Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Freddd, May 8, 2011.
Just realised that answer to my own question is probably General Vitamin Neurological Health Formula
Hi Lisa...I was corresponding with Rich on this issue, and an ideal situation is to take a vitamin + methylfolate, and no folic acid. However, if you do take a multivitamin, and if that multivitamin does contain folic acid then ensure that there is a gap of at least two hours between that and the taking of the methylfolate so as to minimise the opportunity for competition/uptake to be hindered.
I am not sure, but I think it is methylfolate that we need to take instead of regular folic acid. I now get a B complex called "Activated B" from Swanson's, which uses the active methyl folate rather than the regular folic acid. I have also bought the methyl folate separately in the past, and was taking that and all otehr B's individually, before I found the Activated B's.
There is another thread, or more than one, in which Rich Vank gets into great detail about this protocol, and also Fredd. I haven't looked at any of the methylation threads for a long time.
By the way, I started doing most of the methylation protocol, as well as I could understand it, many months ago, and between that and magnesium L Threonate, I am finding my cognitive skills improving, and have had other improvements as well, over time.
Hi, Thanks for the info. I've just realised that General Vitamin Neurological Health Formula also contains folic acid. I've been searching for multivits that don't and can't find any but there must be at least one. Have you any ideas? Is this discussion on another thread?
So far I haven't found a multi that has all the benefits of the Neuro Health formula without the disadvantages, including the folic acid as well as dosages of some of the minerals and vitamins that are a little on the low side. I'm seeing test results from people who are low particularly in some of the B-complex vitamins as well as some of the essential minerals. I think this is the reason why some are not responding to the methylation protocol as well as I would have expected. If people can test to see what their deficiencies are, that would be best. If this is not feasible, adding a B-complex that does not have folic acid as well as a multimineral, might be helpful to those who are not experiencing a response from the protocol. As always, I recommend working with a physician while on this type of treatment.
Hi Rich, I bought Biocare's B vitamins which doesn't have any folic acid or b12 and a multimineral and other vitamins like vit C and K individually. The methylation really seems to be helping. I went through a dip when it stopped being effective and then it restarted?? I can not only walk beyond 5 minutes now but can even walk for 30 minutes which is unprecedented! The only thing it hasn't helped with is the chronic inflammation (lymph pain, sore throat etc.). Will it help with that or is that immune aspect a separate issue completely? I was thinking of trying prednisone for the inflammation which shouldn't interfere with the methylation?
I'm glad to hear about your improvement on methylation treatment. Over time, this treatment should help the function of the immune system. Whether the immune system will be able to overcome the infections,and thus whether the inflammation will die down, is hard to say. I think it depends on how well entrenched the infections are, and whether the immune system has any inherited immune deficiencies. You may have to have additional treatment specifically targeting the infections.
With regard to the prednisone, I would just note that the methylation treatment should improve the function of the HPA axis, also, and that should cause the level of cortisol to come up, over time. If you take prednisone in addition, it may suppress this recovery.
Thanks Rich, I'll stay clear of the prednisone!
I've had the inflammation for many years now so it is pretty entrenched. I live in the UK so no treatments available. I'm taking fish oil so that might help. Thanks again - so glad I hadn't gone ahead and ordered the prednisone.
Hi could someone explain why glutamine is on Fredd's "do not use list"?
Also Rich Vank's protocol suggests folinic acid but Fredd's expressly avoids its?
Can anyone explain please?
I don't know about glutamine, but I think Freddd has expressed his opinion on folinic acid.
I think it is because folic and folinic acid block metafolin(l-methylfolate), which causes folate deficiency.
Quoting from the following link:
Folic acid and folinic acid can block metafolin inducing deficiency called "ddtox"
"To sum it up:
Folic acid taken several times per day along with larger amounts of Metafolin blocks the Metafolin causing overt folate deficiency in 6-7 days.
Folinic acid taken as 1 single 800mcg dose daily blocks 4800mcg of Metafolin in about 30 days sufficiently to cause overt folate deficiency symptoms.
Glutathione starts causing overt folate deficiency symptoms starting within hours of a sufficient dose and is called a "detox" reaction.
