I've read this quite a lot - it is important to not take folic acid before supplementing with B12 if you have a deficiency in both. The reasons given are 1. It can mask the megaloblastic anaemia caused by B12d, delaying a diagnosis of B12 deficiency. and 2. It can exacerbate the neurological damage caused by low B12.
Now the first reason is fine. There are well argued reasons why this is he case. But it's irrelevant if you're already diagnosed as B12 deficient .
I posted something about the second reason and the laughable explanation given on Wikipedia. This morning I realised that the explanation I gave was also wrong. So I've been doing some searching this morning.
The first interesting snippet was from 2007.
"Although it was thought that folic acid might exacerbate vitamin B12 deficiency and its symptoms, it is probably not the case"
I finally found a study from 2013 that claimed to have found evidence for high levels of folic acid to impair cognition in elderly subjects with low B12. This is what they said...
"Participants with low serum vitamin B12 (<250 pmol/L) and high red cell folate (>1,594 nmol/L) levels were more likely to have impaired cognitive performance"
However, a few lines further on they say
"Participants with high folate levels, but normal serum vitamin B12, were also more likely to have impaired cognitive performance"
"Unfortunately folic acid was synthesized first in 1945, 3 years ahead of the isolation of vitamin B12, and was immediately utilized in the treatment of “pernicious anemia” as the possibly deficient dietary factor (Chanarin, 1969). These trials were encouraged by some initially promising improvement in the megaloblastic anemia. However, over the subsequent 5 years and beyond there followed several disturbing reports of aggravation or precipitation of the neurologic complications of “pernicious anemia” by the vitamin (Hall and Watkins, 1947 and Schwartz et al., 1950). In fact, folic acid was also often associated with later deterioration in the anemia after the initial improvement (Schwartz et al., 1950); and in some reports there was some temporary improvement in neurologic symptoms before the more florid deterioration (Hall and Watkins, 1947 and Reynolds, 1976)."
"These developments in the period 1945–1950 had a profound effect on subsequent concepts. The introduction of vitamin B12 treatment, with its beneficial effects on both the blood and the nervous system, coincided with the height of concern about folic acid. In the third quarter of the 20th century it was therefore erroneously assumed: (1) that the neuropsychiatry of megaloblastic anemia, so carefully documented in the preceding half century, was that of vitamin B12 deficiency only; (2) that folic acid was only harmful to the nervous system and there was no neuropsychiatry of folic acid deficiency (see Reynolds, 1976 and Reynolds, 1979a)."
"The 1945–50 experience indicates that treatment of patients with vitamin-B12-deficiency with folic acid is inappropriate because it may precipitate or aggravate neurological complications or allow them to progress by masking the anaemia (figure 2). 7,8,10 Larger doses of folic acid for longer periods are more likely to lead to neurological progression. Savage and Lindenbaum 32 reviewed 38 cases of vitamin-B12 deficiency treated with less than 1 mg folic acid, which had little haematological effect. Only six patients had neurological deterioration, but remarkably they had been treated for much longer than the remaining cases, illustrating the importance of duration of treatment in relation to the nervous system.32"
Not sure if you will be able to read these reviews and the references they both quote for much of the work from the 40s and 50s and up to late 70s are not online. Heck some of the refs from the 90s are not online either. The 2nd one above shows a figure from the Schwartz 1950 paper mentioned in the first but the timescale for problems is in months.
BNF says that B12 and folic acid can be given concurrently if necessary.
"should never be given alone for pernicious anaemia and other vitamin B12 deficiency states (may precipitate subacute combined degeneration of the spinal cord); interactions: Appendix 1 (folates)"
Yes, the 2007 mentioned older studies suggesting that folic acid alone may precipitate neurological damage, but the studies weren't very reliable. That's one reason I restricted my searches to the last decade.
I really posted this because I've been worried that some people who have been worried unnecessarily. If they have been supplementing with folic acid, then find they may have a B12 deficiency, some of the dire warnings could cause concern - at a time when they really don't need more to worry about.
