Posted by Larry Hoover on May 25, 2005, at 7:50:51
In reply to RE: sulphur metabolism » Larry Hoover, posted by JLx on May 24, 2005, at 22:53:57
My, my, you do keep me on my toes.
:-)
> I said,
>
> "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.
>
> You said,
>
> "Yes. Good idea."
>
> So, what do you think now?
I'm going to contradict myself. Sort of.It really doesn't make one bit of difference where the methionine comes from. It simply must be present in the liver for SAMe to be created. If you are having some trouble forming SAMe despite adequate methionine, then increasing methionine will be of no effect. In contrast, if SAMe output is low because of poor recycling of homocysteine to methionine, then increasing that rate with TMG and/or B12 and folate *might* be sufficient to optimize methionine recycling, and thus SAMe output.
I cannot recall for certain exactly what I meant, but I suspect I was speaking to the "foolproof" argument about methionine supply. What if a person does not have a homocysteine backlog (where the cycle usually stalls in depression)? Optimizing homocysteine recycling will have little effect. Then, only dietary intake will solve the methionine deficiency.
So, in summary, if SAMe output is low despite adequate methionine, SAMe supps might be a good idea. (What makes SAMe output low is a separate issue, involving (probably) mitochondrial dysfunction.) If high homocysteine is the problem (stalled recycling), then SAMe supps are contraindicated (they'll simply make homocysteine worse). In that case, increasing remethylation with TMG and/or B12-folate solves the problem. If and only if methionine is deficient despite proper remethylation is methionine supplementation formally indicated.
Like I said, I suspect I was giving you the foolproof "increase the methionine without doubt" answer.
>
> I'm really intrigued with this methylation stuff, especially given the homocysteine/heart disease/depression connection. In that last discussion I was trying to sort out what Dr. Walsh said about folate, which you seemed to agree was contradictory to some of his other comments.
>
> Since then, this past winter, when I wasn't taking TMG, MSM or methionine, I felt a good effect from folic acid, 800 mg/day, I thought. I wasn't taking methylcobalamin either. At least now I know that folate doesn't bother me, so whatever Walsh was saying there, I don't think I have to worry about it.Your liver stores vast amounts of B12. It is believed the average person stores 5 years' worth. I would dispute that, as the liver just doesn't suddenly run out. All B12 dependent rates decline as the reserves decline.....
> Of these things:
>
> TMG
> METHYLCOBALAMIN
> FOLATE
> METHIONINE
>
> what is the best combination to duplicate SAM-e (which I had good effect from in the past for about 2 months) AND prevent homocysteine buildup?Methionine is not the answer, if you are concerned with homocysteine increases. Same goes with SAMe. What you want is enhanced recycling. There are two distinct recycling processes. The "standard" one, the one doctors believe is virtually foolproof (despite the cases of hyperhomocyteinemia they see all the time) is the B12-folate pathway. That one needs both nutrients in a 1:1 ratio (not intake, available). A distinct inducible mechanism (kind of like a reserve capacity that can be brought on line) requires TMG. So, my answer involves three of the four nutrients listed. No methionine (unless the other interventions fail).
> Is there a way of knowing when one might become OVERmethylated?I have reservations about that diagnostic category's existence. Rather than being overmethylated, I would characterize the syndrome as being differently malnourished. The body needs balancing, but I don't see the solution as suppressing methylation. It would be to bring the other processes up to a balanced capacity.
> And how about MSM and taurine? Choline?
>
> The pdf file you gave me says, "There is a metabolic relationship between methionine and MSM." http://www.findarticles.com/p/articles/mi_m0FDN/is_1_7/ai_83582816
>
> And also,
>
> "Sulfur containing compounds include methionine, cysteine, taurine, thiamin, biotin, alpha lipoic acid, glucosamine sulfate. They're all synthesized from methionine except thiamin and biotin."I think it is a gross oversimplification to say that e.g. taurine is synthesized from methionine. It is true, but there are 8 (?) intermediates. I've been simplifying things myself. Cysteine comes from homocysteine (alternate pathway to the one that makes methionine). Taurine comes from cysteine. All kinds of enzymes and hormones require cysteine (insulin, for example). Sulphur metabolism is complex.
There is an excellent diagram here:
http://www.bbriefings.com/pdf/26/ept032_t_axis.pdfThe first two also have diagrams, but the third is specific to depression:
http://www.thorne.com/altmedrev/fulltext/meth1-4.html
http://www.thorne.com/altmedrev/fulltext/homo2-4.html
http://jnnp.bmjjournals.com/cgi/content/full/69/2/228> Is it advisable to supplement with thiamin and biotin, or not?