NAC is reported by others, to cause an identical "detox" reaction as glutathione within some unknown period, probably dependent upon dose.
Hard folate deficiency symptoms are commonly called "detox" reactions."
Thanks for the reply.
I read the link and it was informative. I myself can attest to the accidental intrusion of folic acid with a protocol using the L-5MTHF supplement. But the folinic acid is unclear to me. Seems that Fredd has a particularly challenging set of genetic / metabolic variants (of course who am I to speak, I have a very crazy rare autoimmune disorder). I was just wondering if depending on people's SNP variants some may be ok with folinic acid while others are not. I know Rich Vank included folinic acid in his protocol (albeit a small amount) to allow for the many other roles of folates in the body. But then again I suppose most of us who eat healthy get some amount of folates in our diet for that purpose. I will probably try the removal of folinic acid and replace with increased Metafolin. But as a scientist I like to understand the theoretical basis as well.
As far as the glutathione goes, that confuses me. Seems like Fredd is doing everything possible to have only active forms of B12 permeate the cells and bypass all machinery for B12 processing. As a sufferer of an autoimmune disease, rebuilding my glutathione (via enhancement of ATP and vitamin C) was critical to the reduction of symptoms.
Glutamine is the single most abundant amino acid in your body. And your brain is excellent at shuffling it with your body. Not supplementing small amounts of it, will have almost zero impact on your body's stores as it makes hundreds of grams a day as needed.
Cysteine is a different matter but in my case I had absurdly high levels until I got the glutathione construction machinery on track. Your body consumes quite a bit of its cysteine stores in order to make glutathione. Most people with a methylation block have low cysteine in the trans-sulfuration pathway. Ironically I have low cysteine now since it is the rate limiting step.
High vitamin C is one of the best ways to recycle glutathione and things like D-ribose are excellent at boosting ATP production another limiting factor. I increased my whole blood glutathione levels by 2.5 times in a few months by removing the other rate limiters for my particular case. This was after being on Rich Vank's methylation protocol for many months. But via conversations with Rich, he pointed me to the vitamin C angle while my own research pointed me to the ATP problem.
So simply avoiding the amino acids glutamine and cysteine and glycine will not stop the making of glutathione, unless you have malfunctioning machinery (like me), while things like vitamin C and D-ribose will boost glutathione production if the substrates exist. Yet both of those are in Fredd's protocol on page 1.
Still I am confused why inter-conversion to glutathionylb12 is bad unless someone has specific genetic polymorphisms that preclude conversion back to the active forms. I understand how cyanocobalamin is a waste product, but glutathione is often a needed cofactor to make the intermediary state to build the methyl B12 to get into the methionine synthase enzyme. So hence the confusion.
Don't get me wrong Fredd has some very interesting insights. Without him I would still be taking folic acid (and maybe folinic acid) and shooting myself in the foot
Personally I am looking to reduce my high histamine levels, my high MCV, and increase my own body's melatonin production so my circadian rhythm can be reasonable. I know my high histamine levels contribute to a number of lingering pain symptoms that my other meds and supplements are not adequate to handle. Hence I am trying to 're-tool' the methylation protocol I have been following for 2 years in the hopes of improving some of the things.
You are welcome.
I agree, it does seem like Freddd has a set of challenging genetic variants.Maybe others tolerate it quite well. It must be dependent on the SNP variants, I think. You can find some discussions on the mthfr.net website. Freddd has written quite a lot about paradoxical folate deficiencies, and intolerance of veggie folates. I think he was working on folate quite a lot the last time he was online. As far as the theoretical basis goes, you might want to search PubMed and read the threads he has posted for the biochemistry of it. Do share if you find something.
All threads posted by Freddd:
I think even Rich has replied to many of his threads, which might be useful to you.
