Some of the areas covered are well-known. Such as not treating B12 deficiency with folic acid.
But, in the more speculative parts, I think it does raise questions over the prescribing of high dose (e.g. 5 milligrams a day) of folic acid in those who are currently low in B12. With the implication it could reduce their achieving adequate B12 levels.
It is difficult to extract quotes from the paper as so much of the paper builds on what has gone before and a simple quote would be misleading. So I have posted the Abstract with the suggestion that if it is at all interesting, do read the whole paper.
Excess Folic Acid and Vitamin B12 Deficiency: Clinical Implications?
Abstract
Background:
In the 1940s to 1950s, high-dose folic acid supplements (>5 mg/d) were used clinically to reverse the megaloblastic anemia of vitamin B12 deficiency caused by pernicious anemia. However, this treatment strategy masked the underlying B12 deficiency and possibly exacerbated its neuropathological progression. The issue of masking and exacerbating B12 deficiency has recently been rekindled with the institution of folic acid fortification and the wide-spread use of folic acid supplements.
Objectives:
The objectives of this review are to describe clinical and epidemiological evidence that excess folic acid exacerbates B12 deficiency, to summarize a hypothesis to explain this phenomenon, and to provide guidance for clinicians.
Results:
Cognitive function test scores are lower and blood homocysteine and methylmalonic acid concentrations are higher in people with low B12 and elevated folate than in those with low B12 and nonelevated folate. High-dose folic acid supplementation in patients with pernicious anemia or epilepsy cause significant reductions in serum B12. It is hypothesized that high-dose folic acid supplements cause depletion of serum holotranscobalamin and thus exacerbate B12 deficiency.
Conclusion:
The evidence for excess folic acid exacerbating B12 deficiency is primarily correlative or from uncontrolled clinical observations, and the hypothesis to explain the phenomenon has not yet been tested. Nonetheless, the evidence is sufficiently compelling to warrant increased vigilance for identifying B12 deficiency in at risk individuals, including older adults and others with low B12 intake or conditions that are associated with B12 malabsorption, who also ingest excessive folic acid or are prescribed folic acid in high doses.
Another good study - thank you for sharing Helvella.
Even more to think about. It is rather good that there are more studies on B12 going on.
I am now thinking ...more and more... that there is a set of specific enzyme/vitamin ratios here i.e. " the right mix/blend" of things to get right in a B12 regime for each individual..which will help avoid overloads..
What I mean is ....AS AN EXAMPLE .. if you take B12 Hydroxy, say daily 3 times a week - @ 6mg B12.
You also take lower levels for other supplements.. i.e. just 500mcg Folic Acid, 500mcg Betaine, 500mcg Potassium etc - for each daily dose of 6mg of B12. This is your personal "recover/repair" B12 cocktail.
Anyways, thank you (as ever ) for the update and thoughts shared.
A recent paper on the tolerable upper limit for folate (including folic acid) intake.
I leave the implications/inferences to be discussed by others!
Scientific opinion on the tolerable upper intake level for folate.
Abstract
Following a request from the European Commission (EC), the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for folic acid/folate. Systematic reviews of the literature were conducted to assess evidence on priority adverse health effects of excess intake of folate (including folic acid and the other authorised forms, (6S)-5-methyltetrahydrofolic acid glucosamine and l-5-methyltetrahydrofolic acid calcium salts), namely risk of cobalamin-dependent neuropathy, cognitive decline among people with low cobalamin status, and colorectal cancer and prostate cancer. The evidence is insufficient to conclude on a positive and causal relationship between the dietary intake of folate and impaired cognitive function, risk of colorectal and prostate cancer. The risk of progression of neurological symptoms in cobalamin-deficient patients is considered as the critical effect to establish an UL for folic acid. No new evidence has been published that could improve the characterisation of the dose-response between folic acid intake and resolution of megaloblastic anaemia in cobalamin-deficient individuals. The ULs for folic acid previously established by the Scientific Committee on Food are retained for all population groups, i.e. 1000 μg/day for adults, including pregnant and lactating women, 200 μg/day for children aged 1-3 years, 300 μg/day for 4-6 years, 400 μg/day for 7-10 years, 600 μg/day for 11-14 years and 800 μg/day for 15-17 years. A UL of 200 μg/day is established for infants aged 4-11 months. The ULs apply to the combined intake of folic acid, (6S)-5-methyltetrahydrofolic acid glucosamine and l-5-methyltetrahydrofolic acid calcium salts, under their authorised conditions of use. It is unlikely that the ULs for supplemental folate are exceeded in European populations, except for regular users of food supplements containing high doses of folic acid/5-methyl-tetrahydrofolic acid salts.
