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Simpliefied and Active Protocols, Paradoxical Folate Deficiency, Metafolin and Balanc

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Kicked off by this post by Drex on top of all the questions of late about mb12-Metafolin-adb12 balance and some individuals swtiching from SMP to ABP many questions have been brought up.



Hi Freddd,

I seem to be the paradox to the paradox. My timeline for the last two weeks or so goes like this. I was taking Hb12 and methylmateB, from which I have had pretty good results, and ran out, so I decided to take the Jarrow mb12 and Solgar Metafolin I had on hand. Within in 4 days I felt awful. I know this could be potassium, but i was taking potassium. I developed bad ibs symptoms (as I have everytime I have tried to take Mb12 and Solgar Metafolin, which leads me to suspect it may be the sugar alcohols used to sweeten both. I have had issues with sorbitol in the past) I also developed cheilitis at the left corner of my mouth, as well as muscle pain. After stopping both, and going back to hb12 and methylmate and folinic, the cheilitis went away, the other stuff is going away, and 4 days after adding the folinic, my nose peeled. I have ordered a methylfolate w/ no sweeteners to see if it makes a difference.


Hi Drex,

I seem to be the paradox to the paradox.

Actually, your description has brought to the forefront something that has been chasing around in my brain for a while, the nature of the induced folate deficiency by mb12. This has to do with the question of the amount.

Play along and picture the situation. This might have everything to do the limited conversion of folic acid or folinic acid to methylfolate. Let' say that person AAA can convert 200mcg a day of non-active folic or folinic to methylfolate. With 10mcg of mb12 available via conversion from hycbl, methylation goes along, semi broken (partially blocked) and some things are handled via internal triage. A few cells get started with the limited mb12 and there is enough folate for those limited cells, and those things keep puttering along, unlike those people like me who have less internal folate conversion and have continual IBS, cheilitis and other problems. Then Mb12 is taken and some methylfolate. A gazllion cells all get started and need even larger quantities of methylfolate so that the amount of methylfolate that could get it started isn't enough to maintain that activity, leaving cells broken off part way through and the damage shows up, the peeling skin, the cheilitis, the IBS.

This begins to make sense of the ragged area beteen the two different methods.

This also expands the definition of Paradoxical Folate Deficiency to include an induced methylfolate deficiency by mb12 and low dose methylfolate. No wonder the prescription forms of Metafolin have such higher doses. It makes sense. So with Metanx we have maybe 25mcg of absorbed mb12 to 5mg of metafolin. Cerefolin is similar. Deplin comes in 7.5 and 15mg doses.


With the active b12 protocol there was a jumping in with both feet, methylation started in a day and low potassium in 3 days. The startup was intense but the problems were generally limited to low potassium and a lot of intensity with symptoms shifting around. They did not follow the expereince or logic of the SMP startup.

With the Simplified methylation protocol, there were a multitude of various problems that from somebody coming to it from the active b12 protocol experience seemed "weird". There were not simply a "light" version of active b12 startup, they were very different. The differences are visible to the naked eye. They didn't follow the same experience or logic of the ABP startup.


I have repeated over and over that the experience of each the SMP and ABP did not predict the other response. I think that anybody that looked at both would agree with that. There were two distinctively different things going on.

Needless to say, applying the methods of the SMP to the ABP exposed an entirely different set of problems that neither was adequate preparation for the hybrid approach.

What now that has been exposed is this triggering of methyaltion startup with ABP, not slow, more a binary ON/OFF effect which I mentioned before. When it STARTS, and it dosesn't start slowly, it needs enough methylfolate and everything else required for it to run through the initial startup without stopping in it's midst, stalled for lack of something, right in the middle of total unbalance.

This brought up the question that has been asked by many, what is the correct BALANCE amongst the components, and I haven't had an answer. I can see now where the problems are cropping up, epitomized by Drex in this post, and many thanks to Drex for being able to state it so clearly. No blatent PFD while on hycbl and folinic, some kind of balance there. In some people though PFD starts anyway. Then starting mb12 with a relatviely small amount of Metafolin, and running into PFD. It would appear an induced deficiency in this as the need created by the mb12 outruns the folate available, an out of balance situation.