I think I will think the same if I switch to Rich's protocol. About glutathione, Freddd goes on to say that it is dangerous. I have not considered glutathione and folinic acid but have been working on titrations with things like metafolin,adb12,l-carnitine(for ATP), as Freddd has mentioned in his protocol. So I can't offer you my experience with glutathione, as I have not tried it. I have read Freddd's view on glutathione and folate, here it is:
Quoting from the comments section of http://chriskresser.com/b12-deficiency-a-silent-epidemic-with-serious-consequences
"FredddApril 25, 2012 at 2:33 pm
Chris Kessler, There is all sorts of nonsense out on the web. I assure you glutathione is quite dangerous and can cause Subacute combined degeneration in 6 weeks. I repeat the warning frequently because glutathoone has bexome a FAD. It is quackery and dangerous to the neurological health of anybody taking it. The people claiming “relief” are having an effect on symptoms by destroying all active b12 in the body that isn’t in the mitochondria and causing massive folate deficiency via “methyl trap”. The people having relief have very strong responses to mb12, adb12 and Metafolin becasue they are desperately low. They get rid of the troublesome b12 and block methylfolate , their nerves numb out and they have relief. It is a very dangerous relief caused by damaging the the nervous system, both peripheral and central. The glutathione combines amost instantly to any unbound b12 converting it to glutathionylcobalamin and flushing it out in the urine very visibly and very quickly. I can demonstrate this very easily in anybody willing to volunteer risking something that will cause brain and cord damage. It is 100% predictable and repeatable if the directions are followed precisely. In people not currently in folate or b12 deficiency acute folate deficiency symptoms can start showing up in 2 hours, mb12 deficiency in 3 days and adb12 deficiency in 30-60 days. We ran a 10 subject trial. All 10 were having good results with the Active B12 Protocol. All 10 has the same response with timing variations. This was equally true for IV g;utathione, oral reduced glutathione, glutathione precursor pairs like NAC & l-glutamine (including commercially paired supplements), whey and NAC all by itself. The only difference was speed of onset which was based on dosage of glutathione and/or precursors. Further anybody already on it was 100% prevented from having any benefit from mb12,adb12 or Metafolin and these people were able to start healing after takling corrective doses of adb12, mb12 and Metafolin after discontinuance of glutathione. People getting all upset about theoretical possibility of a few mg of mb12 causing mercury toxicity were at the same time taking somethiong doing genuine brain damage to themselves. You know, In this game of YOU BET YOUR LIFE we each have to be self responsible and weed out what works and what is bogus information. Your life and quality of life depends upon the choices you make. Choose wisely. Now if you wish to characterize a delivery of information as bullying, that’s your choice. You are welcome to pursue dangerous fads if you want. If you want to ignore what works, that is your choice too. The information reaches far more than you.
As far as “rare gentic” polymorphisms, let;s consider that. The only one I can truely admit to being pragmatically proven is that like 20% of the population I can’t convert folic acid to methylfolate, or maybe like 30% of population I can only convert a small amount of folic acid to methylfolate leaving lots of unconverted folic acid in my system that competes with methylfoalte effectively blocking it. As the other 50% of population can only convert about 800mcg max of folic acid to methylfoalte they too can have folic acid blocking and outrun the converted folate supply in the body if they actually take some mb12 and Metafolin and switch on healing. Some of us also can’t convert folinic acid and that is even worse in it’s blocking effectiveness. Both folic acid and folinic acid can block up to 10 or more times as much Metafolin. As folini acid is the major folate in veggies, eating too many veggies can also put me into folate deficiency or insufficincy (same symptoms, not as severe). As this type of folate deficiency will always hinder b12 retention and use in the body, b12 deficiency always follows. This makes it very difficult to determine whether I actually have any b12 related polymorhisms at all. I appear to have the most serious form of folate polymorphisms, and this can be demonstrated. As I share that with at least 20% of population I wouldn’t exactly call that “rare”. You are repeating biased hearsay by Rich, somebody trying to protect their theories of a disease cause and treatment, which doesn’t work. He also does not suggest using glutathione but he is very careful not to step on the toes of true believers. I foresee a class action lawsuit in the future on glutathione and NAC” therapies” from people damaged by them. I think that Cerefolin with NAC is a time bomb of neurological damage I can tell you how to demonstrate each and everything I have said. It is highly predictiable and easily demonstrable. The main occurance with a 5 star mb12 and Metafolin is that it turns on healing, about 50mcg of mb12 is quite sufficient for that, and most people need 1500-3000mg of additional potassium for cell formation or they become symptomatic of low potassium even with serum potassium as high as 4.2 or 4.3, and there is usually an induced folte insufficiency. A typical startup pattern for somebody titrating starting at or below 50mcg is that the healing staeted by 50mcg requires 2000-3000mg of potassium supplement and 2-3mg of Metafolin.
