THE STAGES OF METHYLATION AND HEALING

pela

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Thanks for the info. How much methylfolate do you take now? Also how many doses do you split your b12s and methylfolate up into?
I'm taking around 8400-9200 mcg of Solgar methylfolate, divided into 4 doses. B12 3x a day.
 

dbkita

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I'm taking around 8400-9200 mcg of Solgar methylfolate, divided into 4 doses. B12 3x a day.
Thanks. Btw do you normally take the methylfolate with food or on an empty stomach?

So looking back at your other post you are taking 3.5 grains of NatureThroid (per grain 38 mcg T4 and 9 mcg T3), correct? I would love some day to be off pure T3 and on something like NT. Ironically though the equivalent strength assuming normal conversion from T4 to T3 and equilbrium values of T4 in plasma is about 25 mcg of Cytomel to one grain at steady state. So the 3.5 grains is in the ball park of my 75 mcg / day. That being said it is always preferable to use a hybrid T4 / T3 treatment than a pure T3 if possible. Hopefully someday my autoimmune disease will let me :)

I can see how the selenium is important for the proper conversion. Luckily living in California with volcanic soil the selenium content is pretty reasonable. I get about 200-250 mcg in my diet and take another 200 mcg as a supplement.
 

Lou

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The Krebs cycle and methylation cycle are interconnected and affect each other. Methylation is fundamental process of the body that at its core affects gene transcriptional regulation for production of expressed protein products, in other words among its many other hats it literally interacts with the machinery that encodes mRNA from your DNA.

But the Krebs cycle is about energy generation. Along with oxygen and water, energy is essential to life. Period. In fact the whole objective of oxygen is to help you make energy in the Krebs cycle (not exactly true but close enough). So the Krebs cycle interacts with EVERY system in the body. So yeah the Krebs cycle pretty much trumps all biologically speaking. I think Freddd's protocol addresses this co-dependence of methylation and Krebs cycle function with his deadlock quartet (+ things like other B vitamins, alpha lipoic acid, CoQ10, etc.).

But there are a lot of reasons that the Krebs cycle may be blocked and it is hard to say if there is a one size fits all solution for all of them. The biochemistry regulation is pretty complicated. On the other hand what I like about Freddd's reasoning is blindly throwing Krebs boosters at the problem is not going to do much.

I also think inflammation needs to be addressed as well otherwise the immune system can basically block everything including hormones and neurotransmitter production. This is a bit tricky since methylation can both reduce inflammation and increase it. I think the Adb12 plays a critical role in lowering inflammation based on the Gorilla in the Room paper in another thread.



Thanks, dbkita, for this succinct and understandable information re the Krebs cycle. Very helpful.
 

Lou

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Hi dbkita

Interesting that I am also on the skinny side, 5'8" 120 pounds and lost weight slowly and steadily for years desptite eating all day. I stopped counting calories when I went gluten free/ Paleo-ish, but 2500-3000 is probably close. Only recently did I hear that inability to gain weight is a B12 deficiency symptom. And since switching from T3 to NTH I've gained a couple of pounds.

The hydrocortisone is a long story--I ended up at around 45 mg for several months. 0.1 mg florinef sounds right. A nurse practioner began giving me Myers Cocktails with hydroxyB12. It got me off HC and FC almost immediately, but it took me almost 2 years to figure out it was the b12 that was working for me. I was already off HC and FC when I began Freddd's protocol in May 2012. I was 5 months into MB12, ADB12 and folate when I began the switch off T3. I had last tried NTH 2 years ago and within 5 days knew it was a big mistake. I felt horrible for seven weeks after taking 5 grains of Naturethroid. This time, Naturethroid made me feel great. I'm currently at 3.5 grains of Greater Pharma Thiroyd.

When I was taking T3 only, I took it in four doses throughout the day. Since I eat so much, only the first dose was on an empty stomach. I took the final 25 mcg dose at bedtime.

I started Freddd's protocol when Jarrow had gone bad, but no one knew it yet. I was taking 5000 mcg Jarrow Mb12, one Enzy, 1/3 Source Naturals ADB12. I can't remember my starting dose of methylfolate. I slowly increased all of the above and now take 6 Enzys, one Anabol ADB12, a lesser brand of MB12 at around 15 mg, 9 mg folate daily, and take one Doctor's Best l-carnitine fumerate about twice a week. I also take 400 mcg organic selenium daily. Selenium is essential for converting T4 to T3. I live in a selenium deficient region in addition to having malabsorption issues.

