THE STAGES OF METHYLATION AND HEALING
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Freddd
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Adb12 comes in at the point where one gets MMA as a partial product. It appears that perhaps that can be confusing becasue perhaps the same break happens without the l-carnitine fumarate also yielding MMA (or not, hard to tell on that one without beibg able to test directly).
Right and that is the branch that leads to succinyl COA and then succinic acid, I am pretty sure.
Yes -- that's what has helped me finally tolerate these methylation supps -- TMG. I don't think I've tried any niacinamide since starting the TMG about 3 months ago (along with folinic, and a bit of methylfolate), so perhaps I should give it a try?
Folinic and TMG were the two main things that helped. I gave them a try after reading Jill James study with autistic kids:
http://ajcn.nutrition.org/content/80/6/1611.full
Well, we're all different of course. While I agree that we need some of every vitamin and/or mineral, 500 mgs of B3 would make me feel like death. I need more methyl donors...
Perhaps but contrary to information otherwise it only lowers SAMe through the reaction I listed to my knowledge. For me the tradeoff is important since I need ATP. I have tried 250 mg B3 before during the day and I feel more tired. I may be able to have some success with experimenting with that again now that the playing field is different.
Freddd
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Right, COA. AdoCbl is not consumed in this. It appears to act as a catalyst or something of the sort. If it breaks here, no ATP.
The catalytic power of AdoCbl lies in the homolytic cleavage of its weak (30 kcalmol) organometallic C–Co bond ...
http://www.pnas.org/content/101/45/15870.full.pdf
It is intriguing since when I have a Genova Diagnostics NutrEval test done is fall 2010 before any methylation, while my MMA levels were fine, my Krebs cycle had a large pile-up with alpha-keto-glutaric acid and really low or undetectable levels of succinic acid, fumaric acid, and malic acid as if the TCA was blocked at AKG. Makes me wonder ...
Lou
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Hi Fredd,
After reading your post about liver tablets I bought some called uni-liver from Argentinian beef. I noticed on ingrediants (too late) that it includes whey, doesn't say how much. Have I wasted my money, do you think the whey will be a problem for your protocol? Thanks.
After reading your post about liver tablets I bought some called uni-liver from Argentinian beef. I noticed on ingrediants (too late) that it includes whey, doesn't say how much. Have I wasted my money, do you think the whey will be a problem for your protocol? Thanks.
Freddd
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Hi Lou,
Whey MIGHT me a problem in any of several ways. "Whey, let me count thy ways...". The only way you will know is to do an A-B trial. Or if you have known problems with milk and milk products or specific problems with whey , you know in adavance. I don't think that small amounts of whey, used as a binder mostly, is a problem as a glutathione precursor but I could be wrong. My partner has developed a sensitivity to dairy producs that leaves here wirth terrible intestional inflammation and a whole diarhea and constipation cycle from a single piece of almond rocca which as some whey in it.
Good luck.
Freddd
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Hi Lou,
Looking up the exact specs on uni liver, it is NOT hte same as the one I mentioned made from pure liver.
http://www.iherb.com/Solgar-Desiccated-Liver-250-Tablets/11320
Solgar Dessicated liver contains 100mcg of b12 per 2 grams of protein. Uni-liver has 5mcg of b12 per 3 grams of protien. http://www.bodybuilding.com/store/univ/liver.html
I would say that you need to get the real thing. Uni-liver is not dessicated liver. It contains 1/33 of the amount of b12 of real dessicted liver. It must be way more whey than actual dessicated liver to bring the b12 so far down. I can't understand why bodybuilders are so enamored of whey.
Interesting. Long before I started on the methylation protocol, I found that SAMe was the only thing that helped me when it came to both mood and functioning better physically as well.
This morning I took one capsule of chromium polynicotinate w/breakfast, which has one milligram of niacin. I feel okay, but just that one mg caused a definite niacin flush about an hour later. Not sure what that means...but am definitely sensitive to it.
I also did that in fall 2010, and have the low succinic and basically nonexistent malic acid levels, although the AKG was right in the middle.
Maybe we should start a separate thread on the NutraEval panel -- 2+ years later, and I still can't make sense of half of it. (My niacin need was rated as '1' (on a scale from 1 to 10), folate at a 9, and b6 at 9 as well. But haven't been able to tolerate any b6 since a little after starting the methylation protocol...
Freddd
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Hi Dan,
You have given me one BINGO already. If you would like to try for another perhaps you could explain, in trems of symptoms, order of onset, intensiity etc of what happens with B6 and with p5p and the differences. This is so intimately wrapped up in interactions with methylfolate and MeCbl all sorts of things could be happening
A niacin flush is considered rare below 100mg I believe, but is also considered harmless. It is sometimes used as an active placebo to get a handle on people's interpretations.. A hyper response like that often says to me, here is a very deficient limiting item.
Lotus97
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Enzymatic Therapy has two Krebs Cycle chelates supplements. One is magnesium and potassium and the other is a multi mineral supplements. All the minerals are a combination of succinate, citrate, malate, fumarate, and AKG. After listening to the discussion here I think I'm going to try them out.
Reading this thread has me wondering if the reason DMSA makes me feel better is because of the succinic acid, rather than any chelating effects. Succinic acid is hard to find though, so far I've only found dodgy looking russian brands. DMSA made a whole lot of other supps tolerable all of a sudden.
