Molybdenum

[EiCa]

Hi, I was recently diagnosed as extremely deficient in B12, extremely high MMA and homecysteine. (highest MMA he has on record) The bio-chemist I am working with (lifelong research with B12 and B vitamins in general) insists that I need to get Molybdenum on board before effectively supplementing with B1, B2, biotin and eventually adenosyl B12. I have had no success ever with supplementing with the B vitamins, causing these deficiencies. Turns out I have two positive genetic mutations, probably causing my inability to methylate B12. Any comments on molybdenum?

[fbirder]

This biochemist says that your biochemist is talking balderdash.

If you take too much molybdenum then you may find that you can get relief from some of the symptoms by taking B 12. But very few people need molybdenum supplements. cabdirect.org/cabdirect/abs...

You do not need to take adenosylcobalamin. ncbi.nlm.nih.gov/pmc/articl...

You do not have mutations that cause you to be unable to methylate B12. Otherwise you would be dead. You may have mutations in an enzyme called MTHFR that converts methylenetetrahydrofolate into methyltetrahydrofolate. But so does everybody (just about). b12science.com/B12Science/D...

There's some more about MTHFR in this document - b12science.com/B12Science/D...

[EiCa in reply to fbirder]

thank you for this. I posed this question because this biochemist is insistent that the fix all starts with molybdenum but I realize that this is a very unusual deficiency.

Actually, the research, opinions and protocols for B12 deficiency are all over the place (as evidenced right here on this site) and I am spending an awful lot of time trying to sort it all out. It is quite over-whelming.

I am very aware of my MTHFR 1298 mutation for which I am heterozygous so I know that I MAY have a decreased ability to methylate. I don't sweat it much. I tried very small amounts of methylcobolamin and got so sick I stopped trying. Now I am really sick. I have many of the associated problems with this mutation in either myself of among my family. I recently had a genomic test panel done and my MTRR A66G was homozygous positive. I am assuming this information given by Genova Labs is accurate?...

"Health Implications

• MTRR polymorphisms result in decreased enzyme activity and therefore a decreased capacity to recycle oxidized cobalamin (vitamin B-12). This decreased enzyme activity can affect methylation capacity by limiting the amount of active B-12 available for homocysteine conversion.1

• Both MTRR polymorphisms can result in homocysteine elevation, independent of folate, B-12, or B-6 levels.2

• The A66G polymorphism is the most commonly studied MTRR SNP. It has been associated with numerous clinical conditions, such as various cancers, birth defects, metabolic syndrome, mood disorder, and elevated homocysteine.3−5

• The A66G polymorphism has also been shown to correlate with global DNA hypomethylation, which is a direct marker for methylation impairment."

I have been advised to use molybdenum, and then bring up my B1, B2, B3, B6 and biotin levels which are all very low and only then begin supplementing with adenosylcobolamin. It is my, perhaps faulty, understanding that this is the form of B12 most easily absorbed and handled by people like me? cobolamin to hydroxy to methyl to adenosyl? Yes, I am new to all this and just learning. I am not a biochemist and if any or all of what I say is inaccurate or a misunderstanding, please just give me the facts. I am exhausted from defending myself for asking dumb questions or not understanding the conflicting facts, advise, and opinions on the best way to proceed.

Would you say that an extremely low B12, an extremely high MMA and homocysteine is something that can be ignored? I ask because you tell me what not to take and what I don't have, which leaves me right back where I started...who do I believe and what do I do? It seems that the health implications of the genetic mutation listed above has indeed affected me. Regardless if it is genetically influenced or not, I still don't know what to do...Where is the absolute best protocol for someone like me who is very very sick and intolerant of B vitamins but can't ignore the deficiency any longer...

Thank you. It is hard to be this sick and not ask questions and to just trust one person's protocol when the advise is all over the place. The first link on molybdenum did not work and the second one on adenosyl was way over my head. I am just learning. I know there is a learning curve but I am way too sick to suffer needlessly because I didn't do my due diligence.