Yes I believe it was B12 deficiency that got me into this mess. I suspect many (but not all) who are diagnosed with adrenal fatigue have B12 deficiency. In my case B12, even hydroxy, "cured" my adrenal fatigue. Now I'm working on curing everything else.


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.
 

Freddd

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Hi Dbkita,

I got clobbered on the krebs cycle. I had lactic aicid burn in my mucles for 17 years. That told me something was very wrong. I couldn't find a single doctor willing to look at that or any of the specifics. They all preferred to call me names for having "yuppie flu", conversion disorder, etc. The only yuppies we have around here are the Young Urban Peregrines flying the canyons of the city eating pigeons.

What I did learn is that chasing individual results rather than the root cause didn't work well. I had hundreds of apparantly unrelated symtpoms and the docs were 100% puzzled. Finding what the MOST LIMITING FACTOR was turned out to be very important. When I said "everything worked better after MeCbl", and I could also have said that about AdoCbl if taken first, and you have noticed it, you have identified one of your most limiting factors. Things happen fast when you identify that. Then while maintaining that, the next item in each individual's line becomes the most limiting factor.

For the methylation line it looks something like MeCbl, L-methylfolate, Choline, SAM-e, B6, TMG; and some others

For the Krebs Cycle in the mitochondria, AdoCbl, L-carnitine fumarate, Alpha Lipoic Acid, Vit C, L-methylfolate, D-ribose and some others.

However, every vitamin is essential and any of them can become most limiting factors as can various minerals. A difference with potassium, it brings things to a halt via death rather than a breakdown in healing. Also, kidney damage, adrenal hormones, insulin and many other things get mixed up with potassium regulation. I was fortunate to have simple uncomplicate hypothyroid that responded to standard therapies but that can be a real problem too.
 

Freddd

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DESICCATED LIVER TRIAL 35,000 MG, 1979-1982
Desiccated liver per 700mg, 33mcg b12, 667MG PROTEIN
1700mcg of AdoCbl and MeCbl by labels averages by current 2013 labels
6000mcg of l-methylfolate estimated as water soluble vitamin which would be retained in fat extraction, connective tissue extraction and water evaporation in desiccated liver

I HATE LIVER. After doing my research and finding out all about the REAL b12s instead if CyCbl I had to try the real b12s. The only way possible was liver. I grew up in a mixed neighborhood; Jewish and Catholic. The only thing in common was that most all the Catholic mothers and most all the Jewish mothers served liver each week. My mother HATED liver, she never served liver. She was an atheist. I hated liver too. I decided that the only possibility of me trying it was desiccated liver. I ordered 10 jars of 1000 350mg tablets each for a 3 month trial. I HATE LIVER BURPS. That was the first thing I figured out. The next thing I figured out was that it was working. For the first time in my life the lights went on. Over the next 3 years the lights were on for a few months at a time until I got sick each time. Then they shut off for 6 months and then they came back on. I went through that 3 more times. Each time they went off it was like a descent into hell again as the depression and inflammation and pain spread throughout my body. I had a big garden then, about 3,000 square feet. NOW I recognize the pattern as paradoxical folate deficiency (partial methylation block) and intermittently worse. So going on nutrition information on liver and desiccated liver, 100 tablets of Argentinean Beef Liver, of 350mg each could have 1700mcg of AdoCbl and MeCbl and 6000mcg of L-methylfolate. I took them in 2 doses of 50 tablets each. Looked at via various absorption modes, the desiccated liver could deliver 25mcg twice a day from active absorption, and perhaps another 15-20mcg from direct diffusion. That is 65-70mcg of mixed active b12 and 6000mcg of L-methylfolate a day.

