THE STAGES OF METHYLATION AND HEALING

[Adster]

The definition of obese is being excessively fat.

Are you calling me fat, Freddd?

 

[Freddd]

Hi Adster,

Seriously though, I would love a functional definition of the forms of detox and what specific actions are needed reduce, remove or functionally manage the symptoms, knowing what can be done, what is generally a sign of healing in all this and knowing the symptoms that don't appear to be dangerous, have no known fix besides waiting for certain things in the body to complete or reset. For instance, most of the symptoms given for hypermethylation typically is an MeCbl, AdoCbl and/or L-methylfolate deficiency symptom. Most respond to being given these items. Most of the "detox" symptoms are MeCbl, AdoCbl and/or L-methylfolate deficiency sympotms and/or low potassium symtpoms. The symptoms that don't respond in the expected ways or the several most frequent variants almost certainly have something that is causing that. It's always that same 95% barrier. Somehow I always land outside of 95% medicine. Three chears for statistics. I don't use statistical methods as much I use pattern matching, each where appropriate. If I can select the people for specific pathways that are most likely to work for them, there will always be the mysterious few. However, if we can define "overmethylation" by symptoms that don't match and respond to the AdoCbl, MeCbl, Meththylfolate or anything else we check it for, that is some progress, something that makes it stand out even it is a seried of elliminations of other possibilities. If it ties to high MeCbl doses like 10-100mg absorbed, that would certainly be interesting. In any case, over methylation is very theoretical as long as a person has any of the several forms of folate insufficiency blocking methylation to various degrees. Is a functional part of the definition "there is no normal methylation possible"? That seems to be an assumption.

 

[dbkita]

Hi Adster,

Seriously though, I would love a functional definition of the forms of detox and what specific actions are needed reduce, remove or functionally manage the symptoms, knowing what can be done, what is generally a sign of healing in all this and knowing the symptoms that don't appear to be dangerous, have no known fix besides waiting for certain things in the body to complete or reset. For instance, most of the symptoms given for hypermethylation typically is an MeCbl, AdoCbl and/or L-methylfolate deficiency symptom. Most respond to being given these items. Most of the "detox" symptoms are MeCbl, AdoCbl and/or L-methylfolate deficiency sympotms and/or low potassium symtpoms. The symptoms that don't respond in the expected ways or the several most frequent variants almost certainly have something that is causing that. It's always that same 95% barrier. Somehow I always land outside of 95% medicine. Three chears for statistics. I don't use statistical methods as much I use pattern matching, each where appropriate. If I can select the people for specific pathways that are most likely to work for them, there will always be the mysterious few. However, if we can define "overmethylation" by symptoms that don't match and respond to the AdoCbl, MeCbl, Meththylfolate or anything else we check it for, that is some progress, something that makes it stand out even it is a seried of elliminations of other possibilities. If it ties to high MeCbl doses like 10-100mg absorbed, that would certainly be interesting. In any case, over methylation is very theoretical as long as a person has any of the several forms of folate insufficiency blocking methylation to various degrees. Is a functional part of the definition "there is no normal methylation possible"? That seems to be an assumption.

I have to admit I am starting to wonder how much of what is perceived as overmethylation at least at the doses being discussed is actually other factors. Somehow by adding adb12 and increasing T3 and Krebs cycle support, I am better able to tolerate many things and that appears to include methylfolate and mb12. I guess this fits in with your deadlock quartet principle.

I also wonder if some things like P5p or R5p can have effects beyond methylation that translate into higher levels of catecholamines or other unwanted excitotoxicity effects. I also wonder looking back if folinic acid for some may directly alter the balance in histidine to glutamate conversion by way of amping THF without the proper folate cycle conversions going the right direction. These are just speculations.

If I understand correctly one theme is that for some people small levels of methyfolate can lead to a paradoxical worsening of symptoms. There instead has to be enough of an increase in methylfolate to push through into "clear sailing" and break out so the folate and methylation cycles become balanced and self sustaining. Does this sound like an accurate interpretation of what you have been posting?

In my own case it looks like adding Adb12, getting off Jarrows to Enzymatic Therapy, and moving vitamin C away from my methylfolate dose opened a door that I could exploit letting me go after the Krebs cycle. I also needed more effective T3 support (for other reasons) but before I could not seem to handle it well (too much stimulation, etc.) Now the tables have shifted.

