ) is commonly thought of as resulting exclusively from emotional or psychological causes, this popular misconception could not be further from the truth. The ability of certain infections to cause severe unremitting internal biochemical stress is fundamental to CFS. Transient emotional stress is inconsequential when compared with the type of chronic unremitting stress that may result from infections or the persistence of microbial toxins. Chronic Fatigue Syndrome and Adaptive Energy Since it appears that adaptive energy drives the entire process of adaptation, the nature and origin of this energy is of vital importance. The available evidence suggests that adaptive energy is related to adrenal reserve capacity ( see Traditional Medicine page ). Of further interest here is the previously mentioned similarity between adaptive energy and the Chinese concept of Qi. While both Qi and adaptive energy are basically Yang in nature, adrenal reserve capacity, being fundamentally a Yin entity, is perhaps best compared with the Chinese concept of "Jing"(or Ching). Jing or "vital essence", which "is the Substance that underlies all organic life" ( 10 ), is stored in the Kidney (adrenal), and although being fundamentally Yin in nature, is the source of the Qi and the Yin and Yang of the body. Jing (Ching) is described by Teeguarden ( 11 ) as "reserve energy" or "stored energy", and "pure vital force", and is "undoubtedly related to substances produced, stored and secreted by the adrenals and reproductive glands". Qi therefore, may be considered to be the energetic or Yang aspect of the stored energy of the Jing. From this point of view, adaptive energy, which according to Holmes ( 12 ) corresponds to Qi "very exactly", may perhaps be likened to the Yang aspect of adrenal reserve capacity. Chronic Fatigue Syndrome or General Adaptation Syndrome? According to Dr David Bell ( 2 ), a well-known authority on CFS, the symptoms of CFS are not caused "by something injuring the body, but by the body trying to protect itself from something". Bell refers here, in specific terms, to overreaction of the immune system such as occurs in allergic reactions. This point is of vital importance since this type of defensive reaction is the very essence of an adaptive disease. In other words, it would seem that the symptoms of CFS, as is also the case with allergic reactions, are caused by an inappropriate adaptive response. It is interesting to note that, according to Bell ( 2 ), up to 60% of CFS patients suffer from allergies. Additionally, many patients also suffer from hypersensitivity to a wide range of chemicals and odours. Although Western medicine differentiates between allergic reactions and chemical hypersensitivity, the occurrence of both types of reactions in CFS patients who suffered from neither prior to contracting CFS, tends to suggest that both are the result of a single cause. Of interest here is the fact that CFS, allergies, and also hypersensitivity reactions, have been related to impaired adrenal function ( 1 ). This hypersensitivity to numerous diverse stressors that occurs in CFS is most noteworthy in view of the fact that the Stage of Resistance of the GAS is also characterised by hypersensitivity to general non-specific stressors (during this stage selective resistance to the original stressor is acquired at the expense of resistance to other stressors). It is suggested by Selye ( 4, 5 ) that this reduction in the ability to cope with other stressors is caused by the focusing of available adaptive energy on resistance to the initial stressor. It is noteworthy that chemical hypersensitivity does not usually occur, according to Bell ( 2 ), until more than one year after the onset of CFS. Interestingly, hypersensitivity to general non-specific stressors also does not occur in the first stage of the GAS ( 4, 5 ). As has previously been noted, the fact that many diverse stressors are capable of producing the same symptoms of CFS is one of the puzzling aspects of this disease. However, this is one of the very hallmarks of the GAS. The GAS only includes those common symptoms that may be caused by a variety of different stressors ( 4, 5 ). In view of these facts it is hardly surprising that CFS has been described by Poesnecker ( 1 ) as being due to "a poorly functioning ability to adapt", or more specifically, "that condition of the neurohormonal system that produces a weakening or breakdown in the body's general adaptive mechanism" ( 1 ). This breakdown in "the general adaptive mechanism" results in an inability to adapt to numerous diverse stresses including infections and allergic reactions ( 1 ). Poesnecker further claims that the different stages of CFS merely reflect different stages of the GAS which occur as the body continues its attempt to cope with a stressor. Chronic Fatigue Syndrome and the Three Stages of the GAS According to Davis ( 13 ) "during every illness" we are in one of the three stages of the GAS. Davis further claims that we may "experience repeated 'alarm reactions' and live through hundreds of 'stages of resistance', one piled on top of the other, before pituitary and adrenal exhaustion threaten our lives". Poesnecker, in his landmark volume on CFS ( 1, 1b ), refers to a chart by Hans Selye which illustrates the various stages of the adaptive process. According to Poesnecker: "this classic chart outlines the various stages of CFS dramatically, thus giving evidence to our contention that CFS is nothing more or less than the body's biological reaction to long-term unremitting stress." Poesnecker continues: "Every patient with this condition resides somewhere on the chart of Dr. Selye. If they do not, they don't have CFS." Although Poesnecker notes the extremely close correlation between the different stages of the GAS as described by Selye, and the various stages of CFS, he also emphasises the fact that, unlike the acute stresses which were the subject of Selye's research, CFS involves a more chronic process. According to Poesnecker ( 1 ), recent