How to Titrate to Get Out of Donut Hole Insufficiency

zzz0r

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being scared of all the big doses of folate that some people are mentioning in this thread, I would like to ask a question.
Lets say that someone uses 800mcg of mfolate for start up and then start up indeed happens then when the first set back happends you realise that this person needs to raise the dose of mfolate in order to control the paradoxial defeciency symptoms. However in order to do that he needs to triple the dose and not just go from 800mcg to 1000mcg. Lets say 2400mcg are enough for him to control the symptoms. Is there any person stayed there and that dose was sufficient for him to control the symptoms, or everyone here need to constantly increase their mfolate doses?
 

ahmo

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Hizzz0r. this response from Freddd might be helpful. I'm still in the process of raising my folate, more slowly than was necessary. cheers, ahmo

Increasing MeCbl quantities isn't likely to change the amount of l-methylfolate needed. Adding AdoCbl might increase need somewhat because it opens up other layers of healing. Deplin is Metafolin which is a specific stable form of l-methylfolate You are aiming for the amount that will keep you out of paradoxical folate deficiency/insufficiency. It might be 4mg it might be 30mg. At this point I'm inclined to say that having to go as high as 30 probably indicates a lack of other things. I found that I reached that point fastest by increasing the dose by 50%-100% a day until the symptoms were fully controlled or at least visibly healing, which now goes to my earliest onset symptom, retaining water. After dropping the extra B1, B2 and B3 I appeared to have folate deficiency minimized but after a few months the skin around my fingernails is too ragged. It is appears to be the most mild symptom that takes months to show. So I have increased my dose to 8mg a day, from 4 to try for the next few months and see what heals. Things get slower as you pick off the quick incremental changes.
http://forums.phoenixrising.me/index.php?threads/b-12-the-hidden-story.142/page-145
 

zzz0r

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Thanks Ahmo I have read that post but I could not remember it. Thanks for pointing this out! These doses are scarying me still and I hope when someone manage to find the proper dosage that keeps him out of mfolate defeciency whatever that dosage may be, after an appropriate time of healing he will be able to lower the dosage again..... How much folate are you taking now @ahmo , how old are you and much time are you suffering from cfs?
 

ahmo

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Hi zzz0r. I'm just at 2.3 mg, tomorrow to 2.4 mg. I'm using both Nutricology MTHF, which is a 500 mcg capsule, and Solgar methylfolate, 800 mcg, which I cut into quarters, so I can increase at 200 mcg increments. When I've added 2 of those pieces, ie. 400 mcg, I next switch to an additional Nutricology, so that makes a 100 mcg increase. If you go further back in the thread I linked, I ask Freddd re increasing dosages. I'd been looking all day for the correct way to go about it, so asked about the relationship between B12/folate and their dosages, resulting in the above answer. It's taken me nearly a year to comprehend, and to experience in my body, the way B12 and folate are interacting, the meaning of the shifting symptoms. On another thread I asked for help understanding my recurrent blood blisters in my mouth, a new symptom. Freddd suggested this might be folate, as a presentation of epithelial cells demonstrating deficiency. This finally sunk in, and I committed to raising my dosages, and have been now doing so successfully.

My limited understanding is that for those of us in this poor methylator cohort, we will always need significant doses of all 4 of the Deadlock Quartet supps (MethylB12, AdenoB12, Methylfolate, L-Carnitine Fumarate), as we don't have what it takes to run our methylation cycle otherwise. That doesn't mean we'll need in the 30 mg range, but quite likely several milligrams rather than micrograms.

I'm 64, crashed with ME/CFS June 2003 in the European heat wave. But I had been "chronically fatigued" for some years before that, had suffered a range of inflammatory ailments throughout my life. I now believe folate/B12 deficiency underlies it all. In fact, though I'd noted it a year ago, when I got my 23andme results, my MTRR mutation is directly linked to inadequate methylation, need for B12. cheers, ahmo
 
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@ahmo @Freddd
I seem stuck Always in the donut hole. I have a feeling I can't truly heal this way. I will take 3-4000 Mcg of folate and go into major potassium deficiency (taking Rx 20meq several times daily) - so much I can't up the folate. I feel I'm circling the drain here. Any thoughts on what to do? Thank you!!
 

Freddd

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@ahmo @Freddd
I seem stuck Always in the donut hole. I have a feeling I can't truly heal this way. I will take 3-4000 Mcg of folate and go into major potassium deficiency (taking Rx 20meq several times daily) - so much I can't up the folate. I feel I'm circling the drain here. Any thoughts on what to do? Thank you!!
Let's look at the things that could account for such that I am aware of.

1) folic acid or variations
2) Folinic acid or variations
3) Vegetable extract b-complex or too much folate rich green drinks
4) too much b1 (15mg/day), b2 (10,2mg/day), b3 50mg/day or inositol (unknown). The amounts given are approximate, the exact cause(s) or amount is unknown to me, just that it does.
5) Your assumption that potassium goes up proportionately to folate dose.

