7 ms·

> Vitamin B12 deficiency can cause PGH through unknown mechanism. About 55% of patients with pernicious anemia had graying before 50 years as compared to 30% in

by notamy 2y ago

> Vitamin B12 deficiency can cause PGH through unknown mechanism. About 55% of patients with pernicious anemia had graying before 50 years as compared to 30% in the control group.[32] /soapbox Get your B12 tested (before taking supplements!). B12 deficiency is known to present in many ways, and also to be often overlooked in clinical settings[1]. It’s known that not everyone presents with the anaemia from it[2], which is often why it’s skipped as a diagnostic option. Additionally, long-term/severe deficiency can present with symptoms almost identical to multiple sclerosis[3]. Deficiency of other B vitamins, such as B2, can cause a functional B12 deficiency as well[4]. It’s also known that supplementation will falsely elevate levels even in the presence of a deficiency. /unsoapbox [1] https://www.mcpiqojournal.org/article/S2542-4548(19)30033-5/fulltext https://www.mcpiqojournal.org/article/S2542-4548(19)30033-5/... [2] https://www.bmj.com/content/383/bmj-2022-071725 https://www.bmj.com/content/383/bmj-2022-071725 [3] https://researchonline.nd.edu.au/cgi/viewcontent.cgi?article=1215&context=health_article https://researchonline.nd.edu.au/cgi/viewcontent.cgi?article... [4] https://www.iomcworld.org/articles/paradoxical-vitamin-b12-deficiency-normal-to-elevated-serum-b12-with-metabolic-vitamin-b12-deficiency.pdf https://www.iomcworld.org/articles/paradoxical-vitamin-b12-d...

jimbob45 2y ago
It’s also known that supplementation will falsely elevate levels even in the presence of a deficiency. It sounds to me that what you’re saying is that a daily multivitamin would not help in this case.
- notamy 2y ago
  It may help, but it will also throw off lab tests while you’re taking it and for a time after. Also, B12 absorption depends strongly on good gut health (ex. no SIBO[1], low gastric acid, pernicious anaemia, etc.), as well as on other medications (ex. metformin[2]) not interfering with absorption. [1] https://en.wikipedia.org/wiki/Small_intestinal_bacterial_overgrowth https://en.wikipedia.org/wiki/Small_intestinal_bacterial_ove... [2] https://en.wikipedia.org/wiki/Metformin https://en.wikipedia.org/wiki/Metformin CTRL-F "B12"
  - FollowingTheDao 2y ago
    Genetics will play a huge role in B12 absorption. Transcobalamin to be specific. https://ashpublications.org/blood/article/114/22/1989/111148/Mutations-of-TCN1-Cause-Transcobalamin-I https://ashpublications.org/blood/article/114/22/1989/111148...
- OutOfHere 2y ago
  Most multivitamins are useless because they generally contain suboptimal forms, doses, and ratios. If you want to see good effects, consider individual vitamins in appropriate forms and doses.
  - SOLAR_FIELDS 2y ago
    It’s one of the reasons that regulation would help a lot here. One simple example is chelation. Your body absorbs magnesium when it’s chelated at a rate many multiple times higher than what you might typically get from an OTC multivitamin. So a multivitamin might contain some magnesium, but what it doesn’t tell you on the label is that the form of magnesium they give you is not going to be absorbed at all and just pass right through your body. Most people need some other formulation of magnesium to actually be absorbed. I would go so far as to say that a fair amount of what goes into a lot of multivitamins on the label is borderline fraud because of stuff like this
  - dotancohen 2y ago
    The barrier to entry is far too high for most people. A safe, minimal dosage that will help in cases of severe deficiency can be had with an inexpensive pill and negligible time investment. Regular blood tests and dosing is expensive in mental effort, time, and money.
    - OutOfHere 2y ago
      A regular blood test is mainly needed just for vitamin A, vitamin D, and sometimes for vitamin B6. The rest won't silently cause critical issues if somewhat exceeded. As for minerals, it is possible to manage the dose without a need for testing.
      - dotancohen 2y ago
        Thank you. I will go get those tests.
        OutOfHere 2y ago
OutOfHere 2y ago
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.
SOLAR_FIELDS 2y ago
The reason I take B12 as a supplement is unrelated to this - I have MTHFR mutation and as such I need to take methyl folate (methylated B9). Apparently this form of B9 absorbs better if it’s combined with the methylated form of B12 (methylcobalamin) I guess if it will keep my hair color longer that’s a nice side effect!
- notamy 2y ago
  > Apparently this form of B9 absorbs better if it’s combined with the methylated form of B12 (methylcobalamin) B9 and B12 are interdependent. When the body uptakes cobalamins, the ligands are pulled off and replaced with ligands sourced from other processes. IIRC in the case of methylcobalamin, the methyl group is pulled off and replaced with a methyl group that’s moved over from methylfolate via a riboflavin-dependent reaction. Been a hot minute since I looked into this so I may have some details incorrect.
snthpy 2y ago
Interesting. I had it 5 years ago and then it went away. It started again a few weeks ago and I halved my vitamin B supplementing a while before that.
pcb-rework 2y ago
I take supplemental B12 and a B-complex because I get hair thinning, brittle nails, and peripheral edema and neuropathy without them. (Also taking levothyroxine and slo iron.) I feel way better with it than without it, and it ain't placebo because I have a terrible habit "memory", forget it often, and remember forgetting after my feet remind me. There's a noticeable point 30 to 90 minutes later at which they spontaneously feel better, but I completely forget about taking or not taking them. (I really need a pill planner like an old person.) I wasn't aware of the apparent connection until after numerous episodes and connecting the two.
- OutOfHere 2y ago
  Use a pill box. It's not just for old people. It's good for everyone.
Solstinox 2y ago
Also, over half the world's population has H. Pylori, which interferes with B12 absorption.

