Circles of SAM-E

Figuring out biochemistry is rather like watching a group of kids playing on the playground. Lots of kids bounce off each other, swing from jungle gyms for no apparent reason, and toss balls around. In the end, energy was consumed and fun was had.

One of the ball-carriers in our livers and brain is the vitamin co-factor SAM-E (pronounced "Sammy"). Otherwise known as S-Adenosyl methionine, SAM-E has a cute little sulfur moiety on it (the "S") that can carry around biochemical balls known as methyl groups (-CH3). You're probably really excited to learn that carrying around methyl groups is an extremely important job, and SAM-E is the go-to running back, the Earl Campbell or the pre-marijuana Ricky Williams of the vitamin crew.

SAM-E is important in depression because, along with folate, B6, and B12, it helps create three of the major neurotransmitters from their dietary amino acids - dopamine, norepinephrine, and serotonin. We can make SAM-E, but without enough essential vitamins (including B6 and B12) and the amino acid methionine, we can't make enough of it or recycle it. And studies have shown that people with depression tend to have lower serum levels of SAM-E.

A new study and editorial about SAM-E came out in this month's Green Journal (the American Journal of Psychiatry - which I'm embarrassed to say I can never remember the proper name of because we always call it the Green Journal). The research team is from the Mass General - George Papakostas, David Mischoulon, Jonathan Alpert, and Maurizio Fava. Full disclosure, back (a while ago!) when I was a chief resident, I had the opportunity to sit in on their weekly research meetings. They were doing some initial planning about SAM-E, but at the time they were mostly focused on the STAR-D trial. They were always pleasant, professional, and would toss brilliant ideas back and forth - it was quite invigorating just to be in the room, though we were all stuffed into a small space for the amount of people, with research assistants sitting on tables on the perimeter, and several of the key players (Alpert or Mischoulon) doing the same, if they arrived late!

Anyway, this current study, "SAMe Augmentation of Serotonin Reuptake Inhibitors for Antidepressant Nonresponders With Major Depressive Disorder. A Double-Blind, Randomized Clinical Trial" is pretty similar to drug industry trials of pharmaceuticals, though it was funded by an NIH grant, and the SAM-E and matching placebo were freely provided by Pharmavite (who makes SAM-E, I assume). They used healthy depressed adults with no history of bipolar disorder, no risk of getting pregnant during the trial, no psychosis, and no substance abuse who were already taking antidepressants. This is an augmentation trial - as we know from every antidepressant study in history and STAR-D (Sequential Treatment of Resistant Depression), antidepressants (no matter what variety) help about 30% of people feel pretty normal, 30% of people feel a bit better, and 40% of people feel the same or worse. SAM-E has a bunch of trials (between the IV and oral trials, I think I count 20!) showing it has similar efficacy to antidepressants, mostly tricyclics. Because SAM-E has a different mechanism than the standard antidepressants, it's important to see how the two might work together. Alone, they are all pretty "meh" unless you are in the lucky 30%. Together, you might start to approximate the body and brain environment that we would have with the types of stress, exercise, and nutrition for which we were evolved, without the excess inflammation and autoimmune reactions that cause depression in the first place... sigh. (I think these trials are interesting because they tell us a bit about the biochemistry of depression. And medicines can help! I've seen it many times. But if we don't find and address the possible dietary and environmental and psychological causes, adding medication can be a bit like pissing into the wind, if you pardon the expression. Just like with diabetes.)

In this preliminary study of 73 already-depressed on antidepressants individuals, the SAM-E augmented the effect pretty well, and without side effects, for the most part (most common ones are upset stomach and diarrhea, like any vitamin). SAM-E (dosed at 800mg twice daily by the end of the study) dropped the Hamilton D depression score by 10 points from baseline, while the placebo-treated group dropped only 6 points. I know that doesn't sound too exciting - but there are only a few FDA-approved medications for the treatment of resistant depression, and they can have some pretty horrible side effects, and they didn't work as well as SAM-E did in this particular study. There are reasons that it is not quite fair to compare the studies of other medicines to this SAM-E study, and they are all duly discussed in the editorial (which appears to be free online and linked above!).

Sweet! Take a vitamin (basically) and boost your antidepressant! SAM-E has also had some studies showing that it can protect the liver and reduce joint pain in arthritis. Win-win! What are the down sides?

Well, like any antidepressant worth its salt, SAM-E can cause mania and anxiety. In fact, I would feel remiss in recommending that anyone start it without at least talking about it with their doctor or therapist, and having a family member watch for signs of mania. Theoretically, if you take SAM-E and you don't take enough of the co-factors, you can end up with a lot of homocysteine lying around. Homocysteine is a marker for heart disease, but that doesn't stop some articles I read from suggesting that SAM-E could increase your risk of heart disease by increasing homocysteine if you don't take a multivitamin with it. (SIGH. Correlation does not equal... ah, never mind). I would be more concerned that it wouldn't work as well without the necessary vitamin cofactors - so take a multi with it! Also, it's expensive. The 800 mg twice a day dose would cost $111 dollars a month at this national chain (though some people might be able to get away with lower doses). For that, you could get a prescription antidepressant and a couple of visits to a therapist covered by insurance. Also, like any over the counter supplement, "buyer beware." Some of them are sold by milligram weight rather than by milligram dose - you wouldn't want to spend big bucks for half the amount you thought you were getting! In 2000, early tests of SAM-E products by an independent laboratory showed that half of the products had less SAM-E than claimed. By 2007, it seems the companies cleaned up their act, and testing of 11 brands showed they were what they claimed to be.

And, of course, no one knows the long term side effects of piling on SAM-E.

Better that we avoid all this in the first place by having an all-star vitamin football team from your terrific, organic and local grown, grassfed and pastured all natural foods diet and a clean, anti-inflammatory playing field from childhood. But sometimes the works are already a bit gunked up. We have some professional cleaning solutions, though those have some down sides, it may not be as much of a down side as leaving the works gunked up.