![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 87. This is the beginning of the thread.
Posted by JLx on November 10, 2003, at 6:49:03
I've been following the discussion on other threads, checked the archives, been doing some reading and am still confused about folic acid and TMG too.
On the Alternative Mental Health site, in comments by Dr. Walsh of the Pfeiffer Clinic, http://www.alternativementalhealth.com/articles/walshQZ.htm#Ta, he says for the under-methylated (as I think I am, due to my positive response to SAMe in the past),
"Treatment focuses on the use of ANTIFOLATES such as calcium, methionine, SAMe, magnesium, zinc, TMG, omega-3 essential oils, B6, inositol, and A, C and E. The dose of inositol is 500 to 1000mg. Choline is anti-dopaminergic and often makes undermethylated patients worse. Also bad are DMAE, copper and FOLIC ACID." (my emphasis)
From Mindboosters by Dr. Ray Sahelian, http://www.mind-boosters.com/chapter_10.html
"Both these vitamins [FOLIC ACID and B12] occupy a key position in the remethylation and synthesis of S-adenosyl-methionine (SAMe), a major methyl donor in the central nervous system. Therefore, deficiencies in either of these vitamins leads to a decrease in SAMe and an increase in homocysteine, which can be critical in the aging brain." (my emphasis)
Elsewhere on that site, Dr. Walsh again,
"The mechanisms of action of SAMe and TMG are quite different. Most of our methyl groups come from dietary methionine. The methionine is converted to SAMe in a reaction with magnesium, ATP, methionine-adenosyl-transferase, and water. SAMe is a relatively unstable carrier of methyl groups and is the primary source of methyl for most reactions in the body. Once the methyl group has been donated, the residual molecule is s-adenosyl-homocysteine which converts to homocysteine. TMG (betaine) is a biochemical which can donate a methyl group to homocysteine, thus converting it back to methionine. The TMG route is secondary to the 5-methyl-tetrahydroFOLATE/B-12 reaction which the primary route for restoring methionine. Methionine and SAMe supplements directly introduce new methyl groups into the body. TMG can provide a methyl group only to the extent that there is insufficient FOLATE/B-12 to do the job. In some persons, the methylation effect of TMG is very minimal. In addition, persons who are undermethylated have a SAM cycle which is "spinning very slowly", much like a superhighway with little traffic. The answer for them is NOT to more efficiently convert the small amount of homocysteine to methionine (using TMG), but rather to directly introduce more methionine or SAMe into the body. A small percentage of persons with sufficient dietary methionine cannot efficiently produce SAMe --- These persons need supplemental SAMe, and not methionine or TMG and are the exception to the rule. In most other cases, methionine supplements alone are sufficient. TMG is a great way to treat individuals with dangerously high homocysteine levels. TMG can be very useful in augmenting methionine therapy along with B-6/P-5-P , serine, etc. The challenge is to supply enough methyl groups to help the patient, without creating dangerously high levels of homocysteine. Use of TMG is an "insurance policy" against this happening. (Jan 22, 2003)" (my emphasis)
So, is folic acid contraindicated for the undermethylated or not?
I'm not sure I understood that distinction about the slow SAMe cycle, but what I concluded was, not knowing if I'm a "slow cycler" or not that I'd hedge my bets and take both TMG AND methionine...using the TMG to counteract homocysteine for one thing, especially if I decrease folic acid. (I had a great result with SAMe, but found it too expensive and when I was taking it as my only anti-depressant remedy, that it pooped out after about 2 months.) I recall Larry's explanation to Ron Hill re why this might happen and concluded that with methionine, it might not.
Should I be concerned about the folic acid in my B-complex? Is 400 or 800 mg per day a good amount or is it contraindicated? (I don't eat green leafy veggies, so I figure my dietary amount is pretty neglible.) Is this something one could evaluate "in real time" with trial and error? (i.e. take some TODAY, feel better or worse TODAY)
Thanks,
JL
Posted by JLx on November 10, 2003, at 7:01:39
In reply to Confused about methylation...Larry H., DSCH, help?, posted by JLx on November 10, 2003, at 6:49:03
Again from Dr. Walsh, on Alternative Mental Health, (this is from a discussion with other doctors apparently),
"A quick way to test for need for methylation therapy is to carry out a cautious trial of SAMe. Within a week or two you should have your answer. If she clearly is improving on the SAMs (which is frightfully expensive)..... you can get usually the same benefits (albeit more slowly) using methionine plus calcium, magnesium, and B-6. This should be side-effect free unless (a) the methylation is begun too abruptly or (b) the patient has a rare genetic enzyme disorder which disrupts the SAM cycle. We've found that direct methylation is usually more successful than tinkering with the SAM cycle. The primary way humans receive most of their methyl groups is from dietary methionine. It's often hard to improve on Mother Nature. (Jan 20, 2003)'
So, "methionine, calcium, magnesium and B6" is SAMe equivalent?
How much of each would be likely?
When I've tried SAMe not only was I less depressed but I had more energy too.
I've been "trial and error" with tyrosine for about 6 weeks now and it's going pretty well. But when I first tried it, I also was using up some SAMe I already had, about 18 days worth. I really noticed when I ran out...less good mood, and considerably less energy.