refinements in testing technology which are still largely unknown and not yet generally available, have now made it "possible to determine not only if the patient has CFS or not, but also what stage of the condition he is in and what is the best treatment for a complete recovery." With this test termed the Adrenal Stress Index (ASI), it is claimed that the different adaptive stages of CFS may be readily diagnosed ( 1c ). CFS patients who are diagnosed in the first stage of the GAS, may, with correct treatment, experience a rapid recovery and may be prevented from experiencing the devastating chronic illness which would otherwise have occurred ( 1 ). Most patients however, are not diagnosed until they have reached the second stage of the GAS ( 1 ). Since this second stage of the GAS is characterised by profound metabolic changes, such patients generally experience a slower recovery ( 1 ). A further implication concerning the GAS, relates to the fact that CFS patients sometimes experience adrenal overcompensation due to the constant stimulation of the adrenal glands by the Hypothalamic-Pituitary Axis ( 1 ). This represents an attempt by the body to stimulate the exhausted adrenal glands in an effort to maintain the adaptive process ( 1 ). As is noted by Poesnecker ( 1 ), it is important to recognise this condition since when such patients receive correct treatment this adrenal stimulation will cease and they will become, temporarily, even more exhausted. This is considered a normal part of the recovery process for such patients. This subject of adrenal overcompensation or overadaptation, which may be referred to in traditional Chinese medicine as an Excess condition, has very important implications for both the diagnosis and treatment of CFS. Chronic Fatigue Syndrome, Stress, and the Adrenal Glands It would seem, from the evidence so far cited, that CFS is merely an example of the GAS or, in other words, an adaptive disease. What then causes this adaptive disease or susceptiblility to stress? Why is it that some people seem to be able to successfully adapt to a huge amount of stress while others are completely overcome by much smaller amounts? To explore the answers to these questions we must consider the role of both stress and reduced adrenal capacity in the cause, and predisposition towards CFS, especially given the ability of infections and toxins to cause chronic unremitting stress. The central role of adrenal capacity in CFS is highlighted by the fact that CFS shares 39 of the symptoms and signs of adrenal insufficiency ( 85 ). There is extensive evidence of reduced stress tolerance in CFS patients. In fact, if we utilise a broad physiological definition of the term stress, it is clear that CFS is characterised by general stress intolerance to a very diverse range of stimuli. As is noted by Bell ( 2 ), stress is not only commonly responsible for exacerbating CFS but it has even been implicated in the initial onset of this illness. According to Bell ( 2 ), the importance of stress is such that "avoidance of stress is a standard part of treatment" and "nearly all techniques designed for stress reduction may be appropriate for someone with CFIDS". As is acknowledged by Bell however, stress is not believed to be the cause of CFS. While stress ( ie. infections ) may be the trigger for the onset of CFS, the predisposition to this disorder seems to be determined by constitutional factors. Disturbances in adrenal function in CFS patients, which may take various forms, have been widely documented. Mostly these reports indicate a degree of cortisol deficiency or subnormal adrenal function ( 14, 15, 63, 64, 65, 66, 67, 69, 79, 83, 89 ) even though normal medical tests may not always be sufficiently sensitive to detect the minor degree of adrenal deficiency which commonly occurs in this disorder ( 1 ). Behan ( 16 ) has even suggested that CFS may be due to a mild form of Addison's disease. Total urinary cortisol levels have been found to be significantly lower in CFS patients than in normal controls ( 61, 68 ) although, in contrast to CFS patients, cortisol excretion in depressed patients was actually increased ( 61 ). The fact that Scott and coworkers ( 62 ) found normal cortisol levels in CFS patients in a subsequent study perhaps underlines the superiority of total cortisol excretion as a means of evaluating adrenal status. Furthermore, the recent discovery that "CFS patients have a significantly lower adrenal gland volume compared to depressed patients" ( 17 ) further confirms the importance of adrenal gland size which was reported by Hartman and Brownell ( 18 ), and also Tintera ( 19 ). In view of these facts it is hardly surprising that CFS has been described as the "Adrenal Syndrome", or "Functional Hypoadrenia" ( 1 ). In addition to lacking cortisol, CFS patients may also be lacking in other adrenal hormones such as DHEA ( 1, 62, 80, 82, 90 ). Interestingly, since DHEA and pregnenolone are precursors of other adrenal hormones, levels of these hormones may reflect the reserve capacity of the adrenal glands. According to Poesnecker ( 1 ), the depletion of DHEA levels in CFS patients indicates that stores of adrenal hormones are becoming depleted and the patient is moving into the exhaustion stage of adaptation as described by Selye. By measuring levels of cortisol and DHEA it is possible to assess the progress of the CFS patient and determine precisely which stage of the illness he/she is experiencing ( 1 ). It is also interesting to note that alkalosis is common in CFS patients ( 72 ). Alkalosis may also be associated with endocrine disturbances ( 73, 74 ), potassium depletion ( 75 ) and stress ( 76 ). The reasons for the diminished adrenal capacity in CFS, according to researchers, is threefold. Firstly of course, CFS patients have been exposed to a significant stressor such as an infection or toxin which causes a hormonal stress response. Secondly, CFS patients seem to have a diminished ability to properly respond to this stressor, either because