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Folinic acid and CFS

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Clinical activity of folinic acid in patients with chronic fatigue syndrome.

Journal: Arzneimittelforschung. 2006;56(6):399-404.

Lundell K, Qazi S, Eddy L, Uckun FM.

Parker Hughes Institute and Parker Hughes Clinics, St. Paul, MN 55113, USA.

NLM Citation: PMID: 16889122

A high incidence of severe B-cell immunodeficiency and chronic reactivated
Epstein-Barr virus (EBV) infection in patients with chronic fatigue
syndrome (CFS) is reported herein.

Of the 58 patients evaluated, 100% had evidence of prior EBV exposure and
72% had evidence for reactivated EBV infection. Notably, 94% of CFS
patients had B-cell immunodeficiency with a marked depletion of their
CD19+IgM+ mature B-lymphocyte population.

A remarkable 81% of CFS patients experienced subjective improvement of
their symptoms after treatment with folinic acid (CAS 58-05-9, leucovorin).

The findings provide unprecedented evidence that CFS frequently is a
folinic acid responsive clinical entity accompanied by B-cell
immunodeficiency and inappropriate antibody responses to EBV.[This Message was Edited on 08/08/2006]


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This abstract has highlighted the role of folate in illnesses like CFS. Though coming from a different direction this is linked to a topic posted by Winsomme titled "Autism treatment for CFS".

I had tests indicating low folate and poor folate metabolism (using a 24 hour urine test) many years ago. I also had the classic large red blood cells.

Folic acid was Rx but did not help much. It's only recently that I have begun to understand methylation and folate metabolism better. Now I am supporting methylation with 4 supps.

Blocks in methylation usually require taking more than just folonic acid or methylfolate.

TC, Tansy[This Message was Edited on 08/08/2006]


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I have been avoiding gluten for a year and a half now and I have been concerned that I may not be gettting enough foic acid.

What specifically have you been doing to help with this? I am assuming follanic acid is the same as folic acid. Is this a British study?


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and folate anaemia (with large red blood cells) is one of the reasons why a doctor in the 80s recognised my gluten intolerance. However, a gluten free diet did not bring my folate levels up to normal and my RBC remained large. Folic acid supps had a minimal effect.

I realised a long time ago that it wasn't just deficiencies in my case, but conversion within the body.

Blocks in methylation exlained why methyl B12 worked when my blood levels of B12 were at the top end of the normal range, and why folic acid didn't work as had been expected.

There were more clues for me when I researched methylfolate just as there were when I looked into sulphur metabolism. Folinic acid works well for many, I find methylfolate even better but I use other supps to support methylation as well.

TC, Tansy[This Message was Edited on 08/08/2006]


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hey tansy,

interesting article - I read the post by winsomme and found him on the autism board he linked us to, and was reading all of the information on that site. I also sent the link to my uncle, as my little cousin is autistic.

There is another cycle besides methylation that has to be corrected, right? I can't remember what it's called. Are you going to try and do the entire protocol, with the genetic tests and everything?



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What other supps do you use?

Some of what you are saying is new to me. You have given me a lot think about and research.

I brought up the connection between folic acid and a gluten free diet because many grains are enriched with folic acid. Since we don't eat many grains, I suspect we may be low in folic acid.


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Hi Chris

The tests’ results indicate patterns rather than absolutes in all patients ie, blocks at different stages of methylation and other pathways. I worked out the sulphur metabolism problems for myself; Prof Hooper in the UK had written about it so I knew that there was good chance molybdenum would help: it did.

I have neither the physical nor the financial resources to access these tests just now, if I could I would because I feel they help explain why we become so ill through toxins and infections. Though I tested positive for borelliosis/lyme and CPn, I felt they were just part of the soup. I had problems prior to what was first Dx as ME (CFIDS), but each time prior to "ME" I would eventually recover.

There are many related problems in my family, my son is affected too, so I want to get as close to the root causes as I can for both our sakes.

I aim to follow the parts of the programme which seem most relevant to me and are affordable, I have already being doing a lot that's in stage one, but will think about a few possible changes. Since the temp dropped, and I'm doing relatively well atm, I may well wait until the next plateau or set back.

The piece below is a good resume of how I feel about these DDs.

TC, Tansy

Extract from
Townsend Newsletter. 270: 69. 2006
“Biomolecular Nutrigenomic Analysis of the Methylation Cycle”
Dr. Amy Yasko

**Most health conditions in society today are multifactorial in nature. There are genetic components, infectious components and environmental components. A certain threshold or body burden needs to be met for each of these factors in order for multifactorial disease to occur. However, part of what makes the methylation cycle so unique and so critical for our health, is that mutations in this pathway have the capability to impair all three of these factors. This would suggest that if an individual has enough mutations or weaknesses in this pathway it may be sufficient to cause mutlifactorial disease, as methylation cycle mutations can lead to chronic infectious diseases, increased environmental toxin burdens and have secondary effects on genetic expression.**[This Message was Edited on 08/08/2006]


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Is common in celiac disease and gluten intolerance, hence my doctor’s belief that a gluten free diet and folic acid supps would return my folate to normal, but it didn’t happen. My 24 hour urine test for folate metabolism was arranged several years after becoming gluten free, and taking relatively high doses of folic acid.