I've taken methionine (500 mg) now for a few days and think it has some slight bit of the same impact. I've also added TMG, about 400 mg per day for about 5 days.
I already take magnesium and B6 with all my aminos, but don't take calcium as a rule except in tiny amounts as it makes me crazy. ;)
Posted by Larry Hoover on November 10, 2003, at 9:11:12
In reply to Confused about methylation...Larry H., DSCH, help?, posted by JLx on November 10, 2003, at 6:49:03
> I've been following the discussion on other threads, checked the archives, been doing some reading and am still confused about folic acid and TMG too.
I'm not surprised. It's complicated.
> On the Alternative Mental Health site, in comments by Dr. Walsh of the Pfeiffer Clinic, http://www.alternativementalhealth.com/articles/walshQZ.htm#Ta, he says for the under-methylated (as I think I am, due to my positive response to SAMe in the past),
>
> "Treatment focuses on the use of ANTIFOLATES such as calcium, methionine, SAMe, magnesium, zinc, TMG, omega-3 essential oils, B6, inositol, and A, C and E. The dose of inositol is 500 to 1000mg. Choline is anti-dopaminergic and often makes undermethylated patients worse. Also bad are DMAE, copper and FOLIC ACID." (my emphasis)I don't understand Pfeiffer's argument to avoid folate.
> From Mindboosters by Dr. Ray Sahelian, http://www.mind-boosters.com/chapter_10.html
>
> "Both these vitamins [FOLIC ACID and B12] occupy a key position in the remethylation and synthesis of S-adenosyl-methionine (SAMe), a major methyl donor in the central nervous system. Therefore, deficiencies in either of these vitamins leads to a decrease in SAMe and an increase in homocysteine, which can be critical in the aging brain." (my emphasis)Folate and B-12 are essential for the conversion of homocysteine to methionine.
> Elsewhere on that site, Dr. Walsh again,
>
> "The mechanisms of action of SAMe and TMG are quite different. Most of our methyl groups come from dietary methionine. The methionine is converted to SAMe in a reaction with magnesium, ATP, methionine-adenosyl-transferase, and water. SAMe is a relatively unstable carrier of methyl groups and is the primary source of methyl for most reactions in the body. Once the methyl group has been donated, the residual molecule is s-adenosyl-homocysteine which converts to homocysteine. TMG (betaine) is a biochemical which can donate a methyl group to homocysteine, thus converting it back to methionine. The TMG route is secondary to the 5-methyl-tetrahydroFOLATE/B-12 reaction which the primary route for restoring methionine.That's a functional argument. The enzyme which employs TMG (betaine-homocysteine methyltransferase) is inducible, meaning that dietary intake of TMG causes the liver to produce the enzyme to make use of the TMG.
> Methionine and SAMe supplements directly introduce new methyl groups into the body.
Methionine doesn't. Not literally. Only if it's been converted to SAMe.
> TMG can provide a methyl group only to the extent that there is insufficient FOLATE/B-12 to do the job.
Not true. B-12 and TMG are both methyl-donors, but the molecule which takes part in methylation reactions that are of concern in mood disorders is SAMe. B-12 and TMG provide the methyl group to homocysteine to turn it back into methionine.
Here's a visual representation:
http://www.thorne.com/altmedrev/fulltext/meth-fig1.jpg
Note that cyanocobalamin *consumes* SAMe. That's why methylcobalamin is the preferred form of B-12.
> In some persons, the methylation effect of TMG is very minimal.
Yes, it's variable.
> In addition, persons who are undermethylated have a SAM cycle which is "spinning very slowly", much like a superhighway with little traffic. The answer for them is NOT to more efficiently convert the small amount of homocysteine to methionine (using TMG), but rather to directly introduce more methionine or SAMe into the body.
It depends on why it's spinning slowly. If it's because of hyperhomocysteinemia (high blood homocysteine, a risk factor for heart attack, more common in depressives), then the slow SAMe might be caused by poor recycling of homocysteine. There's a blood test for homocysteine.
Your body recycles homocysteine to methionine because dietary sources of methionine may be unreliable (in an historical sense, in evolutionary history). If that cycle gets stalled at homocysteine, only dietary supply can give you methionine. Moreover, homocysteine is doing damage that places even more burden on SAMe. It can set up a vicious cycle. If you think of homocysteine as the basic raw material, which is then methylated (to methionine), then adenosinated (to SAMe), it makes sense to have most of that core stuff already to use, rather than used up. That's just my way of looking at it.
> A small percentage of persons with sufficient dietary methionine cannot efficiently produce SAMe --- These persons need supplemental SAMe, and not methionine or TMG and are the exception to the rule. In most other cases, methionine supplements alone are sufficient. TMG is a great way to treat individuals with dangerously high homocysteine levels.
Which seems contrary to earlier statements, non?
> TMG can be very useful in augmenting methionine therapy along with B-6/P-5-P , serine, etc. The challenge is to supply enough methyl groups to help the patient, without creating dangerously high levels of homocysteine.
I don't understand this statement at all. Supplying methyl groups reduces homocysteine, unless all the "supply" is in the form of cyanocobalamin.
> Use of TMG is an "insurance policy" against this happening. (Jan 22, 2003)" (my emphasis)
>
> So, is folic acid contraindicated for the undermethylated or not?My personal opinion is, no, it is not contraindicated. However, you have to "do the experiment" on yourself to have any insight whatsoever.
