What are possible scenarios to having an overramped methylation cycle?

[learner2life]

What are some of the possible outcomes that can occur from having an overramped methylation cycle? Trying to peice things together it sounds like the homocysteine is all directed towards the methylation cycle. Thus leaving very little for the transulfuration pathway to react with causing low glutathione, taurine and sulfate levels? That would impair a person's ability to detox right? If one suspects that this is going on would it make sense to just supplement with taurine and sulfate. The NAC and glutathione isn't a good idea to take from what I've read. Would it be best to be doing some form of detox if this was happening? Would this mean more b12 is reacting with toxins because of low glutathione? Would this essentially rob b12 from the methylation cycle? Hypothetically speaking, would the fix be to try and decrease the b12 and take more b6 and magnesium to divert more homocysteine and try and be patient with it. Just trying to sort thru some of the possible outcomes and hopefully get a better idea of what could be happening. Just feel like I am wandering on and off the beaten path without an idea of which way to go...
Thank You so much!!
David

 

[alex3619]

Hi david, I don't have answers to your questions, but I would be careful of taking too much B6. I think it can be neurotoxic in excess, and is something best approached with care. I am also not convinced that NAC or liposomal glutathione is necessarily a bad thing, though I do know that some people can have problems with NAC. Magnesium on the other hand is usually well tolerated and beneficial. My current areas of reading are methylation and LDN, so I might have more to say in a few months. Bye, Alex

 

[richvank]

What are some of the possible outcomes that can occur from having an overramped methylation cycle? Trying to peice things together it sounds like the homocysteine is all directed towards the methylation cycle. Thus leaving very little for the transulfuration pathway to react with causing low glutathione, taurine and sulfate levels? That would impair a person's ability to detox right? If one suspects that this is going on would it make sense to just supplement with taurine and sulfate. The NAC and glutathione isn't a good idea to take from what I've read. Would it be best to be doing some form of detox if this was happening? Would this mean more b12 is reacting with toxins because of low glutathione? Would this essentially rob b12 from the methylation cycle? Hypothetically speaking, would the fix be to try and decrease the b12 and take more b6 and magnesium to divert more homocysteine and try and be patient with it. Just trying to sort thru some of the possible outcomes and hopefully get a better idea of what could be happening. Just feel like I am wandering on and off the beaten path without an idea of which way to go...
Thank You so much!!
David

Hi, David.

I think you have the first part right. If the methionine synthase reaction is overdriven, it causes a bias toward converting homocysteine back to methionine, and lowers the flow down the transsulfuration pathway. This can be seen in lab testing on people who are taking high simultaneous dosages of methyl B12 (either sublingually or by injection) and methylcobalamin, because supplying these together directly removes control of the methylation cycle from the cells themselves.

This situation shows up particularly on the comprehensive amino acids panels, either in plasma or urine, such as the larger Metametrix amino acids panels available from www.directlabs.com. A more complete picture can be obtained if other types of tests are also run at the same time, in particular the methylation pathways panel from Health Diagnostics, the organic acids test called the Metabolic Analysis Profile from Genova Diagnostics (available from www.directlabs.com) and the urine toxic and essential elements test from Doctors Data Lab, also available from www.directlabs.com

In my view, if this occurs it is best to lower the dosages or switch to hydroxocobalamin, so that the cells can control the amount of methylcobalamin produced. Having adequate levels of B6 (and B2, which is necessary to convert B6 to its active form, P5P) and magnesium is also important, to ensure proper operation of the enzymes in the transsulfuration pathway. Serine is also necessary to send homocysteine into this pathway, so its levels need to be adequate.

My intent is to correct both the partial methylation cycle block and the glutathione depletion, which usually accompanies it, as well as to re-establish normal function in the entire sulfur metabolism, which is quite dysfunctional in many PWcs.

Rich

Best regards,

Rich

 

[Freddd]

Hi, David.

I think you have the first part right. If the methionine synthase reaction is overdriven, it causes a bias toward converting homocysteine back to methionine, and lowers the flow down the transsulfuration pathway. This can be seen in lab testing on people who are taking high simultaneous dosages of methyl B12 (either sublingually or by injection) and methylcobalamin, because supplying these together directly removes control of the methylation cycle from the cells themselves.