As the effectiveness of the simplified methylation protocol is < 1:10,000 in producing actual recovery and that of the active b12 protocol is more like 1:2-1:10, I would love to see some suitable matched pair A-B crossover trials. The basic problem is that hydroxcbl is 100 to 10000 time less effective for EVERYBODY than a 5 star mb12 and adb12. Metafolin is 100% effective for 100% of population whereas folic acid and folinic acid are about -100% effective for some unknown percentage of poputation, 0% effective for at least 20%, 20% effective for 30% of population and perhaps 50% effective for 50% of population. It would appear that almost everybody with ME/FMS/CFS has one or more of the troubling folate polymorphisms. Research has shown that those with CFS/FMS have low Cerebral Spinal Fluid cobalamin along with those with ALS, MS, Parkinsons' Alzheimer's, Supra Nuclear Palsy. The pragmatic test for detecting these CSF deficiencies is easy. They can be spotted decades in advance of diagnosis. People who are on 1mg injection of cyanocbl a month for pernicious anemai are barely liveing zombies on that can be fully restored to health with mb12, adb12, metafolin, l-carnitine fumatate and the usual vitamins and minerals needed as a backround with avoidance of folic acid and folinic acid. Vegetable food folate problems can be overcome by taking 4mg of Metafolin at each meal. An perceived intensification of symptoms occurs as soon as mb12 starts working (5 minutes to a couple of hours) and is normal startup. People with anxiety as a symptom need to start titrating at 10mcg of 5 srtar mb12 and adb12 or so, others can start with 1mg of a 5 star mb12. The neurological damage pattern is different for those with anxiety. Admittedly I'm more comfortable with a database of a million or so persons. However, as the Active B12 protocol works in almost everybody with a selection of the 300 symptoms that it affects, you can hardly miss. It doesn't affect anybody in any way who doesn't have symptoms. Low potassium appears on the third day after methylation startup and cell reproduction startup, which occurs in hours after consumption."
Hope it helps.
Thanks for the links.
I tried a day with no folinic acid and to be honest the results were mixed. I think most of my body was better in terms of calmness, clarity of thought, basic energy, etc. but to be honest my low dopamine symptoms started to set in at night which was not fun. I am also hypokalemic (3.2 serum) so I have to be careful as I know methylation support can affect that (I take a lot of extended release KCL and other potassium per day for a total of 3000 mg / day). But then again I have been borderline hypokalemic for a decade or more. Reduction of folate for other biological purposes beyond methylation will lower biopterin levels indirectly through folate intermediates and lower catecholamine production, while increased methylation will metabolize catecholamines faster via the COMT enzyme. So it is a sticky situation.
I read the post you attached from Freddd in reply to another forum post.
I agree with some his points. Namely that taking glutathione exogenously is a fad and a waste of money.
But not for the same reasons.
Glutathione is notorious for breaking down into glutamine and cysteine and glycine. In fact to get through the cellular membrane it must disassemble and be re-assembled inside the cell. Period. When taking glutathione exogenously even via IV at most some gets uptaken by the liver and maybe a little in the kidneys, the rest is broken down.
But glutathione is a key cofactor in multiple parts of the Krebs cycle. You never want to down-regulate the Krebs cycle. Second of all glutathione is a major anti-oxidant and a major component of immune function. Low glutathione also greatly exacerbates autoimmune conditions. These things are all well known in the scientific literature having nothing to do with the quacks and charlatans like Suzanne Sommers who are pushing glutathione itself.
Ironically Freddd puts vitamin C and D-ribose both into his basic protocol. Vitamin C is the main way to break the GSSG complex and recycle glutathione. D-ribose and L-carnitine fumarate all lead to increased ATP through different mechanisms (as does magnesium and CoQ10 for example). ATP is a major rate limiting step in making glutathione from glutamine and cysteine. ATP is the energy currency of the body. So on hand he blasts glutathione,
says no precursors and then includes supplements that will increase glutathione. I think we would all agree ATP is extremely important to health.