Further, previously I and other have noticed the increased problems in switching from SMP to ABP and that it is not straight forward, at least not the way people are trying it.
 

drex13

Senior Member
Messages
186
Location
Columbus, Ohio
Hi Freddd,


With the active b12 protocol there was a jumping in with both feet, methylation started in a day and low potassium in 3 days. The startup was intense but the problems were generally limited to low potassium and a lot of intensity with symptoms shifting around. They did not follow the expereince or logic of the SMP startup.

With the Simplified methylation protocol, there were a multitude of various problems that from somebody coming to it from the active b12 protocol experience seemed "weird". There were not simply a "light" version of active b12 startup, they were very different. The differences are visible to the naked eye. They didn't follow the same experience or logic of the ABP startup.


I would agree with this. I experienced "start up" effects with both protocols, but they were distinct and different. With the SMP, I experienced asthma type symptoms with start up, which eventually settled down and an increase in energy and stamina over time, but I still felt like there was something missing. Like I was almost there, but not quite. With the active protocol, I have attempted it 3 different times now, with the same result by the 4th day, with increases in ibs, fatigue, muscle pain, malaise. Again, I could feel the start up, but then I could also feel the wall in a big way on day 4. I am not as debilitated as some here on PR. I work full time. But, the 4th day takes me from upright to near fetal position. Distinct and different. Maybe, it is a sudden decrease in methylfolate, I don't know. If so then this brings me back to my question from the other day. If a large dose of Methylfolate is going to be required, might it be worth trying the methylfolate product from Metabolic Maintenance, since it provides 10mg per capsule ? This may be cheaper (and easier) than taking alot of Solgar tablets,or getting a prescription for Deplin. Granted, the L-methylfolate in it is not Metafolin, but it may be worth a trial.
 

Pea

Senior Member
Messages
124
So for a person without Paradoxical Folate Deficiency (assuming for now), is it more dangerous having too much metafolin than not enough, or vice versa?

My friend had been on the MethylB but with a ton of Folic Acid and lots of slow improvement in various symptoms (except for the 2 main symptoms) but no bad start-up or detox effects. Today going to have him start the Jarrow MB 5mg and a Metafolin. Just one Metafolin in the morning, or should he take another one in the evening? Yasko seems to think too much metafolin is dangerous, what is her theory?

I'll post how it goes.
 

adreno

PR activist
Messages
4,841
Most multivitamins contain higher levels of folate, compared to b12, usually at least a 2:1 ratio.

I'm taking 5mg mb12, 2.5mg adb12 and 1mg mf. I've been on the protocol for a month, taking all cofactors, no folic or folinic, but I still can't seem to shake the startup symptoms. I'm also more exercise intolerant than before.
 

maddietod

Senior Member
Messages
2,859
I got a very positive physical response to the SMP for the first few weeks. I was suddenly able to garden, and was on my bed less during the day. Over time I lost some of that gain, but not all. All of my other symptoms fluctuated, and eventually went back to baseline. I was on that protocol for 9 months.

I started adrenal support a few months ago, and my physical stamina has improved. It hasn't particularly helped cognitive issues.

I decided a month ago to test myself for paradoxical folate deficiency. Because this required I stop the multivitamin and folic acid from the SMP, I shifted to all of Freddd's supplements except for the B12s - I decided to see what would happen if I stuck with the hydroxy. It seemed possible that the intensity of start-up is related to the power of the active B12s, and I'm too brain dead to feel safe playing with that.

Stopping all sources of folates worked like a charm for me. I feel much better in all areas when I eat nothing but meat/fish/dairy/eggs. [As I was already eating low-carb and grain-free, this is not a carbohydrate or gluten issue.]

I'm trying to figure out how much metafolin I need, on what kind of schedule, to be able to eat some fruit/vegetable/nuts/grains. This is very hard for me to figure out, which implies that I'm extremely sensitive to folates. I'm holding open the possibility that this level of sensitivity is temporary, while my body re-sets.

I had minor, temporary start-up problems (crazy sleep 2 nights, muscle cramps, nausea, headache). I added potassium immediately, and quickly settled on 5 caps 3x a day.

I'm very interested in the discussion of balance: how much metafolin just for basic use, plus how much more to overcome my problems when I eat folate, plus how much potassium, all related to the amount of B12s.
 

Dreambirdie

work in progress
Messages
5,569
Location
N. California
I'm trying to figure out how much metafolin I need, on what kind of schedule, to be able to eat some fruit/vegetable/nuts/grains. This is very hard for me to figure out, which implies that I'm extremely sensitive to folates. I'm holding open the possibility that this level of sensitivity is temporary, while my body re-sets.

