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Open Trial of Vitamin B12 Nasal Drops in Adults With [ME/CFS]: Comparison of Responders and Non-Responders, 2019, van Campen et al
So there was a bit of difference between those whose B12 level went up by the end of treatment being a bit more active, but they were just as fatigued and had no change in cognitive function at the end of the trial.
I guess it's just about enough evidence to justify a double blind trial.
I guess it's just about enough evidence to justify a double blind trial.
Jonathan Edwards
Senior Member (Voting Rights)
In the non-responders, only a small but significant increase in vitamin B12 levels was observed. In contrast, in responders, the number of steps, the physical activity scale of the RAND-36, and the vitamin B12 serum levels increased significantly.
I cannot be bothered to read more than the abstract but the results above seem t be saying:
There was a significant increase in B12 in both responders and non-responders (not surprising since they were given B12).
The responders were responders (i.e. measures of response were positive in the responders).
Does this mean anything at all?
I cannot be bothered to read more than the abstract but the results above seem t be saying:
There was a significant increase in B12 in both responders and non-responders (not surprising since they were given B12).
The responders were responders (i.e. measures of response were positive in the responders).
Does this mean anything at all?
I think the point they are trying to make is that the subgroup who reported some improvement (and walked a bit further and had a small increase in SF-36PF) turned out to be the ones whose B12 had increased significantly when tested at the end of the trial.
Assuming they didn't know their B12 had increased more than the others, that may mean there is something real happening. Does this imply a dose related response? Not enought information to tell.
It may simply mean that those whose B12 didn't increase significantly knew perfectly well they hadn't used the drops properly, so had lower expectation of improvement. There are lots of possible confounding factors.
It's too small a study, and open label, so all they can really say is there might be something here worth testing in a double blind trial.
Assuming they didn't know their B12 had increased more than the others, that may mean there is something real happening. Does this imply a dose related response? Not enought information to tell.
It may simply mean that those whose B12 didn't increase significantly knew perfectly well they hadn't used the drops properly, so had lower expectation of improvement. There are lots of possible confounding factors.
It's too small a study, and open label, so all they can really say is there might be something here worth testing in a double blind trial.
James Morris-Lent
Senior Member (Voting Rights)
If b12 supplementation was an effective treatment it would have already been shown by textbook clinical trials. Possibly as early as the 80's depending on if any particular form / administration route were needed.
I suppose putting it straight into the csf would be novel but it doesn't seem like there's good reason to try that on people.
I suppose putting it straight into the csf would be novel but it doesn't seem like there's good reason to try that on people.
I thought that they abstract indicated fatigue had also reduced?
I also thought the abstract suggested that the responders and non responders had different raises in serum B 12
They have also demonstrated that nasal drops work to raise b12 as good as injections. If this does prove a treatment worth trying, knowing that in the UK where drs are being struck off for B12injection is useful. As long as they do a good follow up study I think that this Is to be welcomed as a potential to offer some relief.
Jonathan Edwards
Senior Member (Voting Rights)
According to the abstract B12 increased significantly in both groups.
Given the table in Trish's message where responders B12 levels increased from 379 to 1445 but the non-responders increase is a lot less 265 -> 395; I was wondering if the difference in the amount raise was interesting and particularly why it would be small in the non-responder group. Of course from this info we don't know what a normal increase would be. But I was wondering if it could show something strange in the non-responder group?
Jonathan Edwards
Senior Member (Voting Rights)
I suspect the non-responders could not cope as well with the faff of going on sticking stuff in their nose and were non-responders because they didn't really buy in to the placebo effect on offer.
I thought B12 absorption was supposed to be dependent on intrinsic facts in the stomach and since people with ME are not deficient in intrinsic factor I don't understand why it should be good to put it up your nose.
I thought B12 absorption was supposed to be dependent on intrinsic facts in the stomach and since people with ME are not deficient in intrinsic factor I don't understand why it should be good to put it up your nose.
Jonathan Edwards
Senior Member (Voting Rights)
There is also the puzzle that the responders already had higher B12 levels at the start. Maybe they 'responded' because they were into vitamins and had taken more before. The possible confounders here could fill a book. There is no justification for not just doing a double blind trial.
It's a post trial division into the two groups, so there is presumably some characteristic that distinguishes the two groups. It could be as simple as those in the responder group tried harder to comply with the treatment, and expectation bias meant they reported more improvement.
I think the idea is that nasal and sublingual drops are a way of bypassing the digestive tract and getting the B12 absorbed through the mucus membrane direct into the bloodstream, so a similar effect to injections, and not needing intrinsic factor. The fact that the B12 levels for some of the patients increased substantially suggests this works.
But as you say, if they have intrinsic factor (as far as I can see they were in normal range at the start of the trial, so not B12 deficient), then oral B12 should have been equally effective.
