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CBS and cofactors. Are CBS+ low in B6?

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
I believe eliminating caffine can be most beneficial in controlling excitoxicity and balancing electrolytes, vitamins, minerals etc.

I just can't seem to absorb much stuff when drinking caffine and get all kind of other issues like frequent urination or weak shut off. I tend to be highly excitoxic. Maybe it is a potential CBS upregulation thing with dysfnctional cysteine exchange from these various antiporters and other receptors like the EAAT3 maybe?? I haven't done all the homework on the yasko stuff, but this draining thing is something I can't comprehend.

I'm wondering if the CBS draining thing may actually be more of a higher requirement for cysteine, but that is just speculation based on futzing around with NAC and ALA.

I wondering is my intolerance in my to those sulfur prodcuts now might be related to a stomach infection of leaky gut?

I tend to be adrenal fatigued, mental fatigued and cognitive dysfunction more than the imobilizing physcial fatigue. However, I do know what being bed bound is like and do get PENE.
I posted a study here somewhere recently showing that olive leaf extract (which I take for b.p.) raises glutathione. I take a cruciferous veggie extract from Life Extension every day because broccoli has been shown to help you make non-cancer causing estrogen metabolites instead of cancer-causing ones. Cruciferous veggies contain cysteine so I am always full up on cysteine (amino acid test showed 103% of cysteine...a tad over but not enough that anyone was concerned).

I don't have time to respond to your note more that this right now.
 

Valentijn

Senior Member
Messages
15,786
More specifically I have never supplemented glycine. Don't know why I would?
Those of us who have ME/CFS often have elevated glutamate, plus low cysteine, low glycine, or low cysteine and low glycine. Adding cysteine and/or glycine into the mix can help reduce glutamate by combining with it to form glutathione.
 

juniemarie

Senior Member
Messages
383
Location
Albuquerque
I am still confused about CBS defect as it relates to B6 requirement and whether it matters what type of B6. Also about CBS and homocysteine. Can anyone explain it clearly. I read this thread and the links for articles posted but its not sinking in. If you have CBS defect and high homocysteine do you follow the regular CBS protocol or does the high homocysteine require a different approach or tweaking when your treating
CBS
 

Lotus97

Senior Member
Messages
2,041
Location
United States
This is from Rich in regards to supplementing with B6/P5P for those with a CBS upregulating SNP:
Ammonia is produced in the body in three ways that I know of. Normally, the main one is the burning of amino acids for fuel by the mitochondria. When this is done, the nitrogen has to be disposed of, and that is done by carrying it, mostly in glutamine, via the blood to the liver, where the urea cycle converts it into urea. The urea is put back into the blood and is extracted by the kidneys, which excrete it into the urine.

Ammonia can also be produced via the transsulfuration pathway, which is why Dr. Yasko recommends lowering the B6 intake if a person has an upregulated CBS enzyme.

The third way ammonia is produced is by anaerobic bacteria in the gut. If this gets too high, and the liver cannot deal with it, so that the ammonia level rises in the blood, it can cause trouble in the brain, called hepatic encephalopathy.

If the urine tends to be too much on the acid side, because of a person's diet or another cause, the kidneys can produce ammonia from glutamine and put it in the urine to balance the acid. This prevents frying one's nether parts! :)-)

If the bacteria in the gut are producing too much ammonia, they will need to be dealt with. The treatment for high ammonia in the blood coming from the gut includes giving oral levulose. Bacteria in the gut will convert this to lactic acid, pushing the pH in the gut in the acid direction. That will cause ammonia (NH3), which is a gas, to shift more to NH4+, ammonium ion, which will stay in solution and pass out in the stools rather than diffusing from the gut into the bloodstream.

The situation involving B6 is complicated. If a person has a CBS upregulating SNP, it's a good idea not to go too high on B6 until this is dealt with. Later on, it is important to have enough B6 so that the transsulfuration pathway can proceed at a normal rate. Also, B6 is needed to make some of the neurotransmitters, and it's also very important in the metabolism of the amino acids, to name a few. So in the longer term, B6 needs to be brought up, and B2 is needed also, to convert B6 to its active form, P5P.

