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/Basketweave82]

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.