> I'm not sure I understood that distinction about the slow SAMe cycle, but what I concluded was, not knowing if I'm a "slow cycler" or not that I'd hedge my bets and take both TMG AND methionine...using the TMG to counteract homocysteine for one thing, especially if I decrease folic acid.
Yes. Good idea.
> (I had a great result with SAMe, but found it too expensive and when I was taking it as my only anti-depressant remedy, that it pooped out after about 2 months.) I recall Larry's explanation to Ron Hill re why this might happen and concluded that with methionine, it might not.
Let's hope.
> Should I be concerned about the folic acid in my B-complex? Is 400 or 800 mg per day a good amount or is it contraindicated? (I don't eat green leafy veggies, so I figure my dietary amount is pretty neglible.) Is this something one could evaluate "in real time" with trial and error? (i.e. take some TODAY, feel better or worse TODAY)
I don't think it would be that quick. How fast did you respond to SAMe?
> Thanks,
>
> JLFrom your next post:
"So, "methionine, calcium, magnesium and B6" is SAMe equivalent? "Presuming you form SAMe in reasonable amounts, i.e. you don't have a genetic defect in SAMe synthesis.
There is no clear "one-size-fits-all" answer, IMHO. Try a nutrient, or groups of nutrients(based on reasonable educated guesses), and see if they help you feel better, or not.
Lar
Posted by Larry Hoover on November 10, 2003, at 9:16:49
In reply to Confused about methylation...Larry H., DSCH, help?, posted by JLx on November 10, 2003, at 6:49:03
http://www.thorne.com/altmedrev/fulltext/meth1-4.html
http://jnnp.bmjjournals.com/cgi/content/full/69/2/228
http://www.thorne.com/altmedrev/fulltext/homo2-4.html
http://circ.ahajournals.org/cgi/content/full/99/1/178
http://lpi.oregonstate.edu/f-w99/vascular.html
Bottom line: Do it for your heart. Brain effects are bonus.Lar
Posted by DSCH on November 10, 2003, at 12:40:29
In reply to Re: Confused about methylation...Larry H., DSCH, help? » JLx, posted by Larry Hoover on November 10, 2003, at 9:11:12
Good post, Lar. Seeing as you're the one with formal education on biochemistry, I don't have anything to add, other than ask why methylcobalamin is bad if it appears necessary for the methionine synthase reaction. Only the 'used-up' form of methylcobalamin consumes SAMe (but at what ratio does the synthase reaction require the methylcobalamin? If it is less than 1:1 you come out ahead on SAMe it seems to me).
Also, I find DMAE's being on the contraindication list for under-methylated persons curious. Sahelain classifies it as a methyl-donor.
I will again state that in my experience, the most dramatic thing that kicked TMG "on" was taking supplementary magnesium.
Posted by DSCH on November 10, 2003, at 12:48:46
In reply to Re: references » JLx, posted by Larry Hoover on November 10, 2003, at 9:16:49
> http://www.thorne.com/altmedrev/fulltext/meth1-4.html
"Methylcobalamin's only known biological function in humans is in the remethylation of homocysteine to methionine via the enzyme methionine synthetase, also known as 5-methyltetrahydrofolate-homocysteine methyltransferase. In order to originally form methylcobalamin from cyanocobalamin or other Cob(III)alamin or Cob(II)alamin precursors, S-adenosylmethionine (SAM) must be available to supply a methyl group. Once methylcobalamin is formed it functions in the regeneration of methionine by transferring its methyl group to homocysteine. Methylcobalamin can then be regenerated by 5-methyl-THF (see Figure 4). The cell's ability to methylate important compounds such as proteins, lipids and myelin will be compromised by a deficiency of either folate or vitamin B12.37 Shortages of active folic acid, SAM, or a dietary deficiency of cobalamin will lead to a decrease in the generation of methylcobalamin and a subsequent impairment in homocysteine metabolism. Since lack of methylcobalamin leads to depressed DNA synthesis, rapidly-dividing cells in the brain and elsewhere are affected.
At least 12 different inherited inborn errors of metabolism related to cobalamin are known. Abnormalities are detectable by urine and plasma assays of methylmalonic acid and homocysteine, and plasma and erythrocyte analysis of cobalamin coenzymes, which can reveal deficiencies of methylcobalamin or adenosylcobalamin.38
Low plasma vitamin B12 levels have been shown to be an independent risk factor for neural tube defect in one study.39 This was an original finding and needs to be confirmed still in further studies. If methionine synthetase is the critical enzyme, methylcobalamin might be able to stimulate the abnormal enzyme as folic acid does, since active folic acid acts to provide the methyl group to cobalamin. It is quite probable that a deficiency in Vitamin B12, folic acid, or any of the cofactors required for their activation may result in a similar dysfunction."
