THE STAGES OF METHYLATION AND HEALING

Freddd

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Approximate timing of my startup of individual items that being considered here, this gives a quite distinctive pattern for each nutrient or set of nutrients: 03/04/13, Version 1.1

Others mentioned similar patterns and variations.

1. Initially – Mecbl

2. +5 months 400mcg SAM-E

3. + 4 months AdoCbl

4. + 3 months titrate +50mg zinc

5. +4 years 400mcg Metafolin

6. +1 year LCF

7. + 1 month TMG 1000mg/day

8. 30mg MeCbl injections (3 or 4) daily,

9. +0 Reduce SAM-e to 200mcg

10. + 4 years remove TMG

11. +6 months increase SAM-E to 800mcg

12. Next 1 year titrating Metafolin and finding all the reasons I get folate insufficiency, early partial methylation block by effect.



These symptoms are what responded very well to CNS penetrating doses of MeCbl either as 50mg sublingual single 4-5 hour dose or 4 x 7.5mg or 3 x 10mg or for some 2 x 15mg subcutaneous MeCbl injections. Metafolin in some way enhances retention of AdoCbl and MeCbl with excretion visibly decreased. A sublingual dose of 1-2 tablets each hour added for 12 hours appears to generate substantial CNS penetration as well.



CNS penetrating dose MeCbl – AdoCbl – Metafolin – Omega-3 oils


Elevated CSF Hcy
Low CSF cobalamin
limbs feel stiff
Drowsy


CNS penetrating dose MeCbl – AdoCbl
dimmed vision - usually not noticed going into it because change can be very slow or present for life
Clumsiness


CNS penetrating dose MeCbl – AdoCbl - Metafolin


Slow to adapt to night vision


CNS penetrating dose MeCbl – AdoCbl – Metafolin – LCF


Difficulty in word finding



CNS penetrating dose MeCbl – AdoCbl – Metafolin – Omega-3 oils


Brainstem or cerebellar signs or even reversible (with mb12) coma may occur
demyelinated areas on nerves
subacute combined degeneration
axonal degeneration of spinal cord
unsteadiness of gait
ataxic gait, particularly in dark
positive Romberg
positive Lhermittes
Loss of motor control over some or all of toes
Loss of motor control over part or all of feet
Loss of sense of joint position
sudden electric like shocks/pains shooting down arms, body, legs shooting down from neck movement
sudden "ice pick" pain
decreased reflexes
brisk reflexes
Foot Drop
tripping over toes
injuring toes catching top of toes on floor
general feeling of weakness

 

Freddd

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Approximate timing of my startup of individual items that being considered here, this gives a quite distinctive pattern for each nutrient or set of nutrients: 03/04/13 Version 1.1

Others mentioned similar patterns and variations.

1. Initially – Mecbl

2. +5 months 400mcg SAM-E

3. + 4 months AdoCbl

4. + 3 months titrate +50mg zinc

5. +4 years 400mcg Metafolin

6. +1 year LCF

7. + 1 month TMG 1000mg/day

8. 30mg MeCbl injections (3 or 4) daily,

9. +0 Reduce SAM-e to 200mcg

10. + 4 years remove TMG

11. +6 months increase SAM-E to 800mcg

12. Next 1 year titrating Metafolin and finding all the reasons I get folate insufficiency, early partial methylation block by effect.


These symptoms are what responded very well to L-carnitine fumarate AND AdoCbl for the first two items


L-carnitine fumarate – AdoCbl – Metafolin - MeCbl


weight loss involuntary
muscular atrophy
exercise does not build muscle



L-carnitine fumarate – Metafolin – AdoCbl - MeCbl

weight gain, watery fat
edema


L-carnitine fumarate – AdoCbl – MeCbl – Metafolin


mild to extremely severe fatigue
continuous extremely severe fatigue
easy fatigability
severe abnormal muscle fatigue up to and including apparent paralysis leading to death
weakness
muscle pain especially around attachment points to bones
Eighteen severely tender muscle spots of FMS



AdoCbl – L-carnitine fumarate


exercise debilitates for up to a week, making things much worse
accumulating muscle pains following exertion
sore muscles throughout body
lack of muscle recovery after exercise
High urinary MMA



AdoCbl – L-carnitine fumarate – Metafolin

congestive heart failure
Elevated CSF MMA
Elevated uMMA

 

Freddd

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Approximate timing of my startup of individual items that being considered here, this gives a quite distinctive pattern for each nutrient or set of nutrients: 03/05/13, Version 1.1

Others mentioned similar patterns and variations.

