Is there anything published in a journal?
@Valentijn -
It was my intention to reply far more quickly. I wrote it and that was a few days ago when suddenly what I had WRITTEN disappeared into cyber space with a "internal server error" from PR.
The last 8 weeks has been non stop misery with what appears to be antibiotic injury to my liver and/or maybe other factors unknown, a repeat of 18 months before. Tests; and more tests and trying to figure out what damaged my liver and what to do. I've been too sick to do much of anything.
By late 1987 I had published a variety of technical reviews and computer articles in BYTE, S-100 BUS JOURNAL and SUPERMICRO. I was invited to write a significant article on reusable code for the Encyclopedia of Microcomputers, a foundational article for Oject Oriented Programing which was developing but not yet named as far as I know. I got too sick to write it and had to excuse myself.
Peer reviewed research articles are all asking questions. Then they go through asking the questions in a very specific way and then attempting to give the research evidence as proving or disproving their hypothesis ("question"). Disproving a hypothesis is also needed to find out what works and what doesn't.
Often the type of question is of the "what changes occur"? A couple of years ago I saw a study of a new brand Cyancobalamin. The company had "proven" that their brand of CyCbl with an amendment for improving absorption did in fact double the passive absorption; from 1% to 2%. Isn't that wonderful, and they proved it. My questions was "Why was it even worth spending one cent on this research?" If it had any effect for me it would be to ruin my health twice as fast.
In any case, this type of study "proves" it has hit the target, it increases absorbtion. However, there is no evidence of improved healing.
It doesn't change the 10 mcg a day that the body MIGHT be able to convert to MeCbl & AdoCbl from CyCbl. It's the same 10 mcg that is converted from 1000 mcg CyCbl injection which research tells us is 99% excreted unchanged. I trust that the numbers are "real", that they ran the trials and got the results they claimed. Isn't the point about improving health? Or is it to ask questiuons that hit your desired target suggesting they might do something. Injected CyCbl is about 1% as active as an injected five star MeCbl. Daily oral 1000mcg CyCbl was "proven" decades ago to absorb enough to equal the "steady" serum levels of the monthly injection for days other than the day following injection, 99% excreted unchanged in a day or two.
I realize that one has to use surrogate endpoints. As a systems analyst in health care I used all kinds surrogate endpoints. Antibiotics are supposed to kill the bacteria and not the patient. If it gets rid of the bad bacteria it is a success. If it causes potentially eventuial toxic liver damage and even death, not so sucessful. I ran my own longitudinal study of my treament by 100+ various doctors over 20 years,their efficacy at diagnosing and treating what I have now demonstated to be nutrient deficiencies by following a plan of nutrition that healed, visibly. I can't prove I would have died at some time from 11 years to 24 years after diagnosis of congestive heart failure. I can't prove that another 13 years of ascites would have killed me.
But I did survive with a damaged liver and had problems all over again from antibiotics. My internist I started with in 2002. I looked like death slightly warmed over at that time. At my first appointment following MeCbl startup, about 3 weeks after May 21st, 2003, everybody in the office commented on how different I looked. They could all see additional healing at each 3-4 week interval I was having appointments. He said after a year "I have never seen anybody come back from so far over the edge". After several more years of healing my ex wife who hadn't seen me for 9 months came over to see me. I opened the door for her, she looked at me and looked at somebody else she knew there and asked "Where is Fred, I was supposed to meet him here at 1:00? I said "Right here" and her jaw dropped. We had been married for 33 1/3 years (the breakable vinyl anniversary.)
Surrogate endpoints that are "subjective" especially for therapies that don't directly affect readily observable symptoms and signs can be difficult. And worse, it is all statistical.
My object was never to provide a few little foundational bricks in a wall that wouldn't be figured out for anothger 100 years at the rate science was getting B12 and folate totally wrong. I needed to HEAL. NOW! Or I was going to die, soon. So I needed a completely different approach than the contributing of small bricks. I needed to do the research in a way that it gave me answers every day that might make the difference, that could make a change that would keep me alive for another day or week or year or decade. I had to gain days of life faster than I expended them doing the work.
Research is supposed to form a chain of logic. The current research is supposed to be the basis and one builds off of that. So that now, after 70+ years of B12 and folate research one would hope that they have been buidling a valid logic. That vaild logical chain requires valid citations and that important research be validated by additional research. The chain of nutritional logic that was built since 1930 on folates and cobalamins one would think that 87 years of scientific researxch would actually be able to recognnize B12 and folate deficiencies and fix them.