[deniseinmilden in reply to EiCa]

I feel for you. Don't worry too much about what fbirder says - although he's usually very emphatic about what his opinions are, while he does post some good information he also gets things wrong too so you have to sort the wood from the trees a bit when reading his replies - something that I appreciate you are currently finding difficult while you are so unwell. Whatever happens you don't need to be bullied!

If the biochemist you are working with has a background of relevant research I am curious to know why you are questioning his suggestions... you have said it is because molybdenum is such a rare thing to be deficient in (and I agree) but I wonder if there is something more to it than just that?

Instincts have kept us alive for many generations before science was invented and knowledge could be disseminated so if your instincts are saying something doesn't sound/seem right then I'd go with them and be cautious.

If it seems OK then I'd speak with them, explain that you are currently too unwell to cope with more than a few words at a time and ask them to be very patient with you. Then ask them what the pros and cons of the treatment they are suggesting are.

Have they any practical experience of treating people like you or are you a guinea pig?

Are they supplying their guidance and products free of charge - at least until you are well? I.e. Do they believe in their recommendations without personal gain? (Some people recommend weird things just so they can charge a fortune for saying something different!).

My only knowledge of molybdenum is that of simple plant and animal nutrition and although life cannot do without it, if it is in plentiful supply in the soil, it is taken up too readily by plants, and therefore the animals that eat them, and because it is quite highly reactive it locks up other minerals, particularly copper and selenium, so causing problems of apparent deficiency that way. These may be got around by supplying the required minerals artificially bound to a protein molecule so that they are "protected" in the gut and may be absorbed that way.

I'm sorry that this doesn't answer your question but I hope it gives some simple background (which you might already know) on why molybdenum is rarely supplemented - it is more reactive than many other minerals so availability isn't usually a problem and it can easily exceed the upper intake limit, causing other problems if this happens.

However! That said, it is necessary for life and like all essential vitamins and minerals, if you need it, you need it!

As far as methylation is concerned there are various things, including genetics, that affect the process so that it barely functions or functions badly which is what you meant (as opposed to "doesn't happen at all" which is where the belittling comment you received came from).

(Unfortunately some people - for instance those with higher level autistic spectrum disorders - cannot understand normal parlance and take everything too literally. My (ex)husband is like that all the time but I know I can err that way too if I get too short of B12. It is a nightmare to deal with when you are not well enough to find precisely the words that the pedantic person will find acceptable!!)

Having a methylation problem doesn't mean that you can't live at all but it does mean you feel terrible - I know from personal experience.

I haven't done any genetic testing so I don't know if I have a genetic problem but I do know that when I became seriously ill with the B12 deficiency it messed up my ability to methylate so it is possible to run for many years OK and then develop a problem.

It could be that your body has managed OK on a low level until now but the problem has become worse until it is now affecting you badly.

I think I am missing a large piece of the picture but would it be impossible for you to have hydroxocobalamin injections and methylfolate tablets to go with it because of your B vitamin intolerances?

I'm afraid I don't feel I've been much help but I guess at least I haven't been unfriendly!!

I'd love to know what you think and how you get on, how you came across a B12 biochemist, etc, etc but I appreciate that at the moment you have to concentrate on getting the treatment you need to get well ASAP.

Good luck! 🍀

[fbirder in reply to EiCa]

Sorry, but the advice you’re being given is rubbish.

No it does not ‘all start with molybdenum’. Ask your biochemist for one scientific paper to show that molybdenum is essential for anybody with a B12 deficiency.

No, your mutations will make no difference at all to your health. There is not evidence that being heterozygous for A1298C has any measurable effect. Which is fortunate, because half of the whole population have that mutation.

There are some people on the interwebs who make a lot of money by spreading scare stories about ‘methylation’ and how it causes everything from piles to pleurisy. It is all rubbish.