Dr. Amy Yasko has argued that this can cause an increase in ammonia production if the methylation cycle is supported without first treating to limit the flow into the transsulfuration pathway. She recommends lowering B6 supplementation and considering her "ammonia support RNA formulation." In the clinical study that Dr. Nathan and I carried out, there were some people who had such polymorphisms. We ignored them and gave all the patients the same basic protocol. Our lab testing showed that the recovery of the methylation cycle was slower in the people who had these polymorphisms, but by 6 to 9 months they had caught up with the others.

Best regards,

Rich
Thought you might be interested in this
 

Lotus97

Senior Member
Messages
2,041
Location
United States
dbkita also posted about B6/P5P and CBS
One mechanism so that p5p enhances thiol intolerance is CBS activity is increased, so more flux on top of what is directly being transplanted by raising cysteine. On the other hand molybdenum or manganese will help anyone with trans-sulfuration issues in principle since one helps with processing sulfites and the other with clearing ammonia in the urea cycle.

My point is that thiol intolerance leading to high cysteine levels via whatever mechanism is just another route into the trans-sulfuration pathway. Another is driving of the methylation cycle and the more excess methionine produced the more flux presumably down through CBS and hence more cysteine again. But the downstream results will be similar.

If I use urine sulfate strips as a biomarker, both large consumption of protein and eating servings of broccoli, asparagus, etc. lead to higher levels of excreted sulfates several hours later. For me I eat three to four large servings of such vegetable a day on my 3500-4000 calorie diet. But I consume 200-225 grams of protein a day, leading to a total of 6-7 grams of methionine + cysteine ingested per day. Personally if I add a couple of grams of M+C to my intake via say eating a steak I get a larger bump 3-4 hours later than if I eat more vegetables. So while both effects are present, the high protein is a bigger factor for me. That being said, the single biggest way to bump my urine sulfates up is to take more p5p. Going from 25 to 50 mg raises my urine sulfates by about 50-75%. Hence my point that a 10% difference in flux for a homozygous mutation can easily be simulated in a wild type person by upping p5p. I think therefore bigger issues are functioning of SUOX and urea cycle which is where molybdenum and manganese come into play. Note raising methylfolate also raises my urine sulfates.
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
Oh, I take a cysteine supplement everyday and thus am on the border of high cysteine. I also take 1g of Olive Leaf Extract every day and that has been proven to raise glutathione. We do not know what I may have if I did not take my extensive list of supplements since I have been doing so my whole life...I only know that everytime I fall off on anything I get strong repercussions. For instance, glutamate could kill me w/o estrogen to protect me from glutamate toxicity, the estrogen I make from 75mg DHEA I take daily. During PMS before I took DHEA I had such a bad MSG reaction I thought I might die and doubt I would have survived it had I been older. Many such inexplicable reactions were not solveable due to the cyclical nature of hormones, it was a bf who helped me figure it out. I have been supplementing B vitamins in particular since infancy. I still get glutamate toxicity when I am sick because some infections (all?) use up DHEA and then I don't have enough to protect my NDA receptors.
Those of us who have ME/CFS often have elevated glutamate, plus low cysteine, low glycine, or low cysteine and low glycine. Adding cysteine and/or glycine into the mix can help reduce glutamate by combining with it to form glutathione.
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
HOLY SHIt! dbkita eats TOO MUCH protein! Protein is acidic and its byproduct is ammonia no matter what your genes are. It requires magnesium to excrete ammonia. SO the more protein you eat, the more magnesium you need. And your body will strip the NMDA receptors (causing glutamate toxicity) to get that magnesium if you do not get enough. High protein diets are linked to astromomically higher rates of all sorts of cancer. Your body has to buffer that ph somehow, robbing alkaline minerals from wherever it can, including bones and NMDA receptors.

idk what special requirements exist for olympic athletes, but the average American does not need more than 80g of protein (and even that might be excessive). There is an ammonia blood test. You can eat 80g of protein / day and then test your blood for ammonia levels. That s what I did and I find despite CBS +/+ and CBS +/- that I have no problem with 80g (a normal) amount of protein and do not need special supplements like charcoal or yucca or levulose.

Studies show there is only about a 2% difference between whether you have the CBS mutation vs. not and the studies were in children (hromones that develop later regulate the CBS gene expression, so it may not be an issue AT ALL in adults).

