Talk:S-Adenosyl methionine

Merge from S-adenosylmethionine
I have added a mergefrom. Shouldn't be hard to do! --Slashme 11:33, 28 November 2005 (UTC)
 * Done Kcordina 09:22, 16 March 2006 (UTC)

I've yet to read a tutorial on how to redirect a query to a specific page, so I was hoping that someone could assist me. SAMe is also known as 'ademetionine' - and searching for it should redirect you to this article on SAMe - irrespective of whether 'ademetionine' is merely employed by supplement companies to sound pharmaceutical (I'm unclear about the legitimacy of the word) substantiate 15 Feb 2007

added a redirect --Substantiate 02:03, 17 February 2007 (UTC)

Cleanup
I will have a look at cleaning this up some time! --Slashme 11:33, 28 November 2005 (UTC)

I've made a start on cleaning this up, and will need to begin adding references. As you can tell, I'm better at the biochemistry side than the supplement section. --TimVickers 16:35, 25 June 2006 (UTC)

I added a reference from the Am J Psychiatry re depression efficacy --Substantiate 02:05, 17 February 2007 (UTC)

I think this article should have a one or two-paragraph introduction written for someone other than those who have majored in organic chemistry. After the intro, written in lay men's English, you can jump into the erudite, impenetrable jargon. Teo del Fuego —Preceding unsigned comment added by 174.16.159.8 (talk) 23:39, 23 March 2011 (UTC)

Misc
Sure I don't know how to add hyperlinking or add references that only authorized people may have access to. -RS

The comment below was copied from Talk:S-adenosylmethionine during merging. Kcordina 09:22, 16 March 2006 (UTC)

I'm pretty new to Wikipedia, but "being bold." I added the pharmocology stub tag to this article, in the hope that Wikipedians with relevant expertise will expand it. SAM-e is taken for depression and joint pains. It is prescribed in Europe, but can be purchased in the US over the counter in supplement stores. It is generally quite expensive. Because it has become a trendy anti-depressant (usually self-prescribed in the US), I feel that it is important to give people more information about this supplement. It has medical advocates, most notably Dr. Richard Brown (author of "Stop Depression Now"), but I have come across many articles advising caution, as long-term effects are not established. Of most concern is that the supplement breaks down to homocysteine, high levels of which are apparently sometimes indicative of (or causative??) of heart disease.

As with so many supplements, a Google search is flooded with very positive explanations of this supplement by companies selling it. The few negative articles are by medical experts who often seem to reject it reflexively, because its effectiveness has not yet been adequately researched. There is a real need for an objective, in-depth summary of how this supplement works, and what is known about its effectiveness and side effects.

I am not a medical or pharmacological expert, even remotely, so I labeled this a stub in hopes that someone who has expertise in a relevant field can expand it. (StrangeAttractor 15:47, 10 December 2005 (UTC))

Although this article and many others state that SAM-e is invoplved in the synthesis of dopamine and serotonin (others add epinephrine or norepinephrine), the metabolic pathway is not described, neither here nore under the articles refering to the respective neurotransmitters. Thye synthesis pathways for dopamine and serotonin which are given in their respective articles do not mention either SAM-e or methylation. I think it would be good to understand what role SAM-e plays in those synthesis paths, and especially whether it plays a role in the rate-limiting step. 66.245.159.152 20:49, 6 March 2007 (UTC)Andrew Hoerner

degradation and dosage
"SAM is still liable to degradation leading to distributors that may advertise a dose higher than what is actually being ingested." I'm not sure what this is saying. Are you saying the maker, for example, puts 400mg in the tablet and prints 400mg on the box and then you get 300mg due to degredation? (I just got Zentonil 400 for my dog today.) --Gbleem 20:45, 22 April 2006 (UTC)


 * Yes. It appears that SAMe is somewhat difficult to make and has poor stability. Most articles suggest the blister packs and enteric coating to improve stability but I can not find any research to back this up. Some articles recommend against refrideration but the best article used it and documented the degradation with time.
 * The various companies have developed newer salt forms but this may have been mainly an attempt to avoid other patents. I can find very little (almost no) information comparing off the shelf potency of various salt forms, their stability, and bioavailablity.
 * &mdash;  Who 123 17:41, 8 December 2006 (UTC)

dosage
though i've yet to find a reliable source to site via internet, the therapeutic dose of SAMe is not usually 800-1600mg/day. in fact it is usually 200mg/day. 1600mg would be considered a very large dose. —The preceding unsigned comment was added by Harlequence (talk • contribs) 01:28, 17 January 2007 (UTC).

for depression, dosages in the range of 800 - 1600mg would be considered therapeutic. run a pubmed search and note the abstracts that used oral administration, i.e. Obstetrics and Gynecology Department, University La Sapienza School of Medicine, Rome, Italy.

