The role of tryptophan in fatigue in different conditions of stress

Abstract:

Tryptophan is the precursor for the neurotransmitter 5-hydroxytryptamine (5-HT), which is involved in fatigue and sleep. It is present in bound and free from in the blood, where the concentration is controlled by albumin binding to tryptophan. An increase in plasma free tryptophan leads to an increased rate of entry of tryptophan into the brain. This should lead to a higher level of 5-HT which may cause central fatigue. Central fatigue is implicated in clinical conditions such as chronic fatigue syndrome and post-operative fatigue. Increased plasma free tryptophan leads to an increase in the plasma concentration ratio of free tryptophan to the branched chain amino acids (BCAA) which compete with tryptophan for entry into the brain across the blood-brain barrier.

The plasma concentrations of these amino acids were measured in chronic fatigue syndrome patients (CFS) before and after exercise (Castell et al., 1998), and in patients undergoing major surgery (Yamamoto et al., 1997). In the CFS patients, the pre-exercise concentration of plasma free tryptophan was higher than in controls (p < 0.05) but did not change during or after exercise. This might indicate an abnormally high level of brain 5-HT in CFS patients leading to persistent fatigue.

In the control group, plasma free tryptophan was increased after maximal exercise (p < 0.001), returning towards baseline levels 60 min later. The apparent failure of the CFS patients to change the plasma free tryptophan concentration or the free tryptophan/BCAA ratio during exercise may indicate increased sensitivity of brain 5-HT receptors, as has been demonstrated in other studies (Cleare et al., 1995).

In post-operative recovery after major surgery plasma free tryptophan concentrations were markedly increased compared with baseline levels; the plasma free tryptophan/BCAA concentration ratio was also increased after surgery. Plasma albumin concentrations were decreased after surgery: this may account for the increase in plasma free tryptophan levels.

Provision of BCAA has improved mental performance in athletes after endurance exercise (Blomstrand et al., 1995, 1997). It is suggested that BCAA supplementation may help to counteract the effects of an increase in plasma free tryptophan, and may thus improve the status of patients during or after some clinically stressful conditions.

 

Source: Castell LM, Yamamoto T, Phoenix J, Newsholme EA. The role of tryptophan in fatigue in different conditions of stress. Adv Exp Med Biol. 1999;467:697-704. http://www.ncbi.nlm.nih.gov/pubmed/10721121

 

Melatonin levels in women with fibromyalgia and chronic fatigue syndrome

Abstract:

OBJECTIVE: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are stress associated disorders mainly affecting women. FM is characterized primarily by widespread musculoskeletal pain, and CFS by profound debilitating fatigue, but there is considerable overlap of clinical symptoms between these 2 syndromes. Neuroendocrine abnormalities have been noted in both FM and CFS and desynchronization of circadian systems has been postulated in their etiology. The pineal hormone melatonin is involved in synchronizing circadian systems and the use of exogenous melatonin has become widespread in patients with FM and CFS.

METHODS: We examined the characteristics and relationship of melatonin and cortisol levels in premenopausal women with FM (n = 9) or CFS (n = 8), compared to age and menstrual cycle phase matched controls. Blood was collected from an indwelling intravenous catheter every 10 min over 24 h, and plasma melatonin and cortisol were determined by radioimmunoassay at 60 and 10 min intervals, respectively.

RESULTS: Night time (23:00-06:50) plasma melatonin levels were significantly higher in FM patients compared to controls (p<0.05), but there was no significant difference in melatonin levels between CFS patients and controls. No differences in the timing of cortisol and melatonin secretory patterns and no internal desynchronization of the 2 rhythms were found in either patient group, compared to controls.

CONCLUSION: Raised plasma melatonin concentrations have been documented in several other conditions that are associated with dysregulation of neuroendocrine axes. Increased melatonin levels may represent a marker of increased susceptibility to stress induced hypothalamic disruptions. These data indicate that there is no rationale for melatonin replacement therapy in patients with FM and CFS.

