methylcobalamin vs hydroxocobalamin

[Plum]

Hi

Apologies if this has been answered elsewhere - I did a search but due to not feeling great may have missed it.

The simplified protocol calls for hydroxocobalamin but I thought the methyl version was the best? I have some methylcobalamin which doesn't give me any stomach upset so wondered if it had to be the hydroxo form?

Also, I thought a previous version of the protocol included a product with some intrinsic factor in it - does anyone have experience with this? I know my gut doesn't work properly so wonder if I need some.

Thanks in advance

 

[Jarod]

I'm not sure, but it may be the hydroxycobalamin losenges are working best for me at the moment. However, I've had good luck with methyl b12 losenges also in the past. Hard to say.

Never noticed anything going on with my gut in relation to b12.

 

[Plum]

Mmmm. Thx. When I take cyanocobalamin I get indigestion. Meant to be hard for the body to breakdown.

 

[Sparrow]

There is a lot of debate over this here...

Hydoxocobalamin was recommended by Rich because it allows the body to control it's own conversion process - to take as much as is needed and make it's own methylcobalamin. So it is the "safer" choice, though perhaps not as effective.

Some practitioners recommend hydroxocobalamin specifically because it is a good scavenger of particular things that we might have too much of (do a quick Google search on NO/ONOO or Martin Pall if you're interested).

Hydroxocobalamin may be important to begin with if one has both a folate and B12 deficiency, to prevent permanent central nervous system damage (methylcobalamin can't fill that role on its own - it has a different role in the body, whereas hydroxocobalamin can be converted to multiple forms for multiple purposes).

Methylcobalamin doesn't require conversion, so it saves the body having to do that, and also gets around difficulties the body may be having in the conversion process. On the down side, some believe that too much will force the body into a state of overmethylation (which has its own crummy symptoms), since this form bypasses the body's natural regulation.

Many of us take a combination of hydroxy, methyl, and adenosyl (dibencozide), to try to cover our bases. I personally have found methyl and adenosyl to be very useful, but I would keep an eye on your symptoms while taking them, and if possible get methylmalonic acid tested to determine the point at which your body is taking in enough for your cells to get what they need (or have a Methylation Pathways Panel run if you can afford it). It can take a lot sometimes, but more is not always better. I would also start off with some hydroxy as well, just in case you have enough deficiency for CNS damage to be an issue for you. Better safe than sorry.

 

[Freddd]

Hi

Apologies if this has been answered elsewhere - I did a search but due to not feeling great may have missed it.

The simplified protocol calls for hydroxocobalamin but I thought the methyl version was the best? I have some methylcobalamin which doesn't give me any stomach upset so wondered if it had to be the hydroxo form?

Also, I thought a previous version of the protocol included a product with some intrinsic factor in it - does anyone have experience with this? I know my gut doesn't work properly so wonder if I need some.

Thanks in advance

Hi Plum,

HyCbl works poorly at best. It is about 1% as effective as AdoCbl and MeCbl. It is dependent upon already havimg some of each of those, plus l-carnitine fumarate and l-methylfoalte. CNS damage can continue for many people even while taking HyCbl.
I would like to combine several things that have come to my attention recently to once again discuss why hydroxycobalamin might not work to start a methylation cycle that is either blocked or depleted.

As I have mentioned multiple times through the years, in any given study on the use of hydroxycbl for the relief of several b12 deficiency symptoms and signs, approximately 1/3 of people in the study have zero effectivness on the symptoms or signs being studied. As the study symptoms are selected only from the list of those items KNOWN TO RESPOND to some extent to cyanocbl and hydroxycbl, about 1/3 of the total of all active mb12/adb12 deficincy symptoms, there are clearly some issues that prevent 1/3 of the people from responding.

So let's consider first several chains of reactions. Assume sufficiency of other needed items such as magnesium, l-carnitine and folate for this discussion.

methylb12 yields SAM-e
methylb12 yields glutathione
adenosylb12 yields ATP


hydroxycbl with assumed glutathione and assumed ATP and assumed SAM-e yields methylb12 and adenosylb12 in processes

The flaws in this are that these reactions can be deadlocked. It takes ATP produced by adb12 to produce adb12 and mb12. It takes glutathione to produce mb12 to produce glutathione. It takes ATP and mb12 to produce SAM-e to produce mb12


Without enough adb12 to produce ATP hydroxcbl doesn't produce adb12.
Without enough mb12 to produce glutathione, hydroxycbl doesn't produce glutathione.
Without enough SAM-e to produce mb12 hydroxycbl doesn't produce mb12 to produce SAM-e.
Without enough adb12 to produce ATP hydroxcbl doesn't produce mb12

Each of these are classic deadlock situations. The reactions are dependent upon sufficiency of the items or related items to be produced. In other words this has to act like a biochemical perpetual motion machine.

