Is Molybdenum necessary for methylation?

[outdamnspot]

I got in touch with Greg from b12oils.com. I don't know how familiar people here are with his approach, but he suggests that for methylation one needs Iodine, Selenium, Molybdenum and B2. The former three should help the body convert B2 to its active form; then B12 can be added .. which should overall should negate problems like the paradoxical folate deficiency seen on Freddd's protocol. The protocol seemed a lot more simple and easy-to-follow than Freddd's .. since I am so unwell and hyperreactive, I am concerned about trying to balance everything.

He suggests the Iodine etc. can be obtained from food sources -- i.e. salt, brazil nuts etc. However, I am on a Ketogenic diet and therefore can't get Molybdenum from food sources (beans, lentils). But I've also been reading that Molybdenum shouldn't be taken if one has an overgrowth of H2S forming bacteria .. since the Moly will accelerate Sulfate conversion, which is turned into H2s, and you get more sick (I have a Strep and Prevotella overgrowth).

So I'm wondering if I should leave Moly out? I've also asked Greg why one can't just directly take the active B2 form in this case, but am waiting for a reply ..?

 

[PeterPositive]

Strictly speaking of methylation I am not aware that selenium or molybdenum play a direct role. Maybe they do in the metabolism of B2 but you could also take the active form of B2 (R5P) and avoid adding minerals that may cause you problems.

I am taking this one:
https://www.thorne.com/products/dp/riboflavin-5-phosphate

good luck

 

[outdamnspot]

Strictly speaking of methylation I am not aware that selenium or molybdenum play a direct role. Maybe they do in the metabolism of B2 but you could also take the active form of B2 (R5P) and avoid adding minerals that may cause you problems.

I am taking this one:
https://www.thorne.com/products/dp/riboflavin-5-phosphate

good luck

Thanks, I hope he doesn't mind me posting what he said here:

You need functionally active vitamin B2 though, but there is also a swag of things that you need in addition.
In order for your body to transform B2 (riboflavin) to the two active forms of the vitamin, the cell needs to have a signal to do it. The signal comes from T4 binding to a receptor on the cell. In order to make T4, tetraiodotyrosine, you need iodine, so you need to have some form of iodine in your diet, or you need to supplement with it.
Once the T4 is taken up by the cell it is converted to the active form, T3, by an enzyme that requires selenium, so you need selenium as well.
T3 turns on the cell to convert riboflavin to R5P, or FMN, which is one of the active forms of vitamin B2.
In order for the cell to make the other active form FAD, you use an enzyme that requires molybdenum.
If you leave out any of the iodine, selenium or molybdenum, then you basically can't use the B2 and you pee it out.
Before you start with the B12, you need to be supplementing or eating foods that containe all of iodine, selenium, molybdenum and vitamin B2.
To do this you start at the top (iodine) and work through the supplements (Se, then B2, then Mo) to see how you tolerate them. If you have any reaction to them, then firstly you were very deficient in one of them, and secondly you need to back off and slowly build up. If you have no reaction (which is pretty normal) you just keep upping the dose. The best way is to do this over a period of a month, and then start titrating in Ado/Me B12.

So, yeah, it looks like those things are required to convert the B2. I have asked him why one can't just take the active form and will see what he says.

 

[PeterPositive]

Keep in mind that, unless you have a terribly restricted diet, you will still be getting some B2, iodine, molybdenum etc... from food. So the extra active B2 is just there to help the folate and B12 doing their job, if there's a real need...

You can try the extra B2 and see if it helps, if it does then you may investigate strategies to increase it via the diet otherwise I would not bother.

 

[outdamnspot]

Keep in mind that, unless you have a terribly restricted diet, you will still be getting some B2, iodine, molybdenum etc... from food. So the extra active B2 is just there to help the folate and B12 doing their job, if there's a real need...

You can try the extra B2 and see if it helps, if it does then you may investigate strategies to increase it via the diet otherwise I would not bother.

I am on a pretty restricted Keto diet, I don't think I would be getting much Molybdenum looking at the list.

 

[outdamnspot]

@PeterPositive so is there anything else vital I would need, if I am getting Iodine, Selenium etc. from diet? I react badly to everything, so am trying to start simply. Initiating Methyl-B12 on its own has been a pretty horrible experience, so I'm really looking to simplify. I will order the active B-2 and the B12 oil .. wondering if I need the other B's as well? I take a protein/nut mix that is high in Zinc, has some copper etc. Main thing I'm missing is magnesium, which I can't tolerate, but I try to get that from diet too, and green smoothies for folate.

 

[PeterPositive]

Usually the problem with horrible starts is dosage
Typically you need to start at 50 mcgs of both (B9 and B12) and if you tolerate it you can push it up in little increments over time (weeks or even months...)

For some even 50mcg can be too much, especially B12. It has taken me years to be able to handle B vitamins, for reasons I still don't understand.

Can you eat quinoa? Technically it's not a cereal so it might work with your diet. If you can quinoa, is high in Magnesium. Roughly 150mg of Mg per 100g of quinoa.

cheers

 

[alicec]

I have asked him why one can't just take the active form and will see what he says.