S-adenosyl-L-methionine (SAMe) is a naturally occurring substance which is a major source of methyl groups in the brain and has been found in previous studies to be an effective antidepressant. The aim of this study was to assess the efficacy of oral SAMe in the treatment of depressed postmenopausal women in a 30-day double-blind placebo-controlled randomized trial. During the course of the study, 80 women, between the ages of 45 and 59, who were diagnosed as having DSM-III-R major depressive disorder or dysthymia between 6 and 36 months following either natural menopause or hysterectomy, underwent 1 week of single-blind placebo washout, followed by 30 days of double-blind treatment with either SAMe 1,600 mg/day or placebo. There was a significantly greater improvement in depressive symptoms in the group treated with SAMe compared to the placebo group from day 10 of the study. Side effects were mild and transient.

also, http://www.umm.edu/altmed/ConsSupplements/SAdenosylmethionineSAMecs.html, an excellent, objective resource for information on 'alternative medicine' that is provided by the University of Maryland Medical Center notes that:

Depression: The majority of studies have used between 800 and 1,600 mg of SAMe per day for depression. The daily dosage is typically split between morning and afternoon. --Substantiate 01:28, 17 February 2007 (UTC)

Are these dosages for the tosylate or butanedisulfonate salt? The latter is strongly reccomended in this areticle but is now almost impossible to find in the U.S. 66.245.159.152 20:40, 6 March 2007 (UTC)Andrew Hoerner

Salt forms
We presently list the various salt forms along with (what appears to be?) the manufacturers that supply each. Or the commercial/brand-names that have them (I don't even know what some of the named companies are). The adjacent cite (University of Maryland Medical Center webpage) seems to be silent on the whole issue of suppliers, so that ref seems misplaced and the whole "who supplies what" uncited. I'm not sure it's worthy content (WP not a product directory) but it might be useful; I have no objection to keeping it with proper citation. Or is there some external product guide that we could just link? DMacks 20:36, 25 April 2007 (UTC)


 * Hi. There was not enough room but the revert was to: 16:10, April 25, 2007 DMacks. The reference does support multiple forms: "Available Forms: S-adenosylmethionine butanedisulfonate S-adenosylmethionine disulfate ditosylate S-adenosylmethionine disulfate tosylate S-adenosylmethionine tosylate". In order to provide the information as to which manufacturer is using which form one must go to the manufacturers sites. These could be included. &mdash;  Who 123 20:51, 25 April 2007 (UTC)

I think that it is ridiculous to cite a 1999 Newsweek article as evidence that the butanedisulfonate salt is more stable than other salts. Also, the next sentence in the Oral Forms section states that butanedisulfonate is 5% bioavailable compared to 1% for tosylate, but the reference [Stramentinoli 1979] has no comparison of the two products, and is an animal study anyway. Unless someone can come back with better evidence by the end of January I am going to rewrite the entire section.David notMD (talk) 20:09, 23 January 2008 (UTC)

Possible copyvio in "Usage" section
The "Usage" section is in need of a major rewriting...it's written as an instruction manual, not an encyclopedia entry. While reading the refs to figure out what was actually supported, I noticed that even worse, our section is nearly verbatim copy of the cited wholehealthmd ref, so I'm commenting it out until at least the copyvio issue can be resolved. DMacks 21:42, 25 April 2007 (UTC)


 * It may be more helpful to re-write aspects to improve them rather than commenting the section out. With the section commented out, it is difficult to improve. &mdash;  Who 123 22:40, 25 April 2007 (UTC)


 * I have rewritten the section. If it is thought that the section no longer potentially violates copyright then the tag should be removed. &mdash;  Who 123 23:26, 25 April 2007 (UTC)


 * Looks much better. I just worked on it some more too...now it's clearly not copyvio. I would have worked on it if I'd had time when I first noticed it, but otherwise, "remove copyrighted material" is always a viable thing to do per WP:COPYVIO policy. DMacks 00:10, 26 April 2007 (UTC)