of alterations in the Hypothalamic- Pituitary Axis which drives the adrenal response ( 26, 66, 70, 71, 78, 79, 81, 84, 86, 88 ) or else because of reduced adrenal capacity ( 1 ), perhaps because of undersized adrenal glands ( see below ). Although most studies of Hypothalamic-Pituitary function in CFS report a lowering of adrenal drive ( 26, 78, 84, 86 ), there is also evidence that when a small dose of ACTH is used there is actually an exaggerated response ( 26 ). This is interesting in view of the fact that there has been one report of increased cortisol levels in CFS ( 77 ). Upregulation of the Hypothalamic-Pituitary Axis is also a feature of fibromyalgia ( 70 ). It is possible that these apparent inconsistencies merely represent different stages of CFS. Since depletion of adrenal reserves ( ie. exhaustion stage ) would not be expected to occur in the earlier stages of CFS, it is interesting to note that patients with elevated cortisol levels were found to have a shorter duration of illness than those with lower cortisol levels ( 77 ). If the earlier stage of CFS is characterised by elevated cortisol levels then recognition or diagnosis of CFS during this early stage would be most unlikely. The possible consequences of these various hormonal changes becomes incredibly complex when it is realised that many hormones have opposing or antagonistic effects. Not only are mineralocorticoid and glucocorticoid hormones often antagonistic, but some adrenal hormones are catabolic while others are anabolic. Since DHEA for instance, is claimed to counteract the effects of cortisol ( 46, 47, 48, 49 50, 53, 54, 55 ), the lowering of DHEA levels, such as occurs in CFS ( 1, 62, 80, 82 ),may result in symptoms of cortisol excess even when cortisol levels are normal ( 46, 47, 48, 49, 50 ). It is the DHEA/cortisol ratio which is of fundamental importance. Clearly, a reductionist approach to CFS involving measurement of single hormones may be quite confusing and misleading, even assuming the tests themselves are otherwise 100% reliable. As in the case of thyroid disorders ( see Thyroid page ), the practitioner should be focussed upon the patient and should not be obsessed with laboratory data. According to Poesnecker ( l ), whose assessment of CFS patients is based upon 40 years of practical experience, it is the combination of genetically reduced adrenal capacity and excessive adrenal stimulation which causes the unique features of CFS: "what happens with the Hypothalamic-Pituitary Axis in the CFS patient is either one of two things: either his adrenal gland is so weak by nature that the only way the body can stand up to the needs of his daily life is to force the Hypothalamic-Pituitary Axis to regularly overstimulate the weakened adrenal gland in a vain effort to help the patient maintain his chosen life-style. In my office I give patients the analogy of the whipping of an exhausted horse to get a little more out of him. In the second instance we have a patient who started out with a fairly normal adrenal gland but whose life-style involves such heavy unremitting stress that eventually, here too, the Hypothalamic-Pituitary Axis starts working overtime to meet the need." Poesnecker continues ( 1 ): "it is this combination of an exhausted adrenal gland and an overactive Hypothalamic-Pituitary Axis that produces a symptom pattern unique to CFS. That is the nearly simultaneous appearance of exhaustion and anxiety in the patient. While the patient is basically fatigued, he also feels as though he has a motor running inside him that just will not shut off." Since both stress and adrenal malfunction contribute significantly to CFS it is necessary to determine the precise role each of these factors play in the individual patient. As is noted by Poesnecker ( 1 ), it is the genetically determined adrenal capacity which determines the stress tolerance of a person, and therefore, the susceptibility of that person to CFS. The person with signicantly reduced adrenal capacity, who will be very prone to CFS, will develop CFS from a much lower stress burden than will a person with greater adrenal capacity. On the other hand, a person with normal or above normal adrenal capacity (ie. an Adrenal type) will be able to endure enormous amounts of stress without developing this disorder. According to Tintera ( 19 ), the "person with very poor adrenals may never be affected by it if he lives a completely sheltered life, free of extraordinary stress" but " if the adrenals are not thoroughly competent, each stressful incident cuts into their reserves. The day must come when those reserves are exhausted and the whole body is in trouble". It would seem that the important point here, is how much reserve capacity the adrenals have ( see also Traditional Medicine page ). Poesnecker ( 1 ) makes a definite distinction between the abovementioned two groups of CFS patients. Those patients who have greater adrenal capacity but who have had a greater stress burden (described by Poesnecker as "hyperstress types") have a better prognosis than the second or "chronic adrenal type" of patient whose adrenal capacity is such that they react to even relatively minor stresses. These latter patients may be recognised, according to Poesnecker ( 1 ), by the degree of their hypersensitivity to stress and by the fact that their difficulties usually start early in life due to their genetic weakness. In my opinion, Poesnecker's classic publication, Chronic Fatigue Unmasked 2000 ( 1 ) makes a unique and indispensable contribution to the understanding of CFS. It reflects rare insight into the plight of CFS sufferers. Individual susceptibility to stress and CFS may perhaps be partly explained by genetic differences in the utilisation of various B vitamins ( see B Vitamins page, Nutrition and Megavitamins ). In view of the fact that B vitamins are known to effect adrenal function it is interesting to note the results of recent research which revealed the presence of B vitamin deficiencies in CFS patients ( see B Vitamins