Hi Dbkita
I find that I need to respond to a piece at a time to do it right. It’s good of you to participate in a stimulating dialog. Thank you. Perhaps a change of understanding will give the clues you need to work it out for yourself the desired balance with healing. Just give this the possibility of a willing suspension of disbelief until this whole thing can be laid out.
Yes I am certain it is not induced paradoxical folate deficiency as you put it. Folinic acid has similar effect to 5mthf for me though maybe not quite 1:1 ratio. I have only have the MTHFR A1298C deficiency heterozygote
The only reason I mentioned that is that there is kind of donut hole induced folate insufficiency. It occurs usually in the startup phase when a person has taken doses of a folate effective for them that are enough to start up a whole lot healing but not enough to maintain it. Then a person develops any number of the folate insufficiency specific things, often angular cheilitis, acne type lesions on scalp and face especially, IBS, mood changes, and such. It is not severe like a methyltrap shutoff or glutathione induced methyltrap. A certain number of symptoms overlap with the hypokalemia. When more effective folate is added then those things heal, promptly.
Then usually the need for potassium goes up in a spiral with the folate. One of the things I have found is that unless a person actually trials L-methylfolate they don’t know if it will actually work better for them. It is very clear that the various polymorphisms are only weakly linked to the effects I’m speaking of. There is a big gap in the interpretation. People that rely on those tests for choosing folate don’t generally have the effectiveness that a person who has trialed theme. They are poor predictors of response. These tests are done in a population which chronic deficiency conditions and the meaning is obscured by that. In at least some of the testing the corruption of the system is evident, the norming population is suffering the effects caused by the lesser activity of the inactive vitamirs and more of the inactive vitamirs are given trying to adjust the test results. As a result a very simple test has had the range of alert for MCV and other measures move in to abnormal territory and that is now “normal”. About 30 years ago > 92 or 93 was alerted. About 15 years ago it moved to > 96 or so. Now it is as high as > 102 depending upon the lab. I talked to a lab rep (labs are, from where I worked, a provider of services). I was told that with the average having moved up to > 96, they adjusted the upper limit to > 100 (2 standard deviations?) so they wouldn’t have to “alert all the tests and have the doctors ignore us”. That is a system corruption. That establishes these deficiency diseases as “normal”.
Another factor, at least with L-methylfolate is a short serum halflife, about 3 hours. I normally take 4 doses a day. Distributed across 4 doses, first thing, last thing and 2 meals I get by on 16 mg. At two doses a day I need 30mg daily to have the same effect.
With folic acid plenty of research has indicated that approximately 20% of USA population can’t convert folic acid to L-methylfolate at all, 30% can do so to more limited degree and 50% to the biological capacity limit of approximately 800mcg/day. I don’t know what the comparable
What can apparently happen, according to many researchers, though I have seen no research supporting it directly, is that folic acid can block the folate absorption and distribution mechanism. That appears to be supported empirically. Many a person taking 400 mcg of folic acid and HyCbl or CyCbl has no folate insufficiency symptoms.
1. Then the person increases to 800 or 1200 or 2500mcg of folic acid. They start getting folate insufficiency symptoms.
2. The switch to MeCbl/AdoCbl and start getting folate insufficiency symptoms.
3. The add 200-800mcg of L-methylfolate and all sorts of epithelial tissues start visibly healing, potassium need goes up and “donut hole” folate insufficiency starts as the Metafolin starts more healing than it can maintain and folate is directed away from some of the epithelial tissues.
4. Folic acid appears to compete directly with L-methylfolate in the absorption and transport systems. L-methylfolate must be taken at a high enough dose with each meal as well as other times per day in order to compete. If Metafolin not taken with meals then the folates in the meal or other supplements taken with food dominate all day and can trigger a person in folate insufficiency. Folic acid appears to clear sufficiently in 24-48 hours for l-methylfolate to have an effect again.
5. Folic acid appears to be most effective at lower doses and effectiveness turns negative as doses increase. This causes all sorts of unreliable, unrepeatable, frustrating, conundrums etc related to interpreting folic acid research. See other post for the reasons folic acid doses is a poor predictor of effects. The results of adding folic acid to food supply (white flour) for neural tube defects was “disappointing”. It is unknown how many additional cases it caused, bringing the returns well below the expected reduction.