Also as I pointed out in the earlier post, your body makes hundreds of grams of glutamine a day. That is fact. Glutamine is a major indirect branch off the Krebs cycle and is the backbone of glutamate and GABA. Low levels
of glutamine in the body or the brain have all sorts of nasty consequnces, which is why it is so hard to achieve unless someone is on a starvation diet or has zero Krebs cycle activity. So taking an extra 5 grams of glutamine a day, is like 2-3% of your bodies budget and somehow that extinguishes all benefits of the methylation protocol as seen in a 10 patient unpublished trial?? I don't get that.
Many people with CFS, may confuse problems with the NMDA glutamate receptor as being due to other problems.
Excess glutamate is a problem. If conversion of GABA is limited by low P-5-P, magnesium, etc. then a build up of glutamate is bad, and extra glutamine is not helpful. Trust me over-activation of the NMDA receptors = neurological pain that cannot be reduced by any medicine including opiates. The only answers are taurine, magnesium, glycine and GABA for different reasons (too long to discuss here). Trust me I have lived this nightmare, since my autoimmune disease is in fact Stiff Person Syndrome. Personally IV glutathione was a disaster for me, since prior to my real diagnosis, I was getting infused with large amounts of glutamate that I could not process and my NMDA receptors went wild making my muscles cramp like crazy.
NAC is another matter. NAC has a lot of nasty side effects. Most notably in the brain. The side effects have exactly zilch to do with glutathione production. But what is hilarioius (ignoring NAC) is if the methylation protocol works
(whoever's you use) then you will increase cysteine production and ultimately some amount of glutathione (unless you are blocked with ATP like I was). So more methylation = more cysteine production which with the high intrinsic amounts of glutamine in most people = more glutathione provided ATP is present.
So there is a circular logic here that simply makes no sense to me.
I suspect Freddd was dealt a particularly bad genotype with active B12 processing and thus walks a razor's edge not being able to convert from any of the inactive forms.
Don't get me wrong I respect the heck out of his research and passion and his obviously difficult health story, but the like I said your body will make glutathione if you are healthy and have methyl groups and ATP and there is nothing you can do to stop that ...
- THE 95% REASONS B12 AND FOLATE THERAPIES FAIL
Version 2.0 - 03/10/11, Version 2.1 - 05/08/11. Version 3.0 – 10/25/2012, Version 3.1 10/26/2012
1) They take an inactive b12, either cyanob12 or hydroxyb12. The research validating their use was primarily for reducing blood cell size in Pernicious Anemia, keeping the serum b12 level over 300pg/ml at the end of the period between injections. They make a statistically significant effect that can be seen in lab tests in a significant percentage of people compared to placebo. They do not heal most damage done by active b12 deficiencies and have little or no effect on the vast majority of symptoms. They may even block active b12 from receptor sites hindering the effects of real b12. They both cause a keyhole effect of having only a very limited amount (estimated at 10-30mcg/day) that can actually be bound and converted to active forms. They in no way increase the level of unbound active cobalamins which appear required for most healing. They do nothing beneficial in a substantial percentage of people (20-40%) while giving the illusion that the problem is being treated and if it doesn’t work, oh well, that’s the accepted therapy. There is no dose proportionate healing with these inactive b12s because it all has to go through this keyhole. Some people are totally incapable of converting these to active forms because they lack the enzymes or ATP
2) They take active b12 as an oral tablet reducing absorption to below 1%. A 1000mcg active b12 oral tablet might bind as much as 10mcg of b12. Again the b12 has to be squeezed through a keyhole that limits the amount and is subject to binding problems in the person whether genetic or acquired.3. They take a sublingual tablet of active b12 and chew it or slurp it down quickly reducing absorption back to that same 1% and limited to binding capacity. With sublingual tablets absorption is proportionate to time in contact with tissues. I performed a series of absorption tests comparing sublingual absorption to injection via hypersensitive response and urine colorimetry.
