B-12 - The Hidden Story

[Freddd]

So Freddd - Are you saying that the B12 protocol rarely seems to work for thyroid patients, for whatever reason (their own reluctance, etc.)? Or are you saying you don't agree with their conclusion regarding B12 affecting the adrenals (and then thyroid function) in any significant way, and therefore recommend continuing?

Iow, it seems that you believe it would be worth going ahead even with the concerns I have raised, is that right? I'm just trying to get sense of whether this will be worth trying, or just has the potential to cause a worsening like so many other things.

I'm also extremely leery of pumping in that much methyl b12 with known mercury poisoning issues. Can you summarize any effects or dangers that b12, adenosyl or methyl form, is known or theorized to cause in mercury patients? I get a day-long effect from 1/8 of a tablet - I really can't imagine taking 8 of those in a day, esp. if I'm going to end up methylating a ton of mercury and causing more neuro damage.

Finally, if the Source Naturals adenosyl-b is crap and the Country Life isn't tolerated, what other brand do you recommend? I think you said there were two good ones, with CL being the best? I don't care if it's not as good, as long as it's somewhat active and doesn't contain folate.

Hi Starcycle,

Are you saying that the B12 protocol rarely seems to work for thyroid patients

I'm not saying that at all. I have been hypothyroid since childhood and the active b12 protocol worked fantastically for me.

Or are you saying you don't agree with their conclusion regarding B12 affecting the adrenals (and then thyroid function) in any significant way,

I don't know how it affects adrenals and thyroid funtion. What I do know is that an unussually large percentage of people responsive to the active b12s and methylfolate also are hypothyroid. Hashimotto's is specifically linked causually to b12 deficiency, an autoimmune reaction caused by low b12. B12 does not change or heal hypothyroidism. During startup it is certainly possible that there are transitory effects of various hypothecized sorts as there are a multitude of temporary fluctuations as the body changes from a very shutdown mode back to an operating mode and a multitude of functions start coming back.


and therefore recommend continuing?

Most of the people who have various hypothyroid conditions continue the active b12s and their path through the startup symptoms and afterwards appears approximately the same as those with no thyroid issues. ALso, as they emerge from the startup period and things settle down, there appear to be no effects on the thyroid funtioning and there have been very few changes in test resuts or medications over the short or long run.


Iow, it seems that you believe it would be worth going ahead even with the concerns I have raised, is that right? I'm just trying to get sense of whether this will be worth trying, or just has the potential to cause a worsening like so many other things.


People without possible deficiency symptoms don't normally have any effect at all from active b12s. I know that sounds strange to a person who has had a lot of reaction, but a lot of people, probably a majority, have no reaction at all. I think that this has a lot of potential at correcting all sorts of problems for a person who is hypothyroid but not the hypothyroid condition itself. The NORMAL course of somebody who is deficient is to have a startup reaction ranging from barely noticable if at all to extreme startup reaction involving potentially hundreds of symptoms. All the symptoms are perceived in an intensified way at the very least as mb12 affects the very wetware of perceptions. Some things may actually be intensified. They certainly shift around and change dramatically often within minutes to hours. One of the most common effects is that of being energized. It happens at the very least because adb12, and some of the mb12 converts to adb12 in most people, starts occupying the mitochondria increasing the amount of ATP being produced. Sometimes the extreme fatigue chracteristic of severe b12 deficiency is relieved starting in less than an hour. When a person has been at 1% energy for years, a sudden increase to 10% is quite a shock and feels very abnormal and may interfer with sleep as well. Further the nervous system is "energized" and starts working more. Again, "normal" funtioning feels totally abnormal after years of non functioning.


I'm also extremely leery of pumping in that much methyl b12 with known mercury poisoning issues. Can you summarize any effects or dangers that b12, adenosyl or methyl form, is known or theorized to cause in mercury patients?

This was discussed at some length much earlier in the thread. Rich mentioned knowing of two patients that had trouble after huge IV infusions in that they demonstrrated what appeared to be some mercury toxicity. I built a model based on information on mercury and methylmercury in a number of places and came up with the number of mgs IV that could reasonably be expected to perhaps cause a problem, and that was 700mg as a single dose. As a 5000mcg sublingual dose can put 1mg into the bloodstream, a single dose of 700 5mg tablets might cause problems. Also, 1 mg of mercury in the body could disable 100% of the methylb12 a person has in their body now and for the next 5 years or more possibly explaining why 80% of mercury symptoms are also b12 deficiency symptoms. At normal level of mb12 input a very small amount of mercury is converted by the body to methylmercury and elliminated by the liver at the rate of 1% per day. So over a 1 year period, 97% of the mercury converted to methylmercury is cleared from the body. Each year after that another 97% is elliminated. A steady stream of methylb12 then appears to cause the removal of mercury from the body. With a small but steady stream the peak amount present at a given dose of mb12 appears to occur around day 300 where it remains level as more is released and 1% is elliminated daily. Now this is only a first draft model and I am awaiting any comments on it or references that suggest other rates of excretion or anything that would require a refinement of the model.


I get a day-long effect from 1/8 of a tablet - I really can't imagine taking 8 of those in a day,

Becasuse of the way serum halflife works, a larger dose doesn't last a whole lot longer. Also 64x the dose might only have twice the effect. It is not linear. The first 250mcg appears to make the most observable differences. In running a series of comparisons with injections, the amount of effect appeared to increase the most in the first 1mg, a small amount more with the second mg and very little going to 5mg. Then at 7.5mg there is one more sudden increase we have noted as the dose that gets into the CNS for some people, and then no difference in effect up to 25mg.


esp. if I'm going to end up methylating a ton of mercury and causing more neuro damage.