1. Initially – Mecbl

2. +5 months 400mcg SAM-E

3. + 4 months AdoCbl

4. + 3 months titrate +50mg zinc

5. +4 years 400mcg Metafolin

6. +1 year LCF

7. + 1 month TMG 1000mg/day

8. 30mg MeCbl injections (3 or 4) daily,

9. +0 Reduce SAM-e to 200mcg

10. + 4 years remove TMG

11. +6 months increase SAM-E to 800mcg

12. Next 1 year titrating Metafolin and finding all the reasons I get folate insufficiency, early partial methylation block by effect.





MeCbl - AdoCbl – L-carnitine fumarate – Metafolin

shortness of breath, oxygen hunger
heart palpitations


MeCbl - AdoCbl – L-carnitine fumarate

extremely sore neck muscles reversing normal curvature of neck
painfully tight, stiff muscles, especially legs and arms
frequent muscle spasms anywhere in body
weak pulse



MeCbl - AdoCbl

Confusion
Disorientation
Difficulty in word finding


MeCbl - AdoCbl - Metafolin

irritable
depression
SAD - Seasonal Affective Disorder
mental slowing
personality changes
chronic malaise
poor concentration
moodiness
tiredness
mood swings
memory loss
listlessness
impaired connection to others
mentally fuzzy, foggy, brainfog
dizziness - even unable to walk
Vertigo


MeCbl – Metafolin – AdoCbl – L-carnitine fumarate

psychosis, including many of the most florid psychoses seen in literature, megaloblastic madness
Alzheimer's
delirium
dementia
paranoia
delusions
hallucinations - multisensory
anxiety or tension
nervousness
mania
Widespread pain throughout body



A caution, those with anxiety and panic symptoms may respond with extreme moods of increased fear, anxiety, panic, anger rage, homicidal rage and profound depression, usually in repeatable sequences following LCF or ALCAR even at levels of 1mg oral. A micro titration of carnitine would be cautious. While most find the moods intolerable, certain persons have been able to tolerate these (both past) and current, to find they can fade after some months of consumption. A few people may find similar, maybe somewhat lesser, response to MeCbl or more likely AdoCbl. As these are less controllable than LCF which can be micro dosed, they should be considered first.
 

Lotus97

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I did get the Thorne Prenatal (!!!), which has lower doses, and I seem to be tolerating it okay -- maybe a little more tingly in the toes, but not certain -- lots of things can cause tingling, twitching. But I started with a third of a cap a day, and am now doing about 2/3rds...working up slowly. Haven't noticed any awkward flushing so perhaps the 'balance' is helping.
I assume you're low in iron because 45 mg a day (in 3 capsules) seems kind of high otherwise.
Oh, just realized you said 1/3 of a capsule. Never mind:oops:
 

Lotus97

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Do you have any thoughts on L-carnitine's inhibitory effect on the thyroid? As someone with hypothyroidism, I am cautious about supplementing until I understand how it works better.

Thanks for all your work. It is very interesting.

Ema
Some people here have reported success with carnitine supplementation, but if you're concerned about your thyroid Rich seemed to think improving methylation would help increase carnitine levels naturally.
I just want to note that several studies have shown that carnitine is low in ME/CFS. I think the reason is that methylation is required to make carnitine in the body. One of the main roles of carnitine is to usher fatty acids into the mitochondria of cells to be burned as fuel. In the urine organic acids test results that many people have posted or sent to me, I usually find that the fatty acids markers are showing buildup of omega oxidation of fatty acids, which occurs when there is a carnitine deficiency. Under these conditions, it makes sense that your muscles would respond to carnitine supplementation, since it raises the supply of fuel to their mitochondria. When the methylation cycle partial block has been lifted, the cells should be able to make enough carnitine for themselves.

SAMe is produced in the methylation cycle and is the main supplier of methyl (CH3) groups for a large number of methylation reactions in the body, including the methylation of DNA and the biosynthesis of creatine, carnitine, phosphatidylcholine, coenzyme Q10, melatonin and epinephrine. This measurement is made in the red blood cells because the level there reflects an average over a longer time and is less vulnerable to fluctuations than is the plasma level of SAMe.