3) Of the many brands of sublingual methylb12 only some are very effective. Some are completely ineffective and some have a little effect.
4) For injectable methylb12, if it is exposed to too much light (very little light actually is too much) it breaks down. Broken down methylb12 is hydroxyb12. It doesn’t work at healing brain/cord problems of those who have a presumed low CSF cobalamin level. That requires a flood of unbound methylb12 and adenosylb12 (2 separate deficiencies) that can enter by diffusion. Adenosylb12 from sublinguals can ride along with injected methylb12.
5) They don’t take BOTH active b12s.
6) They don’t take enough active b12s for the purpose.
7) Lack of methylfolate
8) Lack of sufficient Methylfolate, a dose can start more healing than the same dose can complete.
9) Paradoxical Folate Deficiency - Folic acid is taken which can block at least 10 times as much methylfolate from being active inducing folate deficiency even if methylfolate is also taken. These induced deficiency symptoms are often called "detox" symptoms. Folinic acid is taken which can block at least 10-20 times as much methylfolate from being active inducing folate deficiency even if methylfolate is also taken. These induced deficiency symptoms are often called "detox" symptoms.
10) Lack of other critical cofactors.
11) Lack of basic cofactors
12) Glutathione, glutathione direct precursors, NAC and /or whey is taken causing what is often called "detox" while actually being induced folate and b12 deficiencies.
13) Having many additional supplements and herbs of unknown interactions and effects.
I have such problems with sugar (mannitol, xylotol, flavorings, etc) in all the b12 sublinguals and folates.
I am attempting Freddd's protocol and realize in order to do this, the brands will be different. I am just hoping there are adequate.
I have found a Methy B12 from Pure encapsulation. I realize it is a capsule, very pure.
*I was wondering if I could open the capsule and put the contents under my tongue?
Throne puts out a very pure 5 mthfr folate (like solgar metafolin minus the mannitol)
I can provide a online supplement store i use, very reasonable and brands that are typically only used by NP care providers ex. Design for Health
I have contacted a compounding pharm in Lakewood Colorado, spoke to a pharmacist Tina and they make drops for sublingual use with no fillers, no sugars, just the B12 and water
They have a Methyl B12 as well as a Hydro B12. She did not have a price for the Methyl but thought it might be less than the hydro,
which is about $60 for 5ml, 450 drops, which would last a pretty long time.
She is also looking to her sources and getting back to me for compounded drops for Dibencozide, fingers crossed.
I will keep you posted if anyone is interested
The pharmacy is Belmar
800 525 9473
303 763 5533
a script is needed.
One other question...
I just read that Freddd says, for the protocol to be as effective as possible, you must use the 2 active B12,
but in reading his protocol 3 critical B's are listed
*Why are there 2 methy B12? They seem to be the same type of Methy B12.
I am hoping to use the compound drops of Methyl B12, Dibencozide and the Throne Methy folate
and supplements and critical co factors (although the ribose has sugar and maybe the carnitine, not sure, will have to check.
Thanks for the help
I can only find the following in a chewable when it sounds likes like a sublingual/chewable in the protocol on Page 1
enzymatic therapy 1 mg b12 infusion
That's the one I use. Just stick it under your tongue or up by your gums.
OK, in addition to my current regimen (D3, fish oil, CoQ10, Mg, Potassium, Probiotic, ZINC) I will take the following:
Jarrow Formulas 5mg Methyl B12
Enzymatic Therapy 1mg B12 infusion
No Folic Acid
Comments? Should I add anything else?
PLEASE HELP me nail down my B12 regimen! I really need to try something quickly!! See my post immediately above.
I will try Fredd's regimin as feature in Cort's B12-the hidden story thread.
Did you read Freddd's thread where he seems to have had problems with the Jarrow b12?
The thread is entitled 'Learning from a crash'.I think he also suggests taking adenosylcolabamin (adb12 also called dibencozide), and possibly may need to add TMG (trimethylglycine) and l-carnitine fumurate. There is discussion also about the importance of taking extra zinc.
I'm also trying the protocol and having been doing all except with start with adb12 tomorrow.
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