Safe Folate Level With 5-MTHF?

[deepocean]

When supplementing folate in 5-MTHF form, is a high blood Folate reading still considered high as far as the cancer dangers - or, is it sort of a false-positive?

[Foggyme Administrator]

Deepocean. Briefly...

Folate is folate, whatever form you take.

If your folate levels are over 20 (above the measurable range) you are over supplementing with folate and don't need to supplement with folate, in any form.

Long-term supplementation with folate can cause unpleasant side effects and be detrimental to long term health (including potentially irreversible neurological damage.

I suggest you stop supplementing with any form of folate and then get levels checked in three months to ensure that your levels are being maintained. Some need to take 400mcg as a maintenance dose, some don't need any folate once an original deficiency has been rectified.

I'm assuming that you originally took methyfolate to rectify a proven deficiency? I'm saying this because some Facebook groups and internet websites mistakenly state that those who inject regularly with vitamin B12 need to take folate (sometimes in ridiculously high doses) to 'make B12 work'. This is not true. Folate is only required when it is proven via blood tests that folate levels are deficient or cannot be maintained - usually due to absorption issues which often (but not always) go hand on hand with a B12 deficiency that is caused by absorption issues. Also worth noting that some medications impact on folate absorption and metabolism, in which case folate levels are monitored by a GP or specialist and folate supplements prescribed accordingly.

So...since your folate levels are above the measurable range, suggest you stop the methyfolate, ask your GP to test folate levels in three months, then decide if low dose maintenance doses are required.

Good luck.

[fbirder in reply to Foggyme]

Everything Foggyme says, plus...

For the vast majority of people there's no need to splash out the extra cash for methylfolate rather than folic acid. Both are easily converted to all the different types of folate your body requires.

So if your folate levels do drop to the bottom of the range after a few months of no supplements then you should be fine with a supermarket brand of 400 mcg of folic acid a day.

[deepocean in reply to fbirder]

Thanks Fbirder, do you find that B12 injections generally drop Folate levels much, or require say 400 mcg supplementation for every 1mg injection or that sort of ratio?

[fbirder in reply to deepocean]

B12 injections do not drop folate levels at all. That's a Facebook myth.

If you have PA then you have low stomach acid. If you have low stomach acid then you cannot absorb folate in food as well as normal people.* So PA often means low folate, whether you inject or not.

All women of childbearing potential are advised to take 400 mcg of folic acid a day. So that level of supplementation should be OK for everybody.

*Folate in food comes attached to several molecules of glutamate. These need to be removed by protease enzymes in the small intestine before the folate can be absorbed. Those enzymes need to be activated by acid from the stomach to work properly. Without the acid the glutamate molecules aren't removed and the folate isn't absorbed.

[deepocean in reply to fbirder]

Thank you for the reply.

[fbirder in reply to deepocean]

If you have a deficiency with no known cause then it's almost certainly Pernicious Anaemia.

Half of those with PA test negative for IF antibodies. Ultrasound cannot diagnose PA.

[deepocean in reply to Foggyme]

Thanks Foggy, totally agree - I will pause supplementation and get tested in a few months.

[Foggyme Administrator in reply to deepocean]

Apologies but I need to be brief...

My view is that supplements aren't required unless you know they are needed. As to ‘balancing B vitamins' - dubious about that - taking extra of all B vitamins if they are not needed can cause issues, particularly with vitamin B6, which can cause neuropathy (and parasthesia) and potential permanent neurological damage if over supplemented long-term. Not sure how taking extra of all the B's vitamins can have a 'balancing' effect (all you’re doing is increasing levels of everything, whether it’s needed or not) 🤷‍♀️.

Some B complex's have over 300% of RDA of vitamin B6. This excessive for most people and can be dangerous if taken long term.

I'm also asking myself the question...how many molecules are contained in 1mg B12 - and how many molecules of folic acid are contained per mcg - keeping in mind folic acid is best obtained from diet... ( fbirder are you able to comment on this and deepoceans question?).

To be honest, I'm suspicious of the specialists idea of 'going by feel' in terms of folic acid dose, especially as the symptoms of folate deficiency are almost exactly the same as the symptoms of over supplementation with folic acid.

Was this specialist an appropriately qualified medical professional?

What I do know is that your folate levels are over the top of the reference range so you don't need to supplement with any form of folate (this may well have dangerous long term consequences).