I have said previously that amounts greater than 3000-4000 mg/day and you are taking several times that, appears to be caused by something increasing kidney action on the potassium and/or absorption is lousy.

When walking through hell, keep walking. Don't stop and set up housekeeping at what may well be the worst possible place to stop.

Are you taking AdoCbl and L-carnitine (fumarate works for about 90%, ALCAR for about 10% of persons)?

Based on my experience so far, I know of nobody who continued at very high potassium doses after reducing at least all 4 of those items mentioned. I quit inositol entirely. I went to a very low dose b-complex with no folic acid and no CyCbl to get it under control, and then 1/2 tablet twice a day. This would be my most likely guess followed by another item with that same effect possible.

Basically we have multiple compartments for B12 and folate . So, in one of the posts I made on level of methylation, I detailed something like 8 or 9 "triage" levels they called them in some journal articles assuming that this precious resource was applied where it is most critical. So there epithelial tissues, endothelial, various sets of organs, muscles, heart, central nervous system, peripheral nervous system, bone, blood and so on, either start or don't start healing.

How much methylfolate does ones body actually need? 400 or 800 mcg was to avoid inducing B12 deficiency in the brain if somebody takes enough to heal the blood cell size but not enough b12 for the brain causing damage in the CNS, Sub Acute Combined Degeneration. At 400 mcg of methylfolate my potassium need jumped up 1200 mg. I had already started MeCbl, AdoCbl then 400 mcg of l-methylfolate and then LCF. By that time I was up 3000 mg/day and having a tough time keeping it stable. At 4000 mcg methylfolate I ran into the too much b vitamins (B1, B2, B3) and that side tracked me for 6 months. After getting rid of those all that taking more methylfolate did nothing but reduce folate deficiency symptoms.

At 400 mcg I had 30, at 800 I had 30 with about half more intense, at 4000 mcg I had about 30 but less intense except for some that were much more intense. At 8 mg/day, about 15 symptoms remained and reducing in intensity, at 15 mg about 4 symptoms remained at reduced intensity, at 30 mg of l-methylfolate a day there were 1 or 2 barely noticeable folate deficiencies to zero. During a copper deficiency some of the usually folate deficiencies were back. My problem is absorbing copper right now. I can tell by the hours how well my folate is working becasue I can watch my urine, the more B12 that shows up, the less effective my folate is being. I'm taking 30mg MeCbl as 10 mg injected SC a day. My potassium need increased each time I added AdoCbl, and LCF, and by amount of LCF, and copper, and boron and manganese and molybdenum. However, those were down to 100mg increases each, not much. And over the years the amount slowly decreases until something notches up some healing.

If I were in your situation KNOWING everything I now know, I would move up to 4 mg of methylfolate 4 times a day after removing or reducing all of the items I mentioned. You will know in a few days,(you might know in a few hours) move out the area with the worst potassium loss I experienced and the worst intensity of methylfolate deficiency symptoms I experienced in my whole excessive painful slow titration. I would never do it so ,miserably as I did then, now that I know. I was doing it for maximum knowledge, not fastest healing, of course I didn't know that then..

Also how is your digestion? Normal or messed up in a way different than without the potassium?
 
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Let's look at the things that could account for such that I am aware of.

1) folic acid or variations
2) Folinic acid or variations
3) Vegetable extract b-complex or too much folate rich green drinks
4) too much b1 (15mg/day), b2 (10,2mg/day), b3 50mg/day or inositol (unknown). The amounts given are approximate, the exact cause(s) or amount is unknown to me, just that it does.
5) Your assumption that potassium goes up proportionately to folate dose.

I have said previously that amounts greater than 3000-4000 mg/day and you are taking several times that, appears to be caused by something increasing kidney action on the potassium and/or absorption is lousy.

When walking through hell, keep walking. Don't stop and set up housekeeping at what may well be the worst possible place to stop.

Are you taking AdoCbl and L-carnitine (fumarate works for about 90%, ALCAR for about 10% of persons)?

Based on my experience so far, I know of nobody who continued at very high potassium doses after reducing at least all 4 of those items mentioned. I quit inositol entirely. I went to a very low dose b-complex with no folic acid and no CyCbl to get it under control, and then 1/2 tablet twice a day. This would be my most likely guess followed by another item with that same effect possible.

Basically we have multiple compartments for B12 and folate . So, in one of the posts I made on level of methylation, I detailed something like 8 or 9 "triage" levels they called them in some journal articles assuming that this precious resource was applied where it is most critical. So there epithelial tissues, endothelial, various sets of organs, muscles, heart, central nervous system, peripheral nervous system, bone, blood and so on, either start or don't start healing.