All of this happens because hydroxcbl competes for methyl groups instead of providing them and needs energy (ATP) to complete these up hill energy transactions. In each case hydroxcbl needs one or more of the items it is supposed to produce in order to produce the items.

Any ONE of these is enough to cripple hydroxycbl.

Methylb12 and adenosylb12 and Methylfolate start methylation and cell reproduction almost immediately and confirms it by depleting potassium within 3 days and epithelial tissues obviously starting healing in 10 days.

Adenosylb12 often starts mitochondrial functioning to improve starting within 10 minutes.

Hydroxycbl and folinic acid can take days to never to start methylation and cell reproduction, and then only paritally. This can be demonstrated as no duration of Hydroxcbl usage prevents mb12 startup responses. Hydroxycbl almost never adequately causes mitochondria to function fully. This can be demonstrated by no duration of hydroxycbl use preventing adb12 startup reponses.

After a period of hydroxycbl and folinic acid usage startup response of mb12 and adb12 tend to be more intense than if nothing at all had been taken. Many deficiency symptoms tend to worsen while these are taken.

Hydroxycbl usually needs lab tests to show effectiveness.
Adb12 and mb12 provide naked eye results almost always.


http://forums.phoenixrising.me/show...nversion-of-OH-B12-to-methyl-B12-new-evidence

Will Marsden recently called my attention to a recent paper from Prof. Richard Deth's group (abstract below) that provides evidence from a rat experiment that major glutathione depletion blocks the conversion of hydroxocobalamin to methylcobalamin.

This has been one of the main propositions of the pathogenesis model that I have proposed for ME/CFS, i.e. the Glutathione Depletion--Methylation Cycle Block hypothesis. So far, this model has continued to be supported as more research is being completed.

One of the things this has brought home to me is that in cases in which glutathione or SAMe are extremely low, it will be difficult to get the methylation cycle going using hydroxocobalamin as the form of B12. This is the form included in the simplified protocol I have suggested, and it was found to be helpful for more than two-thirds of the people in our clinical study, but this may explain why some of the people did not receive benefit from this protocol.

Note that the protocol recommended by Freddd uses methylcobalamin as one of the forms of B12. Methylcobalamin is also used by Dr. Amy Yasko in some cases, depending on genomic polymorphisms. It is also used by Dr. Neubrander and other physicians participating in the DAN! project for treating autism.

Recently I have been suggesting that if the simplified protocol does not produce benefits within three months, either testing should be performed to determine why, or a change should be made in the protocol used. One possibility would be to add methylcobalamin, starting at low dosage and working up, as tolerated.

Best regards,

Rich



Alcohol Clin Exp Res. 2011 Feb;35(2):277-83. doi: 10.1111/j.1530-0277.2010.01343.x. Epub 2010 Dec 1.

Ethanol lowers glutathione in rat liver and brain and inhibits methionine synthase in a cobalamin-dependent manner.

Waly MI, Kharbanda KK, Deth RC.
Source

Department of Food Science and Nutrition, Sultan Qaboos University, Muscat, Sultanate of Oman.
Abstract
BACKGROUND:

Methionine synthase (MS) is a ubiquitous enzyme that requires vitamin B12 (cobalamin) and 5-methyl-tetrahydrofolate for the methylation of homocysteine to methionine. Previous studies have shown that acute or chronic ethanol (ETOH) administration results in the inhibition of MS and depletion of glutathione (GSH), and it has been proposed that GSH is required for the synthesis of methylcobalamin (MeCbl).
METHODS:

We measured GSH levels and investigated the ability of different cobalamin cofactors [cyano- (CNCbl), glutathionyl- (GSCbl), hydroxo- (OHCbl), and MeCbl] to support MS activity in liver and brain cortex from control and ETOH-treated rats.
RESULTS:

