I have joined a Facebook group called Understanding B12 deficiency where members are recommended to get iodine, selenium and molybdenum up to a good level, one by one, only then add B2, and only then add B12 (injections or in oil that is absorbed through skin...) All very gradually. Don't know yet if it works, but the message in that group is that if you take B12 too soon, and the wrong type, will get nasty side effects... My daughter now at the stage where (after several months) we have ordered the B12... She has EDS and suspected POTS and Mcas, and paediatrician has said she has all the symptoms of ME. Just posting in case it helps someone - we don't know yet if it works ourselves...
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B12/Folic Acid and D3/K2 Supplementation
- Thread starter Little Bluestem
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Just to say that - although most doctors don't know about it - functional B12 deficiency (B12 deficiency despite normal or even high levels in blood) is in fact recognised by the NHS: 'Functional vitamin B12 deficiency Some people can experience problems related to a vitamin B12 deficiency, despite appearing to have normal levels of vitamin B12 in their blood. This can happen as the result of a problem known as functional vitamin B12 deficiency, where there's a problem with the proteins that help transport vitamin B12 between cells. This results in neurological complications involving the spinal cord.' (https://www.nhs.uk/conditions/vitamin-b12-or-folate-deficiency-anaemia/causes/). Am I right that the only way you can tell if you have Functional B12 deficiency is by trying B12 injections and seeing if they help?
Arnie Pye
Senior Member (Voting Rights)
Anyone interested in vitamin B12 might find this paper of interest :
Title : The pathophysiology of elevated vitamin B12 in clinical practice
Link : https://www.researchgate.net/public..._of_elevated_vitamin_B12_in_clinical_practice
People can download and save a copy of the full paper as a PDF if they want.
Title : The pathophysiology of elevated vitamin B12 in clinical practice
Link : https://www.researchgate.net/public..._of_elevated_vitamin_B12_in_clinical_practice
People can download and save a copy of the full paper as a PDF if they want.
You can test for functional b12 deficiency by looking at methylmalonic acid levels in the blood.
The following are some excerpts from something I drafted in response to Dr Vallings promoting B12 injections in the treatment of ME/CFS in a recent editorial in a journal for doctors:
Vitamin B12 injections is one treatment that illustrates a number of the issues. Dr Vallings suggests in the editorial that B12 injections have been shown to be useful, noting that ‘cerebrospinal fluid levels maybe depleted’. The reference given for this is a 2015 Finnish study that did not in fact measure levels of B12 in cerebrospinal fluid (CSF) or in blood. The retrospective study consisted of 38 patients who had been having at least weekly injections of B12 and folic acid for varying lengths of time, from 6 months up to 20 years. All of the included patients had previously ‘reported an evident and favourable response to B12 injections in an open clinical environment’. None of the possibly many people who did not find B12 injections useful were included in the study.
There are many more issues, summarised here as:
· No patient had been treated exactly the same over the years, with dosages and types of B12 varying.
· B12 was combined with folic acid, making separation of the effect of B12 impossible.
· Patients self-reported global improvements on a scale of 1 to 3, making the study open to a range of biases, particularly as ME/CFS is a fluctuating condition.
· An evaluation of current illness level was made and it was this that was used to determine whether a person was a ‘good’ or ‘mild’ responder (15 and 23 people respectively). But current illness level says little about improvement. Furthermore, the evaluation gave points for both fatigue and fibromyalgia symptoms, so those with both fatigue and fibromyalgia unsurprisingly scored worse.
· It was confounded by high rates of analgesic and thyroid medication use.
That 2015 study quotes a 1997 study as finding that ‘levels of CSF B12 were generally low’.
The 1997 study had its own set of problems:
· Small size - 24 patients ranging in age from 22 to 64. However, CSF B12 data is only reported for 12 patients, with no explanation for the drop outs.
· Poor selection criteria - the criteria did not require that the patients had the core ME/CFS symptom of post-exertional malaise but did require fibromyalgia symptoms
· There was no control group to ensure that approaches to CSF collection, storage and processing were consistent with comparison data
· The authors noted that the ‘method we used to analyse the concentration of CSF-B12 needs to be further validated’.
· There is no information as to how the normal range of CSF B12 was determined including whether it was appropriate for the patients’ age range.
· Only one of the 12 patients was found to have a level of CSF B12 that was deemed low (with most of the others being deemed borderline, and two in the normal range).
Therefore, the recommendation for B12 injections is based on a single 1997 study with 12 participants (who may or may not have had ME/CFS), no controls and a quantification method that the authors acknowledged ‘needs to be further validated’. Even then, the study did not find overwhelming evidence for low levels of B12 in cerebrospinal fluid. And the 2015 study of 38 hand-picked self-reported responders to B12 injections described the majority as being only ‘mild responders’.