I had enough clues to decide to double the amount after about 2 years. The changes were great, but very fragile. I ordered twice my usual order and they were all moldy. I re-ordered a different brand. I ordered again and from a different company. They were ALL moldy. They were all from the same source despite various labels and names. I stopped ordering them. Doubling the dose to 200 tablets a day in 4 doses (ceiling on active absorption keyhole, no keyhole of conversion) might very well have carried me into the generalized healing startup by what I know today and enough methylfolate to possibly give me 15 days of healing a month as I would pass in and out of insufficiency. I came so close to maybe being able to live a much more healthy life. Any semblance of ordinary life diasappeared before Christmas when I was 39, 1n 1987. That was when for most intents and purposes that I entered my dying years. A twenty year chunk of my life is lost in that. 1987 was my best year in the consulting and software business and it was all downhill from there.The next year I couldn't work for more than a year.


Perhaps I can help distinguish between different levels of things.

Partial methylation block creeps up on you.
Paradoxical folate deficiency, several levels, creeps up on you except when suddenly induced
MeCbl body and/or CNS creeps up on you
AdoCbl body and/or CNS partial mito blockage creeps up on you


AdoCbl/LCF-CNS partial mito blockage can correct like a ton of bricks especially with anxiety present.


When MeCbl gets low enough Methyl-trap (severe mfolate deficiency symptoms, CNS and/or body) - hits like a ton of bricks and so does getting out of it



When AdoCbl/LCF gets low enough below a certain ATP generation level, sometimes muscles switch to workaround with lactic acid, prodcution, 1/6 energy. A different group of researchers from Rich (local to where I live) was looking for this situation, I had it. It hits like a ton of bricks and so does it’s correction.


Methy-trap and Partial mito block (or something) together may set off each other or by the same stress; combined hits like 10 tons of bricks, and so do their corrections
 

pela

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Thanks. Btw do you normally take the methylfolate with food or on an empty stomach?

So looking back at your other post you are taking 3.5 grains of NatureThroid (per grain 38 mcg T4 and 9 mcg T3), correct? I would love some day to be off pure T3 and on something like NT. Ironically though the equivalent strength assuming normal conversion from T4 to T3 and equilbrium values of T4 in plasma is about 25 mcg of Cytomel to one grain at steady state. So the 3.5 grains is in the ball park of my 75 mcg / day. That being said it is always preferable to use a hybrid T4 / T3 treatment than a pure T3 if possible. Hopefully someday my autoimmune disease will let me :)

I can see how the selenium is important for the proper conversion. Luckily living in California with volcanic soil the selenium content is pretty reasonable. I get about 200-250 mcg in my diet and take another 200 mcg as a supplement.
The first batch of methylfolate in the morning is on an empty stomach. The rest of the time with food, but not after a big meal, usually snacking.

I had some Naturethroid in the freezer, but now I'm using a different brand Greater Pharma Thiroyd. I tried Armour a few years back and did not do well with it.
 

Shoesies

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Look guys. I am newly diagnosed, in a severe relapse which means BRAIN FOG and cognitive issues. Is there not a methylation fro dummies thread or post that can just tell me what to order and when to take it? I understand the basics but right now this technical expose is much too clinical for me. HELP!
 

pela

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DESICCATED LIVER TRIAL 35,000 MG, 1979-1982
Desiccated liver per 700mg, 33mcg b12, 667MG PROTEIN
1700mcg of AdoCbl and MeCbl by labels averages by current 2013 labels
6000mcg of l-methylfolate estimated as water soluble vitamin which would be retained in fat extraction, connective tissue extraction and water evaporation in desiccated liver

I HATE LIVER.
You know liver is not so bad if you barely saute it in bacon fat so it is seared on the outside and raw on the inside, maybe add a little onion or pineapple. I buy grass-fed beef liver once a week and I like it fine if I'm hungry and it's got some bacon with it.

I admit I wonder what else is in liver that we don't know much about. Unidentified vitamins? Seems like eating liver is a good idea. I highly recommend it.
 

Lotus97

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Look guys. I am newly diagnosed, in a severe relapse which means BRAIN FOG and cognitive issues. Is there not a methylation fro dummies thread or post that can just tell me what to order and when to take it? I understand the basics but right now this technical expose is much too clinical for me. HELP!
This article explains methylation in very simple language. Keep in mind, when the author mentions "folic acid" he is referring to folinic acid and methylfolate rather than the folic acid you see in most supplements.
http://www.prohealth.com/fibromyalgia/library/showarticle.cfm?libid=16138

Keep in mind that if you are in very poor health you should approach methylation very cautiously. I posted on that here:
http://forums.phoenixrising.me/inde...hylation-and-healing.21725/page-4#post-333085