How much methylfolate does ones body actually need? 400 or 800 mcg was to avoid inducing B12 deficiency in the brain if somebody takes enough to heal the blood cell size but not enough b12 for the brain causing damage in the CNS, Sub Acute Combined Degeneration. At 400 mcg of methylfolate my potassium need jumped up 1200 mg. I had already started MeCbl, AdoCbl then 400 mcg of l-methylfolate and then LCF. By that time I was up 3000 mg/day and having a tough time keeping it stable. At 4000 mcg methylfolate I ran into the too much b vitamins (B1, B2, B3) and that side tracked me for 6 months. After getting rid of those all that taking more methylfolate did nothing but reduce folate deficiency symptoms.

At 400 mcg I had 30, at 800 I had 30 with about half more intense, at 4000 mcg I had about 30 but less intense except for some that were much more intense. At 8 mg/day, about 15 symptoms remained and reducing in intensity, at 15 mg about 4 symptoms remained at reduced intensity, at 30 mg of l-methylfolate a day there were 1 or 2 barely noticeable folate deficiencies to zero. During a copper deficiency some of the usually folate deficiencies were back. My problem is absorbing copper right now. I can tell by the hours how well my folate is working becasue I can watch my urine, the more B12 that shows up, the less effective my folate is being. I'm taking 30mg MeCbl as 10 mg injected SC a day. My potassium need increased each time I added AdoCbl, and LCF, and by amount of LCF, and copper, and boron and manganese and molybdenum. However, those were down to 100mg increases each, not much. And over the years the amount slowly decreases until something notches up some healing.

If I were in your situation KNOWING everything I now know, I would move up to 4 mg of methylfolate 4 times a day after removing or reducing all of the items I mentioned. You will know in a few days,(you might know in a few hours) move out the area with the worst potassium loss I experienced and the worst intensity of methylfolate deficiency symptoms I experienced in my whole excessive painful slow titration. I would never do it so ,miserably as I did then, now that I know. I was doing it for maximum knowledge, not fastest healing, of course I didn't know that then..

Also how is your digestion? Normal or messed up in a way different than without the potassium?
Thank you so much for your helpful response @Freddd

My digestion and absorption are both awful. I've had reflux for twenty years and multiple food allergies. I'm sure the gut is a disaster. I always have tried to eat healthy and correct it, but it didn't respond to a clean diet (since it was prob vitamin deficiency related).

I have started and stopped b12 protocols many times because I wind up stuck in the potassium issue. I've always thought low potassium was because I had so damage much to heal. I have extreme nerve damage (totally numb thru most of body and spine). I have greatly increased mfolate before to 5-8mg being the most at one time, and my body feels overwhelmed like it just can't handle it(maybe not enough b12?) I weigh approx 110.

I am currently taking mb12 and methylfolate along with cofactors. I've added l carnitine fumarate and adeno here and there. I was hoping that by not taking them so much I'd lower potassium need since they all heal various things. I've been taking the other basic vitamins and a basic b complex. I eat some veggies for potassium (potatoes, bananas and tomatoes). Maybe that's not the best way to get it? I just feel I'm overdoing the RX kind. I also use coconut water.

I also don't retain the mb12 and methylfolate I take for very long. I feel the need to take again every few hours if not sooner. I worry about sleeping and not taking it then. I have the sensation of tissues like shoulders and gut coming apart if not taking folate often. It's very scary.

I will try upping folate again and see if potassium improves. I wish I could feel overall improvement and know I was doing something right. If I'm taking 4mg mfolate should I also be taking same amount b12 absorbed? Thx!
 

Freddd

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Hi Nikki,

Nobody retains these things long. If you got an injection for instance and it all absorbed in an instant, just as an illustration, 75% or so would be excreted in your urine. Fortunately 10 MCG of MeCbl is about all that can possibly be used in a day. One of the things about holding the sublingual for an hour or two is that it gives you a long relatively high serum level and enough absorbtion that the MeCbl is distributed throughout the body. A study a few years ago calculated that an oral dose of 125 mcg (absorbs about 10-11 mcg average) and is enough for the transcobalamin 2 is saturated becoming holotranscobalamin 2. With the 1000mcg sublingual, beyond that you get perhaps 100-200 mcg absorption and that is distributed throughout the body very quickly (except cerebral spinal fluid, and that is a different story) and reaches about 80% (my best estimate). of potential healing rate at the same time. My body would likely do fine on a 1000 mcg dose, but for some reason some people have a problem getting B12 into the brain or some lose it fast, or both. An injection of 10mg SC for me allows about 8-10 hours of CNS improvement. The body dose of 1000 mcg sublingual keeps things going for at least 24 hours and keeps deficiency symptoms from returning sooner than 3 days after the previous dose.