Best regards,
Rich
 

Freddd

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ANOTHER PATTERN IS CONFIRMED

Early symptoms apparent as child of veggie folate paradoxical folate insufficiency

Sub Acute Combined Degeneration - SACD - as adult, various ages

To achieve improvement in SACD:

  1. Requires high perhaps equal levels of injected MeCbl AND AdoCbl, ie 37.5mg each
  2. Requires high levels of Sublingual AdoCbl AND MeCbl also.
  3. Requires high levels of Metafolin ie 50mg
  4. Requires average LCF

A degree of anxiety is present and considerably augmented by AdoCbl/LCF. It is tolerated for a number of months before fading. As it fades neurological healing becomes apparent.
 

dannybex

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Just to add my experience with B6.

B6 in the non-active form aggravates my neuropathy -- increased in tingling, in hands feet, legs face, mouth etc.

Not so sure P5P does the same, seems to, can't be definitive. I have high levels of P5P in the blood -- very high in fact, but have been able to get them down to just above normal levels recently, simply by not supplementing with B6 (this reduces the some of the intensity of neuropathy but certainly does not remove it.).

(I have only ever taking small amounts of B6, nothing that should correlate with such a high blood reading.)

Despite high levels of P5P in blood, Rich's interpretation of my Organic Acids Urine test was that I have low B6. Blood ALP levels were fine, suggesting high P5P not simply result of low zinc -- thus reduced Alkaline Phosphatase..

Rich Van K also suggested a possible partial B2 deficiency, his logic:

"I've been doing some more thinking about your case. More and more, I suspect that the problem is a partial deficiency in vitamin B2.

Here's how it could work: The liver is going to get its B2, even when B2 is scarce, bodywide, because the liver is in position to receive what comes in from the gut, via the portal vein. Therefore, if there is a partial deficiency of B2, the liver will have it, but perhaps the other organs will have a deficiency. If this is true, the liver would be able to phosphorylate the B6 and put it out in the blood as P5P. Then, if there was sufficient alkaline phosphatase, it would be able to remove the phosphate so that the B6 could diffuse into the cells. However, if the cells do not have enough B2, this B6 will not be phosphorylated, and it will then exert backpressure on the reaction that is supplying it via the dephosphorylation of P5P on the outside of the cells."

I have tried B2 (R5P) on it's own to see if it has a different impact then when taking it as part of a complex. I could only tolerate small levels -- and broke it up throughout the day. No noticeable improvement, in general symptoms or neuropathy. Cleared sinus a little. At times seemed to help sleep. If I took to much just really stirred things up.

I think there is something significant in the high blood levels of P5P and reactions to taking B6, but I've not seen or read anything that is revealing (apart from Rich's supposition).
.
I have exactly the same problem -- even tiny amounts of b6 or p5p cause tingling, at least in my toes and feet -- sometimes in my hands. My NutrEval results also suggested I needed b6 (for certain parts of the Krebs cycle) and I believe Rich suggested it as well, but I never had a blood test to see what my levels were.

So I was wondering...what is the specific test to ask for for accurate levels of b6 or p5p?

I did find that b2 helped me tolerate b6 just fine, but had to stop all b6 or p5p for months first. And then eventually the b2 caused increased sensitivity to light...so I'm back to avoiding both, at least temporarily. Also, there's a post on another site where a woman with high blood levels of b6 brought them down by taking methyl-b12. I'll see if I can find that again...although I think she ended up taking more and more methylb12 and had to keep increasing it. If she stopped, the tingling would come back.

Neuropathy can also be related to calcium deficiency, thiamine deficiency (benfotiamine is helping me lately), pantothenic acid deficiency, and as others have mentioned, long term oxidative stress.

Thanks in advance.
 

SJB944

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So I was wondering...what is the specific test to ask for for accurate levels of b6 or p5p?
Hey dannybex, I think our paths and similarities have crossed before.

I didn't ask for a specific blood test other than to ask for B6 and to find out it measured P5P. Originally the test it had no upper scale just had to be over 3.5 ug/L and I was 210. More recently, the upper scale is about 29 and I've been around 32.

So I guess ask to test P5P levels. Most the research I've seen talks of issues of tingling and the like for B6, but not necessarily for P5P. Do you find specific differences to taking B6 and P5p?

Question is what does it actually mean? And how do we test if B6 is getting into the cell?
 

dannybex

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I'm not sure for certain if I've noticed a difference between b6 or p5p. It's been awhile since I tried one or the other separately. Right now I try small amounts of a thorne b-complex every other day or so.

And yes, what does it mean? I think, perhaps that it may be due to other things like perhaps insufficient minerals (magnesium?) and/or perhaps low sulfate/sulfur...who knows? :) Certainly will try to figure this out.