Also from my own observation, there is no way to hurry up a biochemical path and it does not make sense to ever (EVER) let your homocysteine go above 6.3 in which case it will damage blood vessels and kidneys etc. Think of it this way...a homocysteine of 6.3 IS A QUEUE of homocysteine waiting for any other pathway to suck it up. If there is ALREADY homocysteine IN THE QUEUE NOT GOING ANYWHERE, what is the point (there IS no positive point) to raising the amount in the queue not going anywhere. Your mfolate+mB12 pathway can only go so fast. If you supply what they need they will go at a rate governed by the fact that it takes two chemical reactions to traverse that path. If you supply extra P5P, you will only drain away homocysteine away at a rate governed by the fact that it takes two chemical reactions along THAT path. If you supply B6 instead of P5P it will take more than two reactions (three? Or more?). The BHMT is the only path that can cart homocysteine away any faster because it requires only one chemical reation along that path. And even that path has a limit ue to it takes time to perform even one chemical reaction. The reason it is crucial to ingest TMG is to prevent the BUILDUP of homocysteine that otherwise occurs after meals (in anyone!) because of the time it takes for the other chemical reactions - it is sort of a pressure valce to prevent a bad occurrance of homocysteine overload. The body is supposed to have enough TMG and mB12 and mfolate to cycle the homocysteine around the methyl cycle 3 times, without rising much above 6.3, before it is excreted through the CBS pathway. So if you have 6.3 of homocysteine in the queue, your queue is full and avoiding TMG to raise this value is detrimental and helps nothing.

Yasko is wrong, wrong, wrong about CBS...I am CBS +/+ and +/- and was told my CBS is upregulated and yet I had the common sense to look at my bloodwork and see that - NO - my homocysteine is ELEVATED not lowered like she claimed. You cannot trust anything anyone says about these genes - this is all new and insufficiently studied. I think the purpose of the genetic mapping is to find clues of what you need to test to see if it affects you. Everything you are exposed to affects your gene expression and there has been little study of what these genetic mutations do in combination. In the case of CBS, the testing Yasko references was done on children, and may not apply at all to adults!

I do applaud Rich's methodical listing of possible sources of ammonia. Because if you test for ammonia levels and find yours is elevated it may not even be genes...it may be bacteria in the gut as he lists. It is important to consider every possibility. Also don't forget if you have kidney issues (including a simple urinary tract infection), you will have trouble excreting ammonia. Also it takes 2 BH4 to excrete a single molecule of ammonia and people with genetic defects making BH4 (like me) could potentially have ammonia buildup regardless of diet and regardless of CBS gene. So you wpuld have to cover all bases - take steps to raise BH4, take steps to kill gut bacteria, etc, eat/supplement sufficient magnesium, eat 80g (a normal amount) of protein, then test to see if you have a problem with ammonia due to CBS. The key is to suspect and understand the possibilities, but not to assume.
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
Oh, so fyi...I measured my homocysteine with my regular protocol which includes a 50mg P5P. Then I ordered a higher dose P5P (I believe I tried 300mg, don't remember exactly) and I remeasured my homocysteine. There was no change. You cannot speed up that pathway if it is not clogged by nutritional deficiency! Extra does not mean faster!
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
I believe eliminating caffine can be most beneficial in controlling excitoxicity and balancing electrolytes, vitamins, minerals etc.

I just can't seem to absorb much stuff when drinking caffine and get all kind of other issues like frequent urination or weak shut off. I tend to be highly excitoxic. Maybe it is a potential CBS upregulation thing with dysfnctional cysteine exchange from these various antiporters and other receptors like the EAAT3 maybe?? I haven't done all the homework on the yasko stuff, but this draining thing is something I can't comprehend.

I'm wondering if the CBS draining thing may actually be more of a higher requirement for cysteine, but that is just speculation based on futzing around with NAC and ALA.

I wondering is my intolerance in my to those sulfur prodcuts now might be related to a stomach infection of leaky gut?

I tend to be adrenal fatigued, mental fatigued and cognitive dysfunction more than the imobilizing physcial fatigue. However, I do know what being bed bound is like and do get PENE.
Sorry I did not see this before - I only get an alert if you use reply.

