New method of dosage of B12--Discredited!

[WIZARD6787]

The below is without citation and I may be incorrect.

Statement of Facts: Edit-I was using a form of analysis. The 'Statement of facts' Is what I was using and accepting as true to form my hypothesis and conclusion. It was not an absolute which would be reasonable to assume. My bad for assuming the people of this forum used this type of form for analysis. I then compounded this error by continuing on after the results of my experiment to describe my self treatment plan going forward . I meant no offence and will not do it the same way again.

— B12 is a water soluble vitamin with no known adverse effects in the 60 years since it was first synthesized, including in large doses.

— injections of B12 are limited to 1-2 ml due to adverse effects on tissue at higher amounts.

— 2% +- of any B12 administered is retained in the body and the remainder is excreted in the urine within 6 hours. Typical dosage used for evaluation of retention is 1mg/ml. This is incorrect. And is my error. I did some reading on what happens after an injection and could not find any studies that address that issue in a comprehensive manner. Pretty much a whole lot goes on. It is back to symptoms as being the best way to determine what dosages to take.

— An increase in the amount of B12 administered results in the percentage retained decreasing and the excreted amount increasing. Diminishing returns.

— The efficacy of B12 sublingual has not been tested and therefore has not been proven or disproved.

Hypothesis:

A dose followed by another dose within 6 hours may result in an increase of B12 available at the cellular level due to a longer period of time that B12 is continuously available.

Experiment:

Yesterday I administered 3mg of B12 sublingual liquid at 7:00 am. I then administered 3mg of B12 sublingual liquid at 10 am. I then administered 6 mg of B12 sublingual liquid at 7:00 am.

Results:

Not definitely positive, certainly not negative. I did experience a minor increase in tingling and numbness in fingers and toes and an increase in brain fog which I see as signs of healing.

Self Treatment Plan of B12 Supplementation going forward:

Repeat yesterday's regiment and monitor for 7 days then evaluate on April 1 2023.

Current Supplementation:

B12 as above.

25mg B6 as Pyridoxal 5 Phosphate twice a day.

Edited: Corrected to .4 mcg per day Folic Acid

187.5mg Magnesium per day

50mcg D3 and 75mg K2 in spray twice a day.

Hair of newt so I can grow gills and swim under water.

Self Treatment Plan Going Forward:

As above until I finish my work on a nutritional supplement designed for autism which is a neurological issue. I then expect I will choose to only supplement with that supplement, B12 and B6. Note: I experience peripheral neurotherapy that is more severe when I do not take B6.

I feel that my review of supplementation is complete and I am in conformance with the current science of B12 deficiency and what is best for my healing is to focus on life again. I will continue to monitor PAS site for any breakthroughs in the understanding of B12 deficiency or PA.

[Midnight_Voice]

Without citations, these just have to be your personal observations, but hey, whatever works for you.

Certainly, on retention, I have seen 48 hours quoted as the retention period; the NICE guidelines would indicate a retention period of 2-3 months; during COVID, we were told that B12 was stored in the liver for up to a year.

(So maybe citations are valueless anyway).

On sublingual, we are told that the B12 molecules are too big to be absorbed that way, and any benefit comes from what you swallow and have absorbed in the usual way.

(Except of course, you are using sublingual because you can’t absorb the usual way).

Injection amount limits have been variously set at 3ml and 5ml, with some caveats that large muscles should be used, and SC should not go that high.

In the end, we all do what works for us. We started with extra folic acid a couple of weeks ago, just the tablets and 4mcg dosage used in pregnancy, to keep up the B12/folate/iron balance (we already supplemented the iron), and two weeks have passed, without any flagging so far, from what was before a weekly routine.

We thought the folate might help, as it is in the relevant metabolic pathway, but we are staggered at this result.

Our general takeaway is that we are very lucky that we can experiment in this way with safe, non-prescription, adjuncts to the IM hydroxycobalamin.