Now all I need is to figure out which direction to press the attack. Hmmm.


One last thing. On your stages of healing you wrote the following for stages 4 and 5:

4. Severe abnormal fatigue. Muscles don’t repair well. Severe muscle pains of many types. No exercise tolerance. Exercise doesn’t increase muscle or mitochondria increase. Edema, congestive heart failure. MeCbl & AdoCbl 1000mcg absorbed & L-Carnitine Fumarate & L-methylfolate 3200+mcg will start correcting and titrate to sufficiency, 1000mcg diffusion level, greater insufficiency of all factors before treatment.

5. Severe abnormal fatigue. Muscles don’t repair well. Severe muscle pains of many types. No exercise tolerance. Exercise doesn’t increase muscle or mitochondria increase. Muscles atrophy. Everything is breaking down. Edema and congestive heart failure. Only watery fat, if anything, increases. Large weight gains on minimal food. MeCbl & AdoCbl 1000mcg absorbed & L-Carnitine Fumarate & L-methylfolate 3200+mcg (titrated to sufficiency) will start correcting, 1,000mcg daily diffusion level, greater insufficiency of all factors before treatment.

Both have the identical amount of the deadlock quartet. But in the very beginning of your first post on this thread you mention the first four stages need 100 mcg of active B12s absorbed. Is stage 4's description for the amounts correct as I re-posted or should it be 100 mcg?

 

[dannybex]

Freddd
I'm mostly taking B12, but it's kind of a hassle taking all my B vitamins separately to avoid folic acid since there's no b complex without folate so I'm thinking of trying a b vitamin with a low dose of methylfolate. If it's just overmethylation then I can take potassium and niacin, but if it's something else then I want to be prepared.

This one by Thorne has no folic, but 200 mcgs of folinic, and 200mcgs of methylfolate:

http://www.naturalhealthyconcepts.c...esearch.html?gclid=CO2qnavwwbUCFeeDQgodPBYAgA

I just wish it didn't have so much niacinamide...but they all seem to.

 

[dbkita]

Freddd
Maybe I do expect too much from you to pinpoint my exact issue. I guess what I'm wondering is if eliminating folic acid is going to solve my problem or if I'm still going to react strongly to methylfolate regardless, but maybe I'm just going to have to try it and see what happens. My health got a lot worse after my last experience so I'm being very careful now. I'm mostly taking B12, but it's kind of a hassle taking all my B vitamins separately to avoid folic acid since there's no b complex without folate so I'm thinking of trying a b vitamin with a low dose of methylfolate. If it's just overmethylation then I can take potassium and niacin, but if it's something else then I want to be prepared.

I take my B vitamins always separately so I can control them carefully. Especially the amount of B6 and of course avoiding folic acid.

 

[adreno]

I have to admit I am starting to wonder how much of what is perceived as overmethylation at least at the doses being discussed is actually other factors.

Okay, but excess methylation seems to carry its own set of problems:

http://forums.phoenixrising.me/inde...e-nad-p-h-and-methyl-group-homeostasis.18026/

 

[dbkita]

Okay, but excess methylation seems to carry its own set of problems:

http://forums.phoenixrising.me/inde...e-nad-p-h-and-methyl-group-homeostasis.18026/

But I think we can agree one can supplement with B2 and B3. I have supplemented 100 mg B2 and 500 mg B3 for a long time. Ironically I have discovered of late that adding another 250 mg niacinamide at night helps me sleep. It could be its due to B3's known stimulation of the benzodiazepene receptor site or its role in mopping up methyl groups.

Niacinamide is converted to 1-methylnictonamide via Nictonamide N-methyltranferase with the reactions SAMe + nicotinamide = SAH + 1-methylnicotinamide.

 

[Xara]

I crashed and upped my doses of methylfolate, mB12 and potassium. Here's a short report.

Last week I had been doing reasonably okay, fatigued of course, and not being able to do much (I am housebound, not capable of doing any household chores) but clear mind, a few spasms every day. Taking several supplements, including mB12, aB12, methylfolate and a bunch of others. Started taking them in December.

Last Thursday I introduced zinc and increased P5P.

