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Elevated Lactate Is Indicative Of Tissue Hypoxia, Hypoperfusion, And Possible Damage

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

Shungu DC, Weiduschat N, Murrough JW, Mao X, Pillemer S, Dyke JP, Medow MS, Natelson BH, Stewart JM, Mathew SJ.


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


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.


Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study.

Mathew SJ, Mao X, Keegan KA, Levine SM, Smith EL, Heier LA, Otcheretko V, Coplan JD, Shungu DC.


Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA.


Chronic fatigue syndrome (CFS) is a controversial diagnosis because of the lack of biomarkers for the illness and its symptom overlap with neuropsychiatric, infectious, and rheumatological disorders. We compared lateral ventricular volumes derived from tissue-segmented T(1)-weighted volumetric MRI data and cerebrospinal fluid (CSF) lactate concentrations measured by proton MRS imaging ((1)H MRSI) in 16 subjects with CFS (modified US Centers for Disease Control and Prevention criteria) with those in 14 patients with generalized anxiety disorder (GAD) and in 15 healthy volunteers, matched group-wise for age, sex, body mass index, handedness, and IQ. Mean lateral ventricular lactate concentrations measured by (1)H MRSI in CFS were increased by 297% compared with those in GAD (P < 0.001) and by 348% compared with those in healthy volunteers (P < 0.001), even after controlling for ventricular volume, which did not differ significantly between the groups. Regression analysis revealed that diagnosis accounted for 43% of the variance in ventricular lactate. CFS is associated with significantly raised concentrations of ventricular lactate, potentially consistent with recent evidence of decreased cortical blood flow, secondary mitochondrial dysfunction, and/or oxidative stress abnormalities in the disorder.

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So possibly correcting a possible B1 deficency and working on mito issues - might help to correct this problem? (Just remember, alternative doctors say that if you take a B vitamin by itself - you should also use a complete complex -because a higher strength of one B will throw all the B's out of balance and then there will be more problems.) There are a couple of things that I can think of that works on mito issues, one is CQ10 the other is PQQ. Both seem to be stimulating co-enzymes - the later supposedly works more like a B Vitamin. I've tried both of them and they both are very energyzing. I, personally, would have to take very small amounts of them to take either of them. So, with CFS this might really be beneficial; but, with POTS and things over activating our sympathetic systems we'd have to be careful to not over activate it. We had another member talk about B1 recently and the fact that it will also activate the sympathetic system. I recently tried B1 and PQQ and both did that to me. I plan to add them back one at a time, but in lower dosages when I finish doing the cleanse that I'm doing - to see what happens. The PQQ is supposed to help with mito and neuro transmission, so in theory - it should be good for brain fog and the firing of nerve signals - supposedly to regulate the autonomic system. But, I would have to take it slower and less than I tried before. It sent me into overdrive.


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reduced blood flow = hypoxia = impaired glucose metabolism = mitochondrial disfunction = increase lactate = reduced antioxidant bioavailability.

Notice how the mitochondrial disfunction is secondary.

Do POTS patients typically have a reduction of blood flow. I thought pooling meant an increase in blood flow?

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Abstract— In order to evaluate the influence of hypocapnia upon the energy metabolism of the brain, lightly anaesthetized rats were hyperventilated to arterial CO2 tensions of 26, 15 and 10 mm Hg respectively, with subsequent measurements of intracellular pH and of tissue concentrations of carbohydrate substrates, amino acids and organic phosphates. At Pco1= 26 there was a moderate increase in the intracellular pH but when the Pco2 was reduced further to 10 mm Hg the intracellular pH returned to normal, or slightly subnormal, values. The reduction in PCo2 was accompanied by increased cerebral cortical concentrations of lactate, pyruvate, citrate, α-ketoglutarate, malate and glutamate and by decreased aspartate concentrations. It is concluded that the accumulation of metabolic acids explains the normal value for intracellular pH at very low CO2 tensions. Previous results obtained in man indicate that there is an increased anaerobic production of lactic acid in the brain in extreme hypocapnia. At comparable CO2 tensions the present results showed a small fall in phosphocreatine and a small rise in ADP. However, since the ammonia concentrations were normal or decreased and since there was an increase in citrate, the results give no direct support to the hypothesis of an activation of phosphofructokinase. Since the cerebral venous Po2 was reduced to 20 mm Hg at an arterial CO2 tension of 10 mm Hg the accumulation of acids was probably secondary to tissue hypoxia. However, since there was no, or only a very small, increase in the calculated cytoplasmic NADH/NAD+ ratio, it appears less likely that acids accumulated due to lack of NAD+.

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