Methylfolate has a halflife of maybe 3 or 4 hours it appears. Depending upon how my body is working on a specific day I find that 15mg 2 to 4 times a day works well, and I can see the difference. When the methylation is working well, I don't see any MeCbl in my urine. When methylation isn't working well I see proportionately more b12. It appears that the folate can double or more the period of the serum half life of circulating MeCbl or circulating AdoCbl. Also, the folate symptoms are fast actors so that you can see the effects rapidly. I have angular cheilits at the corners of my mouth. The crack starts forming and burning feeling in 24-36 hours after going deficienct in the epithelial compartment. Also when very deficient the finger tips peel and crack deeper. The thumbs especially can have the cracks at the corner of the nails. A week ago I was working with cherries. They stained the cracks to be, DAY 2 of MeCbl deficiency. They were not cracks yet but the skin in the v-shaped crack to be was already dead and stained with cherry juice. I had started seeing b12 in my urine the day before, day 1 of deficiency, and having already been on 30mg, went to 60mg.. On day 3 the dead skin started coming of. Day 4 there was a 3mm wide crack and 3mm deep. On day 5 the crack was half as wide and half as deep. On day 6 the crack was all but filled with pink new skin and day 7 very faint remains can be seen if one knows what to look for, The angular cheilitis and finger cracks and peeling heal at the same rate. The burning feeling at the bottoms of the cracks starts within a day and stops a few hours after a large enough methylfolate dose. The only size I bother with these days 15mg. I keep the 800 mcg tablets around when I need them for other people and my cat; she gets only a tiny pinch of ground up pill. She gets 2 injections a week (300mcg). She had an inflammatory digestive disease and was losing weight and vomiting and really miserable. Since the vet suggested the MeCbl, it helped a little, but the folate. WOW She has gained perhaps 4 pounds and has gone in weeks from a young small cat to a noticeably larger more solid cat without a sore tummy and food intolerances requiring a "single protein" cast food at high price and she hates it.

It is obvious for me that many things can heal. What takes so long is when normal healing and replacement doesn't take place at the needed speed and that goes on continuously. I had missed out on decades of normal healing with degeneration for years. I lost 50 pounds of muscle atrophy from lack of b12 and folate. If you get.canker sores, burning tongue, mouth, sores down the throat, IBS, also acne type lesions, all sorts of rashes and so on. Hundreds of those can heal in a week or two of enough folate, and they will stay gone with enough methylfolate. I had them come and go learning this lesson hundreds of times before I got it. WHen you get rid of the IBS you will likely absorb much better. My partner had a real stomach pain, bleeding, and other problems. Without having all the external problems like me, without any extra potassium needed, she started on 4mg of methylfolate, and it helped a little but it came and went. at 15mg methylfolate it doesn't come back, and with a single 10mg injection a day of MeCbl because of neurological damage from neck injury and fusion. The doctor no longer wants an endoscopy done.

http://www.methylpro.com/ various sizes, ie 90 caps, 15mg $75.00 - works same for me. I do find that changing brand even for a day each few months makes a difference. That was one of the factors I was exploring.

On the LCF (AdoCbl really makes no difference, either you have enough or you don't) it is the one thing that you really can titrate. I started at 64 mg a day, and then 128, 256 and then 500mg a day. Starting at 500 was way too muchjfor me. If you stop and go it STOPS cell formation. Making this stop and go increases damage and reduceses healing,. It works best to get it going and keep it going. One of the things that happens is that it allows things to really heal. With the AdoCbl/LCF it promotes more mitochondria being made to restore exercise tolerance. LCF promotes neuroblasts, osteoblasts, helped heal my muscles and heart. It also helped repair my liver along with the methylfolate and losing 85 pounds of water from my abdomen.

Stop and start makes the swings crazy. It's best to get it stable. And everything smooths out. If one doesn't get enough methylfolate, it comes and goes and never quite heals.

I have another "slow clock" also that backs up my visual B12 in urine method. My MCV responds to haw many days a month I have effective methylation. Most of my life and with folic acid, my MCV was 99.8 or more. At 8mg a day my MCV went down to 98.?. At 15mg it went down to 95-97.? At 30mg it's down around 93-94.? When things get worse, symptoms wise, the MCV goes up. I can count the number of day of skin worsening or improving. and it matches with up or down on the MCV.

I take a 15mg at bedtime and again when I get up and 2 other times. If you feel the MeCbl wearing off, take one in the evening too. None of these EXCEPT LCF has a near linear response. I already described the response curve of methylfolate, MeCbl varies something like this, @ 10 mcg absorbed, 1% effective. 100mcg absorbed, 80% effective, 1000mcg absorbed 95% effective, 10,000 mcg absorbed, 99+%.effective. This again is my best approximation. I hope this clarifies things. If you are taking too much b1, b2, b3 and inositol, that will help right away.