page ). In view of the apparent adrenal weakness of many CFS patients and the adverse effects of stress upon the adrenal glands, it is interesting to note, according to Landis ( 20 ), that although the whole stress response system should be reserved for emergency situations, there is today a "low-grade constant arousal" which may result in us constantly "bathing in our own stress hormones". Landis lists various stresses such as "toxic exposure, over-exercising, not enough sleep, trauma, injury and illness", which may contribute to this situation. Any type of chronic stress, including chronic illness or pain ( 1, 42 ), exposure to excessive noise ( 43 ), bereavement ( 94 ), infections ( 96, 97 ) and numerous illnesses ( 95 ), or excessive exercise from athletic training ( 91, 92, 93 ), may cause chronic elevation of cortisol levels. To make matters worse, many people initially experience such a high from stress hormones that they become addicted and deliberately seek to prolong this effect ( 41 ). Of course, when the exhaustion stage is reached cortisol levels will become depleted. Since stress hormones may cause a type of hormonal "drunkeness" with more serious consequences than alcoholic intoxication ( 4 ), and may alter our perception of reality (see Body Types page ) , these facts are very relevant to modern society. The importance of the above facts is further highlighted by the difficulty of accurately assessing normal cortisol levels. Due to the wide range and fluctuating diurnal rhythm of serum cortisol values in normal people, and the effects of stress during blood sampling, normal laboratory tests are very unreliable when it comes to accurately determining adrenal status ( 44, 45 ). These problems are further accentuated by the interaction of various hormones which makes measurements of single hormones of rather limited value. The failure of cortisol therapy in CFS patients ( 87 ), even in spite of considerable evidence of reduced adrenal capacity in such patients, further underlines the importance of building adrenal reserves rather than simply increasing levels of single hormones. Although this is a foreign concept to modern medicine there is increasing evidence to justify such an approach. In this respect the use of adrenal "mother" hormones such as DHEA and pregnenolone to treat CFS patients ( 1, 1a ) may have considerable potential. While elimination of nutritional deficiencies which may effect hormone levels should surely remain the primary consideration, if this does not have the desired effect then the use of DHEA and pregnenolone may perhaps have various benefits ( 46, 47, 48, 49, 50, 53, 54, 55 ). Pregnenolone, being the source of all other adrenal cortical hormones ( 53, 54, 55 ), may tend to have the effect of increasing adrenal reserves of all other cortical hormones. Hormones such as pregnenolone and DHEA have the advantage that they tend to balance the adrenal gland and, particularly in the case of DHEA, may counteract symptoms of cortisol excess while simultaneously rebuilding adrenal reserves ( 46, 47, 48, 49, 50, 53, 54, 55 ). Given the possible side effects of DHEA however, 7-keto DHEA should perhaps be the preferred form of this hormone ( 51, 52 ). The potential for use of DHEA or pregnenolone in CFS is further highlighted by the positive effects of these hormones on mental function, memory, insomnia and depression ( 46, 47, 48, 49, 53, 54, 55, 60 ). Additionally, since CFS may involve a deficiency of T3 and a compromised ability to convert T4 to T3 ( 56, 57, 58, 59 ), adrenal hormones such as DHEA, which are claimed to stimulate conversion of T4 to T3 ( 49, 50 ), may also assist in normalising thyroid function. Hormone therapy of course, should be carried out using minimum doses ( 10mg or less daily ) and under the guidance of a practitioner ( for more details about DHEA and pregnenolone see Body Types ). It is also worth noting recent trials of the herbal product Relora indicate that this product may be useful for lowering stress and cortisol levels while simultaneously increasing DHEA levels. The Size of the Adrenal Glands in Chronic Fatigue Syndrome In view of the importance of adrenal size in determining our constitutional make up and our adaptive capacity and the relevance of these factors to CFS, it is indeed exciting to see the results of new medical research by Scott et al ( 26, ) indicating that some CFS patients have adrenal glands which are 50% smaller than normal. These findings raise some very important questions. Firstly, what is the significance of this reduction in adrenal size and how does it effect CFS sufferers? Secondly, what has caused this reduction in adrenal size, and is this reduction in adrenal size the cause of CFS, or the result of it? The importance of adrenal gland size relates to the fact that it is the reserve capacity of the adrenal gland which is of vital importance ( 26 ). The adrenal gland must have sufficient reserves to be able to respond instantly and completely to stressors such as physical or emotional stress or the onset of an acute infection. As I have discussed previously, excessive reduction in adrenal size will reduce the capacity to cope with all types of stress, whether the stress is physical, emotional, or immunological. If such stresses are avoided however, then even quite small adrenal glands can sustain life. It is interesting to note at this point, that this concept of reserve capacity equates with the Chinese concept of Yin. Yin of course, is said to originate from the Kidney/adrenal area. According to Scott et al ( 26, ), the reason the adrenal glands are 50% smaller than normal in the CFS cases which they tested, is because, for some reason, they have become 'atrophied'. The term 'atrophy' refers to a "wasting" away or "decrease" in size ( 27 ) of a previously normal organ or gland. It is therefore implied by Scott et al that these victims of CFS had previously had normal sized adrenal glands. This conclusion appears to be based upon an assumption since their