Hi Fred,
I think if we're both thinking about the same thing, that first BINGO turned out to be a false one, at least for me, as folinic acid is helping me finally tolerate the methylation protocol -- and improve overall as well. Maybe for you eliminating it was very helpful? We're all different after all (I know, my broken record...).
B6 or p5p gave me serious and quite rapid neuropathy in my feet. p5p seemed to be worse than B6 in that regard. I did find a post on another site a year and a half ago where a woman was having similar symptoms -- and tested to find out her b6 was sky-high even though she had just started supplementing and could barely tolerate any amount -- that by taking high-dose methylb12 for several months (6 months???) she was then finally able to tolerate the b6/p5p.
Thanks Fred.
Lotus97
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I've heard of a few other accounts of people having problems with B6 although one of them was actually able to tolerate P5P, but not B6. I'm not sure about the others. I wonder what's going on.
Freddd
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HI Dan,
The bingo was real enough. You made a distinction that pointed to an understanding. However it happened, the QUESTION you asked about things was what brought the understanding via thinking about it and coming to all sorts of understandings thereby. So, we are looking at an accumlation of b6, a water soluble vitamin. The serum haflife is commonly goven as 15-25 days. It sure could accumulate, loosing only about 3% of serum level a day.
Taking very high doses of vitamin B6 may lead to nerve damage in your arms and legs. This condition, called sensory neuropathy, can cause abnormal and painful sensations in your extremities, loss of sensation in your extremities and difficulty coordinating movement. Fortunately, discontinuing large doses of vitamin B6 usually results in a full recovery within six months, according to the University of Maryland Medical Center.
http://www.livestrong.com/article/517581-negative-effects-of-too-much-b6-vitamin/
So what is happening that b6 builds up to such high levels.
You are correct that vitamin B6 is a water-soluble vitamin and that its half-life is 15 to 20 days. You are also correct that excess water-soluble vitamins are quickly removed from the body by the kidneys. Vitamin B6, also known as pyridoxine, is metabolized in the liver after it is ingested to its active form called pyridoxal-5'-phosphate or P5P. P5P is highly bound to protein in the blood, and drug that is bound to protein cannot be excreted by the kidney. So when your body gets the dose that it needs, it converts almost all that dose to P5P which is then tightly held onto by protein resulting in a half life of 15 to 20 days. Eventually, P5P is again metabolized in the liver to 4-pyridoxic acid which is then eliminated by the kidneys. It is when you take pyridoxine in excess that it is quickly eliminated. If the liver receives more pyridoxine than it can handle, additional drug reaches the blood without being converted to P5P. Pyridoxine is not as highly bound to protein and can then be more easily eliminated by the kidneys. Also, if there is too much P5P in the blood, more P5P will be unbound and also able to be metabolized and then eliminated until your body again reaches equilibrium.
http://www.netwellness.org/question.cfm/81287.htm
Why would P5P not be further metabolized and not elliminated? Why don't you go into full ellimination mode when there is excess b6?
Another question, why does b6 handle cholesterol differently from p5p and does it do so in your body? Do you have cholesterol abnormalities?
I don't have answers but do have some things to think about.
The bingo was real enough. You made a distinction that pointed to an understanding. However it happened, the QUESTION you asked about things was what brought the understanding via thinking about it and coming to all sorts of understandings thereby. So, we are looking at an accumlation of b6, a water soluble vitamin. The serum haflife is commonly goven as 15-25 days. It sure could accumulate, loosing only about 3% of serum level a day.
Taking very high doses of vitamin B6 may lead to nerve damage in your arms and legs. This condition, called sensory neuropathy, can cause abnormal and painful sensations in your extremities, loss of sensation in your extremities and difficulty coordinating movement. Fortunately, discontinuing large doses of vitamin B6 usually results in a full recovery within six months, according to the University of Maryland Medical Center.
http://www.livestrong.com/article/517581-negative-effects-of-too-much-b6-vitamin/
So what is happening that b6 builds up to such high levels.
You are correct that vitamin B6 is a water-soluble vitamin and that its half-life is 15 to 20 days. You are also correct that excess water-soluble vitamins are quickly removed from the body by the kidneys. Vitamin B6, also known as pyridoxine, is metabolized in the liver after it is ingested to its active form called pyridoxal-5'-phosphate or P5P. P5P is highly bound to protein in the blood, and drug that is bound to protein cannot be excreted by the kidney. So when your body gets the dose that it needs, it converts almost all that dose to P5P which is then tightly held onto by protein resulting in a half life of 15 to 20 days. Eventually, P5P is again metabolized in the liver to 4-pyridoxic acid which is then eliminated by the kidneys. It is when you take pyridoxine in excess that it is quickly eliminated. If the liver receives more pyridoxine than it can handle, additional drug reaches the blood without being converted to P5P. Pyridoxine is not as highly bound to protein and can then be more easily eliminated by the kidneys. Also, if there is too much P5P in the blood, more P5P will be unbound and also able to be metabolized and then eliminated until your body again reaches equilibrium.
http://www.netwellness.org/question.cfm/81287.htm
Why would P5P not be further metabolized and not elliminated? Why don't you go into full ellimination mode when there is excess b6?
Another question, why does b6 handle cholesterol differently from p5p and does it do so in your body? Do you have cholesterol abnormalities?
I don't have answers but do have some things to think about.
Right SAMe is known for that. But you need to sleep also. If 1mg of niacin sets you off (you may want to repeat with a pill with only 1 mg of actual niacin or titrate in water to be sure it is the niacin), then that suggests you are hyper low. Do you take any B3 of any form at all? B3 is so critical to so many things.