Once upon time back in the dark ages, for me in 2003, I started MeCbl all by itself. Not exactly all by itself, but, without AdoCbl, L-methylfolate or LCF. I was taking all the basics, vitamins, minerals and fats. In a backwards look I can see the layers. I had partial methylation block, methyltrap and partial ATP block at the start. I was skin and bones balloon all filled up wirh water and watery fat. I had to rest halfway up a flight of stairs. I needed help in the shower. I couldln't comb my hair or shave, arm and shoulder pain). I could barely brush and floss. When I started taking MeCbl I had incredibly intense neurological startup. I went from depressed to a realization "I could be happy now" in an hour.. The buring mouth and burning red tongue and and burning bladder stopped burning in 10 days, months longer to heal all the way. I regained a normalized sense of smell and taste. The lights literally came on that day have have stayed on since, going on 10 years now. Previously they stayed on several times for a few months during the desiccated liver trial. My burning muscles had the fire go out that first day and the burning subsided 100% in 10 days.
Mentioned at the time by me and orthers, was skin lesions. The acne type lesions started spreading and got much worse and infected. The IBS was terrible then because of food intolerances and IBS as such. The angular cheilitis got ever so much worse. So the methyltrap was broken but the partial methylation block was not. As I apparently do convert MeCbl to AdoCbl reasonably well (this is based on CURRENT understanding, at the time I thought anything not 100% effective was not good) and the partial ATP block reduced to about 75% of what it had been, enough to allow overdoing and crash and recrash. The partial methylation block remained in place. A person can have hypokalemia at the same time as partial methylation block in these reactions. They are not mutually exclusive.One layer can be healing and others breaking down at the same time.
Basically I went from constant mild folate specific symptoms to severe donut hole paradoxical folate deficiency. I took more folic acid but that didn't help at all and I had no idea at all. I focused on what I could affect. The inflammatory muscle pain continued or worsened. Joint pain worsened. MCS, asthma, allergies varied all over the place but didn't go away for several years more, after adding AdoCbl and 400mcg of methylfolate. That was when I started needing noticably more potassium. I think I was doing 200mg twice a day originally.
With just Mecbl added to basics, SACD continued to worsen, muscles contiuned to atrophy, edema and congestive heart failure continued to worsen. blood pressure WITH CoQ10 got dangerously high right away and I had to discontinue CoQ10 until AFTER the AdoCbl, LCF and Metafolin were in place (repairing the inferred cardiomyopathy of congestive heart failure). To start, or complete, tissue healing on all levels took the entire Deadlock Quartet.
Ok that makes sense. I understand more now. You are saying with only the methyb12 and other basics you ended up with some definite improvements in some ways but drove yourself into folate insufficiency that was made worse by folic acid and plant folates and only improved when you brought in sufficient levels of the deadlock quartet. Got it.
If it DIDN"T use fatty acid chains, then the LCF would make no CNS difference much lass a massive energy difference. Further AdoCbl processes the fatty acids into the form needed for myelin repair in the brain and elevated CSF MMA wouldn't be apparent in Parkinson's, a suspected cause of Parkinson's. For people so afflicted AdoCbl and LCF make an unbelievably huge CNS difference in CNS healing and even many functional items.
I think you are mixing two things up here to reach your conclusion. You are assuming that fatty acids are used directly in brain energy metabolism because you and others feel better and think better on LCF. The two are not necessarily linked.
Your brain / CNS and body are interconnected. If your body has more energy and vitality, your autonomic nervous system will be happier. And vice versa. There is often a false division when looking at clinical symptoms sometimes. The BBB prevents most fatty acids from getting across. The lipid regulation in the brain is very tight. Has to be. There are transport channels for choline and acetyl COA but not to be used for energy metabolism. More for myelin, membranes and acetylcholine formation, etc.. So yes fatty acids can help the CNS but is it NOT for energy. That is glucose and to a lesser extent ketones.
I agree adb12 is important. But adb12 has importance to the health of the mitochondria and peroxynitite removal. I don't dispute the elevated MMAs in Parkinson's, et al. But that does not say anything about the primary metabolic aspects of neurons. Not even close. Also why do you never bring up the high levels of microglial activation and inflammation now know to be signatures of most of the CNS diseases you listed. You focus exclusively it seems on the MMA levels. Why not the inflammation? Can't that tie back into adb12 / BH4 and peroxynitite removal and the low MMAs are a correlative finding?
