The 12th Invest in ME Conference, Part 1
OverTheHills presents the first article in a series of three about the recent 12th Invest In ME international Conference (IIMEC12) in London.
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B12 Supplements - Latest Developments and efficacy?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Journeyman, Jan 7, 2018.

  1. Journeyman

    Journeyman Senior Member

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    Hi all,

    B12 supplementation seems to be such a grey area. Even when searching for journal literature to confirm the efficacy or otherwise of the latest B12 treatments such as nasal sprays or transdermal oils I'm finding inconclusive findings.

    I made a point of learning B12 some 2 years ago with the most useful information coming from Fredd's postings here on the issue. More recently in 2015 after 2 years of using sublingual b12's I faced an enormous dental bill to fix my teeth where the enamel had been destroyed by the consistent B12 usage (taking regular pineapple fruit didn't help either!) I tried transdermal b12. As to how effective it is I can't really say. Having read all the symptoms people describe following a given b12 its hard to know whether the symptamologyg is the result of the product being inadequate or perhaps too effective (healing reactions or toxic metal mobilisation?)

    I recently had elevated MCV's on a standard blood test and noticed an upward trend over the past year. I suspect that I never actually built my B12 levels to a substantial level, or the coffee enema's I did following B12 supplementation have somehow drained the liver stores of it meaning that after 9 months of no B12 supplementation my levels are finally low again?

    Either way I'm about to do an order of some form of B12 and am baulking at doing another transdermal order. I know theres talk in these forums about 80% absorption from these oils, but this seems grossly exagerrated given recent journal articles I've read on the issue where they struggled to make an oil that would even deliver 5% effective dose.....

    I've got 6x 1mg hydroxy b12 ampoules ready to go and was thinking about doing a short term flood of the system of B12 but I recognise I'll need something longer term as this nanny state we live in here in Australia makes it so hard to source syringes needed to administer these shots.

    What about Nasal delivery systems. Having read http://forums.phoenixrising.me/index.php?threads/methylcobalamin-inhalation-therapy.33045/page-11
    I see things might have moved on in terms of B12 supplementation. @ahmo @caledonia @Learner1 @alicec I'd be keen to get your thoughts on this. Particularly taking into account this:
    https://pure.uva.nl/ws/files/3653062/3331_30771y.pdf
    contrasting with this:
    https://b12researchgroup.wordpress.com/warning-about-the-use-of-b12-sublingual-tablets/

    Keen to get your thoughts relating to the best value but most effective active b12 delivery option...

    Regards

    Journeyman
     
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  2. CCC

    CCC Senior Member

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    We moved across to transdermal b12 from b12oils.com and haven't looked back. No teeth issues, slow-release, no issues with teenager compliance.

    Over the past two years, we've gone from two slurps each of ab12/m12 and mb12 a day (so 4 slurps on the back every morning) to just 1 slurp of the ab12/mb12 combo on most days. And now we even skip the odd day without penalty. A key for us was also to take B2 and folinic throughout the day, with a nigh-time top up of mfolate (as quatrofolic).

    And, it's an Australian company. So just for once, we get to see other people complaining about international postage and customs rather than being the victim!
     
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  3. Moof

    Moof

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    Can you not buy syringes overseas, or obtain them from needle exchanges? I have injections, and they've made an enormous difference to my health. Injectable hydroxocobalamin can't be bought over the counter in the UK, so people just order it from abroad in large batches and share the cost. Syringes can be bought easily and cheaply here, although folk sometimes encounter difficulties disposing of their sharps boxes – some local authorities seem happy to clean up syringes left lying around the streets by drug users, but won't support people who're trying to dispose of them safely! – but again, needle exchanges will always take them.
     
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  4. Learner1

    Learner1 Forum Support Assistant

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    The key is to get enough into your bloodstream to get to where it needs to go. For me, a combination of oral and injectible works fine. I need a high dose, and when I investigated oils, it seemed too difficult to get the dose I needed.

    The more important question is what type of B12. While there is benefit to some HB12, most of us have an increased need for methylation, which is essential for immune system function, DNA replication, neurotransmitter production, detoxification, etc.

    Therefore, we need MB12. Some people around here claim they can't tolerate MB12, but I suspect its because they are lacking the cofactors needed to feed the entire process, including B6, B2, magnesium, potassium, amino acids, B1, and molybdenum. If you don't have adequate amounts of cofactors, you may experience all kinds of unpleasant symptoms and falsely conclude MB12 is bad for you, when in fact, your body desperately needs it.
     
  5. swatch

    swatch

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    I would be interested in reading this research. Do you have a link?
     
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  6. Journeyman

    Journeyman Senior Member

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    Yeh I've actually just placed an order for my first folinic acid supplement (source naturals iirc) for the first time in 7 years noting Ben Lynch's video that explained the importance of folinic for the DNA integrity which methyl folate doesn't really address??
     