This article gives a brief explanation of the theory behind glutathione depletion and methylation blockade in simplified language
http://phoenixrising.me/research-2/...etion-theory-of-mecfs-by-rich-von-konynenburg

After that, you can check out the sticky threads in this forum which are about Rich's and Freddd's protocol. If you do decide to follow Freddd's protocol you might also want to check you his micro titration thread which isn't sticky. Rich is the person mentioned in that first article, is quoted in that second link and also the author of the third article. Good luck.
 

dbkita

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DESICCATED LIVER TRIAL 35,000 MG, 1979-1982
Desiccated liver per 700mg, 33mcg b12, 667MG PROTEIN
1700mcg of AdoCbl and MeCbl by labels averages by current 2013 labels
6000mcg of l-methylfolate estimated as water soluble vitamin which would be retained in fat extraction, connective tissue extraction and water evaporation in desiccated liver
Now that explains something. Several years back my neuroendocrinologist wanted me to get my iron up. He recommended Beef Liver Pills. A serving size of six pills would provide 9000 mg of Argentinian beef liver, which would be about 1/4 the amount you were testing (or about 1500 mcg methylfolate for instance). They gave me energy and me feel better in general except constipation went bonkers (may be due to the iron, dunno). But they also tend to CNS stim me with norepinephrine at night trying to sleep. I was already on a Jarrows 5000 mcg sublingual, but this was otherwise before going on actual methylation support in general. Makes me wonder now how some effects I ascribed to iron were actually from the methylfolate. Hmmm food for thought.

On another note, what is the best place to read up about the paradoxical ("donut hole") folate deficiency just so I understand it clearly.

Based on my earlier questions I am still trying to figure out if I should be increasing B12 or methylfolate at this point. At the moment I am on the fence for either.
 

Freddd

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Now that explains something. Several years back my neuroendocrinologist wanted me to get my iron up. He recommended Beef Liver Pills. A serving size of six pills would provide 9000 mg of Argentinian beef liver, which would be about 1/4 the amount you were testing (or about 1500 mcg methylfolate for instance). They gave me energy and me feel better in general except constipation went bonkers (may be due to the iron, dunno). But they also tend to CNS stim me with norepinephrine at night trying to sleep. I was already on a Jarrows 5000 mcg sublingual, but this was otherwise before going on actual methylation support in general. Makes me wonder now how some effects I ascribed to iron were actually from the methylfolate. Hmmm food for thought.

On another note, what is the best place to read up about the paradoxical ("donut hole") folate deficiency just so I understand it clearly.

Based on my earlier questions I am still trying to figure out if I should be increasing B12 or methylfolate at this point. At the moment I am on the fence for either.
Hi Dbkita,

You raise some interesting questions. I hadn't really considered the iron situation. That was in a period when my digestion was so bad I had a an 8 hour transit time and all diarhea except when occasional constipation hit. It was the only time in my life that my MCV normalized until adequate L-methylfolate most of the time.

On another note, what is the best place to read up about the paradoxical ("donut hole") folate deficiency just so I understand it clearly.

Most of it is right here off of the Methylation menu in a variety of posts. If you want to watch the historical development of it, starting with identifying a significant part of "detox" as folate deficiency after that was identified clearly by the glutathione trial inducing a severe methyltrap folate deficiency. In one or more of the videos of Rich's posted on a European website and probably elsewhere, he describes paradoxical folate deficiency in various contexts and does all but name it. That can probably be identified by search as I posted the where of it.

When making a listing of the various types of paradoxical folate deficiency I called the one described most often by starting small doses and having "detox" in which cases it was folate deficiency symptoms that increased, I called it "donuthole" to distinguish it from a methyltrap sittuation like glutathione, or a blocked by folic acid, folinic acid, veggie folates situation.

It takes a whole lot of understanding of folate insufficiencies to even be able to ask questions about the "donut hole" folate insufficiency. Paradoxical folatge deficiency was first noted in a journal, THE HORSE, in treating a horse with folic acid. Methylfolate wasn't available then. Just in the last few years can comparisons be made of L-methylfolate to other folates. I would guess, based on past behaior regarding understanding vitamins that some time about 2070 one might see some journal articles about this and by 2100 it is understood at least as functionally well as it is right here right now.

