SAMe pathway

S-adenosylmethionine a.k.a. SAM-e

What is S-Adenosylmethionine? What Does It Do?

S-adenosylmethionine, or better known as SAMe for short, is a natural substance that our body makes naturally from the food that we eat. Our bodies make SAMe from methionine, an amino acid found in protein-rich foods.

SAMe is one of the best methyl donors that our body can have. Like other methyl donors, such as DMAE, folic acid and B12, S-adenosylmethionine is needed in the production of neurotransmitters, such as serotonin, melatonin, dopamine and adrenaline, which affect mood, energy, alertness, concentration, and visual clarity. Multiple researches and clinical trials have shown the benefit of taking SAMe on a regular basis in fighting depression, liver disease, and alleviating pain from osteoarthritis.

The methyl group (CH3) that is attached to the methionine in SAMe is very chemically reactive. This allows the methyl group to be released easily and be transferred to an acceptor substrate. SAMe is involved in more than 40 metabolic reactions involving various substrates, such as nucleic acids, proteins, lipids and secondary metabolites.

When a SAMe molecule loses its methyl group, it becomes homocysteine, which becomes toxic if it builds up within cells. Generally with the help of vitamins B6, vitamin B12 and folic acid (all B vitamins), our bodies is able to convert homocysteine into glutathione (our body’s detox superstar) or back to methionine via re-methylation with the help of TMG (Trimethylglycine).

SAMe and homocysteine are essentially two versions of the same molecule—one benign and one malicious. Generally, our body maintains a low level of homocysteine with good supply of B vitamins. However, homocysteine can start building up quickly when methyl-donors, such as vitamin B6, vitamin b12 and folic acid intake is low. The build-up of homocysteine slows the production of SAMe and subsequent health problems. Elevated homocysteine level is associated with heart attack and stroke; it increases risk of spina bifida and other birth defect during pregnancy.

How does S-adenosylmethionine help in ADHD?

Depression is common in children and adults with ADHD. SAMe may enhance the mood-enhancing effects of serotonin and dopamine—either by regulating their breakdown or by speeding production of the receptor molecules they latch on to. SAMe may also make existing receptors more responsive. If the membranes get thick and sticky, due to age or other stresses, the receptors lose their ability to move and change in response to chemical signals. By methylating fats called phospholipids, SAMe keeps the membranes fluid and the receptors mobile.

Since the 1970s, researchers have published over 40 clinical studies involving roughly 1,400 patients. These maybe small studies by FDA standards, findings are remarkably consistent. In 1994 Dr. Giorgio Bressa, a psychiatrist at the University Cattolica Sacro Cuore in Rome, pooled found that “the efficacy of SAMe in treating depressive syndromes…is superior [to] that of placebo and comparable to thea of standard…antidepressants.”

SAMe is not exceptionally better than current prescription antidepressant, but it’s clearly less toxic and more tolerable. Common antidepressants, such as Prozac, Zoloft and Paxil, have known side effects ranging from headaches and diarrhea to agitation, sleeplessness, sexual dysfunction, and manic episode in people with bipolar disorder. And SAMe? Maybe a mild stomachache; and possibly manic episodes in people with bipolar disorder, just like other antidepressant.


You can’t really get SAMe from eating any particular food. But you can eat a high protein diet, which will supply the methionine needed for making SAMe. Otherwise, supplementation is your best option.

SAMe comes in two forms, tosylate and a more stable form called butanedisulfonate. Only Nature Made and GNC sell the new butanedisulfonate version. Choose enteric-coated SAMe as it is absorbed mainly through the intestine. The enteric coat will ensure that the S-adenosylmethionine molecule is protected from stomach acid, and reach the intestine intact for absorption.

It is best to take SAMe twice a day on an empty stomach. You may start at 400mg/day divided into two doses.


Frequently dosing of supplements are based on adults. As we all know, children have smaller body size and thus require different dosage of many vitamins and supplements, especially medications.

Here is a formula that you can use simply to estimate the dose for children:

Adult dose divided by 150, then multiply by your child’s weight in pounds. This will give you the dose for your child.

Remember, it is just an estimate. Always check with your pediatrician or registered dietitian to get the proper amount for your child.