Yes, and yes. Thiamine is B1. It is certainly an essential nutrient. Biotin is considered to be conditionally essential, but I wouldn't want to assume that I'm in the condition where it isn't essential.
> This is interesting considering Louise Gittlelman's advice to women about excess copper and depression:
>
> "Excessive copper ingestion impairs sulfur containing amino acids and increases the dietary requirement for SAA as well."Far far worse is mercury. Mercury is toxic precisely because of what it does to sulphur. It loves sulphur. It can't get enough sulphur. If you want to protect sulphur from mercury's rapacious appetite, you need selenium.
I've looked a lot at copper, and although it is essential, and it can easily become toxic, I doubt very many people are deficient. Zinc is a pretty good regulator of copper. Zinc deficiency exacerbates any effects of copper.
> > Here's a good review of the various essential sulphur compounds:
> >
> > http://www.thorne.com/altmedrev/.fulltext/7/1/22.pdfEmphasizing again.....this reference covers supplemental sulphur specifically.
> > The thing is, sulphur loves to oxidize. I think of depression as being characterized by excessive oxidation (oxidative stress). That's why antioxidants (e.g. polyphenols) and vitamins can have such effects as they do. That's why we need fish oil....our long chain PUFAs have been burned up (oxidized) long ago.
> >
> > Sulphur compounds are easy targets for oxidation. But sulphur bridges (or disulphide bonds across cystine residues) are essential for enzyme structure. Reactive sulphur aminos are in many enzyme active sites. Many antioxidants depend directly on sulphur activity (e.g. glutathione). Liver health depends on sulphur supply. Oxidation wrecks all this.
> >
> > I think that sulphur supplementation is a good thing. It's in finding the balance.....too much too quickly makes you feel yucky, IMHO.
> >
> > Perhaps a better angle is to unblock an internal logjam, i.e. homocysteine to methionine. TMG does that. B12 and folate do that together. A little cysteine (NAC) or taurine to smoothe out the load.
> >
> > Hard to get it right, but really worth a try, IMHO.
> >
> > Maybe a long-term SAMe supp is the answer for some.
> >
> > Lar
>
> SAM-e is too expensive for me to experiment much with. It did help me in the past but then so did TMG. And I like the way MSM feels too. I'm not so sure about methylcobalamin.It is possible that TMG does other things than just to enhance homocysteine recycling. If instead of losing a methyl group to homocysteine, it gains a methyl group, it has become choline.
> What did you mean by too much sulfur makes you feel yucky? And for what reason?
Overdoing sulphur intake can make you feel sick. That goes for any sulphur substance (I think). I'm not sure why (I've never looked at it). It's just pretty good feedback that you've exceeded your capacity for using whatever it is you're taking.
> When I was taking SAM-e, I noticed I didn't have my former craving for eggs.Interesting. I believe in cravings, as a message. I'm not sure what this one indicates, though.
> Is it possible to get over-antioxidented? I noticed that article said something about MSM being a free radical scavenger, so that seems like another good reason to take it.
No, I don't think you can become over-antioxidanted. Not without overdosing on a specific one, anyway. And I would call that a toxic effect, in any case.
> I'd really like to sort this out into some kind of plan as to what to try in what combinations. I haven't been very systematic about it in the past, and now don't even remember what I'd tried before either. So I kind of feel like I'm starting from scratch. And as usual, not very patient about trying just *one* thing at a time. :)Shortcuts give you less information. I know you know that. Sorry, no magic.
> Actually right now I am also trying NADH for the first time. I'm taking 5 mg, 3 days now. The first day I didn't even feel it. Yesterday, I felt more anxious about an hour after I took it. Today, it's hard to say as I've had a lot of things on my mind. I don't feel the energy boost though, unfortunately. I was hoping to be speeding around my house cleaning by now. Now THAT would really be something! :)
>
> JLIn my readings about NADH, it seems there are two reactions. One is immediate (I know I get a buzz the day I use it). The literature, however, says it takes a couple of weeks to reach a stable level, and *that's* when the energy benefit comes.
I dunno. I get irritable after a few weeks on it.
NADH with TMG was Ron Hill's and my favourite. They seemed to be synergistic, rather than additive.
Lar
poster:Larry Hoover
thread:476058
URL: http://www.dr-bob.org/babble/alter/20050510/msgs/502639.html