 * I agree that it is much better. I think it is better to rewrite to avoid potential copyvio than lose information. Thanks! &mdash;  Who 123 02:15, 26 April 2007 (UTC)


 * I cut parts from the Usage section. Brands should not be identified as using specific salt forms because companies will change formulas based on changes to cost of ingredients. Also, there is no clear evidence that one salt form is superior to another, either for stability or absorption.David notMD (talk) 21:37, 30 January 2008 (UTC)

Dead link
Guys, the link http://www.umm.edu/altmed/ConsSupplements/SAdenosylmethionineSAMecs.html is dead. Thought you'd like to know. — Preceding unsigned comment added by 167.206.188.3 (talk)
 * Thanks for noticing that! I changed the article's link to point to (what I think is) the same page on their re-organized webdite. DMacks 22:42, 9 July 2007 (UTC)

Study Bias
In the Therapeutic Uses section there is a link to a study (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat1a.chapter.2159) In the conclusions section of this report under the heading "The Use Of SAMe For The Treatment Of Depression" There is the sentence "Possible publication bias was identified that may temper the strength of the conclusions we report." This is a blatant admission that this study is biased and therefore it should not be included as a reference. Mikef777 (talk) 07:42, 19 July 2008 (UTC)


 * Publication bias is a technical term describing the tendency of people to publish positive findings and not publish negative ones. This needs to be corrected for in meta-analyses. The fact that the authors in this meta-analysis were not able to measure how large this effect was does not make them biased themselves, in the usual sense of the word. Tim Vickers (talk) 15:46, 19 July 2008 (UTC)


 * oh, ok makes sense. Mikef777 (talk) 21:29, 20 July 2008 (UTC)

Absurd disclaimer
Someone actually had one of those legal disclaimers in here: "You should consult with your physician before and during use". Now WP:MEDICAL aside, is there any one moon man in the world who actually would do this? I can just picture you out there, having waited two and a half months for your appointment, sitting in the waiting room with the swine flu sneezers and the diarrhea infants, so you can rattle your bottle of pills before the doctor's eyes and get his sage advice on this remedy he would never prescribe. Your insurance company would probably get you prosecuted for fraud and thrown out on the chain gang! You'd be there telling your sad, sad story, and they'd laugh and say, "You trusted medical advice you found on Wikipedia???..." Wnt (talk) 03:46, 14 December 2009 (UTC)

Subjective reports
While subjective reports obviously can't be used in a Wikipedia article, I think those experimenting with the compound might be able to identify useful topics for further evaluation. I think it would be productive if a few tasters would post "trip reports" and compare notes. (Those interested might prefer not to read these comments until making their own:)

On three trials I found this substance to have a far more dramatic effect than usual nutritional supplements, which seemed entirely centered on the circulatory system, which I perceived (perhaps erroneously) to be an opening of capillaries or small vessels. The most striking effect of a 400mg dose, coming on about an hour after use, was a sense of much greater circulation in the most lateral parts of the cerebrum (the area supplied by the middle cerebral artery, at least approximately); this was paired with the reverse sensation of apparent constriction between 36-48 hours afterward in the same region. (Note however that the effect also felt similar to that which caffeine produces in the front of the brain and eyes, and caffeine actually reduces blood flow - the sensation could be deceptive). The withdrawal was somewhat unpleasant but not as bad as for caffeine. This period of effectiveness also involved greater apparent blood flow in most muscles, but a substantial chill in the fingers and toes. There was a much increased hissing in the ears from blood flow during the period of effect (not the sort of tinnitus following a loud noise but not pulsating either). All this blood flow was matched by an uncomfortably high burden on the heart rate. It was also my opinion that blood did not pool in the tissues normally, but flowed quickly back sometimes putting uncomfortable pressure at the entrance to the heart.

During one of the tests I continued taking the pills for three days; the effect of additional pills was quite mild. For another I used 2/3 of a dose with similar effects, but experienced the withdrawal after 24 hours. I felt that the drug had little or no effect on pain from sore tendons/muscles, but might be useful for other indications.

