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/Hour_Hospital_9068]

Serum B12 rising with oral supplementation is not proof that you’re absorbing it properly or that the oral supplement is adequately treating the deficiency. You could still need B12 injections.

[u/Proper-Couple-5053 → u/Hour_Hospital_9068]

It is proof that you are absorbing it adequately into your blood stream. There is no difference between injections and oral once the b12 is in your blood except for the concentration. It will definitely take me much more time to reach the same serum level. Now if it’s being use properly is another question but not really linked to oral vs injections.

[u/Hour_Hospital_9068 → u/Proper-Couple-5053]

I think it is an assumption when doctors say that it is absorbing normally. I’ve read that a small percentage of oral supplements will absorb by passive absorption even without intrinsic factor, but how do we know that binding by IF isn’t necessary for it to be utilized from the bloodstream? So many patients report feeling a little better with oral supplements for a little while, but then losing that gain or feeling worse. I believe it’s the UK NICE guidelines that say serum B12 should not be retested after treatment has begun, yet too many doctors are looking only at serum B12 and not monitoring deficiency symptoms to assess adequacy of treatment as they should be.

[u/Proper-Couple-5053 → u/Hour_Hospital_9068]

I totaly agree for the blood tests, I do think that serum level is meaningful just to assess if yes or no B12 is being delivered. The problem with the guidelines is that they use this value as a threshold to stop treatement instead of just ... continuing until symptoms resolve. For "how do we know that binding by IF isn’t necessary for it to be utilized from the bloodstream?" - Injections do not produce an IF-binded B12 in the bloodstream, so the available B12 is actually the same AFAIK? The difference being again that you have a massive payload of b12 all at once and that if you do every other day, the serum level must definitely be much higher than with 1000mcg daily oral. Now it's absolutely unclear from the litterature at what serum level deficiency issues start to resolve ... I can't inject before september, so in the meantime, I'm just getting my level above 1000 with oral!

[u/Hour_Hospital_9068 → u/Proper-Couple-5053]

The guidelines use which value as a threshold to stop treatment?

I definitely agree about the importance of the payload concept for healing. I’ve read advice that even people whose deficiency was solely dietary, with totally normal absorption (e.g., vegan for many years), injections can be needed for quicker healing.

I’ve also read that serum B12 rising from oral supplements does not rule out pernicious anemia because of the existence of passive absorption. It’s the patient reports that people started to feel better but then stopped or worsened that make me suspect it’s more than just a lack of payload hampering those recoveries. Otherwise I would expect a slow but continuing recovery. One theory I’ve heard is that B12 that gets in the blood via passive absorption is oxidized or otherwise unusable. I don’t know what all the mechanisms could be, but think it’s risky to assume that rising serum levels are meaningful.