Sunday my lower lip cracked.
Monday I woke up with a very nasty pain in my right knee, never had that before in my entire life. I did not do anything in particular with that knee. I was also extremely fatigued, my muscles were very weak, filling a glass with water for example was tough. After breakfast, and after having taking my usual lot of supplements, I got a brain fog, I got groggy. Reading was impossible, thinking clearly became hard. I felt cold to the bone. I got irritated easily, and cried easily, I felt unstable, insecure, depressed. Later that day I became nauseous too, and I got a lower backpain. I got tingling sensations. My muscles were tight and painful. Muscle spasms throughout the day got worse (last week I had them too but a couple per day), several spasms per hour, and they were stronger than last week.

My husband and I discussed what to do. I crashed a while ago, prolly thanks to a lack of potassium. At that time I upped the potassium and stopped the methylfolate.
We looked at the symptom groups of Freddd, and the decision tree. We figured I had symptoms of group 1, 2 and 3. Probably because of zinc or P5P that had set (new) things in motion.
We could not decide what I was short of. Potassium, yes, that was clear, but maybe methylfolate and/or methylcobalamine too.
We decided to increase all three.

I have no trouble with my kidneys, and was not near the danger zone of 18 g potassium per intake. We placed the Real Niacin, time release, of Drs Best and the Now Foods Bio-Curcumin Phytosome on a visible spot; in case of things going wrong with methylfolate those two would have to be my rescue. And as far as the mB12 is concerned I did/do not expect much danger from that one (all I hear and read in my country is that an excess will leave the body, and in Japan IIRC they inject lots of it).

I was taking 2.16 g of Potassium via supplements, so still room for titration. Upped K to 2.7 g that day. Doubled methylfolate to 1200mcg (excluding the 400 mcg in my vitamin B complex, but that one is taking after my meals, and prolly reacting with vitamin C and iron intake). I melted the methylfolate (Solgar) in my mouth to have a quicker response. MB12, from taking 2 tablets ET twice a day to 3 tablets twice a day, as well as an extra injection of 1 mg intramuscular ( In my country all I hear and see is people urging to inject it in the muscle, meaning in the outer side of the upper quadrant (if not you'll hit an important nerve) of the thigh or buttocks muscle, if not intramuscular it'll leave the body far too soon, at least that's what they say. AFAIK Dutch bodybuilders inject it intramuscular too).

Today I feel better than yesterday, physically and mentally. I woke up having spasms, probable because I lacked potassium all night. I slept very well, had my usual Melatonin, I did not wake up once (unlike the two nights before last night).
AFAIK, methylfolate may take some time to have its full effect, so I am curious what will happen today and tomorrow. Again, I am not expecting much trouble from the extra mB12.

I'll continue taking extra K, mb12 and MF today and tomorrow.

On Thursday I'll probably up the methylfolate again. Then I'll also decide whether to up my adenoB12 ( I had pain and pressure in my sinuses first time I tried to up my dosis from 1/4 of a capsule AN every other day to a 1/4 of a capsule AN every day) - I am a bit scared when it comes to adenoB12.

For now I am quite happy with having taking the risk of upping the methylfolate and mb12.

Thank you Freddd for all your words and explanations, hard somethimes to understand and sometimes even harder to implement, but so far it has turned out to be very promising. Thanks also for your telling about your personal life and experiences, it's all very helpful and interesting.
BTW what does mito mean?

Thanks as well to dbkita, your own struggle, your questions and explanations are helpful and interesting.

Ps
Some people have been so kind to reply to things I said in other threads, I'll hopefully reply later today, if not I'll try this week.

Thank you all for reading this. And good luck, good health to you all.

 

[adreno]

But I think we can agree one can supplement with B2 and B3.

But aren't we then just canceling out the effects of the methyl donors (with the B3)? If we could just take megadoses of everything, things would be pretty simple, wouldn't they?

 

[triffid113]

This one by Thorne has no folic, but 200 mcgs of folinic, and 200mcgs of methylfolate:

http://www.naturalhealthyconcepts.c...esearch.html?gclid=CO2qnavwwbUCFeeDQgodPBYAgA

I just wish it didn't have so much niacinamide...but they all seem to.

Dannybex, that is the multi I take (from iherb). Genetically I need the folinic acid anyway. It is a mild B complex. Didn't cause my Dad any problems either, who had hs own set of methylation issues and broken genes.

Can I ask you if you ever considered taking TMG to add methyls and balance out any issues niacinamide may have for you? If you can get yourself to tolerate niacinamide, it has wonderful skin-healing properties.

