Folinic acid (a derivative of Folate) was found to be effective according to a study (PDF).
Folinic acid was used at 25 mg a day for 1-2 months. Because there was already an established association between ME/CFS and Folate deficiency, this study did not look at the folate status of their participants. Nevertheless, 81% of patients reported significant improvement in pain and energy level within these one to two months.
This level of improvement is significant for CFS because CFS patients don’t respond favorably to many treatments. Furthermore, contrary to popular belief, CFS patients of a low placebo-response rate at only 19.6% after meta-analysis.
This study also showed immune problems such as marked depletion of their CD19 B-Cell mature B-cell population. This comes as no surprise as this been replicated in many other studies.
This study that I am referencing was done in 2006. Since then, according to what’s indexed in PubMed, nobody has looked at folate in ME/CFS. No, this wasn’t a huge study with a huge number of participants, but the 81% response rate should prompt further research and studies.
You may be wondering: If this data isn’t new, why am I talking about it?
This is a call to researchers. So many researchers with CFS research things that come to a dead-end. The patient community can tell you that supplementing B12 and Folate works, but you (researchers) have to listen to the clues from patients. If you listen to the clues patients have been presenting for years, you can make new discoveries.
An idea for the research community
Here is my study idea for the research community (Stanford, Harvard, Johns Hopkins, UCLA, Columbia University, UCSF, or whoever happens to be listening to this blog post).
Please do a medical study where you look at various genes such as MTHFR, MTR, MTRR. Use the methylcobalamin form of B12 with L-methylfolate (most preferable) or folinic acid. Do not use folic acid.
Look at markers such as serum and RBC folate (and compare differences), serum B12, serum methylmalonic acid (a better indicator of B12 status), homocysteine, total glutathione, reduced glutathione, and oxidized glutathione.
If patients have normal B12 and folate status, still treat them the same as the rest of the patients in the study. In other words, if levels are normal, still treat.
The treatment group may be difficult because some patients can’t handle large doses of B12 and Folate, and some patients need large doses of folate and B12. Careful study design in this regard is important. I would suggest using sublingual methyl B12 tablets instead of injections because they work just as well, and patients are likely to be more compliant. It wouldn’t be wise to use pharmaceutical doses of folate, as you will be likely to have a significant patient drop out rate. 800 mcg of Folate may be a good dose.
Also, to see if this protocol changes immune markers, assess CD19, CD56+/CD57 Natural Killer Cells along with any other immune related paramaters gathered from studies. The study should be minimum of 3-6 months (the longer the better). Re-evaluate all markers at the end of the study, and have patients assess how much improvement they experienced.
It’s very important to treat these patients whether or not they present with a B12/Folate deficiency or not.
Use strict inclusion criteria such as ICC or CCC criteria.
Finally, if this study demonstrates improvements, try using a similar study on other neurodegenerative diseases. I think a study like this could possibly be successful in Autism and on controversial patient populations such as those with chronic Lyme Disease.