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Glutathione & Precursors - Detox or Induced Methylb12 and Methylfolate Deficiencies?

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
This is an important map of certain biochemical cycles. There are some other versions I have seen that show the place various forms of b12 have in the process and the extra cycles needed for the hydroxyb12 and cyanob12 conversions to methylb12 for its active part. Comparing the versions can be very informative too. I'll try to locate where they are.
 
Messages
6
Location
So. CA
Hi Fredd, I had started Glutamine (for leaky gut and glutathione production as per doctor)in high doses 3 weeks ago and was in heaven for a week as i had nervous energy but that was bettter than no energy, then had severe energy crash and detox type symptoms like I have not seen in quite awhile. I stopped the Glutamine a few days ago. I have been injecting Methlcobalamin 1000mcg on and off for a year 2x a week for 10 times. Yesterday I started your protocol with 5000mg Jarrow mb12 and had a good day! I was already on the other critical minimums- methylfolate, potassium, omegas, but need to get some multi vitamins etc . Today I thought to use my mb12 IM (hoping they have not been broken down by light but was kept in closet).So I did the 8th one in 4 weeks. I did have some glutamine last night and am still crashed today. I am getting convinced of your theory! Now I am thinking I would like to speed up this process. So far my reactions to mb12 have not been to severe but there seems to be some reaction. After reading your above experience on reversing the gluathione set-back, I am thinking about increasing my mb12 IM to every day for the few days I have left of supply, then move on to the sublinguals and increase, meantime increase the methylfolate up from 800mcg. I am just afraid. I have not done a serum test as my Doc says they are unreliable.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Hi Fredd, I had started Glutamine (for leaky gut and glutathione production as per doctor)in high doses 3 weeks ago and was in heaven for a week as i had nervous energy but that was bettter than no energy, then had severe energy crash and detox type symptoms like I have not seen in quite awhile. I stopped the Glutamine a few days ago. I have been injecting Methlcobalamin 1000mcg on and off for a year 2x a week for 10 times. Yesterday I started your protocol with 5000mg Jarrow mb12 and had a good day! I was already on the other critical minimums- methylfolate, potassium, omegas, but need to get some multi vitamins etc . Today I thought to use my mb12 IM (hoping they have not been broken down by light but was kept in closet).So I did the 8th one in 4 weeks. I did have some glutamine last night and am still crashed today. I am getting convinced of your theory! Now I am thinking I would like to speed up this process. So far my reactions to mb12 have not been to severe but there seems to be some reaction. After reading your above experience on reversing the gluathione set-back, I am thinking about increasing my mb12 IM to every day for the few days I have left of supply, then move on to the sublinguals and increase, meantime increase the methylfolate up from 800mcg. I am just afraid. I have not done a serum test as my Doc says they are unreliable.

Hi Thku4myhealing,

Allow me a few suggestions for maintaining improved performance from your mb12 injections. For one, go to SC injections. It stretches out the serum peak considerably giving a lot more time for it to penetrate the tissues before it is excreted. Second, refrigerate it. Third, wrap it in foil, never to be exposed to light for even a minute each time you draw from it. I agree with your doc. A serum test won't tell you anything useful. A single steak dinner can raise it 200pg/ml. In one study with uremic patients a 500mcg injection raised the serum level to 50,000pg/ml or so before dialysis. With that kind of variability a high level doesn't mean a thing. Also, with perople having responsive to mb12 symtoms at and above the top of the scale, it isn't poredictive of who will respond. All in all the 5000mcg Jarrow when retained for an hour is fully equivalent to a 1000mcg injection. You might do well to get the Country Life Dibencoizide 3mg as well. It is en entirely different thing from the mb12 and could help a lot. Good luck. I'm glad this has helped. I tried reducing the methylfolate and some of the symptoms retured within 16 hours. Keep in touch.
 

jenbooks

Guest
Messages
1,270
Glutamine taken as a supplement could lead, depending on your bacterial infections and genetics, to excess glutamate which is a neurotoxin.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Glutamine taken as a supplement could lead, depending on your bacterial infections and genetics, to excess glutamate which is a neurotoxin.

Hi Jenbooks,

Good point. It ties in well to the mb12 issue. Mb12 is protective against glutamate toxicity in the nervous system and is likely inactivated in the process. I didn't know how to get from the glutamine to the glutamate.
 