Clinicians may say ‘I don’t need trial evidence’, I see some of my patients responding, they tell me it helps’. But the placebo treatment in the blinded rituximab trial produced a self-reported improvement in 40% of the participants in that cohort. ME/CFS is a fluctuating disease and patients typically reduce activity over time, by for example, giving up work, in order to reduce symptoms. In these circumstances, especially when both patients and doctors want to believe that an intervention is helping, self-reported improvement is not a reliable measure of efficacy.
Some may say, ‘well, what does it matter? If the patient is happy that they are doing something that helps, isn’t that giving them hope, isn’t that good enough?’. Similar arguments may be made for other treatments Dr Vallings suggests such as acupuncture, ‘good breathing technique’ and self-hypnosis.
But it does matter. A person with ME/CFS is having to make hard decisions about how to ration their energy. They may only have one shower a week instead of two, in order to have enough energy to get to the clinic for the treatment. They may be sick from the exertion of the trip for several days afterwards and not be able to interact with their child during that time. A person with ME/CFS is probably not able to work and so is having to make difficult decisions about how to ration funds. The cost of the B12 injection, or the acupuncture, may mean that they cannot afford to have fresh food delivered or donate to research efforts. If there is no reasonable chance of a benefit, there is harm.
Furthermore, listing unevidenced and probably ineffective treatments obscures the fact that there is really very little that significantly helps the actual disease other than reduced activity levels. It can suggest to skeptics that all people with ME/CFS need is a good placebo and some encouraging words.
Dr Vallings is absolutely right that so much is lost by people with ME/CFS; it is a devastating disease. Care needs to be taken to ensure that clinical practice is based on sound evidence and acknowledges remaining uncertainties.
And urine
Sue Jacksons blog carrys a lot of info presented in an easy to understand way.
B12 is a NO scavenger and this may be why it has an effect for some.
https://livewithcfs.blogspot.com/2014/04/vitamin-b12-and-mecfs.html?m=1
Certain genetic expressions also control the rate of B12 use / need for b12
You could have high blood serum but low cellular use - a kind of functional deficiency.
Tagging @Midnattsol who may be able to better explain this.
B12 is a NO scavenger and this may be why it has an effect for some.
https://livewithcfs.blogspot.com/2014/04/vitamin-b12-and-mecfs.html?m=1
Certain genetic expressions also control the rate of B12 use / need for b12
You could have high blood serum but low cellular use - a kind of functional deficiency.
Tagging @Midnattsol who may be able to better explain this.
It is as you say, the B12 is there but the cells can't use it. When this happens, the levels of methylmalonic acid rises, as it is metabolized in a process dependent on B12.
spinoza577
Senior Member (Voting Rights)
There might be one nevertherless.
Obviously actions in the body take place in a range of degrees.
These actions will be boosted or slowed down by molecules to be released, or even atoms.
Furthermore, there are different influences on an action (directly and indirectly),
it´s a web (which must stay stable enough).
If now a certain action has been slowed down,
and is itself in a single cell nevertheless within a normal range,
though an aggregation of this kind of action is too small (and this would be not normal)
one might want to boost cells of this action, although everything behaves as normal,
and there is no deficiency.
In this logic it would be important not to counteract the wanted influence
(which easily will happen, as the body is a web of different influences).
Here it would be crucial to do the molecule or atom without other stuff to the body.
It could even be important to do it in small dose to the body,
otherwise other actions might start (or maybe the reception will get close for such a too high influence).
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Arnie Pye
Senior Member (Voting Rights)
Merged thread
Association of Plasma Concentration of Vitamin B12 With All-Cause Mortality in the General Population in the Netherlands, 2020, Flores-Guerrero et al.
In a January 2020 issue of JAMA (Journal of the American Medical Association) a paper about the dangers of having a high level of vitamin B12 was published.
1) I've linked the paper, then followed it up with
2) another link showing how this was reported in the media, then linked
3) a very good debunking of the paper. The statistical shenanigans in the paper in JAMA are very clearly described for a non-medical and non-scientific reader.
----------
1)
Title : Association of Plasma Concentration of Vitamin B12 With All-Cause Mortality in the General Population in the Netherlands
Link : https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2758742
----------
2)
Title : High levels of B12 were associated with an increased risk of early death in a new study
Link : https://www.insider.com/b12-supplements-could-be-lethal-in-high-doses-study-finds-2020-2
Notice the difference in the title and the actual web page link - apparently B12 supplements could be lethal in high doses! Shock, horror!