Seems to me you *might* have it the other way around on the subject of B12, Larry. Care to discuss? :-)
Posted by Larry Hoover on November 10, 2003, at 13:08:35
In reply to B12: Methylcobalamin vs. Cyanocobalamin » Larry Hoover, posted by DSCH on November 10, 2003, at 12:48:46
> > http://www.thorne.com/altmedrev/fulltext/meth1-4.html
>
> "Methylcobalamin's only known biological function in humans is in the remethylation of homocysteine to methionine via the enzyme methionine synthetase, also known as 5-methyltetrahydrofolate-homocysteine methyltransferase. In order to originally form methylcobalamin from cyanocobalamin or other Cob(III)alamin or Cob(II)alamin precursors, S-adenosylmethionine (SAM) must be available to supply a methyl group. Once methylcobalamin is formed it functions in the regeneration of methionine by transferring its methyl group to homocysteine. Methylcobalamin can then be regenerated by 5-methyl-THF (see Figure 4). The cell's ability to methylate important compounds such as proteins, lipids and myelin will be compromised by a deficiency of either folate or vitamin B12.37 Shortages of active folic acid, SAM, or a dietary deficiency of cobalamin will lead to a decrease in the generation of methylcobalamin and a subsequent impairment in homocysteine metabolism. Since lack of methylcobalamin leads to depressed DNA synthesis, rapidly-dividing cells in the brain and elsewhere are affected.
>
> At least 12 different inherited inborn errors of metabolism related to cobalamin are known. Abnormalities are detectable by urine and plasma assays of methylmalonic acid and homocysteine, and plasma and erythrocyte analysis of cobalamin coenzymes, which can reveal deficiencies of methylcobalamin or adenosylcobalamin.38
>
> Low plasma vitamin B12 levels have been shown to be an independent risk factor for neural tube defect in one study.39 This was an original finding and needs to be confirmed still in further studies. If methionine synthetase is the critical enzyme, methylcobalamin might be able to stimulate the abnormal enzyme as folic acid does, since active folic acid acts to provide the methyl group to cobalamin. It is quite probable that a deficiency in Vitamin B12, folic acid, or any of the cofactors required for their activation may result in a similar dysfunction."
>
> Seems to me you *might* have it the other way around on the subject of B12, Larry. Care to discuss? :-)What I said, in reference to the diagram, was:
"Note that cyanocobalamin *consumes* SAMe. That's why methylcobalamin is the preferred form of B-12."The article quote, above, says:
"In order to originally form methylcobalamin from cyanocobalamin or other Cob(III)alamin or Cob(II)alamin precursors, S-adenosylmethionine (SAM) must be available to supply a methyl group."These appear to be equivalent statements, to my eye.
Cyanocobalamin is not normally found in nature. The cobalt-porphyrin complex typically has a hydroxyl group or a methyl group on it. Cyanocobalamin was actually created by accident, via filtration through impure charcoal during the first attempts to isolate the complex. Cyanide, the CN- moiety, is toxic, and stresses the liver glutathione system. Moreover, in order to turn the B-12 into a methyl donor, it consumes a methyl donor. There *must* be more to the picture, as oral cyanocobalamin is helpful when used for proven B-12 deficiency, but why not just use methylcobalamin in the first place?
Posted by DSCH on November 10, 2003, at 13:18:01
In reply to Re: B12: Methylcobalamin vs. Cyanocobalamin » DSCH, posted by Larry Hoover on November 10, 2003, at 13:08:35
> What I said, in reference to the diagram, was:
> "Note that cyanocobalamin *consumes* SAMe. That's why methylcobalamin is the preferred form of B-12."Ah yes, my mistake. :-o
Posted by McPac on November 10, 2003, at 17:54:55
In reply to Re: Confused about methylation...Larry H., DSCH, help? » JLx, posted by Larry Hoover on November 10, 2003, at 9:11:12
"A small percentage of persons with sufficient dietary methionine cannot efficiently produce SAMe --- These persons need supplemental SAMe, and not methionine or TMG and are the exception to the rule."
>>>>>>>>>> I wonder if I am in this small percentage? Pfeiffer recently increased my methionine to 2,500 mg/day, as 1,500 mg/day for MANY months wasn't doing anything....in this small % of folks, WHY is their methionine not converted to SAMe?
Posted by DSCH on November 10, 2003, at 20:38:47
In reply to Re: Confused about methylation...Larry H., DSCH, help?, posted by McPac on November 10, 2003, at 17:54:55
> "A small percentage of persons with sufficient dietary methionine cannot efficiently produce SAMe --- These persons need supplemental SAMe, and not methionine or TMG and are the exception to the rule."
>
> >>>>>>>>>> I wonder if I am in this small percentage? Pfeiffer recently increased my methionine to 2,500 mg/day, as 1,500 mg/day for MANY months wasn't doing anything....in this small % of folks, WHY is their methionine not converted to SAMe?Not enough ATP or magnesium to spare from other duties? A deficency in the enzymes that accomplish this task?
Posted by JLx on November 11, 2003, at 7:22:16
In reply to Re: Confused about methylation...Larry H., DSCH, help? » JLx, posted by Larry Hoover on November 10, 2003, at 9:11:12
> I don't understand Pfeiffer's argument to avoid folate.
Well, I'm glad to hear you say that because it seemed to contradict everything else I've read. What gave me pause is that this is this guy's life's work! "How can he be so wrong?", I thought. I thought I just was misunderstanding this stuff because the chemistry is incomprehensible to me.
> Methionine doesn't. Not literally. Only if it's been converted to SAMe.
>
> > TMG can provide a methyl group only to the extent that there is insufficient FOLATE/B-12 to do the job.
