RDI: None established. The estimated requirement for methionine and cystine (a related amino acid) combined is 13 milligrams per kilogram of body weight, or about 1 gram per day for a 160-pound person. 
 

Dosage and administration: SAMe is a very unstable compound. Unless a brand contains stabilized, enteric-coated SAMe, it may be inert. Currently, Nature Made's SAMe, which is imported from Italy, is the gold standard. 

Oral SAM: Despite the high dosage of 1,600 milligrams per day used in most clinical trials, anecdotally, some people seem to respond to as little as 200 milligrams per day. Columbia University psychiatrist Richard Brown usually finds 400 to 800 milligrams effective, especially for mild to moderate depression. For severe depression, he says the higher doses may be required, alone or with other antidepressants. Brown recommends taking SAMe about half an hour before meals (unless it gives you heartburn), starting at 400 milligrams for the first two weeks (200 milligrams if you tend to be sensitive to medications), then doubling the dosage if you have little or no response. 

For Brown's patients and many other users, oral SAMe usually works fast: "On average," Brown and associates write, "SAM-e begins to relieve depression in seven days, although some people may need more time." 

L-methionine: Usually I to 2 grams per day. 
For safe and efficient utilization of methionine and SAMe, a generous intake of vitamins B6 and B12, folic acid, magnesium, and calcium is essential. A high-potency multi should fill that need, though an additional milligram of folic acid per gram of methionine (and perhaps SAMe) would also be advisable. [Post-publication note: Because the sulfur in methionine and SAMe leaches calcium from the body, doses over 500 milligrams should probably be augmented with more calcium than you'll get in a multi - perhaps an extra gram or so.] 

Cost: Methionine: moderate; SAMe: very expensive (more than $3 per day). 

Safety and side effects: According to Brown et al., SAMe has been associated with fewer side effects than placebos in clinical trials, causing "almost no one" to drop out, despite the high dosages used. Typically mild and transient, SAMe's side effects include dry mouth, thirst, nausea, vomiting, gas, bloating, diarrhea, urinary delay, blurred vision, headache, sweating, anxiety (especially in people with panic disorder), rapid heart beat, insomnia (if taken in the evening), and restlessness. One user tells me his excellent reponse to SAMe has been marred by numbness and burning in his extremities and "a flushed feeling and pounding heart," even at very low doses. 

SAMe can also induce hypomania or mania - usually transient, but sometimes persisting even after discontinuing the supplement - in about 10 to 15 percent of users, mostly bipolar depressives. Bipolars should use SAMe "under cover" of mood stabilizers like lithium and tryptophan and with medical supervision. 

Methionine's negligible, but little known, side effects (Braverman et al. report flatulence and uneasy feelings) likely resemble SAMe's. 

One case of serotonin syndrome (see page 177 in chap. 13 for a description) was reported by lruela et al. It was triggered by injections of SAMe in a woman already taking the strong serotonin reuptake inhibitor, clomipramine (Anafranil). For this reason, SAMe (and methionine) should only be combined cautiously with strongly serotonergic drugs, as well as lithium, tryptophan, 5-HTP, and other supplements that may boost serotonin (e.g., omega-3s, St. John's wort, and Ginkgo biloba). That said, Brown has used SAMe safely "with nearly every antidepressant available" except MAOls, and claims it only improves his patients' response to the drugs. 

Brown et al. also believe the literature suggests SAMe is probably safe during pregnancy and lactation. There are a few other safety considerations. In a study by N. Orentreich et al., a lifetime of severe methionine restriction completely stunted the growth of rats, but it increased their lifespans by 30 percent. Although it doesn't follow that methionine supplements would shorten human lifespan, we do know that extra methionine without extra folic acid (and to a lesser extent vitamins B6 and B12) to prevent the accumulation of its dangerous metabolite homocysteine would promote life-shortening diseases. 

Animal studies by Charlton and Crowell suggest excessive methylation by SAMe fosters the degenerative process underlying Parkinson's disease. This seems to conflict with evidence cited by Brown et al. that SAMe levels are extremely low in people with PD (L-dopa, the principal treatment for Parkinson's disease, uses up SAMe), and clinical studies in which therapeutic doses of SAMe as high as 3,300 milligrams per day improved depressive and even neurologic symptoms in patients with Parkinson's disease. Perhaps, in Parkinson's disease, there is a therapeutic window for SAMe. Too little leads to insufficient synthesis of dopamine and serotonin, both of which are lacking in the disease. Too much leads to increased catabolism (breakdown) of these neurotransmitters. Judging by the clinical research, therapeutic dosages of SAMe (and perhaps methionine, with protective nutrients on the side) fall safely within that window. 

Dealing with Depression Naturally 
Complementary and Alternative Therapies for Restoring Emotional Health
Amazon.com | Chapters.ca

Other Books by Syd Baumel

	Serotonin: How to Naturally Harness the Power Behind Prozac and Phen/Fen
	Natural Antidepressants: Tried and True Remedies from Nature's Pharmacy

 
 

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