Taking even large sublingual doses can't methylate a ton of mercury, metaphorical or literal. The methyl group consitutes 1.6% by mass of mb12 as only this part methylates mercury. As mercury has about 1/7 the mass of mb12 it takes about 7mgs of mb12 to methylate 1 mg of mercury assuming 100% effeciency. As efficiency is actually only a microscopic portion of the mb12 as the body uses and/or retains perhaps 20 mcg (1000mcg per mg) with all the rest being excreted in the urine, 99% unchanged within 24 hours. So even a 10% rate looks generous, such that it takes 70mg to methylate a mg of mercury and at a more realistic 1% efficiency then 700mg of mb12 to methylate 1mg of mercury. That is two years of 5mg sublingiual daily of a 5 star mb12 sublingual brand, and most of that would be excreted during that time. The beginning of very mild toxic symptoms is considered to be around 40mgs of methyl mercury.

Mb12 is a vitamin with neuroprotecticve characteristics and promotes healing even from damage from other sources.


Finally, if the Source Naturals adenosyl-b is crap

I didn't say that. I said that their sublingual methylb12 5mg was not effective. I don't know if their other sizes or types of sublingulas use the same mix of ingrediants or if the pill base itself is the responsible party. There are variations in the effectiveness of injected mb12 similar to those in the sublingual mb12 so it may be the different bacterial variations of mb12 that are causing the problem. All I can say about their adb12 is that we didn't test it. At the time we could only find the Country Life and it was great. I use and have used other Source Naturals products without any problem.



and the Country Life isn't tolerated,

Have you tried it? It has folic acid in it but not methylfolate. Methylfolate is the most critical cofactor with the two active b12s.



what other brand do you recommend? I think you said there were two good ones, with CL being the best? I don't care if it's not as good, as long as it's somewhat active and doesn't contain folate.

If you could do a side by side test of the two adb12s that would be good but would take a lot longer than an mb12 test. What kind of reaction do you have to what kinds of folates? Folic acid? Folinic acid? methylfolate? are they different for the different forms. What are the exact reactions?

 

[Freddd]

Hi, Janis

OMG - I have just spent Christmas with gallbladder problems - indigestion, backache, pain and nausea - seemingly out of the blue. I did blood tests but there was no inflammation, no infection, no high LFTS - so my doctor is stumped. I had upped my B12 to 10g shortly before it started. I stopped all B12s except the folate, but have recently reintroduced mB12 at 1g.

Why would too much mB12 and possible over-methylation lead to inadequate bile production / gallbladder problems? I had no detectable liver problems - at least none that showed up on tests. I had put it down to coincidence, but now you have got me wondering....

In your case, what supplement do you have to take to complete the methylation cycle?

Nicola

Hi Nicola,

I can't picture it as anything but a coincidence perhaps contributed to by holiday foods. There is no reason at all to think that having 2 mgs of b12 in your blood with 75% of it leaving in the first 2 hours has a thiong to do with it at all. Any effects on liver b12 contents are delayed. The bile output contains small amounts of b12 isn't regulated by it. I suspect you mean 10mg instead of 1000 times more as 10 g. It is highly unlikely that 2mg in sertum for a few minutes is going to overdrive methylation. It's not miraculous in terms of methylation power, just a necessary part of it.

 

[starcycle]

Hi Freddd,

Okay, let me summarize your answers to my concerns as I understand them so far:

1. In your view, b12 protocol is not likely to have any effect on hypothyroidism at all, not worsening it, and not improving it. However, because you believe hashimoto's could be related to b12 deficiency, b12 loading theoretically could affect or reverse that?

2. b12 is not likely to methylate any significant amount of mercury except in doses several hundred times higher than what we are talking about, doses that would be impractical if not impossible to take orally.

3. reaction to b12 is not linearly related to dosage.

4. SN ab12 has not been tested, so we don't really know how effective (or ineffective) it is in regard to this protocol. It might even be more effective than CL, we don't know.

and the Country Life isn't tolerated,

Have you tried it? It has folic acid in it but not methylfolate. Methylfolate is the most critical cofactor with the two active b12s.

what other brand do you recommend? I think you said there were two good ones, with CL being the best? I don't care if it's not as good, as long as it's somewhat active and doesn't contain folate.

If you could do a side by side test of the two adb12s that would be good but would take a lot longer than an mb12 test. What kind of reaction do you have to what kinds of folates? Folic acid? Folinic acid? methylfolate? are they different for the different forms. What are the exact reactions?

I react with severe, almost catatonic depression from ordinary folate and from folinic acid (e.g., Thorne Folacal). The effects persist until the folate is worn off, usually I think about 6 hrs. at least. To my knowledge I have never tried methylfolate.

 

[Freddd]

Hi Freddd,

Okay, let me summarize your answers to my concerns as I understand them so far:

1. In your view, b12 protocol is not likely to have any effect on hypothyroidism at all, not worsening it, and not improving it. However, because you believe hashimoto's could be related to b12 deficiency, b12 loading theoretically could affect or reverse that?

2. b12 is not likely to methylate any significant amount of mercury except in doses several hundred times higher than what we are talking about, doses that would be impractical if not impossible to take orally.

3. reaction to b12 is not linearly related to dosage.

4. SN ab12 has not been tested, so we don't really know how effective (or ineffective) it is in regard to this protocol. It might even be more effective than CL, we don't know.



I react with severe, almost catatonic depression from ordinary folate and from folinic acid (e.g., Thorne Folacal). The effects persist until the folate is worn off, usually I think about 6 hrs. at least. To my knowledge I have never tried methylfolate.

Hi Starcycle,

1. In your view, b12 protocol is not likely to have any effect on hypothyroidism at all, not worsening it, and not improving it. However, because you believe hashimoto's could be related to b12 deficiency, b12 loading theoretically could affect or reverse that?