>
> Not true. B-12 and TMG are both methyl-donors, but the molecule which takes part in methylation reactions that are of concern in mood disorders is SAMe. B-12 and TMG provide the methyl group to homocysteine to turn it back into methionine.
>
> Here's a visual representation:
>
> http://www.thorne.com/altmedrev/fulltext/meth-fig1.jpg
>
> Note that cyanocobalamin *consumes* SAMe. That's why methylcobalamin is the preferred form of B-12.I've heard that the methylcobalamin is preferred, but not that the cyanocobalamin form of B12 was actually CONTRAINDICATED...is that what you mean there? (If one wants to increase SAMe) I bought some of the methyl form, but have been taking it with the other because I had two bottles of the other.
> Your body recycles homocysteine to methionine because dietary sources of methionine may be unreliable (in an historical sense, in evolutionary history). If that cycle gets stalled at homocysteine, only dietary supply can give you methionine. Moreover, homocysteine is doing damage that places even more burden on SAMe. It can set up a vicious cycle. If you think of homocysteine as the basic raw material, which is then methylated (to methionine), then adenosinated (to SAMe), it makes sense to have most of that core stuff already to use, rather than used up. That's just my way of looking at it.Ok ... we don't have to ever worry about having not-enough-homocysteine to do the conversion (ultimately) to SAMe if we have methionine per diet but we do have to worry about excess homocysteing if enough of it's not converting. So the core stuff we want to increase is either/ both the methionine or the anti-homocysteine. Hence the usefulness of TMG, methionine supplementation (or per diet) and other anti-homocysteine agents such as the B vits. Btw, I know eggs are a dietary source of methionine, and I eat them regularly and even looked forward to eating them...until I started taking SAMe, when they became less of a draw. (I'm a firm believer that the foods we find ourselves craving or drawn to are often an indication of what our body actually NEEDS....although I didn't notice these things very well until I started taking magnesium.)
> Which seems contrary to earlier statements, non?
> > [Quoting Dr. Walsh] TMG can be very useful in augmenting methionine therapy along with B-6/P-5-P , serine, etc. The challenge is to supply enough methyl groups to help the patient, without creating dangerously high levels of homocysteine.
> I don't understand this statement at all. Supplying methyl groups reduces homocysteine, unless all the "supply" is in the form of cyanocobalamin.It's enough to make me doubt the entire Pfeiffer Clinic, quite frankly, if this guy is supposed to be one of the big shots there.
> > So, is folic acid contraindicated for the undermethylated or not?
> My personal opinion is, no, it is not contraindicated. However, you have to "do the experiment" on yourself to have any insight whatsoever.I've usually taken a B complex but never noticed feeling either better or worse taking it or not taking it suggesting to me that I'm not very sensitive to folic acid in either direction.
> > I'm not sure I understood that distinction about the slow SAMe cycle, but what I concluded was, not knowing if I'm a "slow cycler" or not that I'd hedge my bets and take both TMG AND methionine...using the TMG to counteract homocysteine for one thing, especially if I decrease folic acid.
>
> Yes. Good idea.Good, glad I got something right out of all that. :)
> > (I had a great result with SAMe, but found it too expensive and when I was taking it as my only anti-depressant remedy, that it pooped out after about 2 months.) I recall Larry's explanation to Ron Hill re why this might happen and concluded that with methionine, it might not.
>
> Let's hope.Indeed! SAMe pooping out was very crushing to my hopes of realizing a dream for natural remedies in place of ADs.
> > Should I be concerned about the folic acid in my B-complex? Is 400 or 800 mg per day a good amount or is it contraindicated? (I don't eat green leafy veggies, so I figure my dietary amount is pretty neglible.) Is this something one could evaluate "in real time" with trial and error? (i.e. take some TODAY, feel better or worse TODAY)
>
> I don't think it would be that quick. How fast did you respond to SAMe?Most recently, I felt better within a day or two, but I was also newly supplementing with tyrosine too. When I tried SAMe previously it was also prior to magnesium supplementation. My experience now is that ANYTHING I tried in the past before mg, works differently now.
> From your next post:
> "So, "methionine, calcium, magnesium and B6" is SAMe equivalent? "
>
> Presuming you form SAMe in reasonable amounts, i.e. you don't have a genetic defect in SAMe synthesis.
>
> There is no clear "one-size-fits-all" answer, IMHO. Try a nutrient, or groups of nutrients(based on reasonable educated guesses), and see if they help you feel better, or not.Right. Thanks! :)
JL
Posted by JLx on November 11, 2003, at 7:31:27
In reply to Re: Confused about methylation...Larry H., DSCH, help? » JLx, posted by Larry Hoover on November 10, 2003, at 9:11:12
> > I'm not sure I understood that distinction about the slow SAMe cycle, but what I concluded was, not knowing if I'm a "slow cycler" or not that I'd hedge my bets and take both TMG AND methionine...using the TMG to counteract homocysteine for one thing, especially if I decrease folic acid.
>
> Yes. Good idea.On that, any idea what might be a reasonable amount of each to take...to achieve a SAMe-like result without raising homocysteine too high? (I can't afford the blood test at this time.)