I had minor, temporary start-up problems (crazy sleep 2 nights, muscle cramps, nausea, headache). I added potassium immediately, and quickly settled on 5 caps 3x a day.

I'm very interested in the discussion of balance: how much metafolin just for basic use, plus how much more to overcome my problems when I eat folate, plus how much potassium, all related to the amount of B12s.

I am eager to hear what you figure out about this, Madie.

How big of a dose of potassium are you taking? And what brand?
 

maddietod

Senior Member
Messages
2,859
All the potassium I've seen on shelves is 99mg per capsule. I bought Twinlabs first, and then found a huge cheap bottle at Sam's Club, so I also use that. I take 15 caps per day, divided into 3 doses. When I forget a dose, I get a headache and neck cramps.

I'm also eager to see what I discover! Things fluctuate pretty wildly at this point, and there are a lot of variables to sort through...........because of course my energy is also affected by how much I'm doing, if I'm getting sick, if I'm reacting to some other supplement than the ones I think I'm testing......etc.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Most multivitamins contain higher levels of folate, compared to b12, usually at least a 2:1 ratio.

I'm taking 5mg mb12, 2.5mg adb12 and 1mg mf. I've been on the protocol for a month, taking all cofactors, no folic or folinic, but I still can't seem to shake the startup symptoms. I'm also more exercise intolerant than before.

Hi Adreno,

I suspect more Metafolin might turn the trick. You have enough mb12 going for you right now and ample adb12. The thing on the low side is metafolin. One way to test it is a larger dose for a day and see if it helps. Metafolin doesn't usually make a huge difference espeically when coming up from underneath. The effect then is one of releife usually. Titrate the Metafolin to comfort. Getting this balance the first time is the toughest because it's where you learn the aiming points. Once you find that balance it's easier to tell what direction. Going into folate deficiency is very different from potassium, once you have determined what each feels like. Take another 800 or 1600mcg and see what it does. I had to take the bit in my teeth and go for 8000mcg when I was trying tio shake off the glutathione. Nothing less worked. It wasn't a matter of 800 or 1600 helping a little and 8000mcg a lot. Nothing helped until suddenly it was enough. So what I had to do was keep increasing a single dose until I found the one that worked and then titrate the repeat doses to retain that.
 

SJB944

Senior Member
Messages
178
Do you mean each day you added an extra tablet of Metafolin, or just kept adding a dose throughout the day until it made a difference?
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Do you mean each day you added an extra tablet of Metafolin, or just kept adding a dose throughout the day until it made a difference?

Hi SJB,

I worked up to about 4000mcg a day one table at a time. I finally got disgusted with not making any progress and took 8000mcg, after somebody's suggestion to try a Deplin sized dose, and the results were quite sudden.
 

adreno

PR activist
Messages
4,841
Hi Adreno,

I suspect more Metafolin might turn the trick. You have enough mb12 going for you right now and ample adb12. The thing on the low side is metafolin. One way to test it is a larger dose for a day and see if it helps. Metafolin doesn't usually make a huge difference espeically when coming up from underneath. The effect then is one of releife usually. Titrate the Metafolin to comfort. Getting this balance the first time is the toughest because it's where you learn the aiming points. Once you find that balance it's easier to tell what direction. Going into folate deficiency is very different from potassium, once you have determined what each feels like. Take another 800 or 1600mcg and see what it does. I had to take the bit in my teeth and go for 8000mcg when I was trying tio shake off the glutathione. Nothing less worked. It wasn't a matter of 800 or 1600 helping a little and 8000mcg a lot. Nothing helped until suddenly it was enough. So what I had to do was keep increasing a single dose until I found the one that worked and then titrate the repeat doses to retain that.

I figured that, from the basis of your posts, so I took another 4000mg after posting that. I felt better immediately. Later I took another 5000mg, and again felt improvement. In the evening I took yet another 5000mg dose. This time I felt no improvement, but instead felt a slightly worse.

From this I deduce that somewhere between 5 and 10mg is the sweet spot for me at the moment. Using the same ratio as metanx (1:1.5), 5mg mb12 would require 7.5mg of mf, the small deplin dose. I am going to stick to this ratio, until we know more.