published report supplies no evidence of earlier studies indicating the presence of normal adrenal glands in these cases. This is an extremely important point since without evidence of prior adrenal normality it would surely be equally valid to conclude that these CFS victims had always possessed undersized adrenal glands. Interestingly, these workers were also unable to document any definite cause for this apparent atrophy of the adrenal glands. Evidence of individuality in glandular sizes and nutritional needs has long been known thanks to the pioneering studies of the famous American scientist, Roger Williams ( 21 ), who pioneered the concept of biochemical individuality ( 22, 23, 24, 25 ).As has been reported by Williams ( 15 ), the thickness of adrenal glands in normal people has been found to display a tenfold variation. Williams claims that this individuality in glandular sizes and metabolism, or "biochemical individuality", is responsible for many of the unique differences we each possess. Williams' classical studies into biochemical individuality have revealed numerous glandular variations between people who are considered to be medically normal ( see also Traditional Medicine page ). Although this variation in glandular sizes may not have resulted in an illness which was medically diagnosable at that time, such variations may nevertheless correlate with an enormous range in health, stamina, and vitality of different people. The results reported by Scott et al should therefore be interpreted in the light of the previous research by Williams. It is therefore the constitutional implications of having undersized adrenal glands which must be emphasised. If, as the evidence suggests, people who inherit undersized adrenal glands also inherit a less stress tolerant constitution, then such persons would be expected to be particularly susceptible to various stress related disorders, including CFS. In fact it is now known that the adrenal gland is underactive in various stress related diseases, including asthma ( 28, 29 ) Irrespective of the shortcomings of the report by Scott et al, this study represents a significant step forward. It has considerable implications for the treatment and understanding of CFS. Confirmation of these findings may not only provide conclusive proof of a constitutional basis for CFS, but furthermore, if further studies reveal that these adrenal abnormalities are not the result of CFS, but rather actually preceded the onset of this condition, then the importance of endocrine body typing and biochemical individuality would be further substantiated. Chronic Fatigue Syndrome: Deficiency, Excess, or Dampness? A "Deficiency" condition is one in which a deficiency of Yin, Yang, Blood, or Qi constitutes a predominant part of the illness. In traditional Chinese medicine CFS has been associated with both a Qi deficiency ( 31, 32 ), and a Yin deficiency ( 32, 33 ). However, in addition to Deficiency conditions, such as Qi deficiency, or Yin deficiency ( see Traditional Medicine page ), there are two other concepts of Chinese medicine that may be relevant to CFS. The first of these is "Dampness" which is regarded as one of the six external and five internal causes of disease in Chinese medicine. The other causes of disease include Heat, Cold, Dryness, and Wind. "Wind", I should perhaps point out, refers to aches, pains, muscle spasms, and other symptoms that have the characteristics of wind in that they are not fixed in one location but tend to fluctuate and move around the body. The second concept that may be of relevance to CFS is that of an "Excess" or "Strength" condition. The terms "Excess" and "Deficiency" refer to the diagnostic categories of Chinese medicine which also include Yin or Yang, Hot or Cold, and Interior or Exterior. I will now consider the possible relevance of these concepts to CFS. Dampness The term Dampness refers to an accumulation of moisture or phlegm within the various tissues or organs of the body. Dampness is by nature stagnant, heavy and difficult to move. Since the Spleen (which includes the pancreas) is said to control the transport and metabolism of water within the body, Dampness of internal origin is associated in Chinese medicine with malfunction of the Spleen and a Spleen Qi deficiency. External Dampness may also result in a disruption of the function of the Spleen. Symptoms of Dampness depend upon the area of the body affected and whether the Dampness is associated with Hot or Cold symptoms. Common symptoms include indigestion, food allergies, nausea, bloating, loss of appetite, abdominal distension, chest discomfort, diarrhea or loose bowel movements, painful joints, tiredness, oedema, dizziness, vertigo, sensation of tightness in the head, mental dullness, depression, increased weight, and a feeling of sluggishness and heaviness, or a feeling of being congested ( 10, 32, 34 - 36 ). Since Dampness is a Yin entity which is associated with heaviness and immobility, the accumulation of Dampness in an organ or tissue may result in damage to the Yang Qi of that organ, and a feeling of heaviness or immobility of the tissues so affected. It is indeed interesting to note that arthritis sufferers commonly complain that their discomfort is aggravated by humid or wet weather. Since arthritis, according to Chinese medicine, is commonly considered to be due to Dampness (in combination with Heat, Cold or Wind) in the joints ( 10, 32 ), aggravation of this condition by damp weather or environment (external Dampness) is totally understandable. This ability of Chinese medicine to understand and explain the interaction of man and his environment is one of the many strengths of this form of medicine, and something we can all learn from, especially in the West. From my point of view as a CFS sufferer, since I have been diagnosed as suffering from Dampness in addition to both Yin and Qi deficiencies, these three concepts are of particular interest. Yin deficiency is of interest, not only because of the persistent "heat