Posted by JLx on November 11, 2003, at 7:43:40
In reply to Re: Confused about methylation...Larry H., DSCH, help? » Larry Hoover, posted by DSCH on November 10, 2003, at 12:40:29
> Also, I find DMAE's being on the contraindication list for under-methylated persons curious. Sahelain classifies it as a methyl-donor.
Graham Blake has that same info on the link you posted previously in your exchange with Francesco. (His website has really been spruced up!) http://www.nutritional-healing.com.au/condition.php?category=neuro&condition=Depression
I wonder what the deal is with choline too, if they're right or wrong on that one. What do you think? I was taking a choline/inositol combo, and also taking additional lecithin. I stopped taking both recently per that recommendation but am not sure if I feel an impact.
> I will again state that in my experience, the most dramatic thing that kicked TMG "on" was taking supplementary magnesium.
I feel as if I have a whole new baseline for physical reactions since I've been taking magnesium. I was tempted to say, "a whole new body"...wouldn't that be nice? ;)
You're doing ok on TMG? And no longer any amino acids, I believe you said on another thread. I couldn't understand why you thought TMG would be so helpful until I really tried to sort out all that methyl info.
I've been really helped by the tyrosine, however, and am leery of cutting it out altogether though I have cut it down from my original dose.
Posted by Larry Hoover on November 11, 2003, at 8:35:39
In reply to Re: DMAE, choline, TMG » DSCH, posted by JLx on November 11, 2003, at 7:43:40
> I wonder what the deal is with choline too, if they're right or wrong on that one. What do you think? I was taking a choline/inositol combo, and also taking additional lecithin. I stopped taking both recently per that recommendation but am not sure if I feel an impact.Just for the sake of getting past the terminology, choline is tetramethylglycine, while betaine is trimethylglycine. If choline donates a methyl group, which it does in some reactions, it becomes TMG. Supplemental TMG will also be somewhat converted into choline.
Lar
Posted by Larry Hoover on November 11, 2003, at 9:07:07
In reply to Re: Another question » Larry Hoover, posted by JLx on November 11, 2003, at 7:31:27
>
> > > I'm not sure I understood that distinction about the slow SAMe cycle, but what I concluded was, not knowing if I'm a "slow cycler" or not that I'd hedge my bets and take both TMG AND methionine...using the TMG to counteract homocysteine for one thing, especially if I decrease folic acid.
> >
> > Yes. Good idea.
> On that, any idea what might be a reasonable amount of each to take...to achieve a SAMe-like result without raising homocysteine too high? (I can't afford the blood test at this time.)First, you won't raise homocysteine, if you're taking TMG.
The dose of TMG that is effective varies substantially in different people. I can't tolerate more than a couple grams, tops. And I can't take it every day. I take 500-1000 mg, occasionally. But I know people who take eight or ten grams, every day.
Posted by Larry Hoover on November 11, 2003, at 9:17:12
In reply to Re: Confused about methylation...Larry H., DSCH, help? » Larry Hoover, posted by JLx on November 11, 2003, at 7:22:16
> > I don't understand Pfeiffer's argument to avoid folate.
>
> Well, I'm glad to hear you say that because it seemed to contradict everything else I've read. What gave me pause is that this is this guy's life's work! "How can he be so wrong?", I thought. I thought I just was misunderstanding this stuff because the chemistry is incomprehensible to me.I think you're comprehending quite well. My thinking is that Pfeiffer didn't keep up with more recent work. His thinking fossilized. Good start, but no finish.
> I've heard that the methylcobalamin is preferred, but not that the cyanocobalamin form of B12 was actually CONTRAINDICATED...is that what you mean there?If the diagrammed pathways were all there were to consider, it would be contraindicated. But that's not what I meant. You do get a benefit from cyanocobalamin, despite the fact that it seems to use up the very stuff you're trying to create, at a molecular ratio of 1:1. It looks like there should be no net benefit, but there obviously is one.
> (If one wants to increase SAMe) I bought some of the methyl form, but have been taking it with the other because I had two bottles of the other.
I take both, too, and for the same reason.
> So the core stuff we want to increase is either/ both the methionine or the anti-homocysteine. Hence the usefulness of TMG, methionine supplementation (or per diet) and other anti-homocysteine agents such as the B vits.That's the take-home message, yes.
> Btw, I know eggs are a dietary source of methionine, and I eat them regularly and even looked forward to eating them...until I started taking SAMe, when they became less of a draw. (I'm a firm believer that the foods we find ourselves craving or drawn to are often an indication of what our body actually NEEDS....although I didn't notice these things very well until I started taking magnesium.)
Cravings can be good indicators, but they can also just be cravings.
> It's enough to make me doubt the entire Pfeiffer Clinic, quite frankly, if this guy is supposed to be one of the big shots there.
There's a lot of good in the Pfeiffer conceptualization. Recognizing some flaws does not invalidate the entire body of work. Unfortunately, recognizing the flaws is the harder part.
> > > So, is folic acid contraindicated for the undermethylated or not?
>
> > My personal opinion is, no, it is not contraindicated. However, you have to "do the experiment" on yourself to have any insight whatsoever.
>
> I've usually taken a B complex but never noticed feeling either better or worse taking it or not taking it suggesting to me that I'm not very sensitive to folic acid in either direction.It can't hurt to take B-vitamins. That's my bottom line concept. Can't hurt, might help, might not notice the help.