In control animals, MS activity was higher in liver than in cortex for all cobalamins and MeCbl-based activity was higher than for other cofactors. S-adenosylmethionine (SAM) was required for OHCbl, CNCbl, and GSCbl-based activity, but not for MeCbl. Feeding an ETOH-containing diet for four weeks caused a significant decrease in liver MS activity, in a cobalamin-dependent manner (OHCbl ? CNCbl > GSCbl > MeCbl). In brain cortex, OHCbl, CNCbl, and GSCbl-based activity was reduced by ETOH treatment, but MeCbl-based activity was unaffected. GSH levels were reduced by ETOH treatment in both liver and cortex homogenates, and addition of GSH restored OHCbl-based MS activity to control levels. Betaine administration had no significant effect on GSH levels or MS activity in either control or ETOH-fed groups.
CONCLUSIONS:

The ETOH-induced decrease in OHCbl-based MS activity is secondary to decreased GSH levels and a decreased ability to synthesize MeCbl. The ability of MeCbl to completely offset ETOH inhibition in brain cortex, but not liver, suggests tissue-specific differences in the GSH-dependent regulation of MS activity.

Copyright 2010 by the Research Society on Alcoholism.

PMID:
21121936

 

[Dreambirdie]

Rich would STRONGLY disagree with Fredddd's following statement, especially the part about "CNS damage":

"HyCbl works poorly at best. It is about 1% as effective as AdoCbl and MeCbl. It is dependent upon already havimg some of each of those, plus l-carnitine fumarate and l-methylfoalte. CNS damage can continue for many people even while taking HyCbl."

Here's a video of a talk Rich did in Sweden back in 2011 on the Simplified Methylation Protocol, which has helped quite a number of CFS patients to achieve partial recovery.

http://iaomt.media.fnf.nu/2/skovde_2011_me_kroniskt_trotthetssyndrom/${weburl}

 

[Plum]

Thank you Sparrow and Fredd. What amazing info! I really appreciate the scientific perspective as it's how I learn best. What brands of hydroxy and adenosyl do people take as I'm struggling to find some here in the UK?

I do feel good on the methyl version as in slightly more alert but not wired or anything else negative. Maybe a bit more tired but that's not a problem for me.

I had no idea about the adenosyl version so something else I have learnt today - thank you

I wish I could afford to get a test done. But I'm trying the protocol to see how I go. If not good then I will save up for testing but so far so good!

 

[Plum]

Thanks Dreambirdie. I have spent several days going through Rich's talks from Sweden and learnt a lot! I have taken detailed notes as I like knowing exactly what's going on. It is all very interesting and something which I wish Dr's here would consider or at least be 'open' too!

 

[Sushi]

Hi Plum,

HyCbl works poorly at best. It is about 1% as effective as AdoCbl and MeCbl. It is dependent upon already havimg some of each of those, plus l-carnitine fumarate and l-methylfoalte. CNS damage can continue for many people even while taking HyCbl.
...

Agreeing with Dreambirdie.

You have not substantiated this statement that I can see. The best form(s) of B12 seems to be individual depending on many variables. It is a matter of discussion, debate, research and trial and error.

From what you have written, it would seem that your statement that

CNS damage can continue for many people even while taking HyCbl.

is a hypothesis rather than something established by research and clinical experience.

Sushi

 

[Freddd]

Agreeing with Dreambirdie.

You have not substantiated this statement that I can see. The best form(s) of B12 seems to be individual depending on many variables. It is a matter of discussion, debate, research and trial and error.

From what you have written, it would seem that your statement that



is a hypothesis rather than something established by research and clinical experience.

Sushi

Suchi,

MeCbl at low levels for people who already have SACD going allows such damage to continue. That is equally true of HyCbl. This is easly demonstrated by clinical experience. Further, HyCbl, the lomnger it is continued, about 90% of b12 deficiency sysmptoms continue to worsen since it is totally ineffective on most of them. Instead of flogging a dead horse repeating the same old same old, why don't say read the Large Gorilla ... Adenosylcobalamin and see the "RADICAL" greater effectiveness of AdoCbl than HyCbl on inflammation. Lots of people have experienced. That Radical difference of effectiveness Wheatly speaks of is what I speak of. AdoCbl, and MeCvbl are "RADICALLY" more effective. HyCbl was introduced in the UK in the 70's following a famous letter to the LANCET Journal warning of the dangers of the CyCbl. It was a sidestep to a less dangerous inactive cobalamin becasue the real ones were not avaialable.

