Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by JanisB, Apr 25, 2010.
oh this may be how FA/PGA form competes with the other forms as per yasko.
When Labcorp and buds are measuring serum FA, what form are they measuring?? PGA or tetrahydrofolate?
The protocol is supposed to improve methylation as well, right? So how can it do that if it is cell blocking active forms of FA? Thats the same as blocking methylation.. ??
I know I felt like I was coming out of the grave when I took my first 500mg methionine pill. My mucles were breathing again and had a tiny bit of recovery. My homocysteine is low, which is supposed to be an indicator of low methionine. I was a vegetarian for 23 years and started eating meat again last year. I cannot stand red meat. I force myself to eat it. I wonder if you were overdriving methylation. I started taking two 500mg a day recently and will see how I feel. I am concerned about my MTR++ "condition" which I read can be associated with inability to wake up from anesthesia. My grand mother did not wake up after heart surgery (I was a toddler).. makes me wonder, and I think a precaution for this possibility is methionine. So I want to learn more about it.
I am wondering about the plasma and urine tests and what they mean. Yasko UAA suggests I need methionine, lysine, arginine, carnosine, NAC (I think).
Good point. It may not be about addressing snps at all. Im concerned about hypomethylation as well. I see the combo mopping up aldehydes and glutamates and the FA interfacing with the noradrenalin receptor.. also wondering about the role of FA on the heart muscle in strenghtening it.
If the body is biochemincally hyper-responding, I think it would take a yogi to "amydalize" it down.
Infections like Lyme can also cause a stress as you lay out above and as per Rich's hypothesis. I can see needing to address the SNS very much, also concerned as stated above. Research can be contradicting as well. Is this definitive research regarding the action of PGA to block active forms of folates from the cells?
Back to methionine.. I wonder about the research which indicated that low homocysteine (potentially caused by low methionine (caused by ??) can result in active FA not being able to stay in the cells? Does homocysteine play a role in the FA blocking the active FAs or am I stretching too far?
On another track here.. is creatine a sign soley of methylation or can it be created in other ways? Can you create the products of methylation without methylation?
Excitotoxicity & SNS Symptoms
Janis, you are probaby aware of this, but posting anyway. Its just not black and white is it?
http://www.heartfixer.com/AMRI-Nutrigenomics.htm#CBS:* Cystathionine Beta Synthase
"Sulfite is neurotoxic. Sulfite will be over produced by the CBS up regulation, and then requires conversion in to the less toxic sulfate molecule by the enzyme Sulfite Oxidase (SUOX). SUOX can easily be overwhelmed. Molybdenum is required for SUOX function, and is typically depleted in CBS (+/+) or (+/-) individuals. Molybdenum supplementation (3 drops or 75 mcg of e-lyte Molybdenum twice a day), Boron 3 mg/day, Vitamin E succinate 400 IU/day, and hydroxy-B12 2000 mcg/day are also utilized to speed up SUOX activity.
While sulfate is less toxic than is sulfite, it will stimulate the adrenergic (fight or flight) limb of the autonomic nervous system and stimulate a cortisol stress response, revving you up into an unrelenting biochemical overdrive. If you have a CBS defect, we need to restrict your sulfur intake, at least until your urine sulfate (and your body sulfate burden) has decreased. The amino acids methionine, taurine, and cysteine all contain sulfur; they are concentrated in animal protein (thus the restriction on animal protein intake). Many nutritional supplements (MSM, N-acetyl cysteine, glutathione) that are good for most people are a problem for you. While certain aspects of your health will benefit from these agents, they will add to your sulfate/sulfite overload problem, adversely affecting the Methyl Cycle
Defect that is the common denominator to all of your health problems. Many drugs are loaded with sulfur (sulfates, sulfites, metabolically active sulfur), so if you are CBS positive and I treat your hypertension with the diuretic hydrochlorothiazide, your diabetes with the sulfonylurea drug glipizide, and your urinary tract infection with a sulfa containing antibiotic, I will be lowering your blood pressure, lowering your blood sugar, and clearing bacteria from your bladder, but I will also be adding to your sulfate burden, compromising your biochemistry, and contributing to an ongoing decline in your health. I will be treating the manifestations of an underlying problem and at the same time adding to the underlying problem. If I treat your Mercury overload with DMSA or DMPS, I will remove a toxin from your body, but if you are CBS (+), I will be adding to your sulfate/sulfite pool, and sulfate/sulfite overload due to the CBS up regulation is likely playing a key role in your sensitivity to heavy metals and/or your inability to clear them. We can avoid this. We can hold sulfur containing agents until your sulfate burden has come under control. Learn all you can about the sulfur content of foodstuffs, supplements, and prescription drugs. Sulfites and Chronic Disease by Rick Williams (available at the office or at www.readingtarget.com/nosulfites) is an invaluable resource. Do not expect us to know the sulfur content of foodstuffs. Some tips on low sulfur eating are included at the end of this document, but do not expect us to tell you what to eat. We can’t do this. We do not have this knowledge. Please attend our monthly Methyl Cycle support groups meetings, and you may sign up for individual (or group) dietary change counseling. It is your responsibility to become expert in this area. I will work with you to phase out high-sulfur drugs and nutritionals from your program, but don’t expect me to get in right every time – please study your food, drug, and supplement labels.