I have just reread a book by a chap called Mike Newman about B12 deficiency which I find very informative. He says that he found Folic Acid 5mg was too much for him and caused all sorts of problems. I started on Folic 5mg EOD at the end of May when I started my B12 injections, then switched to Methylfolate every day for a couple of weeks. I was suffering more aches and pains and fatigue so was recommended to go back to Folic 5mg every day. Needless to say I am still suffering and after reading Mike Newmans book again, I think I am going to go back to the Methylfolate. It’s all a bit of a minefield when it comes to cofactors and there are so many different opinions, it’s difficult to know who to listen to. I just wish I could start to see some improvement in my symptoms then I think I might feel more positive I am going to get better. ☹️
About the only thing I am sure of - some people need more than others! And the amount needed could well be closer to the standard upper tolerable limit for some.
Have you considered folinic acid? I can’t tolerate anything greater than 100mcg of methylfolate and folic acid doesn’t agree with me either, but a small daily dose of methylfolate and a larger dose of folinic acid with injections seems to work well for me.
The point isn't that all people cannot possibly tolerate 5 milligrams a day.
But that some might not tolerate that much. And highlight that even lower doses might contribute to widespread failure to diagnose and treat B12 deficiencies.
And to question whether a lower dose might be as effective and avoid the risk of intolerance by keeping the doses lower - e.g.. 1 milligram a day.
This was a really interesting read. I wonder how they would actually go about testing their hypothesis?
As well, the fortification of foods with folic acid, as well as the current societal norm of taking multivitamins could very well be masking quite a lot of people struggling with B12 levels. But doctors really don’t know about this, do they? So they look at the levels, observe no anaemia, and send the patient on their way. Or whack the anxiety label on them and prescribe anti-anxiety meds 🙄
Fortification of wheat flour has been progressing slowly through the processes in the UK - and I think has not yet hit the statute book.
But these issues are major reasons to question the approach.
At the same time, desperately trying to ensure that neural tube defects caused by inadequate folate are eliminated.
But I do not know anything about the effects of (relatively) low B12, or overt deficiency, in pregnancy and on the baby. Perhaps we need that to be more fully appreciated?
A very useful fox amongst the Folate/B12 chickens there Helvella
Like others have said, its all about what you can actually absorb from food/supplements through Tummy or SubLing - plus what your body can cope with...Also...i thought we just weed out excess B6 as its water soluable...?
Like WIZARD and others..I am using "personal" trial regimes now - defo not the NICE recommenations the GP's seem to love to sing about.
I am using lowish levels of supplementation i.e. Folate, B9,B1, etc - in relation to high levels of B12, as I eat a decent diet. My goal is to reduce the pain, fatigue and brain troubles i am having with peripheral neuropathy... and get some degree of repair / pain lessening. So, I will edge them up over time and see what works for me best...
I am super keen on the idea of building your own " recovery mix " as you CAN get repair to peripheral nerve systems as you body is repairing them all the time - your body needs to be functioning well enough to do it...that's the key I feel.
You might have seen me ask in here about other people "regimes" as I am looking for the mixes they have gone for and experiences they have had. Health detectives never sleep..!
Being water soluble is necessary in order to dispose of an excess, but it is not sufficient to protect against issues.
Just think, potassium cyanide is very water soluble. But it kills you before is gets urinated out.
All this water-soluble business is to clarify that they are not fat soluble - like vitamins A and D. Once you have an excess of a fat soluble vitamin it is very difficult to get rid of it.
As well as to highlight that because they are water soluble, you would expect to see your levels lowering because urination will carry some away.
It is exploited by vitamin salesmen to encourage you to buy more whether or not you need them.
Before anyone jumps into a folate supplementation routine, I think many forget that it is important to get your folate levels checked. If your levels are in the high normal range, perhaps 400 - 800 mcg is sufficient if you are injecting EOD or more. If your levels are low, you may need 5mg daily for a period of time until your levels return to an optimal level. Using me as an example, I inject 1 mg B12 twice daily and take 800 mcg folic acid most days. My folate levels remain above the high limit. I tried the 5 mg daily and it made me feel horrible with all sorts of nasty GI issues. So get your folate levels checked before you decide what routine to start.
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
Folic acid vitamin warnings 
Folic acid mask b12 deficiency?
Dementia or Folic Acid Deficiency ?
Folic acid supplementation in b12 deficiency 
folic acid and b12