Here is what the DNA testing company say about MTHFR...

blog.23andme.com/health-tra...

Based on the existing data, scientists at 23andMe have concluded that people should not interpret their genotypes at the common MTHFR variants as having an effect on their health.

There is even less chance of an MTRR mutation having any measurable effect. Which is also fortunate, because 60% of people have a mutation at that location.

No. Adenosylcobalamin is not most easily absorbed. And once it enters the cell is is, as is all B12, converted to cob(II)alamin. All forms of B12 are converted to cob(II)alamin as the enter the cell. They are all identical.

If you have a severe B12 deficiency, high hCys, and high MMA then you need to stop listening to idiots.

You need a course of B12 injections, cyanocobalamin or hydroxocobalamin, three a week for at least two week, then often enough to keep your symptoms at bay. You do not need molybdenum.

[Gambit62 Administrator]

EiCa

I haven't been able to find anything specifically linking molybdenum to MTRR - it doesn't appear to be a cofactor in the reaction so would suggest that you ask the biochemist you are working with why he thinks it is so important for this process.

raised MMA and homocysteine are markers for B12 deficiency and as such normal protocols seem to be to treat the B12 deficiency as quickly as possible with injections. Adenosyl isn't generally used because it is the least stable form of B12 and it shouldn't really be necessary as the process that allows B12 to pass into your cells seems to make the form of B12 (cyano/hydroxo/methyl/adenosyl) pretty irrelevant though there do appear to be some genetic variants that can affect the efficiency/ability of breaking the original bonds outside the cells but these are also very, very rare - I've seen a few reported cases of people having problems breaking the methyl bond so were unable to use this form to make adenosyl cobalamin.

Processes going on in cells use methyl or adenosyl cobalamin.

It doesn't sound right to me that someone is suggesting delaying B12 treatment.

I'm not a biochemist or a medical professional.

Please also note that this forum is really about a specific B12 absorption problem - PA - and genetics of how B12 is processed and used are generally off topic.

[EiCa in reply to Gambit62]

Thank you everyone for your replies. I did not know this is just a pernicious anemia thread. I thought all B12 deficiencies could be discussed. After all PA is often misdiagnosed. I am trying to be patient to see the doctor who is ordering all this testing. She will continue to try and determine if I have pernicious anemia. Is there another thread for serious B deficiciencirs somewhere here’s?

Thank you for your input.

[Gambit62 Administrator in reply to EiCa]

EiCa - I'm not aware of another forum for other B vitamin deficiencies

- my main point was that genetics really is beyond the scope of this forum - though if we understood the genetics of PA that would be a big help, but, like so many other disorders the genetics aren't well understood.

That means that the genetics of B12 metabolism - and what you are talking about in relation to MTRR is the metabolism of B12 rather than a B12 absorption problem.

If your serum B12 levels are low and you aren't a vegan / vegetarian who avoids dairy and eggs, the conclusion would be that you do have an absorption problem, and PA is the most likely candidate.

Whilst there are a few absorption problems that are cureable, most aren't leading to the need for lifelong injections.

Generally if people have problems with metabolising B12 then they show up with high homocysteine and MMA with normal levels of B12 as the genetic variants mean they need higher levels of B12 to have sufficient B12 available, and this can generally be dealt with using high dose oral treatments

- which brings me back to feeling that you should be being treated for the low B12 as a priority rather than looking at other factors that seem to have no relevance.

[EiCa in reply to Gambit62]

Thank you Gambit. I will try to restrict my questions to the learning curve of dosing, etc. Hopefully we will get some sort of definitive answer on PA though my study shows that some of this is subjective.

Is it at all relevant that I had a very bad reaction to a sublingual adenosyl B12 at only 750 mcg. 12 days ago? My nervous system is still ramped up. The last B12 shot I had gave me anaphylaxis (more than a decade ago). I had high serum levels then so I just abandoned B12. I am dairy free and only eat egg sparingly cooked or baked in something for 8 years. I do eat meat (poultry only).