Part of the problem with potassium is that if you take too much it cause irritation that reduces absorption. Too much at once makes more loss in the urine. I find taking potassium gluconate in water more effective, sipping it all day than taking huge doses by pills. Time release PILLS are dangerous. High dispersion multi time pill capsules are better and less damaging. Drinking low concentration water for all your water helps. The potassium in water can be absorbed in 15 minutes or a little more. Food potassium serum peaks 14 hours after consumption.
 
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Hi Nikki,

Nobody retains these things long. If you got an injection for instance and it all absorbed in an instant, just as an illustration, 75% or so would be excreted in your urine. Fortunately 10 MCG of MeCbl is about all that can possibly be used in a day. One of the things about holding the sublingual for an hour or two is that it gives you a long relatively high serum level and enough absorbtion that the MeCbl is distributed throughout the body. A study a few years ago calculated that an oral dose of 125 mcg (absorbs about 10-11 mcg average) and is enough for the transcobalamin 2 is saturated becoming holotranscobalamin 2. With the 1000mcg sublingual, beyond that you get perhaps 100-200 mcg absorption and that is distributed throughout the body very quickly (except cerebral spinal fluid, and that is a different story) and reaches about 80% (my best estimate). of potential healing rate at the same time. My body would likely do fine on a 1000 mcg dose, but for some reason some people have a problem getting B12 into the brain or some lose it fast, or both. An injection of 10mg SC for me allows about 8-10 hours of CNS improvement. The body dose of 1000 mcg sublingual keeps things going for at least 24 hours and keeps deficiency symptoms from returning sooner than 3 days after the previous dose.

Methylfolate has a halflife of maybe 3 or 4 hours it appears. Depending upon how my body is working on a specific day I find that 15mg 2 to 4 times a day works well, and I can see the difference. When the methylation is working well, I don't see any MeCbl in my urine. When methylation isn't working well I see proportionately more b12. It appears that the folate can double or more the period of the serum half life of circulating MeCbl or circulating AdoCbl. Also, the folate symptoms are fast actors so that you can see the effects rapidly. I have angular cheilits at the corners of my mouth. The crack starts forming and burning feeling in 24-36 hours after going deficienct in the epithelial compartment. Also when very deficient the finger tips peel and crack deeper. The thumbs especially can have the cracks at the corner of the nails. A week ago I was working with cherries. They stained the cracks to be, DAY 2 of MeCbl deficiency. They were not cracks yet but the skin in the v-shaped crack to be was already dead and stained with cherry juice. I had started seeing b12 in my urine the day before, day 1 of deficiency, and having already been on 30mg, went to 60mg.. On day 3 the dead skin started coming of. Day 4 there was a 3mm wide crack and 3mm deep. On day 5 the crack was half as wide and half as deep. On day 6 the crack was all but filled with pink new skin and day 7 very faint remains can be seen if one knows what to look for, The angular cheilitis and finger cracks and peeling heal at the same rate. The burning feeling at the bottoms of the cracks starts within a day and stops a few hours after a large enough methylfolate dose. The only size I bother with these days 15mg. I keep the 800 mcg tablets around when I need them for other people and my cat; she gets only a tiny pinch of ground up pill. She gets 2 injections a week (300mcg). She had an inflammatory digestive disease and was losing weight and vomiting and really miserable. Since the vet suggested the MeCbl, it helped a little, but the folate. WOW She has gained perhaps 4 pounds and has gone in weeks from a young small cat to a noticeably larger more solid cat without a sore tummy and food intolerances requiring a "single protein" cast food at high price and she hates it.

It is obvious for me that many things can heal. What takes so long is when normal healing and replacement doesn't take place at the needed speed and that goes on continuously. I had missed out on decades of normal healing with degeneration for years. I lost 50 pounds of muscle atrophy from lack of b12 and folate. If you get.canker sores, burning tongue, mouth, sores down the throat, IBS, also acne type lesions, all sorts of rashes and so on. Hundreds of those can heal in a week or two of enough folate, and they will stay gone with enough methylfolate. I had them come and go learning this lesson hundreds of times before I got it. WHen you get rid of the IBS you will likely absorb much better. My partner had a real stomach pain, bleeding, and other problems. Without having all the external problems like me, without any extra potassium needed, she started on 4mg of methylfolate, and it helped a little but it came and went. at 15mg methylfolate it doesn't come back, and with a single 10mg injection a day of MeCbl because of neurological damage from neck injury and fusion. The doctor no longer wants an endoscopy done.

http://www.methylpro.com/ various sizes, ie 90 caps, 15mg $75.00 - works same for me. I do find that changing brand even for a day each few months makes a difference. That was one of the factors I was exploring.