> > I don't think it would be that quick. How fast did you respond to SAMe?
>
> Most recently, I felt better within a day or two, but I was also newly supplementing with tyrosine too. When I tried SAMe previously it was also prior to magnesium supplementation. My experience now is that ANYTHING I tried in the past before mg, works differently now.I respond to TMG within one hour. Just curious. I never used SAMe. Too expensive, and if you're prone to hyperhomocysteinemia, it's exactly the wrong thing to use.
> > From your next post:
> > "So, "methionine, calcium, magnesium and B6" is SAMe equivalent? "
> >
> > Presuming you form SAMe in reasonable amounts, i.e. you don't have a genetic defect in SAMe synthesis.
> >
> > There is no clear "one-size-fits-all" answer, IMHO. Try a nutrient, or groups of nutrients(based on reasonable educated guesses), and see if they help you feel better, or not.
>
> Right. Thanks! :)
>
> JL
Welcome.Lar
Posted by DSCH on November 11, 2003, at 10:35:45
In reply to Re: Confused about methylation...Larry H., DSCH, help? » JLx, posted by Larry Hoover on November 11, 2003, at 9:17:12
> > > I don't understand Pfeiffer's argument to avoid folate.
> >
> > Well, I'm glad to hear you say that because it seemed to contradict everything else I've read. What gave me pause is that this is this guy's life's work! "How can he be so wrong?", I thought. I thought I just was misunderstanding this stuff because the chemistry is incomprehensible to me.
>
> I think you're comprehending quite well. My thinking is that Pfeiffer didn't keep up with more recent work. His thinking fossilized. Good start, but no finish.Carl Curt Pfeiffer, MD, PhD, passed on in 1988 not very long after he and William Walsh, PhD (PhD in chemical engineering, worked into hair analysis and orthomolecular psychiatry via his volunteer work at Illinois prisons while an employee of Argonne National Laboratory) compared notes.
http://www.hriptc.org/introducing_HRIxPTC.htm
Posted by DSCH on November 11, 2003, at 11:20:41
In reply to Re: DMAE, choline, TMG » DSCH, posted by JLx on November 11, 2003, at 7:43:40
> I wonder what the deal is with choline too, if they're right or wrong on that one. What do you think? I was taking a choline/inositol combo, and also taking additional lecithin. I stopped taking both recently per that recommendation but am not sure if I feel an impact.
As I consume virtually no eggs and milk, I have started taking lecithin which has both phosphatidylcholine and phosphatidylinositol. I started fish oil at the same time. I noticed a modest improvement from this in visual clarity and greater tendency to feel "grounded" in the present objective/subjective outer reality. Having read a little about the dissociative drugs (DXM/DXO, Ketamine) I feel that before all this, I was "naturally" dissociated to some degree!
Regarding inositol: I took it for a number of weeks in August. I had what I first believed to be a quite strange reaction (but in the end, postive) to the first dose, however I think that experience was more likely a result of the "Sacksian" cumulative tinkering I had been doing on myself up to that point (I would recommend seeing the deNero/Williams movie and getting the book "Awakenings"). The parallel was erie enough for me to worry that I would run into an analgous predicament to his post-encephalitic patients on L-DOPA, but fortunately most of those concerns of mine have faded in the months since then as things stabilized.
For a number of weeks there I felt like the neurochemical equivalent to the semi-transparent model of the human body! :-/ ;-)
> > I will again state that in my experience, the most dramatic thing that kicked TMG "on" was taking supplementary magnesium.
>
> I feel as if I have a whole new baseline for physical reactions since I've been taking magnesium. I was tempted to say, "a whole new body"...wouldn't that be nice? ;)
>
> You're doing ok on TMG? And no longer any amino acids, I believe you said on another thread. I couldn't understand why you thought TMG would be so helpful until I really tried to sort out all that methyl info.
>
> I've been really helped by the tyrosine, however, and am leery of cutting it out altogether though I have cut it down from my original dose.Yes, although I had great successes with DLPA, protein powder drinks, and L-tyrosine (at various times), they were "brittle" and I was dismayed at finding it necessary to treat myself at such short intervals. I also found it unconvincing that amino acid metabolism was my root problem. So I eventually was brought around to reconsider methylation, which I had discounted due to a less than impressive response to TMG (pre-Mg).
Posted by McPac on November 11, 2003, at 16:59:44
In reply to Re: Confused about methylation...Larry H., DSCH, help? » Larry Hoover, posted by JLx on November 11, 2003, at 7:22:16
"SAMe pooping out was very crushing to my hopes of realizing a dream for natural remedies in place of ADs".
>>>> Have you tried tryptophan?
Posted by McPac on November 11, 2003, at 17:11:58
In reply to Carl Curt Pfeiffer, MD, PhD (?-1988) » Larry Hoover, posted by DSCH on November 11, 2003, at 10:35:45
"I respond to TMG within one hour. Just curious. I never used SAMe. Too expensive, and if you're prone to hyperhomocysteinemia, it's exactly the wrong thing to use".
Lar---WHAT do you notice the TMG doing for you?
JLx, what do you notice also?
I seem to notice very little from supplements...but not that glorious tryptophan though, THAT I notice!Lar, so are you saying that SAMe
is WRONG to take if you have high homocysteine levels? Later!
