Thesis Eccentrically Induced Skeletal Muscle Damage in Patients With Chronic Fatigue Syndrome CFS, With Reference to Overtrained Athletes, 1995, Wright

SNT Gatchaman · Dec 14, 2023

Eccentrically Induced Skeletal Muscle Damage in Patients With Chronic Fatigue Syndrome CFS, With Reference to Overtrained Athletes
David L. Wright

Bachelor of Applied Science (Sports Science) with Honours: Faculty of Science and Technology, Edith Cowan University

Chronic fatigue syndrome (CFS) and Overtraining syndrome (OTS) are separate, complex conditions which have so many similar debilitating effects that it has led some researchers to conclude that OTS is a sub-condition of CFS. The purpose of this research was to compare the force and damage-recovery characteristics of skeletal muscle in CFS patients and control normals, after a single damaging bout of eccentric contractions in the non-dominant forearm flexors.

The subjects (n = 25), a convenience sample were assigned to three groups; [1] CFS + eccentric damage (n = 8), [2] Control Damage (CD) + eccentric damage (n = 10), and [3] Control (ND) + no damage (n = 7). The research was carried out over a four week period using the following format. CFS & CD groups received eccentrically induced muscle damage of the forearm flexors by 35 isokinetic eccentric (7 x 5, 2 minutes recovery between sets) contractions at 90° sec-I with the forearm returning passively at 15°sec-1.

Testing was undertaken pre-damage and 1, 2, 4, 6, 8, 12, 16, 20, 24, & 28 days post-damage, by measurements of voluntary maximal concentric isokinetic force at l 50°sec-l, isometric maximal voluntary contraction at approximately 90° elbow flexion, electrically stimulated 20 : 50Hz isometric force ratio at approximately 90° elbow flexion, muscle pain, and blood CK. Groups were compared on these variables using Students independent t-test and repeated measures two way ANOVA with simple contrasts. Alpha was set at 0.05 level.

The results of this study were significant for the eccentric force produced in the damage bout with the CFS group producing less force after the 4th set (p < 0.05). Serum CK concentration, which following eccentric damage was significantly higher in the CFS group than the CD group (p < 0.01), and the ND group (p < 0.001). The low frequency fatigue (LFF) ratio was significantly lower in the CFS group 2, 4, 6 & 8 days post-damage when compared to the CD group. Maximal isometric voluntary force and isokinetic concentric peak torque (PT) & average peak torque (AT) loss was significantly greater in the CFS group compared to the CD group (isometric p < 0.01, PT p < 0.01; & AT p < 0.001) and ND group (isometric p < 0.01; PT p < 0.001; & AT p < 0.001).

The intensity of delayed onset muscle soreness (DOMS) was significantly less 6 days post-damage in the CFS group, when compared to the CD group (p < 0.05).

The combination of an increased CK efflux and low frequency fatigue, that is of both greater depth and longer lasting, together with greater isometric and concentric force losses, indicates that the subjects with CFS have a lower threshold for muscular damage, that is more profound and slower to recover than in healthy individuals.

Link (Thesis, open access)

SNT Gatchaman · Dec 14, 2023

Recruitment of 25 subjects was undertaken. From these 25 subjects three experimental groups were formed of; Chronic Fatigue Syndrome (CFS)+ eccentric damage n = 8, Control Damage (CD) + eccentric damage n = 10, and Control (ND)+ no-damage n = 7, as shown in Table 3.1.
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The subjects of the study were a convenience sample selected via responses from an advertisement (Appendix B) placed in the local press for volunteer subjects who had been diagnosed as suffering from CFS or PVFS, and from Edith Cowan University student and staff response to a flyer distribution (Appendix C). Though the subjects are a convenience sample, the subjects who volunteered for the control groups were randomly assigned to CD and ND groups.
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Subjects that presented with CFS confirmed that they had been diagnosed with CFS, or as with CFS3 Fibromyalgia, by a General Practitioner (GP) or Specialist. In addition CFS subjects were requested to voluntarily complete an additional questionnaire (Appendix D) regarding their illness that provided information on: a) the longevity of their CFS; b) whether heavy bouts of exercise were implicated in their CFS; c) the presence or not of myalgia, and; d) what, if any medications were being taken by the subject, so that known effects of medications being taken could be accounted for.
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SNT Gatchaman · Dec 14, 2023

Hypothesis 3 proposed that the time course of CK efflux and the concentration of serum CK would be different between the CFS and CD groups. This hypothesis was partially satisfied, in that, the serum CK concentration was significantly different, whilst the time course for CK efflux did not differ. Serum creatine kinase efflux peaked in the CFS & CD groups 4 days post damage with a peak mean of 8388 ± SEM 1224 (UI/L) in the CFS group and a peak mean of 2583 ± SEM 753 (UI/L) in the CD group. As expected the ND group serum CK levels remained constant. Serum CK levels began to diminish after day 4, returning to normal levels in the CFS & CD groups by 12 days post-damage.
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Following eccentric damage, serum CK was significantly higher in the CFS group (Figure 4.2) when compared to both control groups (p < 0.001), with simple comparison showing significant difference between CFS and CD groups (p < 0.01), CFS and ND groups (p < 0.001). Within subject events with time as main the effect (p < 0.001), and interaction (p < 0.001).
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There was no significant difference in the time course of CK efflux between the CFS and CD groups (Figure 4.3).
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SNT Gatchaman · Dec 14, 2023