There are two steps in converting riboflavin to the active vitamin - first to FMN, then to FAD. Molybdenum is used in the second step. Thyroid hormone is used in the first step hence the need for iodine and selenium.

FMN (also known as riboflavin 5 phosphate) is available as a supplement but not FAD.

Note also that swallowed FMN is largely processed before it is absorbed from the intestine. This involves clipping off the added phosphate group which negates the point of taking the active vitamin. There does appear to be a second route of direct uptake but this is not well understood.

Sublingual FMN should be directly absorbed.

 

[CCC]

We found we needed the Active B2 (as FMN - sublingually) to kickstart things. After a while, we were able to switch to the much cheaper B2, and avoid the potential tooth issues of so many sublinguals.

The B12 oils are a lot easier than the Freddd approach, and easier on the gums/teeth. My only caution is that the oils can be too stimulating for some - so maybe start with a small drop and build up to that whole slurp.

We started with the subligual tablets as per Freddd and built the dose up before switching to oils.

As for your question about Mo, we don't think we need it having tried it and experienced nil effect.

 

[aaron_c]

Can anyone find where he is getting that molybdenum is a cofactor for FAD synthase (gene: FLAD1)? All I can find is a reference to it having a "Molybdenum cofactor biosynthesis protein-like region" which "may not be functional." Even if it is functional, the name makes it sound like would serve to form molybdenum cofactor rather than require it.

 

[aaron_c]

Having read Greg's comments above, I am not sure how much faith I would put in him. Here is my thinking:

While I imagine that some of us have mild selenium or iodine deficiencies that we would do well to address, the same could be said of a lot of things like magnesium, folates and carnitine. The problem he is trying to fix with the selenium and iodine appears to be related to metabolism--he wants to make sure we are producing enough ATP to convert riboflavin to FMN and FMN to FAD. Since people with ME/CFS have problems with ATP production that can only be helped so much by fixing thyroid stuff... *shrug* I think there are a number of places one could start supplementing.

I am somewhat concerned with his strategy of taking iodine, selenium, b2 and molybdenum until symptoms appear, then backing off and ramping up. While high doses of iodine might be helpful for some people--maybe even people with Hashimoto's--people at risk for Hashimoto's should be aware of the risk it poses as well. Some minerals do not signal immediately when you take them in excess, allowing toxic amounts to build up over time. I am concerned that selenium is one of them. Very high doses of b2 can deplete one of boron, and very high doses of molybdenum can deplete one of copper.

Granted, I have had success in judging the right molybdenum dose for myself by looking at symptoms (supported by periodic testing), but I judged it by the symptoms Mo removed rather than the side effects it caused. Greg suggests that if one of the above supplements causes symptoms then we are on the right track--and if molybdenum makes you tired I would tend to agree. But if molybdenum causes gout-like symptoms or psychosis (only happened in one case as far as I know) I would back off.

I am concerned that, being a generalist rather than a specialist in ME/CFS, Greg's treatment priorities may not align with what works best for us and that, furthermore, he is a bit cavalier in his dosage guidelines. Other than all of that, I don't see a problem with what he suggests. I take selenium, a whole lot of molybdenum, and a decent amount of riboflavin and riboflavin-5-phosphate myself.

Unfortunately, I don't know of a good protocol to direct you towards. Perhaps if Rich Van Konynenburg was still alive and updating his protocol I would send you that way. Good luck experimenting.

 

[alicec]

Can anyone find where he is getting that molybdenum is a cofactor for FAD synthase

With so many things to delve into and limited brain capacity I have never followed up Greg's claims about the requirement for molybdenum in forming FAD.

You are right - there is no obvious requirement.

"Molybdenum cofactor biosynthesis protein-like region" which "may not be functional."

That domain in described in other publications as a molybdopterin binding domain (molybdopterin is the prosthetic group that the molybdenum metal is complexed to in molybdenum-requiring enzymes).

As to the functional status of the domain, I found this recent paper which suggests that it does have activity - FAD hydrolase activity. This would convert FAD back to FMN.

I don't have the energy to follow this up at the moment but the Wikipedia entry on FAD hydrolase indicates that it is an important part of riboflavin metabolism.

It seems not a lot is known about the human enzyme. Delving into the bacterial enzyme (where the two steps are contained in a single enzyme, unlike the two separate enzymes in human) might reveal more but there is certainly nothing terribly obvious about the Mo requirement that Greg insists on.

I agree that Greg is a generalist with a great interest in B12 deficiency, but not necessarily really appreciative of the problems of people with CFS/ME.

I've always been happy to put his ideas to the test and have gotten some benefit from them (and love his B12 oil products) but the more I have tried to understand B12 metabolism and why so many people with CFS/ME seemed to be helped by it to at least some extent, the more I realise that too much is just unknown.

 

[outdamnspot]

There are two steps in converting riboflavin to the active vitamin - first to FMN, then to FAD. Molybdenum is used in the second step. Thyroid hormone is used in the first step hence the need for iodine and selenium.

