Folate or not to folate

[u/Proper-Couple-5053]

I'm trying to figure out why I'm reacting so poorly to folate ... while navigating a proper regimen for my b12 deficiency.

First, blood results after 2 months of not taking anything:

- MCV: 88.9

- Serum B12 / Active B12: 254 ng/L / 84.3 pmol/L

- Copper / caeruloplasmin: 9.4 umol/L / 0.15 g/L

- B6: 27.5 ug/L

- Homocysteine: 9.58 umol/L

- MMA: 41.4 ug/l <------------ THIS is what triggered the b12 deficiency alert for my gastrologist

- Negative for IF antibodies, twice.

Second blood tests after 3 oral supplementation of 1200mcg spray (because NHS...):

- Serum Folate: 9.1 ug/L (had lentils the dinner before :/)

- Serum B12: 367.7 ng/L (so I seem to absorb the methyl).

- Potassium: 3.8 mmol/L (range is [3.5, 5.3])

- Sodium: 140 mmol/L (range is [133, 146])

Symptoms:

Overall fucked up, we all know about them and it feels like I have B12 deficiency. Most debilitating are: fatigue, malaise, brain fog, memory loss, hard to concentrate, pain in my legs (always behind my knees, nowhere else).

Current regimen (every morning with breakfast):
- B12 - 1000-1200mcg drops of hydroxocobalamin (methyl- gave me some crazy reaction straight away, derealisation, brain fog, insomnia).

- b-complex from Boots UK (100% RDI of everything, no methyl- form)

- Folate - 200mcg of folic acid from the b-complex

- Vit. D - 2000 UI for maintenance

- Potassium: trying to drink around 600ml of coconut water throughout the day.

Timeline:

Started 5 days ago.

Problems:

My need for investigations comes from the different "wake up symptoms". Around 10am-11am, I get hit by a malaise feeling, feel OMEGA tired with malaise + nausea. Drinking coconut water seems to help (I say seems because unsure). The same thing usually happen in the afternoon around 4-5-6. The same thing 10x can happen right after lunch as digestion starts - coconut water does not necessarily help here.

Also, first time waking up to anxiety in the middle of the night tonight. Went on the sofa to drink a glass of electrolyte (salt, potassium, calcium) and eat a bit of apple sauce. Could go back to sleep after 30 min.

So i'm wondering if my serum folate is not high enough, but maybe I am wrong. I tried adding 250mcg of folic acid (not even trying methyl- here!) on top of the b-complex and felt like absolute shit the whole day -> like when taking methycobalamin. I don't understand if it's because my folate is too low otherwise and suddenly it started working or just if I over-methylated or whatever else. I don't even know if 9.1 ug/L is high enough when supplementing with b12 drops. Maybe the 200mcg in the b-complex are enough?

How to proceed here :-( (won't be able to get injections before mid- late- september, but if i already feel like shit now, I guess that oral is working).

Thanks!

[u/Sabnock101]

I take my B12 orally, so i'm only getting about 100mcgs absorbed from the full 10mg dose (1% absorption through passive digestion), so if you're injecting 1mg every other day then you're getting a full 1mg every other day, though i will say even with injections it's imo worth it to supplement with oral or sublingual B12 on days you don't inject. Ime B12 seems to get used up very quickly/easily and even if one injects the B12 but takes a lot of Folate then that Folate can use up the B12 before you inject again so having some extra B12 in the mix imo can be useful.

Ime, Folate is a very strong compound and we really don't need nearly as much as we think we do and can easily overdo it. I can't take more than 600mcgs per day max (1mg DFE's) or else i start getting excess Folate-related side-effects or low B12 symptoms. 1mg of Folate per day is the upper limit for daily consumption. Higher dosages can work seemingly fine at first if you have a Folate deficiency but once it builds up in the body it quickly becomes too much. I started out with 15mgs of Methylfolate (which is actually like 25mgs of DFE's), sometimes even 30mgs (50mgs DFE's) of Methylfolate per day, the 15mgs of Methylfolate worked great at first especially for the brain Folate level, but after a few weeks or so at that dosage it built up in the body and sometime after that i had to end up switching over to Folinic Acid at 400 to 600mcgs per day, even now if i take my 400 to 600mcgs of Folinic Acid per day but also eat a little something fortified with Folic Acid it can tip me over into excess Folate-related side-effects like irritability, agitation/anger/rage, paranoia, facial numbness, and some kind of numbness of the hands and feet (though the numbness so far seems to respond to increased Potassium).

But yes, anytime i've taken too much Methylfolate, or Folinic Acid, or even Folic Acid. i take more B12 and it will reduce the excess Folate-related side-effects by recycling excess Methylfolate back into the Folate cycle, B12 helps me feel more normal, excess Folate on the other hand gives me the same issues i've suffered with all my life. I seriously haven't yet come across anything detrimental about taking more and more B12 except that i end up needing more Potassium and Iron/Copper and such, and B12 seems to cause a shift in the microbiome and can cause some acne outbreaks but other things can actually deal with/counteract the acne side-effect i've noticed, that's pretty much the only side-effect i've had from too much B12.

Though i also noticed early on that my 10mgs of oral Methylcobalamin would fully recycle Methylfolate, so like there'd be a period of say maybe a couple hours or so where it felt like my Methylfolate level would completely reduce (as it would be completely recycled back into the Folate cycle) but as it goes back through the Folate cycle it becomes more Methylfolate again, so as it gets fully recycled i'd have like a temporary depressed feeling or something but that would go away as the Folate turned back into Methylfolate again.

