There has been a lot of talk of late about folate and Parkinson’s and lots of confusion. I first mentioned the effects and links about 3 years ago. I know a lot more now. Below I attempt to describe it as it happened, with many variations, from descriptions given me as it happened by a number of people. There are many variations and I offer my hypothetical model using partial methylation block, methyltrap and partial ATP block to put it together. This happens with a multitude of variations. The diseases that we can link from certain characteristics in common are these; CFS, FMS, SACD (Sub Acute Combined Degeneration), MS, Parkinson’s, (Progressive) Supra Nuclear Palsy and ALS. All of these specifically have low cerebral spinal fluid levels of cobalamin. MS has elevated homocysteine. Parkinson’s, (P)SNP and ALS have elevated homocysteine and elevated MMA. Elevated homocysteine signifies depressed methylation from partial methylation block or methyltrap. Elevated MMA in the CSF signifies partial ATP block from lack of AdoCbl and/or LCF. In addition to the low CSF MeCbl and/or AdoCbl, there may also be low body levels independently of the CSF. CFS, FMS, SACD (Sub Acute Combined Degeneration), MS, Parkinson’s, (Progressive) Supra Nuclear Palsy all have the same basic CFS/FMS symptoms. Virtually all of the symptoms of these diseases are also MeCbl, AdoCbl, l-methylfolate and LCF deficiency symptoms in various combinations along with other nutritional deficiencies and insufficiencies. Note that ALS is not included in this section. I haven’t collected enough information to be able to say anything possibly meaningful. Parkinson’s And (Progressive) Supra Nuclear Palsy are very similar symptomatically. They tend to have the general CFS/FMS symptoms more confined to the CNS than in CFS/FMS, but not always. What really distinguishes Parkinson’s and (P)SNP from CFS/FMS in what appears to be an early pre-diagnosis stage is the presence of anxiety as a general symptom and/or the characteristics of the “Parkinson’s personality”. This appears often as an avoidance of “risk” activities and recreations, more fearful. Also, many who take benzos of various kinds have a distinctive side effect. In the popular language it is called “tolerance withdrawal”. This occurs when the person becomes tolerant of the main benzo effects and a little known side effect starts to predominate. They become hypersensitive to very small benzo dose decreases. The benzos can decrease the dopamine sensitivity of neurons in some areas of the brain potentially causing some Parkinson’s type symptoms. Parkinson’s has demyelization damage in the limbic system of the brain. (P)SNP appears to have the same limbic damage and is often mistaken as Parkinson’s until a couple of more specific symptoms occur; difficulty with the eyes and especially looking upwards and difficulty swallowing, also shared with ALS. So now we get to the relationship of Parkinson’s with folate, and the other 3 of the Deadlock Quartet. Any of the 4 of the Deadlock Quartet can maintain the deadlock on ATP. According to research a few years ago the damage to the limbic system in Parkinson’s to be the hypothesized accumulated damage from decades of mitochondrial malfunction making MMA instead of ATP.. Such malfunction can be caused by the deficiency of AdoCbl in the CSF and possible LCF. Lack of methylation (homocysteine result - lack of methylfolate and/or MeCbl) can also hinder the ATP production, which is what makes it a 4 way deadlock. The non-functional methylation evidenced by homocystein also “dims” the vision and the sensorium in general so the MeCbl turns the gain up perhaps 4x for such people and then LCF helps put the mitochondria back at work making ATP which is used in making dopamine which then kicks these damaged neurons with dopamine and the hyper response turned on with a dose as little as 300mcg of LCF or so and the mood progression goes something like this; anxiety, fear, panic, anger, rage, homicidal rage and deep depression, in repeatable order, over about 36 hours. There could certainly be many variations on this and may be damage dependent. There may very well be many physical neurological symptoms but they were not mentioned by people far more terrified by their mood responses. If the person is not deficient in LCF then any of the other three might cause a hyper response, including l-methylfolate. Then one gets the brightening and the ATP startups together and that kicks the neurons right in the dopamine. LCF or ALCAR when it works instead of LCF, is the easiest one to control because using the liquid freebase form one can take it down to micrograms and keep the startup under control, but the other ones all have to be started first, MeCbl, AdoCbl, L-methylfolate and then finally LCF. As AdoCbl can be deficient in the CSF separately from the MeCbl the exact nature of a person’s problem depends on how these two line up proportionately. I had both separate deficiencies, which each corrected separately with 50mg doses of the appropriate MeCbl or AdoCbl. In addition I required LCF and l-methylfolate to have good functioning. In Parkinson’s and (P)SNP people may have the most extreme hyper response to LCF and varying degree of hyper responses. AdoCbl, L-methylfolate and MeCbl may each cause hyper responses of varying intensity, duration and repeatability. These hyper-responses include Parkinson’s type symptoms as the ATP turns on and off with LCF serum level and/or L-methylfolate serum level and/or AdoCbl mitochondrial level and/or MeCbl serum level The missing link is that so far those with CSF/FMS and anxiety and limbic hyper-responses with Parkinson’s type symptoms have not yet been known to me, to become diagnosed with these diseases though some have stayed away from a doctor that might diagnose such. Some people have titrated very carefully and gotten through all these hyper responses and it is unknown if that means that the ongoing damage is stopped, slowed or reversed or changed in any way. It will take a few more years to see what happens. The usual FMS/ME/CFS symptoms are progressing in the usual ways and variations. So what differences set us up for the various diseases? As first mentioned there are the variations caused by the relative degrees of AdoCbl, MeCbl, L-methylfolate and LCF deficiencies. Parkinson’s seems most affected by LCF, with the most severe deficiency such that < 1mg orally makes a huge hyper response. Researchers have attempted to treat Parkinson’s with carnitine, probably ALCAR, without much success. It seems like the whole family tree needs carnitine of a specific type as a vitamin but Parkinson’s and (P)SNP need it most. Parkinson’s and (P)SNP, like the other family tree diseases, appear to have some varieties of problems with folates and are prone to having paradoxical folate deficiency symptoms. Typically there is strong responsiveness to all 4 of the Deadlock Quartet. From the N=1000 questionnaire development research I did, it appears that people without the symptoms of these deficiencies have no noticeable response to these nutrients. People with symptoms, whether they remember them initially or only after a response, tend to have strength of responses in line with the quantity and intensity of symptoms. In other words, the more sensory dimming symptoms a person has the more sensory brightening they have with nutrient startup. This is a first draft, an approximation. It needs refinement. All this is based on models and hypotheses piled on top of each other, in order to be able to match the hypothesis to the pragmatic effects on symptoms. The researchers that hypothesize that the damage takes decades, Rich and partial methylation block, methyltrap, partial ATP block aka mitochondrial failure, my hypothesis that these early “non specific” symptoms can predict in some ways, by combinations, which disease paths might be getting taken while the damage is being done, maybe in time to head it off because the nutrients can reduce or eliminate many of the symptoms. Also at the basis of these diseases there are relatively ineffective forms of folate and Cycbl/HyCbl. These each are partially effective for a small part of all the symptoms of the active forms deficiencies. The 200 or so, ”leftover” symptoms, which are AdoCbl and MeCbl deficiency-insufficiency symptoms are orphaned. They are separated from their causes because of how “b12 deficiency” and “folate deficiency” are defined. Genetics has its play in all this too, affecting what forms we can use of various nutrients. By default they become unsolvable mystery diseases because the real answers are precluded from consideration.