No, it is unlikely the B12 will have any effect on Hashimoto's. Once the autoimmune damage is done, it isn't reversed by taking b12. It's just that the malfunction in the immune system is listed as a b12 deficiency result in a number of b12 symptoms lists from a variety of countries.


2. b12 is not likely to methylate any significant amount of mercury except in doses several hundred times higher than what we are talking about, doses that would be impractical if not impossible to take orally.

That is a hypotheical statement based on actually looking a molecular weights, rates of excretions etc. The model has not been validated in any way and no studies have been done attempting to measure this result. However, the only known such cases used large doses unlikly to be normally encountered. The question iteslf was of personal interest. I had lots of decalcified areas under braces and ended up with lots of amalgams. As the child of a dentist I also played with mercury. I was likely as contaminated as anybody here except those eating a lot of contaminated fish. What was my danger? Since I went through the first few years of mb12 with increasing doses of mb12 and no adverse reactions, though lots of startup symptoms, there wasn't anything that wasn't transitory or caused increased impairment.

3. reaction to b12 is not linearly related to dosage.

Correct. In hydroxyb12 and cyanob12 there is no dose related activity, no dose proportionate healing, at all. It reach maximum when the transport system is saturated, which happens a a very low level. The effects of mb12 and adb12 increase with dose, to a point but the rate of increase slows down. The falloff starts happening in a pronounced way after reaching perhaps 250mcg to 1000mcg entering into serum.

SN ab12 has not been tested, so we don't really know how effective (or ineffective) it is in regard to this protocol. It might even be more effective than CL, we don't know.

That is correct. Perhaps the big factor is whether the cause is the sublingual base or the mb12 itself. Without knowing that it's all a guess.

Interestingly, folate is involved with mb12 and adb12. It's interaction with both also appears to result in situations that reduces depression. We don't know how this might affect your results.

 

[richvank]

I tried 5 mg of methyl B12 for about 2 months as well as 3 mg of adenosyl. When I tested plasma aminos, my methylation cycle was stuck at methionine. And nothing was going down the transulfuration pathway to cystathionine either. Rich thought the methyl B12 could be speeding it up too much, yet my organic acid testing showed that I needed more folate and more B12. In previous tests (before introducing the methyl and adenosyl B12), my tests showed adequate folate and a mild need for B12.

The point I'm making, through my rambling fogged brain, is that taking high amounts of methyl B12 can mess things up for some of us.

Much better to test than to screw up your physiology. The impact on my methylation led to liver problems for me, like high enzymes (AST, ALT), inadequate bile production experienced as inability to digest a high fat meal (an omelet with a little cheese and avocado) which previously had been no problem.

Hi, Janis.

Here's a possible explanation for the low bile production:

Glutathione is used by the liver to produce the fraction of bile that is not associated with bile salts. So if the methylation cycle is overdriven to the point that the flow down the transsulfuration pathway goes very low, as appears to be what happened in your case, then the glutathione production will drop, and lower bile volume would be one consequence of that. High liver enzymes could reflect high oxidative stress in the liver cells, also a consequence of lowering glutathione.

Rich

 

[Suzy]

methylb12 - bile output

Oh crap. I'm taking 5mg methylb12 sublingual daily as well.

How to know how much to take ?

 

[Freddd]

Oh crap. I'm taking 5mg methylb12 sublingual daily as well.

How to know how much to take ?

Hi Suzy,

On the basis of one person having a bile problem perhaps contributed to by one thing or another is no cause for you to panic as the normal reaction to a 5mg sublingual mb12, or even 3 or 4 of them is to heal and to heal a little faster. There are lots of different roadblocks different people run into on the way back to healthy. If one were to generalize every hypothetical cause of a specific reaction one couldn't take any vitamins or supplements or even eat anything. So just remember what Ferdinand Feghoot told his son at the cannibal feast "One man's meat is another man's poi, son"

 

[anne_likes_red]

Much better to test than to screw up your physiology. The impact on my methylation led to liver problems for me, like high enzymes (AST, ALT), inadequate bile production experienced as inability to digest a high fat meal (an omelet with a little cheese and avocado) which previously had been no problem.

Janis how did you experience the inability to digest a high fat meal?
Gut symptoms...bloating or something? Reflux?

I probably eat too much fat....no complex carbs for me, so I use fats for calories and a feeling of fullness - perhaps not the ideal approach.

 

[imgeha]

Hi Nicola,

I can't picture it as anything but a coincidence perhaps contributed to by holiday foods. There is no reason at all to think that having 2 mgs of b12 in your blood with 75% of it leaving in the first 2 hours has a thiong to do with it at all. Any effects on liver b12 contents are delayed. The bile output contains small amounts of b12 isn't regulated by it. I suspect you mean 10mg instead of 1000 times more as 10 g. It is highly unlikely that 2mg in sertum for a few minutes is going to overdrive methylation. It's not miraculous in terms of methylation power, just a necessary part of it.

Hi Freddd

OK - so I got my sums wrong! Of course I meant 10mg

I wasn't quite clear in my post. I have been having gallbladder problems since the beginning of December, not just over Christmas, and I don't overindulge, as I follow quite a strict diet. So it's not food related. It's something else.

Something I'm not understanding is if the B12 leaves the body pretty quickly as you say, why my serum B12 is was above the upper range in recent blood tests? I know serum B12 means very little in terms of how much is getting where it needs to, and I would expect it to be above range at that rate of supplementation, but the fact that it was so high must mean that it stays in the body for some length of time? In the first blood test my B12 level was in excess of 2000, 10 days later it had come down to 1600.

thanks

Nicola

 

[richvank]

Hi Freddd


Something I'm not understanding is if the B12 leaves the body pretty quickly as you say, why my serum B12 is was above the upper range in recent blood tests? I know serum B12 means very little in terms of how much is getting where it needs to, and I would expect it to be above range at that rate of supplementation, but the fact that it was so high must mean that it stays in the body for some length of time? In the first blood test my B12 level was in excess of 2000, 10 days later it had come down to 1600.

thanks

Nicola

Hi, Nicola.

