Trying Out SAM-e (Smart People Can Do Dumb Things)

Screen Shot of image search for SAM-e

Another girlfriend suggested SAM-e, and since it connects to methylation and we know I have mega-MTHFR challenges as well as other methylation problems like COMT, I figured I’d give it a try. Before you read too far, the end of the experiment for me is a big fat “NO, DON’T DO THIS.” But, of course, it isn’t that simple. I’m still not feeling well, so I’m trying to keep this simple. In part, this is an example of how to research something before you decide on a new course of treatment for yourself, and in part it is a cautionary tale.


What is SAM-e used for? The big ones are depression, osteoarthritis, fibromyalgia, and liver disease, but these are also mentioned.

back pain
chronic fatigue syndrome (CFS)
heart disease
lead poisoning
liver disease
multiple sclerosis
premenstrual dysphoric disorder (PMDD)
premenstrual syndrome (PMS)

Well, with a list like that, I figure a lot of folk think the same thing I did: “Gee, several of those apply to me or my family. Who knows? Maybe it might help. Let’s give it a try.” The first piece I looked at clustered these into categories of (1) bone and join problems, (2) nervous system problems, and (3) organ health. Two of those are themes in my life, so it was making sense that it might be part of the picture. And I really really wanted to feel better.


No, I’m not so foolish as to simply dive in and start taking something on a whim. Everything we ingest can have effects like a drug; everything has a minimum and maximum recommended dose; everything has interactions and side-effects, indications and contraindications. I looked it up, in major drug databases as well as Google Scholar, Pubmed, and some drug databases. I looked for the interactions and side-effects (there are LOTS). I looked at signs of an overdose. Turns out there are two kinds of overdose: (1) over-methylation, which makes you jittery, anxious, sleepless, etc.; and (2) serotonin syndrome, which can be fatal, and starts out with agitation, restlessness, confusion, tachycardia, high blood pressure, muscle twitches, sweating, diarrhea, headache, shivering, fever, goosebumps.

I felt pretty prepared at that point, but there were a few more things I wanted to know. The importance of SAM-e in the methylation process was obvious with even a superficial web search. Since I have MTHFR deficiency and that is also a big problem with the methylation cycle, I wanted to make sure the two don’t interact in nasty ways. So I searched for information about interactions between SAM-e and methylfolate, warnings, precautions, etc.

This was more interesting. First off, it turns out that methylfolate helps people make their OWN SAM-e! They are part of the same cycle, and SAM-e is one of the by-products from MTHFR processing. Regarding taking both, there was virtually no solid evidence floating up to the top, but an awful lot of opinion and personal experience. (Guess I’m adding to that body of unclear literature.) I saw a lot of people saying, “If you have MTHFR deficiency, do not ever take SAM-e!” This was balanced by an equal number of folk saying the opposite. The overall picture was unclear. There was a lot that said to take them together, almost nothing about if you have an MTHFR deficiency.

I found one woman who described it as helpful for brief periods, and she described her genetics as similar to mine — heterozygous MTHFR, homozygous COMT (H62H & V158M), and celiac. She described reacting with an over-methylation response after a couple weeks, and I had gone through that when I started taking methylfolate and felt I know what to do. Just to be careful, I started out with the smallest dose I could find – 200mg.


Part of what was motivating this was that general feeling of being unwell that I’ve had ever since I returned from my trip. I really want to feel better, but am feeling crummy. I thought about waiting to start SAM-e until I feel better, but based on what information I’d found I thought I knew what to expect. Either it wouldn’t do much, or I’d feel better.

I took a half dose on Monday. I felt basically the same as I’ve been feeling — generally crummy. Tuesday the same thing. I wasn’t sure if I’d been glutened or not. I took a couple days off, just to see. Then I thought maybe I hadn’t taken enough to notice a difference. [The problem with this was I had forgotten to look at how long it takes to feel an effect, and it varies depending on the problem.]

I was taking Friday as vacation, and thought I’d risk taking a larger dose, since I didn’t want to experiment if I was going to try to work. Instead of 200, I took 400. I continued to feel vaguely crummy, and then I started to feel as if I’d been glutened. I’d been eating “whole foods,” so I couldn’t imagine what it would have been, but I recognized the feeling. Fatigue. Brain fog. Wobbly. But not a hint of any digestive symptoms, no bloating, no hives. I was puzzled, but sleeping too much to figure it out. I had trouble sitting and standing, my joints hurt. I felt too weak to do much. Not normal symptoms included feeling hot, sweaty, feverish, flushed, confused, congested, chilling, spaced out, distractible. Then I got a headache, and my head feels strange in the back. So far, this has lasted three days. Each day has had a couple brief periods when I felt ok, before it would start up again, slightly milder than the day before.


I went back and looked again at SAM-e overdose. Nope, these symptoms don’t match up, except for the headache. My symptoms were more like those indicators that someone needs more SAM-e. Very puzzling. I kept digging into literature about SAM-e. I tried taking extra methylfolate, but didn’t notice a difference. I did notice that my clear-headed time was in late afternoon, and every day I take a B-complex vitamin with my lunch. Then I stumbled into some information that SAM-e can cause problems if someone is deficient in B-vitamins (like me). Basically, it creates a lot of homocysteine, which the body can’t clear out because it needs more B-vitamins to do so.

I put 3 and 3 together. Maybe this was a SAM-e overdose, but my body couldn’t properly process the SAM-e? I tried taking extra B-vitamins to see if this helps clear the fog and confusion and fatigue. I’m not trying to do it all at once. I took a B12 and my usual B-complex, then waited a few hours and took another B-complex. So far it seems to be working. I’ll add an addendum tomorrow.

SOURCES, Alternative Medicine: SAMe, What Should I Know About It?

Mayo Clinic: SAMe: Safety:

Mayo Clinic: Serotonin syndrome:

Natural Database: SAMe:

University of Maryland Medical Center:

WebMD: SAMe: Uses, Side Effects, Interactions, and Warnings.

UPDATE June 24, 2014:

Looks like I probably guessed right. The extra B-vitamins are helping, allowing me to get through the day. I couldn’t find anything about the length of time it takes to clear SAM-e from the body (personal reports range from on day to a couple weeks). I’ll probably have to take extra B-vitamins for a few more days.