Excitotoxicity – The CBS up regulation leads to excess production of alpha-ketoglutarate, which is converted in to glutamate, a stimulatory neurotransmitter. Under normal circumstances, glutamate will be converted in to GABA, a calming neurotransmitter, but the enzyme systems that convert glutamate in to GABA are compromised by lead and mercury, the clearance of which seems to be compromised in individuals with methyl cycle defects (here is a situation where dysfunction of a genetically abnormal enzyme leads to acquired dysfunction of a genetically normal enzyme system). The result is “excitotoxicity”, stimulatory behavior in autistic kids (“stims”) and anxiety and sleeplessness in adults. We approach this problem by limiting alpha-ketoglutarate and glutamate rich foods from your diet (more on Excitotoxicity to follow; diet tips in appendix) and by supplementing you with GABA, aiming to restore GABA:Glutamate balance. GABA is initiated at 500 mg once or twice a day, advancing the dose as you see fit by your response."
You wont methylate properly under stress (look at all the needed do dads that are used up scavenging "stress")... another view of the folate trap. How many ways can you trap folate? Not sure what it means to be saturated with methyl groups.
During a reaction to stress situations, demand for methyl group donors (like SAMe) suddenly increases, in accordance with the Methylation Priority Principle 20 , driven by the need to perform additional “Methylation Functions” (Table 1.) Specific stressors requiring methylation further exacerbate the stressed state, thereby destabilizing the autonomic nervous system.
Metabolically active folates like 5-methyltetrahydrofolate can be created in the body via a complex process known as “liver metabolism” from dietary folic acid (vitamin B9)—complex mixtures of polyglutamate (multiple glutamate molecules attached) conjugate compounds. For the purpose of this invention, dietary supplements denoted as first compound, in less complex forms of folic acid, folates, folinic acid and its salts—folinates (like calcium folinate known as leucovorin calcium) that do not need liver metabolism for transformation to methyltetrahydrofolate are preferred. However, the dihydrofolate form functions exceptionally efficiently as a scavenger for aldehydes and glutamate, hence should be considered, even if it needs to be administered as an active component.
Similarly, supplement denoted as second compound—aquacobalamin, methylcobalamin, glutathionylcobalamin and adenosylcobalamin—biochemically close to the metabolically active hydroxocobalamin (OH—B12) are preferred for the current invention.
Folate scavenges 30 for aldehydes and glutamate and recycles aldehydes through hydroxocobalamin to homocysteine. Hydroxocobalamin is reduced by glutathione but also scavenges for nitric oxide (NO) 40 and peroxynitrite. Hydroxocobalamin can be inactivated by NO. Aldehydes, NO and peroxynitrite, if allowed to accumulate, can severely disturb balance and functions of both branches of the ANS.
Glutathione (GSH) scavenges 50 for mercury, pesticides and solvents and metabolizes acetominophen. Glutathione can be inactivated by NO, can reduce ascorbate (vitamin C) or can be reduced 60 by it. Taurine scavenges 70 for hypochlorite and other chlorine-containing compounds. Taurine, magnesium and pyridoxine (vitamin B6) encourage the production of glutathione when homocysteine is converted to cysteine 90 .
Oxidative stress leads to increased aldehydes, nitric oxide and oxidized glutathione (or less available reduced GSH). Nitric oxide causes increased pain and inflammation through the inducible nitric oxide synthase pathway, which is potentiated by formaldehyde, glutamate and solvents.
When nutrients are diverted for scavenging or are inactivated alone or in combination, methylation will become inadequate under stress. If hydroxocobalamin is insufficient or dysfunctional, then methylation cannot proceed. When GSH is insufficient or dysfunctional, hydroxocobalamin is dysfunctional. In either instance, folate becomes functionally insufficient, even when levels are elevated, because it is saturated with methyl groups and aldehydes. This condition is called the folate trap.
Here's a quote from Rich...
"However, creatine also requires methylation for its synthesis, so it was actually decreased as well, and moreso than choline, so that the ratio of choline to creatine went up, but both were actually lower in absolute terms."
...from an excellent, comprehensive post here:
Creatine V puts this last among methylation priorities because once the methyl group is used to make creatine it cannot be recycled.