M

markmc2000

Guest
NAC reactions

Hi freddd,

Can I run a situation by you? I think it is more of a blog statement and I don't really have a question, but rather a statement of where I am at. please forigve my communication abilities today I am having some cognitive disfunction.

I mentioned I was doing well with NAC and ALA/L carnitine for awhile. My sex drive was improving, mood, and so forth. It all came to a screeching halt.

I quit the NAC for two weeks, and started some jarrow b-12 5000. my buring feet and buring bladder went away. I slept alot for a week or so. I got totally fatigued, my hair softened, my feet got cold, my feet no longer burned, bladder felt good, everything was feeling better from the B-12.

I started the NAC again just to check and see if I can get back to that energy and mood I experienced before my crash. My hair became dry, my feet started burning, my bladder started burning, my hamstrings are kind of tingling, my hair started falling out. DOes this sound like a methylfolate deficiency you describe? It feels like one because when I add more b vitamins my hair softens and the burning feet go away.

I am going to try your whole program soon, but need to check in with my doctor to get him to buy in on your methylation protocol and get his opinion too

Thanks for all your effort, I have certianly benefitted from your countless hours of forum posts.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Hi freddd,

Can I run a situation by you? I think it is more of a blog statement and I don't really have a question, but rather a statement of where I am at. please forigve my communication abilities today I am having some cognitive disfunction.

I mentioned I was doing well with NAC and ALA/L carnitine for awhile. My sex drive was improving, mood, and so forth. It all came to a screeching halt.

I quit the NAC for two weeks, and started some jarrow b-12 5000. my buring feet and buring bladder went away. I slept alot for a week or so. I got totally fatigued, my hair softened, my feet got cold, my feet no longer burned, bladder felt good, everything was feeling better from the B-12.

I started the NAC again just to check and see if I can get back to that energy and mood I experienced before my crash. My hair became dry, my feet started burning, my bladder started burning, my hamstrings are kind of tingling, my hair started falling out. DOes this sound like a methylfolate deficiency you describe? It feels like one because when I add more b vitamins my hair softens and the burning feet go away.

I am going to try your whole program soon, but need to check in with my doctor to get him to buy in on your methylation protocol and get his opinion too

Thanks for all your effort, I have certianly benefitted from your countless hours of forum posts.


Hi Markmc,

My hair became dry, my feet started burning, my bladder started burning, my hamstrings are kind of tingling

Those are clearly methylb12 deficiency symptoms. Methylfolate and b12 are tightly linked and work together. Losing the methylfolate can then prevent b12 from reaching the tissues or working effectively. So with the NAC methylfolate, mb12 and adb12 are all impacted in my experience.

I am going to try your whole program soon, but need to check in with my doctor to get him to buy in on your methylation protocol and get his opinion too

I don't work from a methylation theory basis. However, lack of methylation is just one of the many problems casued by mb12/methylfolate deficiencies. Because of that the active b12 deficiency theory and the methylation theory protocols overlap considerably in the supplements used. My opinion is that the active b12 active folate theory produces faster better results with many people.

As some brands of sublingual mb12 and adb12 are far more effective than others, the specific brands specified are important to success. I found that all the deficiency type NAC effects started reversing within hours of adequate (larger than usual) doses of metafolin, mb12 and adb12. Otgher basic nutritional factors can also be very important such as Omega3 oils for healing the nervous system and Potassium to prevent Hypokalemia from sudden healing. Also B-Right b-complex or equivalent is important for healing ther nervous system. B-Right is a moderate dose balanced component b-complex with multiple coenzyme forms of the b-vitamins suitable for twice a day usage without stomach upset.

Unfortunately a lot of docs don't know a thing about nutritional supplements or how they can be used in this way. Good luck.
 
M

markmc2000

Guest
oops?

"Those are clearly methylb12 deficiency symptoms. Methylfolate and b12 are tightly linked and work together. Losing the methylfolate can then prevent b12 from reaching the tissues or working effectively. So with the NAC methylfolate, mb12 and adb12 are all impacted in my experience."

Freddd, did you mean to say "methylfolate" deficiencies?

I currently take folapro, but will try metafolin next time around.

thx
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
"Those are clearly methylb12 deficiency symptoms. Methylfolate and b12 are tightly linked and work together. Losing the methylfolate can then prevent b12 from reaching the tissues or working effectively. So with the NAC methylfolate, mb12 and adb12 are all impacted in my experience."