In ME, leaky gut was caused by insufficient zinc. I reasoned this out because of the studies proving that zinc "closes the crevices in the nose through which cold germs enter" thus providing a barrier against the common cold. Skin is made of zinc and if you have insufficient zinc your skin will be made like swiss cheese, with progressively larger pores, in order to make the most of the available zinc. Allergies use up zinc for instance, and in dogs, who eat same stuff every day (they canot modify their diets based on cravings, allergies cause actual open sores. Anyway, I tried it in me and found my wheat intolerance (caused by leaky gut allowing absorption of undigested wheat) went away.

zinc is also heavily required by the thyroid. It has been described on a thyroid forum as a dial to turn up the thyroid. It is also used by the adrenal gland. Hypothyroid causes brain fog. (Not saying it is the ONLY possible cause). So it is possible that zinc is your missing link. However IMHO there is never a SIGLE 'missing link'. Usually people who are deficient in one nutrient are deficient I many nutrients. I only suggest that zinc may be one of them. See here and run a TSH lab to see if your thyroid is functioning correctly: http://www.lef.org/protocols/appendix/blood_testing_02.htm?source=search&key=TSH reference range

idk anything about cysteine vs. CBS. I have 2 of the Yasko CBS defects, one +/+ and one +/-. I take a cruciferous veggie supplement every day (Life Extension, but I order it from www.iherb.com) because my hormone lab (www.meridianvelley.com) says that broccoli helps make the non-cancer causing hormones vs. the cancer causing ones. SO I take it every day with my hormone pills to ward off cancer. I have no sensitivity to it and it contains cysteine. I also have taken garlic pills (containing cysteine) for years and also milk thistle (containing cysteine) for years. No issue.
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
The takeaway from all of this is that we're all different. What "works" for one person may indeed be harmful for others.
IMHO the takeaway is that the genetic map is only a guide and should be backed up by lab work to confirm or deny its 'conclusions'.
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
I am still confused about CBS defect as it relates to B6 requirement and whether it matters what type of B6. Also about CBS and homocysteine. Can anyone explain it clearly. I read this thread and the links for articles posted but its not sinking in. If you have CBS defect and high homocysteine do you follow the regular CBS protocol or does the high homocysteine require a different approach or tweaking when your treating
CBS
Well to understand it clearly, you need to search the internet for pictorial biochemistry of the methyl cycle. You can see where homocysteine occurs in the methyl cycle. You can see that it takes 2 biochemical reactions to recycle homocysteine via the mB12+mfolate path and also via the P5P path, but only one chemical reaction via the BHMT path (which is thus FASTER). I have read tons of studies about this and learned that the BHMT path's purpose is to prevent the rise of homocysteine after meals (caused by the time it takes to perform 2 chem reactions on the other paths) and that in healthy people with normal methyl cycle genes, homocysteine is recycled 3 times before it is drained via the P5P path. It also requires working kidneys to dispose of homocysteine so yours will rise if you are taking any drug that disturbs your kidneys, such as NSAIDs. (I get this from a www.lef.org article - an experience of William Falloon's about 'stubborn' homocysteine).

B6 has to be converted to P5P to be used and some people have difficulty converting it. if you have more B6 than you can convert it causes neuropathy. B6 does nothing to protect your kidneys whereas P5P protects your kidneys from glycation. Hence I will not take B6 at all.

If your homocysteine is high *I* would take more TMG and P5P to get it down. If you are not taking any mB12 and mfolate I would be sure to take some, but not a high dose. It appears to ME that there is some relation between high doses of either of these and all the rest of the methylation substances...I personally feel unstable (as in life threateningly so) if I raise either of these two supplements w/o raising P5P and TMG and potassium and B complex (B2). I would not take mB12 or mfolate w/o taking an active B complex. I would not do anything to add methyls w/o making SURE to get enough supplements to recycle immediately and also drain away the extra homocysteine it will cause. This strategy works for me. I have 18 out of 30 Yasko methylation defects, most in the methyl cycle.

Perhaps it is because I am careful to provide nutrients to drain excess homocysteine immediately that I am not sensitive to methyls the way some are.
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
I also agree with dbkita that SUOX may have a big effect regarding P5P/methyls. I do not have a SUOX mutation.

Also, it looks like I did not mention it above, but I have also repeatedly tested my ammonia and I do not have too much ammonia despite genes that say I should, so I do not atke levulose, tucca, or charcoal. IF I ate an Atkins diet (TOO MUCH protein) then I am sure I would hav ethis problem. But I have no problem on a normal 80g or protein/day diet. A high protein diet is linked to over 200% greater chance of many types of cancer so I am not interested I Atkins/paleo anyway. (IMHO paleo is also high protein).
 