This situation shows up particularly on the comprehensive amino acids panels, either in plasma or urine, such as the larger Metametrix amino acids panels available from www.directlabs.com. A more complete picture can be obtained if other types of tests are also run at the same time, in particular the methylation pathways panel from Health Diagnostics, the organic acids test called the Metabolic Analysis Profile from Genova Diagnostics (available from www.directlabs.com) and the urine toxic and essential elements test from Doctors Data Lab, also available from www.directlabs.com

In my view, Having adequate levels of B6 (and B2, which is necessary to convert B6 to its active form, P5P) and magnesium is also important, to ensure proper operation of the enzymes in the transsulfuration pathway. Serine is also necessary to send homocysteine into this pathway, so its levels need to be adequate.

My intent is to correct both the partial methylation cycle block and the glutathione depletion, which usually accompanies it, as well as to re-establish normal function in the entire sulfur metabolism, which is quite dysfunctional in many PWcs.

Rich

Best regards,

Rich

Hi Rich,

if this occurs it is best to lower the dosages or switch to hydroxocobalamin, so that the cells can control the amount of methylcobalamin produced.

The only problem with this is that hydroxycbl only affects about 2/9 of person-symptoms, and then only partially. 1/3 of people are NOT HELPED by hydroxycbl at all becasue something in the lineup of assumptions isn't working as assumed. As many of us have been taught, NEVER ASSUME because it makes ASSUME. I think a much better answer is to take a controlled amount of mb12. Of course the interpretation of these tests is based on testing on a population with chronic b12 and folate deficiencies. I feel it is far better to let the healing of your symptoms be the guide. Treating to "test results" with b12 and folate has a very very bad history of not actually healing people while getting "normal" results. I choose out and out naked eye healing to "normal" test results. Further as the research has not been done we have no idea what the results look like with people who have sufficiency of mb12, adb12 and methylfolate and are healthy. Right now the advice you give only prevents healing without detailing what the actual detrimental symptoms might actually look like.

 

[learner2life]

Thank you for the posts! Thank You Rich and Freddd for all the information and insight that you have provided on this forum. Its incredible and I really appreciate it. It sounds like I need to cut back on my b12 a little just from what I am experiencing. After being on the destructive path of mono for 3+ years I developed a b12 deficiency along with neuropathy and lots of other things.. From my experiences of dealing with neuropathy adb12 was probably the most influential vitamin that I took. Especially after I decided to cut down on eating red meats to 2-3 days a week. The neuropathy really progressed and I just kept on adding on the adb12 (up to 10mg/day) and mb12 (up to 5mg/day). I have been doing that at those doses for about 3 months. Within the last two weeks my neuropathy has been minimal. I have backed off of the adb12 (7.5 mg/day) but I feel now like generally I have been given an enormous dose of a ssri. I can only conclude that I am sending too much b12 to the methionine synthase. Don't know this stuff well enough but I thought the methionine synthase is a precursor to serotonin or the pathway that leads to serotonin. This drugged feeling has only been happening for the last 2 weeks and the neuropathy isn't as prevalent. So, I think cutting back might be something I should do. I am grateful to have the option of choosing between both protocols honestly. I think both of the work it's just is it right for the individual at the time. Theoritically speaking once the methylation block has started to lift it would take less and less b12 to maintain it's proper function? Maybe since I have only been sick for 3+ years the 7 months I have been taking varying doses of b12 is enough to make a dent and start to lift it? I am not sure. But, the drugged feeling I am confident is coming from the b12. So, Thank you for all the responses. I am sorry this message is jumbled... Have a hard time connecting my thoughts for some reason.. Thanks for the responses!!!
David

 

[Freddd]