On the LCF (AdoCbl really makes no difference, either you have enough or you don't) it is the one thing that you really can titrate. I started at 64 mg a day, and then 128, 256 and then 500mg a day. Starting at 500 was way too muchjfor me. If you stop and go it STOPS cell formation. Making this stop and go increases damage and reduceses healing,. It works best to get it going and keep it going. One of the things that happens is that it allows things to really heal. With the AdoCbl/LCF it promotes more mitochondria being made to restore exercise tolerance. LCF promotes neuroblasts, osteoblasts, helped heal my muscles and heart. It also helped repair my liver along with the methylfolate and losing 85 pounds of water from my abdomen.

Stop and start makes the swings crazy. It's best to get it stable. And everything smooths out. If one doesn't get enough methylfolate, it comes and goes and never quite heals.

I have another "slow clock" also that backs up my visual B12 in urine method. My MCV responds to haw many days a month I have effective methylation. Most of my life and with folic acid, my MCV was 99.8 or more. At 8mg a day my MCV went down to 98.?. At 15mg it went down to 95-97.? At 30mg it's down around 93-94.? When things get worse, symptoms wise, the MCV goes up. I can count the number of day of skin worsening or improving. and it matches with up or down on the MCV.

I take a 15mg at bedtime and again when I get up and 2 other times. If you feel the MeCbl wearing off, take one in the evening too. None of these EXCEPT LCF has a near linear response. I already described the response curve of methylfolate, MeCbl varies something like this, @ 10 mcg absorbed, 1% effective. 100mcg absorbed, 80% effective, 1000mcg absorbed 95% effective, 10,000 mcg absorbed, 99+%.effective. This again is my best approximation. I hope this clarifies things. If you are taking too much b1, b2, b3 and inositol, that will help right away.

Part of the problem with potassium is that if you take too much it cause irritation that reduces absorption. Too much at once makes more loss in the urine. I find taking potassium gluconate in water more effective, sipping it all day than taking huge doses by pills. Time release PILLS are dangerous. High dispersion multi time pill capsules are better and less damaging. Drinking low concentration water for all your water helps. The potassium in water can be absorbed in 15 minutes or a little more. Food potassium serum peaks 14 hours after consumption.
Thanks so much for sharing and being detailed for better understanding on my part. I think I may be way too low right now on my methylfolate and mb12. I'm going to try and up, hoping for further healing. I appreciate your kindness and the info. I'll keep trying. :)
 

Eastman

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@Nikki7

Have you ruled out B1 deficiency? Your symptoms seem to better match some of those listed for B1 deficiency according to Vitamin Mineral Information.

A deficiency may result in muscle weakness, fatigue, muscle cramps, and stiffness.

Vitamin B1 deficiency can result in digestive problems including a loss of appetite, nausea, digestive discomfort, constipation, weight loss, and incorrect production of hydrochloric acid.

A thiamin deficiency can negatively affect the nervous system resulting in tingling, numbness, irritability, poor memory retention, and depression. A severe deficiency can result nerve damage and potentially lead to psychosis.

A vitamin B1 deficiency can also negatively affect heart function and cause the heart muscles to weaken.
 
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@Nikki7

Have you ruled out B1 deficiency? Your symptoms seem to better match some of those listed for B1 deficiency according to Vitamin Mineral Information.
Thanks for bringing this to my attention..I started some B1 this morning and felt immediately better, though that wore off in a few hours. I am curious. Is this caused because of taking the basic methylation supplements? Am I depleting anything else by taking extra B1? Thanks! You truly helped me. @Eastman
@Nikki7

Have you ruled out B1 deficiency? Your symptoms seem to better match some of those listed for B1 deficiency according to Vitamin Mineral Information.
 

Eastman

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Thanks for bringing this to my attention..I started some B1 this morning and felt immediately better, though that wore off in a few hours. I am curious. Is this caused because of taking the basic methylation supplements? Am I depleting anything else by taking extra B1? Thanks! You truly helped me. @Eastman
My observations suggest that methylation protocol causes B1 to be depleted. B12, folate and B6 supplementation has been associated with kidney problems and an increase in vascular events. B1 helps with these.

B1 works with magnesium, so you want to make sure that you have enough of that.

Freddd says that B1 aggravates potassium deficiency, so you want potassium too.

Mary has reported phosporus deficiency symptoms after B1 supplementation. Phosphorus is found in lecithin, which is often recommended with the methylation protocol, and can also be found in milk and sunflower seeds.
 
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aaron_c

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Hey Yall,

So I recently changed up supplements a bit including adding back magnesium after spending maybe a year off of it. Over the past week or three a muscle on one side of my tailbone has gotten quite tense and painful. I noticed that pain in that area is mentioned as a symptom of "donut hole folate deficiency" so among the things I've tried to get rid of the pain has been methylfolate.