Freddd, did you mean to say "methylfolate" deficiencies?

I currently take folapro, but will try metafolin next time around.

thx


Hi Markmc,

No. Those are methylb12 deficiency symptoms. Methylfolate is somewhat different.

FolaPro features Metafolin, the active, preferred form of folate called L-5-methyl tetrahydrofolate (L-5-MTHF).♦

Folapro is methylfolate, Metafolin by brand name. You already have it.

The NAC caused deficiencies symptoms that could be clearly backtracked to mb12, adb12 and methylfolate by what each one cleared up.

The burning bladder and neuroplogical problems are mb12 deficiency symptoms with maybe a little overlap to folate but methylfolate by itself won't clear them up where as mb12 will as long as there is also enough folate.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
A small update on my glutathione precursor experience.

The recovery period of the NAC/glutamine specific problems now appears to have come to an end. I'm back to approximately where I was before starting except for my muscles which still have more pain, but much more defined now. This kind of pain took months to clear last time As I described a couple of days ago the specific pain and inflammation caused by NAC/l-glutamine has finally faded. A little less noticable is something that happened 6 years ago in the initial period of mb12. As areas of generalized pain decreased, quite suddenly the perception of all sorts of specific pains sharpened, became much more defined. This clarity of perception has been lacking the last 10 months or so. This is such a major defining part of the mb12 experience, this clarity and sharply delineated perception; out of the fog, into the smog.
 
Messages
2
A Question for Fredd

I'm new to this B-12 detox theory. Before I consider trying it I would like you to tell me how many people actually get well from doing this. Let's say out of 100 people how many got well? My e-mail address is edwardscse@cbbmail.com. I would really like you to write and answer this then I will make up my mind as to whether I want to go down the road of trying to get well again.
Thank you,
Carol
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
I'm new to this B-12 detox theory. Before I consider trying it I would like you to tell me how many people actually get well from doing this. Let's say out of 100 people how many got well? My e-mail address is edwardscse@cbbmail.com. I would really like you to write and answer this then I will make up my mind as to whether I want to go down the road of trying to get well again.
Thank you,
Carol

Hi Carol,

Did you receive my email? Your question as you state it is currently unanswerable as healing can take more than a year and nobody here has been trying the active b12 protocol for more than a few months though there are quite a few making good progress. Elsewhere that are considerable numbers of people who have done well and even some that stop in every now and then to update on their progress which in many cases, has allowed them to get back to a normal life.
 

Athene

ihateticks.me
Messages
1,143
Location
Italy
I think Fredd's analogy of the elephant was very good.
There is lots of info reporting wonderful results with glutathione for some people. There is plenty of info reporting that it has very bad effects on others.
As we all know, the methylation cycle can break down in different places and to different degrees for different people. Some can move glutathione on through the cycle and use it properly, others cannot. Fredd is not unique in getting bad symptoms from glutathione. Ask any DAN doctor and they will tell you.
Thank you again Fredd for your help, research and explanations of this very complex topic.
 

Hysterical Woman

Senior Member
Messages
857
Location
East Coast
Methylation

I think Fredd's analogy of the elephant was very good.
There is lots of info reporting wonderful results with glutathione for some people. There is plenty of info reporting that it has very bad effects on others.
As we all know, the methylation cycle can break down in different places and to different degrees for different people. Some can move glutathione on through the cycle and use it properly, others cannot. Fredd is not unique in getting bad symptoms from glutathione. Ask any DAN doctor and they will tell you.
Thank you again Fredd for your help, research and explanations of this very complex topic.


Yes, Fredd, thank you for you research.

I am just beginning to get my feet wet in understanding methylation. I came across the following in my search and wondered whether it might help to post it here. Please forgive me if this has already been posted or discussed, I am finding it difficult to do searching here. I thought the article points out as Athene commented above at how complex this issue is.

The excerpt is from the following site:

enzymestuff.com/methylation.htm

HTH,

Maxine


Methylation

Copyright August 2002. Kd. last updated 8.25.05

This is a discussion which tries to outline the points of methylation and establish some relationships that will result in the practical application of the information. Special thanks to andrew who contributed many links and much understanding to this discussion.

This link has a nice picture of what this process looks like. You may want to refer to it often during the following discussion. http://www.nutriwest.com/articles/homovmsm.htm
The issue of a person being an under or over methylator can be confusing. It may not be one of the all time critically defining issues, but it may help in the general sense. Several common supplements often recommended for those with autism spectrum conditions are involved in this process (this is just one of the processes these supplements may help with).