6. Folic acid is dependent (enzyme and ATP and methyl groups) upon the Deadlock Quartet being present to be converted to l-methylfolate.
7. Folinic acid competes for absorption.
8. Folinic acid in veggies or supplements, above the level that can be converted to l-methylfolate by the body appears to be able to block the system same as folic acid does causing folate insufficiency symptoms. This appears to be quantity related at least. It appears to take folinic acid about 48-96 hours to clear sufficiently after blockade has been established for l-methylfolate to be effective again.
9. Folinic acid is dependent (enzyme and ATP and methyl groups) upon the Deadlock Quartet being present to be converted to l-methylfolate.
10. Folinic acid and folic acid both only can produce as much l-methylfolate as the keyhole will let them. When more l-methylfolate is required than the body can produce from folic and/or folinic acid, folate insufficiency symptoms appear
The only place where the various polymorphisms come into play in these terms is at what level is the body maxed out for conversion. People that become depleted methylators, those who have been taking methyl competing vitamirs instead of methyl donating vitamirs can watch effectiveness wear off over time and folate insufficiency symptoms appear in many cases. This is the Deadlock Quartet again. Again, it is quite unknown if polymorphisms matter at all in this. It is this “wearing out of response” that was so common in research that what should be GOOD results were viewed as placebo effect, leading to incorrect conclusions.
Folate insufficiency symptoms can be caused by any number of medications. They can be caused by some herbs.
Glutathione, NAC and sometimes Whey can cause sudden onset of the most severe folate deficiency symptoms if they are not already present, as a result of the “methyl trap”. It typically starts with inflammation and rapidly add other symptoms. If you are feeling good methyltrap onset feels like that mysterious severe flu like or “viral” disease that starts or worsens FMS, CFS and ME. If a person already has these symptoms severely there is no noticeable change
Group 1 – Hypokalemia onset. Symptoms may appear with serum potassium as high as 4.3. May become dangerous if ignored. Considered “rare” with cyanocobalamin it is very common with methylb12 and adensosylb12 and less so with hydroxycobalamin..
IBS – Steady constipation , Nausea, Vomiting, Paralyzed Ileum, Hard knots of muscle, Sudden muscle spasms when relaxed, Sudden muscle spasms when stretching , Sudden muscle spasms when kneeling, Sudden muscle spasms when reaching , Sudden muscle spasms when turning upper body to side, Tightening of muscles, spasms and excruciating pain in neck muscles, waking up screaming in pain from muscle spasms in legs. Muscle weakness, Abnormal heart rhythms (dysrhythmias), Increased pulse rate, Increased blood pressure, Emotional changes and/or instability, dermal or sub-dermal Itching, and if not treated potentially paralysis and death.
Group 2a - Both
IBS – Diarrhea alternating with constipation, IBS – Normal alternating with constipation
Group 2b – Either or both
Headache, Increased malaise, Fatigue
Group 3 - Induced and/or Paradoxical Folate deficiency or insufficiency
IBS – Steady diarrhea, IBS – Diarrhea alternating with normal, Stomach ache, Uneasy digestive tract, increased hypersensitive responses , Skin rashes, Increased acne, Skin peeling around fingernails, Skin cracking and peeling at fingertips, Angular Cheilitis, Canker sores, Coated tongue, Runny nose, Increased allergies, Increased Multiple Chemical Sensitivities, Increased asthma, rapidly increasing Generalized inflammation in body, Increased Inflammation pain in muscles, Increased Inflammation pain in joints, Achy muscles, Flu like symptoms, Depression, Less sociable, Impaired planning and logic, Brain fog, Low energy, Light headedness, Sluggishness, Forgetfulness, Confusion, Difficulty walking, Behavioral disorders, Dementia, Reduced sense of taste, Increase irritability, Loss of reflexes, Fevers, Old symptoms returning, Heart palpitations, Bleeding easily.
Group 4 - Hydroxycbl onset, degraded methylcbl onset, methylcbl after photolytic breakdown onset.
Itchy bumps generally on scalp or face that develops to acne like lesions in a few days from start.
Group 3 symptoms, induced paradoxical folate deficiency or insufficiency are corrected quickly with titrated doses of Metafolin, methylb12 and adenosylb12. If glutathione (precursors) are the cause then larger doses of Metafolin, 7.5-15mg,or maybe more are needed. Different tissues are affected at different levels of methylfolate, it comes or goes in stages. Very strong dose proportionate characteristics are present. Serum folate levels may be high or even very high despite Metafolin responsive deficiency/insufficiency symptoms.