 

Source: Korszun A, Sackett-Lundeen L, Papadopoulos E, Brucksch C, Masterson L, Engelberg NC, Haus E, Demitrack MA, Crofford L. Melatonin levels in women with fibromyalgia and chronic fatigue syndrome. J Rheumatol. 1999 Dec;26(12):2675-80. http://www.ncbi.nlm.nih.gov/pubmed/10606381

 

Psychological symptoms in chronic fatigue and juvenile rheumatoid arthritis

Abstract:

OBJECTIVE: To determine if psychological morbidity in youth with chronic fatigue is caused by the stress of coping with a chronic illness.

STUDY DESIGN: Case-control study comparing pediatric patients with debilitating chronic fatigue and matched subjects with juvenile rheumatoid arthritis, a chronic medical illness with similar functional sequelae.

SETTING: Pediatric Infectious Diseases Clinic and Juvenile Rheumatoid Arthritis Clinic of Kosair Children’s Hospital.

PARTICIPANTS: Nineteen children and adolescents with debilitating chronic fatigue and 19 age- and sex-matched peers with juvenile rheumatoid arthritis. Outcome. Structured Interview, Kaufman Brief Intelligence Test, Child Behavior Checklist, and Youth Self-Report.

RESULTS: Intellectual functioning on the Kaufman Brief Intelligence Test Composite was average (103, standard score) for both groups. Pediatric patients with chronic fatigue had higher levels of internalizing psychological distress than patients suffering from juvenile rheumatoid arthritis, despite the fact that both groups had a similar pattern of decline in social and physical activities. Duration of illness did not explain the difference in psychological symptoms.

CONCLUSIONS: Psychological factors may play a more active role in debilitating chronic fatigue in pediatric patients than can be explained by the stress of coping with a similar chronic, non-life-threatening illness.

 

Source: Carter BD, Kronenberger WG, Edwards JF, Marshall GS, Schikler KN, Causey DL. Psychological symptoms in chronic fatigue and juvenile rheumatoid arthritis. Pediatrics. 1999 May;103(5 Pt 1):975-9. http://www.ncbi.nlm.nih.gov/pubmed/10224175

 

Chronic fatigue syndrome among overseas development workers: A qualitative study

Abstract:

BACKGROUND: A relatively high proportion of overseas development workers may develop chronic fatigue syndrome (CFS). A qualitative study was conducted in order to investigate how such people perceived their condition.

METHODS: Twelve people who had developed CFS while working overseas with development organizations, or shortly after visiting development projects, were interviewed about their experiences. Their responses were analyzed using a grounded theory approach.

RESULTS: Most of the participants considered themselves to have been extremely healthy before they developed CFS. The syndrome did not appear to have been caused by depression. The symptoms which were reported covered the range of symptoms typically found in studies of CFS. Respondents described difficulty in receiving, and accepting, a diagnosis. All of the participants attributed the CFS to multiple causes, the principal causes being overwork, stress and infections. Among the consequences of CFS reported to be the most difficult were having to leave the development project prematurely; pain; powerlessness; loss of independence, and the unpredictability of CFS. Factors which had helped respondents cope with these difficulties included religious beliefs; comparisons with people who were worse off than they were; thinking about positive consequences of the condition, and talking with supportive people.

CONCLUSIONS: Some theories have suggested that CFS symptoms arise as a result of depression or other emotional difficulties, which the individual is not able to acknowledge. The results indicated that such theories may not apply to this subgroup of people with CFS. Further research on the etiology of CFS is warranted. Respondents described high levels of work-related stress as common to the experience of development work. It might be beneficial to train development workers in stress management techniques. Development organizations should be encouraged to ensure that their workers take sufficient time to rest, and attempts should be made to reduce work pressures.