It is apparent from the results that DOMS in subjects with CFS is activated in much the same way as with healthy subjects. This is evidenced by the observation that little difference was noticed in the time course and movement of DOMS within the CFS and the CD groups. Therefore it would seem that the chemical activation of nociceptors, and removal of these chemicals, function normally in subjects with CFS.
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More surprisingly perhaps, was the difference in the perceived intensity of DOMS, whereby the intensity of DOMS in CFS subjects was significantly less than with the CD group. This result was in some ways unexpected as the intensity of DOMS is linked to serum CK concentrations whereby low (peak <500 U.L- 1 ) CK responders to eccentric damage had significantly less pain than medium (peak 500 - 2000 U.L- 1 ) or high (peak > 2000 U.L- 1 ) responders (Clarkson et al., 1992). In this study the means of both groups had a peak> 2000 U.L· 1 and similar pain intensities would have been expected. Furthermore, as hypochondria and histrionics amongst CFS sufferers has been reported (Parker, 1990; Wessely & Thomas, 1990) lower levels of pain may have been described as more severe by these individuals.
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However, as previously stated this was not supported by the evidence, which instead supports the notion of a higher threshold of pain as evidenced by a lower intensity of pain for a greater amount of damage (see Chapter 5.5). What is not clear is whether the myalgia sometimes reported by CFS sufferers is of the same intensity as eccentrically-induced DOMS, and whether the observed lower intensity of DOMS in the CFS subjects was perhaps due the modulation of pain receptors.
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SNT Gatchaman · Dec 14, 2023

The greater concentration of serum CK in the CFS group following damage when compared to the control groups is of particular interest, indicating a greater degree of eccentrically induced damage. Whilst it is accepted that serum CK activity is "a useful tool for the detection of muscle damage, since it is generally considered to be highly sensitive and relatively specific to muscle" (Dioszeghy & Mechler, 1988, p. 175), doubt remains about the concentration of serum CK being used as a determinant of the amount of damage due to the large inter-subject & gender differences reported in serum CK efflux (Ebbling & Clarkson, 1989 ). Evans & Gannon, ( 1991, p. 104) state: "It is likely that postexercise rise in circulating CK activity is a manifestation of skeletal muscle damage but not a direct indicator of it".
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SNT Gatchaman · Dec 14, 2023

I came across this 1995 thesis when I was trying to reconcile evidence of muscle necrosis against evidence of no CK rise, or even reduced CK. I searched but couldn't find it referenced on S4ME or PR. It looks like a useful study, made more remarkable by the fact that it's nearly 30 years old and done at Bachelor's level.

EndME · Dec 14, 2023

Great find, could be valuable if someone shared this with the team of Rob Wüst, perhaps they haven't seen it either.

SNT Gatchaman · Dec 14, 2023

Along with this, LC biopsy data from earlier this year and another older paper, I've gone to speculation town here.

Trish · Dec 14, 2023

Thanks for finding this. I had a quick skim read through the thesis and am impressed by the quality of the study and interesting findings. As he points out in the concluding discussion, the differences found may be a consequence of the controls not being well matched with the CFS group, since the CFS group were recruited from the local community, and the controls were mostly sports science staff and students, so likely to be much fitter and mostly younger.

I think the setup and method of carrying out the exercise study with all sorts of instruments to ensure everyone had the same physical task and measurements was impressive. I guess that's the big advantage of doing such studies in sports science labs where they have this sort of equipment.

Also doing a study just using repetitive exercises on a single muscle, the biceps in the non dominant arm may be less likely to cause PEM than CPET testing, so more likely to be acceptable for ME/CFS patients practically and ethically.

I wonder whether the tests have been repeated in larger groups with properly matched controls. It seems worth suggesting to researchers.

Trish · Dec 14, 2023

Like you I was particularly struck by the difference in pain intensity reported by the two groups which makes Wessely and his chums characterisation of people with ME/CFS's reports of pain as hysteria particularly judgemental and wrong.

Another thing that struck me was the literature review the student did which showed that around the late 1980's and early 90's there was active research on biology of ME/CFS in the UK which as far as I know was pretty much killed off by the Wessely/White/Sharpe psychosomatic hypothesis and burying ME/CFS with PEM in the wider Oxford criteria that explicitly also included people with fatigue due to a depression, anxiety, hyperventilation, any unexplained fatigue as well as post infectious fatigue. I've been getting more interested in the early history around 1990 again as result of trying to write something about the Cochrane review and harms. It seems more and more evident that the Oxford was a huge and deliberate step backwards for ME/CFS research and hijacking of ME/CFS by psychiatrists.

Getting back to this study, another striking thing is the rationale given for including overtraining syndrome among athletes as a subset of CFS.
I came across this idea a couple of years ago when two different researchers who had been doing CPET studies surprised each other in the question time at an IACFSME conference with both having independently of each other come up with the idea of a parallel with overtraining syndrome. It's like science keeps having to rediscover old ideas.

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Thesis Eccentrically Induced Skeletal Muscle Damage in Patients With Chronic Fatigue Syndrome CFS, With Reference to Overtrained Athletes, 1995, Wright

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Thesis Eccentrically Induced Skeletal Muscle Damage in Patients With Chronic Fatigue Syndrome CFS, With Reference to Overtrained Athletes, 1995, Wright

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