Group 1 symptoms respond readily to potassium. The symptoms and response to potassium may occur at a serum level of 4.3 or less.
INDUCED HYPOKALEMIA AND FOLATE INSUFFICIENCY DECISION TREE
Note: ATP startup is not yet in this tree.
IF taking Glutathione, NAC, Cerefolin-NAC, whey, all glutathione or glutathione precursors
AND often sudden onset of several group 3 symptoms (“Detox”) maybe in a sequence, ie pain and inflammation the first day, cheilitis occurs on day 2-3 and IBS on day 5-6, plus any group 2 symptoms. Symptoms increase for weeks or months and can vary from mild to extreme.
THEN Induced Paradoxical Folate Deficiency onset. B12 deficiencies follow in a week for methylb12 deficiency symptoms and several weeks for adenosylb12 deficiency symptoms. None of the other supplements can overcome the effects of glutathione or NAC.
ELSE - all other conditions
IF injecting b12
AND itchy bumps and acne type lesions appear mostly on scalp and face but not exclusive
THEN B12 was hydroxycbl OR photolytically deteriorated methylcbl OR cyanocbl, Lesions can be reversed in days with methylcbl injections not exposed to light at all.
IF starting or adding methylb12, adenposylb12 or hydroxycbl, AND OR Metafolin (perhaps 80%)
AND the approximately 3rd day or later onset of symptoms (“Detox”) from Group 1 and/or group2
THEN this can be the onset of Hypokalemia triggered by sudden widespread healing onset. This usually occurs as soon as methylation therapy starts widespread healing process by allowing DNA replications with methylb12 and methylfolate.
IF adding adenosylcobalamin AND OR L-carnitine fumarate AND OR SAM-e to program (perhaps 50%)
AND the approximately 3rd day or later onset of symptoms (“Detox”) from Group 1 and/or group2
THEN this can be the onset of Hypokalemia triggered by sudden healing and /or muscle growth. This usually occurs when the person has experienced muscle shrinkage perhaps from decades of inactivity, as soon as these supplements step up mitochondria functioning.
IF adding or increasing any of Vitamins D, A, E, or C, magnesium, zinc (perhaps 10%)
AND on the approximately 3rd day or later onset of symptoms (“Detox”) from Group 1 and/or group2
THEN this can be the onset of Paradoxical Folate Deficiency (or Insufficiency). Folinic acid is the primary form found in vegetable source. In some unknown percentage of people who appear unable to convert folinic acid adequately to methylfolate the accumulating unconverted folinic acid can actually block the methylfolate.
IF starting or increasing folic acid
AND usually takes a number of days to accumulate to a level leading to onset of symptoms (“Detox”) from Group 3 and/or group2
THEN this can be the onset of Paradoxical Folate Deficiency (or Insufficiency). Folic acid is the most oxidized form of folate that anybody can use. In some unknown percentage of people who appear unable to convert folic acid adequately to methylfolate the accumulating unconverted folic acid can actually block the methylfolate.
IF starting or increasing folinic acid
AND usually takes a number of days to accumulate to a level leading to onset of symptoms (“Detox”) from Group 3 and/or group2
THEN this can be the onset of Paradoxical Folate Deficiency (or Insufficiency). Folinic acid is a less oxidized form of folate than folic acid.. In some unknown percentage of people who appear unable to convert folinic acid adequately to methylfolate the accumulating unconverted folinic acid can actually block the methylfolate.
IF an increase in dietary vegetable folate, “green drinks”, a garden feast
AND usually takes a number of days to accumulate to a level leading to onset of symptoms (“Detox”) from Group 3 and/or group2
THEN this can be the onset of Paradoxical Folate Deficiency (or Insufficiency). Folinic acid is the primary form found in vegetable source. In some unknown percentage of people who appear unable to convert folinic acid adequately to methylfolate the accumulating unconverted folinic acid can actually block the methylfolate.