Rich I'm sure would have read the Wheatley's Gorilla paper had he been able. Who knows. it might have had an effect. With newer information Rich was changing

Rich:
Will Marsden recently called my attention to a recent paper from Prof. Richard Deth's group (abstract below) that provides evidence from a rat experiment that major glutathione depletion blocks the conversion of hydroxocobalamin to methylcobalamin.

He is pointing out the deadlock quartet problem in this post. So instead of flogging a dead horse, evaluate new information. While CyCbl is the worst possible choice for a cobalamin that might do anything, HyCbl is the second worst possible cobalamin. Dispute me on the 1% as effective and present some research showing it is fully effective, if you can find any. As Rich said it's repeated rateof 20-40% compeltely ineffective for the symptoms or signs being studied must be due to lack of cofactors. I agreed and pointed out the 4 cofactors, the deadlock quartet and documentted many ways that deadlocks HyCbl including the quote from Rich. Everywhere one looks, at the conversion of HyCbl to MeCbl and AdoCbl, requires enzymes and ATP. To convert HyCbl to active b12s requires all four of the deadlock quartet in the body already. Show how that is not correct. Or of course you can keep flogging a dead horse but it doesn't advance understanding in any way.

Claim that HyCbl repeatedly doesn't work on 20-40 percent of people in the studies, and I will agree. Claim that it works partially on perhaps 30 symptoms and signs out of the hundreds that the Deadlock Quartet (AdoCbl, MeCbl, L-carnotine fumarate and LCF or ALCAR) works on and I will agree. Claim that it does everything the active cobalamins do I will disagree. Claim that it is as effective and I will disagree. Claim that it is vastly inferior in effectiveness but does work on some symptoms for some people I will agree.

 

[Sushi]

Freddd

I am not disputing anything you say only asking for backup as you are making bold statements on controversial subjects where there is not clinical or research agreement.

Sushi

 

[Dreambirdie]

There is absolutely NO documented clinical evidence to Fredddd's conclusions about HB12 being ineffective on B12 deficiency symptoms and actually worsening them.

This is all conjecture based on Freddd's personal experience, which IMO is often highly biased and sometimes even dangerously fanatic.

When it comes to Freddd's unproven theories, CAVEAT EMPTOR: Let the buyer beware.

 

[Freddd]

Freddd

I am not disputing anything you say only asking for backup as you are making bold statements on controversial subjects where there is not clinical or research agreement.

Sushi

Sushi,

I spent lots of time reading papers. How many papers do you need quoted to convince you that HyCbl has no effectivetivess on the symptoms studied at the 20-40% rate. Or would the quote from Rich acceeding that and saying "It's got to be lack of cofactors" or something similar be sufficient? Please define what you would consider acceptable.


Then of course rhere are the other near 300 or so symptoms and signs which I am laying out section by section on another thread, that is as subsets of symtpoms affected. Or is it that you would rather have 300 symptoms and signs as uncurable mystery diseases ratther than admit that they are predictable and correctectable with active b12s and folate and the effective for the person form of carnitine and oter cofactors.

Only the Japanese are really concerned with the neurological effects in their research. Many researchers and physicians of many varieties here and in the UK are still glued to the old 1950s idea that only pernicious anemia is REAL b12 deficiency.

And don't worry. I'll write up my analysis of Rich's and Dr Nathan's study. It produced some usefull information. It won't be finished until I get all the various symptoms and effectivenes of the active system up and then I will look at the effectiveness of this specific study, based on the published data only. I don't really have any complaint with the study at all. It does point the way and gives some valuable hints that can be followed up on. My big criticism and one Rich also made to me personally, was that he would have preferred that Dr Nathan design the data set collected more broadly, more items, more detail. As a pilot study was done, the items selected were the ones he could have positive resulots with. He constructed his data set with items he knew could be affected. Of course he did. Everybody tries to be selective in picking from a suitable population, one that has the condition one desires to study

 

[Freddd]

There is absolutely NO documented clinical evidence to Fredddd's conclusions about HB12 being ineffective on B12 deficiency symptoms and actually worsening them.

This is all conjecture based on Freddd's personal experience, which IMO is often highly biased and sometimes even dangerously fanatic.

When it comes to Freddd's unproven theories, CAVEAT EMPTOR: Let the buyer beware.