As for if it's getting into the cell -- I did a SpectraCell test a year ago (seems like 3!) which measures nutrients in white blood cells. It's supposed to be more accurate (it came highly recommended, so I raised $ for about 8 months to pay for it), but I'm not sure. For example, my vitamin C levels were completely normal, almost a little 'high-normal', yet I hadn't at that point, taken vitamin C for years, and ate mostly cooked food.

The only things that were "deficient", were vitamin d and zinc, and inositol was very close to officially deficient. The rest of the b's including b6 were borderline (close to deficient), except for b12, which was high-normal.

But also high normal was choline (haven't had eggs in years, am trying to increase them) and 'oleic acid', which I'm guessing is from olive oil (although there is some in evening primrose oil). Hadn't had much olive oil, if any, so the results are kind of puzzling/frustrating. And frustrating that they didn't measure other fatty acids, or iron levels.

??? :)
 
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Oh wow. This sure is a lot to digest. I need to get the 23andme test, but at the moment I have only had the MTHFR done. I am compound heterozygous. I am taking 1 mg MTHF (+ a little B6 non activated), but I cannot tolerate the methyl B12. Started at 500 mcg and it brings on symptoms (raynauds in hands, trouble swallowing) to an autoimmune disease I have antibodies for, but never had symptoms. I stopped it and now I am better. I saw Rich said methyl B12 mobilizes mercury, has this been disproven? Problem now is I am pregnant (6 weeks) and I was fine but now I am having anxiety, heart palpitations and shortness of breath. I can not eat foods now with tyrosine either. I'm lost and worried for my baby. have h. pylori too so worried ab Thorne prenatal and the iron feeding it. HELP!!!!!!!!!!!!!!!!!!!!!!!
 

Jarod

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EveG

When pregnant doesn't seem to be the time to experiment/change vitamins too much in my opinion. Maybe try something that you are comfortable with and stick to it until the baby is born?

The heart palpitations (potentially from low potassium) are not uncommon with Freddd's protocol. Low potassium is something that can be problematic if not addressed. Low potassium can be checked with a common blood test your doctor can run.

Lotus97 you have that quote from Rich on how to best supplement potassium? The safest way is with 100 mg capsules spread out over time to avoid stomach irritation I believe.

Rich felt Hydroxy-12 was less likely than Methyl B12 to cause over-methylation. I've heard the mercury thing before but not sure what research Rich was referring to.

You may want to spend some time checking out Ben Lynch's website, he specializes in MTHFR issues and is especially interested in younger people and new Moms.
 

Lotus97

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Lotus97 you have that quote from Rich on how to best supplement potassium? The safest way is with 100 mg capsules spread out over time to avoid stomach irritation I believe.
I've heard different things from different people. Rich said pills in general could cause problems and recommended powder mixed with water. Freddd said only the time release pill were dangerous. When I told Ema what Freddd said she said that she though the time release were safe. I take potassium in powder form because it's cheaper.
Rich felt Hydroxy-12 was less likely than Methyl B12 to cause over-methylation. I've heard the mercury thing before but not sure what research Rich was referring to.
I'm not sure about the methyl b12 and mercury. Rich talked about it a few years ago and even though he cited a guinea pig study he also said "there's not a whole lot of evidence". In his most recent protocol he recommends switching to methylcobalamin (and possibly also increasing methylfolate dosage) if you don't experience improvement with hydroxocobalamin so I don't think Rich thought the possibility of methylcobalamin methylating inorganic mercury into methylmercury was a problem. And I know he was still concerned about mercury because in his most recent protocol he also said he decided against a multivitamin that had lipoic acid in it since some people say alpha lipoic acid and R lipoic acid could cause problems for people with mercury toxicity.

Methylation in general can cause metals and other toxins to be released, but that's a different issue. Rich recommended taking charcoal as a binder. There are plenty of other binders as well. Different people have different opinions about which binders are the best. Certain ones like charcoal will bind to most everything so it's good to take those binders away from prescription medication and supplements.
 

Critterina

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whoa!
"These are the first things to appear when paradoxical folate deficiency occurs or for some when HyCbl is consumed and epithelial methylation is shut down (2-3 days), acne type lesions first on scalp and face and spreading to body, angular cheilitis (sores at corner of mouth)..."
That's the best description of what's going on with me that I've read so far! I've been on MB12 (5000mcg sublingual) and MTHF (1 mg) for 6 months, and these appeared after 3 months, which happened to be 10 days after I started hormone replacement (progesterone, DHEA, estriadiol, estriol, and testosterone). I thought it was hormone replacement doing it.
 

