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April 2007

By Tiesha D. Johnson, BSN, RN


SAMe is most frequently available in 200-mg or 400-mg tablets. The typical oral dose for depression is 400-1600 mg daily. For bone and joint health, the typical dose is 200-1200 mg a day, in divided doses. For liver problems, up to 1600 mg may be taken daily in divided doses. Some of the scientific literature suggests that once positive effects are achieved, the dose of SAMe can be reduced. SAMe’s effects often manifest in two weeks or sooner.56

For optimal effects, stable, enteric-coated SAMe tablets are recommended. SAMe should be consumed on an empty stomach, either one hour before or two hours after meals.56


SAMe has a well-established track record of safe use, with minimal side effects. Some researchers, however, have worried that it may contribute to elevated levels of homocysteine, one of the products of SAMe’s chemical cycle in the body.26 Elevated homocysteine is a risk factor for cardiovascular disease.

Fortunately, a 2004 study provides powerful reassurance about this concern. Researchers studied 15 healthy volunteers who took oral SAMe supplements (1600 mg/day) for four weeks.57 None of the subjects experienced any increase in homocysteine levels during the treatment. Nonetheless, to prevent the possibility of elevated homocysteine, the Physician’s Desk Reference® recommends taking supplemental vitamins B6, B12, and folic acid, and possibly trimethylglycine (TMG), while using supplemental SAMe.56

People with bipolar disorder (previously known as manic-depressive illness) can develop mania (excitability, grandiose thinking, excessive energy, etc.) in response to supplementation with SAMe, and should therefore not use SAMe unless under medical supervision.14,58 Individuals taking antidepressant medications should likewise consult their physicians before taking SAMe in place of or in addition to those medications.56

SAMe is not recommended for use in children or nursing mothers. Pregnant women should use SAMe only under a physician’s recommendation.56


When Life Extension introduced SAMe to American consumers over 10 years ago, few recognized it as a major step forward in the science of natural health care. Yet decades of accumulating studies show that this remarkable natural compound matches the efficacy of many popular prescription drugs in combating conditions as varied as depression and arthritis—with minimal or no side effects.

SAMe was a relatively expensive nutrient when introduced to the US market a decade ago. Since then, the cost of synthesizing pharmaceutical-quality SAMe has been greatly reduced. Its affordability, enviable safety record, and growing number of diverse health applications—including promoting the health of the liver and endothelium—make SAMe worthy of inclusion in every well-rounded supplement regimen.


While SAMe is best known for its effects in treating depression, liver disease, and arthritis, recent findings reveal its promise in supporting healthy endothelial function. Endothelial dysfunction occurs when the cells lining small blood vessels fail to respond to the demand for increased blood flow.59 It underlies both atherosclerosis and high blood pressure,60,61 and has many causes, including oxidative damage due to metabolic and other disorders.62,63

In 2005, researchers examined 608 elderly people to determine how well their arteries responded to nitroglycerin, a drug that stimulates increased blood flow.64 They found that subjects with naturally higher SAMe levels had better arterial responsiveness compared to those who had lower levels. This suggests that SAMe helps support healthy endothelial function, and that it could find further applications for individuals suffering from the effects of endothelial dysfunction.

Endothelial damage can result from ischemia, or low oxygen levels, as occurs in heart attacks and strokes. Ischemia and resulting endothelial damage can also occur following an organ transplant, as this surgical procedure temporarily interrupts blood and oxygen supply. In a promising animal study, pre-treatment with SAMe prevented ischemia-induced damage to endothelial tissue and organs following an organ transplant.65

This finding has tremendous implications, and suggests that SAMe may one day be used to protect blood-vessel endothelium and organs from ischemia-induced damage.


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