Some things that seem to improve are skin around nails, ibs, allergic symptoms, mucous membranes, cold extremities (blood flow is back), burning brain. The extra mf has caused my need of potassium to increase a bit, but not much. 2g per day, plus lots of veggies and fruits seems to do it.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
I figured that, from the basis of your posts, so I took another 4000mg after posting that. I felt better immediately. Later I took another 5000mg, and again felt improvement. In the evening I took yet another 5000mg dose. This time I felt no improvement, but instead felt a slightly worse.

From this I deduce that somewhere between 5 and 10mg is the sweet spot for me at the moment. Using the same ratio as metanx (1:1.5), 5mg mb12 would require 7.5mg of mf, the small deplin dose. I am going to stick to this ratio, until we know more.

Some things that seem to improve are skin around nails, ibs, allergic symptoms, mucous membranes, cold extremities (blood flow is back), burning brain. The extra mf has caused my need of potassium to increase a bit, but not much. 2g per day, plus lots of veggies and fruits seems to do it.

Hi Adreno,

Ok, So increase that amount by 50 percent and take 1/3 3 times a day. Then you play that amount up or down by a pill at each dose until you find what you need for 2 doses a day. The mb12 in the metanx is swallowed so only provides 25mcg absorbed whereas a 5mg Jarrow held as directed is in the 750-1250mcg absorbed range, much much more that 2.5mg swallowed. This should make a substantial difference for you. Potassium need may increase so be careful. You want to keep it singing along now. Very good. You now have your aiming point.
 

topaz

Senior Member
Messages
149
Greetings

This thread plus Freddd's post on Confirmed Folate Deficiencies has pushed me posting some info I have been mulling over a little earlier than planned. I've been thinking about these issues these last few weeks and have yet to order my thoughts (brain fog despite starting methylation protocol but I push on) but will post in any event to contribute to the discussion.

I have tabled below my google search results of some methylation protocol supplements which I searched to give me some indicative guidelines for B12:Folate ratios. The B12 and Folate forms are the preferred forms of methylcobalamin and MEtafolin unless otherwise noted.

the ratio of Folate:B12 from these random products sampled ranges from almost 1:1 to 2:1.

I was unable to copy the table from my word doc and retain the formatting. I spent some time adjusting the info below on screen to only find that when it is posted, the formatting isnt retained. Can any one let me know how I can fix this as the way in which it saves makes the info illegible?!! The only way Ive been able to find to do this is by converting to a jpeg image which you will need to click on the thumbnail to enlarge.


Methylation supplements.jpg


MENTAX INTRISI B12 METHYL XCEL 60C HOMOCYSTEX
Vitamin B-12 (methylcobalamin) 2 mg 500 mcg A 1000 mcg 1000 mcg
Folate (Metafolin) 3 mg 800 mcg B 2000 mcg C 800 mcg
TMG 500 mg 600 mg
Vitamin B-2 (R5P) 25 mg 30 mg
Vitamin B-6 (P5P) 35 mg 10 mg 15 mg
Intrincsic Factor 20 mg

A Folic Acid+ 5 MTHF
B Cyano cblmn
C Folic Acid




Although finetuning dosages varies from person to person, at this early stage I tend toward a ratio around 1.5:1 ratio of Folate to B12 on the basis of MTHFR (refer below) and that Deplin's smallest dose is 7.5mg, some 9.4 times greater than one Solgar 800mcg tablet.
 

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Rosebud Dairy

Senior Member
Messages
167
@drex

Part of the puzzle may be for you, as some of the rest of us have found, is that one of the LISTED side effects of folic acid is diarrhea -- whether from a supplement or a fortified food.

Several of us now avoid any food fortified with folic acid............Yes, that is right. A big pain.

One way of doing that, other than just a whole food diet with no processed foods, is also to go gluten free. I am trying this, as most or many gluten free breads are NOT fortified with any vitamins, so you just have to find ones that fit that requirement. I even mentioned this the other day to a nutrition expert who HAS an MTHFR SNP, and she had only just now begun to leave folic acid out of her own supplements, but was still eating foods fortified with folic acid, as "It (folic acid) is everywhere.....you can't avoid it!"

Well, I beg to differ. It can be avoided, and it just may be possible to feel better upon doing so. Going gluten free for me now still allows me to satisfy some carb cravings without throwing myself into an IBS/fatigue crash.