signs" which I have experienced since contracting CFS, but also because of my intolerance of thyroid medication. Confirmation of a Qi deficiency, I also find interesting because of my longstanding susceptibility to infectious illnesses. The symptoms of Dampness are also of special interest to me in view of the prominence, since I contracted CFS, of symptoms such as abdominal distension, bloating, a sensation of heaviness and sluggishness, irritable bowel syndrome, weight gain, and fluid disturbances. Most of these symptoms may be considerably aggravated by drinking (any non-alcoholic beverage). Although it may be tempting to assume that symptoms like heaviness and sluggishness are totally due to the weight gain I have experienced, these symptoms, although chronic, may fluctuate remarkably even in the absence of any changes in body weight. In view of these facts, it is hardly surprising that Dampness has been shown to play an important part in the symptoms of CFS ( 32, 33 ). The importance of Dampness in CFS prompts the question: is the onset of Dampness a primary event, or is it secondary to constitutional changes caused by an improper adaptive process? Dampness, it should be noted, is a feature of the Earth type of constitution ( 8, 33, 37 ). In ancient Greek medicine, this would be the Phlegmatic type ( 8 ), while in Auyrvedic medicine this would correspond to the Kapha type, who, interestingly, is comprised of the Elements of Earth and Water ( 20, 38 ). In Western terms, it is the Adrenal type who has a Phlegmatic disposition ( 39 ) and is most prone to develop disorders of fluid retention ( 39 ). Although any type of constitution may suffer from Dampness, the occurrence of Dampness in, for example, a Fire type of person, indicates that such a person is suffering from an Earth imbalance or disorder ( 37 ). The occurrence of Dampness in CFS therefore may be an indicator of constitutional changes caused by an ongoing adaptive process. If this is the case the occurrence of Dampness would probably correlate with other symptoms which would indicate the presence of a general metabolic disturbance. Such complex changes would probably not be understood however, unless they are viewed from a holistic perspective which is capable of acknowledging the interconnectedness of numerous diverse symptoms. In fact, the whole process of adaptation is a classical example of a phenomena that may not be understood, and may be extremely confusing, unless it is viewed from a holistic perspective. To dissect the numerous biochemical and physiological changes which may occur during an adaptive process and fail to see their relationship to one another, is clearly not helpful. Excess Condition The concept of an Excess condition, referred to earlier, may also be of relevance to CFS. Although at first glance many Excess symptoms may appear rather unlike typical CFS symptoms, a detailed examination of this concept may contribute significantly to an understanding of the complex symptoms that may occur in CFS sufferers following an infectious illness. Although the term Excess may be used in Chinese medicine to refer to any excess entity (ie. Yin, Yang, Fluid, Hot, Cold, etc.), it is its more common use to describe conditions of excess Qi (Yang) with which we are concerned here. An Excess condition exists, according to Ziyin and Zelin ( 35 ), when "exogenous pathogens dominate". These authors continue: "this is conceivable because genuine Qi is generated in excess as a reaction to, or as a defence mechanism against, pathogenic insults". In other words, an Excess or Strength condition may be considered to be part of an adaptive process. According to Teeguarden ( 11 ), an Excess condition is "generally the result of a hyper-reaction of the body-mind to some pathological agent". It is interesting to note that according to Teeguarden, an Excess condition is only possible if there is an obstruction to the free flow of Qi. Since an Excess condition appears to be part of an adaptive process, an attempt to cope with an assault by a toxic or infectious agent, it is clear that it should not be seen in isolation but rather as just one part of this overall process. In this respect it may be helpful to compare an Excess condition to the three stages of the GAS. During the first stage of the GAS excess adrenal hormones are released to assist the body to cope with a stressor. During an Excess condition on the other hand, excess Qi is generated for the same reason. Depending upon the effectiveness of this first stage therefore, and the persistence of the stressor, the Excess condition will either resolve or lead to the second stage of the adaptive process. It will be recalled that during this second stage, the Stage of Resistance, resistance or adaptation to the original stressor which is increased during this stage, is only achieved at the expense of reduced resistance to other stressors. If an Excess condition is actually an adaptive process that can be compared to the GAS it would be expected that the Excess condition would be achieved at the expense of strength or stress tolerance in other areas. In other words, as is the case with the GAS, the Excess condition would also produce a Deficiency condition. Such combined disorders are not new to Chinese medicine which describes combinations such as strength in weakness, weakness in strength, exterior weakness and interior strength, and so on ( 34). In such a situation it would not be unreasonable to expect Excess symptoms to be accompanied by symptoms of general stress intolerance including perhaps, general hypersensitivity or reduced exercise tolerance. In this event it is important to recognise the fact that the Deficiency condition is the result of, and/or has been preceded by, an Excess condition. If exposure to the stressor continues until the adaptive capacity becomes totally depleted, the final stage, the Stage of Exhaustion, will ensue. In practice, since this entire process represents an ongoing struggle within the body, these different