[WIZARD6787 in reply to Midnight_Voice]

Hey Midnight Voice, Thank you for your reply it is appreciated. Great information. I did note it was without citation. 😀

The data I was referring to was a measurement of the B12 in the urine after an injection. It did not address if the retention or use of the B12 just that if it was in the urine it was not in the body.

My choice to try sublingual was driven by my desire to travel for 6 months and avoid needing syringes. After a 4 month trial I determined to my satisfaction than there was no determinable difference between the 3 mg of Hydroxocobalamin I was injecting twice a day IM and the sublingual.

Nice work on discovering the benefit of Folic Acid for you.

What is flagging?

I agree it is fortunate we can look for a solution with non-prescription supplementation.

[tomdickharry in reply to WIZARD6787]

Just wondering what method you use for measuring B12 in urine?

I have some of my own but they use a colorimeter or spectrophotometer.

Also there are supplements and food ingredients that can give false readings.

[WIZARD6787 in reply to tomdickharry]

I don't personally measure I was referencing others work.

My only expertise is turning beer into urine. 😀

[Midnight_Voice in reply to WIZARD6787]

flagging - google.co.uk/search?q=flagg...

[WIZARD6787 in reply to Midnight_Voice]

Thank you!

[helvella in reply to Midnight_Voice]

The "stored in liver"/retention period is, as I understand, a misapprehension.

It is a figment of incorrect analysis - where enterohepatic recirculation itself is ignored but its effects interpreted as being due to stored B12.

Take away that recirculation and the storage claim fails.

And I think there is something very wrong about 4mcg folic acid dose!

Should it be 400 micrograms or 4 milligrams?

[WIZARD6787 in reply to helvella]

Hey helvella, Thank you for your reply, it is appreciated.

You are correct I made an error in the amount of Folic Acid I currently take. It is .4 mcg and I corrected it in my post. My folic acid tests have consistently shown mid range. I take the folic acid only as a precaution in consideration of how B12 and Folic acid might work together.

I did not save the full information on where I got my information on the bodies retention of B12 from an injection. This is what I saved.

>>The specialist says of that of the 1500mg - body uses what it can in first 6 hours. Approximately 1% only is used by body for repair, 1% stored and the rest excreted in my wee.

I was not referring to storage or retention. I was accepting this to be true for my analysis.

[Sea-blue]

Hi Wizard, maybe rethink the amount of B6 you’re taking daily. B6 toxicity can manifest itself with similar symptoms to B12 deficiency. 10 mg a day is safe. There are plenty of peer reviewed studies on this on Google scholar. Just thought I’d mention . I take a B Complex with 10mg daily , then have a break from B6 and take a B complex without for two months .

[WIZARD6787 in reply to Sea-blue]

Thank you Sea-blue for your reply. B6 in the form of Pyridoxal or Pryidoxal HCL is known to cause peripheral nephropathy as it interferes with Pyridoxal 5 Phosphate. Which is why I use Pyridoxal 5 Phosphate.

[Sea-blue in reply to WIZARD6787]

That’s interesting Wizard. I like it when I learn new things. Will look this up myself too about the different forms of B6

[WIZARD6787 in reply to Sea-blue]

This is the information I used to decide on my B6 intake.

The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function

Misha F Vrolijk 1 , Antoon Opperhuizen 2 , Eugène H J M Jansen 3 , Geja J Hageman 4 , Aalt Bast 4 , Guido R M M Haenen 4

