Folic acid and folate supplementation

[helvella]

The paper linked below was published by EFSA journal. European Food Safety Authority, 13 Nov 2023.

The extremely brief summary is that the tolerable upper limit for folate supplementation - by methylfolate or folic acid - should be 1000 micrograms a day - or lower (e.g. in children).

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.

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4. CONCLUSIONS

The following ULs are established for the intake of supplemental folate (i.e. folic acid, 5‐MTHF‐glucosamine and L‐5‐MTHF‐Ca; Table 12) from fortified foods and food supplements:

[ see attached image of table ]

europepmc.org/article/MED/3...

In addition to that summary, there is also the possible issue of unmetabolized folic acid appearing in our blood.

The paper below suggests that threshold below which this does not happen is around 200 micrograms a day and but the time we supplement folic acid at 400 micrograms a day, this will appear (at least, for most of us).

The significance is more difficult to assess.

Folic acid fortification and public health: report on threshold doses above which unmetabolized folic acid appear in serum.

Conclusion

Our findings suggest that persons exposed to the current US fortification programme supplying an average of 100 microg per day or less are unlikely to have unmetabolised folic acid in serum. It also seems that daily consumption of the higher level of 200 microg or less is unlikely to be problematic. Increasing the level however to 400 microg on the other hand is likely to lead to unmetabolised folic acid appearance.

europepmc.org/article/MED/1...

Given these two papers, why do GPs in the UK prescribe 5000 micrograms (5 milligrams) of folic acid so often?

The simple answer is that, for most of us, that is their only choice. Lower dosages have specific limitations (e.g. ion pregnancy).

My conclusion:

● We should be more cautious about folate supplementation.

● Up to 200 micrograms a day - maybe it really doesn’t matter what form we take.

● From 200 to 1000 micrograms a day - choose methylfolate at least for most of it.

● Do not take more than 1000 micrograms a day unless there are special circumstances.

I would avoid taking 5000 microgram doses even on a once a week basis - but that is my choice.

It might be necessary to go to a higher dose for people who are severely deficient and urgently need their levels to be raised.

This is not because I am knowledgeable about folate. But I have been reading. And I have seen a number of people post about feeling bad on 5000 micrograms daily. (Mostly Pernicious Anaemia Society members.)

Feel free to comment.

[helvella Administrator]

Table 12 repeated to make it more readable (I hope).

Table repeated to make more readable

[BB001]

Good find thank you helvella. As usual, more isn't necessarily better.

[humanbean]

I am shocked (and have been for quite a long time) that the NHS prescribes 5mg (5000 mcg) folic acid for people who are low or deficient in folate and who hope to get pregnant soon or are already pregnant. There is plenty of evidence that people don't do well on such massive doses of folate. And if a pregnant woman doesn't do well, I'm guessing that the child won't either.

web.archive.org/web/2024022...

link.springer.com/article/1...

sciencedirect.com/science/a...

[helvella Administrator in reply to humanbean]

It was that a member mentioned 5 milligram folic acid earlier today that prompted be to look out the recent tolerable upper limit advice.

[helvella Administrator]

Just adding something that might be relevant to some:

While I refer to methylfolate, there is also the option of taking folinic acid.

For reference, this is its entry in the British National Formulary:

bnf.nice.org.uk/drugs/folin...

It is relatively expensive and, for some, might provide no advantages at all. But I want readers to be aware of its existing.

This is a link to search the Pernicious Anaemia Society forum where it is mentioned much more often than here:

healthunlocked.com/pasoc/se...