Hi Fredd, thanks for the very detailed reply to my query - im not able to read through it all in one go, will have to go over it a few times. I wonder if you are suggesting that excitotoxicity doesnt exist? it was explained to me as a build up of glutamate, causing the symptoms. I understand your point about perception, but my symptoms where not at all the same as yours - my symptoms are of extreme agitation - as if i had drank 10 espresso's and eaten a LOT of sugar. I dint actually notice it until i had taken 500mcg a day (sub cut) for 10 days - up until that point i noticed no real difference. Alongside the bad side effects i did feel great as well for a couple of days. Now ive gone back down to every other day, half dose i dont have the bad effects or much of the good. The side effects were literally unbearable and on the 3rd day i had to taker a valium - which totally sorted me out.
Justy
Hi Justy,
as if i had drank 10 espresso's and eaten a LOT of sugar.
Funny you should mention that. To become functional in social situations 9 or more years ago I used to have 3 quad espresso shot cappacinos with sugar. My onset of mb12 the first time and for a several months until I titrated to equilibrium was on intensity alone, very much like a goodly dose of LSD, say about 1000mcg, one hell of a rush.
are of extreme agitation
Agitation is a RESPONSE. Mb12 was highly excitatory because it is turning the nervous system on. If your nervous system is carrying 1% of "healthy normal signal" the volume of the receivers has to be turned way up and that causes a vast increase in noise in which the signal is almost lost. If it goes up to 5% with a dose of mb12, this is a massive increase. In the sensory area, 1/2 of a doubling of intensity is a Just Noticable Difference. Let's use taste of sugar for example. If you have one cup of coffee and you can taste the effect of 1 teaspoon of sugar, the difference between 1 and 1.33 tsbs would be barely noticable. If instead it goes up to 5 tsbs it is likely way too sweet. From 5 tsbs to 6 tsbs would not be perveivable When one is very deficienct going up from 1% to 5% is a massive change. We perceive things based on percentage change over base. To have the same change from 5% it would have to go to 25%. However, that same difference isn't available again so when it gors from 25%$ tp 50% it is noticable but only somewhat stimulating. When it goes from 1% to 50% it knocks your socks off.
Perceived differences are what our nervous system see. We see something moving that might be quite invisible if holding still. We can read a newspaper by the light of a candle or full direct sunlight. If it changes suddenly from candle to sun it is temporarily blinding but not actually blinding unless one looks directly into the sun.
500mcg a day (sub cut) for 10 days - up until that point i noticed no real difference
Most likely that was how long it took for enough mb12 to penetrate the CNS to cause perceptual changes.
Now ive gone back down to every other day, half dose i dont have the bad effects or much of the good
Exactly. You are not getting enough b12 into the CNS for it to start restoring function.
I wonder if you are suggesting that excitotoxicity doesnt exist
Not at all. I am saying that calling perceptual changes caused by mb12 excitotoxicity is a misaplication of that word. Here is the question for you. How does one get from 1% to 100% without going through the adaptation process?
If you were to take the approach of escalating doses I would make several predictions. One of them is that increasing the dose does NOT cause a linear increase in an excitatory response. Approximately each doubling of dose will cause perhaps a 25% increase of effects and that falls off dramatically as the effect approaches the limit. A 10mg dose (injected) won't be perceptually different from approximately a 3mg injection. The difference is how much is retained, about 1% of the dose each day. If you injected 10mg a day, I would predict that within 2-4 weeks it would have no excitatory effect at all.
Dribbling it in maximizes the excitatory effect as to how intense and duration. At 250-50 mcg a day the onset excitatory mode will last indefinitely. At 10mg a day it will start to falloff in a matter of days and end in a matter of weeks. You are taking a dose that is at probably 80% of maximum effect and will remain there for months and months becasue it isn't a large enough dose to actually bring tissue levels all the way back up. If you were to take a 10mg Source Naturals adb12 you can get rid of the mitochondrial portion of the excitatory response (perhaps half of the total) in a week or less. Adb12 really only does 1 thing, processes fats for energy. More than there are receptor sites for in the mitochondria are quickly elliminated. Equalibrium of adb12 can be reached in days. That's what makes testing different brands so difficult; one has to starve ones self of adb12 for a month to see any change from it at all whereas mb12 symptoms return in no more than about 3 days withourt.