How long folic acid (PGA) stays in the system: I found this at http://[URL="http://www.inchem.org/documents/pims/pharm/folicaci.htm"]www.inchem.org/documents/pims/pharm/folicaci.htm[/URL]
It seems that overdose can be dealt with by activated charcoal as per above webpage.
All this makes me less worried about taking high doses for a period of time to calm the ANS.
I am guessing that the reason I continued to have high serum folic acid on Rich's S. Five protocol, was due to this explanation in V's patent:
My low creatinine levels showed I was not methylating well, and I am guessing that folate was functionally insufficient. This became evident when added 5 mg methyl B12 daily for awhile and ending up with very high methionine, high glycine, high sarcosine, and a miserable liver.
Maybe this is why we are all stressed out!
Climacteric. 2008 Oct;11(5):397-403.
Norepinephrine activity, as measured by MHPG, is associated with menopausal hot flushes.
Dormire SL, Bongiovanni R.
The University of Texas at Austin, School of Nursing, Austin, Texas 78664-1499, USA.
OBJECTIVES: Baseline norepinephrine levels, as measured by a metabolite (plasma 3-methoxy-4-hydroxyphenolglycol, MHPG), have been reported to increase in women who experience hot flushes. However, norepinephrine is also discharged in a counter-regulatory attempt to increase brain glucose as normal daily variations occur. .... [rest of abstract deleted]
Here's my argument. Let me know what you think?
Once we get low brain glucose, experienced as fatigue and brain fog, our body compensates by increasing norepinephrine to raise brain glucose, leading our heart to start pounding and our pulse to race. We experience the feeling of stress, and the fatigue that inevitably comes after it. Increase NE leads to increased oxidative stress. Extra demands are put on methylation to break down the norepinephrine and to handle the damage from increased stress hormones. In the end, we become deficient in folates, B12, cortisol and DHEA, and glutathione.
Thank you for the info, Janis.
I see the SNS calming through scavenging aldehydes and glutamates and binding the the norepinephrine sites.
Makes sense that methylation will be thwarted if nutrients are diverted for scavenging.. and I think more nutrients than FA and hydroxo are scavenging.
Need glut for hydroxo to work, I think even to scavenge.
My brain is completely halting on the folate trap. Why does folate become functionally insufficient? because it is scavenging... thats what "saturated with methyl groups (which ones ??) and aldehydes.. so once the folate is saturated, it cannot be convereted or metabollized to its active forms.. a folate trap is then just the loss of "functional" folate?
So when you added more b12 (methyl) you put pressure on or upregulated methylation in an unhealthy or imbalanced way because you did not have enough folate on hand because it was diverted to scavenging esp due to high stress activity?
I wonder if this is also why Freddd is finding a higher need I think up to 4000mcg of methyl folate a day? I wonder how well methyl folate scavenges.
Well, this is the same as insulin resistance? Dr K is working on that with d-galactose for autistic kids. This was newly presented at the Lyme Induced Autism conference. Specifically referring to the brain and glucose I think.
Low insulin = low glucose in brain = glutamate and ammonia "poisoning" of the brain = upped SNS activity and excitotoxicity
(Cant find it again.. found a resource that pointed to ketosis and a primitive diet was a way to keep on in ketosis and SNS more balanced.. could have read that wrong, though. Continual ketosis doesnt seem safe to me.)
Emerging type III diabetes theory of autism
developed by: Professor Werner Reutter, PhD, Chantee, Berlin and presented in English by Dietrich Klinghardt, MD at the Lyme Induced Autism (LIA) Foundation Conference on April 18, 2010
Dr. Klinghardt Dietrich, MD, an autism and lyme specialist in Washington state, presented the following information today at the LIA Foundation conference.
The issue: the growth and development of the brain is largely insulin dependent; insulin is needed to feed the brain cells with glucose. Autistic children have a great disturbance of the insulin receptor in the brain, possibly combined with insulin resistance and other issues, which leads to failure of the system.
Common result: high ammonia levels in brain, glutamate toxicity, elevation of TNF-alpha and IL-6, structural abnormalities and others.
Solution: D-galactose (a mono sugar) 4 grams twice daily in water.
He also mentioned that D-galactose has been used successfully in cancer and Alzheimer’s treatment programs. It does not appear to be offered currently on his BioPure product website but keep checking back: biopureus.com.
(1) What happens to nutrients that have been saturated with "methyl group" (and what methyl groups from where?) and aldehydes?
Can they be used for methylation? Or do they leave the body with all attachments?
(2) Hydroxo b12 works with the FA (the dihydrofolate or the PGA???) to take the aldehyde from the FA which has scavenged it. The HB12 then makes homocysteine from it.
So again.. can this HB12 once it has contributed to making homocysteine then recylce back in some way to contribute to methylation?