So I would suggest that, in future, rather than warnings, suggestions might be preferable.
have come across reports of cases in which early treatment with folate seems to have precipitated SACD but of course I can't find one at the moment but there is a discussion in this article of the risks of treating with high doses of folate in an unidentified B12 deficiency - suggesting further study for clarification but suggesting a mechanism by which treating with high doses of folate can induce SACD (though its based on effects in trials involving fruit bats).
In summary, folic acid directly interferes with the natural history of both the anaemia and the nervous system manifestations of vitamin B12 deficiency. It has been suggested that it does so by aggravating the methyl folate trap/block.41 Experimental studies with vitamin B12 deficient fruit bats have confirmed that pretreatment with folic acid or formyl tetrahydrofolate speeds up the appearance of nitrous oxide induced subacute combined degeneration.42 The risk to the nervous system is probably related to both the dose and the duration of vitamin therapy. It is also the case that in the absence of controlled trials, which will never be undertaken, the exact risks of different doses and durations of therapy will be difficult to quantify.
References are
41 Scott JM, Dinn JJ, Wilson NVB, et al. Pathogenesis of subacute combined degeneration: a result of methyl group deficiency. Lancet 1981;ii:334–7.
42 Van der Westhuvzen J, Fernandes-Costa F, Metz J. Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats: protection by methionine and aggravation by folates. Life Sci1982;31:2001–10.
fbirder In the NICE guidelines you posted ( cks.nice.org.uk/anaemia-b12... ) in reply to Barry1955 there's a section on folic acid: "Treatment For Folate Deficiency", and it states "treatment can improve well-being such that it can mask underlying B12 deficiency and allow neurological disease to develop." It also says "A possible link has been found with folic acid and an increase in the progression rate of pre-cancerous lesions to cancer" - for people's anxiety levels, it does say 'possible' and that no links have been found so far in human trials.
The nice link doesn't say that high folate and low B12 can cause neurological problems. It says that high folate can mask low B12 and, hence, allow neurological problems to develop. As I say above, this is correct. But irrelevant to anybody with a diagnosed B12 deficiency.
Does the possible increase in cancer progression only happen in high folate low B12 situations? Or is it high folate alone?
The study you cite last is not at odds with the suggestion that folate might exacerbate neurological issues. The two groups with neurological impairment had either low or normal b12, but they both had high b9. This would seem to imply that something about the ratio is important.
I understand that this is anecdotal, but my doctor started me on high dose methylfolate, methylcobalamin, and hydroxocobalamin all at once. I wasn't deficient in folate. I had severe adverse reactions, got much worse, and developed the neuropathy within a few months.
I doubt I can prove it but I think this is a contributing factor in how i am now.
I didn't know I was low in b12 (153pg) until October and bought a multivit spray from Amazon in May.
It had 400mcg of folic acid in it and only 6ug of b12.
I used it for 5 weeks from the end of May but began to feel more fatigued so I stopped it. Then I noticed quite bad light glare then burning skin on my right thigh. I'd also been to the dentist with 'tooth ache' that he couldn't find a reason for so said it could be neuralgia.
In August I went for a brisk walk and fell into bed when I got back. I was pretty much flat on my back for four weeks with postural tachycardia. Resting pulse of 58 rising to 120+ upon standing.
I'm beginning to wonder if the folic acid caused a worsening of my b12 situation.
IN 1977 I read that giving Folic acid without B12 would precipitate SACD.
Unfortunately I don't remember the source. It could be Goodman and Gilman or even Ganong. The explanation was " Folic acid stimulated erythropoiesis and used up B12 for maturation". Therefore there was a deficiency which affected the nervous tissue. I have seen one case. The resulting damage was also supposed to be permanent. Luckily the patient respond to treatment. Would be glad if someone could give the reference if they had come across this statement.
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The 2nd one above shows a figure from the Schwartz 1950 paper mentioned in the first but the timescale for problems is in months.
Folate instead of Folic acid
Checking on my understanding of Folic Acid
Treated for low B12 and now low folic acid
Folic acid mask b12 deficiency?