And it has worked--sort of. It reduces the pain for about half an hour, and then it starts coming back, so I have to take more. And the amount I've needed has just grown and grown. Yesterday (day two of the experiment) I took almost 90 mg of methylfolate. At some point it seems I shouldn't take any more because I start getting a painful zapping sensation above my left eye. So I suspect that 90 mg will be more-or-less my limit. But even with that ridiculous amount that I'm taking, I'm often in pain and in fact I woke up twice in the night from the pain and had to take more methylfolate before I could sleep again.

I also take L-carnitine, 9 mg of adenosycobalamin, 1 mg of methylcobalamin and some potassium. In fact the first thing I tried to fix this was potassium, but it seems that THIS tight muscle doesn't respond to that (plus the extra potassium gave me insomnia).

I'm wondering if there's anything I'm missing. Should I be increasing my methylcobalamin dosage as well as methylfolate? Can I expect this to clear up in a few days? Any other words of advice?
 

Victronix

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"My observations suggest that methylation protocol causes B1 to be depleted. B12, folate and B6 supplementation has been associated with kidney problems and an increase in vascular events."

Parts of that 2010 study are refuted in later studies looking more closely at subgroups and relevant details, which can really muddy the outcomes of large clinical trials. A 2011 commentary referencing that study points out a number of these key details which make or break large studies of vitamins, especially Bs, which will vary depending on the type of vitamin, the age of the subjects, the status of their levels before the start of the study, etc. --

"The question of whether B vitamin therapy to lower homocysteine levels may reduce the risk of stroke is becoming more complicated, and analyses that depended on grouping all patients together may have obscured important differences among patient (and perhaps population) subgroups. For instance, the main results of the Vitamin Intervention for Stroke Prevention (VISP) trial3 showed no effect of B vitamins (folic acid/pyridoxine/cyanocobalamin) on the risk of recurrent stroke, death, or myocardial infarction, whereas a subgroup analysis4 of the VISP trial showed benefit of B vitamins in a defined subset of the population.

More recently, House et al5 reported that B vitamin therapy was shown to increase cardiovascular risk in patients with diabetic nephropathy. Hence, subgroup analyses have shown beneficial as well as adverse effects of B vitamin therapy.

The VISP subgroup analysis4 excluded patients with B12 deficiency (because they were all receiving injections of cyanocobalamin, regardless of the treatment to which they were randomized), and patients with significant renal impairment (because it was thought they would not respond to vitamin therapy). There was a significant reduction of stroke or myocardial infarction with B vitamins in the remaining participants, and this finding was more pronounced when patients were stratified by baseline serum B12 level.

The difference between patients who entered the study with a serum B12 level above the median (ie, they could absorb B12 reasonably well) and received high-dose vitamins and those who entered the study with a serum B12 level below the median and received low-dose vitamins was a 34% reduction of stroke, death, or myocardial infarction (P=.02).

At the time, it seemed that the findings were explained mainly by exclusion of patients receiving vitamin B12 injections, and this seemed supported by the finding in the Heart Outcomes Prevention Evaluation 2 (HOPE-2) trial (the only large trial to use an adequate dose of B12 for elderly patients) that B vitamins significantly reduced the risk of stroke. In 2011, Hsu et al6 reported that in the VISP trial, a subgroup of patients with the GG phenotype of transcobalamin 2, a transport protein for vitamin B12, were responsive to high-dose vitamin therapy. Vitamin B12 may thus have a key role in stroke prevention interventions involving vitamin therapy used to lower homocysteine levels."


I find that it's best to use the most recent research that summarizes conflicts in past studies.
 

Eastman

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I find that it's best to use the most recent research that summarizes conflicts in past studies.
In general, I agree with this, notwithstanding the fact that some of the studies cited in the 2011 commentary quoted are older than the 2010 study cited in my previous post.

However, the point of my previous post was to help the other member with her problem by suggesting that an increased need for B1 is a possibility. The increased B1 requirement hypothesis was initially derived after several members on the forum reported problems after undergoing methylation treatment, problems that were apparently resolved with B1 supplementation. There is, as far as I know, no formal study directly supporting this hypothesis. The 2010 study finding - which is not wrong as a whole - was cited as support for this hypothesis but obviously does not prove it.

I would add that, in my opinion, the findings in the 2011 commentary are not incompatible with the increased B1 requirement hypothesis. According to the commentary, nephropathy appears to be a factor in the effect of B vitamins, and there is some evidence that B1 is a factor in nephropathy. However, the 2010 study specifically found greater decrease in GFR, which suggests that the other B vitamins are detrimental.

I'm wondering if there's anything I'm missing. Should I be increasing my methylcobalamin dosage as well as methylfolate? Can I expect this to clear up in a few days? Any other words of advice?
90 mg of methylfolate is huge. Personally, I would try something else before trying to increase methylfolate further. What to try would probably depend on other symptoms you may have.
 

