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Starting SMP, preferable to just take B12 first?

sregan

Senior Member
Messages
703
Location
Southeast
When something that worked excellently for 9 years suddenly doesn't , and it is in the most subtle place, the CNS, and suddenly hard CNS symptoms of a certain type hit hard, it isn't subjective is the sense of wondering if anything is even happening. That was clear. It was also clear what had happened. A bunch of people had already been asking about the change before I got clobbered. Then when all of us recovered that I know of by a change of brands, it's pretty well confirmed. So if you are asking what the confidence level is, it's 100% that something in the Jarrow MeCbl changed such that it was no longer CNS neurologically effective. And I did have startup all over again.

Thanks Freddd, then evidence is anecdotal although I have no doubt in this case if there was an appropriate test before and after some change would have been found. I just want to add that anecdotal doesn't imply any lesser of evidence especially when it involves larger number of people. And in fact IMO the internet has completely validated and improved substantially the value of anecdotal information by allowing collection places for first hand accounts such as this forum and allowing everyone to have a "global" voice. We all become part of an ongoing clinical study which is probably our best hope for having anything cured in the future since cures don't seem to be coming from anywhere else these days.

Now that zero doubt only belongs to people who interpret the startup of MeCbl as healing startup and adjust to the startup responses based on that theory. Then when healing has been going solidly for a month or five, when it suddenly turns off, it is very obvious. It makes it so each person can tell what works for them often within hours. One tries a different brand of MeCbl and healing stops and symptoms start coming back in 3 days or whatever. Same with various type of folate. If folic acid or folinic acid doesn't work for a person, whether alone or in combination, it becomes very obvious. One a person succeeds in turning healing on, they can stop guessing and hoping and believing. and floundering around. They can do a comparison, A-B, and know very quickly.

Are you referring to when the supps stop the ongoing stimulation of the Methylation cycle or a deeper action of the B12 you indicated in CNS healing?

I knew in less than an hour that the ENZY was massively superior to the Jarrow when I was in a position to try. When one has compared 20 or more brands it gets very easy. Normally I don't let myself get so debilitated all at once. When one is loosing neurological sensitivity all sorts of things fail to be noticed because of that very lack.

I trust what you say. I think you are the proverbial canary in the coal mine as far as B12 sensitivity goes from what I've been reading here.
 

sregan

Senior Member
Messages
703
Location
Southeast
Exercise is critical in this recovery. So many have exercise intolerance. I did. For me, the exercise intolerance ended with the AdoCbl. Then exercise ability increased vastly when the LCF was added and I was able to grow muscle again.

Thanks Freddd, this is some good info. The only AdoCbl I have (Country Life) has folate. I'll have to get some solgar. I do have the LCF wondering when I can/should start titrating that in? I've been doing pretty good on 1/8 Jarrow MCbl and 1/8 Folapro for a few days now. I f I can keep this up then that will be my SMP starting dosages. My question in the last message I was hoping to answer for myself is should I toss my Jarrow and start the ENZ Mcbl? Or is the Jarrow good enough for keeping methylation going? It is doing something for me. Much more than the Hcbl I started this third round with. If I switch to the ENZ any idea of the equivalent dose form Jarrow...1/4 Jarrow = 1/16 Enz?

There are about 4 or 5 aspects of sleep disorders that appear with the various deficiencies. A common one is sleep paralysis which basically a part of the brain not falling asleep as quickly or maybe waking up more quickly than the freeze on the body muscles that keeps one from acting out all dreams. This can result in a prolonged period of entry or exit from sleep and some people are disturbed by it. Sleep will change a lot in the first few months as the neurology itself changes. Don't worry about it. The studies on MeCbl and sleep indicate that while people end up sleeping shorter times they get restorative and restful sleep. If one is all anxious about the changes in sleep it becomes self defeating. Other experiences of my own and those of other people indicate that AdoCbl, LCF and l-methylfolate are all important in different ways.

I went through a period years ago when I had sleep paralysis more frequently. Wouldn't be as bad if I didn't always feel like I was suffocating. Sleep is changing for sure I did have one night which reminded me of what good sleep used to be like. Beautiful and sad at the same time when I realize what I have lost.