----------
3)
Title : Guest post by GP David Morris - Unravelling the alarming misinformation in a recent study on vitamin-b12
Link : https://www.b12deficiency.info/blog...information-in-a-recent-study-on-vitamin-b12/
The website that the article comes from is very annoying and has had copying of anything disabled, so I can't quote any of it on here in the normal way - I've had to use the snipping tool instead.
Association of Plasma Concentration of Vitamin B12 With All-Cause Mortality in the General Population in the Netherlands, 2020, Flores-Guerrero et al.
In a January 2020 issue of JAMA (Journal of the American Medical Association) a paper about the dangers of having a high level of vitamin B12 was published.
1) I've linked the paper, then followed it up with
2) another link showing how this was reported in the media, then linked
3) a very good debunking of the paper. The statistical shenanigans in the paper in JAMA are very clearly described for a non-medical and non-scientific reader.
----------
1)
Title : Association of Plasma Concentration of Vitamin B12 With All-Cause Mortality in the General Population in the Netherlands
Link : https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2758742
----------
2)
Title : High levels of B12 were associated with an increased risk of early death in a new study
Link : https://www.insider.com/b12-supplements-could-be-lethal-in-high-doses-study-finds-2020-2
Notice the difference in the title and the actual web page link - apparently B12 supplements could be lethal in high doses! Shock, horror!
----------
3)
Title : Guest post by GP David Morris - Unravelling the alarming misinformation in a recent study on vitamin-b12
Link : https://www.b12deficiency.info/blog...information-in-a-recent-study-on-vitamin-b12/
The website that the article comes from is very annoying and has had copying of anything disabled, so I can't quote any of it on here in the normal way - I've had to use the snipping tool instead.
Last edited by a moderator:
Wonko
Senior Member (Voting Rights)
I am not qualified to give an opinion but it occurs to me that possibly the people taking very high doses of B12 might have been doing so for a reason, and that it may not have been taking high doses of B12 that killed them, even indirectly.
It might, just possibly, have been whatever the reason they were taking B12 for that did, even indirectly.
The quick scan that I have done would suggest that this is like concluding that chicken sandwiches are lethal simply because they were found in the stomachs of people who died by being shot, or who died in a traffic accident, or an avalanche.
It all appears, from a cursory glance, by someone with no medical training or experience, to be the height of stupidity to assume that correlation equals causation.
Of course B12 may actually be lethal, I have no clue, but the 'argument' given doesn't appear to show this.
It might, just possibly, have been whatever the reason they were taking B12 for that did, even indirectly.
The quick scan that I have done would suggest that this is like concluding that chicken sandwiches are lethal simply because they were found in the stomachs of people who died by being shot, or who died in a traffic accident, or an avalanche.
It all appears, from a cursory glance, by someone with no medical training or experience, to be the height of stupidity to assume that correlation equals causation.
Of course B12 may actually be lethal, I have no clue, but the 'argument' given doesn't appear to show this.
This is also true for other studies where high b12 is linked to cancer or all cause mortality (there are a few).
However, if you have high B12 without using supplementation it is cause for a more thorough check-up. There are many non-pleasant reasons this can occur. And as someone with high b12 levels, I wish researchers could differentiate between people who use supplements and those of us who don't.
Arnie Pye
Senior Member (Voting Rights)
This is one of the absurdities of the paper I linked from JAMA. The researchers had no idea who was supplementing.
Jonathan Edwards
Senior Member (Voting Rights)
I have only read the abstract of the paper but it seems perfectly fair to me. There is an association between high B12 levels and death. That proves no causal relation, as they say, but it raises a distinct possibility that having a high B12 level is bad for you. It is then very logical to assume that B12 supplementation might be harmful. As with all adverse effects, like damage from GET or suicides on psychiatric drugs, the level of evidence needed is very low.
I think it highly likely that anyone criticising this paper on the net has a very substantial axe to grind of their own. Since there is no evidence as far as I know that supplementing with B12 other than in proven deficiency is useful I think the original paper is a pretty good reason to be wary of supplementing over and above that.
I think it highly likely that anyone criticising this paper on the net has a very substantial axe to grind of their own. Since there is no evidence as far as I know that supplementing with B12 other than in proven deficiency is useful I think the original paper is a pretty good reason to be wary of supplementing over and above that.
I agree there are reasons to be wary, I would still like to know if the patients were supplementing or not, and if there is a difference between high levels due to supplementation and high levels without supplementation.
There has been a study on high b12 and all-cause mortality in Denmark as well, high levels were associated with higher mortality. Then there are cancer studies, the knowledge that high b12 can be caused by liver and blood disorders and probably things we don't know yet as high b12 got in the shadow of low numbers (even if it is relatively common), so it's not surprising.