Really Dreambirdie, You are the one sounding fanatical. You want your questions answered in your way, loaded dice, and refuse to answer any questions or anything. You repeat the same allegations and never address questions.

 

[Lotus97]

methylb12 yields SAM-e
methylb12 yields glutathione
adenosylb12 yields ATP

hydroxycbl with assumed glutathione and assumed ATP and assumed SAM-e yields methylb12 and adenosylb12 in processes


The flaws in this are that these reactions can be deadlocked. It takes ATP produced by adb12 to produce adb12 and mb12. It takes glutathione to produce mb12 to produce glutathione. It takes ATP and mb12 to produce SAM-e to produce mb12


Without enough adb12 to produce ATP hydroxcbl doesn't produce adb12.
Without enough mb12 to produce glutathione, hydroxycbl doesn't produce glutathione.
Without enough SAM-e to produce mb12 hydroxycbl doesn't produce mb12 to produce SAM-e.
Without enough adb12 to produce ATP hydroxcbl doesn't produce mb12

Rich and Dr. Nathan's study with hydroxocobalamin proved hydroxocobalamin to be effective in these areas for the majority of the patients participating. I'm not sure why this study needs your analysis especially since you already seem to have formed your opinion.
http://www.mecfs-vic.org.au/sites/w...Article-2009VanKonynenburg-TrtMethylStudy.pdf

 

[Red04]

I don't want to sound like a broken record. But I feel it's necessary to state the positive in case a new reader is stumbling across this. Freddd and his unproven theories saved my wife's life, health, our financial situation, and we have a healthy 7 month old son to prove it. Her recovery was fast and miraculous and she had been in "CFS remission going on 2.5 years". No prozac, lyrica, klonopin, or any other crazy chemicals. I assume most people who have success like my wife did with Freddds protocol don't stick around here and post things as they don't have much to contribute. So the comments are slanted to the negative.

Of course the science isn't there yet. It might not be in most of our lifetimes. What has clinical evidence proven that's helped people with CFS? Parkinsons? MCS? ALS? Autism? Not very much. Is there clinical evidence for anything you have to get off the internet? That's why everyones here looking for answers....

If you had a bad experience with Freddds theories post it up here. Did you follow it exactly? How long until you quit? Did you microtitrate everything? How fast? Do you have other things going on? That would be more useful than just pointing out the lack of clinical studies. Did you use Rich's protocol and get completey healed after Freddds failed? Post that up here for all to read.

I would suggest a person get the methylation testing run (if you can) and pick a protocol Freddd or Rich's or other and follow it EXACTLY as prescribed based on your comfort level. A lot of people on here start off mixing protocols and get caught up in these arguments. If it doesn't work, try the other one. Get someone to help you, document the changes and reactions, post here for help.

CAVEAT EMPTOR: having success with Freddds protocol may greatly improve your life to that point that you may feel a little sad about how bad it was before.

 

[adreno]

I believe Rich recommended hydroxy because it is the safe choice, not because it's more effective than methylb12. He was worried about overdriving the methylation cycle, and also worried about heavy metal detox and excitotoxicity. But I never saw him claim anywhere that hydroxy was more effective. It is true that some cofactors (methyl groups, glutathione, ATP etc) are needed in the conversion of hydroxy to active forms of b12. I think it was Rich's opinion that most people would be able to handle this conversion.

We have to remember that Rich never claimed that the SMP was the final word. He said himself that the protocol was a compromise. A safe, simple and affordable protocol for anyone suffering from ME. But he actually recommended that those who had access to the resources got tests, and based their supplementation on the results of those tests. So please don't understand the supps or dosages in the SMP to be set in stone, this was never his intention.

My personal view is that methylb12 is more effective, but might also be harder to tolerate for some. Maybe this is because of side effects, or just because it is actually working and doing something. I felt no improvements or side effects from the hydroxy. I do believe RIch was right in his concerns about hypermethylation and excitotoxicity, but personally I will rather carefully titrate methylb12 as tolerated than stay with the hydroxy.

Now we also have access to the knowledge from the gorilla study (thanks, freddd), which shows that hydroxy is not the preferred substance for mopping up peroxynitrite, as was formerly believed. The preferred substance for this is actually adenosylcobalamin. It must be noted that Rich did not have access to this knowledge.