Let's talk about aiming points. Reduced or removed depression is an important aiming point. Quality of sleep doesn't appear to be an effective aiming point. It alters slowly over 1 year or so indicating to me that there is some actually healing that has to occur. Things that change in days or immediate functional items. However, there is a whole chain of functional things that awaits some prior healing. Rapid epithelial healing is a good aiming point. Both lowering depression and increasing healing go together. Increase sensation in nerves, tingling, pain and all that usually indicates healing can be occurring. Some areas of numbness may increase before decreasing as the nerves start changing around. The FMS muscle pains are good aiming points. A decrease of burning pain can occur near 100% in 10 days. The "18" muscle points took about 2 years to fade after MeCbl, but only 9 months and 3 months respectively after AdoCbl and LCF.

Very good detail on what I just asked you in the previous post. Wish I had read this first. But there is still a question of parhaps using mcuh higher dosages of B12 for this healing than the SMP wants.

So the epithelial sores are good aiming points for l-methylfolate. In the presence of sufficient b12 their healing is almost entirely driven by l-methylfolate if all other needed cofactors (you know, A, D, C, zinc etc) are present. In each group of symptoms, by those pages of symptoms and nutrients I put up, a person can find their most active "aiming point" symptoms that signal nutritional effectiveness or not for that group. When healing is turned on differences are noticeable daily at first, then each few days and then a week or two, then barely perceptible over a month and then it's gone. In a month it can settle down from hundreds of things happening in a day to a few noticeable changes daily.

That's where I'm at now is trying to figure out what other supplements I need to add. I'll have to find your post on the cofactors. (symptoms post here: http://forums.phoenixrising.me/inde...adoxical-folate-deficiency.14596/#post-240023)

Wondering if I need to for example:
Add TMG and DMG?
Support the Sulfation pathway at all with P5P?
What supps should I take to support the SMP?
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Thanks Freddd, this is some good info. The only AdoCbl I have (Country Life) has folate. I'll have to get some solgar. I do have the LCF wondering when I can/should start titrating that in? I've been doing pretty good on 1/8 Jarrow MCbl and 1/8 Folapro for a few days now. I f I can keep this up then that will be my SMP starting dosages. My question in the last message I was hoping to answer for myself is should I toss my Jarrow and start the ENZ Mcbl? Or is the Jarrow good enough for keeping methylation going? It is doing something for me. Much more than the Hcbl I started this third round with. If I switch to the ENZ any idea of the equivalent dose form Jarrow...1/4 Jarrow = 1/16 Enz?



I went through a period years ago when I had sleep paralysis more frequently. Wouldn't be as bad if I didn't always feel like I was suffocating. Sleep is changing for sure I did have one night which reminded me of what good sleep used to be like. Beautiful and sad at the same time when I realize what I have lost.



Very good detail on what I just asked you in the previous post. Wish I had read this first. But there is still a question of parhaps using mcuh higher dosages of B12 for this healing than the SMP wants.



That's where I'm at now is trying to figure out what other supplements I need to add. I'll have to find your post on the cofactors. (symptoms post here: http://forums.phoenixrising.me/inde...adoxical-folate-deficiency.14596/#post-240023)

Wondering if I need to for example:
Add TMG and DMG?
Support the Sulfation pathway at all with P5P?
What supps should I take to support the SMP?

Hi Sregan,

The Enzy MeCbl is qualitatively superior. It isn't the dose. The one brand of AdoCbl that is clearly superior is Anabol, which is in an oral capsule and can be pour out to use between lower lip and gum. It stays in place as a gummy paste for a couple of hours while the b12 enters the system.

Unless it is an old glass jar Jarrow bottle. I tossed them when I found how much they reduced the activity of the ENZY.

First, retitrate with a mix of AdoCbl and MeCbl. If it makes you more comfortable, start with crumbs. You can do a crumb an hour until you feel it turn on. Take the amount of Metafolin with it, actually 1 hour before if possible to aid absorption and/or retention. Once things start up then the folate needs titration until the donut hole insufficiency symptoms diminish. Watch out for the low potassium as that is the more serious thing and should be titrated as soon as the symptoms are apparent. Things can be kept simple. My approach was a b-complex that had moderate amounts of all the various active vitamins before even starting the MeCbl etc so that it wasn't a stop and start guessing game on p5p or pantithine and others. However, SAM-e and TMG I prefer to leave until the base is solidly built unless they are so low as to block startup, which happens 5-10% of the time. Then after partial methylation block is unblocked and methyltrap is untrapped and partial ATP block is at least started on the road to function, then I think it's good to circle around, titrate up on the B12s for better tissue penetration and healing and in the process determine when CNS changes are occurring. There are two types that I have observed, functional mood and personality changes and various changes because of damage. The functional ones start changing as soon as the neurological brightening occurs. As the healing starts and the tissues start functioning from abundance instead of starvation how they function changes. When hundreds of things change all it once it is turmoil. After a month or so it starts to sort out pretty well. If the epithelial healing is going well, most gastro lesions and inflammation will be healing or healed. If you don't have that the missing items need to be looked for. Zinc is often one of them. When zinc is the missing item it's startup can be very intense. It is needed with AdoCbl in dealing with inflammation. I had to titrate zinc, increasing by 12.5mg once a week until I got up to the added 50mg which total 65mg with what I had been getting.