  7. Journeyman

    Journeyman Senior Member

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    Yeh I believe here in Australia needle exchanges would be the most viable option but I know the types of people I'm likely to encounter upon visiting such a place and if its the case that intranasal, sublingual or transdermal b12 sources are just as good (even for deep neurological healing) then I'd rather avoid the risks inherent to both injecting B12 and visiting the exchange. (drug addicts)
    I though IM injections were risk free if done correctly, but after reading this I have yet another reason to give pause before doing a B12 injection, particularly if I find obtaining a micro filter for the injection difficult or expensive to obtain. (PS I know that article talks about risks associated with IV rather that IM but I found a related article weeks ago that I can't find now which confirmed a risk due to fine glass particles being treated by the immune system as foreign bodies when encountered in muscle tissue)
     
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  8. Journeyman

    Journeyman Senior Member

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    Hi Swatch, I think it was this article, though it does conclude that delivery of therapeutic amounts of b12 may be possible...
    I'm pretty sure that either deep within this article or in a related one I found something that suggested that even with optimal emulsifiers etc. the highest penetration percentage was in the order of no more than 5% and that would be v important for those here who are of the understanding that its more like 80% (of which I was one)
     
  9. gettinbetter

    gettinbetter Senior Member

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    I have just started using B12 oils from Australia and it is very potent
     
  10. Galixie

    Galixie

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    It's odd that you can get injectable b12 without a prescription in Australia but you need a prescription for the syringes?

    I have the opposite problem though. I live in a state where it's legal to buy syringes without a prescription (as long as the pharmacist is willing to sell them), but I need a prescription for the b12. :rolleyes:

    I realize that there are many people who have opted to believe the marketing about methylcobalamin. Research has indicated that no delivery method of any of the cobalamin forms goes directly into the cells as active b12 without going through a series of steps. So it does take the same amount of work for your body to process either cyano, hydroxy, or methylcobalamin forms. Your body also has to create sufficient adenosylcobalamin out of whatever form you take.

    I've been on b12 for nearly 10 years and my personal experience is that cyano injections work best for me. I never did well with any sublinguals that only contained b12, but I got a limited benefit from one that had a mixture of b vitamins and folic acid. Trial and error seems to be the only way to find out what works.

    While the discovery of b12 was a Nobel prize winning feat over 80 years ago, science has pretty much dropped the ball on figuring out why some people need higher or more frequent amounts than others. There isn't even accurate testing available for deficiency or for the disease, pernicious anemia, that they were originally trying to cure. It became an orphan disease and b12 injections became so associated with the placebo effect that there are still many doctors who don't realize how debilitating a b12 deficiency truly is. It's heartbreaking.

    If I could make a change in the world I would want all doctors to be aware of how important this vitamin is in all age groups and to have them actually think of it when coming up with a differential diagnosis.

    Sorry for the long post. I hope you find a solution that works well for you. :)
     
  11. Moof

    Moof

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    I guess it depends what your local delivery system is – it may not compare to ours at all. Our local pharmacy is one of several needle exchanges in the area, and during the daytime is usually just full of elderly folk picking up their prescriptions and parents with poorly young children. I've been going there for 20+ years, and had no idea it was a needle exchange until I looked up the details for someone who was having trouble disposing of their sharps boxes. I've since seen one recovering addict being taken into the cubicle for his dose of methadone, but that's it.

    I have to admit, I do now use a filter needle when drawing up my B12. I'd never heard of the ground glass risk at the outset, but as soon as I discovered it, I bought filters as well. Having said that, the NHS never uses them when giving B12 injections. Someone trying to find out more surveyed a B12 deficiency support group, and none of the pernicious anaemia sufferers had ever seen a GP or nurse use a filter to draw up from glass ampoules – mine doesn't, either. I think the risk is probably pretty minuscule.

    Just to explain why I self-inject at all: as per general NHS policy, my GP will only give me injections every three months. I get symptoms unless I have them much more frequently, so I top up myself; I don't inject IM, though, I do sub-cut into tummy fat, which is easier and safer for people without medical training. My deficiency symptoms were quite extreme at the outset (I was close to being diagnosable with dementia), but they failed to respond to other delivery methods; they improved within three weeks of starting injections, so I think they're the only option for me. That doesn't mean, of course, that other methods won't work for you. My problem is almost certainly down to years of gastric problems, leading to an inability to absorb B12 from food or oral supplements.

    Sorry this is rambling and over-long...brain fog!
     
  12. Sonegar

    Sonegar

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    I took a look at your link but the article doesn't cover the difficulty you mentioned when you said : "struggled to make an oil that would even deliver 5% effective dose". Perhaps it was another article? It would be interesting to know.

    I am about to buy some expensive B12 oil and don't want to waste my money if there is something equally good for less cost.
     
  13. alicec

    alicec Senior Member

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    I've bought them online without problems.
     
  14. alicec

    alicec Senior Member

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    I agree there is a lot of hype about the active B12 forms designed to sell supplements. At the same time the situation is not nearly as clear cut as you suggest in this statement.