I had NOT A CHANCE IN HELL of healing on the "scientifically PROVEN" B12(CyCbl, HyCbl) and folate (folic acid). So by deciding to ignore symptoms and the people with responsive to CyCbl symptoms, and insist on qualifying by tests, they elliminated the ability to even recognize the symptoms of B12 deficiency and said "DON'T LOOK THERE" and go by tests only, they could cut down the number of people to be treated by something like 95%. Of course that caused 200 symptoms to become "mystery diseases" instead of nutritional deficiency symptoms, and made millions of people have long term chronic illnesses that first they accuse people of being fakers who have them as they explode in frequency, many lives ruined and many killed.
As a contrarian I paid attention to all those "so-called" non-specific "placebo" effects and they told me everything. So it worked like this.
approximate days
Already taking a complete set of vitamins including CyCbl and folic acid.
Day 1 - Find out that MeCbl works on more than 30 symptoms immediately, vast increase in energy, lifelong depression started lifiting, eyesight brightening, literally.
Day 2 - Even more symptoms affected by MeCbl
Day 3 - A severe blossoming of hypokalemia symptoms happened, titrated to the necessaRY 1200MG of potassium daily, other symptoms (methylfolate deficiency) explode also, but of unknown cause.
Day 4 through 270, titrate MeCbl and alternating with potassium
Day 270 - AdoCbl - another 50 or so symptoms start being affected with a vast increase in energy.
Day 273 - A large increase in potassium, a large increase in folate deficiency symptoms.
Day 300 400mcg l-methylfolate, blew my socks off. All those worsening symptoms got a little better.
Day 303 - Folate deficiency starts worsening in other compartments.
And on it continued as I started L-carnitine fumarate and titrated folate as more healing took place. And after the Deadlock Quartet was established in all compartments, my muscles grew back, then it was adjusting all the b-vitamins by titration to maximum effectiveness. So I I have had 20,000+ trials in 14 years, running as a system.
Every day I learned something and was able to correct my titrations towards desired results.
All the vitamins and minerals are all dependent on each other. I had set out to make a dynamic working system, not snapshots of single items having a "provabler" microscopic effect that adds up to a non working system becasue of the way they are tested,
During the 14 years to date I do urine colorimetry multiple times per day. It tells me when I am becoming for unknown reasons, periodicly folate deficient so I can up my dose for a few days each 2 weeks. It gives me a one or two day warning when something is going wrong.
With titrations effects being observable in 1 to 4 days, I may be doing several different titrations per day and several colorimetries and so forth. Finding that the meaningful period for gather nutritional defic iency data and responses takes 4 days per cycle. I look for the fearliest saymp[toms to show up, not the most severe by letting it run a month or a year before adjusting. So all in all I have run thousands of trials each year. First there is the correction of the earliest to respond syumptoms on day 1, then there are the increases in refeeding syndrome sympotms, their correction by day 4, and once I distinguished the potassium and folate, they both could be titrated together.
So, in the 30s, they started looking for the causes of pernicious anemia nd then pinned down liver extract concentrate as containing "protein mystery factor". More studies with liver extract concentrate demonstrated that women with postpartum depression could be released from the hospital CURED, in 3 days of. A similar study with hallucinating schizophrenics also showed that they could reach discharge criteria in 3 days of the protein mystery factor in the liver extract concentrate. And it turned out that 2 liters of raw liver puree daily could be used as treatment for pernicious anemia.
When Cyanocobalamin was identified as protein mystery factor it wasn't until 1971 that the mistake leading to that failure of the correct identification was known. However, CyCbl was tested to replicate the post partum deptression and the hallucinating schizophrenics and failed, and failed. It was clear that CyCbl wasn't "protein mystery factor". It did get around pernicious anemia for about 2/3s of sufferers after a while. The other third simply died. Liver extract concentrate could work on 100% of those with PA. Some time in 1950s when they ignored the failure and suddenly the failure to validate failed to matter. They got a disastrous Nobel Prize and became sanctified.
So somehow, despite total failure at replication of the effects of "protein mystery factor" suddenly CyCbl was a complete success. They lost all my trust while I was still a kid suffering from AdoCbl, MeCbl and l-methylfolate deficiencies. Then when correctly identified in 1971 as Methylcobalamin and Adenosylcobalamin, did they get rid of the fraud, CyCbl? Nope. And that is why my body suffered from the degeneration diseases of CFS, FMS, IBS, and so on for decades, why I've been sick most of my life.
Research based on the logic chain of CyCbl replacing the effectiveness of "protein mystery factor" is bogus. CyCbl being the human active forms of B12 is BOGUS. This reveal of the real B12s that works for essentially 100% of persons when cofactors are present, rather than the official b12 that works pretty poorly for about 2/3 of the people in any given study.
