ME/CFS, FM, B12, MTHFR and Thyroid

This Thyroid UK forum often discusses related issues - and this is one very big and important related issue! With interesting links among ME/CFS, fibromyalgia, thyroid and B12.

As so often, far too few subjects, etc. - but worth a read.

PLoS One. 2015 Apr 22;10(4):e0124648. doi: 10.1371/journal.pone.0124648.

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

Regland B1, Forsmark S1, Halaouate L1, Matousek M1, Peilot B1, Zachrisson O1, Gottfries CG1.

Author information

1 Gottfries Clinic, affiliated with Institute of Neuroscience and Physiology, Gothenburg University, Gothenburg, Sweden.



Patients with myalgic encephalomyelitis (ME, also called chronic fatigue syndrome) may respond most favorably to frequent vitamin B12 injections, in vital combination with oral folic acid. However, there is no established algorithm for individualized optimal dosages, and rate of improvement may differ considerably between responders.


To evaluate clinical data from patients with ME, with or without fibromyalgia, who had been on B12 injections at least once a week for six months and up to several years.


38 patients were included in a cross-sectional survey. Based on a validated observer's rating scale, they were divided into Good (n = 15) and Mild (n = 23) responders, and the two groups were compared from various clinical aspects.


Good responders had used significantly more frequent injections (p<0.03) and higher doses of B12 (p<0.03) for a longer time (p<0.0005), higher daily amounts of oral folic acid (p<0.003) in good relation with the individual MTHFR genotype, more often thyroid hormones (p<0.02), and no strong analgesics at all, while 70% of Mild responders (p<0.0005) used analgesics such as opioids, duloxetine or pregabalin on a daily basis. In addition to ME, the higher number of patients with fibromyalgia among Mild responders was bordering on significance (p<0.09). Good responders rated themselves as "very much" or "much" improved, while Mild responders rated "much" or "minimally" improved.


Dose-response relationship and long-lasting effects of B12/folic acid support a true positive response in the studied group of patients with ME/fibromyalgia. It's important to be alert on co-existing thyroid dysfunction, and we suspect a risk of counteracting interference between B12/folic acid and certain opioid analgesics and other drugs that have to be demethylated as part of their metabolism. These issues should be considered when controlled trials for ME and fibromyalgia are to be designed.



[PubMed - as supplied by publisher]

Full paper freely available here:

[ Feel free to re-post elsewhere - e.g. the PAS forum. I shall only post it here. ]

16 Replies

  • Thanks for that. Very interesting and it also fits with my own personal experience of improving significantly once on B12. Have yet to try folic acid though.

  • Seems a lot of people are careful to recommend folate (e.g. methylfolate) rather than folic acid. Maybe worth reading up before choosing what to try?

  • After one horrendous journey of seeing 6 specialists total of 15drs,2brain &thyroid scans I finally got a diagnosis 6 mths later of Vitamin b12 deficiency with genetic mutation MTHFR A 1298C .Sadly my B12 level was in normal range so it was dismissed even though I had severe neuro symptons.Vit b12 level should be >500 if one eats red meat.So if anyone has ongoing profound fatigue,brain fog,headache nausea,pins & needles,anxiety ,tinnitus,,depression,falls,memory loss I advise to have serum B12,folate,ferritin,iron,Vitamin D.If treated early can prevent permanent nerve damage.

  • Many thanks for this. I was diagnosed with ME in the late 1980s though I suspect (undiagnosed) associated thyroid problems (usual problem of result being in range), as per Dr Myhill's research. Interestingly, My B12 is off the scale in the positive direction, but I've just had active B12 testing and am awaiting results. I've been informed that serum B12 may be in range but it is the active that is important. Will read the full paper to see if it mentions active B12.

  • Have you checked folate levels?

  • Latest folate (27 Feb 2015): 5.8 (4.6-18.7) so at the lower end.

    Serum B12: 887 (191-663), so off the scale!

    Other results:

    TSH 2.53 (0.35-6.00, though apparently there has been a change of range recently so the range may actually be 0.27-4.2, given that in May 2014 the TSH was 3.36)

    FT3 (as at July 2014): 3.14 (2.63-5.70) (private test)

    FT4 (as at July 2014): 13.6 (9.0-22.0) (private test)

    Ferritin: 124 (15-350)

    Total cholesterol: 5.0

    Vit D: 162 (> 50; was 51 in July 2014, so great improvement since taking D3 supplements)

  • That certainly concurs with my experience Rod. I have had ME type symptoms all my life. On the two occasions when I have had B12 injections, I have been dramatically improved. I am currently fighting to get injections despite my blood tests being in the dreaded 'normal' zone.

    Oral B12 ( 5 mg daily) does give me a slight improvement, but nowhere like the effect that I get with an injection.

    I have an appointment to see a haematologist in June (13 months after requesting it) and will take the above when I attend.

  • Best of luck with that.

    Have you tried adding any form of folate?

  • Yes, I added a folic acid tab a day when I started taking the B12 every day.

  • Not following the trend towards folate (e.g. methylfolate) rather than folic acid?

  • I hadn't really thought about that. Is it worth me buying some folate?

  • I really don't know - there are other people here and over on Pernicious Anaemia Society who know far, far more and would be better able to advise.

    It was a real question from me!

  • I've long ago given up on expecting definitive answers, so where budget allows, I like to try stuff for myself, and see what happens. So I will try some folate when the folic acid runs out, and see if I notice a difference.

    Of course, the problem with that approach is that when we have more than one medical condition (as most with chronic conditions do), and those conditions can vary in their intensity, it is hard to tell if a new supplement or medication is making a difference, or if one of the ailments is just temporarily in some stage or remission.

    On the positive side, I reckon that I may have another 20 years to continue experimenting. LOL

  • Very interesting. I was diagnosed with ME 13 years ago and my ME specialist at the time advised my GP to start me on B12 injections once a month.I have had them ever since although my GP has tried several times to stop them I have said no as I feel I need them. I recently had a test and my B12 is very high but my folate is only 4 I do have methylfolate ready to supplement but have yet to start.

  • Do post back when you have been taking them for a while. Always interesting to hear how things go.

  • Thankyou will do

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