Jarod

Senior Member
Messages
784
Location
planet earth
Lots of info. Thanks triffid113

Have you done any testing on a regular basis for methylation(or any kind of testing for that matter) to determine which things you are high or low in, so you can adjust your protocol? For instance some people have done this metamatrix or other amino acids profile that sounds interesting, but expensive.

You know your infections and trying to directly treat those? Or do you think you can get it with just methylation?

From my experience, It seems like the idea is to treat the infections to get the organs working again, while somehow mastering vitamins and detox to function. The end goal being to function with a maintenance level vitamin protocol.

Probably depends on what one has and how sick they are of course.

Jarod
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
Lots of info. Thanks triffid113

Have you done any testing on a regular basis for methylation(or any kind of testing for that matter) to determine which things you are high or low in, so you can adjust your protocol? For instance some people have done this metamatrix or other amino acids profile that sounds interesting, but expensive.

You know your infections and trying to directly treat those? Or do you think you can get it with just methylation?

From my experience, It seems like the idea is to treat the infections to get the organs working again, while somehow mastering vitamins and detox to function. The end goal being to function with a maintenance level vitamin protocol.

Probably depends on what one has and how sick they are of course.

Jarod
I have had the Metametrix OATS test (is that what it's called? anyway it's their basic panel) and it showed some things I have had no counseling what to do about. For instance I had low CoQ10 (which - duh! -governsenergyas it's part of the Kreb cycle, so I switched from ubiquinone 100mg to ubiquinol 50mg (ubiquinol is more expensive!), but I have not retested as it is expensive). I was on the lookout for the biochemistry involved in turning ubiquinone->ubiquinol and finally found that thyroxine is required-! And, huh, my thyroid isn't what it used to be. Well my TSH runs 2.1 (should be <2.0) except it is worse (3.2 in winter due to allergies using up zinc needed by the thyroid). People say they feel better - ore energetic - when their TSH is closer to 1.0 but I have no clue how to get it that good. There was nothing else in the profile I had a clue what to do about, but basically it was not too bad except I think it indicated dopamine and serotonin problems (unless I am thinking of another panel...I consistently show this on panels and no clue how to fix it).

I had an amino acid profile from www.lef.org and it showed low normal on BCAA's and slightly high (3%) on 2 amino acids - cysteine was one, can't recall the other (taurine?). Maybe it was taurine because I know I am high (but not problematically high) in taurine. So I never supplement taurine although Yasko said I should. verything else was midline normal.

I don't know my infections but I don't hang on to infections...what I mean is that I supplement to get rid of any that I get. I take 1g. olive leaf extract every day and it kills all kinds of shit. I take enough zinc and p5p and copper to maintain stomach acid as stomach acid is the main line to killing pathogens. I have low stomach acid because I can barely keep up with zinc and copper requirements so I hover about enough and not enough, but I always correct towards normal. zinc and p5p are known to be needed to make stomach acid and I forget how I deduced the need for copper for stomach acid but it proved to be true. (The clue was from www.ithyroid.com). The zinc requirement is higher than the copper requirement. I can't claim to know the ratio except that it differs depending on you... infections and allergies use up zinc but not so much copper in my observation. hormones help you absorb copper so those who are younger seldom need it and those that are older usually do.

If I get a bad infection I take oregano (oil of oregano) which kills even gram negative bacteria, such as from a tooth infection. I also want to say that DHEA itself (which I take) kills stuff and lowers T NF-alpha. If I am worse off I have taken colloidal silver. When I fell on the ice and hit my head real hard I took my whole arsenal of antioxidants to protect adjacent brain cells from free radical destruction (this strategy minimizes brain cell loss). So usually I take daily 2g mineral ascorbates, 1g Vit E, 200mg CoQ10, but I would also take whatever else I have like astazanthin, astragalus, zinc, garlic, etc.
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
http://www.ncbi.nlm.nih.gov/pubmed/6877313



N Engl J Med. 1983 Aug 25;309(8):448-53.

Homocystinuria--the effects of betaine in the treatment of patients not responsive to pyridoxine.

Wilcken DE, Wilcken B, Dudman NP, Tyrrell PA.

