Paper on the design of B12 deficiency treatment protocols

[Technoid]

This might be one of the most fascinating papers I've read on B12 deficiency and treatment, with several sections exploring how symptoms relate back to the particular biochemistry processes that go wrong in deficiency. The paper was produced in 2021 for the B12 Institute, Netherlands, a specialist B12 deficiency treatment center.

It is highly technical but worth the effort IMO and should be mostly accessible to many members with some experience in reading about B12 deficiency. It also explores possible treatments/supplements other than B12 that might help the recovery process. These supplements include Glycine, NAC(N-Acetyl-Cysteine), CDP-Choline, Phosphatidylserine, Betaine (Tri-methylglycine), Vitamin C, Alpha-Lipoic Acid, Antibiotics and Probiotics.

The section on choline is quite interesting:

"Phosphatidylcholine, the major constituent of myelin sheath, is biosynthesized via two pathways:

• The CDP-choline pathway (Kennedy pathway) using choline as an essential precursor [133]

• By phosphatidylethanolamine methylation by SAM [134]

During cobalamin deficiency/inactivity, the methylation of PE into PC is inhibited due to the lack of SAM. Therefore, while the methionine cycle is slowly repaired by cobalamin supplementation, choline may act in two ways to accelerate the repair of myelin sheaths:

• choline supplementation can help to accelerate the synthesis of PC via the Kennedy pathway,

• choline is also the precursor of betaine, the coenzyme of BHMT for the alternative methylation

of homocysteine; thus choline could increase the synthesize SAM during MS slow running"

There is also a fascinating hypothesis on a possible link from formaldehyde production to the often reported "early treatment decline" that often happens when treatment begins, as follows:

"it is expected that an excessive folic acid consumption without a proper flow of folate cycle may exacerbate oxidative stress by generating more formaldehyde. However, further investigation on the flux of formaldehyde from folate oxidation must be carried out to confirm the significance. In addition, it was suggested that the oxidative damage of the unstable folates can be enzymatically repaired in mammalian cells.

...

the endogenous formaldehyde from folate oxidation might also explain the worsening of symptoms in patients at the early period of treatment. Patients with a prolonged MS inactivity may accumulate 5-MTHF. Once given a high dose of cobalamin, MS is activated and a burst of THF may occur. In the case of an elevated oxidative stress, the pool of THF may be oxidized into formaldehyde, which create more damages to the body.

We expect that it is a challenge to prove this hypothesis, as it will be difficult to simultaneously capture the moment of 5-MTHF trap release, THF oxidation, and formaldehyde production throughout the metabolism."

There is a lot more in here but I would end up excerpting the whole paper so I'll leave it there.

The paper: Design of a treatment protocol to improve the health of B12 deficient patients

pure.tudelft.nl/ws/portalfi...

[JGBH]

Thank you for this interesting post.

[Mixteca]

Thanks Technoid, fascinating but over my head atm. The bit about a possible link from formaldehyde production to early treatment decline is especially relevant to me as I'm experiencing new and very nasty and scary symptoms over 7 months into SI I can neither explain nor understand.

If anyone can simplify that explanation for me that might help a lot! 🙏🏼

[WIZARD6787]

Thank you for that!!!🙂

"Design of a treatment protocol to improve the health of B12 deficient patients. Diagnostic tools and corrective measures to analyse and improve cellular function of vitamin B12."

Pretty much my approach to my self treatment starting 6 months ago.

Finally documentation that we are all not just different some need different treatment as there are different causes. More of the same treatment is not effective. Time is required, it does not follow that waiting will cause results for a certain treatment.

I have no hope that many GP's will be of any use in applying this science. They do not even follow a simple flow chart for reasons unknown.

I was well pleased that my self treatment included 6 of the 8 supplements listed in this post. (4 included in "Simple Supplements.")

I am not going to start adding the two missing supplements without more thought.

Welcome to 2020!

[Narwhal10]

Thank you.

Saved for a later date. At a quick glance, I am pleased to see that folate, glycine, glutathione and collagen are mentioned.

[tomdickharry]

Very interesting!

Noting the paragraphs on betaine, SAM, and choline, does anyone have experience of supplementing with them?