When you speak of the effects of over-methylation - I suspect that you were experiencing the effects of over supplementation with folate. It's much more likely that any feeling of improvement was due to the effect of the B12 - especially since you never had a folate deficiency.

The answer about folate and supplementation with folic acid (in any form) is that you only need it if levels are deficient or constantly low due to absorption issues - and then rarely above 400mcg daily (unless other issues are involved), for most people. And that’s due to absorption issues rather than having B12 injections.

One copy of C677T has little to no impact on folate metabolism (despite much that is written on the internet - usually by those selling methyl folate - or with their own agenda).

Just wondering... have you been diagnosed with B12 deficiency? Had consistently low or dropping B12 levels? Asking because we often find here that people are actually being made unwell because of supplementing with vitamins that they don't need? Not saying that this is the case with you but worth considering if B12 deficiency has not been diagnosed.

Interestingly, not so long ago someone posted to say that following advice given here, they’d stopped all supplements (excepting B12 injections) and there had been a dramatic improvement in their health.

Also worth saying that there are some here who have to take very high levels of supplements. But that’s the exception, not the rule, and is always done via keeping an eye on levels via testing and taking the time to determine the correct doses for them (we're all different and there’s no such thing as an 'ideal' dose or 'optimal' level.

It’s all very tricky. If I was you, I'd stop all vitamin supplements (including the B complex but excepting the vitamin B12 and any taken for a proven deficiency), then track and monitor symptoms and take it from there.

Good luck.

[fbirder in reply to Foggyme]

Just out of interest.

1 mg of B12 contains about 450,000,000,000,000,000 molecules (4.5 x 10^17).

1 mcg of folic acid contains about 1,500,000,000,000,000 molecules (1.5 x 10^15).

B12 has a molecular weight of about 1330. Folic acid has a molecular weight of 441. So a molecule of B12 is about 3 times heavier than a molecule of folic acid.

To take equal amounts of each you would need to take B12 and folate in the ratio 3:1.

But, as I explain in my reply to deepocean , that is a ridiculous idea.

[deepocean in reply to fbirder]

But to your math, so what would a 3:1 ratio be then in actual grams - like would it be 1mg B12 to 3mcg of Folate?

[fbirder in reply to deepocean]

It would be 1 mg of B12 to 0.333 mg (330 mcg) of folate.

[deepocean in reply to Foggyme]

Foggy, thanks again for taking the time to respond.

[fbirder in reply to deepocean]

"a specialist who runs a clinic injecting B12 in patients for Fibromyalgia/Chronic Fatigue type issues told me that you need one molecule of Folate for every molecule of B12 you inject"

A specialist in talking rubbish because he really doesn't understand biochemistry, although he thinks he does.

There is one reaction that involves B12 and folate, the conversion of homocysteine (hCys) to methionine (met). That reaction does, indeed, involve one molecule of cob(ii)alamin (which comes from one molecule of B12) and one molecule of methylfolate (MTHF) (which is made from one molecule of folic acid). The reaction can be written as...

hCys + MTHF + cob(II)alamin -> met + THF + cob(ii)alamin

Notice how cob(ii)alamin is on both sides. It doesn't get used up in the reaction. Once it's been involved in converting one molecule of hCys into met it's still there ready to convert another one. It's a catalyst. It can do that same reaction thousands and thousands of times. So that knocks out the 'need one molecule of each' nonsense.

But there's more. What is THF and what happens to it?

THF is tetrahydrofolate and it goes on to make more MTHF as well as methylenetetrahydrofolate and formyltetrahydrofolate. These last two are vital for making DNA. See here for more information. b12science.com/B12Science/D...

So that molecule of folic acid you consume goes round and round, making different types of folate, each doing different jobs thousands of times before it gets flushed out.

And yet more!

hCys to met isn't the only reaction B12 is involved in. It's also required for converting methylmalonyl CoA into succinyl CoA. And that reaction doesn't use folate at all!

So if the hCys-met conversion were the only thing that those two vitamins were used for, and if neither were recycled then your idiot specialist might be close to correct. As it is, he is spectacularly wrong.

[deepocean in reply to fbirder]

Thank you for the reply.

[fbirder in reply to deepocean]

This is word for word what he said "Every molecule of cobalamin needs a molecule of folate. The more cobalamin you get, the more folate you need to keep pace."

