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The paradoxical B12 deficiency might have a relation with the inactive form being supplemented. If one supplements cyanocobalamin, and one expects the body to c

The paradoxical B12 deficiency might have a relation with the inactive form being supplemented. If one supplements cyanocobalamin, and one expects the body to convert it to methylcobalamin, and if this conversion doesn't happen for whatever reason, and if the measured form includes the inactive form, then "paradoxical B12 deficiency" can be observed. There is a more insidious form of it whereby the active form doesn't enter the brain. Symptoms are: difficulty speaking, tremors and ataxia. This can be tested by CSF (cerebrospinal fluid) testing. This assumes that the active form is supplemented and it is present in blood. It can be remedied by a course of corticosteroid pills, followed by megadosing B12 orally daily. Refer to PMID 38924428. I take a triple active form of it which is methyl+hydroxy+adenosyl, covering all bases, but a total of just 500 mcg per day, above which it harms my sleep.

notamy 2y ago
> The paradoxical B12 deficiency might have a relation with the inactive form being supplemented. Yup, not everyone can convert cyanocobalamin or hydroxocobalamin to adenosyl-/methylcobalamin. Especially in severe cases, anecdotally I’ve seen people not make progress with the standard cyanocobalamin injections, but then make huge progress with methylcobalamin injections. Unfortunately, methylcobalamin is often not preferred in injectable form due to very quick degradation into hydroxocobalamin upon exposure to light.
- deleted 2y ago
  [deleted]
- FollowingTheDao 2y ago
  Subligual methylcobalamin works just as well as the shots and you can buy it anywhere. Also, get a Methylmalonic Acid Test with you B12 levels. An MMA test is more useful because it is an enz=yme which uses B12, so when the active form of B12 is low, so will MMA in most cases.
  - notamy 2y ago
    > Subligual methylcobalamin works just as well as the shots It does not. The cobalamin molecules are quite large and don’t penetrate the sublingual mucosa very well. On top of that, the proteins in saliva that bind to B12s will cause any bound B12 to not absorb sublingually, instead having to wait to make it through the digestive system for intestinal uptake. Sublingual is still certainly a better option than oral pills, but the injections are preferable in severe cases for a reason.
    - FollowingTheDao 2y ago
      > The cobalamin molecules are quite large and don’t penetrate the sublingual mucosa very well. Absolute nonsense. Did you even bother to look for one paper on the subject? Here are a few: https://www.scielo.org.mx/scielo.php?pid=S0034-83762020000600380&script=sci_arttext https://www.scielo.org.mx/scielo.php?pid=S0034-8376202000060... https://pubmed.ncbi.nlm.nih.gov/34871525/ https://pubmed.ncbi.nlm.nih.gov/34871525/ https://www.proquest.com/openview/e9a25963dbc92150e420a3a8475f6b24/1?pq-origsite=gscholar&cbl=1056335 https://www.proquest.com/openview/e9a25963dbc92150e420a3a847...
- cjsawyer 2y ago