Thank you for the posts! Thank You Rich and Freddd for all the information and insight that you have provided on this forum. Its incredible and I really appreciate it. It sounds like I need to cut back on my b12 a little just from what I am experiencing. After being on the destructive path of mono for 3+ years I developed a b12 deficiency along with neuropathy and lots of other things.. From my experiences of dealing with neuropathy adb12 was probably the most influential vitamin that I took. Especially after I decided to cut down on eating red meats to 2-3 days a week. The neuropathy really progressed and I just kept on adding on the adb12 (up to 10mg/day) and mb12 (up to 5mg/day). I have been doing that at those doses for about 3 months. Within the last two weeks my neuropathy has been minimal. I have backed off of the adb12 (7.5 mg/day) but I feel now like generally I have been given an enormous dose of a ssri. I can only conclude that I am sending too much b12 to the methionine synthase. Don't know this stuff well enough but I thought the methionine synthase is a precursor to serotonin or the pathway that leads to serotonin. This drugged feeling has only been happening for the last 2 weeks and the neuropathy isn't as prevalent. So, I think cutting back might be something I should do. I am grateful to have the option of choosing between both protocols honestly. I think both of the work it's just is it right for the individual at the time. Theoritically speaking once the methylation block has started to lift it would take less and less b12 to maintain it's proper function? Maybe since I have only been sick for 3+ years the 7 months I have been taking varying doses of b12 is enough to make a dent and start to lift it? I am not sure. But, the drugged feeling I am confident is coming from the b12. So, Thank you for all the responses. I am sorry this message is jumbled... Have a hard time connecting my thoughts for some reason.. Thanks for the responses!!!
David

Hi David,

You would be very premature ion cutting back. WHile the neuropathy ios improved it takes MUCH LONGER to heal all the way so that it doesn't come galloping back. What you are feeling is a chnage in balance between adb12 and mb12. You needed more mb12 than you were getting compared to the adb12. Usually the ratio is suggested at between 1:10 and 1:3 (3-10 times as much mb12 as adb12. Adb12 is important for powering the nerves and healing the myelin. The mb12 is equally important for healing and then the fuinctioning. That you had this "but I feel now like generally I have been given an enormous dose of a ssri." reaction indicates that NOW the mb12 is getting into the CNS at the ratio that would help you. Everybody who wants to "return to normal" has to go through this. To duck and run as soon as you are seeing the signal that the mb12 is starting to help would be a huge mistake. The healing response is most effective the FIRST time. Trying to get it back after stopping and having a reversal, the response is not as effective. One of the things you are seeing is that mb12 is returning the neurotransmitters to normal. When the mb12 is way low the "volume" on the nerves gfets "turned up" which also amplifies the noise (pain, paresthesias and depressed mood, hallucinations). Then when you take the mb12 with the internal volume cranked all the way up trying to maintain functionality, there is some overshoot but it rapidly returns to normal as the internal volume is turned down to normal. This response of yours is a GREAT! not something to run in fear from. The atmosphere of fear so present is preventing many from healing. So don't take the signal of neurological benefit as something bad. Enjoy it while it lasts.

 

[learner2life]

O.k. Thanks Freddd.
I have come this far and I know the adb12 has definitely helped. I will tweak these doses and see what happens. I will keep you updated. Should I go try and start with the 3-1 right away or ease into it. I appreciate the different points of view.
David

 

[Freddd]

O.k. Thanks Freddd.
I have come this far and I know the adb12 has definitely helped. I will tweak these doses and see what happens. I will keep you updated. Should I go try and start with the 3-1 right away or ease into it. I appreciate the different points of view.
David

HI David,

The ratio that is best for any given person is a custom thing. There are doctors working with mb12 that have said that it takes 5 years of continuous treatment to achieve stable neurological healing. I found that each cycle of neurological healing takes at least 9 months. Because of the paradoxical folate deficiency I have NEVER put more than 2-3 months of healing together back to back. In the past 8 years I have managed about 2-3 years of healing. Good luck.

 

[learner2life]

Freddd,
Since I increased my mb12 I have felt a little better honestly. I think I may be treating more of a b12 deficiency more than anything else. I am in a more relaxed environment so my gastritis is almost gone. My neuropathy has just barely sticking around, very very faint. I can handle the same amount of adb12 without the headaches with adding the mb12. I believe your advice is helping. This is very interesting topic. Do you know offhand of where I can find more information about this neurological healing? I never specifically looked but nevere came across anything that mentioned it while researching b12 except referencing the benefits to M.S. Thanks again for all the help.
David

 

[Freddd]

Freddd,
Since I increased my mb12 I have felt a little better honestly. I think I may be treating more of a b12 deficiency more than anything else. I am in a more relaxed environment so my gastritis is almost gone. My neuropathy has just barely sticking around, very very faint. I can handle the same amount of adb12 without the headaches with adding the mb12. I believe your advice is helping. This is very interesting topic. Do you know offhand of where I can find more information about this neurological healing? I never specifically looked but nevere came across anything that mentioned it while researching b12 except referencing the benefits to M.S. Thanks again for all the help.
David

Hi David,

There are some good studies of mb12 and peripheral neurological healing. One in the UK was based on symptoms and not tests and found that when admitted to the study based on symptoms that the average cobalamin serum level was 700pg/ml with some as high as 1500pg/ml. There was "normal uMMA and Hcy as well. 63% of positive responders to mb12 and getting healing would never have been admitted to studies based on test results as their test results were all completely normal or even "high" cobalamin. They also found dose proportionate healing to be quite prominent regardless of initial serum level. The central neurological healing is unstudied. Only the Japanese are looking into it and using 50mg doses and injections into the cerebral spinal fluid.

