Study Suggests Higher B-12 and Folate Levels Needed in ME/CFS (Take the Poll)

Discussion in 'Chronic Fatigue Syndrome (ME/CFS) Research' started by Cort, Apr 30, 2015.


Have Your MTHFR Mutations Been Tested and If So - Did It Help?

  1. Never been tested

    56 vote(s)
  2. No Polymorphisms found

    4 vote(s)
  3. ME/CFS patient - Polymorphisms found - treatment regimen based on them - helped a lot

    2 vote(s)
  4. ME/CFS patient - Polymorphisms found - treatment regimen based on them - helped moderate

    4 vote(s)
  5. ME/CFS patient -Polymorphisms found - treatment regimen based on them - helped somewhat

    15 vote(s)
  6. ME/CFS patient - Polymorphisms found - treatment regimen based on them - made things worse

    3 vote(s)
  7. Fibromyalgia patient - Polymorphisms found - treatment regimen based on them - helped alot

    0 vote(s)
  8. Fibromyalgia patient - Polymorphisms found - treatment regimen based on them - helped moderately

    2 vote(s)
  9. Fibromyalgia patient - Polymorphisms found - treatment regimen based on them provided little/no help

    0 vote(s)
  10. Fibromyalgia - Polymorphisms found - treatment regimen based on them - made things worse

    0 vote(s)
Multiple votes are allowed.
  1. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    The Gottfries Clinic in Sweden is a bright spot in Scandanavia. With it's six doctors it sees about 2,500 chronic fatigue syndrome (ME/CFS) patients a year.

    It recently examined one of the most intriguing but poorly studied treatment questions in chronic fatigue syndrome and fibromyalgia: how to effectively use B12 and folic acid. B12 and folic acid have long been used by alternative health practitioners to treat ME/CFS and FM but go gold standards or validated protocols exist.

    B12 deficiency is associated with a host of symptoms including depression, irritability, poor muscle functioning, inflammation, poor detoxification. It's

    Many people with ME/CFS use B-12/folic acid, but are they using the right amounts?

    usually easily treated with oral B-12, but the clinic's 15 years of experience indicated that most ME/CFS and FM patients require B12 injections and higher doses of folic acid to get the full effect. The need for such high levels of B12 and folic acid suggested something is blocking the B-12/folic utilization in ME/CFS patients.

    A small (n=11) 1997 cerebral spinal fluid (CSF) study underscored the clinic;s findings. Homocysteine levels were increased relative to normative values for healthy controls, and B12 levels appear to be "generally low". This suggested that homocysteine conversion to B-12 was being blocked.

    Reduced levels of methylation have been found in several studies as well. Because methylation is responsible for gene activation low methylation levels could result in reduced cellular activation. Two studies, in fact, suggest low methylation rates in ME/CFS could contribute to reduced immune activation/regulation.

    B12 and folate come into play in methylation because they provide the methyl groups needed to activate many genes. Because B-12 is also an antioxidant low brain B12 levels could contribute to the signs of increased oxidative stress found in some studies.

    The authors proposed that polymorphisms in a gene responsible for producing the methylenetetrahydrofolate reductase (MTHFR) enzyme could play a role. People with MTHFR enzyme variants require substantially more folic acid to get the substance into their cells.
    The Study

    Response to Vitamin B12 and Folic Acid in Myalgic Encephalomyelitis and Fibromyalgia. Regland B, Forsmark S, Halaouate L, Matousek M, Peilot B, et al. (2015) Response to Vitamin B12 and Folic Acid in Myalgic Encephalomyelitis and Fibromyalgia. PLoS ONE 10(4): e0124648. doi:10.1371/journal.pone.0124648

    They took 38 female ME/CFS patients, 15 of whom fulfilled the criteria for fibromyalgia who'd been giving themselves B12 injections at least once a week for at least six months, and up to 20 years and surveyed them. All had experienced relapses when taking B12 orally.

    This goal of the survey was to determine optimal B12 and folic acid regimens for ME/CFS. They used the Fibro Fatigue Scale and the patient's Global Impression of Change scale to survey how well their patients were doing. They also attempted to assess the effects MTHFR polymorphisms had.