 

Source: Lovell DM. Chronic fatigue syndrome among overseas development workers: A qualitative study. J Travel Med. 1999 Mar;6(1):16-23. http://jtm.oxfordjournals.org/content/6/1/16.long (Full article)

 

Stress-associated immune modulation: relevance to viral infections and chronic fatigue syndrome

Abstract:

The frequent association of an active viral infection with the symptoms of CFS led researchers to hypothesize that chronic fatigue syndrome (CFS) is induced by a virus. Results of these studies indicated that despite clinical support for this hypothesis, there were no clear data linking viruses to CFS. In this overview, we will explore the interrelation of the immune, endocrine, and central nervous systems, and the possibility that stress and/or the reactivation/replication of a latent virus (such as Epstein Barr virus) could modulate the immune system to induce CFS. Relevant research conducted in the developing field of psychoneuroimmunology will be reviewed, with a particular focus on cytokine synthesis, natural killer (NK) cell activity, and T-lymphocyte function, as they relate to CFS.

 

Source: Glaser R, Kiecolt-Glaser JK. Stress-associated immune modulation: relevance to viral infections and chronic fatigue syndrome. Am J Med. 1998 Sep 28;105(3A):35S-42S. http://www.ncbi.nlm.nih.gov/pubmed/9790480

 

Autonomic testing in patients with chronic fatigue syndrome

Abstract:

The purpose of this study was to determine whether chronic fatigue syndrome (CFS) patients show autonomic dysfunction at the cardiac level and if so, to discover whether these abnormalities explain the fatiguability and/or other symptoms in CFS.

The study population consisted of 21 CFS patients (Centers for Disease Control and Prevention [CDC] criteria, 1988) and 13 age- and sex-matched healthy controls. The autonomic testing consisted of: (1) postural challenge: registration of heart rate and blood pressure (BP) and heart rate variability in supine and in upright position (tilted to 70 degrees); (2) Valsalva maneuver; (3) handgrip test; (4) cold pressor test; and (5) heart rate response to deep breathing. Statistical analysis was performed using the Mann Whitney rank sum test; results of the test were considered significant at the 0.05 level. After tilting heart rate was significantly higher in CFS patients compared with healthy controls (mean CFS = 88.9 beats/min vs control = 77.9 beats/min; P <0.01).

Low frequency power after tilting was significantly higher in CFS patients compared with controls (mean CFS = 0.603 vs control = 0.428; P = 0.02). There was a trend toward an increased heart rate during the cold pressor test. Other parameters did not differ between the CFS and control populations.

The observed changes point toward a sympathetic overactivity in CFS patients when they are exposed to stress. Parasympathetic abnormalities could not be observed. Therefore, our findings provide no real explanation for the fatigue and intolerance to physical exertion in these patients.

 

Source: De Becker P, Dendale P, De Meirleir K, Campine I, Vandenborne K, Hagers Y. Autonomic testing in patients with chronic fatigue syndrome. Am J Med. 1998 Sep 28;105(3A):22S-26S. http://www.ncbi.nlm.nih.gov/pubmed/9790478

 

Chronic fatigue syndrome: a qualitative investigation of patients’ beliefs about the illness

Abstract:

The chronic fatigue syndrome is a disabling chronic condition of uncertain cause. Previous studies have found that patients seen in hospital clinics with the syndrome often strongly believe that their illness is physical in nature and minimize the role of psychological and social factors. There is also evidence that patients cope by avoiding activity. However, almost all of these studies have assessed illness beliefs only by questionnaire.

The aim of this study was to explore the nature and origin of illness beliefs in more detail using in-depth interviews and a qualitative analysis of patient responses. Sixty-six consecutive referrals meeting Oxford criteria for chronic fatigue syndrome were recruited. Analysis of responses indicated that, whereas the most commonly described explanation for the illness was a physical one, more than half the patients also believed “stress” had played a role. Patients believed that they could partially control the symptoms by reducing activity but felt helpless to influence the physical disease process and hence the course of the illness.

Patients reported that they had arrived at these beliefs about the illness after prolonged reflection on their own experience combined with the reading of media reports, self help books, and patient group literature. The views of health professionals played a relatively small role. There is potentially a considerable opportunity to help patients arrive at a wider and more enabling explanation of their illness when they first present to primary care.