Propositions from this subjective experience:
 * Because the substance was associated with both an onset and withdrawal during several cycles of use, I view it mechanistically as a drug rather than a nutritional supplement.
 * The effect on arthritis might have to do with physical chilling of the joints or release of swelling by reduced capillary resistance?
 * The effect on depression might be related to brain blood flow patterns, increased muscular circulation, or perhaps autonomic effects from increasing heartrate?
 * The interaction with migraine headache would be interesting to hear about - would it be better or worse?
 * The chilling of fingers/toes seems worrisome if frostbite or autoamputation due to diabetes is at issue. Wnt (talk) 19:22, 4 January 2010 (UTC)
 * Afterword: over the next week, without any further SAM usage, the "sore tendons" I mentioned deteriorated into a newly diagnosed case of gout (85 mg/l uric acid), which resolved in about two weeks with purine avoidance and 6 liters/day water. This probably was not the first such instance; still I think that taking 130 mg daily of adenine (a component of SAM-e) was definitely not a good thing under the circumstances. Wnt (talk) 20:31, 2 February 2010 (UTC)

Subtle mania-spectrum effects: increased arousal, irritability, and energy. Of course taking too much can induce actual mania which is completely distressing and undesirable. I've gotten close to this by taking, say, 600mg within a period of 4 hours, but I never did that again.

I have experience with 1x 200mg Jarrows per day for 4 years. This brand has more of the effect I seek at a lower dosage vs other brands. I believe this is due to chirality, and one handedness is active while the other is not, the difference in brands accountable to concentration of the active form.

It does not have the stimulant properties of caffeine or euphoria-spectrum drugs, and I would not say that it induces a feeling of well-being so much as, simply, increased thought manipulation abilities and the tendency to want engage in activity.

In a work context and with practice, it may help the user to achieve a state of flow, as in the article on "flow (psychology)". This is related to an "earplug" effect: just as earplugs allow environmental noise to go unnoticed, SAM-e allows ambient or environmental thoughts to go unnoticed. Petty annoyances and stray thoughts seem less annoying.

A somewhat strained analogy: SAM-e thinking is to regular thinking as powered steering is to regular steering. 173.239.78.54 (talk) 09:41, 2 December 2012 (UTC)

Which version of the name?
Some places in the article say "SAMe" and others say "SAM-e". Let's be consistent. The question is which. Based on a quick look at the first couple pages of google hits for the full name, it looks reasonable to go either way. In commercial usage, "SAM-e" seems to be more common (perhaps because they want people to be able to find the product on case-insensitive searches like google), whereas the more logical "SAMe" seems to be more common in medical or scholarly discussions. I lean in favor of "SAMe", but I don't really care as long as it's consistent. --Dan Wylie-Sears 2 (talk) 15:20, 3 May 2011 (UTC)

Use "SAM-e", all you have to do is google "same" to understand why SAM-e should be used. NJB (talk) 00:13, 7 January 2014 (UTC)

Actually, few people in science call it SAM-e or SAMe (what does the "e" even stand for?). Usually, it's just "SAM". --Felix Tritschler (talk) 09:59, 31 August 2017 (UTC)


 * I know this is an old topic, but maybe worth revisiting. I second Felix' statement: few call it SAMe or SAM-e. AdoMet or SAM are the ones you read everywhere in literature. Also "Me" as an abbreviation for methionine is somewhat arbitrary, since that would be "Met" or "M" according to the community. So what's the "e" stand for? Brisbane (talk) 18:02, 30 November 2019 (UTC)

Serotonin Syndrome
SAMe is involved in serotonin production. There is no evidence that SAMe increases extra cellular serotonin beyond natural levels or that it contributes to serotonin syndrome in the presence serotonergic drugs. I am removing this section. DrSparticle (talk) 20:35, 30 September 2011 (UTC)

How does SAM-e have anything to do with serotonin? What I mean is google shows a lot of hits for SAM-e and serotonin, but the wikipedia article never even touches on the subject. Since methionine is not serotonin, and SAM-e gets converted to other things such as gluthionine, I don't understand how serotonin even got into the picture. NJB (talk) 00:05, 7 January 2014 (UTC)

Parkinsonism
The reference given for SAMe mediated parkinsonism states that 400mg/kg of SAMe was injected directly into the rats brains. This is the equivelent of injecting 30.4 grams of SAMe into the brain of a 12 stone human. This is nonsense.

