Hi, all.
I'm guessing that you are citing results from Acumen Lab in the UK. This is a wonderful lab. I correspond with Dr. Howard there often and am an admirer of his work on developing mitochondrial testing. However, the test that he runs for glutathione is a red blood cell total glutathione measurement. If this measurement comes out low, it is a good indication that the tissue cell reduced glutathione is likely low. However, if this measurement comes out in the normal range, one cannot be sure that the tissue cell reduced glutathione is in the normal range. There are two reasons for this: First, the red blood cells are normally producers and net exporters of glutathione. They are thus likely to have a better glutathione status than tissue cells (such as in the skeletal muscle). Second, the measurement of total glutathione contains oxidized glutathione, and such a measurement does not distinguish reduced glutathione, which is the active, usable form.
It is much easier to measure red blood cell glutathione than plasma glutathione, because it is about 1,000 times as high. Also, it is much easier to measure total glutathione than reduced glutathione, because reduced glutathione will oxidize during shipping and storage of blood samples, unless a combination of certain enzyme blockers are in the sample vial. As far as I know, only the European Laboratory of Nutrients in the Netherlands and the Health Diagnostics and Research Institute in New Jersey, USA, use these enzyme blockers and are able to measure reduced glutathione in shipped samples. They keep the formulation proprietary for business reasons. They put considerable effort into developing this formulation.
Beyond this, I think it is still possible for a person to have normal tissue cell reduced glutathione (as inferred from plasma measurement of reduced glutathione) and still have a partial methylation cycle block. This can occur if the person has genetic polymorphisms in the enzymes that use glutathione (the glutathione peroxidases and/or the glutathione transferases). I have seen a few Spectracell lab reports (this is a lymphocyte functional test offered in Houston, Texas, USA) in which the glutathione came out normal, but the total antioxidant capacity was low. I suspect that these people fit into this category. For most PWMEs, though, I see both a partial block in the methylation cycle and depletion of reduced glutathione, based on the methylation pathways panel offered by ELN and HDRI, mentioned above.
Best regards,
Rich