Posted by McPac on November 11, 2003, at 17:21:18
In reply to Lar/JLx, Re: Carl Curt Pfeiffer, MD, PhD (?-1988), posted by McPac on November 11, 2003, at 17:11:58
I wonder why one of the nurses at Pfeiffer said for me to get some SAMe...maybe the methionine and TMG that I take would counter the homocysteine-elevating properties of the SAMe, while I'd still be getting the AD effect of the SAMe??
Posted by Larry Hoover on November 12, 2003, at 6:43:46
In reply to Lar/JLx, Re: Carl Curt Pfeiffer, MD, PhD (?-1988), posted by McPac on November 11, 2003, at 17:11:58
> "I respond to TMG within one hour. Just curious. I never used SAMe. Too expensive, and if you're prone to hyperhomocysteinemia, it's exactly the wrong thing to use".
>
> Lar---WHAT do you notice the TMG doing for you?Increased physical and mental energy, focus.
> I seem to notice very little from supplements...but not that glorious tryptophan though, THAT I notice!
>
> Lar, so are you saying that SAMe
> is WRONG to take if you have high homocysteine levels? Later!SAMe turns into homocysteine when its used up. Deal with the homocysteine, by turning it back into methionine, and maybe you don't need SAMe supps at all.
Posted by Larry Hoover on November 12, 2003, at 6:44:43
In reply to Re: Lar/JLx, Re: Carl Curt Pfeiffer, MD, PhD (?-1988), posted by McPac on November 11, 2003, at 17:21:18
> I wonder why one of the nurses at Pfeiffer said for me to get some SAMe...maybe the methionine and TMG that I take would counter the homocysteine-elevating properties of the SAMe, while I'd still be getting the AD effect of the SAMe??
They're clutching at straws, dude. Trying to squeeze success out of failure. IMHO.
Posted by JLx on November 12, 2003, at 16:11:13
In reply to Re: Another question » JLx, posted by Larry Hoover on November 11, 2003, at 9:07:07
> >
> > > > I'm not sure I understood that distinction about the slow SAMe cycle, but what I concluded was, not knowing if I'm a "slow cycler" or not that I'd hedge my bets and take both TMG AND methionine...using the TMG to counteract homocysteine for one thing, especially if I decrease folic acid.
> > >
> > > Yes. Good idea.
>
>
> > On that, any idea what might be a reasonable amount of each to take...to achieve a SAMe-like result without raising homocysteine too high? (I can't afford the blood test at this time.)
>
> First, you won't raise homocysteine, if you're taking TMG.
>
> The dose of TMG that is effective varies substantially in different people. I can't tolerate more than a couple grams, tops. And I can't take it every day. I take 500-1000 mg, occasionally. But I know people who take eight or ten grams, every day.Ok, I know I have to experiment with how it feels but wrt homocysteine, what if there is an imbalance between the homocysteine-increasing effect of methionine and the homocysteine-lowering effect of TMG? Iow, do I have to make sure to take "x" amount of TMG if I take "xx" amount of methionine?
(Forgive me if that's something you've already addressed -- I'm just not "getting" this in terms of the chemistry here.)
Re previous post, just to be clear on this too, choline is NOT contraindicated for the undermethylated....despite what Dr. Walsh says?
Thanks,
JL
Posted by JLx on November 12, 2003, at 16:25:54
In reply to Re: DMAE, choline, TMG » JLx, posted by DSCH on November 11, 2003, at 11:20:41
> As I consume virtually no eggs and milk, I have started taking lecithin which has both phosphatidylcholine and phosphatidylinositol. I started fish oil at the same time. I noticed a modest improvement from this in visual clarity and greater tendency to feel "grounded" in the present objective/subjective outer reality.
Hmm...interesting. I really need to isolate my "trials" more so I can evaluate such things, but I've been so desperate to feel better and get more functional, that I just threw everything at my brain all at once. (Which worked rather well, actually, but I'm nervous about the longer-run.)
> Regarding inositol: I took it for a number of weeks in August. I had what I first believed to be a quite strange reaction (but in the end, postive) to the first dose, however I think that experience was more likely a result of the "Sacksian" cumulative tinkering I had been doing on myself up to that point (I would recommend seeing the deNero/Williams movie and getting the book "Awakenings"). The parallel was erie enough for me to worry that I would run into an analgous predicament to his post-encephalitic patients on L-DOPA, but fortunately most of those concerns of mine have faded in the months since then as things stabilized.
I thought that movie was hideously depressing, but so far I'm the only person I've met who thought so. It reminded me too much of how I would think an anti-depressant (or whatever) was working, I would wake up out of my depressive lethargy for a time feeling like I had my life/self back, and then sink back down again, feeling even more hopeless.
> Yes, although I had great successes with DLPA, protein powder drinks, and L-tyrosine (at various times), they were "brittle" and I was dismayed at finding it necessary to treat myself at such short intervals. I also found it unconvincing that amino acid metabolism was my root problem. So I eventually was brought around to reconsider methylation, which I had discounted due to a less than impressive response to TMG (pre-Mg).
Well, I am hopeful too that this may be a key factor for me too, since I had such a positive reaction to SAMe. I'm going to stick with the tyrosine too for a while, as I believe it's helping other things too, such as my thyroid.
Thanks for the input. :)
JL
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