    It is certainly true that the normal B12 trafficking route removes the upper axial ligand (the methyl, adenosyl, hydroxy, cyano group) and then distributes the cobalamin to be methylated or adenosylated as needed.

    Theoretically, it shouldn't matter what form is taken, but at least in some circumstances, some forms do appear to be superior to others.

    Some of these different effects are merely anecdotal while some have been at least partially investigated.

    This study is particularly telling since it involved a patient with a defect in lysosomal processing of the B12/binding protein/receptor complex that is the usual form in which B12 is taken into cells. B12 can't progress to the next step of removal of the upper axial ligand and subsequent delivery of B12 to the two B12 dependant enzymes.

    Treatment of the patient with cyanoB12 did not help but treatment with hydroxyB12 did. Other forms were not tried. What is relevant here is that the normal trafficking pathways were not working in the cell but hydroxyB12 was able to activate the two B12 enzymes. This suggests there are alternative pathways for B12 uptake and use in the cell, though we don't know what they are.

    Here is another study of effects on neurons, where methylB12 was clearly superior.

    As the different forms become more widely available and patients continue to report more favourable response to some forms compared with others, we can only hope that more will be done to fill in the many gaps in our knowledge of B12.

    Here is a summary table from a recent review, listing the things we still need to understand to decide whether and in what circumstances some forms of B12 are superior.

    In general though I think the cyano form is less and less favoured. Some people have problems processing the cyano group and the hydroxy form has been shown to be better absorbed and longer lasting. This is why it is favoured among treating physicians in the West at least.

    The Japanese have done a lot of work on methylB12 and favour this form, unlike Europe and the USA, which favour hydroxyB12 (at least clinicians treating severe B12 disturbances).

    There has never been a comparative clinical trial as far as I am aware.
     
  15. Hip

    Hip Senior Member

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    Sorry to hear that. There is a thread about this:
    CAUTION: Vitamin B12 Sublinguals — The Citric Acid Additive Can Erode Tooth Enamel

    I think it is the citric acid preservative in B12 supplements that causes the tooth erosion; citric acid is particularly erosive to tooth enamel.

    Perhaps that thread should be placed as a sticky thread at the top of the B12 sub-forum. @Sushi, given @Journeyman's experience of dental problems from B12 sublinguals, do you think it is a good idea to make the above thread about B12 tooth erosion a sticky in the B12 forum?



    I cannot see how transdermal B12 oils will lead to any B12 absorption. The molecular weight of methylcobalamin is 1344 daltons, and hydroxocobalamin is 1346 daltons.

    Now the 500 dalton rule for transdermal absorption states that molecules above 500 daltons cannot get absorbed through the skin. The oral mucous membranes also follow this 500 dalton rule, so in principle B12 sublingual tablets should not work.

    However, I have read elsewhere (see here) that the nasal mucosa can absorb molecules up to 2000 daltons, so by snorting pure B12 powder intranasally, or using a B12 nasal spray, you should be able to absorb quite a bit.

    This study found that compared to intramuscular injection (which we assume has 100% bioavailability), intranasal B12 spray resulted in 6.1% bioavailability. This paper estimated that B12 nasal spray results in approximately 2 to 5% absorption.



    If you are going to try using e-cigarettes to deliver vitamin B12 via the lungs, be aware that the latest research shows the e-fluid propylene glycol can convert into the carcinogen formaldehyde by the heat produced in the e-cig. I am not sure if the other e-fluid often used, glycerine, also does this.



    A new alternative way to orally take high doses of B12 is via the new intrinsic factor B12 supplements. These supplements contain intrinsic factor as well as B12, and this intrinsic factor enables the absorption of high amounts of B12 in the stomach.
     
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  16. Sushi

    Sushi Moderation Resource Albuquerque

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    I made it a sticky--it is an important caution.
     
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  17. alicec

    alicec Senior Member

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    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.
     
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  18. Galixie

    Galixie

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    Cyano is still the most commonly prescribed version in North America. Most likely due to it being the most shelf-stable version than for any other reason. Hydroxy is just not readily available here.

    My point was not that all forms are equal. It is that everybody is different and some trial and error to find the right form for the individual is necessary. That will remain true until science can fill in the knowledge gaps you've mentioned. Personally, I've only tried cyano and methyl specifically because it is difficult for me to get my hands on hydroxy.

    While the debate about what type of B12 might be superior is a valid one, it seems like it overlooks the fact that so many people with B12 deficiency are denied adequate treatment with B12 of any form. In a perfect world, B12 deficiency would be promptly identified, addressed, and the patient would be allowed to try multiple forms to find the right solution for them.
     
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  19. Hip

    Hip Senior Member

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    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.
     
    Last edited: Jan 11, 2018
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  20. Mel9

    Mel9 Senior Member

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    Just be aware that some are allergic to propylene glycol.
     
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