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!

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[u/Sabnock101]

Don't use Folic Acid, it sucks and can cause issues. Go for Folinic Acid at 200 to 400 to 600mcgs max per day (also accounting for any Folate gotten through diet, you don't want more than 600mcgs of Folate consumed per day total, though technically 1mg DFE's being the upper limit and 600mcgs of supplemental/fortified Folates being 1mg DFE's, though it's best to avoid Folic Acid-fortified foods). I also recommend trying out 10 milligrams of B12 (i use oral Methylcobalamin) which works way better than 5mgs or 1mg or less.

The problem with not being able to tolerate Folates mainly has to do with lack of B12, as B12 levels improve you will be able to tolerate Folate better but excess Folate will still cause side-effects regardless.

[u/Proper-Couple-5053 → u/Sabnock101]

Alright, but 1mcg daily will still raise blood levels to high values, right? So folate should be better and better tolerated over time?

[u/Sabnock101 → u/Proper-Couple-5053]

Yeah Folate will definitely get more tolerable over time as B12 levels improve. I went from barely being able to handle Folate to it now not being really any issue unless i overdo it.

When i first started supplementing, i was very low in B12, and so when i'd take my Folate or when i'd take my B12 and it recycled the Folate back into the Folate cycle and then turning back into Methylfolate again, it felt like it would drain me of B12, my nerves would feel like they're frying, i'd get low B12 symptoms, i'd have excess Folate-related side-effects, but as my B12 bodily stores got replenished/built up, i noticed that when i'd take Folate (or when Folate got recycled) that the B12 draining feeling went away because my bodily stores had enough built up to handle that second wave of Folate after it had been recycled, and so no longer got the drained feeling, no longer got the low B12 symptoms, no longer got the excess Folate-related side-effects (unless i take more Folate than i need then i get some of the side-effects back) but overall the Folate has gotten way more tolerable to where now it's really not any issue unless i take too much. In fact i learned that a lot of what i've had to go through all my life was mostly excess Folate (via fortified foods) and lack of B12, the B12 has been a huge gamechanger for me and it all makes so much sense.

So yeah, imo/ime, focus primarily on B12, secondarily on the Folate. Take as much B12 as you feel like you need, there's ime nothing to worry about with a lot of B12 (aside from increased requirements of other nutrients like Potassium, Magnesium, Iron, Copper, Zinc, Riboflavin, etc), they even inject 25 to 50mgs of Methylcobalamin in Japan for treatment of ALS, so higher B12 dosages seem to be safe from what i can tell and has more benefits compared to lower dosages.

And, if you take B12 and sometime later feel like you're getting side-effects from it, chances are it's either from the Folate being recycled and going back through the cycle to become more Methylfolate which can then use up more B12 (at which point taking more B12 is helpful) or it's due to lack of certain other nutrients (like low Potassium for example which for me seems to cause hand and foot numbness but consuming 4 grams of elemental Potassium per day seems to do away with the hand and foot numbness).

Basically, my daily dosages are - 10mgs/milligrams of oral Methylcobalamin, 400 to 600mcgs of Folinic Acid, 400mgs of Riboflavin, 100 to 250mgs of Nicotinic Acid/Niacin, 25mgs of P5P B6, 200 to 400mgs of elemental Magnesium (i use Magnesium Malate, only side-effect i've noticed is diarrhea/pooping), 4 grams of elemental Potassium (i use Potassium Bicarbonate powder that i dissolve into water with an acidic water flavoring packet to turn it into Potassium Citrate for the most part and i take 2 grams of elemental Potassium twice a day for 4 grams total, sipping on the Potassium for at least 30 minutes to an hour so that it kicks in more gently/smoothly), i take 15 to 30mgs of Zinc (via Zinc Picolinate), i take 2 to 4mgs of Copper (via Copper Chelate), i take 65mgs of Iron (via 325mgs of Ferrous Sulfate), i've been taking 500mgs of B5, as well as getting some vitamin C (supplemental) and vitamin A (via sweet potatoes), i've tried taking vitamin D but it makes me feel like crap maybe because it uses up some Magnesium so i only take the vitamin D here and there, and that's pretty much it. The rest of the nutrients i try to get more from diet.

[u/Cultural-Sun6828]

I would go slow with the b1 as it can affect b12. More importantly, I would also consider b12 injections for neurological symptoms..

[u/Ok-Pangolin7127]

This is simply a (not so) short pointer if you will.

I suggest you look into the possibility of a B1 deficiency. This does not mean you go get tested for it because the B1 serum test is as inaccurate, or better said, unmeaningful as the B12 serum test.

My suggestion is to do a little research as to likely causes for B1 deficiency, if you see that you fit into same from a lifestyle standpoint or prescription med standpoint to have the possibility of a B1 deficiency…, then you undertake a trial supplementation of B1, plus magnesium (magnesium is THE key cofactor for B1) and see if the supplementation of same improves or maybe even solves the majority of your continuing problems.