I think it's important to note that the B12 in blood serum can have three components. Some is bound to transcobalamin, some to haptocorrin, and if dosages are used that are higher than the binding capacity of transcobalamin, and the B12 is put in sublingually, transdermally or by injection, then some B12 can be in the serum in the free, unbound state.

These three components have different lifetimes in the blood. The free fraction is filtered out by the kidneys and excreted in the urine in the sort of timescale freddd has mentioned. The transcobalamin-bound B12 is imported into the body's cells in general in a relatively short time, also. Excess B12 is exported from the cells bound to haptocorrin. This fraction has a half-life in the blood serum of a few days, is eventually imported into liver cells, and later is excreted in the bile into the small intestine, where it has another opportunity to be absorbed and be bound to transcobalamin.

So interpretation of a measurement of serum B12 is complicated by the presence of these different components, and the component with the longest residence time is not directly accessible to the body's cells in general.

With regard to a possible effect of high B12 supplementation on bile production, as I suggested in an earlier post to Janis, this might occur through a decrease in glutathione levels in the liver cells, if the methylation cycle is driven rapidly enough that flow down the transsulfuration pathway is decreased, and glutathione production is therefore also decreased.

I favor measuring the levels of metabolites in the methylation cycle and levels of reduced and oxidized glutathione, using the Vitamin Diagnostics methylation pathways panel. If feasible, doing this together with a Doctor's Data blood plasma amino acids panel and a Genova Diagnostics Metabolic Analysis Profile will give a good picture of what is going on in the methylation cycle, the folate metabolism, the transsulfuration pathway, and the glutathione system. (As I've noted, the Vitamin Diagnostics lab is currently involved in a move to a different building, so their panel may not be available again until about the end of January.)

Rich

 

[imgeha]

Hi, Nicola.

I think it's important to note that the B12 in blood serum can have three components. Some is bound to transcobalamin, some to haptocorrin, and if dosages are used that are higher than the binding capacity of transcobalamin, and the B12 is put in sublingually, transdermally or by injection, then some B12 can be in the serum in the free, unbound state.

These three components have different lifetimes in the blood. The free fraction is filtered out by the kidneys and excreted in the urine in the sort of timescale freddd has mentioned. The transcobalamin-bound B12 is imported into the body's cells in general in a relatively short time, also. Excess B12 is exported from the cells bound to haptocorrin. This fraction has a half-life in the blood serum of a few days, is eventually imported into liver cells, and later is excreted in the bile into the small intestine, where it has another opportunity to be absorbed and be bound to transcobalamin.

So interpretation of a measurement of serum B12 is complicated by the presence of these different components, and the component with the longest residence time is not directly accessible to the body's cells in general.

With regard to a possible effect of high B12 supplementation on bile production, as I suggested in an earlier post to Janis, this might occur through a decrease in glutathione levels in the liver cells, if the methylation cycle is driven rapidly enough that flow down the transsulfuration pathway is decreased, and glutathione production is therefore also decreased.

I favor measuring the levels of metabolites in the methylation cycle and levels of reduced and oxidized glutathione, using the Vitamin Diagnostics methylation pathways panel. If feasible, doing this together with a Doctor's Data blood plasma amino acids panel and a Genova Diagnostics Metabolic Analysis Profile will give a good picture of what is going on in the methylation cycle, the folate metabolism, the transsulfuration pathway, and the glutathione system. (As I've noted, the Vitamin Diagnostics lab is currently involved in a move to a different building, so their panel may not be available again until about the end of January.)

Rich

Hi Rich

thanks for the explanation, which makes sense. As a layperson, I am puzzled as to why getting methylation going would decrease glutathione production -my very basic understanding was that it would INCREASE glutathione - but you obviously know way more than me.

If I do this testing, will it give me an idea as to what specific supplements I need and how much? I really haven't got the headspace to get my brain around the whole Yasko thing but I know that I feel better since taking the methylfolate and mB12. I just need to get over this liver / gallbladder thing ...

thanks for any input.

Nicola

 

[Freddd]

Hi Freddd

OK - so I got my sums wrong! Of course I meant 10mg

I wasn't quite clear in my post. I have been having gallbladder problems since the beginning of December, not just over Christmas, and I don't overindulge, as I follow quite a strict diet. So it's not food related. It's something else.

Something I'm not understanding is if the B12 leaves the body pretty quickly as you say, why my serum B12 is was above the upper range in recent blood tests? I know serum B12 means very little in terms of how much is getting where it needs to, and I would expect it to be above range at that rate of supplementation, but the fact that it was so high must mean that it stays in the body for some length of time? In the first blood test my B12 level was in excess of 2000, 10 days later it had come down to 1600.

thanks

Nicola

Hi Nicola,

but the fact that it was so high must mean that it stays in the body for some length of time? In the first blood test my B12 level was in excess of 2000, 10 days later it had come down to 1600.

The serum halflife of b12 is a multicompartment model. That means that it is more complicated than being some steady excretion rate. From research it goes something like this. At the time of the injection, the serum halflife is 20-50 minutes. By about 12 hours that is up to about 4 hours serum halflife. From 12-48 hours the AVERAGE serum halflife is about 12.9 hours. It takes about 2 weeks to decrease to the the same rate as if there had never been an injection. At the end of 2 weeks approximately 6 parts per million of the injection remain. This is based on 1mg injections generally. What changes is that basically 6 mcg per injection remains, regardless of the size of the injection as this is the amount that is bound in HTC1, HTC2 and HTC3, in the mitochondria of muscles and all organs, in the CNS and diffused into the various fluids and places in the body. This is the amount that actually ADDS TO THE "STORES", at best.