In the body's triage system of distributing nutrients, healing turns on in layers. The puzzle to solve is to turn on each layer of healing and maximize that healing. As the startup intensity fades additional titration can keep it going for a while. When equilibrium is almost reached it's time to start adding in LCF. That can very powerfully start another couple of layers of healing as mitochondria appear to proliferate and new muscle tissue is able to be formed. Also, the mitochondria appear to increase in neurons causing various different moods and personality effects that are transient and may be unpleasant. So far the evidence is that the effects, both euphoria, turmoil and anxiety fade as the changes occur over a number of months.

Until the much larger body responses are suitably dealt with it's very difficult to see the deeper CNS issues and healing. Generally one gets some mood and personality changes as the biochemistry changes. However, the deeper remyelination of damaged areas takes longer and problems can continue to increase even while the shallower layer is healing. That again is a separate titration that can take place once a dose increase makes no body difference.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
sregan
There's a thread about the Jarrow methylcobalamin changing.
http://forums.phoenixrising.me/index.php?threads/jarrow-did-it-change.18154/
I'm taking L-Carnitine Fumarate too. Acetyl L Carnitine makes me wired I think. Maybe because it crosses the blood brain barrier. Other people have had similar experiences with ALCAR. Besides improving mitochondrial function which both Rich and Freddd view as high priority, Carnitine is also useful for dealing with ammonia. Methylation can affect ammonia. This is from dbkita
At the same time too much methylation can over-convert histidine into glutamate stimulating the CNS, can lead to too many sulfites, ammonia, and sulfates (which stimulate fight or flight) if you have CBS pathway defects, or to too much neurotransmitter production especially catecholamines.
Add TMG and DMG?
I found something from Rich about DMG and the transsuluration pathway. It sounds like it could be a good thing or a bad thing.
Adding DMG would have the effect of slowing down the flow through the alternate BHMT pathway that is present in the liver and kidneys. Since you already had plenty of folate and B12 in your cells from your supplementation, the result likely would have been to shift the flow of homocysteine more to the methionine synthase reaction and the transsulfuration pathway. The latter would likely have raised the production of glutathione and would also have improved the function of your body's normal detox system. This would likely have increased the rate at which stored toxins are mobilized into the bloodstream, to be dealt with by the liver and kidneys.

Support the Sulfation pathway at all with P5P?
That would depend on your SNP. I found this from Rich about B6/P5P
Ammonia is produced in the body in three ways that I know of. Normally, the main one is the burning of amino acids for fuel by the mitochondria. When this is done, the nitrogen has to be disposed of, and that is done by carrying it, mostly in glutamine, via the blood to the liver, where the urea cycle converts it into urea. The urea is put back into the blood and is extracted by the kidneys, which excrete it into the urine.

Ammonia can also be produced via the transsulfuration pathway, which is why Dr. Yasko recommends lowering the B6 intake if a person has an upregulated CBS enzyme.

The third way ammonia is produced is by anaerobic bacteria in the gut. If this gets too high, and the liver cannot deal with it, so that the ammonia level rises in the blood, it can cause trouble in the brain, called hepatic encephalopathy.

If the urine tends to be too much on the acid side, because of a person's diet or another cause, the kidneys can produce ammonia from glutamine and put it in the urine to balance the acid. This prevents frying one's nether parts! :)-)

If the bacteria in the gut are producing too much ammonia, they will need to be dealt with. The treatment for high ammonia in the blood coming from the gut includes giving oral levulose. Bacteria in the gut will convert this to lactic acid, pushing the pH in the gut in the acid direction. That will cause ammonia (NH3), which is a gas, to shift more to NH4+, ammonium ion, which will stay in solution and pass out in the stools rather than diffusing from the gut into the bloodstream.

The situation involving B6 is complicated. If a person has a CBS upregulating SNP, it's a good idea not to go too high on B6 until this is dealt with. Later on, it is important to have enough B6 so that the transsulfuration pathway can proceed at a normal rate. Also, B6 is needed to make some of the neurotransmitters, and it's also very important in the metabolism of the amino acids, to name a few. So in the longer term, B6 needs to be brought up, and B2 is needed also, to convert B6 to its active form, P5P.

