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Increased ventricular lactate in cfs III. cortical glutathione and oxidative stress

Discussion in 'Latest ME/CFS Research' started by snowathlete, Apr 11, 2013.

  1. snowathlete

    snowathlete

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    http://www.ncbi.nlm.nih.gov/m/pubmed/22281935/

    Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology.

    Don't know if this has been discussed here before?

    AuthorsShungu DC, et al. Show all Journal
    NMR Biomed. 2012 Sep;25(9):1073-87. doi: 10.1002/nbm.2772. Epub 2012 Jan 27.

    Affiliation
    Department of Radiology, Weill Medical College of Cornell University, New York, NY 10021, USA. dcs7001@med.cornell.edu

    Abstract
    Chronic fatigue syndrome (CFS) is a complex illness, which is often misdiagnosed as a psychiatric illness. In two previous reports, using (1)H MRSI, we found significantly higher levels of ventricular cerebrospinal fluid (CSF) lactate in patients with CFS relative to those with generalized anxiety disorder and healthy volunteers (HV), but not relative to those with major depressive disorder (MDD). In this third independent cross-sectional neuroimaging study, we investigated a pathophysiological model which postulated that elevations of CSF lactate in patients with CFS might be caused by increased oxidative stress, cerebral hypoperfusion and/or secondary mitochondrial dysfunction. Fifteen patients with CFS, 15 with MDD and 13 HVs were studied using the following modalities: (i) (1)H MRSI to measure CSF lactate; (ii) single-voxel (1)H MRS to measure levels of cortical glutathione (GSH) as a marker of antioxidant capacity; (iii) arterial spin labeling (ASL) MRI to measure regional cerebral blood flow (rCBF); and (iv) (31)P MRSI to measure brain high-energy phosphates as objective indices of mitochondrial dysfunction. We found elevated ventricular lactate and decreased GSH in patients with CFS and MDD relative to HVs. GSH did not differ significantly between the two patient groups. In addition, we found lower rCBF in the left anterior cingulate cortex and the right lingual gyrus in patients with CFS relative to HVs, but rCBF did not differ between those with CFS and MDD. We found no differences between the three groups in terms of any high-energy phosphate metabolites. In exploratory correlation analyses, we found that levels of ventricular lactate and cortical GSH were inversely correlated, and significantly associated with several key indices of physical health and disability. Collectively, the results of this third independent study support a pathophysiological model of CFS in which increased oxidative stress may play a key role in CFS etiopathophysiology.
     
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  2. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Interesting, thank you.

    I tried to find the full text but a quick search only produced some earlier work on the same issue, which is nonetheless also interesting. It's here:

    http://www.cfids-cab.org/MESA/Mathew.pdf

    That paper expresses doubt over a primary role for mitochondrial dysfunction, but I think we need to keep that possibility/likelihood in mind.

    High brain lactate is consistent with the lactic acidosis hypothesis/hypotheses of ME, and supports the view of some scientists espousing those hypotheses that reducing consumption of acid-producing foods (especially carbohydrates) as we may have an abnormality in how we digest these.

    Lactate can pass from the blood to the brain (and vice versa) quite easily, so the high lactate levels may derive from gut acidosis or muscle acidosis, but some brain lactate arises in the brain itself due to stress.

    (I just did a few quick searches to confirm the above.)

    So it's clear to me that we need to address all three sources of excess lactate at the same time: stress, digestion and exertion.
     
    merylg, Nielk and snowathlete like this.
  3. Simon

    Simon

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    Yes, here
     
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  4. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Valentijn, merylg and snowathlete like this.

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