B12 deficiency treated before folate ... - Pernicious Anaemi...

Pernicious Anaemia Society

32,207 members23,373 posts

B12 deficiency treated before folate deficiency

Nackapan profile image
8 Replies

Please could someone post a link supporting the importance of this fact for PhonixGrace .

Explaining B12 and folate are tested together normally for a good reason.

If folate is supplemented before B12 .

The b12 deficiency can be masked/ missed.

Nerve/neurological damage can occur .

Once B12 injections have started ,treat the folate if low.

B12 then folate.

I've tried to explain to no avail.

Thank you

Written by
Nackapan profile image
Nackapan
To view profiles and participate in discussions please or .
Read more about...
8 Replies
Technoid profile image
Technoid

Historically, it was believed that provision of folic acid to B12 deficient patients could not only "mask" the deficiency, but exacerbate/accelerate the neurological damage. I think this is no longer accepted to be true and is explained in this paper:

Lack of historical evidence to support folic acid exacerbation of the neuropathy caused by vitamin B12 deficiency

ncbi.nlm.nih.gov/pmc/articl...

However I also do not like using the phrase "masking" of B12 deficiency as, in reality, provision of folate can only correct the anemia but does not resolve the neurological damage, which merely proceeds unimpeded unless the B12 deficiency is also treated. It will also not alter a low serum or low active B12 result, nor affect an elevated MMA, which are all (imperfect) diagnostic markers of a B12 deficiency.

The deficiency is only "masked" in the sense that the symptoms of anemia will not present. In reality, as explained by Bruce Wolfenbuttel in his landmark "Many Faces" paper, the presence of macrocytic anemia in B12 deficiency may be the exception rather than the rule (with only 1 in 5 clearly serum B12 deficient patients displaying anemia). It could even be less considering that a normal or high serum B12 does not preclude B12 deficiency.

Per Bruce Wolffenbuttel:

The Many Faces of Cobalamin (Vitamin B12) Deficiency

"there is evidence that in the Western world as well as China, less than 20% of people with demonstrable low serum vitamin B12 levels have macrocytic anemia.

ncbi.nlm.nih.gov/pmc/articl...

The provision of folate, even if a B12 deficiency is present does not, in and of itself, cause neurological damage. This was believed historically but I believe has been disproven. Clinical guidelines are cautious and slow to change which is why I think it's still common to hear warnings to not take folate before a B12 deficiency has been treated. The reality is that the only risk is if the treating clinician has not updated their clinical knowledge since the 1970's and believes that absence of anemia rules out a B12 deficiency.

From a metabolic perspective, it makes sense to provide both at roughly the same time in deficiency situations but I think the level of concern about providing folate before B12 somewhat outran the evidence for harm.

Nackapan profile image
Nackapan in reply to Technoid

Thank you for reply.I still think good practice to start b12 first as only a matter of 24-48 hours needed before starting folate if needed .

Why take the risk.?

There is still uncertainty

As its more theories rather than the initial evidence found of people then not getting treated with B12 and neurological damage happening .

I'm so glad my daughter had B12 injectiond before folate as it turned out she had megobolastic anaemia !

48 hours later high dose ( short term ) folate given.

This was in hospital .

Like everything with B12 more research is needed and needs to be consolidated and formerly 'published' which is the term used .

I trusted a neurologist who had read every paper available.

He said not many with a reliable source.??

He advised B12 before folate every time .

The term 'masking ' is surely relevant and correct term.

Also just read to treat B12 first on the latest NICE guidelines March 2024

Sleepybunny profile image
Sleepybunny

Hi,

If PhoenixGrace is in UK, this link might be useful.

See Cautions section.

bnf.nice.org.uk/drugs/folic...

Nackapan profile image
Nackapan in reply to Sleepybunny

Thank you. I got myself confused with trying to give an explanation

Just knew i would start B12 first incase of any doubt !!

A simple thing to do and once detected should start ASAP as we know to our detriment

FlipperTD profile image
FlipperTD

The musings of a retired scientist, not a medic.

This is a case of 'you can lead a horse to water', I suspect.

B12 and folate are tested together because [Haematologically] it's not possible to tell the difference between megaloblastic anaemias caused by a deficiency of either, or both, of the above. In fact, one regularly used assay method [Simultrac-S] did the tests simultaneously, so it wasn't possible to do either analyte individually; this greatly simplified the lab workload.

It was believed that, in the presence of a low B12, treatment with folate could actually exacerbate the B12 problem by 'using up' the remaining B12 and accelerate the neurological damage. Given that the blood issue [megaloblastic change] can be rapidly resolved by replacing the missing substance, and a response detected within a matter of hours, but the neurological damage takes much longer, if indeed it's possible to resolve, then personally, I'd want to start with B12 whether I was deficient or not, and start the folate a little while later.

This is almost certain to be a gross oversimplification of the matter, and Technoid's link below does show there's a lack of historical evidence for the historical belief.

I hope this doesn't muddy the pond further.

Nackapan profile image
Nackapan in reply to FlipperTD

Thank you

Cherylclaire profile image
CherylclaireForum Support

Article by Ralph Green from 2017 in Blood vol 129: Vitamin B12 deficiency from the perspective of a practicing hematologist.

"Although rarely resulting in megaloblastic anemia, mild deficiency may be associated with neurocognitive and other consequences."

"Failure to diagnose B12 deficiency can have dire consequences, usually neurological."

"B12 and folate are intimately connected through their cooperative roles in one-carbon metabolism, and the hematological complications seen in deficiency of either vitamin are indestinguishable."

There is an explanation of folate becoming "trapped" as methylfolate in B12 deficiency due to B12 being required for conversion to tetrahydrofolate. "Trapping of methylfolate creates a state of functional folate deficiency. Alleviation of the anemia masks the underlying B12 deficiency and allows the neurological damage from B12 deprivation to continue unabated."

More recently, following national folic acid fortification programs (American):

" .... there have been several reports from longitudinal population studies that individuals with low serum B12 levels, who had associated high serum folate levels, had significantly higher levels of methylmalonic acid (MMA) and Hcy and were more likely to show cognitive decline and have lower hemoglobin concentrations than those with low B12 but without high serum folate. Moreover, individuals with low serum B12 and high serum folate had depressed levels of holotranscobalamin (holoTC), indicating an apparent depletion of circulating active B12 when serum folate was high."

In conclusion, Ralph Green mentions this again:

"Several questions still remain unanswered concerning B12 deficiency, including the possible harmful effects of high folate levels in subjects with low B12 status, particularly with respect to neurological damage."

I think this detailed and, in parts, complex article is still worth reading, even though now 7 years old. Hope this helps.

PS: It also discusses, in summary, self injecting more frequently than guidelines suggest:

"No biological basis for this apparent increased requirement for B12 replacement is known, but because there are no reports of adverse effects associated with excess B12 intake, there is no reason to advise against this practice."

This might also help someone.

Nackapan profile image
Nackapan in reply to Cherylclaire

Thankyou

You may also like...

Vitamin b12/Folate deficiency

course of four b12 injections, and to start folate tablets (5mg per day) after two b12 jabs. My...

B12 and folate deficiency

could be a false normal ? After a little cajoling he is starting me on B12 injections tomorrow and...

Folate deficient but am I b12 deficient?

and my feet are tingling. Can folate make b12 go down? Should I be on injections at 240? Thank you 

B12 deficiency not treated

above 6 injections I am no longer B12 deficient, asked should I take tablets or go on a B12 diet,...

Low 'normal' B12 and high folate - B12 deficient?

started the B12 injections and apparently this can affect the result and deliver a 'false normal'....