    The patients had been on a range of B12 and folic acid protocols. Both folic acid doses and the forms and frequency of B12 used (hydroxocobalamin: 1 mL ampoules with 1 mg/mL / methylcobalamin: 2 mL ampoules with 5 mg/mL) varied. Folate was provided by 1 mg or 5 mg folic acid tablets.

    The 38 patients were divided into two groups based on their Fibro Fatigue survey scores: good (very much or much improved; n=15) and mild (mild improvement; n=23) responders. The groups were then compared to determine which B-12/folate regimens were the most prevalent in both. Other aspects of their treatment regimens were also assessed.
    They found that the patients in the good responder group
    1. Did injections more frequently (p<.03)
    2. Used higher doses of B-12 (p<.03) and folic acid (oral) (p< .003)
    3. Had been on the injections for a longer period of time (p<.0005)
    4. More often used thyroid hormones (p<.02)
    Most mild responders (70%) tended to use opioids, duloxetine and/or pregabalin on a daily basis to reduce pain (p<.0005)

    Duration Matters: The most statistically positive factors were the duration and the use of pain medications. Almost 60% of the patients in the mild responder group, but only 13% of the strong responder group had been on the B-12 protocol for less than a year. Because the response rates to B-12/folate are fairly quick - a few weeks- the authors thought the short duration group simply hadn’t had the time to find the dose that worked for them.

    Type of Injection Matters: Methylcobalamin injections were not a guarantee of success but appeared to be a necessary component for it. All but one (93%) of the Good responders used the more powerful methylcobalamin injections. Most of the mild responders used it as well, but a much high percentage (42%) were using hydroxocobalamin.

    Frequency Matters: Patients in the high responder group tended to take their injections every four days or so while those in the mild responder group took them every six or so days.


    Lower than optimal folic acid doses and less frequent injection regimens may be limiting treatment success.
    The authors suggested that the mild responders were most likely receiving suboptimal treatment. They were taking too little folate, weren’t getting B-12 injections frequently enough, and in some cases were using the wrong kind of B-12 (hydroxocobalamin). In particular, they felt that people with multiple MTHFR polymorphisms were probably not taking enough of either supplement.

    MTHFR polymorphism May Matter: The information was anecdotal (not statistically derived). It did appear that patients who were homozygous for the polymorphisms that impacted folic acid utilization were more likely to require more folic acid to have a good response. The results of the Open Medicine Foundations larger MTHFR study soon to get underway should give us more news on the effects of the MTHFR mutations on B-12 and folate supplementation.

    Thyroid Hormone Use May Matter: Significantly more patients getting good results from the B-12 and Folate were using thyroid hormones. In fact, almost fifty percent of the high responders were using thyroid hormone. The authors felt this underscored the need to assess thyroid function in ME/CFS.
    Are 38 Swedish patients representative of ME/CFS patients everywhere? Probably not. Statistically this, like other retrospective studies, was not particularly strong. It couldn't for instance, clearly assess the effectiveness of the B-12/folic acid (no placebo control group.) They findings did make sense though given what we've heard, and they raised some interesting points.

    Even within this experienced group of practitioners B-12/folic acid protocols differed dramatically. A significant percentage of patients (40%) were responding well but most (60%) were not.

    The results suggested that inadequate protocols might be lowering the response rates. Many patients may have been using too little folic acid and not frequent enough B-12 injections (using methylcobalamin) to make a real difference. Higher folic acid supplementation, in particular, appeared important. Given the high percentage of good responders using thyroid it's possible thyroid support may be an important factor as well

    On the other hand, patients with pain severe enough to require the use of prescription painkillers may not benefit or may even regress on B-12/folic acid protocols.

    A three-site study examining MTHFR polymorphisms and B-12 and methyfolate regimens is getting underway at the Open Medicine Foundation.