stages may not be clearly defined. The point must be emphasised that the term "Excess" may be utilised in either a relative or absolute context. In a relative sense, the term "Excess" simply refers to the fact that there is insufficient Yin to balance the Yang ( see Traditional Medicine page ). In other words, a severe Yin deficiency may produce many of the symptoms of an Excess condition. This is a very important point since it means that Kidney (adrenal) Yin deficiency may result in, or predispose towards, the development of various Excess symptoms ( ie. Kidney Yin deficiency with heat signs ). The fact that an Excess or Strength condition may be caused by weakness has been noted by Fan ( 34 ). Although, as is noted by Fan, a Strength condition may occur because of "strong evil Qi" when "the bodily functions and vigour are also strong", it may also have its origin in constitutional weakness. To quote Fan ( 34 ): "extreme deficiency also can give the appearance of strength, that is, false strength". It is clear that if CFS is an adaptive disease, then at some stage of the illness there will appear some features of an Excess condition. Although such symptoms may be relatively minor or transient, it is important nevertheless to be able to recognise Excess symptoms, due to the fact that they may be aggravated by taking tonic herbs. In the words of Teeguarden ( 11 ), a person suffering from an Excess condition "will appear outwardly strong and wilful, and will be easily aroused physically and/or emotionally. The pulse will be strong and quick, and the person may experience an excessive libido. The eyes will appear bright and open and they may tend to talk excessively and show other signs of a hyperactive central nervous system". These symptoms, which are symptoms of Yang excess or Yin deficiency, are typical of the effects of the sudden release of stress hormones, which may cause, irritability, anxiety, excitability, restlessness, emotional instability, palpitations, insomnia, nausea, and so on ( 4 ). Psychologically, such hormones may cause depression, mania, nervousness, or schizophrenia ( 7 ). According to Fan ( 34 ), an Excess condition is characterised by the symptoms of "abdominal distension with guarding, much sputum causing blockage of the airway, chest tightness, difficulty with urination, large and dry faeces or malodorous diarrhea, cold intolerance, firm tongue, and tidal smooth and large pulse". Symptoms of CFS ( 2, 40 ) which could be due to an Excess condition include, cold intolerance, abdominal distension, a feeling of feverishness, and an accelerated heart rate. Other symptoms typical of Yin deficiency include burning hands or feet, insomnia, dizziness, night sweats, feverishness, flushing of the cheeks, and palpitations. Of fundamental importance here is the fact that CFS sufferers "almost always"( 2 ) experience abnormal sensations of body temperature, which is a typical sign of Yin/Yang imbalance. The fact that the sensation of feverishness is usually not accompanied by an elevated temperature ( 2 ), is hardly surprising if it is caused by a Deficiency (Yin) rather than an Excess. From a Western point of view, an Excess condition may also be compared with a condition of excessive adaptation. Although this may seem rather paradoxical, it seems, as previously mentioned, that an inherent adrenal weakness may result in a condition of overcompensation. According to Poesnecker ( 1 ), the only way the CFS patient with weak adrenal glands can function is to rely upon excessive HPA stimulation. It is this condition of overcompensation which greatly complicates the treatment of CFS ( 1 ). Once this stage commences, usually during the counter-shock phase and the Stage of Resistance, then the "stress" of this overcompensation may become a disease in itself. Adaptogens, adrenal tonics and synthetic adrenal hormones may considerably aggravate this condition. Although in the short term treatment may be necessary to reduce this adrenal overcompensation, preventative or long-term treatment should seek to address any underlying deficiency rather than simply increase hormone levels. The concept of an Excess condition also has important ramifications for understanding the way in which the body attempts to cope with illnesses. When a significant systemic infection occurs, the internal Qi of the body increases in an attempt to overcome the "pathogenic" or "evil" Qi (ie. or virulence) of the infecting organism or disease. This represents a struggle within the body that will obviously be unsuccessful if the internal Qi of the body is not strong enough to overcome the pathogenic Qi. In this event the disease will progress from an acute "Exterior" disease to a chronic "Internal" disease. During recovery, these changes will move in the reverse direction, with the disease once again becoming acute and External. This is an additional reason why a purely symptomatic approach should be avoided. If the symptoms experienced by a patient are the result of the body trying to eliminate toxins and restore normality, then any attempt to suppress these symptoms would clearly not be helpful. I should emphasise here that it is vitally important that disease symptoms are not confused with healing symptoms. Since healing symptoms are associated with a recovery process and the associated improvement in vitality, they will be readily identified by a suitable practitioner. Exercise Intolerance in Chronic Fatigue Syndrome It is interesting to note that many health care professionals have had difficulty understanding and accepting the intolerance of exercise which is commonly considered to be the very hallmark of CFS. The fact that exercise intolerance may be due to a compromised ability to adapt to the stresses that exercise imposes upon the body seems to have received little recognition from non-holistic practitioners. It should be emphasised that the condition of exercise "tolerance" (ie. "fitness") merely represents the end result of successful adaptation to exercise. In other