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B12 Supplements - Latest Developments and efficacy?

Moof

Senior Member
Messages
778
Location
UK
[I'M SO SORRY, I CLUMSILY PUT THIS INTO THE WRONG THREAD! PERHAPS AN ADMIN COULD MOVE IT TO THE B12 CONVERSATION FOR ME?]

Interesting article from Wikipedia. I looked it up to see if some areas of the skin are more permeable than others, partly expecting to see nasal tissues and the skin inside the anus mentioned. It seems it is true, though perhaps not in the way I thought! Scrotal application, guys...? :rofl:

They also mention a chemical compound that enhances absorption:

https://en.wikipedia.org/wiki/Absorption_(skin)
 

Journeyman

Senior Member
Messages
193
That rule is someone's proposal based on their observations. In the examples they surveyed, where molecules crossed the skin barrier, they were small.

They didn't show that there is some absolute barrier whereby molecules of larger size can't cross the skin.

Here for example is part of the study linked above on B12 penetration of the skin. Clearly the molecule did cross the skin, even though it is bigger than 500 daltons. Possibly its non-polar nature helped.

Further studies with penetration enhancers considerably increased the penetration.

The 80% penetration figures quoted above were given by Dr Greg Russell-Jones who developed the B12 oils. I have not seen the penetration studies published (I think there is a patent so possibly that can be found) but Greg is a reputable scientists who has done a lot of work on various drug delivery systems and who now consults in this area.

As described here, he has developed transdermal delivery systems which work for peptides and proteins, much larger molecules than 500 daltons.

The delivery systems are based on water in oil microemulsions - the lipid part of the vehicle smuggles the water trapped inside the emulsion, and anything dissolved in the water, into the skin. Liposomes have a similar principle.

Presumably the lipid based delivery system in the B12 oils is equally successful in efficiently transporting B12.
@alicec great to get your input on this topic. I think the importance of B12 for most visitors to this site can't be overstated and it looks like we're finally getting some discussion happening based on scientific literature which always helps.

To clarify, is that a typo where you say "(I think there is a patent so possibly that can be found)" and you intended to say it can't be found? In the interests of his own business and the health of visitors to this forum wouldn't Dr Russell-Jones do well to make this literature available so we can have some confidence in this transdermal b12 delivery system since many of us may be relying on it as the cornerstone of our treatment protocol?

Regards

Journeyman
 

Journeyman

Senior Member
Messages
193
Thanks for those links, alicec, very interesting.

So you are saying that penetration enhancers can make a world of difference to amount of substance absorbed across the skin or mucous membranes.

I find it interesting that in Figure 3 of the study you linked to, the best B12 penetration enhancer was a mixture of 50% ethanol, 10% oleic acid and 40% propylene glycol, which was able to transport around 62 mcg of B12 across each cm2 of skin during a period of 16 hours.

So if you applied this to an area the size of the top of your hand (around 50 cm2), this would absorb around 3,000 mcg of B12 after 16 hours, which is a lot of B12.

So that suggests that the B12 oils developed by Dr Greg Russell-Jones should work pretty well. They are somewhat expensive though, at $50 for 15 ml. I am not sure how long 15 ml will last.

I wonder if it would be possible to formulate your own transdermal B12 oils more cheaply, using the ethanol, oleic acid and propylene glycol mixture. Ethanol you can get from your local chemist as surgical spirit, olive oil is around 70% oleic acid, and propylene glycol is cheaply available (perhaps glycerin might substitute).



Looks like Gregory J. Russell-Jones has been pretty busy on the patent front, with 80 patents to his name via a Google Patent Search.
It seems to me that Dr Russell-Jones transdermal B12 probably does give a strong and lasting b12 dosage (as supported by the experiences of many people in this forum) but in the interests of economy and this whole dalton absorption issue I'm going to try my first nasal b12 system. Especially since it seems that the best way to treat a b12 deficiency when using passive diffusion methods (lacking intrinsic factor?) is to take small doses frequently through the day rather than mega doses once a day (something I used to do myself)
Any recommendations on the best b12 nasal spray (preferably best value but also good quality)?

Regards

Journeyman
 

Hip

Senior Member
Messages
17,824
Any recommendations on the best b12 nasal spray (preferably best value but also good quality)?

Myself I use pure B12 methylcobalamin powder, and snort a small amount (about 5 mg) into the nose using a drinking straw. You can buy B12 powder on ebay (though make sure it is pure, because if it contains say a citric acid preservative it will sting like hell if you snort that; anything acid hurts like hell if snorted into the nose).

You have to store B12 methylcobalamin in the dark, because light causes it to break down. And when you open the jar of methylcobalamin, it's best done in subdued lighting. Other forms of B12 do not have this problem of photosensitivity.
 

alicec

Senior Member
Messages
1,572
Location
Australia
To clarify, is that a typo where you say "(I think there is a patent so possibly that can be found)" and you intended to say it can't be found?

No I meant what I said. If someone cared to search for it I imagine they could find the patent behind B12 oils.