FMN (also known as riboflavin 5 phosphate) is available as a supplement but not FAD.

Note also that swallowed FMN is largely processed before it is absorbed from the intestine. This involves clipping off the added phosphate group which negates the point of taking the active vitamin. There does appear to be a second route of direct uptake but this is not well understood.

Sublingual FMN should be directly absorbed.

This is what Greg said when I asked why I couldn't just take the active form:

No, this is another common concept "pushed" by the supplement companies. If you take the so-called "active" forms of the B group vitamins, back to the inactive forms in your intestine. During your processing of these forms of the vitamins, you add the so-called active bit on the vitamins to keep them inside the cells. Most cells won't take them up. You would just be paying for expensive supplements, that are being pushed by the pill companies.

So taking the sublingual FMN should circumvent that problem?

 

[outdamnspot]

I am concerned that, being a generalist rather than a specialist in ME/CFS, Greg's treatment priorities may not align with what works best for us and that, furthermore, he is a bit cavalier in his dosage guidelines. Other than all of that, I don't see a problem with what he suggests. I take selenium, a whole lot of molybdenum, and a decent amount of riboflavin and riboflavin-5-phosphate myself.

Well, I have already experimented with Selenium and it produced an intolerable 'crash' in me, possibly due to speeding up metabolism? And Rich warned against people with a strong sulfur->H2S converting dysbiosis to avoid Molybdenum (which Greg also disagrees with -- lol).

I am interested in trying Greg's approach because the prospect of juggling Freddd's seems really daunting, so can you see any obvious reason why I couldn't try an active form of B2 (like the sublingual) with the B12, and skip the intermediary factors?

 

[aaron_c]

can you see any obvious reason why I couldn't try an active form of B2 (like the sublingual) with the B12, and skip the intermediary factors?

Seems as good a place to start as any. Honestly, I think you'll be fine wherever you start--you will eventually work your way around to everything else.

I have also read about how R5P is supposedly reduced to riboflavin before it is absorbed, but for me there is a noticeable difference between riboflavin and R5P: Too much R5P gives me insomnia, but the right amount gives me a small boost in energy. And riboflavin and R5P are both pretty cheap as far as supplements go, so the increase in price doesn't really matter to me.

How does B2 help you avoid paradoxical folate deficiency?

 

[CCC]

Well, I have already experimented with Selenium and it produced an intolerable 'crash' in me, possibly due to speeding up metabolism? And Rich warned against people with a strong sulfur->H2S converting dysbiosis to avoid Molybdenum (which Greg also disagrees with -- lol).

I am interested in trying Greg's approach because the prospect of juggling Freddd's seems really daunting, so can you see any obvious reason why I couldn't try an active form of B2 (like the sublingual) with the B12, and skip the intermediary factors?

We took the approach that we were treating a B12 deficiency first and foremost, and adopted Freddd's approach to do it, leading to other things we take (methylfolate/folinic, B2 etc) to prop up everything B12 is involved in. That has worked for us quite well. The only really big difference is that freddd is not a fan of extra B2, whereas we seem to need it.

The best thing about the B12 oils is that it is a time-release dose, and you don't rot your teeth.

 

[CCC]

...How does B2 help you avoid paradoxical folate deficiency?

For us, it seemed to reduce the folate demand overall: reduced demand = lower chance of deficiency. That said, it also reduced the adenosylB12 demand. But then, it also took several weeks to start excreting excess B2. So maybe we're not normal!

 

[outdamnspot]

Seems as good a place to start as any. Honestly, I think you'll be fine wherever you start--you will eventually work your way around to everything else.

I'd love to believe that but everything I seem to try makes me worse :-/ It makes getting anywhere nigh-impossible.

I have also read about how R5P is supposedly reduced to riboflavin before it is absorbed, but for me there is a noticeable difference between riboflavin and R5P: Too much R5P gives me insomnia, but the right amount gives me a small boost in energy. And riboflavin and R5P are both pretty cheap as far as supplements go, so the increase in price doesn't really matter to me.

Would you suggest going with the sublingual B2 over the R5P? My only concern with the sublinguals is the artificial sweeteners, since I have a gut dysbiosis, but I don't know how big a deal that is.

How does B2 help you avoid paradoxical folate deficiency?

I don't know, but @Johnmac has had success with Greg's protocol and significantly reduced his folate needs.

 

[outdamnspot]

We took the approach that we were treating a B12 deficiency first and foremost, and adopted Freddd's approach to do it, leading to other things we take (methylfolate/folinic, B2 etc) to prop up everything B12 is involved in. That has worked for us quite well. The only really big difference is that freddd is not a fan of extra B2, whereas we seem to need it.

The best thing about the B12 oils is that it is a time-release dose, and you don't rot your teeth.

Which B2 were you using, i.e. brand?

 

[aaron_c]

Would you suggest going with the sublingual B2 over the R5P?

I've never tried sublingual R5P.

everything I seem to try makes me worse :-/ It makes getting anywhere nigh-impossible.

I'm sorry to hear that. Do you have the money to get some testing done? Possibly a methylation panel? It might shorten the guessing game.