So how much is that? Take 4 1 liter measuring cups. Fill with 999ml of water each. In the first one, add 1 gram of salt, about 1/6 of a teaspoon, dissolve and fill to 1 liter. Each of the 1000ml in cup 1 has 1mg of salt. Take 1ml of that solution and add to cup 2. Each ml of cup two now has 1 mcg of salt. Take 1ml of cup 2 and add to cup 3. Each ml of cup 3 now has 1 ng of salt. Now take 1ml of cup 3 and add to cup 4. Each ML of cup 4 now has 1pg of salt. These are the units of measurement of b12 in the blood, perhaps 1 billionth of 1 grain of salt if there were 1000 grains of salt in the gram in the first place. So the amount retained by the body would be 6 millionths of one grain of salt.

So lets say you eat a steak dinner with 2 mcg of b12 thast is absorbed. With 5000ml of blood that distributes to 400 pg/ml instantaneuously. As about half of it almost immediate redistributes into tissues where needed the measured serum level is about half that increase. At this level, with the only b12 going into the body being via intrinsic factor and HTC1/HTC2 the kidneys absolutely ignore it as it is bound into proteins that the kidneys ignore. The very small amount absorbed by diffusion is eliminated by the kidneys very rapidly. Remember, the 2 active b12s which are mostly selected for by IF and HTC1/HTC2 are ignored so mostly in a natural situation only junk cobalamins are absorbed by diffusion, any of the other 18 or so naturally occurring cobalamins used by plants and some of various microorganisms and are promptly elliminated by the kidneys. With an injection of 1mg or the sublingual absorbtion of 1mg (from 5mg sublingual) we suddenly have 1mg of unbound cobalamins that happen to be the active ones. They are not bound into proteins and so are fair game for the kidneys. 1 mg of unbound cobalamins put into serum instantaneously will give an instantaneous serum level of 200,000 pg/ml. In real life half the cobalamin is elliminated during the absorbtion period from the muscles in an IM injection so in effect the peak might actually be 150,000pg/ml. After 1 hour that could be down to 38,000pg/ml and by 12 hours it could be down to 6000pg/ml. If the serum level before injection was 200pg/ml then 2 weeks later it might be 400pg/ml with the rest of the retained cobalamin distributed in the tissues. As the concentration goes down the halflife goes up, the kidneys are less efficient at removing it at lower serum levels. As this occurs the liver becomes the primary mechanism of excretion in the bile. Researchers have indicated that 99+% of injected b12, pretty much regardless of type, is excreted unchanged by the kidney's in the first 24 hours. How accurate this "unchanged" is I have no idea. How 5mg or 10mg injection size affects this is ony conjecture. What I have modeled is the dynamics of 3x10mg SC injections per day. It is obvious that SC injection take much longer to diffuse into the blood as some remants of them can often be seen under the skin for 24 hours. So we have a series of overlapping diffusions taking place with a relatively even serum level the whole time with approximate 1.25mg going into serum on the average each hour keeping an unnatural relatively high serum level encouraging diffusion into the CSF.


I would expect it to be above range

"Above range" is a statistical statement meaning that only 2.5% of non supplementing persons have a serum level "above the range". It has absolutely nothing to do with "ideal" level or "optimium" level. As people still have active b12 responsive symptoms well above the "top of range" it doesn't even mean a lack of deficiency symptoms. If half the population has some deficiency symptoms, and the AMA claims that 1% have "clinical deficiency signs" most of the "normal" folks are included in the "has deficiency symptoms" group also.

The MCV alert is currently set to >100 at most labs these days. That doesn't make > 92-94 invalid as the old standard, only saying that a large percentage are walking around borderline macrocytotic and that is now considered normal. It doesn't make an MCV of 99.8 any healthier than it was 10 years ago. It's just that that marker is now so common that it is normal, not healthy. In the kingdom of the blind the one eyed man who tells about what he "sees" is insane.

These "ranges" of cobalamin are based on a population that is used to walking around with borderline macrocytosis and decades of subtle chronic health problems caused by subclinical (again a definition not to be confused with facts) b12 and folate deficiencies. Statistics should NEVER be confused with facts. Statistic are descriptions, not prescriptions. The ranges of cobalamin are based on decades of research on inactive cobalamins. Researchers express their surprise over and over to see how much more methycobalamin raises serum levels compared to inactive cobalamins. If the lab mistake of cyanob12 had never happened, and the two active b12s were used in Special K and other fortified foods, and our food animals were fed feed with the two active b12s added (and they wouldn't need growth hormones to force growth), our serum levels might very well average 2-3 times what they do now and MCV alert would still be <92 and whole classes of disease would just be very rare instead of so common as to not be noticed. The whole world might use a cutoff for low cobalamin like the Japanese do of 550pg/ml. The entire understanding would be different. The effects of unbound b12s would be well known rather than the minisciule amount of the inactive b12s that can fit through several keyholes and depend upon everybody's body working perfectly.

at that rate of supplementation, but the fact that it was so high must mean that it stays in the body for some length of time?