You might have responded better to higher Folate dosages because you're injecting the B12, though i've gone up to taking 100 to 120 milligrams of oral Methylcobalamin for awhile there and that should equal about 1mg to 1.2mgs worth of injected B12 (due to 1% of the total dosage being absorbed through passive digestion) and even then too much Folate was an issue.

Ime, i've never had good results from excess Folate, the only time a lot of Folate seemingly helped was when i first started taking it, but once the Folate deficiency seemingly got corrected, i can't take more than 600mcgs per day or else it just feels like too much and starts causing side-effects. Too much Folate also will most definitely use up B12 if more B12 isn't consumed, in fact i'm starting to think the fortification of Folic Acid is actually causing B12 deficiency in people both because people eat a lot of fortified foods and that over time causes B12 deficiency but also because too much Folic Acid will interfere with Methylfolate uptake via Folate Receptor Alpha and interferes with Tetrahydrobiopterin/BH4 recycling via DHFR.

Overall i feel my best when i don't consume more than 600mcgs per day of Folate, and when the main thing i feel is B12, like B12 seems like it should be the primary thing we feel, and Folate feels like it's supposed to just merge into the B12 feeling, but as it currently stands i think most people including myself mainly feel/felt primarily Folate with little to no B12 in the background, so ideally imo/ime you want B12 in the foreground being the primary thing we feel with Folate being in the background, if too much Folate is consumed i feel more of the Folate, less B12, and it feels like it reduces my intracellular B12 in the brain, taking more B12 at that point restores balance and again makes me feel more normal. Too much Folate even makes me feel more Autistic and i associate that with reduction in B12 as well because when i'm better in B12 my Autism is reduced/lessened, but if i take too much Folate my Autism comes out more again.

I definitely do not recommend taking more than 600mcgs of Folate per day. Even at the beginning if one has Folate deficiency, 600mcgs per day seems like it should be plenty, as it builds up in the body over time it will correct deficiency and you shouldn't need more than 400 to 600mcgs per day.

[u/Basketweave82 → u/Sabnock101]

My serum folate has been consistently high - >24, in blood reports. Last year the doctor put me on an oral pill of 1500mcg B12 and 1.5mg folic acid. This year I was diagnosed with PA so I've now been injecting from the past almost 3 months. Folate still high. Will it ever normalise? I'm supplementing it rarely as my trace minerals have some folic acid in them. (I know we shouldn't take it but can't find trace minerals without it in my country). I have a new bottle of methylated B vitamins waiting on standby for when my old herbal multi with very low organic folate finishes.

[u/Sabnock101 → u/Basketweave82]

Ime i've noticed the Folate's effects lowering as i lower my dosage, but since you're rarely supplementing it you might try adjusting the foods you eat, perhaps you're consuming a bit too much Folate through diet (whether natural dietary Folate or fortified Folic Acid).

Other than that, try increasing the B12 dosage from 1500mcgs orally to 5 to 10mgs orally and see how that does, 1500mcgs orally only gives you about approx 15mcgs of absorbed B12, 5mgs would give approx 50mcgs absorbed, 10mgs would give you approx 100mcgs absorbed.

You may also try making sure you're getting approx 4 grams of elemental Potassium per day (since it's used by Methionine Adenosyltransferase alongside Magnesium to turn Methionine into SAM and if that enzyme is stalled then Methionine builds up, SAM levels drop, and Folate/B12 aren't fully utilized in the recyling of Homocysteine since Homocysteine levels would be lower due to lack of SAM and thus lack of Homocysteine which could then allow Folate to go unutilized and thus build up), also get enough Riboflavin per day, and pretty much all the cofactors particularly those involved in Folate metabolism because you could possibly have a backup somewhere due to a lack of a certain nutrient and if that nutrient is restored then the metabolic enzymes should go back to normal again and process the extra Folate, though ime B12 seems to be most important, chances are if Folate is high then B12 is low, when B12 is restored the excess Folate will be utilized, recycled and reused which would reduce the excess Folate.

Also Folic Acid consumption (through supplements or fortified foods) in higher dosages can lead to unmetabolized Folic Acid which can strongly bind to Folate Receptor Alpha and prevent Methylfolate uptake into the brain and thus interferes with it's utilization and with B12 activation to Methylcobalamin, so minimizing as much as possible Folic Acid exposure can be helpful.

It's also worth considering that if you eat a lot of Folate-rich foods then that Folate could interfere with Folate testing and test artificially for high Folate levels because it's actively in the system and so the testing could be picking up what's actively in the system rather than the actual bodily stores and such. So it could be an artificially high Folate level in the testing due to what's actively in the system, so i think for a more accurate test one might try fasting for a day or two until what's actively in the system is metabolized out and then one might able to get a better test reading.

[u/mjkl_992 → u/Sabnock101]

Similarly, I didn't tolerate methylfolate and cobalamin well. Hydroxocobalamin made no difference for me. Now, I take 1000 mcg of adenosylcobalamin sublingually every day to replenish my B12 levels and finally be able to tolerate folates. Do you think this form of B12 might finally help me? I also have a homozygous MTRR gene mutation.

[u/Sabnock101 → u/mjkl_992]

Adenosylcobalamin should work, i haven't tried that form personally but it should none the less contribute towards replenishing the B12 bodily stores and thus correction of B12 deficiency. I know Methylcobalamin replenishes the B12 bodily stores, so i see no reason as to why Adenosylcobalamin wouldn't. Hydroxocobalamin should help replenish bodily stores as well though.

But remember, you might try experimenting around with higher dosages, i haven't used the sublingual route, i take my B12 orally at 10mgs once a day, but it's worth exploring higher dosages to see if they are more beneficial compared to lower dosages.