Not sure if you are male or female, but females have to be aware of POSSIBLE monthly cyclical variations in potassium needs, so you really do need to learn what the difference is in your own body for low folate (or PFD) , and for low potassium.
 

drex13

Senior Member
Messages
186
Location
Columbus, Ohio
@drex

Part of the puzzle may be for you, as some of the rest of us have found, is that one of the LISTED side effects of folic acid is diarrhea -- whether from a supplement or a fortified food.

Several of us now avoid any food fortified with folic acid............Yes, that is right. A big pain.

One way of doing that, other than just a whole food diet with no processed foods, is also to go gluten free. I am trying this, as most or many gluten free breads are NOT fortified with any vitamins, so you just have to find ones that fit that requirement. I even mentioned this the other day to a nutrition expert who HAS an MTHFR SNP, and she had only just now begun to leave folic acid out of her own supplements, but was still eating foods fortified with folic acid, as "It (folic acid) is everywhere.....you can't avoid it!"

Well, I beg to differ. It can be avoided, and it just may be possible to feel better upon doing so. Going gluten free for me now still allows me to satisfy some carb cravings without throwing myself into an IBS/fatigue crash.

Not sure if you are male or female, but females have to be aware of POSSIBLE monthly cyclical variations in potassium needs, so you really do need to learn what the difference is in your own body for low folate (or PFD) , and for low potassium.

Hi Rosebud,
I am up to date on the folic acid /folinic acid discussion. I don't take any folic acid containing supplements. I do eat bread though. And, not a female. I have gone gluten free in the past, may try it again. And I am hetero for both MTHFR snp's.
 

adreno

PR activist
Messages
4,841
I found this interesting:

The sera and marrow tissues from 47 patients were assayed for their folate and vitamin B12 content. The mean marrow folate and B12 was 135.6 pg/mg and 14.6 pg/mg wet weight of marrow, respectively. Results suggest a size relationship between folate and B12 pools in the serum and marrow with a constant folate/B12 ratio. The ratio of the mean serum folate/mean serum B12 is 9.8 and the mean marrow folate/mean marrow B12 is 9.2. Re-expressed, the mean serum B12/mean marrow B12 is equal to the mean serum folate/mean marrow folate, indicating a similar partition of these two vitamins between serum and marrow. Correlation between serum folate levels and marrow folate levels is poor. Similarly, poor correlation was found between serum and marrow B12.
http://www.ajcn.org/content/27/6/580


So folate levels are almost ten times higher than B12 in the body.
 

Rosebud Dairy

Senior Member
Messages
167
I have been trying to eat just a little whole wheat bread - has natural folates, and I make sure it is not fortified - just a little

If you have an MTHFR SNP , ditching fortified folic acid fortified foods could help IBS-type issues. I just figured for me - using products that are gluten free gives me some insurance against having folic acid in my food, so I have some products I can stick with.

SO, based on that ratio, I could maybe try a mega dose of methylfolate for a healing jolt, assuming co-factors are in place.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
I have been trying to eat just a little whole wheat bread - has natural folates, and I make sure it is not fortified - just a little

If you have an MTHFR SNP , ditching fortified folic acid fortified foods could help IBS-type issues. I just figured for me - using products that are gluten free gives me some insurance against having folic acid in my food, so I have some products I can stick with.

SO, based on that ratio, I could maybe try a mega dose of methylfolate for a healing jolt, assuming co-factors are in place.


Hi Rosebud,

A jolt won't sustain healing. It lasts a few hours. What it can show is if there are symptoms that it will counteract. Also, if there is too much folic/and/or folinic acid in body it won't help.
 
Messages
26
Location
Southern California
Hi all,

Several weeks ago I came across a snippet of a longer treatise @Freddd posted about paradoxical folate deficiency, and now I can't find it. So first question, can someone point me to that page? It was about the various types, and I was most interested in the type where you have skin peeling around the finger nails and from finger tips.

Next, I am a little confused about methylation trapping. I am wondering (and forgive me if this sounds stupid) if that is what happens to me. My main snps are in my sig. I started taking methB12 shots every day, and after a few days, the peeling skin around my fingernails began to heal up. They remained healed for several weeks, and then turned again, despite taking methylB12 shots daily. I've never seen anywhere else that peeling skin around the fingernails could be from folate deficiency!!

Finally, I still have some air hunger after completing antibiotic treatment (two years) for Lyme and Babesia. I am wondering if air hunger could also be a symptom of folate deficiency? Anyone?

Thanks in advance.

Oooh, does anyone know of a holistic MD or nutritionist in Southern California who can help me work with my SNPs?

Pam