• PMID: 28716455

• DOI: 10.1016/j.tiv.2017.07.009

Abstract

Vitamin B6 is a water-soluble vitamin that functions as a coenzyme in many reactions involved in amino acid, carbohydrates and lipid metabolism. Since 2014, >50 cases of sensory neuronal pain due to vitamin B6 supplementation were reported. Up to now, the mechanism of this toxicity is enigmatic and the contribution of the various B6 vitamers to this toxicity is largely unknown. In the present study, the neurotoxicity of the different forms of vitamin B6 is tested on SHSY5Y and CaCo-2 cells. Cells were exposed to pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5-phosphate or pyridoxamine-5-phosphate for 24h, after which cell viability was measured using the MTT assay. The expression of Bax and caspase-8 was tested after the 24h exposure. The effect of the vitamers on two pyridoxal-5-phosphate dependent enzymes was also tested. Pyridoxine induced cell death in a concentration-dependent way in SHSY5Y cells. The other vitamers did not affect cell viability. Pyridoxine significantly increased the expression of Bax and caspase-8. Moreover, both pyridoxal-5-phosphate dependent enzymes were inhibited by pyridoxine. In conclusion, the present study indicates that the neuropathy observed after taking a relatively high dose of vitamin B6 supplements is due to pyridoxine. The inactive form pyridoxine competitively inhibits the active pyridoxal-5'-phosphate. Consequently, symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency.

[Gambit62 Administrator]

I don't really understand your regime - you seem to be confusing delivery methods - sublingual and injections. they are not comparable in terms of absorption or retention.

All of the injectable B12 gets into the circulatory system. Only 1% of sublingual dose gets into the circulatory system.

The rate at which B12 is removed (mainly by the kidneys) is proportional to the excess amount circulating and I've generally seen decreases by 50% in first 24-48 hours from studies on injections. However, there will be limits to how much can be removed and this will be significantly lower in any patients who have kidney disorders.

[WIZARD6787 in reply to Gambit62]

Gambit, Thank you for your reply it is appreciated.

>>All of the injectable B12 gets into the circulatory system. Only 1% of sublingual dose gets into the circulatory system.

This is new to me and contradicts the following which does not mean it is incorrect. I am always suspicious of any studies regarding B12 that does not mention symptoms are what matters.

pubmed.ncbi.nlm.nih.gov/306...

Obviously all injection B12 gets into the blood stream.

This was the information I was using in my analysis. Which I will research later.

"The specialist says of that of the 1500mg - body uses what it can in first 6 hours. Approximately 1% only is used by body for repair, 1% stored and the rest excreted in my wee."

>>The rate at which B12 is removed (mainly by the kidneys) is proportional to the excess amount circulating and I've generally seen decreases by 50% in first 24-48 hours from studies on injections. However, there will be limits to how much can be removed and this will be significantly lower in any patients who have kidney disorders.

I was aware of this information. My questions started when I accepted that people experience a positive change when topping off which means they do not have an excess amount circulating because adding to an excess amount would only mean more excess amount. As I write I wonder if excess amount means an excess amount according to blood levels?

[Gambit62 Administrator in reply to WIZARD6787]

Excretion rates of B12 will also depend on what the B12 has been bound to. One possibility in people who have high levels is that the B12 is bound to a protein that means it is no longer bio-accessible but also prevents it from being excreted. Studies that lead to the '1 month' frequency for injections also showed that in some people blood levels remained high for years after an injection.

The study you quote went on for 3 years so was presumably about results after 3 years so doesn't tell you anything about how much of the supplement gets into the circulatory system.

[WIZARD6787 in reply to Gambit62]

Fascinating about the binding to protein and not being bio available or excreted.

I interpret the study to show that more B12 is measured in the circulatory stream as evidenced by blood serum tests with SL than IM and does not address the issue of bio availability.

It seems I am coming across as against the IM or for SL and that is not the case. I simply wanted to avoid the syringes when traveling abroad.

Show me the symptoms.😀

[WIZARD6787 in reply to Gambit62]

The study does not indicate if the subjects had PA. Could be the sublingual was functioning the same as liquid oral.

[Gambit62 Administrator in reply to WIZARD6787]

passive absorption process which is how high dose oral works is independent of the mechanisms destroyed by PA.

The article is an abstract and it was a long term study, so doesn't tell you anything about short term effects of treatments and absorption rates. The main article is behind a paywall.

[Hidden]

I believe that B12 in high doses can put a pressure on the heart, especially if someone already has heart or blood pressure problems. I took 2,400mcg sub lingual liquid and I almost felt my BP rise immediately. (and I'm generally well). I felt unwell with it. I spoke with a practitioner about this and she said that high doses can cause symptoms. (I'm not totally sure, but I think the BP will rise). I think it's best that people are aware of this.

