Monday, September 15, 2008

SAM-e to methylation to copper overload

I know, you read the title and you're thinking "What??"

No, I haven't gone crazy and started making up words. And I'll apologize in advance for the length of this post. If these issues don't affect you directly, you probably won't want to take the time to read it all. The payoff is information for people who deal with depression, OCD, eating disorders, PMDD, etc.

So last week, I was talking to my sister-in-law about St. John's wort (SJW), and she suggested SAM-e. Commence the research!

In looking up SAM-e, I came across some complaints about SAM-e on this website, which scared the crap out of me.

...insomnia, anxiety, fear, shakiness, and restlessness (especially restless thoughts)...
...For the first two months I took one 200mg tablet per day, and initially experienced a lift in mood and energy. This then changed to a feeling of irritability and sleeplessness. I then doubled the dose, thinking perhaps I wasn't taking enough. I now frequently wake up in the morning feeling very dizzy and disoriented. I have continued irritability and have started to be rude and snappy to my co-workers which is out of character. I read that someone else descibed a speedy feeling...

But about two-thirds of the way down the page, I read this comment:
I do have a theory of why SAM-e has such fantastic results for some,and is awful for others, it is the theory of methylation, Dr. William Walsh has done a lot of research on this at his clinic... My suspicions are that these bad reactions posted here are from low histamine people, who Dr. Walsh says will do terrible on SAM-e. If you want to check out this for yourself, go to, look for the articles link, Dr. Walsh, an article on methylation.
Okay... new direction.

Under the section titled "Depression," Dr. Walsh says this:
Associated with under-methylation, which results in low levels of important neurotransmitters such as serotonin, dopamine and norepinephrine. 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... Choline is anti-dopaminergic and often makes undermethylated patients worse. Also bad are DMAE, copper and folic acid. Three to six months of nutrient therapy are necessary to correct this chemical imbalance.
Interesting little side note, something that I will tuck in my bag of things-to-consider: "Another indicator of B-6 overload is the onset of vivid, troubling dreams."

Also on this site, information regarding copper overload:
The most common depression phenotype for women. History of hyperactivity, tinnitus, and skin sensitivity to metals. Females with this condition usually have significant PMS and are prone to heightened depression during hormonal events such as puberty, gestation, childbirth and menopause.
Interesting, because in The PMDD Phenomenon, the authors said that it is more likely for women with PMDD to also have significant post-partum depression and menopausal depression. Hmm...
Most get worse after chocolate which is very high in copper. This condition is non-existant in males... Nutrient support is zinc, manganese, vitamin C and B6. Nutrients should be introduced gradually to avoid side effects.
Under "Methylation":
One thing that is absolutely certain is that methionine and/or SAMe usually harm low-histamine (overmethylated persons)..... but are wonderful for high-histamine (undermethylated) persons. The reverse is true for histadelic (undermethylated) persons, who thrive on methionine, SAMe, Ca and Mg..... but get much worse if they take folates & B-12 which can increase methyl trapping.
Nearly all severely undermethylated persons have low serotonin levels and present with a history of depression, internal anxiety, and OCD. Many have a history of perfectionism and high accomplishment in the early years.
He's describing exactly what I've gone through... Almost scary, except that it's such a relief to have an explanation! It all fits so well. I was a super-over-achiever throughout school, even in kindergarten. I once came home from school crying because I couldn't cut in a straight line. I was six!! My mother always said she had no idea where I got it from — except that both my parents are also perfectionists, although my dad is worse than my mom. (The serotonin problems seem to run in his side of the family.)

Regarding the connection between eating disorders and OCD:
We have found that nearly all anorexic and/or bulemic patients are very undermethylated, low serotonin persons. Most of then respond very well, albeit slowly, to aggressive doses of methionine, Vitamin B-6, and calcium. A positive response can usually be achieved more rapidly with SAMe...
...In my experience, most anorexics are perfectionistic, obsessive-compulsive, high-histamine, low serotonin persons. Most have a history of high accomplishment in school and were never discipline problems.
Funny that all through high school and college, I thought I was a lazy anorexic... And I guess, if you look at BDD sideways, I was.
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 SAMe (which is frightfully expensive)... you can get usually the same benefits (albeit more slowly) using methionine plus calcium, magnesium, and B-6... SAMe is likely to cause great worsening of symptoms, including mania, if given to an OVER-methylated person.
Sorry for the list of links, but there's just so much information out there. This is not even a tenth of it, just a jumping-off point.
So, I'm very sorry for the informational overdose, but welcome to my world for the past week or so! I'm fascinated by all of the interactions of minerals, vitamins, hormones, neurotransmitters, etc. And I'm surprised that so much of this information is out there, and yet no one I've ever talked to knows anything about it. Doesn't sell pharmaceuticals, I guess, so no one wants to bother? Except that I did see a naturopath a few years ago, but she just wanted to put me on some special diet and have me go to the gym an ungodly amount of hours a week — she didn't offer me a solution, which is what I really want. Even sertraline is not a solution, just a crutch.

