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Glutathione in the brain in CFS/ME

richvank

Senior Member
Messages
2,732
Hi, all.

Professor Basant Puri et al. recently published a paper in which they reported measurement of glutathione in the cerebral cortex of the brain of patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) using proton magnetic resonance spectroscopy.

The abstract of this paper is below. Their conclusion was that they found no evidence that cerebral glutathione levels are decreased in CFS/ME relative to normal levels.

I was surprised at this result, given the large number of test results I have reviewed showing glutathione depletion in blood plasma, as well as some results from red blood cells or whole blood. There are also publications reporting glutathione depletion in CFS/ME patients, some of which were cited by these authors.

On further examination of this paper, I noted that the mean values of the parameter used to quantify glutathione in this study were 2.703 for 13 CFS/ME patients, and 5.191 for 13 matched normal controls. (There are no units on this derived parameter.) However, the standard deviations of the data for these two mean values were 2.311 and 8.984, respectively. Because of these large standard deviations, the difference between the mean values was not statistically significant (p=0.361).

I wrote to Professor Puri and asked if it would be fair to say that their study lacked sufficient statistical power to determine whether glutathione is indeed depleted in the brains of CFS/ME patients. He responded that this potential explanation of their results does make sense. He agreed that a further, larger study with greater statistical power is needed to examine this question, and expressed his willingness to carry out such a study if funding could be found.
I very much appreciated his response.

In view of this, I think it is correct to say that this study does not provide any evidence contradicting the hypothesis that glutathione is depleted in CFS/ME patients, and in particular in the brains of these patients. Im hopeful that a larger study can be done in the future to test this hypothesis.

Rich Van Konynenburg


Prostaglandins Leukot Essent Fatty Acids. 2009 Nov 9

An in vivo proton neurospectroscopy study of cerebral oxidative stress in myalgic encephalomyelitis (chronic fatigue syndrome).

Puri BK, Agour M, Gunatilake KD, Fernando KA, Gurusinghe AI, Treasaden IH.

MRI Unit, Imaging Sciences Department, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0HS, England, UK.

A particularly important family of antioxidant defence enzymes in the body are the glutathione peroxidases, which remove H(2)O(2) by coupling its reduction to H(2)O with oxidation of reduced glutathione (GSH) to oxidised glutathione (GSSG). There are suggestions that GSH in the peripheral blood may be reduced in myalgic encephalomyelitis, which is a highly disabling neurological disease of unknown aetiology. Since many of the symptoms relate to cerebral functioning, it would seem probable that peripheral blood GSH findings would be reflected in lower cerebral GSH levels. The aim of this study was to carry out the first direct assessment of cerebral GSH levels in myalgic encephalomyelitis; the hypothesis being tested was that cerebral GSH levels would be reduced in myalgic encephalomyelitis. Cerebral proton neurospectroscopy was carried out at a magnetic field strength of 3T in 26 subjects; spectra were obtained from 20x20x20mm(3) voxels using a point-resolved spectroscopy pulse sequence. The mean cerebral GSH level in the myalgic encephalomyelitis patients was 2.703 (SD 2.311) which did not differ significantly from that in age- and gender-matched normal controls who did not have any history of neurological or other major medical disorder (5.191, SD 8.984; NS). Therefore our study does not suggest that GSH is reduced in the brain in myalgic encephalomyelitis. At the present time, based on the results of this study, there is no evidence to support the suggestion that, by taking glutathione supplements, an improvement in the brain-related symptomatology of myalgic encephalomyelitis may occur.

PMID: 19906518 [PubMed - as supplied by publisher]
 

richvank

Senior Member
Messages
2,732
Dr. Shungu on measuring glutathione in the brain

Hi, all.

I just received an email from Dr. Dikoma Shungu of Cornell, Columbia and Mt. Sinai medical schools. He does research involving magnetic resonance spectroscopy and is currently funded by the CFIDS Assn. to work on ME/CFS. He wrote that he agrees with me about the Puri et al. study, and that he is currently evaluating the levels of glutathione in the brains of ME/CFS patients himself by a more precise method, which he described to me in some detail. He is not ready to comment publicly on his results yet, but he wrote, "it is safe to conclude that to date, there is no valid study that has rejected your hypothesis about decreased glutathione in ME/CFS." Needless to say, I was very happy to receive his comments.

Best regards,

Rich
 

Marylib

Senior Member
Messages
1,155
Puri

Doesn't Puri sell supplements and books about natural cures for "CFS" and depression? Hmmmm?
 

Frickly

Senior Member
Messages
1,049
Location
Texas
Rich

I don't need a study to tell me that glutathione depletion is directly related to my current state of affairs. My glutathione/ATP injections are what got me out of my bed. My levels have been slowly going up over the last year as I deal with my mycoplasmal infection and EBV. The big question is why are my glutathione levels low? Did the glutathione depletion cause my bacteria and virus'? Or did the bacteria and virus' cause my glutathione depletion. Currently, I am hoping that as I get my EBV and mycoplasmal infection under control, my glutathione levels will increase. If the XMRV thing pans out then this could be the virus that is keeping my glutathione levels down. Anyway....I do appreciate your contributions in finding a cause for CFS. I have always felt that you are on the right path.
 

kaffiend

Senior Member
Messages
167
Location
California
These data weren't sufficiently analyzed. They performed low resolution spect and dumped all the values into a global mean. I've never seen a neuro-imaging study done that way. Most differences between groups (patients/controls) are seen locally, whether they are lesions or metabolic differences. Any differences would wash out when looking at global values.

Localization is the whole point of doing neuro-imaging. I assume they didn't have anyone who knew how to properly analyze the data.
 

kurt

Senior Member
Messages
1,186
Location
USA
The Puri study may have been more enlightening if there had been more characterization of the control group. That was a huge standard deviation in the control group, in contrast to the relatively tight cluster in the CFS group. Clearly there are subgroupings of brain glutathione levels in the general population. What would be interesting I think would be to compare the Puri CFS group scans with a group with other known brain pathologies.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
What also might be interesting is how the glutathione levels line up with CSF cobalamin and methylfolate levels and/or levels of MMA and HCY.