I read through the study, and while certainly interesting, do have some questions about it.
First. this is part of the selection criteria:
Patients were eligible for enrollment if they reported having a positive test for COVID-19 with subsequent new and bothersome fatigue and/or cognitive dysfunction symptoms for more than 4 weeks after recovering from the acute infection
Reading further, I don't get the sense that this is directed toward MECFS patients, as the selection criteria did not use the ICC, CCC or any other MECFS screen that I could find. "bothersome fatigue and/or cognitive dysfunction" is quite broad, and while bothersome if you have it, could perpetuate the "you're just tired" myth that plagues our complaints.
Second, while 52 patients (1/2 were control) participated in the initial phase of the study, only 5 participated in the dose-finding phase. This is such as small sample size that I doubt it is really useful. They did acknowledge this:
However, only 5 patients from the double-blind trial participated in the dose-finding study, 4 of whom qualified for higher lithium dosage therapy. With such a small, open-label study subject to selection bias, it is difficult to draw any reliable conclusions regarding the merits of future neurologic PCC lithium trials.
Also, the Limitations section is accurate, and on point. Thumbs up to the authors for including it.
Lastly, the choice of lithium
aspartate is interesting. Aspartate is a neuroexcitatory compound, much like glutamate. I don't think adding this to someone with gluatmate overload is a good idea. I avoid it when I can. The author's reasoning is:
Lithium aspartate was chosen over lithium carbonate and lithium orotate because lithium aspartate was the lithium salt used by the 10 patients with PCC previously treated by one of us, is readily available as a dietary supplement to maximize patient accessibility, and because orotate increases the occurrence of several cancers in animal models.
I would like to see them compare results between lithium aspartate and lithium orotate at the same doses. Given aspartate's excitatory nature, was part of the lithium counteracting that, thus requiring the higher dose than orotate? Would lithium orotate at the lower dose provide the same result as lithium aspartate at the higher dose? I think the authors need to identify the contribution or detriment of each component.
Not trying to rain on the parade here, just my thoughts.
Update:
I don't want to dismiss the authors' concerns about cancer risk. There are concerns about lithium orotate. While I use it, it does make me a little uncomfortable. There is another alternative:
A neurocytological study on cerebellar granular neurons in culture under conditions of moderate glutamate stress showed that lithium ascorbate was more effective in supporting neuronal survival than chloride or carbonate, i.e., inorganic lithium salts. Biodistribution studies indicated accumulation of lithium ions in a sort of “depot”, potentially consisting of the brain, aorta, and femur. Lithium ascorbate is characterized by extremely low acute and chronic toxicity (LD50 > 5000 mg/kg) and also shows a moderate antitumor effect when used in doses studied (5 or 10 mg/kg)
https://pubmed.ncbi.nlm.nih.gov/35408651/
This is in rats, and these doses would be insane to translate to a human, but something to consider if you're thinking about lithium. There is a product that provides 1mg of lithium in this form.