So if one has been supplementing for some time, the body becomes saturated to an equilibrium point, the tissues lose the same amount of cobalamin that they absorb each day. When one stops supplementing, the kidneys cease to be a factor in excretion. Then the serum level is determined largely by the reabsorbtion rate of the intestines of the bile contained cobalamins. So if you went from 2000 to 1600 in ten days, that might imply a serum halflife of 30 days or so at that level. As the reabsorbtion system is strictly limited to about 10-20mcg a day shared with new absorbtion from food the rate of loss slows down as the level goes down until virtually 100% can be reabsorbed if your body is working well. So if a person's reabsorbtion rate is ideal and they eat meat their natural serum level is over 1000pg/ml and their serum halflife is over 100 days. If their reabsorbtion is essentially zero as in a lack of IF (pernicious anemia for example but not only cause) their serum level is generally below 100pg/ml and has a serum halflife of under 10 days and if that continues much further they generally die before it reaches 50pg/ml. Most everybody else is somewhere inbetween.

I have a friend going through gall bladder problems and is waiting for the new year to incur costs so that it covers next year's deductables. She has no b12 problems that are detectable. There isn't anything she can eat currently that doesn't cause nausea. If you check out the diets for such things, and take them all together, they all disagree and there isn't anything a person can eat that won't cause problems to somebody. I had my GB out in 1995 and it made a big difference in my life. It had been causing problems for at least a decade, maybe longer.

 

[richvank]

Hi Rich

thanks for the explanation, which makes sense. As a layperson, I am puzzled as to why getting methylation going would decrease glutathione production -my very basic understanding was that it would INCREASE glutathione - but you obviously know way more than me.

If I do this testing, will it give me an idea as to what specific supplements I need and how much? I really haven't got the headspace to get my brain around the whole Yasko thing but I know that I feel better since taking the methylfolate and mB12. I just need to get over this liver / gallbladder thing ...

thanks for any input.

Nicola

Hi, Nicola.

The aim of the Simplified Treatment Approach to treatment of CFS is to get the methylation cycle operating back up at a normal rate. If this is done, our testing shows that glutathione does in fact come up to normal levels.

In reference to Janis's case, she has done testing, which she commented upon here, which suggests that her methylation cycle has been overdriven, so that the conversion of homocysteine back to methionine is too rapid.

The problem with this, it seems to me, is that normally there is a branch point at homocysteine, so that some is converted to methionine, and some enters the transsulfuration pathway as cystathionine, proceeds to cysteine, and then some is converted to glutathione.

If too much of the flow is directed toward methionine, there could be too low a flow toward making glutathione. That was my point.

The testing that I suggested will tell whether this type of thing is happening or not, as well as giving quite a bit more information about many aspects of the metabolism. If the methylation cycle turns out to be overdriven, one can decrease supplements tending to speed up the methylation cycle, and can increase those that favor flow through the transsulfuration pathway. It takes some familiarity with these tests to interpret them in the light of CFS, but yes, they will give guidance about which supplements to increase or decrease. The amounts to use come from a consideration of the body's normal needs, and treatment experience.

Best regards,

Rich

 

[Suzy]

Wow, Rich, that means there is a fine line between too little and too much B12 to take in the protocol. It is needed to take homocysteine to methionine to complete the cycle in order ot create more GSH, but too much B12 converts too much homocysteine.

I guess one should really be doing regular GSH testing while on this protocol.

 

[Freddd]

Wow, Rich, that means there is a fine line between too little and too much B12 to take in the protocol. It is needed to take homocysteine to methionine to complete the cycle in order ot create more GSH, but too much B12 converts too much homocysteine.

I guess one should really be doing regular GSH testing while on this protocol.

Hi Suzy,

The question that this inspires me to ask is why does only a very small percentage of people taking the mb12 exhibit any apparant problem at all from what some might call "too much". Most of the people on this active b12 for 1 year or more, the body having gone all over the place in attaining a new equilibrium and having corrected the starvation level accomodations that had been made and have recovered from many many symptoms, and are seeing emerging comorbidities that remain. Very few have any lasting symptoms from anything but decreasing active b12s. Of course there are assumptions like the full range of basic and critical cofactors are in place or have been demonstrated as unneeded.

So what is different? I don't know the answer to that. Perhaps these things are typically lost in the rapid shuffle of shifting symptoms during the startup phase and are present for only a short while until a new equilibrium is established as the body adapts to a new balance and can undo all the starvation triage that took place. So maybe it's the pogo stick with strobe light illusion, that if you look at just the right moments the person is always suspended in mid air. Or could it be suggesting a kidney or liver malfuction so that the serum level is actually much higher at the same dose causing a different set of phenomina?

By all means get the tests done so that you know what is going on rather than jumping to conclusions. As they pointed out with the H1N1 flu vaccine that a certain number of people were going to die the day after they get the injection whether or not they got the injection so sometimes things just look connected. Good luck.

 

[richvank]

I am completely intolerant to the smallest amount of folate (like even at 1-10mcg level), and phosphatidyl serine completely messed up my HPAA a number of years ago (and reportedly changed my personality in some ways, according to friends). I have no idea what's in GVNHF, but based on my intolerance to most things (including most of the B vitamins) I'm guessing that would not be possible for me to take, either. Omega-3s have the opposite effect in me and cause inflammation, raising my liver enzymes and causing noticeable pains in my neck and left-side vasculature. So it looks like that takes care of that protocol.

The methylation pathways test still looks like it would be very interesting to have, but my integrative doctor left the area recently, and then I became basically homebound a few weeks ago with the full-blown CFS crash. So I am not optimistic about finding a local doctor to do the test, if I could even get there. If a chiropractor can order one, I might be able to do that eventually. So thanks for the information at least. I already know I am folate deficient by mainstream medical lab standards, so there is probably little doubt that this test would reveal some more problems in deeper or broader focus.

I think it's generally understood that B12 needs to come after becoming stabilized on thyroid in all people who are intolerant to thyroid hormone because of adrenal dysfunction. If anything, it would seem to apply more to CFS thyroid cases than non-CFS cases, if that's what you're asking.