 

[Lotus97]

Thank you Sparrow and Fredd. What amazing info! I really appreciate the scientific perspective as it's how I learn best. What brands of hydroxy and adenosyl do people take as I'm struggling to find some here in the UK?

I do feel good on the methyl version as in slightly more alert but not wired or anything else negative. Maybe a bit more tired but that's not a problem for me.

I had no idea about the adenosyl version so something else I have learnt today - thank you

I wish I could afford to get a test done. But I'm trying the protocol to see how I go. If not good then I will save up for testing but so far so good!

Actually, in Rich's protocol he says to start with hydroxocbalamin and if you don't experience improvement then switch to methylcobalamin and adenosylcobalamin. He says this because he is concerned about overdriving the methylation cycle which can cause adverse symptoms and even be counterproductive to the healing process. However, if you are already having success with methylcobalamin you might just want to stick with that. Be aware that methylcobalamin is more potent than hydroxocobalamin so you wouldn't want to start out with 2000 mcg of methylcobalamin like Rich says with hydroxocobalamin. 1000 mcg of methylcobalamin might even be too much for some people here. Especially if you're using Enzymatic Therapy's which is reported to be significantly stronger than other brands of methylcobalamin.

Also, be aware that once you add folinic acid and methylfolate the combination of those and the B12 will create a stronger reaction and possibly cause overmethylation so be prepared to lower your dose of B12 if necessary. That's why Rich recommends starting with B12, then adding folinic acid if the B12 is tolerated, and then finally methylfolate of those two are tolerated. I would actually recommend starting with 250 mcg methylcobalamin until you have added both folinic acid and methylfolate. Especially if you're using Enzymatic Therapy's brand. Low potassium is a common and potentially lifethreatening effect of overmethylation and overdriving the methylation cycle so you might want to consider supplementing with potassium even if you are taking hydroxocobalamin. Capsules and tablets are not recommended for potassium supplementation because those can damage the stomach and GI tract. Now Foods sells potassium gluconate and potassium chloride in powder form. Those are both available at iHerb which ships internationally.

If you are interested in trying hydroxocobalamin, the only two sublinguals available at iHerb are by Biotics and AOR. I don't know much about either one.
http://www.iherb.com/Advanced-Orthomolecular-Research-Hydroxy-B12-60-Tablets/33061

The one from Biotics is cheaper, but also has 800 mcg of folinic acid which may or not be a good thing.
http://www.iherb.com/Biotics-Research-Corporation-B12-2000-60-Lozenges/45148


As for adenosylcobalamin, I would wait until you get the methyl b12, folinic acid, and methylfolate in place before adding it. If you take hydroxocobalamin instead of methyl b12 then you might not need adb12 at all because most people are able to convert hydroxocobalamin into methylcobalamin and adenosylcobalamin. Adenosylcobalamin is sometimes also referred to as dibencozide. The only two I know of without folic acid are Source Naturals and Anabol Naturals. Anabol's is in capsule form so people empty it into their lower lip and gum area to absorb it sublingually. I would recommend starting at a very low dose (1/4 tablet or less) and maybe start off taking it orally first. There are some lower dose adb12 sublinguals, but they have folic acid which some people are avoiding. Country Life has one and Source Naturals also has a sublingual b complex with adb12.

 

[Jarod]

Freddd has been around this forum for a long time. He has many threads discussing his experiences with other patients.

I haven't tried enzymatic therapy methyl b12, but I've had good luck with the enzymatic therapy products.


I think I've experienced overmethylation with methyl b12 at times, but it has never given me adverse reactions. It just became unaffective.

 

[Freddd]

I believe Rich recommended hydroxy because it is the safe choice, not because it's more effective than methylb12. He was worried about overdriving the methylation cycle, and also worried about heavy metal detox and excitotoxicity. But I never saw him claim anywhere that hydroxy was more effective. It is true that some cofactors (methyl groups, glutathione, ATP etc) are needed in the conversion of hydroxy to active forms of b12. I think it was Rich's opinion that most people would be able to handle this conversion.

We have to remember that Rich never claimed that the SMP was the final word. He said himself that the protocol was a compromise. A safe, simple and affordable protocol for anyone suffering from ME. But he actually recommended that those who had access to the resources got tests, and based their supplementation on the results of those tests. So please don't understand the supps or dosages in the SMP to be set in stone, this was never his intention.