Abstract

The treatment of homocystinuria that is not responsive to pyridoxine is not usually biochemically or clinically successful, and vascular, ocular, and skeletal complications commonly supervene. Persistent marked homocysteinemia appears to be the most important biochemical disturbance leading to these complications. Ten patients with cystathionine beta-synthase deficiency that was not responsive to pyridoxine and one patient with homocystinuria due to a defect in cobalamin metabolism were treated with 6 g daily of betaine added to conventional therapy, to improve homocysteine remethylation. All patients had a substantial decrease in plasma total homocysteine levels (P less than 0.001) and an increase in total cysteine levels (P less than 0.001). Changes in plasma methionine concentrations were variable. Fasting levels of plasma amino acids became normal in two patients, and in six there was immediate clinical improvement. There were no unwanted effects. We conclude that treatment of homocystinuria that is not responsive to pyridoxine and of disorders of homocysteine remethylation should include betaine in adequate doses to ensure maximum lowering of elevated plasma homocysteine levels.
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
Darn I lost what I typed - not sure I feel like doing it all again. You can go to www.lef.org and search for P5P to find that they recommend doses of 50-250mg 2x/day for slowing kidney disease because it protects proteins and fats from glycation (destruction by sugar). Thus I imagine that the more you eat (higher blood sugar) the more p5p you need. B6 does not confer this benefit. A dose of 100mg is suggested to prevent retinopathy (also due to protection of the retina from glycation). It is used to great benefit in cases of depression as it is required to make the neurotransmitters dopamine and serotonin. (However there is a warning regarding taking it with levodopa if you don't take carbidopa o prevent the dopamine from forming before it gets into your brain). At one place lef says pyridoxine (another active form of b6) is being patented for kidney disease so you can't buy it OTC anymore but P5P is actually more effective.

I also read elsewhere of its being used in cases of autism. So now I look and I find a parent worried that he's overdoes his son on p5p. Someone says: "The pathway of b-6I is to promote the formation of cystein. If your son lacks something to convert cystein to glutathione (GSH: active form), cysteins might bind mercury in the body and bring them to his brain." So idk about that. I take cysteine every day and I take 1g Olive Leaf Extract which raises glutathione levels. I also eat a low protein diet and protein is the main dietary source of B6 so I may need more fr that reason or because of my CBS +/+ and +/-. But I was taking it lifelong because it just makes sense. I also take magnesium so I don't have any problem using P5P.

Here's someone who summarizes some f the many studies on B6 in autism (all favorable, some doses listed are 30mg, 100-600mg, etc): http://legacy.autism.com/ari/editorials/ed_vitb6.htm

and here's from a Mom of an autistic child:

http://biomedicalforautism.com/biomedical-update-doing-great/

It has been a while since I have posted a blog update, but it is only because things are going so well that I hate to take time away from my little one to write. Right now we have Skyler on 50mg of P5P, which is an activated form of the B6 vitamin, and 300mg of DMG, which boosts his immune system. Since implementing this combination, Skyler’s language has increased dramatically. He is also much more social with us and just fun to be around. All of a sudden, our child is singing Christmas songs (and other songs that come on the radio) and is telling “knock knock” jokes. It’s really unbelievable how much fun he has become!
The only side effect has been some hyperactivity due to the P5P so we just recently started him on 100mg of Magnesium Glycinate, which is meant to be used in combination with B6 to alleviate hyperactivity. We just started this last night, so I haven’t seen any change yet. But, studies have shown a combination of B6 and magnesium to work even better than B6 alone, so I am excited about possibly seeing even more gains with Skyler.

---
As speculated before, CFS may be a form of adult autism. Studies show that a high percentage of autistic kids have one or more CFS parents...
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
It may have been on another thread (?) but my methylation strategy is to emphasize getting rid of homocysteine via TMG, P5P, and magnesium. I do not rely on mb12 nor mfolate to get rid of homocysteine as that is too slow to be effective. I only care about those supplements because the entire methyl pathway is not expressed/available in all tissues like they are in the liver. In particular the brain does not express the entire methyl pathway...thus to get rid of homocysteine as quickly as possible in the brain requires at least some mb12 and mfolate. But TMG is the FASTEST way to reduce homocysteine and if you do not get sufficient TMG you will have elevated homocysteine (a NEUROTOXIN) after every meal containing protein or methionine in particular. This has been verified experimentally but it is obvious because it takes only 1 chemical reaction to get rid of homocysteine along that pathway whereas every other way requires 2 chemical reactios (slower).
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
idk how many people click o references so I decided to copy that autism text here:
Autism Research Review International, 1987, Vol. 1, No. 4, page 3
Vitamin B6 (and Magnesium) in the Treatment of Autism

All 18 studies known to me in which vitamin B6 has been evaluated as a treatment for autistic children have provided positive results. This is a rather remarkable record, since the many drugs that have been evaluated as treatments for autism have produced very inconsistent results. If a drug shows positive results in about half of the evaluation studies, it is considered a success and the drug is then advocated for use with autistic patients. However, despite the remarkably consistent findings in the research on the use of vitamin B6 in the treatment of autism, and despite its being immeasurably safer than any of the drugs used for autistic children, there are at present very few practitioners who use it or advocate its use in the treatment of autism.