Hi, starcycle.

It sounds as though you have a very interesting case!

Yes, Vitamin Diagnostics does accept orders from chiropracters. Given that your body is intolerant to many supplements, I do think that doing some biochemical testing to try to understand what's going on in your metabolism in a broader sense would be a good idea. Perhaps your integrative doctor has already done some of this type of testing. Once you know what the issues are, you might be able to target them very specifically, and to make sure the supplements don't have additives that may cause you problems.

Rich

 

[richvank]

To Suzy re: "fine line"

Wow, Rich, that means there is a fine line between too little and too much B12 to take in the protocol. It is needed to take homocysteine to methionine to complete the cycle in order ot create more GSH, but too much B12 converts too much homocysteine.

I guess one should really be doing regular GSH testing while on this protocol.

Hi, Suzy.

I don't think the line is all that fine, but if very large dosages of coenzyme forms of B12 are used, I would say that at least theoretically there is a potential for overdriving the methylation cycle, and I suspect that in Janis's case, that has occurred.

I do think that testing is a wise thing to do. I realize that it costs money, but I've found it very helpful to know what's going on at the biochemical level.
I've studied quite a few cases in detail over the past few years, and my experience is that no two cases are the same in terms of all the things that matter. The partial methylation cycle block does seem to be sort of a common denominator for a lot of cases, but it isn't the whole story in many cases. The physicians who have had the most experience with the Simplified Treatment Approach for lifting the methylation cycle block (perhaps five of them) have told me that it is an important component in their overall protocols, but that they have to address other aspects as well to bring their patients back to health. Some of them are Lyme disease and related coinfections, mold illness, and gut problems, including those due to food allergies and sensitivities.

Rich

 

[starcycle]

Hi, starcycle.

It sounds as though you have a very interesting case!

Yes, Vitamin Diagnostics does accept orders from chiropracters. Given that your body is intolerant to many supplements, I do think that doing some biochemical testing to try to understand what's going on in your metabolism in a broader sense would be a good idea. Perhaps your integrative doctor has already done some of this type of testing. Once you know what the issues are, you might be able to target them very specifically, and to make sure the supplements don't have additives that may cause you problems.

Rich

I might not be able to get any testing, and will just have to risk trying the protocol without it.

Going over the intro posts, I find that except for the A I am perfectly fine with this group:

---------------------------------------------
* Zinc - 50 mg
* Calcium/magnesium supplement
* D - 3000-5000 IU total
* A&D from fish oil, 10,000-(400-800-1000) Vitamin A should be 10,000, D might be any of 3 numbers with additional D to be taken
* Vitamin E, NOW Foods Gamma E complex
* Vitamin C – 4000+mg/day
---------------------------------------------

but completely intolerant to this group:

----------------------------------------------
* SAM-e - 200-400mg/day, makes methylb12 more effective, possibly much more effective, increases energy, improves mood
* TMG - enhances SAM-e, methylb12, l-carnitine
* L-carnitine fumarate (acetyl might work better for some), works with adenosylb12, lack can completely prevent effectiveness of adenosylb12, increases energy, aerobic endurance, improves mood
* Alpha Lipoic Acid - enhances l-carnitine and adenosylb12
* D-Ribose - enhances adenosylb12, l-carnitine, alpha lipoic acid, improves exercise recovery and energy
------------------------------------------------

It's been a long time since I tried SAM-e or TMG, but they had some significant negative psychological effects (at least). L-carnitine is contraindicated in hypothyroidism because although hypo patients are deficient, it blocks the action of thyroid peripherally (it's given to hyperthyroid patients, actually, to mitigate some of the effects of being hyper).

ALA I tolerate in extremely low doses, but after a day I am really sick from it from detox (Cutler protocol). I have some DMSA that I was going to start using to clear out presumably some metal toxins, but then the CFS started and I haven't gotten around to it yet.

D-ribose gives me a "candy bar" boost, complete with sugar crash about 20-30 minutes later. Feels bad, man!

So what might that indicate, especially the SAM-e and TMG in relation to these methylation problems?

Also, what percentage of people, or how likely would you say it is that a person gets overmethylated with this protocol? I know it's difficult to say, but is there any rough estimate of how common it is?

I took some l-glutamine yesterday to see what would happen, and today I've felt really crappy all day. I'm not sure if they're related, I also put some pine cone extract in a dropper bottle, and I think it had some celexa residue in it, so that might have caused some 5-HT effects. But I took about 750mcg of methyl-b today, so I'll see if that gives any effects tomorrow. So far today I didn't really notice anything from it, strangely enough. Usually I react very noticeably to 250mcg.

 

[Freddd]

I might not be able to get any testing, and will just have to risk trying the protocol without it.

Going over the intro posts, I find that except for the A I am perfectly fine with this group:

---------------------------------------------
* Zinc - 50 mg
* Calcium/magnesium supplement
* D - 3000-5000 IU total
* A&D from fish oil, 10,000-(400-800-1000) Vitamin A should be 10,000, D might be any of 3 numbers with additional D to be taken
* Vitamin E, NOW Foods Gamma E complex
* Vitamin C – 4000+mg/day
---------------------------------------------

but completely intolerant to this group:

----------------------------------------------
* SAM-e - 200-400mg/day, makes methylb12 more effective, possibly much more effective, increases energy, improves mood
* TMG - enhances SAM-e, methylb12, l-carnitine
* L-carnitine fumarate (acetyl might work better for some), works with adenosylb12, lack can completely prevent effectiveness of adenosylb12, increases energy, aerobic endurance, improves mood
* Alpha Lipoic Acid - enhances l-carnitine and adenosylb12
* D-Ribose - enhances adenosylb12, l-carnitine, alpha lipoic acid, improves exercise recovery and energy
------------------------------------------------

It's been a long time since I tried SAM-e or TMG, but they had some significant negative psychological effects (at least). L-carnitine is contraindicated in hypothyroidism because although hypo patients are deficient, it blocks the action of thyroid peripherally (it's given to hyperthyroid patients, actually, to mitigate some of the effects of being hyper).