However, your hypersensitivity could be put to good use here. You could do comparative brand testing. You will be able to tell the differnce between various zero start to 5 star mb12s. After your body is no longer starved for mb12 it will lose the hypersensitivity and the only way you will be able to tell the difference is how fast symptoms go away or come back. Unless you starve yoursef into severe deficiency you will never again be hypersensitive as you are now. I and 4 other hypersensitives did all the brand testing. We all agreed 100% becasue we all had the same stuff happening in the same way. How we each interpreted them was different. If I had quit because of my hypersensitive reactions I would be dead now and we would not be having this discussion. You might find that a 3 star brand won't have very much effect and that you can take saturation doses from the beginning. Then when you switch to the 5 star to maximize healing you will only feel a differential effect, not the major onset effects. I have helped hundreds of people work through this. I have yet to see anybody who doesn't loose this onset excitatory effect when they reach equilibrium/saturation if they do it in this way. Superior brand and NOW Foods brand of mb12 are both 2-3 star mb12 or were at the time of my original testing. If you were to do a 10 brand test series it could be very useful for people because the brands may have changed in 8.5 years.
MB12 appears excitatory because it increases neurological signals. It is not TOXIC so it is not excitotoxicity.
methylcobalamin glutamate use this as a search string in google scholar
Methylb12 PROTECTS against glutamate toxicity
Protective effects of a vitamin B12 analog, methylcobalamin, against glutamate cytotoxicity in cultured cortical neurons[DOC] from yimg.comA Akaike, Y Tamura, Y Sato - European journal of pharmacology, 1993 - Elsevier
Abstract The effects of methylcobalamin, a vitamin B 12 analog, on glutamate-induced
neurotoxicity were examined using cultured rat cortical neurons. Cell viability was markedly
reduced by a brief exposure to glutamate followed by incubation with glutamate-free ...
http://www.sciencedirect.com/science/article/pii/0014299993909258
The effects of methylcobalamin, a vitamin B12 analog, on glutamate-induced neurotoxicity were examined using cultured rat cortical neurons. Cell viability was markedly reduced by a brief exposure to glutamate followed by incubation with glutamate-free medium for 1 h. Glutamate cytotoxicity was prevented when the cultures were maintained in methylcobalamin-containing medium. Glutamate cytotoxicity was also prevented by chronic exposure to S-adenosylmethionine, which is formed in the metabolic pathway of methylcobalamin. Chronic exposure to methylcobalamin and S-adenosylmethionine also inhibited the cytotoxicity induced by N-methyl-D-aspartate or sodium nitroprusside that releases nitric oxide. In cultures maintained in a standard medium, glutamate cytotoxicity was not affected by adding methylcobalamin to the glutamate-containing medium. In contrast, acute exposure to MK-801, a NMDA receptor antagonist, prevented glutamate cytotoxicity. These results indicate that chronic exposure to methylcobalamin protects cortical neurons against NMDA receptor-mediated glutamate cytotoxicity.
Clinical trials of ultra-high-dose methylcobalamin in ALS].Y Izumi - Brain and nerve= Shinkei kenky? no shinpo, 2007 - ncbi.nlm.nih.gov
... There is no effective drug therapy for ALS, although riluzole has been shown to prolong life in
sufferers, without tracheostomy. A vitamin B12 analog, methylcobalamin, has a protective effect
on cultured cortical neurons against glutamate-induced cytotoxicity. ...
http://www.ncbi.nlm.nih.gov/pubmed/17969354
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting both upper and lower motor neurons. Weakness may begin in the legs, hands, proximal arms, or pharynx. The course is relentless and progressive without remissions, relapses, or even stable plateaus. There is no effective drug therapy for ALS, although riluzole has been shown to prolong life in sufferers, without tracheostomy. A vitamin B12 analog, methylcobalamin, has a protective effect on cultured cortical neurons against glutamate-induced cytotoxicity. We have shown the ultra-high-dose methylcobalamin (25 mg/day i.m.) slows down the progressive reduction of the CMAP (compound muscle action potential) amplitudes in ALS in the short term (4 weeks). The latencies of SSR (sympathetic skin response) were shorter after treatment (50 mg/day i.v., 2 weeks). In the long-term effect of methylcobalamin (50 mg/day i.m., twice a week), the survival time (or the period to become respirator-bound) was significantly longer in the treated group than in the untreated. Larger-scale randomized double blind trial was started in Japan in order to evaluate the long-term efficacy and the safety of ultra-high-dose methylcobalamin for sporadic or familial cases of ALS.