Sorry. I am not sure what is off topic or not here but I will follow the thread and try to stay on topic. I was not aware that everyone here has PA. Thank you for your comments.

[Gambit62 Administrator in reply to EiCa]

if you had a reaction to a B12 shot years ago that suggests that you are one of the few rare individuals who is allergic to B12. There are protocols for desensitising but it can be difficult to find someone who knows about them.

There are details of treating patients who are allergic on the PA website but you would have to join to be able to access them.

It does sound as if your deficiency may be due to dietary deficiency. As such you would be able to to use smaller oral doses to treat the deficiency and return your levels to normal - usual dosing is 50mcg 2 x daily for a couple of months. Unless you have a family history of lebers syndrome cyanocobalamin should be okay.

Serum levels after a B12 shot don't really mean much - they will be high and then fall over time so interpreting them can be very difficult and the best thing to do is go by symptoms.

You really need to get professional medical advice and ensure that your treatment is being monitored closely by someone who is medically qualified if you have had an allergic reaction in the past.

[EiCa in reply to Gambit62]

Thank you. I will wait and see if I end up with a PA diagnosis. Your advise is helpful. How do I join if I am diagnosed? I thought being on this site meant I was a member. Sorry for the question but it takes a bit to learn the ins and outs of these forums. I will be open to trying low doses or oral B12 and see what happens. I appreciate your time.

[Gambit62 Administrator in reply to EiCa]

The PAS sponsor this site - membership is open to everyone

Apologies - I meant to include a link to membership of the PAS in my reply

pernicious-anaemia-society....

[Nackapan in reply to EiCa]

I haven't a diagnosis of PA . I'm assumed PA .I've used thus forum since 2018 I'm sorry I missed theses posts . Too ill at the time I imagine.

We help each other by personal experiences and pick out what we feel might help us.

There is no fixed protocol consistent worldwide.

It appears everyone needs a slightly different regime too.

I like you ask lots if questions.

I finally found a Gp who supports and admits she us learning from me. Rather than blocking treatment of b12 or trying trying to hard yo send me down the mental health route as no answers.

Have refused lots of medications.

Have trialled some.

I'm still moving forward in the right direction at snails 🐌 pace .The only thing I've kept up consistententlg is B12 injections as its proved to be a mistake doing otherwise.

Hope you keep strong and keep positive.

[Cetus]

EiCa I believe the line of thinking is that molybdenum (along with selenium and iodine) is necessary to activate B2, which is itself necessary for proper processing of B12 and folate. This only becomes an issue, so it is said, if there is a deficiency of one of them.

A discussion I read which mentioned this was rather sceptical that molybdenum was actually necessary, although the other two are said have better defined roles in activating B2.

Don't blame me, I'm just repeating what I came across!

[EiCa in reply to Cetus]

I’m sorry Cetus. I didn’t understand the last statement. What did you mean by “the other two”? I won’t ever blame anyone for sharing their knowledge or even opinion, especially when the information is not straightforward. Thank you.

[fbirder in reply to Cetus]

But I can find absolutely nothing at all in the scientific literature that suggests this might even be slightly possibler.

[Cetus in reply to fbirder]

Hello fbirder

As I understand it, which is not saying much, riboflavin is first converted to FMN and then to FAD. It is said that the second conversion needs molybdenum in the form molybdopterin. However the discussion I read about this was sceptical of the need for supplementary molybdenum.

[fbirder in reply to Cetus]

That may be true. But is irrelevant to B12.

[Cetus]

Hello EiCa . By "other two" I mean selenium and iodine, which I mentioned earlier.

[EiCa in reply to Cetus]

Oh thanks for clarifying. Yes, the advisor who said molybdenum mentioned selenium and iodine as well but based my need for molybdenum on where I live (I guess the soil). I wonder if our soil even matters as I mostly eat food that comes from other states; can’t get local produce for most of the year.