Also read the INSUFFICIENCY VERSUS DEFICIENCY posting. The very specific "donut hole" insufficiency would have been lumped in with "functional deficiency" and got caught up in the dicussion of "true deficiency" versus functional deficiency" and ignored or deprecated for not being a "real deficiency". The idea of b12 and folate deficiencies being arbitray places on a continium of insufficiency from 1 symptom to 400 symtoms and death, doesn't sit well with the defenders of folic acid, CyCbl and HyCbl based on decades of inactive vitamir research.

It just doesn't work the way because decades of misguided research indicate is that there is no system of prediction and effect that makes sense with CyCbl, HyCbl and folic acid as a whole.
 

Lotus97

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When making a listing of the various types of paradoxical folate deficiency I called the one described most often by starting small doses and having "detox" in which cases it was folate deficiency symptoms that increased, I called it "donuthole" to distinguish it from a methyltrap sittuation like glutathione, or a blocked by folic acid, folinic acid, veggie folates situation.
How can you tell whether it's what you call "detox" symptoms or if you're just overmethylating? And since you distinguish this from the Methyl Trap, does that mean someone can still experience it even if they eliminated folic acid, folinic acid, etc?
 

dbkita

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I will take a look.

If I scanned it right, the max dose is 80 mcg / kg bw. For 70-80 kg human that is 5600-6400 mcg not 1000. Correcting for BSA brings it into the 1000 mcg range.

However, not every compound is best described using the BSA corrected value. Nor is it simply advisable to adjust by weight alone. Often the truth lies somewhere in between. I would argue the BSA certainly has limited utility here since we are talking CNS penetration of the injected methylfolate. Ironically the FDA and EFSA still used simple linear weight multiplication to obtain NOALEL, etc. which is silly imo.

Very hard to tell how doses extrapolate going from rat to human. Also I suspect that the delivery mechanism becomes important at high enough doses (the rats were injected) and I am certain at some range the dose response curve is not linear. That is basic pharmacodynamics.

We are also talking single dose. So dosing throughout the day to maintain a target Cmax is another question. So at one end we are looking at 1000 mcg 3-4 x per day (by BSA). At the other end maybe 2-3x that if you shift more towards a hybrid between BSA and weight? (37/6 ~6)
 

Freddd

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How can you tell whether it's what you call "detox" symptoms or if you're just overmethylating? And since you distinguish this from the Methyl Trap, does that mean someone can still experience it even if they eliminated folic acid, folinic acid, etc?
Hi Lotus,

Please define and/or describe overmethylation symptoms and signs as precisely and completely as you can, leaving aside interpretations and assumptions. Also. from where I am coming from while the genetic polymorhisms may someday be helpful in this endeavor they only lead to understandings that don't yield useful results. That way we can be starting on the same page. Don't reason from them either for the same reason. You don't know, I don't know, nobody knows the genetic signature of methyltrap, the various forms of paradoxical folate deficiency/insufficiency or ATP insufficiency from partial mito blockage or whatever we ought to call it..

The interpretations I have heard attempted to be applied doesn't result in much in the way of results. So when you predict what treatments of overmethylation will have results and bring it under control and lead to sigificant healing each month for the next 6 months, I hope you clearly understand them and can convey them well. I don't hypothecize effectivness for anything that doesn't have that characteristic, giving a working decision tree on what to do and the what to do working promptly. Nothing works for everybody, especially without customizing. That process of customizing goes right to the heart of it all.

To work with overmethyation as a working hypothesis what is needed. is a definition of overmethylation that leads to a treatment that leads to healing or things that correlate with healing with the specificities as listed above. Make as few non explicit assumptions as you can or those will be what I ask about next. Thankyou. Without a useful definition of overmethylation I can't identify it or distinguish it from anything else.
 

Lotus97

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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.
 

Freddd

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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.
Okay. Then what I need to do is walk you throigh a process of eliminating the posibilities. I know it is a hassle for doing a basic b-complex (no b12, no folate) plus all the active forms as separates can be a pain. First, go to the decison tree with type 2 and type 3 symtoms groups. Identify all the symptoms possible to those sets and that will give us some idea of what is going on. And of course include all the ones that are NOT part of that list that are the new ones. This will give a much metter idea of what is going on.