Research on the use of vitamin B6 with autistic children began in the 1960s. In 1966 two British neurologists, A. F. Heeley and G. E. Roberts, reported that 11 of 19 autistic children excreted abnormal metabolites in their urine when given a tryptophan load test. Giving these children a single 30 mg tablet of vitamin B6 normalized their urine; however, no behavioral studies were done. A German investigator, V. E. Bonisch, reported in 1968 that 12 of 16 autistic children had shown considerable behavioral improvement when given high dosage levels (100 mg to 600 mg per day) of vitamin B6. Three of Bonisch’s patients spoke for the first time after the vitamin B6 was administered in this open clinical trial.

After my book Infantile Autism was published in 1964, I began receiving hundreds of letters from parents of autistic children throughout the United States, including a number who had tried the then-new idea of “megavitamin therapy” on their autistic children. Most had begun experimenting with various vitamins on their autistic children as a result of reading books by popular nutrition writers. I initially was quite skeptical about the remarkable improvement being reported by some of these parents, but as the evidence accumulated, my interest was aroused. A questionnaire sent to the 1,000 parents then on my mailing list revealed that 57 had experimented with large doses of vitamins. Many of these had seen positive results in their children. As a result, I undertook a large-scale study, on over 200 autistic children, of megadose quantities of vitamin B6, niacinamide, pantothenic acid, and vitamin C, along with a multiple-vitamin tablet especially designed for the study. The children were living with their parents throughout the U.S. and Canada, and each was medically supervised by the family’s own physician. (Over 600 parents had volunteered for the study, but most could not overcome their physicians’ skepticism.)

At the end of the four-month trial it was clear that vitamin B6 was the most important of the four vitamins we had investigated, and that in some cases it brought about remarkable improvement. Between 30% and 40% of the children showed significant improvement when the vitamin B6 was given to them. A few of the children showed minor side effects (irritability, sound sensitivity and bed-wetting), but these quickly cleared up when additional magnesium was supplied, and the magnesium confirmed additional benefits.

Two years later two colleagues and I initiated a second experimental study of the use of megavitamin therapy on autistic children, this time concentrating on vitamin B6 and magnesium. My co-investigators were Professors Enoch Callaway of the University of California Medical Center at San Francisco and Pierre Dreyfus of the University of California Medical Center at Davis. The double-blind placebo-controlled crossover experiment utilized 16 autistic children, and again produced statistically significant results. For most children dosage levels of B6 ranged between 300 mg and 500 mg per day. Several hundred mg/day of magnesium and a multiple-B tablet were also given, to guard against B6-induced deficiencies of these other nutrients. (In all probability, the temporary numbness and tingling resulting from B6 megadoses, reported by Schaumburg et al., were the result of induced deficiencies of other nutrients caused by taking B6 alone in enormous amounts—a foolish thing to do.)

In both studies the children showed a remarkably wide range of benefits from the vitamin B6. There was better eye contact, less self-stimulatory behavior, more interest in the world around them, fewer tantrums, more speech, and in general the children became more normal, although they were not completely cured.

People vary enormously in their need for B6. The children who showed improvement under B6 improved because they needed extra B6. Autism is thus in many cases a vitamin B6 dependency syndrome.

After completing his participation in our study, Professor Callaway visited France, where he persuaded Professor Gilbert LeLord and his colleagues to undertake additional B6/magnesium research on autistic children. The French researchers, although skeptical that anything as innocuous as a vitamin could influence a disorder as profound as autism, became believers after their first, reluctantly undertaken, experiment on 44 hospitalized children. They have since published six studies evaluating the use of vitamin B6, with and without additional magnesium, on autistic children and adults. Their studies typically used as much as a gram a day of vitamin B6 and half a gram of magnesium.