  Taking methylcobalamin B12 supplements essentially fixed my memory problems. Early on I tried out the cyanocobalamin type and got absolutely nothing from it. If I stop taking the supplements for a few weeks, the memory problems come back. If I start again, a week later my memory is excellent. It’s well worth the minor effort.
  - Fire-Dragon-DoL 2y ago
    What kind of memory problems, could you expand? I wonder if I fall on this bucket. I had graying hairs as soon as I finished high school (~19). One of my major problems with studying was an inability to retain stuff in university, which is weird because through middle school a single read was sufficient for me to retain stuff.
    - cjsawyer 2y ago
      Mostly noun recall. I can mentally picture and describe thing or person X, but when I'm having the problem it could possibly take me 30 minutes to figure out the name of X without looking it up.
      - Fire-Dragon-DoL 2y ago
        When I don't sleep enough I definitely have that, but it's not a thing that occurrs otherwise. Thank you!
voisin 2y ago
Ok, so assuming you don’t want to have your CSF tested, is there any risk of harm to supplementing with the active form?
- OutOfHere 2y ago
  There's no risk in non-smokers if you stick to a sane dose. Megadosing it can harm sleep and severely increase blood pressure and heart rate, although these gradually reverse upon cessation. This can take time to manifest. It is why I limit the dose to 500 mcg per day. Older people, such as those over 70, can need more and tolerate more, even 5 mg per day, due to deteriorated absorption. Also, don't forget the other B vitamins. In truth I take them all.
  - vldmrs 2y ago
    Does it help you with grey hair ?
    - OutOfHere 2y ago
      No, it's useless to me in this regard, although it could help someone who is efficient. I think my issue may have more to do with copper.
  - notamy 2y ago
    > Megadosing it can harm sleep and severely increase blood pressure and heart rate https://www.researchgate.net/profile/Osama-Arafat/publication/234135338_METHYLCOBALAMIN_HAS_AN_EFFECT_ON_HYPOTHALAMIC-HYPOPHYSEAL-ADRENAL_AXIS/links/00b7d535ff904b4c57000000/METHYLCOBALAMIN-HAS-AN-EFFECT-ON-HYPOTHALAMIC-HYPOPHYSEAL-ADRENAL-AXIS.pdf?origin=publication_detail https://www.researchgate.net/profile/Osama-Arafat/publicatio... > METHYLCOBALAMIN HAS AN EFFECT ON HYPOTHALAMIC–HYPOPHYSEAL– ADRENAL AXIS In rats, but may apply to humans too.
  - Terr_ 2y ago
    > There's no risk in non-smokers if you stick to a sane dose. Also, B12 is water soluble, which generally means that your body is pretty good at flushing out any excess it can't use, making it difficult to overdose on. (Compared to fat-soluble substances.)
jdhendrickson 2y ago
Would you mind sharing a brand or a link? I have had grey hair since I was in my 20s and struggle with energy. I have been taking nature made multi vitamin for a vitamin b deficiency that was high enough to cause craggy edges on my tongue, caused by the stomach acid suppressant I was prescribed. I would like to compare.
- OutOfHere 2y ago
  https://www.amazon.com/gp/aw/d/B09G6ZDCDP https://www.amazon.com/gp/aw/d/B09G6ZDCDP Use it with a 2-way or 3-way pill splitter, just once piece per day. For acid, use famotidine to the extent possible, in as low a dose as does the job. For overnight suppression, however, omeprazole is useful.
  - jdhendrickson 2y ago
    Thanks!