 

[triffid113]

Hi Adster,

Seriously though, I would love a functional definition of the forms of detox and what specific actions are needed reduce, remove or functionally manage the symptoms, knowing what can be done, what is generally a sign of healing in all this and knowing the symptoms that don't appear to be dangerous, have no known fix besides waiting for certain things in the body to complete or reset. For instance, most of the symptoms given for hypermethylation typically is an MeCbl, AdoCbl and/or L-methylfolate deficiency symptom. Most respond to being given these items. Most of the "detox" symptoms are MeCbl, AdoCbl and/or L-methylfolate deficiency sympotms and/or low potassium symtpoms. The symptoms that don't respond in the expected ways or the several most frequent variants almost certainly have something that is causing that. It's always that same 95% barrier. Somehow I always land outside of 95% medicine. Three chears for statistics. I don't use statistical methods as much I use pattern matching, each where appropriate. If I can select the people for specific pathways that are most likely to work for them, there will always be the mysterious few. However, if we can define "overmethylation" by symptoms that don't match and respond to the AdoCbl, MeCbl, Meththylfolate or anything else we check it for, that is some progress, something that makes it stand out even it is a seried of elliminations of other possibilities. If it ties to high MeCbl doses like 10-100mg absorbed, that would certainly be interesting. In any case, over methylation is very theoretical as long as a person has any of the several forms of folate insufficiency blocking methylation to various degrees. Is a functional part of the definition "there is no normal methylation possible"? That seems to be an assumption.

Just curious -- but is overmethylation supposed to have an effect other than via COMT +/+ - I mean too much dopamine? I have 2 COMT +/+ and never ever overmethylate. If I take a deplin-sized dose of mfolate I get electrolyte disturbances and a great need to rebalance amounts of mB12, TMG, P5P, potassium, zinc,...and well, I never figured it out since I do ok on the 800mcg Metafolin. That was a LOW-methyl reaction though, as it caused the wrist pain etc that is a symptom. (Weird that extra mfolate would cause a low SAMe reaction w/o raising all the other support nutrients). I should mention that there is no single pathway in the methyl cycle in which I do not have multiple genetic defects.

 

[triffid113]

Thanks, pela, a lot of good information here. Interesting that you've gotten up to these dosages (active b protocol) without floundering as I and others have. Total crash in my case, but this thread is getting me back on track. I think.

Another helpful thing you mentioned is the selenium/t3 connection. I just had testing and had plenty of t4 but was low on t3. Will definitely try the selenium for better conversion. Everything else --cortisol, T, other thyroid measures, vitamin d-- was in the normal range except dheaS, which was above the red line high range for my age. Don't know what that means --good, bad or no connection-- in relation to Fredd's protocol.

And just like you and dbkita, I have trouble gaining weight. The only success i've had in years was with 'start up' on protocol before I crashed.

Being high in DHEA is GOOD. It means you prolly won't become diabetic. But I had read that all CFS people were characteristically low in DHEAS. Hmm. I take 75mg DHEA/day and my DHEA is therefore high and that is the only way I can function. My doctors are happy with my hormone test results. The key is whether or not you make healthy hormones out of it. I get my hormone labs at Meridian Valley through www.lef.org (it is a disgusting 24 hour urine test).

I have said this on a number of threads, but you want TSH < 2.0, otherwise you are hypothyroid (and will not be able to convert enough ubiquinone to active ubiquinol (CoQ10, required for the Kreb cycle, required for energy). The lab range is not based on science. See here: http://www.lef.org/protocols/appendix/blood_testing_02.htm?source=search&key=TSH reference range

I don't know which of these substances/cofactors are used where, but these are some of the supplements you need for your thyroid: zinc, tyrosine, iodine, selenium, mB12, copper, SAMe. Perhaps others. I have regular problems with zinc due to allergies using it up (it is used up rebuilding damaged mucous membranes). I also supplement tyrosine (doctor's prescription) due to that I eat a low protein diet. My albumin is 3.9, but it should be 4.0 or above.

 

[triffid113]

A lot of the supplements in Freddd's protocol help with the Krebs Cycle by improving mitochondrial function and increasing ATP, but I would like to know if there's more to the Krebs Cycle than just that.

