Response to Vitamin B12 and Folic Acid in ME and Fibromyalgia, 2015, Regland et al

Hutan

Hutan

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https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124648

Abstract
Background
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.

Objective
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.

Methods
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.

Results
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.

Conclusions
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.

Plos One, peer-reviewed, open access
 
There's a big problem with this study. There were 38 patients who had been having B12 injections and folic acid for varying lengths of time, from six months to up to several years.

We can expect that the people who have stuck with at least weekly injections for several years probably believe that it is helping them, whereas people who have been having them a shorter time may not be so sure.

And that is what is reported: users who have used it longer are more likely to be good responders (p=0.0005). But this is not evidence of B12 injections and folic acid working. It is quite possible that people got better as a result of some other reason, perhaps the normal course of the disease. But, as the people were taking B12 and folic acid at the time, they attributed the improvement to that and so have kept on with the treatment. People who did not get better gave up, and so aren't in this study.

I don't think this study can tell us much about whether B12 injections +folic acid supplementation help people with ME.
 
The authors also say that
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.
Click to expand...
and
Good responders had used ... 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.
Click to expand...

So they appear to be thinking that the drug use prevented the B12+folic acid treatment from working. When, of course, it is quite likely that the people who weren't better were using analgesics because they weren't better.
 
Hutan said:
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124648

Abstract
Background
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.

Objective
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.

Methods
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.

Results
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.

Conclusions
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.

Plos One, peer-reviewed, open access
Click to expand...
There are serious problems with the kind of scale that are used, with "very much improved" just not being a meaningful measure.

When you are stuck on a 300 calories a day diet, a 50% increase is definitely very much improvement. But on absolute terms it's meaningless as it's still well below what is necessary. We have seen this so many times, questionnaires from otherwise useless treatments where respondents rated the experience positive even if useless, just because they had a rare opportunity to break the dreadful isolation of their daily routine.

And the fact that we are so used to insults and mockery that any interaction with medical personnel that isn't hostile is a very much significant improvement over the usual contempt. It's still basically nothing, aka "standard medical care". It's no more significant than the weird "waiting list control" that is sometimes used, as if it was as meaningful when the waiting is for nothing, vs. e.g. something significant like being on a waiting list for a life-saving transplant.

It doesn't really matter here that a vitamin injection is a "thing", rather than therapy trying to influence our responses on a questionnaire. The measure has to be meaningful. We've seen it with Rituximab: a subjective "improvement" that turned out to have been a questionnaire effect.

Honestly we need a damn moratorium on questionnaire as end-points in this disease. Figure something better or just go home, it's better than adding confusion and ultimately contributing nothing of value.
 
Hutan said:
The authors also say that

and


So they appear to be thinking that the drug use prevented the B12+folic acid treatment from working. When, of course, it is quite likely that the people who weren't better were using analgesics because they weren't better.
Click to expand...
Hutan said:
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124648

Abstract
Background
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.

Objective
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.

Methods
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.

Results
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.

Conclusions
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.

Plos One, peer-reviewed, open access
Click to expand...

Small retrospective study. No double-blind placebo control. And what is the hypothesis (if any) for a beneficial outcome? What would the theory be? No labs (such as iron status, anemia, pernicious anemia, low folate) presented in the above abstract. So why would it work unless...

there's a strong expectation when someone's giving you an injection, of improvement (forget what that biais is called--white coat syndrome?)

Maybe some patients do get better for some reason.
 
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