Note this patent would not be the same thing as some in the list linked by @Hip where substances are attached to B12 and the B12-IF absorption system is used to get oral uptake of the linked substance.
 

Journeyman

Senior Member
Messages
193
Myself I use pure B12 methylcobalamin powder, and snort a small amount (about 5 mg) into the nose using a drinking straw. You can buy B12 powder on ebay (though make sure it is pure, because if it contains say a citric acid preservative it will sting like hell if you snort that; anything acid hurts like hell if snorted into the nose).

You have to store B12 methylcobalamin in the dark, because light causes it to break down. And when you open the jar of methylcobalamin, it's best done in subdued lighting. Other forms of B12 do not have this problem of photosensitivity.
Lol the lengths we go to in this quest for health. I wonder what my neighbours will think if I add snorting B12 to my protocol. They're already wondering what the hell's wrong with me every morning when I doll out my numerous vitamins. :)

Ps - I just followed your signature block link re: anxiety only to find that I'd already read and acted on it previously! I used the N Acetyl Glucosamine back about 1.5 years ago with high hopes. Didn't notice much of an effect but rarely are these things for nought. Sure enough, whilst recently revisiting some blood type diet reading material I found something that explained that dietary lectins are effectively treated by NAG! My fairly strict adherence to the blood type diet for the last 6 years may explain the limited gains I experienced on NAG that I otherwise would have got if I followed a 'normal' diet containing wheat and dairy... Am fully on board with the notion of brain inflammation as a causative agent in the bottom up dominant mode of thinking that I suspect accompanies GAD cases. Without enough circulation going to the outer regions of the brain due to the inflammation the top down executive processes arent getting enough opportunity to work. Where the DLPFC is the most relevant structure I believe...
Your insights regarding sinus congestion and anxiety are _extremely_ interesting. I'm putting it together with what I've learnt in TCM that people with weak 'Spleen Qi' (who also tend towards having this congestion of the upper respiratory system) and it supports the notion that the anxiety may be a by product of the sinusitis which in turn is the result of inflammation...
 

Galixie

Senior Member
Messages
219
Other forms of B12 do not have this problem of photosensitivity.

All forms of B12 are light sensitive. Some formulations also require refrigeration.

It is true that methylcobalmin is the least shelf-stable of the forms, so being extra careful with that form is a good idea. It can end up being an awful waste of money otherwise.
 

Hip

Senior Member
Messages
17,824
All forms of B12 are light sensitive.

I was under the impression that you only have to worry about methylcobalamin when it comes to avoiding exposure to light, but you're right, I found this 2013 paper which says that all forms of B12 undergo photodegradation (aka: photodissociation, photolysis) in aqueous solution.

Interestingly though, the study found that methylcobalamin and adenosylcobalamin in water were converted into hydroxocobalamin within seconds by the action of UVA light. They found hydroxocobalamin was the most stable form under UVA light.

So you don't actually lose any B12, it just changes into hydroxocobalamin (although hydroxocobalamin may eventually degrade under the effects of light as well, and I am not sure what hydroxocobalamin degrades into.

They point out that other studies have found methylcobalamin to be around 3 times more sensitive to UVA radiation than adenosylcobalamin. I also found this study which says: "the photochemistry of methylcobalamin is found to depend strongly on excitation wavelength, while the photochemistry of adenosylcobalamin is essentially wavelength independent over the range studied."



The 2013 study also says:
Our pilot study on humans demonstrates that serum vitamin B12 concentrations are not significantly affected during summertime in the Scandinavia. There is no consensus on whether vitamin B12 is degraded during UV exposure of Caucasians living at lower latitudes or using tanning beds, and there is a strong need for further studies of vitamin B12 photodegradation in humans.



I believe B12 is more stable in dry form compared to when dissolved in water, although I can't find a reference for that at the moment.
 
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ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
@Journeyman I love B12 nasal. However, as I've just purchased crystals on my own, instead of part of the original group buy a couple years ago, when my new batch is finished I'll be switching to B12oils. I used the same vendor as the earlier buy, knew I'd be paying more for ordering a smaller amount. but he then billed through Alibaba, and I was charged a massive handling or transaction fee. Tried disputing w/ Alibaba, contacted the vendor. No help there. So when I'm through with this, which I'm hoping is in 4 years, I'll be going w/ Greg's B12 oils. cheers.
 

CCC

Senior Member
Messages
457
It would be really good to understand more about the B12 forms and why some people (like my son) can feel the difference between adenosylB12 and methylB12.

Most of the time, he's happy enough with 1 or 2 slurps of adenoB12 oil at the start of the day, but lately he's also needed a top up of sublingual aB12 in the early afternoon (he doesn't like taking the oils later in the day).

Freddd noticed a difference between the types of B12 as well. He also couldn't tolerate hydroxy B12 at all - it gave him unpleasant symptoms very quickly.

But most of all, I'd like to know why my son needs so much adenosylB12 after two years of fairly heavy duty supplementation. Not methylB12. The demand is for adenosylB12.

A bottle lasts for 60 slurps, which can cover 1-2 months for us.
 

alicec

Senior Member
Messages
1,572
Location
Australia
It would be really good to understand more about the B12 forms and why some people (like my son) can feel the difference between adenosylB12 and methylB12.