ALA I tolerate in extremely low doses, but after a day I am really sick from it from detox (Cutler protocol). I have some DMSA that I was going to start using to clear out presumably some metal toxins, but then the CFS started and I haven't gotten around to it yet.

D-ribose gives me a "candy bar" boost, complete with sugar crash about 20-30 minutes later. Feels bad, man!

So what might that indicate, especially the SAM-e and TMG in relation to these methylation problems?

Also, what percentage of people, or how likely would you say it is that a person gets overmethylated with this protocol? I know it's difficult to say, but is there any rough estimate of how common it is?

I took some l-glutamine yesterday to see what would happen, and today I've felt really crappy all day. I'm not sure if they're related, I also put some pine cone extract in a dropper bottle, and I think it had some celexa residue in it, so that might have caused some 5-HT effects. But I took about 750mcg of methyl-b today, so I'll see if that gives any effects tomorrow. So far today I didn't really notice anything from it, strangely enough. Usually I react very noticeably to 250mcg.

Hi Starcycle,

That second group you mention as being intolerant to, are cofactors to aid the active b12s and methylfolate. For instance, adenosylb12 sits in the mitochondria waiting to participate in the krebs cycle, if the fats are transported. The l-carnitine-fumarate aids that but FIRST the adb12 needs to be in place. Tha alpha lipoic acid aids the efficiency of the l-carnitine in this. After the ATP is produced and used, the D-Ribose helps recycle it. This is just a simplistic description of the chain. Howver, if the downstream pieces are taken without the adb12, they are missing a vital part. In my own trials of things I found that ORDER of components was very important to proper functioning. For instance, people who took the methylfolate before the mb12 and/or adb12 tended to have much stronger reactions to the methyfolate and sometimes to the mb12 and/or adb12. Also, having only taken TMG after l-carnitine fumarate what I noted was a moderation of some of the more excitatory effects of the l-carnitine fumarate and I don't know of it's effect alone as I have never tried that during early recovery.

Also, methylb12 deficiency causes all sorts of neurological and neuropsychiatric problems and adb12 contributes to these as well. When these are actually affected by methylb12 and healing starts, emotional volitility and personality changes can start happening very rapidly. While these all happened slowing going down into the pit of deficiency, coming out is much faster. The SAM-e was also after being well established on the mb12, not before hand, as was everything else. The SAM-e and TMG may not even need to be tried if mb12 and ad12 take care of the lack of energy and brainfog etc 100%. And there are reasons to try the D-ribose that may not exist after the adb12 and l-carnitine fumarate.

So possibly the effects you experienced were contributed to not having the more fundamental items in place first, like trying to build a house by skipping the first floor and starting with the second one. I would suggest first things first, get the mb12, methylfolate and adb12 well established and done with startup symptoms before adding other things, and then remember that order and combinations can cause all sorts of effects. Also consider that there is no way to go through neurological and neuropsychiatric healing without experiencing changes, many of them unpleasant while they are happening.

I took some l-glutamine yesterday to see what would happen, and today I've felt really crappy all day. I'm not sure if they're related... But I took about 750mcg of methyl-b today, so I'll see if that gives any effects tomorrow. So far today I didn't really notice anything from it, strangely enough. Usually I react very noticeably to 250mcg

My experience of l-glutamine, with NAC, was that the combination completely blocked the active folate in my body and I developed hard folate deficiency symptoms rapidly and then the active b12s, both of them, were blocked until I took a much larger dose of methylfolate.

Good luck.

 

[Freddd]

Hi Rich,

Just offerring up for your consideration a few patterns concerning vitamins.

1. Ricketts had disappeared in the USA until recently and that with considered changes in lifestyle and an updating of knowledge the suggested amount of vitamin D per day has increased by roughly a factor of 10. When taking suitable amounts of vitamin D nobody develops ricketts. The effectiveness of vitamin D in preventing ricketts is 100%, not "a statistically significant percentage of people". D3 is taking over as it is superior to thew D percursor thjat was often used.
2. The effectiveness of vitamin C in preventing scurvy in people taking vitamin C is 100%, not "a statistically significant percentage of people".
3. The effectiveness of thiamin in preventing beriberi is 100% in people taking thiamin, not "a statistically significant percentage of people".
4. The effectiveness of niacin in preventing pellagra is 100% in people taking niacin, not "a statistically significant percentage of people".
5. The effectiveness of folic acid in preventing deficiency symptoms that do respond to methylfolate is about 50-70%, but not 100% as with other vitamins.
6. The effectiveness of cyanocobalamin and hydroxyb12 in preventing some deficiency symptoms to some degree is about 70% and their effectiveness in preventing 100% of active b12 responsive deficiency symptoms is about 0%.

Clearly it can be seen that items 5 and 6 are different from the other vitamins as they work comparatively poorly in only some of the people, a "statistically significant number" certainly but give very poor performace as compared to the real folate and the real b12s. At best folic acid, cyanocobalamin and hydroxycobalamin are pseudo vitamins, a poor substitute for the genuine article. If they were the real vitamins they would act like them and produce results like them. We don't see people with scurvy, pellagra and beriberi walking around all about us while people exhibiting some degree of b12 and folate deficiency are terribly common and are seen in every group of people one comes across. Thinking that these are the real vitamins has made the real deficiencies invisible and impossible to solve leaving millions of people with untreatable mysterious diseases and blamed for psychosomatic disease.