Best regards,

Rich​
 

sregan

Senior Member
Messages
703
Location
Southeast
Hi Sregan,
The Enzy MeCbl is qualitatively superior. It isn't the dose. The one brand of AdoCbl that is clearly superior is Anabol, which is in an oral capsule and can be pour out to use between lower lip and gum. It stays in place as a gummy paste for a couple of hours while the b12 enters the system.

Cool, I'll look for that one.

Unless it is an old glass jar Jarrow bottle. I tossed them when I found how much they reduced the activity of the ENZY.

Actually it is GLASS and nearly full. I've had it for a while. I also just received a new bottle in the mail which is the PLASTIC one. Will make a nice paperweight :p

First, retitrate with a mix of AdoCbl and MeCbl. If it makes you more comfortable, start with crumbs. You can do a crumb an hour until you feel it turn on. Take the amount of Metafolin with it, actually 1 hour before if possible to aid absorption and/or retention. Once things start up then the folate needs titration until the donut hole insufficiency symptoms diminish.

This is probably my biggest grey area at the moment. I am concerned that too much MFolate can cause problems (http://mthfr.net/methylfolate-side-effects/2012/03/01/). Is it perhaps eating up all the MCbl if taken alone possibly the cause of the issues?
 

sregan

Senior Member
Messages
703
Location
Southeast

Thanks, I just added that link to my bookmark page. Luckily I've got nearly a full bottle of 100 of the OLD Jarrow MCbl.

I'm taking L-Carnitine Fumarate too. Acetyl L Carnitine makes me wired I think. Maybe because it crosses the blood brain barrier. Other people have had similar experiences with ALCAR. Besides improving mitochondrial function which both Rich and Freddd view as high priority, Carnitine is also useful for dealing with ammonia. Methylation can affect ammonia. This is from dbkita
At the same time too much methylation can over-convert histidine into glutamate stimulating the CNS, can lead to too many sulfites, ammonia, and sulfates (which stimulate fight or flight) if you have CBS pathway defects, or to too much neurotransmitter production especially catecholamines.

I don't remember doing to well with regular CL-Carnitine either. Freddd mentioned I should hold off on the LCF until the SMP gets established. I did get my 23andme.com test mailed out this week. I should know some SNP info soon!

I found something from Rich about DMG and the transsuluration pathway. It sounds like it could be a good thing or a bad thing.
Adding DMG would have the effect of slowing down the flow through the alternate BHMT pathway that is present in the liver and kidneys. Since you already had plenty of folate and B12 in your cells from your supplementation, the result likely would have been to shift the flow of homocysteine more to the methionine synthase reaction and the transsulfuration pathway. The latter would likely have raised the production of glutathione and would also have improved the function of your body's normal detox system. This would likely have increased the rate at which stored toxins are mobilized into the bloodstream, to be dealt with by the liver and kidneys.

This TMG/DMG feedback loop might help someone trying to balance BHMT. As soon as they start taking TMG they will produce DMG which should start slowing that reaction down. Taking DMG must be like really putting on the brakes. If someone was trying to keep their DA and NE balanced this might be the trick?
If the bacteria in the gut are producing too much ammonia, they will need to be dealt with. The treatment for high ammonia in the blood coming from the gut includes giving oral levulose. Bacteria in the gut will convert this to lactic acid, pushing the pH in the gut in the acid direction. That will cause ammonia (NH3), which is a gas, to shift more to NH4+, ammonium ion, which will stay in solution and pass out in the stools rather than diffusing from the gut into the bloodstream.

Interesting that you could have a problem with ammonia and/or lactic acid
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Cool, I'll look for that one.



Actually it is GLASS and nearly full. I've had it for a while. I also just received a new bottle in the mail which is the PLASTIC one. Will make a nice paperweight :p



This is probably my biggest grey area at the moment. I am concerned that too much MFolate can cause problems (http://mthfr.net/methylfolate-side-effects/2012/03/01/). Is it perhaps eating up all the MCbl if taken alone possibly the cause of the issues?