A "methyl" group is simply one carbon connected to three hydrogen atoms. It may be written as CH3 with the 3 being a subscript.

"Methylation" is not just one specific reaction. There are hundreds of "methylation" reactions in the body. Methylation is simply the adding or removal of the methyl group to a compound or other element.
So why do we care about methylation at all? In general, when some compounds receive a methyl group, this "starts" a reaction (such as turning a gene on or activating an enzyme). When the methyl group is "lost" or removed, the reaction stops (or a gene is turned off or the enzyme is deactivated). Some of the more relevant methylation reactions would be:

1. getting methyl groups "turns on" detox reactions that detox the body of chemicals, including phenols. So if you are phenol sensitive, and you increase your methylation, then theoretically your body can process more phenols and you can eat fruits without enzymes!

2. getting methyl groups "turns on" serotonin, and thus melatonin, production. Therefore, if you are a under-methylator, you can increase your methylation and have higher more appropriate levels of serotonin and melatonin. This means you may not have to take SSRIs, or may have improved sleep.

3. if you are an over-methylator you can take certain supplements to decrease methylation and perhaps turn off reactions that need to be off. This may decrease aggression or hyperness, for example.
This is the general idea. To what extent this actually works in real life for any individual is back to "every one is different." But this is one thing that the Pfeiffer Treatment Center really looks at. I hope this explanation helps.

Something to note is that everyone is not EITHER an over OR under methylator. There are more groups than that, and you may be just fine in regards to methylation. Even if the Pfeiffer statistic is exactly correct when they say 45% are under-methylators and 15% are over-methylators, that totals 60%, so almost half the people are neither.

Where this MIGHT be helpful would be in picking supplements. So someone may do badly on the high B6 protocol. If that person does badly on TMG or DMG too this may be a clue that they will do poorly on ALL the methylation precursors so they can steer clear of that group in high doses. And vice versa, if they did really well with one, then they may also do well with others in the group. Of course, they may not see additional benefit if the methylation process is fixed with the first supplement, but it is something that might help a person know why they or their child is consistently doing well or poorly with a group of supplements.

Is there any evidence to support this? Well, I am looking at the ARI data gathered from over 18,500 parent surveys. Let's say Pfeiffer is exactly correct and under-methylators are about 45% of the "autism" population. These are the values for the precursors for methylation:

- calcium 39% saw improvement
- DMG 43% saw improvement
- Folic acid 44% saw improvement
- B6/mag (both of these are precursors) 46% saw improvement
- Zinc 43% saw improvement

So if you look at any of the precursors, really, most are around that 45% mark of under-methylators (calcium was a little low, but it is a supporting element). So we have a mark of consistency here. SAMe, methionine, and B12 were not choices. What this does NOT point out is which came first.

Was zinc low for some reason not related to methylation and because it was low, methylation dropped? or are you a genetically low-methylator to begin with and do not utilize the nutrients at hand well? Or was folic acid the bottle-neck? or magnesium deficiency? Or an injured gut which cannot adequately absorb any of the nutrients? or....

This is how I see it, just as a general guideline that may be helpful, not a cast in stone type of thing.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Hi Maxine,

The actual methylation situation is even more complicated, and you sort of hinted at it with calcium.





So let's look at the numbers as presented above, and I've seen numbers with even higher percentages of "under methylators".
  • 45% are theoretical under methylators, if everything needed to be sufficient methylators is present. This obviously is the most NORMAL situation for the most people.
  • 40% are theoretical adequate methylators, if everything needed to be sufficient methylators is present.
  • 15% are theoretical overmethylators, if everything needed to be over methylators is present.
In my analysis of symptomatic people's results of trials, no testing of any variety included, no theoretical definitions and no statistical definitions I found two main classes of people:
  • Exhausted methylators, which could include members from any of the 3 above groups, who lacked the means to methylate adequately or excessively who might be called "pragmatic undermethylators". This included most everybody symptomatic and most especially those taking cyanob12, hydroxyb12 and folic acid. These people had strong to very strong immediate responses to methylb12. The larger the doses of cyanob12, hydroxyb12 and folic acid the stronger and quicker the responses to methylb12.
  • Non-exhausted methylators. These people generally had none or very few of the usual 300 deficiency symptoms, and generally did not take cyanob12, hydroxyb12 or folic acid except in fortified cereals or multivitamins or such. They did not have immediate methylb12 responses and if they had any responses at all, they were mild and delayed.
Once everything needed to exercise a genetic tendency towards "overmethylation" is in place, according to the theory about 1/6 of the people will be in that camp. However, if lacking the needed raw materials even those with a genetic tendency towards overmethylation, which appears relatively rare, can't do so and can give all the same appearances as any other exhausted methylator. A theoretical overmethylator with a "methylation block" is an exhausted methylator or temporary undermethylator or whatever one might want to call them. However, as long as they lack the raw materials to be an actual overmethylator, the tendency is only theoretical. So what is seen is a theoretical overmethylator with all the symptoms and signs of an undermethylator. Finding a balance for these people may indeed be more difficult.