IF starting or increasing folic acid AND OR starting or increasing folinic acid AND OR an increase in dietary vegetable folate
AND the approximately 3rd day or later onset of symptoms (“Detox”) from Group 1 and/or group2
AND usually takes a number of days to accumulate to a level leading to onset of symptoms (“Detox”) from Group 3 and/or group2
THEN this can be the onset of Paradoxical Folate Insufficiency AND this can be the onset of Hypokalemia triggered by sudden healing
IF starting or Methylfolate – Metafolin starting low and titrating
AND the approximately 3rd day or later onset of symptoms (“Detox”) from Group 1 and/or group2
AND OR usually takes a number of days to accumulate to a level leading to onset of symptoms (“Detox”) from Group 3 and/or group2
THEN this can be the onset of Paradoxical Folate Insufficiency, a “donut hole” deficiency. The effects of folate deficiency/insufficiency comes in layers. Several tissue groups can be healing at the same time as other tissue groups are deteriorating. IBS and angular cheilitis can be worsening at the same time as muscles are healing or growing. There is a dose of Metafolin that can start more tissue formation than the same dose can sustain causing a Paradoxical Folate Insufficiency at the same time. In some people at least as they increase Metafolin the need for potassium increases approximately proportionately. The donut hole can be closed with total daily doses of Metafolin of about 15mg for many people.
HOW TO INDUCE SUBACUTE COMBINED DEGENERATION and enlarged MCV in humans in 3 months or less.
Causing SCD and macrocytic anemia was NEVER our intention, our intention was to induce health benefits from glutathione or precursors as claimed these days amongst certain practitioners. This is just how it turned out, 180 degrees from what we expected.
Individual results will vary but in an N=10 trial, 100% of subjects had the results to varying degrees, perhaps as they used several different precursor combos or infusions. The subjects were all successful with adb12, mb12 and Metafolin. Those not in this group that had never relieved the deficiency symptoms claimed pain relief from the glutathione as their nerves were damaged further into numbness. I experienced this myself in the glutathione trial as my neurological damage was increased.
Method 1 - feed subjects 1 gram of l-glutamine and 600mg of time release NAC twice a day for duration (or frequent glutathione infusions, or NAC or whey in some). In 3 hours after first dose most of available b12 in the body will be flushed out in the urine. Then within the next few hours methylfolate is expelled from the cells via the "methyl trap". Widespread body, muscle and joint, inflammation and pain start within hours and gets worse by the day. This is responsive to NSAIDS generally. Folate deficiency symptoms appear the first day, mb12 deficiency symptoms in several days and adb12 deficiency symptoms - 3 months or so.
Over the next days and weeks, CPR heads for the roof. Hypersensitivity of all sorts starts, MCS, hyper-immune response, hypersensitivity in nerves, etc. In 3 days angular cheilitis starts up in those who are prone to it. In 2 more days IBS starts. At about the same time acne type lesions start up on scalp and face and often infected follicles in other body areas. Oral lesions usually follow. By six weeks centrally mediated numbness and pain of feet and legs, hands, arms, shoulders etc are all spreading and worsening.
Dr Jeckyl leaves the house and is replaced with Mr Hyde for the duration. Sleep disorders increase. In 3 months macrocytosis is obvious, MCV > 100. MS will be dramatically worsened. If the person is also extremely low on l-carnitine and/or adb12 Parkinson's like symptoms may worsen explosively. Then if l-carnitine is given the subject may go absolutely nuts and a walkthrough of the extreme FFF characteristics of the limbic system will be demonstrated in usually the same order each time, dependent upon rising or falling l-carnitine level.
Reversal, if SCD is not allowed to go too far is multiple 15mg doses of Metafolin (Deplin) and three 50mg mb12 doses or 10mg SC injections of SUITABLE 5 star mecbl until healed for at least a year, and of adcbl the first few days. On day 3, the need for potassium will often increase by 2000-3000mg to avoid dramatic sudden onset of Hypokalemia symptoms when backlogged healing starts up. Also on day 3 Metafolin dosage needs increase. In about a month inflammation will be largely gone if all cofactors are present that are needed, CRP <=1.0, multitudes of pains will be fading. MCV corrects when folate deficiency doesn’t exist for several months. Maintaining folate sufficiency for 3 months straight can be extremely difficult for those with paradoxical folate deficiency. Only the remyelization takes about 9 months to correct to the extent that it can but trails on for years as it is an ongoing equilibrium that is either getting better or worse. By careful active management one can approximately tread water otherwise it gets worse.