If not, then in a sense it is LOST b12 isnt it as would be the FA. Lost to methylation????????
explanation in V's patent:
"When nutrients are diverted for scavenging or are inactivated alone or in combination, methylation will become inadequate under stress. If hydroxocobalamin is insufficient or dysfunctional, then methylation cannot proceed. When GSH is insufficient or dysfunctional, hydroxocobalamin is dysfunctional. In either instance, folate becomes functionally insufficient, even when levels are elevated, because it is saturated with methyl groups and aldehydes. This condition is called the folate trap. "
This seems to say that once the FA becomse saturated that they DO NOT participate in methylation...(dihydrofolate seemed to be indictated as best scavenger though I am not sure if PGA scavenges OR what happens to PGA that does not get broken down by the DHFR enzyme)
IF this is so, then are the FAs are able to per form other functions that they do? (or are all functions they do a product of their process in methylation?)
Could one become MORE b12 and MORE FA "deficient" in the process of the scavenging? Asking for a reason. I was using for a week or so and started having irritability (FA deficiency sign) and more creepies (possible methyl B12 deficiency sign.. which has been helped by adding methyl b12).
Can there be a kind of HB12 trap when using this formula? The HB12 is picking up aldehydes from the folate once it is scavenging and making homocysteine from it.
Were you using the Folinrinse drops on the Perque 12 tabs...or using the folates/b12's (and ratios) recommended by Rich?
The 5:2, dannybex.
Relationship between FA and b12 as well as the role of hydroxy to scavenge (post traumatic) stress:
http://www.healthyawareness.com/articles/about-vitamins-minerals/about-vitamin-b12.aspx (entire article is interesting.. recommending very high dose HB12)
The connection between vitaminB-12 and folic acid is also critical. VitaminB-12 reactivates folic acid. If an individual has low levels of vitamin B-12, severe folic acid deficiency may develop. Similarly, a B-12-deficient individual taking only folic acid can make the B-12 deficiency worse. ....
The hydroxycobalamin can be found a www.Perque.com or it can be ordered through a compounding pharmacy. The body will convert it into the active methylcobalamin and adenosylcobalamin. Large doses of hydroxycobalamin have proved useful in the treatment of both fibromyalgia and chronic fatigue. The reason might be due in part to B12’s ability to mop up excess nitric oxide. Dr. Martin L. Pall hypothesizes that elevated nitric oxide and peroxynitrite may be the common etiology of posttraumatic stress disorder, fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity. Hypoxia (lack of oxygen) or any traumatic stress can set in motion a vicious cycle that perpetuates the elevated levels of the nitric oxide and peroxynitrite in the body. See www.ImmuneSupport.com/library/showarticle.cfm?ID=2976...
Another published study documents the use of up to 26 mg a day of B-12 with great benefits, and no side effects. At these high doses hydroxycobalamin rather than cyanocobalamin must be used to avoid the toxicity of the cyanide in the later.
Hmmm.. this is interesting. I didnt know that MTHFr (the folic acid genes) gives non methlylated B12 its methyl group. I have a string of hetero MTHFr snps. Trying to put the 3 diff methylation protocols we have on this board into some sense. So its not whether one is COMT++ or COMT-- so much in regard to availability of methyl groups to give the hydroxy. Its the condition of MTHFr. ?? and the presence of methylated folate.
So is methyl b12 that is made in the body borrowing a methyl group from methyfolate???
I guess this is how folic acid reactivates b12.. but it has to be methyl folate...
Non-methyl-B12 forms of B12 work well to correct a true B12 deficiency. However,
their actions are limited because their primary function is to be incorporated into
the B12 binding site on the methionine synthase molecule. Once they are attached
to this binding site, it is essentially the same as if they were “locked up in prison
cell”. Once imprisoned in this manner, they are now dependent on the classical
interactions of B12 with methionine synthase and methyl-tetrahydrofolic acid
(MTHF), those actions being to accept the methyl group from MTHF and pass
this methyl group onward to homocysteine while continually altering the cobalt-
B12 oxidation/reduction state and repeating the process. “Only methyl-B12 has a
key to the prison” and therefore is not bound to the prison-B12 rules. Only
methyl-B12 has the freedom to bypass the need to receive its methyl group from
MTHF. Only methyl-B12 has its own methyl group to pass onward to
homocysteine. Therefore only methyl-B12 has the ability to act more quickly and
more efficiently than other forms of B12.
Thread I started linked above for specific responses to this info.
Methyl-B12: Doing It Right! Methylcobalamin Update, James A. Neubrander
For autistic children, but... very interesting slightly diff view from yasko... another one to consider looking into. He thinks COMT++ folks (autistic children) still need MB12.
He is specifically focusing on methylation in teh brain, which is a bit diff than in the body. I am going out of a limb and wondering if the brain activity of CFS/ME is also effected by methylation and supply of MB12.
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