And since I don't have a doctor that I'm happy with yet, I'm experimenting with some new things on my own. I wish I did have the support of someone with more knowledge than me, except that I generally bring a lot of new ideas/information to my doctors when I do go see them... But it's nice to have professional support.

Right now I'm trying 400mg of SAM-e every day, plus zinc supplements with magnesium and calcium, and cutting out my multivitamin, which has copper. I take 1000 IU of vitamin D, plus calcium, a B-complex with iron and vitamin C, and I think my diet is healthy enough that I'm probably fine as far as other things go. But I'm going to keep a careful watch on my health and see how it goes.

So far, the SAM-e seems to have worked wonders for me today. I felt great all day long. Will keep posting.


Kristen said...

while googling copper overload i stummbled across your blog and realize that we have struggled with some of the same things in life. I have dealt with depression(mainly post pardum), pmdd, and anxiety.
I just want to share with you something I am taking right now. It is called empower. You can find more information at It has been quite a process for me but I am seeing the light. I also take total amino solution, and some things to clear candida, Olive leaf extract, probiotics(ferm plus), and I'm going to add vit. d and some more ltryptophan. I'm going to keep reading but I wanted to share! Best wishes to you:)

Anonymous said...

I too have pmdd, I take only 10mg og Prozac when onset occurs, usually 3-4 days before my period. I agree- That exercise and diet is key. Cut out that caffine and cigarettes. Cut out of sugar and processed foods. Absolutaly stop eating at fast food chains!!!!! Jogging or biking or getting out and walking is essential. Also go someplace with high negative ion levels such as rushing waterfalls or the ocean.

Do not under- estmate the power of mother-nature!!! Both my sister and have PMDD and it is our life. If you can, move closer into nature ( you already know what calms you: ocean, desert, trees, lakes etc) move there!! No joke .
There's no "quick fix" with PMDD . Don't fight it, just try to
get through it. Talk to family members that you live with and that you effect during episodes. My husband is much more understanding and he doesn't take my problem so personally, and now he is focused on soothing me. Oh did I mention Reiki or compression message is extremely

Anonymous said...

I just started taking SAMe for my PMDD. I think what is most frustrating for me is when I try to researh and read blogs/forums/etc about alternative ways to treat PMDD, I come across people who say, "you just have to learn how to deal with it..." "change your diet" "exercie" "go get a massage"... I've tried them all, diligently, but the results were hardly enough to keep my PMDD at bay. Plus, the amount of work required to 'tame' my PMDD meant I wouldnt have any other part of my life.. its like I have to babysit my PMDD like its a toddler in the terrible twos! Yeah, thats the last thing I want to do when im full swing PMDD monster!... when I hear other people give their two cents about how eatting oranges and smiling at the sun has bettered their PMDD, I have a hard time believing they know what PMDD really is. HOWEVER, your blog is so insightful and is a breath of freshair. Thank you for that..

My PMDD is sooooo severe, that just dealing with it, isnt an option. I tell people that I feel like I am sick with food poisoning, and am miserable, but I cant do a thing about it. I just have to let it runs it course. It has caused me to do embaressing things, makes me so irritable that I could even think the cutest little puppy was annoying! I have ruined relationships, quit jobs in anger and been reallly mean to perfect strangers. : ( its embaressing. I feel trapped.

SAMe is my last resort to alternative treatment, so I am keeping my fingers crossed. I have done alot of research on it, but your links were especially helpful. I am only on my second day of SAMe, but look forward to sharing my results with you.

Ms.M said...

@Anonymous(2): Don't give up! You can find a treatment that works for you. For me, SSRIs helped, but eliminating caffeine was the ultimate answer. My PMDD is now really just moderate-to-bad PMS, and I don't have to take zoloft anymore.

I also take vitamin D, 1000IU, because my Dr. showed that my levels were low — I live in the Pacific Northwest, after all. I also take a supplement with 5-HTP, GABA, and L-Theanine, but not sure how much that really helps anymore.

But you have to find what's right for you. I'm glad my blog has been helpful. I haven't been writing so much lately because my PMDD has been so much better. :) I hope you have a doctor or healthcare provider who is helping you out, and maybe a therapist, too?

Anonymous said...