Freddd

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whoa!
"These are the first things to appear when paradoxical folate deficiency occurs or for some when HyCbl is consumed and epithelial methylation is shut down (2-3 days), acne type lesions first on scalp and face and spreading to body, angular cheilitis (sores at corner of mouth)..."
That's the best description of what's going on with me that I've read so far! I've been on MB12 (5000mcg sublingual) and MTHF (1 mg) for 6 months, and these appeared after 3 months, which happened to be 10 days after I started hormone replacement (progesterone, DHEA, estriadiol, estriol, and testosterone). I thought it was hormone replacement doing it.
Hi Critterina,

Deteriorated MeCbl has substantial amounts of HyCbl-H20Cbl in it that appears able to cause the same skin lesions. Also, the b12, acting as b12 is needed to contribute to paradoxical folate efficiency and more folate heals these lesions. Also, hormones are very much affected by b12/folate and can be increased by them correcting the decreased hormones of deficiency.
 

Critterina

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Hi Critterina,

Deteriorated MeCbl has substantial amounts of HyCbl-H20Cbl in it that appears able to cause the same skin lesions. Also, the b12, acting as b12 is needed to contribute to paradoxical folate efficiency and more folate heals these lesions.
Fred,
Thanks for addressing this. I am not sure I understand your reply, but I think that "more folate" is key. I was taking my folate with my MeB12 and 1000 mg of Vitamin C, so could it be that I was just destroying the folate with the C? Today was the first day I separated them. I think that I'll get "more folate" by separating them, and so won't increase the dose before I give that a chance.
Hi Critterina,

Also, hormones are very much affected by b12/folate and can be increased by them correcting the decreased hormones of deficiency.
I"m sorry. You really lost me here.
Let me tell you what happened and see if it makes sense. First lab tested progesterone (not detectable), DHEA low (17 with reference range 26-200), and testosterone 10 total, 1.1 free (post-menopausal), and low-normal thyroids but high TSH. By mistake we didn't test estrogen or cortisol.
I was on my protocol for 3 months without lesions on my face (could have been on my scalp, but I thought maybe I reacted to shampoo, so didn't track). Besides the supplements, I was on 25 mcg T4. My average morning temp went from 96.4 (range 95.6-96.7) to 97.3 (range 97.0 to 97.6) - enough to make me feel so much better in spite of everything.
After 3 months we retested and I showed improved but high TSH, no detectable progesterone, DHEA dropped to 14, testosterone dropped by half (5 and 0.6), estradiol was 2 total and 0.04 free, saliva cortisol was in the bottom 5% of the range in the morning and not detectable afternoon and evening. Also tryptophan was half the low end of the reference range and Me was just below reference range, so those were added to my protocol first. 2 weeks later, I started hormones, and two weeks after that, increased the T4.
So, if I follow what you say, (doubtful!), when I added the folate and MB12, my hormones should have gone up? The detectable ones dropped about 20% and 50%. Hmmmm...
Oh, interestingly enough, when I started the hormones, my average temp quickly went up to 97.7. With the increased T4, it slowly went up to 97.8.
 

Critterina

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Hi Critterina,

Deteriorated MeCbl has substantial amounts of HyCbl-H20Cbl in it that appears able to cause the same skin lesions. Also, the b12, acting as b12 is needed to contribute to paradoxical folate efficiency and more folate heals these lesions. Also, hormones are very much affected by b12/folate and can be increased by them correcting the decreased hormones of deficiency.
Freddd,
Thank you so much!!!! My face and scalp are mostly healed. Since Thursday. You really helped! :balloons::):balloons:
 

Critterina

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Freddd,

I have a few more questions just now:

What does "titrate to sufficiency" mean? I see it all over. I've done titrations in Chemistry, but that doesn't seem to apply. How is sufficiency determined?

What does "in diffusion" mean?

Thanks!
 

trollo

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Hello guys. Anybody ever tried the dibencozide Magnum by Megabol??? Source natural is difficult to find in Europe and it seems to me it s in a too massive dose 8mg!!! And how about the Holistic health mega drops?? Are they well absorbed?? I also saw that Pure encapsulation makes dibencozide in caps, is it absorbed???
 
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I've been on 1.4g sam-E/day, 2400mg GNC choline 2 capsules, NAC 1800mg/day....
when I added higher doses of vitamin B (1 through 12) I got cystic acne- is this a sign that I need to take more solgar methyl folate?
I also started a protein shake with amino acids but don't know how long I can afford this