And, as I explained, it is complete and utter nonsense.

"Methylcobalamin may make it all the way, but it is a long way with many many passages. There is a very great chance that the methyl group could be lost during this long journey to the target cell, and therefore has to be methylated once again just before it functions as coenzyme."

Also nonsense.

As soon as methylcobalamin enters the cell the methyl group is removed to form cob(II)alamin. Just as the cyano group is removed from cyanocobalamin to form cob(II)alamin. And the hydroxo and adenosyl groups are removed from hydroxocobalamin and adenosylcobalamin, respectively, to form cob(II)alamin.

Cob(II)alamin is only methylated once it has bound to methionine synthase, and the methyl group is only in place fleetingly before getting passed on to hCys. The idea that methylcobalamin acts as a coenzyme is incorrect. It is cob(II)alamin that is the coenzyme. b12science.com/B12Science/D...

[deepocean in reply to fbirder]

Fbirder, thank you. Do you believe in the theory of "Functional B12 Deficiency"?

[fbirder in reply to deepocean]

Do I believe in it? Yes, we have people on here that have all the signs.

Do I believe it is common? Not at all.

Those people who think they have a functional deficiency can ask for an MMA test (or get one privately for about £130. Methylmalonic acid is a chemical used up in one of the reactions mediated by B12. If the B12 isn't getting into the cells then MMA levels will be high.

[fbirder in reply to deepocean]

"I had a DNA test that shows I have one copy of the C677T variant which I believe can affect Folate; however, again my Folate level was always normal prior to starting injections - so this mutation must not affect too much?!"

Being heterozygous (one copy) for the C677T mutation of the MTHFR gene has no effect on folate levels. It means your body is very slightly less efficient at converting methylenetetrahydrofolate to methyltetrahydrofolate. It can easily compensate for that.

Which is lucky, because about 3 billion people have that mutation.

[deepocean in reply to fbirder]

Thank you for the reply.

[fbirder in reply to deepocean]

No. No MTHFR mutations can lower folate levels. Which is lucky because almost everybody in the world has at least one mutation. If MTHFR stopped working completely then folate levels will not drop. All that would happen is that methylenetetrahydrofolate would stop being converted to methyltetrahydrofolate. So the levels of MTHF would drop, but all other folate levels would still be normal. I'm guessing that 23andMe were referring to methylfolate when they say 'folate'.

Interestingly, if you'd read the document I linked to about folate you'd have seen another quote from 23andMe about MTHFR. Here it is - blog.23andme.com/health-tra...

Based on the existing data, scientists at 23andMe have concluded that people should not interpret their genotypes at the common MTHFR variants as having an effect on their health.

In order for a connection between a genetic variant and a health condition to be considered real and clinically meaningful, well-run scientific studies need to show convincing and consistent evidence for that association. As statements from multiple scientific and medical organizations indicate, that is currently not the case for the common MTHFR variants.

[Nackapan]

That happened to me. I was only taking uo to 400mcg daily. Went above 20. I dont need more than 200mcg 3 x a week that's in a multivit.

Annoying the lab didnt test folate last time even though on the form . Offered to do it again but I'm leaving it until next blood test.

I do eat folate rich foods. One thing I can absorb!!

My daughter on the other hand needs 400mcg daily ??

Go by bloods.

[deepocean in reply to Nackapan]

Do you inject B12?

[Nackapan in reply to deepocean]

Yes

[humanbean]

One comment I want to make...

If you want to take any kind of supplement nobody is holding a gun to your head forcing you to take it every day.

I take supplements and for some of them at least, I buy a larger dose than I would need to take every day, and only take it perhaps 2 days a week or whatever. I always do my research to decide if this is safe or sensible first. The aim, of course, is to save money.

[fbirder in reply to humanbean]

Except that you cannot 'bank' most supplements.

It's like only eating once a week, but eating 14,000 calories on that day. It ain't gonna work.

[humanbean in reply to fbirder]

It depends on whether they are fat soluble or water soluble.

The fat soluble ones can become toxic if taken at too high a dose for too long a time which is why testing is a good idea.

Even the water soluble ones almost certainly differ in how long it takes for them to be excreted. They may well hang around in the liver or other tissues for a while.

I doubt that all vitamins and minerals are excreted within 24 hours of consumption in the form of supplements or even in the form of food.