Problems with folate metabolism, and methylation, are not the same as having a straightforward folic acid deficiency. The problem lies in the conversion to folinic acid then methylfolate in the body. Anyone who does well taking SAMe probably has at least one block in methylation.

I take 4 supps: TMG, methyl B12, methylfolate, and P5P (B6).

Yes it's another steep learning curve; more reading, more research, and then connecting all we have learned to see if it's relevant to each of us.

TC, Tansy


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Thanks for writing back. Yea, it is a lot of reading, but then again something as complicated as that can't really be described so simply. Dr. Amy did post on the site that she was originally developing her theories for CFS and other diseases, but then started to focus more on autism.

She went on to say that the protocol for CFS is not as complicated as the autism one. For now I'm just keeping an eye on those forums - there are some people with CFS trying the protocol, but not many. Right now I am working with some of Teitelbaum's ideas, but will keep a close eye on the autism stuff.

It does make sense that there is some basic process that has failed which has affected the whole body. It cannot be coincidence that so many different things have been found to be abnormal in people with CFS.

Hope you feel better.


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Thanks for the info. What is TMG and I have never heard of methyl B-12 and methylfolate. Are they available in the U.S.?


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As Chris pointed out this is not easy to explain in a few sentences. Like other protocols, no one size supps combo for methylation fits all, but there are overlaps.


“Upon absorption, folate is converted into L-methylfolate, which is the predominant form of folate in circulation and is the only type of folate that can cross the blood-brain barrier. Methylfolate does not require enzymatic conversion that folic acid does which is difficult for some people. Preliminary research suggests that it is more bioavailable than folic acid.”

Some use folinic acid -

“In the body folinic acid may be converted into any of the other active forms of folate. Folate coenzymes are responsible for the following important metabolic functions:

1) The formation of purines and pyrimidines which, in turn, are needed for the synthesis of the nucleic acids DNA and RNA. This is particularly important during fetal development in the 1st trimester in preventing birth defects such as neural tube defects;

2) The formation of heme, the iron-containing protein in hemoglobin;

3) The interconversion of the 3-carbon amino acid serine from the 2-carbon amino acid glycine;

4) The formation of the amino acids tyrosine from phenylalanine and glutamic acid from histidine;

5) The formation of the amino acid methionine from homocysteine (Vitamin B-12 as methylcobalamin is also needed for this conversion). Elevated levels of homocysteine have been implicated in a wide range of health disorders including atherosclerosis, osteoporosis, Alzheimers disease, and depression. In the reconversion of homocysteine to methionine the body uses the methionine to make the important amino acid s-adenosylmethionine (SAMe) which is known to be helpful in cases of depression;

6) The synthesis of choline from ethanolamine;

7) The formation and maturation of red and white blood cells; and

8) The conversion of nicotinamide to N'-methylnicotinamide. Other conditions than those mentioned above that may benefit from folinic acid supplementation include: AIDS/HIV, celiac disease, cervical displasia, cleft palate, colon cancer, Crohn's disease, diarrhea, gout, high cholesterol, increased fracture of chromosomes, malabsorption and gastrointestinal inflammation, megaloblastic anemia, restless leg syndrome, postpartum depression, sprue, ulcerative colitis, and vitiligo.

Numerous drugs are known to inhibit the body's ability to utilize folate including: 1) aspirin, 2) cholesterol lowering drugs, 3) oral birth control pills, 4) antacids, and 5) methotrexate when used for rheumatoid arthritis.

When taking folate it is recommended that you take adequate amounts of Vitamin B-12 as methylcobalamin. Folate supplementation may interfere with anticonvulsant drugs.”

Info on methyl b12 can be found at the store here at
I first learned about methylB12 after reading articles in Pro Health’s library.

I posted info on TMG in Winsomme’s post on autism treatment for CFS

TC, Tansy[This Message was Edited on 08/10/2006]


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Thanks for posting this. I will need to take some time to read and figure this all out. Thanks for sharing what you know.


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Thanks for posting this Tansy, I was particularly interested in your big red blood cells. My doctor mentioned this from one of the blood tests I had done and asked me if I drank a lot. The only other explanation for it he said was B12 deficiency, which prompted another test which also came back negative.

Will have to re-read this again.



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I have been reading that some experts think the current recommendation of folic acid probably needs to be increased .


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of B6, folic acid and B12 will help compensate for poor methylation; others will need to take these vits in their converted forms.

TC, Tansy


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400mcg to start with, after that you could gradually raise your dose.

Make sure you are taking enough B12: I use sublingual methyl B12 because I discoverd it helped years ago and I do not have any amalgams in my mouth. Some say sublingual methyl B12 is not advisable if amalgams are contributing to health issues.

TC, Tansy