Thanks for getting back. I was on the SAMe from the day I wrote the last post till now (maybe three weeks) and though I dont think I was on it long enough to notice any change, the biggest problem were the headaches I was getting. I had to stop taking them because the headaches were so painful. : (

I do have a doctor, but every one of them has suggested prozac, and I have been trying to eliminate that option. I did see my doctor most recently and she said that she may be able to get me on a system that allows me to take a small dose of the prozac and only taking it when I am getting ready to PMDD. She said its a process to get to that point and would require a lot of documentation on my part, but I guess its worth a try.

Im upset SAMe was no good for me though. Glad to hear you are feeling better : )

Anonymous said...

I started taking sam-e about a month ago for mild depression that becomes UNBEARABLE from ovulation until day 2 or 3 of my period. On sam-e I felt wonderful the first 2 weeks of my cycle, even during the couple days around ovulation. But the PMS is still a major challenge...not as bad as it was prior to starting sam-e but I feel exhausted by 2 pm, hungry for sweets and salty foods and alcohol and get very easily frustrated and annoyed. If I could reduce the pms to one week instead of two, I would be thrilled. Will continue sam-e a few more cycles and report back.

Anonymous said...

Are any of you on a copper IUD? I am (for 3+ years)and I think that could definitely be a big culprit in all of this crazy hormonal mess i experience each month. I feel crazy right around ovulation until nearing the end of my period. No motivation, very weepy, angry, lethargic. I am getting it out next week. Taking massive amounts of zinc, vit D (I live in a sunless province) and the b complex, manganese... you get the picture. It has helps a bit but during the pms days it seems that it barely works.... but my acne is terrible also. Copper toxicity is a real problem and I really hope it's the answer.. I need an answer!

Kelly said...

Thanks for your blog post.

I must point out that Walsh is wrong when he calls SAMe an "antifolate". He also overgeneralizes about 'overmethylators and undermethylators' but that's another novel.

Here's a study that showed that SAMe INCREASED folate levels:

"The observed metabolic changes suggest that S-adenosylmethionine, at least in concentrations obtained in this study, does not inhibit 5,10-methylenetetrahydrofolate reductase, the 5-methyltetrahydrofolate forming enzyme. Rather they indicate a positive effect on 5-methyltetrahydrofolate, a key cofactor in homocysteine metabolism, which should be considered in homocysteine lowering strategies for the prevention of vascular disease."

Note: "5-methyltetrahydrofolate" is the active form of folate used by the body.

Best regards,


Kelly said...

Just another quick comment:

Walsh is also quoted as saying that undermethylated types "get much worse if they take folates & B-12 which can increase methyl trapping."

That again doesn't make sense, and a quick google search will confirm it. B12 DEFICIENCY is what causes the methyl trap because b12 is needed to convert forms of folate into it's active form.

Anyway, just posting this in case it might help someone. I understand it's nit-picking (it's just the PERFECTIONIST in me!), and probably doesn't mean much if SAMe is helping you. It helps me too, but with proper amounts of methylb12 and folates, you -- and I -- and thousands of others -- might not need the SAMe. It all depends on one's genetics.

And for that...people can google Amy Yasko and methylation. :)

Anonymous said...

Walsh never said b12/folate caused methyl trapping. I don't remember the exact reasoning that was on his published slides and writings, but it had nothing to do with trapping.

What does matter is that for those who are high histamine, some proportion of those will not feel better with b12/methylfolate, but will feel much better. It doesn't depend on genetics, because the NIH genome data shows MTHFR and other mutations that Yasko focuses on are extremely common, yet very few people are sick while there are undermethylators who are affected who do not have these mutations.

There's a methylation youtube video by Dr Albert Mensah that explains this in more detail.

Linda-San-Diego said...

I have been struggling with many similar unsolvable problems for MANY years. When I stumbled across the copper toxicity symptoms and began treating myself 'as if' I am copper toxic, then for the first time things began to make sense (BIG emphasis on this phrase 'for the first time things began to make sense')... I'm going to eat high Zinc / low copper for a couple months, stop the supplement I have taken for 20 years that has 2 mg Copper per serving, keep my copper bracelets off that I've worn for 15 years, and drink distilled water with low copper mineral drops or low copper natural salt added, and then get a hair test in a couple months to see what my copper levels are (they should then show very high because the copper is being mobilized out of my tissues???). This is complicated! BUT I'm excited at least to find what may be the cause of years of hair loss, fatigue, mental fog, racing mind, progesterone intolerance, insomnia, and generally poor life quality. I have to keep reminding myself that there probably isn't ONE MAGIC BULLET to solve my problems, but perhaps copper toxicity is 'the elephant/gorilla in the room' and if I start with this, then I can at least begin to see some health improvements. I could write pages and pages about my experiences with this but my problems are very similar to other postings here, so I'll keep this short and post more later... Linda-San-Diego

Robyn Thomson said...