The other references simply refer to this study. I am going to remove this section. DrSparticle (talk) 20:58, 30 September 2011 (UTC)

Edit From Abbott
Please accept the edits to this page (February 13, 2013). My name is Scott Stoffel, and I work at Abbott in Corporate Public Affairs, and the edits I am providing are all factual, based upon review of the page with Abbott scientists with expertise in this area. If you have questions, please do not hesitate to access my contact information, found here: http://abbott.com/news-media/contacts.htm — Preceding unsigned comment added by ScottStoffelAbbott (talk • contribs) 13:55, 13 February 2013 (UTC) ScottStoffelAbbott (talk) 20:32, 15 February 2013 (UTC)

SAM-e should be used uniformly as the abbr. throughout
The SAM-e spelling should be used exclusively and uniformly throughout the article. The other variants are much less frequently used, both on the web as shown by a Google search and in scientific writing, as shown by a PubMed search.

The other variants were less common to uncommon even before accounting for the fact that


 * SAMe is equivalent to "same," in searches that ignore capitalization, giving it many more hits than it would get by eliminating "same" hits, and


 * "SAM" is a name.

SAM-e, by contrast


 * is a unique spelling,


 * is unambiguous,


 * is the spelling that the largest group of those searching will be looking for, and


 * is the spelling that they will recognize when they arrive.

The other less-used spellings should be mentioned in the intro., and avoided thereafter except where one of the variant spellings may have been used in an exact quotation.


 * Pretty inaccurate from a chemistry point of view, though. It's methionine, not m-ethionine.

Newer secondary literature
Newer reviews than what are currently in the article. I would try to incorporate, but I have a dietary supplement company as a client with this as a product. List from a PubMed search limited to meta-analyses or systemic reviews. David notMD (talk) 23:22, 26 October 2017 (UTC)

Sharma A, Gerbarg P, Bottiglieri T, Massoumi L, Carpenter LL, Lavretsky H, Muskin PR, Brown RP, Mischoulon D; as Work Group of the American Psychiatric Association Council on Research. S-Adenosylmethionine (SAMe) for Neuropsychiatric Disorders: A Clinician-Oriented Review of Research. J Clin Psychiatry. 2017 Jun;78(6):e656-e667. doi: 10.4088/JCP.16r11113. Review. ;.

Sarris J, Murphy J, Mischoulon D, Papakostas GI, Fava M, Berk M, Ng CH. Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses. Am J Psychiatry. 2016 Jun 1;173(6):575-87. doi: 10.1176/appi.ajp.2016.15091228. Epub 2016 Apr 26. Review. .

Guo T, Chang L, Xiao Y, Liu Q. S-adenosyl-L-methionine for the treatment of chronic liver disease: a systematic review and meta-analysis. PLoS One. 2015 Mar 16;10(3):e0122124. doi: 10.1371/journal.pone.0122124. eCollection 2015. Review. ;.

Zhang Y, Lu L, Victor DW, Xin Y, Xuan S. Ursodeoxycholic Acid and S-adenosylmethionine for the Treatment of Intrahepatic Cholestasis of Pregnancy: A Meta-analysis. Hepat Mon. 2016 Jul 23;16(8):e38558. eCollection 2016 Aug. Review. ;.

Zhou F, Gao B, Wang X, Li J. [Meta-analysis of ursodeoxycholic acid and S-adenosylmethionine for improving the outcomes of intrahepatic cholestasis of pregnancy]. Zhonghua Gan Zang Bing Za Zhi. 2014 Apr;22(4):299-304. doi:10.3760/cma.j.issn.1007-3418.2014.04.013. Review. Chinese. .

Gurung V, Middleton P, Milan SJ, Hague W, Thornton JG. Interventions for treating cholestasis in pregnancy. Cochrane Database Syst Rev. 2013 Jun 24;(6):CD000493. doi: 10.1002/14651858.CD000493.pub2. Review. .

Mechanism
The article shows File:SN2 Mechanism of Methyltransferases.png as mechanism for the methyltransfer. It also says it's "SN2"-like - which is correct. Then why does it show a definitely not SN2-like reaction? Also, the cytosine suddenly being flipped doesn't help with the readability. Any objections to deleting this? I might add a new figure in a couple of days. Brisbane (talk) 18:12, 30 November 2019 (UTC)

Sulfure chirality: Ref for future expansion
10.1002/bmb.2005.49403304274 DMacks (talk) 16:45, 3 October 2022 (UTC)