words, the two essential requirements, if a person is to attain a condition of fitness or exercise tolerance, are exercise, and an ability to successfully adapt to that exercise. It is therefore clear that exercise intolerance due solely to a lack of fitness could not cause the severe and progressive ill-effects which are possible if adaptability is compromised. While an inability to adapt to exercise because of serious diseases such as heart disease or respiratory disease is generally accepted, it is obvious that any other reduction in metabolic efficiency also has the potential to reduce our adaptability. By definition, if a person does not adapt to exercise, then he/she will experience physiological "stress", the nature of which will reflect the type and the degree of the underlying metabolic abnormality. For instance, if the weakness is in the lungs, breathlessness will be a prominent symptom. It is rather surprising then, that exercise and fitness routines are still sometimes recommended as a fundamental part of CFS treatment. The reasons for this from a cause-based or scientific point of view, do seem rather unclear, although there is no doubt that limb and mobility exercises may be beneficial for persons who have been immobilised. The fact that exercise may be used as a "treatment" for depression ( 7 ), or for conditions which are caused by a lack of fitness, hardly seems relevant to CFS sufferers. Interestingly, the mood elevating effects of exercise are believed to be due to the fact that exercise is a stressor ( 7 ), which may stress the body and cause the body to produce an adaptive (hormonal) response ( 7 ) which may, in turn, have a pronounced effect on mood. The benefits of exercise are therefore, based upon an assumption of insignificantly compromised adaptability. Especially since it is generally accepted that CFS (which is often referred to as "Post-viral Syndrome") is caused or triggered by viral infections such as influenza or glandular fever, the whole debate about exercise does seem rather irrelevant. After all, exercise would not normally be seen as a treatment for influenza, in spite of the fact that this illness may cause considerable exercise intolerance (and depression). The Use of Glyconutrients in Chronic Fatigue Syndrome Glyconutrients, so the claims stated, could alleviate CFS by giving sufferers an improvement in vigour and sense of well being. Conversely, cessation of treatment, so I was informed, would result in a relapse, even after many months of treatment. Since the nutritional theory underpinning the use of glyconutrients seemed quite logical, I decided to give this new discovery a trial. Within a day or two of commencing the treatment, at the recommended dosage, I did indeed feel an improvement in energy and feeling of well being. This however was short lived. As I continued taking the product I felt increasingly as though I was taking a stimulant which was actually draining my energy reserves and making me worse. As my reserves became more depleted I found that the symptoms of CFS were deteriorating and I could not sustain my previous level of energy and well being. My deterioration forced me to discontinue the treatment after only one week. When I ceased taking the product, much to my amazement, I experienced a severe "crash" and went through two days of severe withdrawals, during which I had to fight the constant urge to resume the treatment. After this two day period I felt better than when I was taking the product. In my case, the results of glyconutrient treatment were most unsatisfactory, although it did seem as though there were dual effects (ie. both good and bad). "Nutritional" supplements of course, do not normally function as stimulants and cause withdrawal reactions. Since the product which I used contained a number of different constituents, it is entirely possible that one of these ingredients simply did not agree with me. The manufacturers however, were at a loss to explain these effects. Conclusion Although the reduced ability of CFS sufferers to adapt to exercise, stress, infections, and chemicals, may seem coincidental from a non-holistic viewpoint, from the holistic viewpoint however, all these symptoms could be the result of a more general mechanism involving both general toxemia and compromised adaptability, resulting from the persistence of an immune stressor, such as a microbial toxin, and an improper adaptive response. The repeated occurrence of these symptoms following exposure to different immune stressors, further supports this explanation, while the use of the ASI test is also claimed to confirm the relationship between CFS and the General Adaptation Syndrome. Reports of adrenal deficiency and reduced stress tolerance in CFS are also consistent with a derangement in the body's anti-stress mechanisms. While it is undoubtedly much simpler to pursue an exclusively symptomatic approach to CFS, or any other chronic illness for that matter, it is quite clear that the effectiveness of such an approach could in no way compare with the much more wide ranging and long-term potential benefits of correctly performed constitutional treatment. Given the complexity of this disorder however, correct treatment is a matter for an experienced practitioner. Perhaps this matter has been best summarised by Bell ( 2 ), who points out that medical specialists have been "unable to make much progress in studying this illness, primarily because of the lack of 'disease'* in the organs in which they specialise". Bell claims that whatever causes the symptoms of CFS, it is outside the scope of "limited specialties". Bell continues: "We are witnessing a disease so fundamental in its origin that it affects all body systems, but causes little damage". While I question the accuracy of the latter comment, I wholeheartedly agree regarding the inadequacies of a non-holistic approach. * Bell's emphasis: Bell refers here to the fact that although disease may be present, it is not detectable by commonly employed techniques.