Just a tiny bit confused, I am an under methylater have 2 copies of the MTHFR mutation and have been taking a Methyl B12 & Methyl folate plus B6
I recently started taking 200 mg SAMe and I can tell you its only been 12 doses, but I did not have the depression I usually fee for the l 2 weeks before my period, plus it has helped me control my appetite which has been crazy for the past 5 years. My confusion is I though I read that if you take SAMe you should avoid folate. I've been avoiding folic acid because of the MTHFR mutation, but I'm feeling good, I don't want to mess anything up. Can the folate impact the SAMe at some point? Should I switch to just the Methyl B12. Thanks if you can clarify.

Robyn San Diego

Ms.M said...

Hi Robyn, thanks for your comment. Unfortunately this post is completely out of date and woefully un-researched; I almost want to delete it, but the comments might be useful to people. I cannot give you an answer, but perhaps someone else can.

Mary Power said...

Not sure if this comment is helpful, more a query really...
Diagnosed last October with mild pyrrholuria, EXTREME copper overload (told I need zinc supplementation for life) I’m an undermethylator with high histamine & VERY low serotonin.
Post-menopausal (now THAT was one dreadful experience, still suffer anxiety + ultridian rapid-cycling bipolar) Blacklisted by doctors, survived one suicide attempt. Regular, prolonged crying fits with persistent insomnia and tendency to totally withdraw from social interaction due to ptsd-like reactions. Unemployable due to fibromyalgia. In short I am a mess.
Taking B6, p-5-p, Zinc picolinate, Magnesium, Vitamins C and E for toxic copper levels (and pyrrholuria). Also L-Methionine, Idéos and extra Vitamin D for undermethylated depression. Most supplements in very high doses, way above the RDA. All prescribed by orthomolecular herbalist. Refuse totally to engage with psychiatrists - they destroyed me with intensive ECT + massive doses of psych drugs, including sodium amytal (I presented at 18, from college with bout of total memory loss, possibly a victim of drug-rape/ date-rape?)
A lot going on, yeah. Fantastic husband of 35 years is the rock on which I stand. Dead but for him (xx Jim xx) Four beautiful children (sadly one died of leukaemia xx Tommy - our angel xx). Others all healthy thank God.
Some interesting points re under- and over- methylation, symptoms, what to take/ not to take etc -
Never any problem with menstruation - until psychiatry intervened. (Periods stopped for 18 months – returned bringing almost-disabling PMS.)
Yet no post-natal depression (probably too drugged-up!!) Took Lithium for 17 years but came off it (against medical advice) fed-up of persistent depression and PMDD. Li did NOT help the rapid-cycling.
Likewise stopped Seroxat due to akathisia and inability to sleep. Doctors would NOT listen. Eventually went back on tricyclic (imipramine) due to persistent ultra rapid-cycling depression with non-stop crying/ PTSD during menopause. Gynaes did not want to know. But I survived. To spite them all!
Still take very small amount of imipramine - mostly to control withdrawal symptoms, reduce neuropathic pain and keep the suicidal thoughts at bay. Tried several times to wean off - sometimes with medical help. No use. The non-stop crying always gets to me, sooner or later
About reactions to supplements:
Could NOT tolerate molybdenum. Caused ibs and a bad pain that lasted non-stop full week.
Taking 2 Idéos at night conked me out so fast doc advised one twice a day instead!
Am advised to NOT take folate. Also avoid vitamin B12 as mine tends to be up-in-the-moon. Strange as mother had very low B12 as does one of my daughters...?
My personality has qualities of both under-and over- methylators. Without blood test, I would have thought me OVER-methylated. Sobering because taking wrong supplements could make suicidal ideation worse.
I would advise EVERYONE to get tested first and not presume they are either under- or over- m'd because "hmmm that sounds like me..." It is quite a complex disorder. Perhaps due to genetic mutation - but moderated nonetheless by many epigenetic factors. What works like a dream for one person may be disaster for another.
I still struggle with rapid-cycling, insomnia, crying fits, intermittent fatigue, PTSD, fibromyalgia... There are days of zero motivation. There are days of amazing creativity... One can never diagnose one's self solely on presence/ absence of one overwhelming emotion. There is ALWAYS a lot going on.
We are, after all, God's most fascinating creation. I DO have the under-m's quality of being strong-willed, stubborn and (even!) oppositional-defiant. And very VERY anti-suicide. Because I am also blessed with an INSATIABLE curiosity for what's-around-the-next-bend. With ultra-rapid-cycling, you don't stay down long enough to make anything like a viable suicide plan. You just exist from day-to-day. And some days are incredibly beautiful. :-) Mary Power (Mrs.)