Of course what would one expect when people with lots of responsive symptoms that are defined as placebo when improved by a CyCbl injection, thereby excluding many people from studies becasue they had the wrong numbers and too many symptoms other than pernicious anemia, the ONE thing CyCbl help some people semi-reliably. Instead 200 symptoms are made orphan symptoms since they have been defined as not CyCbl deficiency and not folic acid deficiency. Instead they don't really exist and they are all placebo and so when we have refeeding syndrome when we start to heal 200 symptoms, we must be lying or something. I've had plenty of doctors say that.
I want to give you some background of why this that I have done was done the way I did it. I had been working on the problem from 1977 or 78 to 2003 and came up with a hypothesis which was only sort of correct and evolved. For 25 years I read all the research from 30s and onwards on B12 and folate. In 1979-81 I did a 2 years trial of dessicated liver tablets, 100 per day. It confimed my hypothesis, the mystery item in liver was not Cyanocobalamin and folic acid. It took six months for the lights to come on each time. Each time I was too sick to continue each time (the ahha to refeeding syndrome now recognized). I hypothesized that AdoCbl, MeCbl and L-methylfolate was the mystery item. By then I had found and read the 1971 paper describing the identification of REAL B12s and that CyCbl was a lab mistake.
I investigated. A small vial of MeCbl was available for experiements at high cost, like $1000, from France. I continued doing trials on every nutrient and nothing made any difference. I crashed in December, 1987. In 2003 I was 10 years into congestive heart failure (cumulative 80% mortality at 10 years post diagnosis). I tried MeCbl. I knew in less than an hour that my life was changed, but only if could stay well. I was prepared for hypokalemia this time. However it took until 2016 to fully solve the folate contradictory symptoms.
I started the N=1000 history questionaire, a few days after the first pill of MeCbl blew off my shoes. It didn't start with any specific number, didn't start with any specific objective except to figure out if others had similar responses to me and learn how to make the "placebo effects" of healing become the real thing. So I took potassium and it cleared up the potassium deficiency symptoms and back to MeCbl inspired healing. I figured to match it up by patterns of symptoms. If it worked as a good questionaire for detecting b12 deficiency, that could be the basis of some data mining patterns for groups.
I was perhaps 30 histories into things and Enzymatic Therapy Methyl B12 became unavailable, backordered for months. So everything else was put on hold doing A-B comparisons for 10 brands with 5 people. I found Jarrow. For the next 5 or 6 years I found another 10 or more items that made large differences, as the most deficienct, next in line. Every one of them was in turn, a most deficienct item, and usually alternated with potassium and an increased unknown which turned out to be l-methylfolate. I started the injection trials in 2005, again necessity. While my body was healing, my CNS was getting worse. The Japanese high dose MeCbl studies pointed the way. And so did the 1-100 mg injection series. I found how much it took to turn on CNS and cord healing to some extent. There was a maximum effective amount. And thousands of comparative urine B12 amounts; 10,000 in all of injections and oral mucosal. I ruined a bunch of perfectly good injections of MeCbl by exposing it to light and seeing where the acne type lesions appear first and then getting rid of it again, over and over to find the curve. Then there was the glutathione trial that turned into how to cause demyelination experimentally.
It took years to do 1000 interviews and in the end there were subdivisions, such as 1 and 5mg, 3mg of AdoCbl with and without MeCbl, and so on. I was working on getting answers as quickly as possible to save my life.
And each compartment that had healing started also caused more deficiency symptoms, potassium and methylfolate and copper and boron and other things. I have worked on healing my body full time since the end of 2002 when I could no longer work reliably. The experience of refeeding syndrome, collecting 1000+ histories, 10,000 colorimetry trials, thousands of titration trials of l-methylfolate and folic acid, and folinic acid and extracted from veggies b-complex, 1 mg to 100mg injection series of MeCbl, a 0.1mg to 60mg 3 times a day injection series, several thousand oral mucosal absorption and colorimetry trials, "how to ruin MeCbl with light", "how to unintentionally cause demyelination taking Glutathione", designing an accurate pharmacokinetics model that complies with all the research. And so on would have taken 40-50+ years if all done serially, and another decade or two to write up all the different studies.
I was building a system for healing, each step based on the previous step, and much previous research on "B12" and "folate" was useless. CyCbl, HyCbl and folic acid give only very poor answers about L-methylfolate, AdoCbl andf MeCbl. And while there is some research and practice on refeeding, mostly in nursing journals, it was good for a list of deficient nutrients but not how to use them. Most of it was about using food for starvation rather than augmented nutrition of vitamins when the starvation was of specific nutrients, not calories.
To survive I had to solve it in real time, I didn't have the time to do 10 PhDs worth of research and writing and actually save my life.