My personal view is that methylb12 is more effective, but might also be harder to tolerate for some. Maybe this is because of side effects, or just because it is actually working and doing something. I felt no improvements or side effects from the hydroxy. I do believe RIch was right in his concerns about hypermethylation and excitotoxicity, but personally I will rather carefully titrate methylb12 as tolerated than stay with the hydroxy.

Now we also have access to the knowledge from the gorilla study (thanks, freddd), which shows that hydroxy is not the preferred substance for mopping up peroxynitrite, as was formerly believed. The preferred substance for this is actually adenosylcobalamin. It must be noted that Rich did not have access to this knowledge.

Hi Adreno,

I believe Rich recommended hydroxy because it is the safe choice, not because it's more effective than methylb12.

I happen to agree with you on this. It seems like people want mutually exclusive results and none of what we are discussing are mutually exclusive. Instead there are a lot more than 50 shades of grey. For good monochorme reproduction one needs at least 65,536 shades of grey, lots of fine distinctions. Relative rates of effectiveness are a side issue. They don't mean that one thing is always effective or that another is never effective. It just isn't all that clear.


When things hit hard, like hypokalemia, and that is truely the most dangerous potential side effect, in my estimation of both potential actual harm and frequency of occurrance, if a person is not prepared for it in my opinion, and of course when it is not identified. That has been traditional in studies of all forms of cobalamin dating back to the 50s. What wasn't in the data Rich sent me was why 9 people dropped out. If they dropped out from too much "detox" that would tell us that the people elliminated would have likely had the best results of all if the reasons for the "detox" had been hypokalemia and/or donut hole folate insufficiency and were dealt with. If that was the cause then inability to deal with these side effects prevented the study from having far better results.


I do believe RIch was right in his concerns about hypermethylation and excitotoxicity, but personally I will rather carefully titrate methylb12 as tolerated than stay with the hydroxy.
I would like definitions of "hypermethylation and excitotoxicity" in terms of symptoms produced by these things that do not match the effects of active b12 deficiencies, folate insufficiency and/or serum potassium low enough to cause symptoms but may not techincally be hyokalemia becasue it is above 3.5 serum level, or other induced deficiencies, and relievable by the pragmatoically correct set of nutrients. For 40 years, my entire vitamin taking lifetime, I have read again and again this warning "Watch out for induced deficiencies" when starting nutrients. I didn't make this up or invent it. This warning I have seen repeated literally hundreds or thousands of times. Though it always seems to be ignored by those selling or pushing (often, I'm NOT including Rich in that) their hypothesis.


We have to remember that Rich never claimed that the SMP was the final word. He said himself that the protocol was a compromise. A safe, simple and affordable protocol for anyone suffering from ME. But he actually recommended that those who had access to the resources got tests, and based their supplementation on the results of those tests. So please don't understand the supps or dosages in the SMP to be set in stone, this was never his intention.

Good sense.

I NEVER claimed to have anything simple though I have tried to come up with the most cost effective things I can. The most active MeCbl and AdoCbl is by far the most cost effective in the long run in my opinion. Utilization cost analysis is something I have more than 20 years of experience in professionally and gave presentations at group medical conferences. Working at the group health level I work with secondary indicators. If a person has benefits because they feel better that is good. If they have "improved test results" it may not mean what one might want it to remain, as som many of the key tests are interpreted in a way influenced by 50 years of misdirected, misunderstaood research making chronic deficiency symptoms part of "normal". If they have sufficient benefits that they cut their doctor visits in half and cut their monthly pharmacy costs by 80%, and cease looking for the answer and go back to work then in my opinion, that is a relatively better response than having some "feeling better" with somewhat different lab reports but increased or unchanged utilization.

Now we also have access to the knowledge from the gorilla study (thanks, freddd), which shows that hydroxy is not the preferred substance for mopping up peroxynitrite, as was formerly believed. The preferred substance for this is actually adenosylcobalamin. It must be noted that Rich did not have access to this knowledge

This was a real eye opener for me. I knew something like this had to turn up since I and a lot of others have outright recovered from CFS/ME/FMS, including very noticably a large change in inflammation which at first I had no idea why that would be so dramatic (radical). By that I mean that while I have symptoms, they are all attributable to injury (automobile, SACD) and I am completely not diagnosable as having CFS/ME/FMS. 90% of my old symptoms are just plain not my symptoms any more. Now the question is can I find the fountain of youth? Anybody have an leads on that?