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
poster:Larry Hoover
thread:278139
URL: http://www.dr-bob.org/babble/alter/20031104/msgs/278173.html