5 replies to this topic

[vasra]

Personal Intro to SAM-e
I have experimented with SAM-e myself for the past 1.5 years after having tapered off escitalopram (e.g. Cipralex), which I used for c. 1.5. years. the SSRI was good in treating my most severe bouts of anxiety and associated depression, but in the end I wanted off it.

Now I've been using SAM-e, first 400mg/day (yes, low, but very effective for me) and now for the past 6 months 200mg/day (low, still seems to work). My goal is to get off it altogether, but going for more than week or two without it and I start to notice my anxity kick back in. Mindfulness-based therapies have helped me immensely, but I'm not yet in good balance, imho, so I benefit from my daily dose of SAm-E

As many people here seem to use SAM-e regularly, I though it would be useful and interesting to look at the potential safety issues of long-term SAM-e use.

Safety of SAM-e for long-term use

Browsing through PubMed (not exhaustively), I came across these:

Excessive S-adenosyl-L-methionine-dependent methylation increases levels of methanol, formaldehyde and formic acid in rat brain striatal homogenates: possible role in S-adenosyl-L-methionine-induced Parkinson's disease-like disorders.
http://www.ncbi.nlm....pubmed/18930743
- rat study, brain injections, excessive levels of sam-E
- generation of formaldehyde => methylation =>

Effect of formaldehyde on cell proliferation and death.
http://www.ncbi.nlm....pubmed/21067524
- SAM-e is a formaldehydogenic compound and indicated in induction of cell death => neurodegnerative processes

Browsing through my books on Parkinson's and neurodegenerative disorders, I came upon these hits:

"Treatment with medications that increase the metabolism of homocysteine [e.g., S-adenosylmethionine (SAM-e)] may attenuate the effects of elevated homocysteine levels (124)", William M. McDonald, Depression (chapter 16), in Factor & Weiner, Parkinson's Disease - Diagnosis and Clinical Management, 2nd ed., Demos, 2008
+ SAM-e is suggested as an addition to PD treatment through lowering of homocysteine levels

There were further studies showing that SAM-E is a primary methyl group donor and as such involved in methylation processes.

Interim conclusion (tentative)?
SAM-e may NOT be safe at all levels and may in fact be a causative agent in inducing neurodegenerative effects, which in turn may turn into Parkinson's Disease (like) symptoms. Again, this is tentative, and based only on a few studies, but the chemical pathway, afaik, supports this conclusion. Yet, take this with a grain of salt.

Now, questions that remain (for myself):

1. Can one take excessive levels of SAM-e orrally?

2. What are excessive level ranges (on the average)?

3. What methods/supplements may be used to counteract the formaldehyde and other methylation processes neurodegenerative risks?

What say ye?

[overfocused]

Interested in this as well, I am on 600-800mg SAM-e a day and find it very useful, even more so than pharmaceuticals but I cannot seam to get off it. I wonder if TMG could be a way to tapper it off ?

Edited by overfocused, 30 June 2013 - 01:20 PM.

[Arjuna]

Great questions. Bump.

Those studies don't say the concentrations injected into rat's brains, and how would they compare to homocysteine injections? Maybe homocysteine is the culprit.

[airplanepeanuts]

According to this

http://www.ncbi.nlm....pubmed/15537554

Formaldehyde problem is insignificant.

[Joe Monroe]

I think it's safe... I mean I guess I haven't read any long term studies but it helps with the methylation cycle. You should be taking b12, b6 and processed form of folate ffind one that is mthf...

[blood]

I don't think there are any serious concerns with respect to SAMe & homocysteine. There are a few studies which find/found that even quite high doses of SAMe (up to 1600 mg/day) for extended periods of time did not induce a rise in homocysteine levels in plasma.

(Coffee is more risky in this respect - a few cups of coffee/day can increase homocysteine - although this effect can be eliminated with a small dose of folic acid or preferably methyl-folate).

Dietary methionine restriction extends life in rats; conceivably consuming high amounts of methionine could be "aging"... but 400 mg/day (in the form of SAMe) seems like a small amount relative to the multi-gram doses people are getting when they eat a very protein-rich diet. I'm not too concerned, and will continue to take my SAMe.