LeLord and his colleagues measured not only the behavior of the autistic children, but also their excretion of homovanillic acid (HVA) and other metabolites in the urine. Additionally, they have done several studies in which the effects of the vitamin B6 and/or the magnesium on the brain electrical activity of the patients was analyzed. All of these studies have produced positive results.

LeLord et al. recently summarized their results on 91 patients: 14% improved markedly, 33% improved, 42% showed no improvement, and 11% worsened. They noted that “in all our studies, no side effects were observed….” Presumably, no physical side effects were seen.

Several recent studies by two groups of U.S. investigators, Thomas Gualtieri et al., at the University of North Carolina, and George Ellman et al., at Sonoma State Hospital in California, have also shown positive results on autistic patients.

While no patient has been cured with the vitamin B6 and magnesium treatment, there have been many instances where remarkable improvement has been achieved. In one such case an 18-year-old autistic patient was about to be evicted from the third mental hospital in his city. Even massive amounts of drugs had no effect on him, and he was considered too violent and assaultative to be kept in the hospital. The psychiatrist tried the B6/magnesium approach as a last resort. The young man calmed down very quickly. The psychiatrist reported at a meeting that she had recently visited the family and had found the young man to now be a pleasant and easy-going young autistic person who sang and played his guitar for her.

Another example: a frantic mother phoned me to ask for information on sheltered workshops in her city, since her 25-year-old autistic son was about to be expelled for unmanageable behavior. I knew of no alternate placements for the son, but I suggested that the mother try Super Nu-Thera, a supplement containing B6, magnesium and other nutrients. Within a few weeks she called again to tell me excitedly that her son was doing very well now and his piecework pay had risen dramatically from the minimum pay of $1.50 per week to $25 per week.

In view of the consistent findings showing the safety and efficacy of the nutrients B6 and magnesium in treating autistic individuals, and in view of the inevitability of short and/or long-term side effects of drug use, it certainly seems that this safe and rational approach should be tried before drugs are employed.

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P.S. I have never taken more than 100mg B6 nor would I due to potential neuropathy. This post postulates that the reason some have gotton neuropathy at high dose B6 is due to induced deficiencies in other Bs and/or magnesium.
 

triffid113

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To continue the P.S. (I was having network problems and thought I'd lose the note if I did not send), I had never heard of any neuropathy from high dose P5P and I wonder if the neuropathy could be from a backlog of B6 due to impaired or slow conversion to the active form or perhaps from shortage of some nutrient required to turn B6 into P5P. So I have had o qualms about experimenting with P5P...anyway should it cause neuropathy it is only temporary until discontinued. I have tried 300mg P5P plus whatever is in 2 Thorne Basic B with no ill effects and found it lowered my homocysteine only 0.2 (went from 6.3 at 50mg P5P to 6.1 at 300mg) which is negligible. So if the neuropathy is from lack of SAMe as homocysteine is drained away to lower than 6.3, it does not happen at high doses in MYSELF (I was going to say ME but I thought some might read it as an acronym). I found no reason to continue 300mg as there is an expense if 50mg was doing the job. I seem to find that if I do not take the 50mg I get symptoms of anemia (short of breath, things - like even my purse - seem heavy, everything seems like too much work). I seem to find that while 50mg is enough for me at DHEA 75mg, that I seem to benefit from an extra 50mg if I lower my DHEA to 50mg (as in it helps against anxiety/low blood sugar attacks). Personally I would test any protocol you adopt by measuring my homocysteine on it. I do not get neuropathy on 50-100mg P5P/day long term. I did not take 300mg long term because I perceived no additional benefit. I wonder if, were I not taking DHEA, I might need the 600mg P5P dose(???)

Also I take 400-600mg magnesium citrate (with an equal amount of calcium citrate) every day. If I do not take at least 200mg magmesium from only 1 day I cannot sleep that night. I would have mounting problems if this lack of magnesium continued for several days (or if I took only 200mg for may days in a row). Lifelong whenever I feel agitated or sleepless I pop cal-mag pills...it has never occurred to me to blame another nutrient like P5P for what to me have always been obviously symptoms of magnesium shortage. Frankly most Americans do not eat REMOTELY the 7-9 fruits and veggies per day required for health according to the FDA and it is veggies which are the main source of magnesium in the American diet...hence most Americans are low in magnesium...to me that trumps all other reasons for low magnesium.