What is interesting is reading on these theoretical states, under and over methylation. I used to have many of symptoms from both varieties. I had many many symptoms and they were pretty evenly divided. Now I have very few symptoms of either. I appeared to be a walking contradiction. So which one I am I can't tell you by symptoms. However, I was an exhausted methylator and now I am not. I never have been able to figure out where I fit in on that system. Most of the symptoms in both directions appear to be active b12 and methylfolate deficiency symptoms looked at from a different viewpoint.

In the presence of both active b12s and methylfolate perhaps the defining characteristic is whether a person benefits from additional SAM-e and/or TMG or not. Nothing else appears to make much sense across the many attempts of defining these symptoms.
 
Messages
6
Location
So. CA
Hi Fredd,
I just posted my update to you, and all, under the B-12 Hidden Story general/intro thread.
All was well with with just ad12 SL- 1/day, 1 methylfolate, zinc, omegas and occasionally 1/4 of a 1000mg mb12, and occasionall 1/4 of a B-Right. This was strated early November. I guess I'll just go slower and try to tolerate "reactions"- just very tired.
Best,
 

dmholmes

Senior Member
Messages
350
Location
Houston
Hi Fredd,
I just posted my update to you, and all, under the B-12 Hidden Story general/intro thread.
All was well with with just ad12 SL- 1/day, 1 methylfolate, zinc, omegas and occasionally 1/4 of a 1000mg mb12, and occasionall 1/4 of a B-Right. This was strated early November. I guess I'll just go slower and try to tolerate "reactions"- just very tired.
Best,

Hi Christina, I wanted to chime in with my 2 cents. The inconsistency of your mb12 and B complex definitely won't help. It would be good to get something, even a very small amount consistently.

How much zinc are you taking? Are you balancing it with some copper?

Take care,
David
 

Athene

ihateticks.me
Messages
1,143
Location
Italy
I posted this elsewhere but I want to share it widely so I'm repeating it.

I saw kenny De Meirleir recently and he told me my "detox reactions" (headache, muscle weakness and palpitations) are coming on when my body runs out of B12 for detoxing. The toxins are mobilised but then the liver does not have enough resources to finish the job, so to get rid of the symptoms you need to take a lot MORE B12, not less.

I have raised my intake to one injection of 10,000mcg a day and the headaches and other symptoms have all gone. So this definitely works.
 
C

Cloud

Guest
Glutamine taken as a supplement could lead, depending on your bacterial infections and genetics, to excess glutamate which is a neurotoxin.

Hmmm that sucks since I use 5-10 Gms daily for Leaky Gut....but then, I never feel any negative response from high dose Glutamine
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Hi Fredd,
I just posted my update to you, and all, under the B-12 Hidden Story general/intro thread.
All was well with with just ad12 SL- 1/day, 1 methylfolate, zinc, omegas and occasionally 1/4 of a 1000mg mb12, and occasionall 1/4 of a B-Right. This was strated early November. I guess I'll just go slower and try to tolerate "reactions"- just very tired.
Best,

Hi Thk u 4,

Small irregular quantities appear to make reactions much worse and to go on indefinitely. ALso, the balance between mb12 and adb12 may be way off. Some say that it needs to be 3-10 times as much mb12 as adb12, closer in proportion to what the body needs and uses. Further, the tiredness and fatigue are often the easiest and fastest things to change if the right things are taken. Of course to really change that can cause a person to feel a bit supercharged while the body adjusts to being able to put out a normal amount of energy. "Been down so long it feels like up to me" says it very well. We lose sight of what "normal" is.