 

Source: Clements A, Sharpe M, Simkin S, Borrill J, Hawton K. Chronic fatigue syndrome: a qualitative investigation of patients’ beliefs about the illness. J Psychosom Res. 1997 Jun;42(6):615-24. http://www.ncbi.nlm.nih.gov/pubmed/9226609

 

Evidence that abnormalities of central neurohormonal systems are key to understanding fibromyalgia and chronic fatigue syndrome

Abstract:

Fibromyalgia (FM) and chronic fatigue syndrome (CFS) fall into the spectrum of what might be termed stress-associated syndromes by virtue of frequent onset after acute or chronic stressors and apparent exacerbation of symptoms during periods of physical or emotional stress. These illnesses also share perturbation of the hypothalamic-pituitary-adrenal axis and sympathetic stress response systems. In this article, the authors discuss the specific neurohormonal abnormalities found in FM and CFS and potential mechanisms by which dysfunction of neurohormonal stress-response systems could contribute to vulnerability to stress-associated syndromes and to the symptoms of FM and CFS.

 

Source: Crofford LJ, Demitrack MA. Evidence that abnormalities of central neurohormonal systems are key to understanding fibromyalgia and chronic fatigue syndrome. Rheum Dis Clin North Am. 1996 May;22(2):267-84. http://www.ncbi.nlm.nih.gov/pubmed/8860799

 

The effect of social adversity on the fatigue syndrome, psychiatric disorders and physical recovery, following glandular fever

Abstract:

Two hundred and fifty patients attending primary care with glandular fever or an upper respiratory tract infection were studied prospectively up to 6 months after onset. Of these patients 228 were interviewed with the Life Events and Difficulties Schedule and the Schedule for Affective Disorders and Schzophrenia, giving Research Diagnostic Criteria for psychiatric disorders.

The experience of severe social adversity (provoking agents) had a significant association with psychiatric disorder at 2 months (odds ratio = 5.3) and 6 months (odds ratio = 5.8) after onset of infection. This association was especially significant for depressive illness (odds ratio = 9.1 at 2 months and 11.9 at 6 months).

In contrast, social adversity had little association with the development of the post-infectious fatigue syndrome, or delayed physical recovery. Social adversity may be an important maintaining factor for psychiatric disorders, especially depressive illness, following acute infections.

 

Source: Bruce-Jones WD, White PD, Thomas JM, Clare AW. The effect of social adversity on the fatigue syndrome, psychiatric disorders and physical recovery, following glandular fever. Psychol Med. 1994 Aug;24(3):651-9. http://www.ncbi.nlm.nih.gov/pubmed/7991747

 

Self help organization’s advice on myalgic encephalomyelitis

Comment on: Outcome in the chronic fatigue syndrome. [BMJ. 1992]

 

EDITOR,-I should like to assure Simon Wessely that neither the ME Association nor ME Action regards Michael Sharpe and colleagues’ findings in patients with chronic fatigue’ as another attack on its credibility. Nor do we see why the paper should “further sour relations between the organisations and the profession.”

As Wessely points out, the apparent relation between functional impairment and membership of a self help organisation at follow up does not mean that membership of such an organisation is responsible for the impairment. Aside from the fact that the study did not focus on myalgic encephalomyelitis, or on the work the ME Association does, Sharpe reassured us that there was no evidence of a causal relation between membership of a patient group and level of disability.

As regards the potential damage resulting from inaccurate information about myalgic encephalomyelitis, it is worth emphasising that the quote that illustrates this came from Nursing Standard and not from a magazine for patients. The British organisations have long been unhappy with the way the media have portrayed the illness and reviewed existing research, and it is often extremely difficult to get erroneous or biased information corrected. Sometimes we get a right of reply, but usually we don’t.

Finally, I wish to make clear that our current advice on exercise and stress is based on sound scientific research, the recommendations of our medical advisers, and 50 years’ experience. Since our aim is to help patients it would be ridiculous for us to ignore good research and to stick instead to outdated explanations, speculation, or even prejudice. No one gains from such a narrow minded approach, least of all us.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1883373/pdf/bmj00091-0063a.pdf

 

Source: Hume MC. Self help organization’s advice on myalgic encephalomyelitis. BMJ. 1992 Sep 12;305(6854):649. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1883373/