As far as carnitine goes with the brain you cannot even ABSORB carnitine in the CNS unless either (a) it is acetyl-carnitne or (b) you have a very leaky BBB. However, if someone has a very leaky BBB, I have no idea how they will react to l-carnitine (note the fumarate will be long gone by the time anything gets past the leaky BBB). Will it be used as a primary pathway for energy metabolism? Dunno.
Elevated CSF MMA in ALS and Parkinson’s and several others (I need to update that survey) is prominent. And the effects of AdoCbl and LCF is truly massive for Parkinson’s and” pseudo” or perhaps “pre”, Parkinson’s and affects dramatically dopamine and response in the limbic system. It’s practically a guided tour of the emotions of the limbic system. Even those not going down the Parkinson’s pathway, no MMA in the CSF, can have major response to CNS doses of AdoCbl and LCF. If a person has a specifc CNS response to MeCbl, most of those folks will have a major CNS response to AdoCbl ANDOR LCF. There are those with no significant MeCbl CNS response who will have massive CNS response to AdoCbl and LCF (down to below 1 mg total dose, HYPER response to minute oral doses of LCF). Your dismissal of this idea is a 100% missing the boat response. While it doesn’t prove anything, it is approximately 90+% predictable from symptoms. I don’t care what the diagnoses are. Those are very poor at predicting these responses generally. For those on the MeCbl & L-methylfolate pathway (SACD, MS) the response to AdoCbl & LCF is reduction of depression and relative euphoria. I call it relative euphoria because each level seems like “Ah, it feels so good that at last I feel good”. “Good” is relative. And that can happen at each step. Compared to feeling indescribably bad, feeling 0.25 better can be euphoric. A middle aged lady I know with MS tried these things, and did the worst possible thing. She danced exuberantly all evening and overdid it outrageously and crashed hard the next day. That is also predictable. I did the same thing over and over. It took me a year to get that tendency under control. Don’t increase distance walked by a mile. Just keep stepping it up at 50 feet a day. It is the most common cause of repeat crashes, feeling so good so suddenly that our common sense goes to the winds.
Again inflammation and microglial activation is elevated also. And I am sorry again to have to re-iterate this but ... without a leaky BBB (which admittedly may be a big component of all of this) you cannot absorb LCF in the brain. It does not cross a healthy BBB. It just doesn't. Now why the LCF has such a dramatic effect on the limbic system as you have observed, I do not know. If it is not an indirect effect through the periphery (which is not impossible given how there is a big chunk of the ANS living in your abdomen) or it is not due to a leaky BBB ... then I don't know why.
Btw I am not sure why you think I am dismissing anything. I am simply trying to understand things. Clinical trial and error is not enough for me being a physicist and bioinformatics professional. Sorry that is just the way I am built.
Nor did I intend my simple response about the Krebs cycle and brain metabolism to in any way be considered adversarial. In fact my intent was to SUPPORT your idea that mitochondria in the brain are relevant. Let me repeat that: I was supporting you.
I have no idea why Rich Vank would ever think mitochondria in the brain are not important for neuronal health. Of course they are. Is adb12 important? Sure. But your conjecture that adb12 is important BECAUSE of the MMA pathways alone is by no means a given. It simply is not going to be the primary adjunct to the Krebs cycle. It could be a block if too low but it will never be the main fuel ... that is all I was trying to say by those comments. Just like burning fatty acids is not the main fuel in the brain. If your only conclusion based on your clinical experiences and people's reaction to carnitine is that burning fatty acids in the brain will bolster the Krebs cycle or the MMA pathway being stimulated will power the TCA on its own ... well then let's just choose to disagree.
In order to form a set of hypotheses that allows one to heal, build a conditional system and model that assumes AdoCbl and LCF with omega3 fatty acids are absolutely critical to the brain affecting personality and moods rapidly. With this in place the understanding of what is happening in the brain with these various nutrients becomes predictable. Build the pragmatic model that works, then look to see why/how it works. I did check out each and every item in the literature before I added it. The difference is I interpreted severe side effects of certain kinds in a different way. The only “mistake” I made was glutathione. Everything else was dead on target. Without the extreme responses of myself and 9 others to glutathione I doubt that I would have recognized paradoxical folate deficiency. I built these items on one at a time, each one having to fit the model and prove it by working consistently on certain groups of symptoms. I build models and systems, not theories. My opinions and theories are just those. The point is I have adopted all sorts of theories and rejected others based on what fits. The model I have built is highly engineered, NOT THEORATIZED.
