SAM-e
The super supplement that can relieve depression, osteoarthritis, and more.
Heading out the door? Read this article on the new Outside+ app available now on iOS devices for members! Download the app.
The super supplement that can relieve depression, osteoarthritis, and more

Back in 1999, SAM-e caused quite a stir when it was introduced in the United States as a dietary supplement. So much so that Newsweek—a magazine traditionally skeptical of anything outside mainstream medicine—wrote a glowing article: “The ‘Sammy’ Solution: A new supplement may help relieve depression and arthritis as well.”
Following the Newsweek story, popularity of the supplement kept growing, prompting researchers to take a thorough look at the evidence. And in 2002, the US Department of Health and Human Services published an Evidence Report. The authors examined 102 clinical studies and drew these conclusions: SAM-e was just as effective as prescription drugs for depression, without side effects such as sleeplessness and sexual problems. SAM-e was just as effective as nonsteroidal anti-inflammatory medications for osteoarthritis, without causing gastrointestinal, kidney, or liver damage. And it could help with some liver conditions.
Considering that this report was published more than a decade ago, why isn’t SAM-e a household word? Likely because the enormous sums of money spent marketing pharmaceutical drugs for depression and arthritis far outweigh anything imaginable for a simple dietary supplement—but that’s no reason to ignore SAM-e’s benefits.
What Is SAM-e?
Pronounced “sam-EE,” short for S-adenosylmethionine, it is not found in food but is made by our bodies from the amino acid methionine. SAM-e exists in every cell and is essential for life.
It was discovered in Italy in 1952, and was initially prescribed as an injection to treat depression. Along the way, patients noticed that their arthritis pain was also disappearing, and studies confirmed SAM-e’s efficacy for the joint disease. European doctors also began prescribing it for fibromyalgia and liver disorders. Eventually, after becoming available in pills, SAM-e emerged in the United States as a dietary supplement.
SAM-e is required for a process known as “methylation,” which occurs continually throughout our lives. SAM-e provides groups of molecules, known as “methyl groups,” to enable our bodies to produce other chemicals that are vital for normal function, including neurotransmitters and substances involved in regenerating joint cartilage and controlling pain. Methylation also influences how genes behave—to cause or heal disease, or to speed up or slow down aging.
In short, SAM-e plays a critical role in our health. Folic acid and vitamin B12 support its production, but as we age, our bodies may not produce enough SAM-e, so supplementing can help.
Multiple Benefits
Since the 2002 government report, evidence of SAM-e’s benefits has continued to be published in scientific journals. For example, Harvard Medical School researchers confirmed its efficacy and safety for depression in the Canadian Journal of Psychiatry. And a detailed review of studies at the University of Aberdeen in Scotland found “consistent evidence” that SAM-e is effective for osteoarthritis.
In other studies, SAM-e relieved fibromyalgia symptoms. Research also shows that people with liver disease aren’t able to produce normal amounts of SAM-e. While the supplement isn’t a cure, it has delayed the need for transplants in people with liver failure, while also helping restore liver enzymes to normal levels. Test-tube studies show that SAM-e may also stop or slow the growth of cancer cells and blood vessels that feed tumors.
What to Take
There is no single dose for SAM-e, as individual needs vary. Although studies report no significant side effects, some people experience digestive upset or anxiety, which may be relieved with a lower dose. SAM-e builds up in your system, so you may need to adjust the dose after taking it for a few days or longer.
Some physicians recommend starting with 50–100 mg daily, first thing in the morning, and building up gradually until you experience relief. These are the highest dosages used in studies:
- For fibromyalgia: 400 mg, twice daily
- For osteoarthritis: 600 mg, twice daily, or 400 mg, three times daily
- For depression: 800 mg, twice daily
According to DrugBank Canada (drugbank.ca), a non-profit scientific organization, SAM-e in pills is absorbed from the small intestine, not the
stomach. To avoid breakdown by stomach acids, SAM-e should be taken on an empty stomach. Enteric–coated supplements that resist stomach acid and
help SAM-e reach the intestine intact are also available.
Good Buys

NATROL SAMe is enteric coated, and features the form of SAM-e shown to be effective in clinical trials.

JARROW FORMULAS Natural SAM-e 400 provides 400 mg of the biologically active form of SAM-e in individually blister-packed tablets.

LUMINA HEALTH CELLFOOD SAM-e Liquid Formula boasts a unique delivery system that gives it a 95% absorption rate—so all you need are a few drops.
Amazing Wellness Contributing editor Vera Tweed has been writing about nutrition, fitness, and healthy living since 1997.