 

[learner2life]

Man, and then the imbalances began...
Today I either ran low on magnesium or electrolytes. I increased the potassium, magnesium (total of 1000mg/day) began to add some calcium because I really am not taking any. My body feels pretty unresponsive. Poor concentration, excessive thirst..(drank 3 liters of gatorade in 15 minutes.) I seem to retain more water with b12. When I increased the magnesium I would generally pee it out so to speak but not the last 2 days or so. Increasing potassium makes oen retain more water? I guess it's just a cofactor being released possibly. Just from looking at what I've added... methylcobalamin 1500-2500mcg/day... additional 600 mg of magnesium.. totalling ~1200mg. 300-500 mg of potassium. 500 mg of calcium with very little outside sources. Still taking around 6mg of adb12. I guess it's just another shift or possibly a blocked cofactor being released. Much less neuropathy but more of this droning desensitized feeling. I don't have the skillset to make a good assessment of what it is honestly. lol.. Offhand I should decrease the adb12 it looks like. I think its time to order some of the tests I have been contemplating. take care everyone..
David

 

[learner2life]

Freddd,
I had in my experience a pretty strong reaction to mb12.. I increased my dosages to a 1:1 ratio (7mg each) and I felt so much better for about 24 hours or so. Then, I felt like my magnesium dropped, probably potassium aswell. But, I started to have huge hunger strikes and from looking at my hands, arms and legs my body just needed amino acids and fat cells. Possibly shifted my body towards ketosis. For about 3 days I tried to address what was going on by eating more. Got back to eating red meats in addition to much more carbs. I couldn't sleep thru the night and woke up because I was starving only to stagger into the kitchen and begin eating anything I could get my hands on. I eventually cut way back on the mb12 and adb12 and just tried to rely on eating red meats, dairy and other sources of b12. It just seemed that the mb12 drastically jump started my metabolism and after 4-5 days of trying to keep up with it I finally had to cut it back. The next 5 days after that I ate 3-4 large meals a day while snacking in between and still continued to loose girth in my neck, my skin became thinner and tendons wihtin my forearms, hands and wrists continued to become more defined. I currently weigh the most I have ever weighed in my life but yet my skeletal muscles and tissues are quite thin. Just wanted to know if that seems like a reasonable start up effect to mb12?? Even after limiting my dosages of adb12 and mb12 to 1 mg/day of each it seems like my body is still struggling to keep up with I assume an higher metabolism? This sounds like a normal startup effect so to speak?? Thank you.

 

[harrycat]

Learner2life - just wanted to let you know that I've also experienced increased hunger, waking famished at night and feeling like I can't eat enough calories. I'm on the simplified protocol and this happened to me even when I was taking the recommended amounts of hydroxyb12 / folate - which I have since increased experimentally. I haven't seen a change in my body mass however. Wishing you all the best as we try to figure this stuff out!

 

[aprilk1869]

Vets routinely give animals b12 injections to boost their appetite. When my old dog was given injections for this purpose her appetite went through the roof although the effects wore off over the week. Unfortunately the injections gave her pain and the vet stopped giving them to her, she then ended up losing so much weight there was practically nothing left of her and when she developed foot drop and ataxia she had to be put to sleep. Unfortunately I didn't understand anything about b12 back then.

 

[learner2life]

Harrycat and AprilK1869,
Thank you for the responses. What a powerful supplement and reaction. It amazes me that those dosages with miniscule amounts actually getting into the bloodstream / cells can have such a strong affect.I guess I should be a little more cautious about my dosages with it. That's somethin. Well, atleast I can consider that reaction to be normal. Everything else within my body feels abnormal.. I get an normal reaction within an abnormal state of being I guess I can consider that progress.. It gets hard for me to tell sometimes..