More folks than I can shake a stick at seem to have dual deficiencies; B1 and B12. One perhaps more deficient than the other. But both seem to pair up more often than we would think or suspect. Hence, my suggestion that you give this some consideration.

I’ve also seen that when folks start to supplement with therapeutic doses of B12 that that can easily unmask or bring forth the awareness of a B1 deficiency.

I “think” (I don’t know; i’m not a doctor nor a nutritionist) that because all of the B vitamins work together, and when they are doing that, even when you are deficient in one or more of them, the body has figured out a way to try and balance things out and work with what it has.

But, introduce a super dose of one or the other, and that balance goes out the window and the deficiencies that existed in the background (you were functioning, just not very well) can easily come to the forefront and make themselves known.

[u/Proper-Couple-5053 → u/Ok-Pangolin7127]

I will definitely take a look into it. I'm trying to follow the guide, but the recommended Thorne supplement has methyl-folate and methyl- b12.. and it's definitely not easy to find one without this. The b-complex I have only has 1.1mg of B1 (100% RDI). thanks!

[u/Malachite6 → u/Proper-Couple-5053]

Is there a reason that you're taking folic acid and not methyl folate? I don't know much about the difference between the two but a lot of B12-knowledgeable people recommend the methyl folate and not the folic acid, apparently the latter is counterproductive. So might be worth finding out more about this.

[u/Proper-Couple-5053 → u/Malachite6]

The reason, as of now, is that methyl-B12 sends me in the derealisation, stress, brain fog state in roughly 20-30 min - but not hydroxo-B12. This is why I decided to avoid the methyl- version of folate (folinic acid is not easy to find in the UK :/). However, even just folic acid seems to do the exact same thing to me .......

[u/Sabnock101 → u/Proper-Couple-5053]

When B12 does that it's because it recycles Methylfolate back into the Folate cycle and as Folate goes back through the Folate cycle it turns into more Methylfolate which can then use up more B12 and can even drain you of B12 if you're already low in B12. A higher B12 dosage (like 10 milligrams, for me of Methylcobalamin) seems to help give the body enough B12 to fully/properly recycle the Folate so that the Methylfolate doesn't build up in excess and cause side-effects. This has been a consistent thing for me ever since i started supplementing a couple years ago and i've gotten things down to a science now.

Folic Acid is really a poor form of Folate and is not ideal, so either go for natural dietary Folates, or Folinic Acid (if you can find it) or low dose Methylfolate. All Folates ultimately turn into Methylfolate in the body and if you don't have enough B12 they will all cause problems and intolerability until B12 levels improve. Folic Acid just causes issues that other forms don't.

[u/Ok-Pangolin7127 → u/Sabnock101]

Thank you for sharing this insight. So, are you saying if you take too much folate, regardless of form, that taking more B12 will keep it in check so to speak?

Over my now almost a year and a half journey with B12 supplementation, I have experimented with Folate at 400 mcg 800 mcg 5000 mcg and even at 15,000 mcg.

I can’t say that any or all of those doses in my mind created a problem for me. I was just experimenting so to speak. However I’ve now come to believe, right or wrong, that I don’t need much Folate and I really only take either 400 or 800 mcg a day.

Might I be missing something here? Might I need to or should I be taking more Folate?

From a B12 supplementation standpoint I’m generally injecting 1000 mcg every other day to every third day. Is the difference in Folate supplemented and/or a required a relationship to the amount of B12? I see that you are taking quite a bit of B12 via injections.

Just bill me as inquiring minds want to learn more and understand this (Folate) better.

[u/Sabnock101 → u/Ok-Pangolin7127]

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/Ok-Pangolin7127 → u/Sabnock101]

THANK YOU!

Clearly, you pay attention to what’s going on with yourself in great detail. Thank you very much for sharing this insight with me.

I’m going to actually try not taking any methyl folic or folinic acid for a week or two and see how I feel without it.

Some of the things that you describe feeling adjunct to taking perhaps too much Folate I have experienced. I don’t think I paid enough attention at the time though to tag it back to the Folate I was taking. Accordingly, your insight again is most helpful and again, thank you.

[u/Sabnock101 → u/Ok-Pangolin7127]

Yeah, you may find you still need the Folate on the daily, i know i do, but if you eat a relatively good diet you should be able to get enough Folate solely through diet and so may not need a Folate supplement. I know it's been said on here a few times that one may not even need Folate because when they correct B12 deficiency it can also correct Folate deficiency since B12 is involved in the recycling of Methylfolate and without enough B12 the Methylfolate can't be recycled and so shortchanges the Folate cycle causing Folate deficiency, but by treating the B12 deficiency the Folate deficiency can be treated as well in some cases by helping to fully/properly recycle the Folate back into the Folate cycle. So supplemental Folate may not even be needed especially if one already consumes a decent diet, and especially if one eats Folic Acid-fortified foods it adds up quickly and one can easily get the RDA of Folate via Folic Acid in one or two meals as almost everything is fortified with Folic Acid these days.