[WIZARD6787 in reply to Hidden]

Thank you for your reply and information. This is the information I used to determine what form of B6 to take.

This is the information I used to decide on my B6 intake.

The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function

Misha F Vrolijk 1 , Antoon Opperhuizen 2 , Eugène H J M Jansen 3 , Geja J Hageman 4 , Aalt Bast 4 , Guido R M M Haenen 4

• PMID: 28716455

• DOI: 10.1016/j.tiv.2017.07.009

Abstract

Vitamin B6 is a water-soluble vitamin that functions as a coenzyme in many reactions involved in amino acid, carbohydrates and lipid metabolism. Since 2014, >50 cases of sensory neuronal pain due to vitamin B6 supplementation were reported. Up to now, the mechanism of this toxicity is enigmatic and the contribution of the various B6 vitamers to this toxicity is largely unknown. In the present study, the neurotoxicity of the different forms of vitamin B6 is tested on SHSY5Y and CaCo-2 cells. Cells were exposed to pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5-phosphate or pyridoxamine-5-phosphate for 24h, after which cell viability was measured using the MTT assay. The expression of Bax and caspase-8 was tested after the 24h exposure. The effect of the vitamers on two pyridoxal-5-phosphate dependent enzymes was also tested. Pyridoxine induced cell death in a concentration-dependent way in SHSY5Y cells. The other vitamers did not affect cell viability. Pyridoxine significantly increased the expression of Bax and caspase-8. Moreover, both pyridoxal-5-phosphate dependent enzymes were inhibited by pyridoxine. In conclusion, the present study indicates that the neuropathy observed after taking a relatively high dose of vitamin B6 supplements is due to pyridoxine. The inactive form pyridoxine competitively inhibits the active pyridoxal-5'-phosphate. Consequently, symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency.

[WIZARD6787]

The statement of facts had an error which rendered the hypothesis not credible. Specifically "— 2% +- of any B12 administered is retained in the body and the remainder is excreted in the urine within 6 hours. Typical dosage used for evaluation of retention is 1mg/ml" is not valid.

The exercise was helpful to me and a thank you to all that commented.

I may in the future rewrite my method of treatment and will now be aware not to write it in a way that might indicate I know what I am doing. 😀

Right now I am going to walk along the River Clyde and think about the way things sometimes are. Likely cry more than a little bit. Enjoying less fatigue!

[Midnight_Voice]

These are my takeaways:-

The science is very complicated, and the studies very uncertain. And many start from B12d which has arisen from causes other than PA, with treatment outcomes that may be inapplicable to PA.

If you have PA, you can’t absorb sufficient B12 from a normal diet. So the possible treatments are high-dose oral, sublingual, subcutaneous injection, and intramuscular injection.

Apart from during COVID, when alternative options from the above were pursued, and largely failed, the NHS preferred route is IM. It seems to me that common sense would suggest this would be the most effective treatment, and only a few outlier studies, often carried out in circumstances and with methodologies we might not find applicable, have suggested otherwise.

Entirely anecdotally, we (PA sufferer and carer) have tried HDO and SL, and neither works for us. We are happy for the people they do work for, but we are not among them.

SC might work, but might as well be hanged for a sheep as for a lamb, and so we get to IM.

There seems to be only two things wrong with the NHS approach to treating PA with IM; lots of people they won’t give it to, and lots of people who do get given it don’t get given it frequently enough.

These are points we address with SI-ing, at a frequency of the patient’s choosing based on their personal perception of when a jab is needed, usually backed up by the carer’s observation of when ‘the clock is running down’.

So we do what the NHS would do, except we do it more frequently, balancing iron, folate and B12 accordingly.

And it works; insofar as we at least avoid the very worst symptoms of PA, and get into a holding pattern with something that can never be cured.

Perhaps one day, the literature will suggest something, or come up with some finding, that would indicate we should do something different, and if so, we will gravely consider it. But it will still have to work as well, or better, than what we do now.

[WIZARD6787 in reply to Midnight_Voice]

Thank you!