notamy 2y ago

> The paradoxical B12 deficiency might have a relation with the inactive form being supplemented. Yup, not everyone can convert cyanocobalamin or hydroxocobalamin to adenosyl-/methylcobalamin. Especially in severe cases, anecdotally I’ve seen people not make progress with the standard cyanocobalamin injections, but then make huge progress with methylcobalamin injections. Unfortunately, methylcobalamin is often not preferred in injectable form due to very quick degradation into hydroxocobalamin upon exposure to light.

deleted 2y ago
[deleted]
FollowingTheDao 2y ago
Subligual methylcobalamin works just as well as the shots and you can buy it anywhere. Also, get a Methylmalonic Acid Test with you B12 levels. An MMA test is more useful because it is an enz=yme which uses B12, so when the active form of B12 is low, so will MMA in most cases.
- notamy 2y ago
  > Subligual methylcobalamin works just as well as the shots It does not. The cobalamin molecules are quite large and don’t penetrate the sublingual mucosa very well. On top of that, the proteins in saliva that bind to B12s will cause any bound B12 to not absorb sublingually, instead having to wait to make it through the digestive system for intestinal uptake. Sublingual is still certainly a better option than oral pills, but the injections are preferable in severe cases for a reason.
  - FollowingTheDao 2y ago
    > The cobalamin molecules are quite large and don’t penetrate the sublingual mucosa very well. Absolute nonsense. Did you even bother to look for one paper on the subject? Here are a few: https://www.scielo.org.mx/scielo.php?pid=S0034-83762020000600380&script=sci_arttext https://www.scielo.org.mx/scielo.php?pid=S0034-8376202000060... https://pubmed.ncbi.nlm.nih.gov/34871525/ https://pubmed.ncbi.nlm.nih.gov/34871525/ https://www.proquest.com/openview/e9a25963dbc92150e420a3a8475f6b24/1?pq-origsite=gscholar&cbl=1056335 https://www.proquest.com/openview/e9a25963dbc92150e420a3a847...
cjsawyer 2y ago
Taking methylcobalamin B12 supplements essentially fixed my memory problems. Early on I tried out the cyanocobalamin type and got absolutely nothing from it. If I stop taking the supplements for a few weeks, the memory problems come back. If I start again, a week later my memory is excellent. It’s well worth the minor effort.
- Fire-Dragon-DoL 2y ago
  What kind of memory problems, could you expand? I wonder if I fall on this bucket. I had graying hairs as soon as I finished high school (~19). One of my major problems with studying was an inability to retain stuff in university, which is weird because through middle school a single read was sufficient for me to retain stuff.
  - cjsawyer 2y ago
    Mostly noun recall. I can mentally picture and describe thing or person X, but when I'm having the problem it could possibly take me 30 minutes to figure out the name of X without looking it up.
    - Fire-Dragon-DoL 2y ago
      When I don't sleep enough I definitely have that, but it's not a thing that occurrs otherwise. Thank you!

voisin 2y ago

Ok, so assuming you don’t want to have your CSF tested, is there any risk of harm to supplementing with the active form?

OutOfHere 2y ago
There's no risk in non-smokers if you stick to a sane dose. Megadosing it can harm sleep and severely increase blood pressure and heart rate, although these gradually reverse upon cessation. This can take time to manifest. It is why I limit the dose to 500 mcg per day. Older people, such as those over 70, can need more and tolerate more, even 5 mg per day, due to deteriorated absorption. Also, don't forget the other B vitamins. In truth I take them all.
- vldmrs 2y ago
  Does it help you with grey hair ?
  - OutOfHere 2y ago
    No, it's useless to me in this regard, although it could help someone who is efficient. I think my issue may have more to do with copper.
- notamy 2y ago
  > Megadosing it can harm sleep and severely increase blood pressure and heart rate https://www.researchgate.net/profile/Osama-Arafat/publication/234135338_METHYLCOBALAMIN_HAS_AN_EFFECT_ON_HYPOTHALAMIC-HYPOPHYSEAL-ADRENAL_AXIS/links/00b7d535ff904b4c57000000/METHYLCOBALAMIN-HAS-AN-EFFECT-ON-HYPOTHALAMIC-HYPOPHYSEAL-ADRENAL-AXIS.pdf?origin=publication_detail https://www.researchgate.net/profile/Osama-Arafat/publicatio... > METHYLCOBALAMIN HAS AN EFFECT ON HYPOTHALAMIC–HYPOPHYSEAL– ADRENAL AXIS In rats, but may apply to humans too.
- Terr_ 2y ago
  > There's no risk in non-smokers if you stick to a sane dose. Also, B12 is water soluble, which generally means that your body is pretty good at flushing out any excess it can't use, making it difficult to overdose on. (Compared to fat-soluble substances.)

jdhendrickson 2y ago

Would you mind sharing a brand or a link? I have had grey hair since I was in my 20s and struggle with energy. I have been taking nature made multi vitamin for a vitamin b deficiency that was high enough to cause craggy edges on my tongue, caused by the stomach acid suppressant I was prescribed. I would like to compare.

OutOfHere 2y ago
https://www.amazon.com/gp/aw/d/B09G6ZDCDP https://www.amazon.com/gp/aw/d/B09G6ZDCDP Use it with a 2-way or 3-way pill splitter, just once piece per day. For acid, use famotidine to the extent possible, in as low a dose as does the job. For overnight suppression, however, omeprazole is useful.
- jdhendrickson 2y ago
  Thanks!