Melatonin Levels in Women with Fibromyalgia and Chronic Fatigue Syndrome, 1999, Korszun et al

An old paper

Korszun, A., L. Sackett-Lundeen, E. Papadopoulos, C. Brucksch, L. Masterson, N. C. Engelberg, E. Haus, M. A. Demitrack, and L. Crofford. “Melatonin Levels in Women with Fibromyalgia and Chronic Fatigue Syndrome.” The Journal of Rheumatology 26, no. 12 (December 1999): 2675–80.

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.

 

This paper was mentioned over on PR recently. The sample size is small ( 8 or 9 women per group), and the criteria for CFS diagnosis was the old CDC Holmes criteria.

It's interesting though, because it provides no evidence for abnormal cortisol or low melatonin in fibromyalgia or ME/CFS. They reported that melatonin in the fibromyalgia group was significantly higher than the controls, but if you compare that group with the controls for the CFS group, it's all looking pretty normal across the board.



The authors concluded

 

Sure, the sample size is a problem, and the selection may well have been one too. But look how much variation there is in the CFS controls, and how different the fibromyalgia controls look to the CFS controls. The ranges encompassed by the healthy controls is quite wide. And there's absolutely no indication that even a substantial subset of the patients have something abnormal going on with cortisol or melatonin.

I think if you did this study as an exploratory study, you'd look at the results and say 'further work like this probably won't bear fruit'. And yet, researchers have repeatedly measured cortisol in ME/CFS since, and in fibromyalgia too I think. And the results continue to be unexciting.

It is interesting to read this paper - the authors are so convinced that these two conditions are diseases of stress in women. It's this belief that has kept researchers measuring cortisol in people with ME/CFS. Perhaps there is something happening with cortisol, it's not doing its job or something. But, if there is, the repeated measuring of it in peripheral blood is not going to reveal the problem.

And melatonin is widely recommended and prescribed for ME/CFS. My son was prescribed it by the fatigue clinic at the Royal Childrens Hospital in Melbourne. And yet, I can't recall any good evidence that melatonin is deficient, or that melatonin helps with ME/CFS symptoms. Surely there should be suitably powered studies showing a benefit in adults before it is prescribed to children? (Especially with the concerns expressed with its use in young humans by the South Australian professor who is an expert in melatonin use in production animals?)