Instead of having a theory and throwing mud up on the wall and analyzing in microscopic detail and statistically saying “0.5% of people have an unexplainable hyper extreme response to LCF of an intolerable level of anxiety and had to be removed from the study. At only a 0.5% rate of such response it is just another side effect and matching placebo rates of anxiety and is only found in those with pre-existing anxiety and so can be safely ignored by prescreening for anxiety, if it isn’t a placebo effect”
I would say “Those people with a specific profile of symptoms including anxiety have a range of extreme responses to LCF at an approximately 95% predictable rate with a small percentage having this response unpredictably and a small percentage not having the predicted response of a mood sequence of anxiety, fear, panic, anger, rage, homicidal rage and severe depression over a 18 to 72 hour period. It is reproducible at will. Further refinement of the screening process may improve the selectivity.
What is so wrong with theory? Theory and experiment go hand in hand. Again I don't doubt your observations. I also NEVER in this or any other posts challenged your deadlock quartet idea. I find it quite attractive. I am just trying to understand why things happen. Is that so bad? Engineering is great but civilization would not have gotten very far if there wasn't theory as well to work with it.
Anyways I already stated my points about adb12 and LCF with respect to the brain. L-carnitine is not absorbable through BBB unless the BBB is damaged ... which may very well be the case for many with CFS and is KNOWN to be the case with MS, ALS and is now being suspected with Parkinson's. The Omega 3s are important for sure. Ironically the DHA is a major component in BBB integrity. So ... maybe a leaky BBB is highly relevant to this discussion. Maybe people with a leaky BBB hyper-react to LCF at the limbic system level. Which if so means I am probably in for a rough ride since my Stiff Person Syndrome only occurs because of a leaky BBB, but that is a separate issue.
Then when we get to Biotin which appears to be a “critical” cofactor because it can basically shut off ATP response by it’s relative deficiency or insufficiency. In these terms than being able to tolerate 4000mcg of biotin when some other critical cofactor is missing and that is no longer broken and biotin tolerance goes down to 1000mcg because it is NOW what then makes the difference, the most limiting factor. This is fits perfectly into the bottom up system I have been building. Then the next step is figuring out what is causing the shortage of biotin and test that. If that works, it kind of confirms the hypothesis and extends the system. Built piece by piece, from the bottom up leads to a working engineered system. It is also something I can walk into an HMO with and tie my compensation by obtaining specified results in XX% of people, based on indirect measures such as lowered pharmacy costs and less utilization all the way around on the selected persons.
No argument. I already posted how biotin affects the Krebs cycle since there seemed to be some confusion on the forums about it. Biotin plays a critical role in the brain. How else do you think the pyruvate from glycolysis gets into the Krebs cycle in the brain? I also agree that biotin can really speed things up and so there is an important balance with other factors. No doubt. Definitely is a good avenue for further research. As would any of the critical cofactors for entry into the Krebs cycle. Biotin though may be of more importance due to its pivotal role in the brain. Btw biotin is also now believed to be a critical cofactor for glutamine synthetase. That could be huge for the brain function as well.
You are working towards a different goal with different measures. I don’t have to prove a thing. All I am doing is to produce a system that is predictive of desirable results at a given or above a certain rate. Further the screening system must be cheap and a mass screening system. The AMA etc says in essence “testing everybody for b12 is not cost effective as it only finds 1% of population and they are expensive to treat forever with all the comorbidities”. 100% of that is based on folic acid, CyCbl and HyCbl. There is zero expectation that anybody will actually heal or reduce expenses. So detecting and treating b12 deficiency is very difficult, expensive and not worthwhile as they won’t really get well anyway unless you define that as getting MCV< 102 these days and maintain serum cobalamin level at or above 300pg/ml just before the next injection or with oral CyCbl tablets. By these definitions it is a complete surprise that mecbl and AdoCbl are completely unpredictable based on CyCbl and HyCbl experience.
I am not sure why this even came up here. I have no clue why MCV is showing up here. I have no disagreement about your views of cycbl or hb12. Nor does what I am saying about the Krebs cycle and brain metabolism have anything whatsoever to do with cycbl or hb12 or their malignant use by the medical community. I am simply talking biochemistry. Ironically a new outsider reading your post would presume that I must disagree with everything that you propose. Huh? Far from that. So why all of this?
No one said you have to prove anything. Thought this was an open forum with dialog. Understanding is important to many of us. Again my comments were to SUPPORT your side of the argument you had with Rich Vank in that brain mitochondria are directly relevant to neuronal health.
Peace.