Arnie Pye
Senior Member (Voting Rights)
From the abstract :
Ideally people should take methylfolate rather than folic acid according to this link :
https://chriskresser.com/folate-vs-folic-acid/
Title : The Little Known (But Crucial) Difference Between Folate and Folic Acid
The difference in reference ranges before and after treatment is decidedly odd. It looks as though the tests were not done using the same testing protocol or testing machines. The top of range before treatment is the lowest I can ever remember seeing in a serum B12 test.
Before treatment the median B12 level, 328 (244–429) pmol/l, was 45.4% of the way through the range.
After treatment the median B12 level, 973 (476–1,476) pmol/l, was 49.7% of the way through the range.
Looking at the percentages the apparent improvement in B12 level is much less dramatic than the raw values would suggest. Do I detect shenanigans and data manipulation?
Does everyone with ME know they don't have Pernicious Anaemia (PA)? Testing for PA is extremely unreliable and false negatives are common.
B12 absorption in the gut is dependent on intrinsic factor. But if someone has PA they can't absorb B12 in the gut because of low or absent intrinsic factor.
Some people with B12 deficiency (but not PA) have discovered that absorption of B12 through the mucous membranes is possible. For those with PA it rarely helps. The vast majority of PA sufferers need injections. If they can't get injections then mouth sprays, nasal drops and patches will keep body and soul together for a while, but they are unlikely to feel healthy and their B12 levels are never likely to be "good", although their serum B12 may be just in range. Another issue is that false negatives abound in testing for PA.
If some of the participants in this trial had PA I wonder if the researchers catered for that in their research design? Or if they even checked for PA before starting supplementation. If they didn't and there were more people with PA in the non-responders group than in the responders group the difference is likely to be because of the PA rather than anything else, surely?
I haven't read the whole paper, so I may have missed some explanations that make my criticisms disappear. But somehow... I think not.
Ideally people should take methylfolate rather than folic acid according to this link :
https://chriskresser.com/folate-vs-folic-acid/
Title : The Little Known (But Crucial) Difference Between Folate and Folic Acid
The difference in reference ranges before and after treatment is decidedly odd. It looks as though the tests were not done using the same testing protocol or testing machines. The top of range before treatment is the lowest I can ever remember seeing in a serum B12 test.
Before treatment the median B12 level, 328 (244–429) pmol/l, was 45.4% of the way through the range.
After treatment the median B12 level, 973 (476–1,476) pmol/l, was 49.7% of the way through the range.
Looking at the percentages the apparent improvement in B12 level is much less dramatic than the raw values would suggest. Do I detect shenanigans and data manipulation?
Does everyone with ME know they don't have Pernicious Anaemia (PA)? Testing for PA is extremely unreliable and false negatives are common.
B12 absorption in the gut is dependent on intrinsic factor. But if someone has PA they can't absorb B12 in the gut because of low or absent intrinsic factor.
Some people with B12 deficiency (but not PA) have discovered that absorption of B12 through the mucous membranes is possible. For those with PA it rarely helps. The vast majority of PA sufferers need injections. If they can't get injections then mouth sprays, nasal drops and patches will keep body and soul together for a while, but they are unlikely to feel healthy and their B12 levels are never likely to be "good", although their serum B12 may be just in range. Another issue is that false negatives abound in testing for PA.
If some of the participants in this trial had PA I wonder if the researchers catered for that in their research design? Or if they even checked for PA before starting supplementation. If they didn't and there were more people with PA in the non-responders group than in the responders group the difference is likely to be because of the PA rather than anything else, surely?
I haven't read the whole paper, so I may have missed some explanations that make my criticisms disappear. But somehow... I think not.
Funny.. Thanks for the giggle!!! My own b12 levels are well above normal range due to supplements and I've steadily declined in past 3 years unfortunately.
I think even the researchers would admit it's nowhere near a cure. The improvements in the responder group were very small.
Jonathan Edwards
Senior Member (Voting Rights)
So what are the statistical chances of more than one person in the trial having undiagnosed PA?
I am sorry but, like most studies of supplements, this is junk and I see little point in trying to find obscure reasons to justify it! They should have done a proper trial and they could easily have done so so one has to assume they preferred to do a trial that would give the answer they wanted.
Arnie Pye
Senior Member (Voting Rights)
Sorry, don't know. I wonder if any of them had diagnosed PA?
In the Patients, Material and Methods section it says :
Unfortunately it doesn't tell us which conditions they looked for in potential participants that would have ruled people out. And given that this was a trial of B12 supplementation it would have been a good idea to have mentioned PA specifically.
I would agree that this is junk. The problem may be the actual writing of the paper itself, rather than the way that the trial was conducted, but they left too many grey areas unexplained for me to think it had value.
How is this any different than someone with low Vit D values eating Vit D supplements to leverage their values? I'm not really sure taking the supplement (B12 or Vit D) matters the way some might hope or theorize, but perhaps more importantly, I would look at both deficiencies as possible downstream effects of...something. Accordingly, identifying the respective causes of the deficiencies seems a likely place to begin.
Of course, we know they don't know how to do that inexpensively - if at all.
Of course, we know they don't know how to do that inexpensively - if at all.