From the International Journal of Tryptophan Research, 21 July 2013.
Kynurenine Pathway Pathologies: do Nicotinamide and Other Pathway Co-Factors have a Therapeutic Role in Reduction of Symptom Severity, Including Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM).
The definition of dual tryptophan pathways has increased the understanding of the mind-body, body-mind dichotomy.
The serotonergic pathway highlights the primary (endogenous) psychiatric disorders.
The up-regulation of the kynurenine pathway by physical illnesses can cause neuropathic and immunological disorders1 associated with secondary neuropsychiatric symptoms.
Tryptophan and nicotinamide deficiencies fall within the protein energy malnutrition (PEM) spectrum.
They can arise if the kynurenine pathway is stressed by primary or secondary inflammatory conditions and the consequent imbalance of available catabolic/anabolic substrates may adversely influence convalescent phase efficiency.
The replacement of depleted or reduced NAD+ levels and other cofactors can perhaps improve the clinical management of these disorders.
Chronic fatigue syndrome (CFS) and fibromyalgia (FM) appear to meet the criteria of a tryptophan-kynurenine pathway disorder with potential neuroimmunological sequelae.
Aspects of some of the putative precipitating factors have been previously outlined.2,3
An analysis of the areas of metabolic dysfunction will focus on future directions for research and management.
From Psychosomatic Medicine, 6 August 2013.
Chronic Fatigue self-management in primary care: A randomized trial
Fred Friedberg, PhD, Anthony Napoli, PhD, Janna Coronel, MA, Jenna Adamowicz, MA, Viktoria Seva, MA, Indre Caikauskaite, BA, Man Chi Ngan, MA, Jeremy Chang, MA and Hongdao Meng, PhD
– From the Department of Psychiatry and Behavioral Science (F.F., A.N., J.C., J.A., V.S., I.C.), Stony Brook University, Stony Brook, New York; Department of Clinical Research Management (M.N.), Columbia University Medical Center, New York, New York; Division
of Psychiatry Research (J.C.), The Zucker Hillside Hospital, Queens, New York; and the School of Aging Studies (H.M.), University of South Florida, Tampa, Florida.
* Address correspondence and reprint requests to Fred Friedberg, PhD,
Putnam Hall/South Campus, Stony Brook University, Stony Brook, NY
11794-8790. E-mail: email@example.com
To assess the efficacy of brief fatigue self-management (FSM) for medically unexplained chronic fatigue (UCF) and chronic fatigue syndrome (CFS) in primary care.
A randomized controlled design was used wherein 111 patients with UCF or CFS were randomly assigned to two sessions of FSM, two sessions of symptom monitoring support (attention control; AC), or a usual care control condition (UC). Participants were assessed at baseline and at 3 and 12 months after treatment. The primary outcome, the Fatigue Severity Scale, measured fatigue impact on functioning. Analysis was by intention to treat (multiple imputation) and also by per protocol.
A group x time interaction across the 15-month trial showed significantly greater reductions in fatigue impact in the FSM group in comparison with the AC group (p <.023) and the UC group (p<.013). Medium effect sizes for reduced fatigue impact in the FSM group were found in comparison with the AC group (d=0.46) and the UC group (d=0.40). The per-protocol analysis revealed large effect sizes for the same comparisons. Clinically significant decreases in fatigue impact were found for 53% of participants in the FSM condition, 14% in the AC condition, and 17% in the UC condition. Dropout rates at the 12-month follow-up were high (42%-53%), perhaps attributable to the burden of monthly telephone calls to assess health care use. CONCLUSION A brief self-management intervention for patients with UCF or CFS seemed to be clinically effective for reducing the impact of fatigue on functioning.
From Gut Microbes 13 August 2013.
Bifidobacterium infants 35624 modulates host inflammatory processes beyond the gut (psoriasis, chronic fatigue syndrome).
David Groeger (1), Liam O'Mahoney (2), Eileen F Murphy (1), John F Bourke(3), Timothy G Dinan (4), Barry Kiely (1), Fergus Shanahan (4,5) and Eamonn M M Quigley (4,5).
(1) Alimentary Health Limited, Cork, Ireland
(2) Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland.
(3) Department of Dermatology, South Infirmary, Victoria University Hospital, Cork, Ireland.
(4) Alimentary Pharmabiotic Centre, Department of Medicine, University College Cork, Cork, Ireland.
(5) Department of Medicine, Clinical Sciences Building, Cork University Hospital, Cork, Ireland.
Certain therapeutic microbes, including Bifidobacteria infantis (B. infantis) 35624 exert beneficial immunoregulatory effects by mimicking commensal-immune interactions; however, the value of these effects in patients with non-gastrointestinal inflammatory conditions remains unclear.
In this study, we assessed the impact of oral administration of B. infantis 35624, for 6‒8 weeks on inflammatory biomarker and plasma cytokine levels in patients with ulcerative colitis (UC) (n = 22), chronic fatigue syndrome (CFS) (n = 48) and psoriasis (n = 26) in three separate randomized, double-blind, placebo-controlled interventions.
Additionally, the effect of B. infantis 35624 on immunological biomarkers in healthy subjects (n = 22) was assessed. At baseline, both gastrointestinal (UC) and non-gastrointestinal (CFS and psoriasis) patients had significantly increased plasma levels of C-reactive protein (CRP) and the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) compared with healthy volunteers.
B. infantis 35624 feeding resulted in reduced plasma CRP levels in all three inflammatory disorders compared with placebo. Interestingly, plasma TNF-α was reduced in CFS and psoriasis while IL-6 was reduced in UC and CFS. Furthermore, in healthy subjects, LPS-stimulated TNF-α and IL-6 secretion by peripheral blood mononuclear cells (PBMCs) was significantly reduced in the B. infantis 35624-treated groups compared with placebo following eight weeks of feeding.
These results demonstrate the ability of this microbe to reduce systemic pro-inflammatory biomarkers in both gastrointestinal and non-gastrointestinal conditions. In conclusion, these data show that the immunomodulatory effects of the microbiota in humans are not limited to the mucosal immune system but extend to the systemic immune system.
Related article: Medical News Today, 13 August 2013.