Hi Sregan,

Most reactions, perhaps 99 out of 100 are to too LITTLE methylfolate. Most people take so little that when healing turns on and low potassium and low folate hit the healing needs more folate than is available and insufficiency symptoms increase.as folate is diverted to the new healing causing insufficiency symptoms at the epithelial level. If one is taking folic acid and/or folinic acid at the same time as methylfolate, a person can't know the cause of the problems except for low potassium. That's the best reason I can think of for trying an initial trial of only methylfolate and not have to play guessing games.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
I don't remember doing to well with regular CL-Carnitine either. Freddd mentioned I should hold off on the LCF until the SMP gets established. I did get my 23andme.com test mailed out this week. I should know some SNP info soon!
I had to start out with 1/5 a capsule with LCF. After a few months I've increased to 2/3 a capsule a few times a day. I'm not sure if it's helping, but I seem to be tolerating it ok. I mailed my 23andme.com a few days ago too. Based on that information from Rich I posted about B6/P5P causing problems for those with CBS upregulating SNP it seems there's a lot of things we need to be aware regarding which supplements we take for methylation. And also what dbkita said about too much methylation can over-convert histidine into glutamate stimulating the CNS, can lead to too many sulfites, ammonia, and sulfates (which stimulate fight or flight) if you have CBS pathway defects, or to too much neurotransmitter production especially catecholamines.
 

sregan

Senior Member
Messages
703
Location
Southeast
The Enzy MeCbl is qualitatively superior. It isn't the dose. The one brand of AdoCbl that is clearly superior is Anabol, which is in an oral capsule and can be pour out to use between lower lip and gum. It stays in place as a gummy paste for a couple of hours while the b12 enters the system.
Unless it is an old glass jar Jarrow bottle. I tossed them when I found how much they reduced the activity of the ENZY.

http://www.iherb.com/Anabol-Naturals-Dibencoplex-10-000-30-Capsules/9849

Freddd, this is the one? Has boron in it.
 

Lotus97

Senior Member
Messages
2,041
Location
United States
Yes that's the one. The easiest way to take it is if you empty out part of the capsule into a spoon and then use the spoon to place the powder between your lower lip in gum. Since most people can convert adenosylcobalamin into methylcobalamin I assume taking a lot of it might increase methylation. I have no idea if it would be to a significant degree though. If you're taking a high dose of methylcobalamin then you probably wouldn't notice a difference. Your body stores adb12 longer than methylb12 so I don't know how much adb12 we actually need.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City

Hi Sregan,

That is the one. Many people find two quite separate responses, one to MeCbl and one to AdoCbl. For most people the AdoCbl is mild but for a few it is the most intense startup.. The AdoCbl has several known functions now; parking in the mitochondria and participating in the Krebs cycle. Then it is involved in processing fats into the form used for myelin formation. The third is anti-inflammatory but only in levels sufficient for diffusion distribution. AdoCbl is not involved in methylation. As the forms of cobalamin originate with MeCbl and other short term forms are formed from MeCbl, and AdoCbl is a methyl competitor, like HyCbl, methylation is not what is felt with AdoCbl. ATP startup is felt and how much that is felt depends upon how low that was to begin with. In the serum AdoCbl has a similar halflife pattern of MeCbl, starting at a 30 minute halflife or so and by the end of 24 hours about a 12 hour halflife heading for much longer. The AdoCbl has about a 71 day halflife in the mitochondria, perhaps the rate of mitochondria turnover and is the main source of cobalamin entering the blood when a person isn't consuming any.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Freddd
Do you have a ratio for methylcobalamin and adenosylcobalamin, or is adb12 dosage independent of methylcobalamin?

Hi Lotus,

There is no one ratio of AdoCbl to MeCbl that is ideal. It appears to be at least tri-modal. Some people appear to do just great on 3mg/week, single dose or multiple. Then at the other end there are people who need 30-40mg/day injected daily along with about the same of MeCbl thought there is variation there too. Then there are the people who need perhaps 10mg a day in varying proportions to MeCbl. There are beginning to be enough people reporting significant success with higher dose AdoCbl arrived at by titration trials to be forming a pattern. Part of that pattern of finding high dose AdoCbl effective is that the people doing so all appear to have CNS damage of the SACD variety. Some people also had initial aggravated anxiety with AdoCbl/LCF startup and it ended in a couple of months with continued doses as the neurology appears to be healing.

Prior to more data coming in one person had indicated some personality shifting as the injected dose got to the 30mg mark. However that was towards greater irritability. It is the same result as less MeCbl had on him so it may be that the ratio is important at least in some people, because of dilution of MeCbl if no other reason. As 99% of both varieties are excreted in 24 hours, it doesn't appear to be any specific ratio that is preferred. At the low end of minimum effective level, about 100mcg absorbed of the combined AdoCbl-MeCbl, a 1:1 ratio appears to work reliably at getting partial methylation block unblocked, methyltrap gets untrapped and partial ATP block unblocks with other needed cofactors.