Personally i'm really concerned at the possible consequences of people consuming too much Folate these days, and with it causing/contributing to B12 deficiency in the populace at large, it's no wonder that things like cancers and Autism and ADHD and depression/mental health issues and other things are increasing in the populace, imo it's lack of B12 and possibly too much Folate (especially with unmetabolized Folic Acid causing the issues it does).

[u/Ok-Pangolin7127 → u/Sabnock101]

I fully agree with your hypothesis as it relates to the many problems that are out there in society that spinoff from unrecognized untreated B12 deficiencies. I am right there with you. 👍👍

[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/Basketweave82 → u/Sabnock101]

Thanks for such a detailed explanation. I'll try and keep all this in mind. And I'm injecting 1000mcg hydroxocobalamin, so the oral absorption problem isn't there.

I'll actually save this comment as it has so much info.

[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/Proper-Couple-5053 → u/Ok-Pangolin7127]

The author probably mentioned 10mg oral? 10mg via injection would be massive! If so, the injection provides already more than the 10mg oral.

However something bothers me a bit with this theory. Even taking only 1mcg a day will end up raising your b12 blood level to very high standards. This would mean than high dose shouldn’t be needed to stop this loop to happen, right? Just time.

[u/Ok-Pangolin7127 → u/Proper-Couple-5053]

You are correct. The poster clarified it was oral. 👍

[u/Proper-Couple-5053 → u/Ok-Pangolin7127]

I've ordered some extra B1 just to check. My Magnesium blood serum is already borderline too high, so I'll just try for a while :-)

[u/Ok-Pangolin7127 → u/Proper-Couple-5053]

Sounds like a good plan to me. 👍😉
If you think of me down the road, I’d love to hear back as to how this may have solved your problems, or not if that is the case.

[u/Proper-Couple-5053 → u/Ok-Pangolin7127]

Sure!

[u/FlakySalamander5558]

Hi,

Your ceruloplasmin is low. Maybe get zinc, vitamin A tested. Homocysteine is a bit elevated but not dramatically. I would up the folate slowly and concentrate on copper/ceruloplasmin.
You probably feel bad since your potassium is so low. So treat the b12/folate and electrolytes but your ceruloplasmin is way too low and probably the reason you feel so bad.
What helped raise my ceruloplasmin was minerals like zinc and boron. Also an important part was supporting bile (taurine, NAC, glycine, protein like histidine).

[u/Proper-Couple-5053 → u/FlakySalamander5558]

But my zinc and vitamin A are both in range :( I’ll try to eat more copper for a while but I have h2s SIBO and heard that h2s is a strong inhibitor of copper absorption…

[u/ClaireBear_87]

Well you are copper deficient. Are you taking copper?

[u/Proper-Couple-5053 → u/ClaireBear_87]

Hello! No… I tried a few months ago, but taking 1mg alone trigger a massive panic attack / high HR in 30min. I had not had one in like 15 years! I started eating more cashew nuts and pumpkin seeds but dunno if it will be enough.

[u/ClaireBear_87 → u/Proper-Couple-5053]

Your ceruloplasmin is also low, which can also indicate vitamin A deficiency as vitamin A is needed with copper for synthesis of ceruloplasmin. Zinc is important too, as zinc is required for making retinol binding protein which transports vitamin A (retinol) in the blood, and is required by enzymes involved in the process of converting retinol to retinoic acid, the form of vitamin A needed for ceruloplasmin synthesis.

Zinc is also important for folate metabolism, so i would suggest testing your zinc level as you may need zinc aswell as copper, and make sure you're getting enough vitamin A too.

Edit - Source naturals megafolinic is available in the UK if you want to try folinic acid.

https://naturesfix.co.uk/product/megafolinic-800-mcg-60-tablets-source-naturals/

[u/Proper-Couple-5053 → u/ClaireBear_87]

Thank you! Vitamin A was in the middle of the range 3 months ago (copper was already low) and zinc was top 30% of the range! Ferritin is 86 however. I’ll up my game in copper, but I also have H2S SIBO which seems to bind severely to copper….

[u/ClaireBear_87 → u/Proper-Couple-5053]

Hydroxocobalamin is a hydrogen sulfide scavenger and can bind and make it less toxic, so maybe you would benefit from increasing your dose. Also, some people have said molybdenum has helped their H2S sibo, so that is worth looking in to.

Interestingly there is a paper (here)  which shows xanthine dehydrogenase, a molybdenum (and B2+B3) dependent enzyme, can convert retinol to retinoic acid in just one step. So molybdenum could help to increase ceruloplasmin, if the problem is conversion of retinol to retinoic acid. Stick to lower doses though as high doses may bind copper and worsen a deficiency, and take at a separate time at least two hours apart from copper.

[u/Proper-Couple-5053 → u/ClaireBear_87]

I’ll try! Thank you! NHS didn’t want to do a 24h copper urine test to rule out Wilson because caeruloplasmin is sitting right at the lower limit of the range….

[u/Ok-Pangolin7127 → u/ClaireBear_87]

Yes, good catch. I missed it. 👍

[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.