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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 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.

> 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.

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.

> 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.

> 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=S0034-8376202000060...

https://pubmed.ncbi.nlm.nih.gov/34871525/

https://www.proquest.com/openview/e9a25963dbc92150e420a3a847...

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.

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.

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.

When I don't sleep enough I definitely have that, but it's not a thing that occurrs otherwise. Thank you!

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

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.

Does it help you with grey hair ?

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.

> Megadosing it can harm sleep and severely increase blood pressure and heart rate

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.

> 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.)

A little extra B12 is easily flushed out, but when it's a lot, meaning several milligrams per day for many days, it can quickly and suddenly cause very elevated blood pressure and heart rate, e.g. 160 for both SBP and HR. This effect is easy to undo using a good beta blocker, e.g. atenolol, but if one doesn't, then an emergency hospital visit is required. The point is that despite being water soluble, this adverse effect does happen.

Even at just one milligram per day, it can significantly harm sleep.

It has a high circulating half life of six days, which implies that it can really build up if repeatedly megadosed in this period.

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.

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.

Thanks!

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.

Use a pill box. It's not just for old people. It's good for everyone.

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.

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!

> 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.

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

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.

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_ove...

[2] https://en.wikipedia.org/wiki/Metformin CTRL-F "B12"

Genetics will play a huge role in B12 absorption. Transcobalamin to be specific.

https://ashpublications.org/blood/article/114/22/1989/111148...

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.

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

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.

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.

Thank you. I will go get those tests.

For B6, it's safer to supplement only the P5P form, as it's much less likely to cause any serious or lasting issue. I would limit intake of P5P to a max of 40 mg per day. If you do this, and you don't have any resulting neuropathy problems (you shouldn't), then you don't need to test it.

In contrast, the inactive cheaper form of B6 which is pyridoxine is more likely to result in problems if taken at above 30 mg/day in the long term.

I very much appreciate your advice. How would I recognize the different forms of B6 in the bottle? Would you say that a multivitamin from a well-respected company, like Centrum, would be a good choice? I'm trying to lower barriers here, for myself and my family.

Again, thank you.

Centrum is a start, but it is not great for dozens of reasons. It would contain B6, the pyridoxine form, not the P5P form, and not in a dose that's sufficient for stress reduction. I take all individual vitamins and individual minerals.

Terrific, thank you.

Going through your posts I see quite a few terms to google and learn about. I appreciate your advice, and for kickstarting a health improvement in my life that I've been meaning to do for years.

Fwiw, I often post in r/FoodNerds.

Great, thank you, I'll take a look.