Victronix

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Yes, the potential B1 benefit is a separate issue - glad you are bringing it up. In my post I was addressing only the idea that B12 and B6 are associated with kidney and vascular issues.

A key part of understanding VITAMIN research studies is making sure the details and the methodology are strong. Why? Because many many mainstream MDs and PhDs haven't really known much about the nuances of the different ways that different types of the same vitamin can behave, like taking only one type of Vitamin E versus mixed tocopherols, or taking cyanocobolamin versus methyl.

Here is the section of the commentary that discusses the 2010 House et al study -

"The finding that B vitamin therapy was associated with increased cardiovascular risk in patients with diabetic nephropathy, and that the increased risk of events was confined to those with a low glomerular filtration rate (less than 50), sheds further light on the VISP subgroup analysis. It seems that benefit or harm from vitamin therapy used to lower homocysteine levels depends not only on adequate dosing and absorption of vitamin B12 but also on renal function.

Several biological effects may help to explain the harmful effect of B vitamins in patients with impaired renal function. High levels of folic acid not metabolized to tetrahydrofolate could increase levels of asymmetric dimethylarginine, an antagonist of nitric oxide. In addition, patients with renal failure who are given cyanocobalamin accumulate cyanide, and cyanide, excreted as thiocyanate, has a central role in the catabolism of hydrogen sulphide, an endothelium-derived relaxing factor analogous to nitric oxide. Among patients with renal failure who were given methylcobalamin rather than cyanocobalamin, levels of both plasma total homocysteine and asymmetric dimethylarginine were lowered. Folate status, B12 status, and renal function are all crucial to interpretation of results of clinical trials of vitamin therapy used to lower homocysteine levels.

The clinical implications of these issues are that metabolic B12 deficiency needs to be better detected and treated, and in patients with renal failure it would be advisable to substitute methylcobalamin for cyanocobalamin. For patients undergoing dialysis, more intensive dialysis and use of thiols such as mesna may represent other potential options."

Using a synthetic form of a vitamin, like folic acid, or cyanocobalamin, neither of which occur in nature, is not a good way to look at the role the vitamin actually plays in health - now that we have the ability to analyze genes we can see what happens to those people whose genes won't let them process synthetic forms of vitamins.
 

Eastman

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Yes, the potential B1 benefit is a separate issue - glad you are bringing it up. In my post I was addressing only the idea that B12 and B6 are associated with kidney and vascular issues.
Just to be clear, my hypothesis is that methylation treatment increased the need for B1, so I don't consider the latter a separate issue.

The hypothesis is unproven, of course. B1 could be helping in those reports by members just as a workaround rather than an actual increased need.
 

Busson

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Just to be clear, my hypothesis is that methylation treatment increased the need for B1, so I don't consider the latter a separate issue.

The hypothesis is unproven, of course. B1 could be helping in those reports by members just as a workaround rather than an actual increased need.
@Eastman I would like to know more about the role of B1 with respect to methylation and B12 deficiency. I find B1 (25mg of thiamine hydrochloride) sometimes helps me when I feel have a bout of feeling physically stressed and have a labored breathing, although it does not always work.

I have B12/folate problems which may be causing the intial symptoms that B1 eases. I have never worked out what B1 is doing inside me nor have I worked out the exact circumstances when it works and when it doesn't. However I had had some impressive responses to a rescue dose of B1 after trying everythnig else I can lay my hands on.
 

Eastman

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@Eastman I would like to know more about the role of B1 with respect to methylation and B12 deficiency.
My hypothesis that methylation treatment increases the need for B1 is based on empirical observation of responses from members on this forum. However, I never found a theoretical basis for this increased need.

I think it is possible that in those cases where B1 helped, it is as a substitute for something else that is affected by methylation. Lithium comes to mind here, since it may have a role in B12 binding proteins (see here and here) and thus get depleted in methylation treatment, and both lithium and at least some forms of B1 are GSK-3 inhibitors (see here and here).
 

Busson

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My hypothesis that methylation treatment increases the need for B1 is based on empirical observation of responses from members on this forum. However, I never found a theoretical basis for this increased need.

I think it is possible that in those cases where B1 helped, it is as a substitute for something else that is affected by methylation. Lithium comes to mind here, since it may have a role in B12 binding proteins (see here and here) and thus get depleted in methylation treatment, and both lithium and at least some forms of B1 are GSK-3 inhibitors (see here and here).
@Eastman Thanks for the links. Those are to improvements in cognitive or mental states but I feel thiamine is doing far more than that. I half-wondered if cells get so disordered that lactic acid builds up because I recall thiamine being very useful for that.

Your links also mention lithum. I read Yasko advocate taking lithum for B12 problems. I ordered lithium orotate but then discovered I couldn't find anything to support the use of lithium for B12 and have never got round to trying it.