[Technoid in reply to tomdickharry]

̶S̶A̶M̶e̶ ̶i̶s̶ ̶p̶r̶e̶s̶c̶r̶i̶p̶t̶i̶o̶n̶ ̶o̶n̶l̶y̶ ̶i̶n̶ ̶E̶u̶r̶o̶p̶e̶ ̶I̶ ̶b̶e̶l̶i̶e̶v̶e̶:̶

mayoclinic.org/drugs-supple...

There are some warnings about Serotonin syndrome.

I have tried CDP-Choline, Alpha-GPC and Betaine(TMG). I take 500mg TMG before exercise but more for the possible exercise benefits than anything else. I dont go overboard on it as high amounts may raise LDL Cholesterol.

The choline supplements I take irregularly but now and then when I feel I need a bit of brain-boost (could well be placebo). For this purpose I also like Bacopa Monnieri and Rhodiola Rosea.

I take 1 teaspoon soya lecithin mixed into breakfast which is a good source of phosphatidylcholine.

I have a Glycine supplement but haven't used it much since the intensive treatment stopped but reading this I might go back to 3g in the evening. It basically tastes like sugar so pretty easy supplement to take 😆

I use(d) too many things to make any objective assessment of what might or might not have helped recovery.

[Technoid in reply to Technoid]

well here's a SAMe supplement for sale to the UK so I guess Mayo Clinic is wrong about prescription only?

lifeextensioneurope.co.uk/s...

SAMe in-depth from National Institutes of Health (US):

nccih.nih.gov/health/sadeno...

[WIZARD6787 in reply to Technoid]

Mayo Clinic is based in USA. Perhaps it is a controlled substance in the USA.

[Mixteca in reply to Technoid]

Where did you buy your glycine?

[Technoid in reply to Mixteca]

Sunday Natural. German company. Powdered form so easier to dose a couple of grams.

[Mixteca in reply to Technoid]

Thanks! I've had some trouble finding a supplier.

[Technoid in reply to Mixteca]

yes its not so common. But try finding Serine 😅

[Mixteca in reply to Technoid]

Bought from Sunday Natural! Any good time of an evening? Do you mix it with water or something else?

[Technoid in reply to Mixteca]

I got the tablet form (of Serine) I don't take it that much but when I do its with NAC outside of mealtimes. The powdered form I guess just mix in a small glass of water, like you would with creatine. Glycine tastes like sugar anyway 🤣

[Mixteca in reply to Technoid]

I bought powdered glycine. It says to mix with 200 ml water before eating but that doesn't really fit with bedtime and sleep 🤔

[Technoid in reply to Mixteca]

meh. I wouldn't get too exercised over how to take it. Its an amino acid and the body is pretty great at absorbing those no matter what. I never bothered to take it with food.

[Technoid in reply to Technoid]

thumbing through "Nutrient Metabolism" (Martin Kohlmeier) I also see

"About 5mg gky/kg body weight is used for daily Creatine synthesis". So by taking adequate Creatine for daily needs (3g or so), that already spares some Glycine to do more interesting work elsewhere, like making some of that all-important Glutathione!

Daily Glycine intake is 38mg/kg body weight (source also Kohlmeier).

[Mixteca in reply to Technoid]

Like everything else at the mo, I'm probably overthinking this...😵‍💫

[Technoid in reply to Mixteca]

😁 stress will do that. You should see my pages and pages of notes on changing symptoms during treatment. 😅 Having seen the B12 institute paper I would like to go back in time and reduce my folic acid supplementation (based on other research and my dietary intake) along with dosing good amounts of Creatine, Taurine , NAC and Glycine to tackle glutathione depletion but that opportunity has passed. I doubt it would have much effect for me now since probably almost everything that could be repaired now has been.

[Cherylclaire Forum Support]

Thanks, Technoid - a quick glance has made me smile:

A page and a half of symptoms ? Mercy me !

A mention of salivary gland haptocorrin in transport chart (fig 4.2) ? Yippee !

Already like these people so much that I'm willing to read the other 80 pages. Asking much of my brain here.

Another great find.

[scnuke]

SAMe is readily available at most retail drug stores and online without Rx in the USA, however it is relatively expensive. I see it listed at around $50/30 tablets. That is more expensive than 30ml of B12. I am not sure I am ready to add this to my already bursting at the seams medicine cabinet at this time.

[MorningMist]

Very interesting paper. I shall read and digest it in sections. I suspect degrees of deficiency due to faulty enzymatic pathways and oxidative stress affect a greater no of people than we know. And the individuals concerned don’t know because they have never felt any other way.