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    Last edited: Apr 30, 2015
    Zapped and Tina like this.
  2. San Diego

    San Diego Well-Known Member

    Perhaps the ME/CFS options could include the following (like the FMS choices) ? :cool:

    ME/CFS - polymorphisms found - treatment regimen based on them provided little/no help
    Tina likes this.
  3. Sam Hall

    Sam Hall New Member

    Tee likes this.
  4. Folk

    Folk Well-Known Member

    I wonder if that's why when I became a vegan everything went downhill so fast... Before I normally ate meat everyday which probably means a lot of B12, and then suddenly I became vegan (no eggs and milk too) so I totally cut any source of B12.
    I even ask a nutricionist about supplementing B12 but she said it takes a lot of time for the body to run out of it... My decline was in something like a month after becoming vegan.
  5. Tee

    Tee New Member

    I've been using cyanocobalamin for years, mainly due to ME/CFS + pernicious anemia. I have no idea where to get the other forms of injectable B12 like methyl--where do patients in the US find it?
  6. Compound pharmacies - college pharmacy and wellness pharmacy are 2 that can make it
  7. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    Whoops! :banghead: :banghead: :banghead:
    San Diego likes this.
  8. VLynx

    VLynx Member

    My B12 status truly confuses me. I had it tested recently and it was off the charts (>2,000 pg/ml). I do take some B12, but it is a relatively small amount, all oral, and mostly cyanocobolamin. Folate was normal. The other thing is that when I have had B12 injections, they make me feel horrible: very low energy, lethargic. I'm hoping to retest soon, having stopped taking B12 supplements to see if the high levels are coming from supplementation, as there as some very bad things that can cause high B12 levels.

    Does anyone here know if you can get extremely high B12 serum levels from oral supplementation?
  9. LorrieL

    LorrieL New Member

    I have read that some people who have MTHR polymorphisms may have high B12 or high folate levels. Have you been tested for MTHR?
  10. VLynx

    VLynx Member

    Thank you. No, I have not.
  11. Tee

    Tee New Member

    Thank you!
  12. Leachim

    Leachim New Member

    Regarding methylcobalamin versus hydroxycobalamin I think the article from Gottfries clinic is a bit unclear. There are two kinds of B12 injections readily available in Sweden – one is 10 mg of methylcobalamin, and one is 1 mg of hydroxycobalamin. That all the good responders have used methylcobalamin might as well be an effect of dosage, especially since one of the main conclusions in the article is that dosage seems to be important. As i recall there was only one anecdotal report referred to that methyl-B12 was more effective than hydroxy-B12. In the ME-communities in Sweden there have been numerous anecdotal reports both ways – some claim to have better effect from 1 mg hydroxy-B12 than 10 mg methyl-B12 even. But most say the methyl-B12 injections are better, but it's not clear if this is an effect of the typ or the 10x dosage.
    Deirdre likes this.
  13. MollyO

    MollyO New Member

    I've never been tested but I started an aggressive vitamin b12 and folate regimen on my own and it has been the most helpful treatment to far. It helped my sleep and fatigue immensely.
  14. Joshua Grant

    Joshua Grant New Member

    Response to Vitamin B12 and Folic Acid in Myalgic Encephalomyelitis and Fibromyalgia...

    Sounds like the perfect 3rd study for Mendus. It seems I can't read one of your posts without wanting to set up a new study for people to try. :) I'm impressed the Swedish group was able to publish in PloS One with 38 people. And with a study we could probably replicate pretty closely.

    Thanks for the post Cort.

    crittercherub likes this.
  15. Tina

    Tina Well-Known Member

    Cort, looking at the options on MTHFR vote, I am positive but no treatment has been offered. I don't see this option on your poll
    Lissa likes this.
  16. marc

    marc New Member

    As I understand it, blood tests for B12 status are useless because they don't measure the B12 that gets into the cells; the measure is what's in the blood serum. Supplementation, therefore, is usually going to result in sky-high B12 levels.
    Tammy7 likes this.
  17. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    I'm glad to hear that VLynx because B-12 injections make me feel horrible as well. Finally I found someone who has the same reaction. In fact B-12 injections are one of the few things that actually make me feel worse.

    I think MTHFR mutations could be involved. I would love to figure that mystery out. I'll have a blog coming up on that shortly.
  18. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    Missed that one. It's not much help to test positive for something and not have a treatment option. I'm sure they're are options though. I am going to do a MTHFR blog shortly.
  19. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    Most people have never been tested. Which kind of surprised me although I have never been tested. We could get a group tested - do an analysis of the results - and then chart treatment responses over time. I like it.
  20. Cort

    Cort Founder of Health Rising and Phoenix Rising Staff Member

    Right - because the methyl injections have more B-12...Thanks for pointing that out.