I have never seen any research that can explain it.

Based on what we know about B12 trafficking in the cell, the form taken shouldn't matter. Once B12 is taken into the cell, the upper axial ligand (methyl, adenosyl, hydroxy etc) is removed and cobalamin is shuttled to either methionine synthase or methylmalonyl CoA mutase as is required by the cell. The methyl or adenosyl group is added prior to use by the relevant enzyme.

Many people though report that the form taken does make a difference to them.

There is a little evidence that some B12 can diffuse directly into cells (often quoted as 1%) and as far as I can make out, Freddd believes that B12 taken up in this way is not processed via the normal pathway and can be used directly by the relevant enzyme. This is why it is important to take both methyl and adenosyl B12 forms in his schema.

I have never found any studies confirming such a mechanism.

Others have speculated that it may be because variations in uptake, transport or processing proteins may mean that some people deal better with one form rather than another, but as far as I can work out, this is just speculation.

I did see one paper which actually explained why a child with cblC disease responded better to a particular form of B12 (can't remember which form).

The defective MMACHC protein in this child was better able to bind that particular form and so go on to process it, while other forms were bound less well and so were poorly processed. (Normally the MMACHC protein can bind all B12 forms.)

Ironically the function of the MMACHC protein is to remove the upper axial ligand, so in this child's case, the reason a particular form worked better was not because it somehow bypassed normal processing and was used directly, but because it was better able to have it's upper axial ligand removed.

That is an unusual case though.

The answer to your question is that we don't know.
 

Journeyman

Senior Member
Messages
193
I have never seen any research that can explain it.

Based on what we know about B12 trafficking in the cell, the form taken shouldn't matter. Once B12 is taken into the cell, the upper axial ligand (methyl, adenosyl, hydroxy etc) is removed and cobalamin is shuttled to either methionine synthase or methylmalonyl CoA mutase as is required by the cell. The methyl or adenosyl group is added prior to use by the relevant enzyme.

Many people though report that the form taken does make a difference to them.

There is a little evidence that some B12 can diffuse directly into cells (often quoted as 1%) and as far as I can make out, Freddd believes that B12 taken up in this way is not processed via the normal pathway and can be used directly by the relevant enzyme. This is why it is important to take both methyl and adenosyl B12 forms in his schema.

I have never found any studies confirming such a mechanism.

Others have speculated that it may be because variations in uptake, transport or processing proteins may mean that some people deal better with one form rather than another, but as far as I can work out, this is just speculation.

I did see one paper which actually explained why a child with cblC disease responded better to a particular form of B12 (can't remember which form).

The defective MMACHC protein in this child was better able to bind that particular form and so go on to process it, while other forms were bound less well and so were poorly processed. (Normally the MMACHC protein can bind all B12 forms.)

Ironically the function of the MMACHC protein is to remove the upper axial ligand, so in this child's case, the reason a particular form worked better was not because it somehow bypassed normal processing and was used directly, but because it was better able to have it's upper axial ligand removed.

That is an unusual case though.

The answer to your question is that we don't know.
Hi @alicec
Re: "I have never found any studies confirming such a mechanism."
Is that in reference to the idea that whilst most B12 is absorbed in the Ileum with the assistance of intrinsic factor there is also a passive diffusion process that explains an absorption of about 1-2% of any given B12 dosage??

Re: this MMACHC protein: did the article explain what the relevant SNP's might be so we can check whether we have the mutations (would be good to get more use out of 23&Me results)

Regards
Journeyman
 

alicec

Senior Member
Messages
1,572
Location
Australia
Re: "I have never found any studies confirming such a mechanism."
Is that in reference to the idea that whilst most B12 is absorbed in the Ileum with the assistance of intrinsic factor there is also a passive diffusion process that explains an absorption of about 1-2% of any given B12 dosage??

No. The passive diffusion process is well established.

I was referring to Freddd's idea that the two active forms taken up in this way are used directly by their respective enzymes, rather than going through the usual processing pathway.

I can't find any studies that support this idea.
 

alicec

Senior Member
Messages
1,572
Location
Australia
Re: this MMACHC protein: did the article explain what the relevant SNP's might be so we can check whether we have the mutations (would be good to get more use out of 23&Me results)

Here is the article. The binding of hydroxy and cyanoB12 was compared for MMACHC proteins carrying three different amino acid changes which have been found in patients.

The protein with G147D couldn't bind either form, with R161Q, hydroxy was bound with similar affinity to the wildtype protein but cyano was bound poorly, with H122A there was reduced binding compared with wildtype but again hydroxy was better bound than cyano.

Here is the ClinVar list of variants in the MMACHC gene and here is the OMIM entry. These should enable you to put an rs number to these variants.

I have no idea whether 23andme tests for any of these variants.

Please note cbcC disease is very rare. You wouldn't have survived to adulthood with this disease without very serious health problems (if at all).

ETA The H122A variant was made to test the idea that the histidine at this position is important to B12 binding. I don't think it has actually been found in patients.
 
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