I know of 2 specific ties (I am sure there are more) but here's a place to start:
(1) You need to methylate to make SAMe; you need SAMe to make thyroxine; you need thyroxine to turn ubiquinone to ubiquinol (active CoQ10); the Kreb cycle needs ubiquinol to make energy (ATP)
(2) The Kreb cycle uses aB12. I do not understand how it uses it...it is shown in some "background way" on charts, but not as part of a specific biochemical reaction. I just know it is required for the Kreb cycle to work to produce energy.

 

[Lotus97]

I know of 2 specific ties (I am sure there are more) but here's a place to start:
(1) You need to methylate to make SAMe; you need SAMe to make thyroxine; you need thyroxine to turn ubiquinone to ubiquinol (active CoQ10); the Kreb cycle needs ubiquinol to make energy (ATP)
(2) The Kreb cycle uses aB12. I do not understand how it uses it...it is shown in some "background way" on charts, but not as part of a specific biochemical reaction. I just know it is required for the Kreb cycle to work to produce energy.

When I was taking mostly B12 about 2 months ago I got overstimulated after increasing the dose. I thought maybe I was overmethylating, but potassium and niacin didn't seem to make any difference. I was only taking adb12 and hb12 so maybe the adb12 was causing ATP startup since I was also taking carnitine at the same time. I'm not really sure. There are so many different things going on in my body right now I can't seem to figure out what's causing what. I actually think it's a combination of many different things.

 

[Lou]

Being high in DHEA is GOOD. It means you prolly won't become diabetic. But I had read that all CFS people were characteristically low in DHEAS. Hmm.



Hi triffid113,

Thanks for this information, but not quite certain what your 'Hmm' references. Surely, you're not questioning if I have CFS. As I've written several times (unlikely you've seen or remembered it, though) I was part of a cluster of cases years ago and with exception of those who have actually died was for first years after becoming ill probably as sick as any here, with practically every symptom associated with it.

But I probably was hinting for some explanation of the high dhea. I don't supplement and the only thing my doctor came up with was conditioning (a lot of outdoor activity including distance mountain running) before illness. That, to me, makes little sense when factoring in the time elapsed since first becoming ill.

You know what, don't take this wrong way, I've been defensive, iritable for last two days, got myself right back into a box with this protocol and can't figure out what to take/not to take to climb out. Complicated. Guess if I didn't think this was the most promising avenue I'd just nix it, go back to 'just survive mode'.



I don't know which of these substances/cofactors are used where, but these are some of the supplements you need for your thyroid: zinc, tyrosine, iodine, selenium, mB12, copper, SAMe. Perhaps others.



Thanks, again. Any idea why tyrosine tends to overstimulate, perhaps run up my bp. I know I already have big problem with phynalalanine, can't tolorate at all, gives almost instant intense brain fog. Not typical PKU as I never had this problem before me/cfs.

 

[Lou]

What a mess my above post is with no color box separation of who said what. I'm very sorry to interrupt this important thread, but would someone be so kind as to pm me with how to fix instruction. I would be most grateful.


Done. Thanks, Lotus. Now if I can just figure out how to do that.

 

[Lotus97]

Thanks, again. Any idea why tyrosine tends to overstimulate, perhaps run up my bp. I know I already have big problem with phynalalanine, can't tolorate at all, gives almost instant intense brain fog. Not typical PKU as I never had this problem before me/cfs.

Tyrosine can cause overstimulation because it increases norepinephrine and dopamine. Phynalaline is a precursor to Tyrosine.

 

[Freddd]

Are you calling me fat, Freddd?

Your name isn't Freddd is it? Fat Albert is a chacter I remember. Just don't call me Shirly.

 

[dbkita]

But aren't we then just canceling out the effects of the methyl donors (with the B3)? If we could just take megadoses of everything, things would be pretty simple, wouldn't they?

You always need some B3. 500 mg is hardly a megadose in my book. Besides you are attenuating the end product which is SAMe. That is very different than mucking with the core parts of the cycles in question. Just my two cents.

 

[dbkita]

I know of 2 specific ties (I am sure there are more) but here's a place to start:
(1) You need to methylate to make SAMe; you need SAMe to make thyroxine; you need thyroxine to turn ubiquinone to ubiquinol (active CoQ10); the Kreb cycle needs ubiquinol to make energy (ATP)
(2) The Kreb cycle uses aB12. I do not understand how it uses it...it is shown in some "background way" on charts, but not as part of a specific biochemical reaction. I just know it is required for the Kreb cycle to work to produce energy.

I think adb12 comes into play on the branch that feeds in at succinic acid.