Arnie Pye
Senior Member (Voting Rights)
I think that the problem with the issue of high levels of B12 is that people don't take into account or know the direction of causation/correlation. So, if someone who has never supplemented has high levels of B12 then this could indicate a problem with some type of solid tumour, or a serious liver problem. It is a known consequence of some types of cancer, and some forms of liver disease e.g. cirrhosis that levels of B12 may become very high.
But if someone has been supplementing B12 then the high level they have tells you nothing. It isn't possible to say whether the person taking the B12 has cancer or liver disease on the basis of the B12 alone. And there is no evidence that taking high doses of B12 causes cancer. The abstract of the paper I first linked in post 1 really is an appalling paper. I think the axes being ground belong to whoever paid for the "research" in link 1.
This paper is mentioned in the debunking paper and it mentions other conditions apart from supplementing, some cancers, and liver disease that can cause high B12 and it is well worth reading :
Title : The pathophysiology of elevated vitamin B12 in clinical practice
Link : https://academic.oup.com/qjmed/article/106/6/505/1538806
This is a very good link on the uses and effects of high doses of B12 from a Dutch deficiency group (it's in English) :
https://stichtingb12tekort.nl/weten...been-shown-to-be-safe-for-more-than-50-years/
It mentions, amongst other info, that smoke inhalation is treated with vitamin B12 injections as follows :
"
The safety of vitamin B12 treatment is further illustrated by the decennia long use of hydroxocobalamin as an antidote for cyanide poisoning, often caused by smoke inhalation. In the Netherlands ambulances, fire departments and emergency rooms have the Cyanokit at their disposal. In life threatening situations 5 g hydroxocobalamin is given intravenously within 15 minutes, an amount that corresponds with 5 000 injections of 1 mg B12.10 Hydroxocobalamin reacts in the body with cyanide, and forms cyanocobalamin, which is excreted in urine.
The serum value of B12 can rise to an average of 560 000 000 pmol/L within 50 minutes.11 If necessary this treatment is repeated within several hours, making the total dose 10 grams. The side effects that occur, like reddening of the skin and urine and changes in heart rate and blood pressure are temporary and harmless. In short: 10 000 injections a day are still not enough for an overdose of vitamin B12."
Jonathan Edwards
Senior Member (Voting Rights)
The authors of the original paper seem to be quite open about that and, as I indicated, it if you are worried about harm the question is whether there might be a causal relation
But as far as I am aware this is a pretty rare situation. I never came across it in my practice. The paper looks at a wide population with no particular link to cancer.
It tells you that there is a high level, and that might be a bad thing.
What makes you say that?
Arnie Pye
Senior Member (Voting Rights)
I think the
Jonathan Edwards
Senior Member (Voting Rights)
I realise you think that but what reasons?
Not sure which paper in link 3 you are referring to.
The paper by Andres looks to me to be pushing a line, with a number of inconsistencies. I doubt a high B12 level is a useful route to diagnosis of any particular disease.
Arnie Pye
Senior Member (Voting Rights)
In post #1 in this thread I gave three links and gave a superficial description of what each of the three links was. I should have said "article in link 3" rather than "paper in link 3".
One of the problems that was discussed in link 3 was dividing the subjects into four quartiles and the way it was done. Before the end of the research, quartiles 2 and 3 were combined, and the results of quartile 2 and quartile 3 were not given separately, presumably because the combined group gave them the result they wanted of an increase in mortality as B12 increased. For all we know quartile 3 may have had lower mortality than quartile 2 - but the information needed is not given. The fourth quartile was open-ended. It included all patients with B12 levels above a certain level. The quartiles were set up as follows :
The other thing that is strange about the splitting up of the subjects is that 455.41 pg/mL is not even a high level of serum vitamin B12. It is well within the reference ranges of any test of serum vitamin B12 I've seen used in the UK. The last NHS test of serum vitamin B12 that I had (5 years ago) had a reference range of 197 - 866 pg/mL.
Although I haven't got any proof, I have frequently seen it mentioned that in Japan a level of serum B12 below 500 is considered to be deficient and the top of the range is around 1300.
But if we accept (and I do) that a high level of B12 indicates the possibility of a problem (which may well not have been diagnosed) it means that quartile 4, which apparently had the highest levels of mortality, included people with levels which were well within any normal range, people with levels which were really, really high, and also included people who must already have been sick. And another thing - the differences between the quartiles was really very small.
It looks as if the researchers went out of their way to set up their quartiles to show the results they wanted.
Oh, and another thing - the subjects in the study were not healthy members of the general population.
Also, the researchers had no information on whether the subjects were supplementing B12.