by notamy 2y ago

jimbob45 2y ago

It’s also known that supplementation will falsely elevate levels even in the presence of a deficiency. It sounds to me that what you’re saying is that a daily multivitamin would not help in this case.

notamy 2y ago
It may help, but it will also throw off lab tests while you’re taking it and for a time after. Also, B12 absorption depends strongly on good gut health (ex. no SIBO[1], low gastric acid, pernicious anaemia, etc.), as well as on other medications (ex. metformin[2]) not interfering with absorption. [1] https://en.wikipedia.org/wiki/Small_intestinal_bacterial_overgrowth https://en.wikipedia.org/wiki/Small_intestinal_bacterial_ove... [2] https://en.wikipedia.org/wiki/Metformin https://en.wikipedia.org/wiki/Metformin CTRL-F "B12"
- FollowingTheDao 2y ago
  Genetics will play a huge role in B12 absorption. Transcobalamin to be specific. https://ashpublications.org/blood/article/114/22/1989/111148/Mutations-of-TCN1-Cause-Transcobalamin-I https://ashpublications.org/blood/article/114/22/1989/111148...
OutOfHere 2y ago
Most multivitamins are useless because they generally contain suboptimal forms, doses, and ratios. If you want to see good effects, consider individual vitamins in appropriate forms and doses.
- SOLAR_FIELDS 2y ago
  It’s one of the reasons that regulation would help a lot here. One simple example is chelation. Your body absorbs magnesium when it’s chelated at a rate many multiple times higher than what you might typically get from an OTC multivitamin. So a multivitamin might contain some magnesium, but what it doesn’t tell you on the label is that the form of magnesium they give you is not going to be absorbed at all and just pass right through your body. Most people need some other formulation of magnesium to actually be absorbed. I would go so far as to say that a fair amount of what goes into a lot of multivitamins on the label is borderline fraud because of stuff like this
- dotancohen 2y ago
  The barrier to entry is far too high for most people. A safe, minimal dosage that will help in cases of severe deficiency can be had with an inexpensive pill and negligible time investment. Regular blood tests and dosing is expensive in mental effort, time, and money.
  - OutOfHere 2y ago
    A regular blood test is mainly needed just for vitamin A, vitamin D, and sometimes for vitamin B6. The rest won't silently cause critical issues if somewhat exceeded. As for minerals, it is possible to manage the dose without a need for testing.
    - dotancohen 2y ago
      Thank you. I will go get those tests.
      - OutOfHere 2y ago

OutOfHere 2y ago

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.

SOLAR_FIELDS 2y ago

The reason I take B12 as a supplement is unrelated to this - I have MTHFR mutation and as such I need to take methyl folate (methylated B9). Apparently this form of B9 absorbs better if it’s combined with the methylated form of B12 (methylcobalamin) I guess if it will keep my hair color longer that’s a nice side effect!

notamy 2y ago
> Apparently this form of B9 absorbs better if it’s combined with the methylated form of B12 (methylcobalamin) B9 and B12 are interdependent. When the body uptakes cobalamins, the ligands are pulled off and replaced with ligands sourced from other processes. IIRC in the case of methylcobalamin, the methyl group is pulled off and replaced with a methyl group that’s moved over from methylfolate via a riboflavin-dependent reaction. Been a hot minute since I looked into this so I may have some details incorrect.

snthpy 2y ago

Interesting. I had it 5 years ago and then it went away. It started again a few weeks ago and I halved my vitamin B supplementing a while before that.

pcb-rework 2y ago

I take supplemental B12 and a B-complex because I get hair thinning, brittle nails, and peripheral edema and neuropathy without them. (Also taking levothyroxine and slo iron.) I feel way better with it than without it, and it ain't placebo because I have a terrible habit "memory", forget it often, and remember forgetting after my feet remind me. There's a noticeable point 30 to 90 minutes later at which they spontaneously feel better, but I completely forget about taking or not taking them. (I really need a pill planner like an old person.) I wasn't aware of the apparent connection until after numerous episodes and connecting the two.

OutOfHere 2y ago
Use a pill box. It's not just for old people. It's good for everyone.

Solstinox 2y ago

Also, over half the world's population has H. Pylori, which interferes with B12 absorption.